Oink: an Implementation and Evaluation of Modern Parity Game Solvers

Parity games have important practical applications in formal verification and synthesis, especially to solve the model-checking problem of the modal mu-calculus. They are also interesting from the theory perspective, as they are widely believed to admit a polynomial solution, but so far no such algorithm is known. In recent years, a number of new algorithms and improvements to existing algorithms have been proposed. We implement a new and easy to extend tool Oink, which is a high-performance implementation of modern parity game algorithms. We further present a comprehensive empirical evaluation of modern parity game algorithms and solvers, both on real world benchmarks and randomly generated games. Our experiments show that our new tool Oink outperforms the current state-of-the-art.Comment: Accepted at TACAS 201

Genetic Reconstruction of Protozoan rRNA Decoding Sites Provides a Rationale for Paromomycin Activity against Leishmania and Trypanosoma

Aminoglycoside antibiotics target the ribosomal decoding A-site and are active against a broad spectrum of bacteria. These compounds bind to a highly conserved stem-loop-stem structure in helix 44 of bacterial 16S rRNA. One particular aminoglycoside, paromomycin, also shows potent antiprotozoal activity and is used for the treatment of parasitic infections, e.g. by Leishmania spp. The precise drug target is, however, unclear; in particular whether aminoglycoside antibiotics target the cytosolic and/or the mitochondrial protozoan ribosome. To establish an experimental model for the study of protozoan decoding-site function, we constructed bacterial chimeric ribosomes where the central part of bacterial 16S rRNA helix 44 has been replaced by the corresponding Leishmania and Trypanosoma rRNA sequences. Relating the results from in-vitro ribosomal assays to that of in-vivo aminoglycoside activity against Trypanosoma brucei, as assessed in cell cultures and in a mouse model of infection, we conclude that aminoglycosides affect cytosolic translation while the mitochondrial ribosome of trypanosomes is not a target for aminoglycoside antibiotics

Understanding the Origins of Bacterial Resistance to Aminoglycosides through Molecular Dynamics Mutational Study of the Ribosomal A-Site

Paromomycin is an aminoglycosidic antibiotic that targets the RNA of the bacterial small ribosomal subunit. It binds in the A-site, which is one of the three tRNA binding sites, and affects translational fidelity by stabilizing two adenines (A1492 and A1493) in the flipped-out state. Experiments have shown that various mutations in the A-site result in bacterial resistance to aminoglycosides. In this study, we performed multiple molecular dynamics simulations of the mutated A-site RNA fragment in explicit solvent to analyze changes in the physicochemical features of the A-site that were introduced by substitutions of specific bases. The simulations were conducted for free RNA and in complex with paromomycin. We found that the specific mutations affect the shape and dynamics of the binding cleft as well as significantly alter its electrostatic properties. The most pronounced changes were observed in the U1406C∶U1495A mutant, where important hydrogen bonds between the RNA and paromomycin were disrupted. The present study aims to clarify the underlying physicochemical mechanisms of bacterial resistance to aminoglycosides due to target mutations

Algal and aquatic plant carbon concentrating mechanisms in relation to environmental change

Carbon dioxide concentrating mechanisms (also known as inorganic carbon concentrating mechanisms; both abbreviated as CCMs) presumably evolved under conditions of low CO2 availability. However, the timing of their origin is unclear since there are no sound estimates from molecular clocks, and even if there were, there are no proxies for the functioning of CCMs. Accordingly, we cannot use previous episodes of high CO2 (e.g. the Palaeocene-Eocene Thermal Maximum) to indicate how organisms with CCMs responded. Present and predicted environmental change in terms of increased CO2 and temperature are leading to increased CO2 and HCO3- and decreased CO32- and pH in surface seawater, as well as decreasing the depth of the upper mixed layer and increasing the degree of isolation of this layer with respect to nutrient flux from deeper waters. The outcome of these forcing factors is to increase the availability of inorganic carbon, photosynthetic active radiation (PAR) and ultraviolet B radiation (UVB) to aquatic photolithotrophs and to decrease the supply of the nutrients (combined) nitrogen and phosphorus and of any non-aeolian iron. The influence of these variations on CCM expression has been examined to varying degrees as acclimation by extant organisms. Increased PAR increases CCM expression in terms of CO2 affinity, while increased UVB has a range of effects in the organisms examined; little relevant information is available on increased temperature. Decreased combined nitrogen supply generally increases CO2 affinity, decreased iron availability increases CO2 affinity, and decreased phosphorus supply has varying effects on the organisms examined. There are few data sets showing interactions among the observed changes, and even less information on genetic (adaptation) changes in response to the forcing factors. In freshwaters, changes in phytoplankton species composition may alter with environmental change with consequences for frequency of species with or without CCMs. The information available permits less predictive power as to the effect of the forcing factors on CCM expression than for their overall effects on growth. CCMs are currently not part of models as to how global environmental change has altered, and is likely to further alter, algal and aquatic plant primary productivity

Preservation of Strawberries with an Antifungal Edible Coating Using Peony Extracts in Chitosan

Strawberries represent a valuable source of bioactive compounds including vitamin C, E, β-carotene, and phenolic compounds, but they are fruits with an extremely short postharvest life. Therefore, the current study was conducted to investigate the effectiveness of an active coating consisting in antifungal microparticles obtained by spray drying of peony extracts (Paeonia rockii (PPR)) dispersed in chitosan (Ch) and subsequent addition to polysaccharide gels to slow the fungal attack of small highly perishable fruits, such as strawberries. The results of the antimicrobial assays indicate that the peony extracts in chitosan are able to counteract effectively the growth of different fungal isolates from deteriorated strawberries. In conclusion, through the treatment with this antifungal coating, it is possible to prolong the shelf life of delicate fruits, such as strawberries, to about 16Ã\u82 days, slowing down the weight loss, affecting the safeguard of important vitamins and antioxidant capacity during storage, without causing any significant alteration of the nutritional and sensorial properties of the product