A Logical Product Approach to Zonotope Intersection

We define and study a new abstract domain which is a fine-grained combination of zonotopes with polyhedric domains such as the interval, octagon, linear templates or polyhedron domain. While abstract transfer functions are still rather inexpensive and accurate even for interpreting non-linear computations, we are able to also interpret tests (i.e. intersections) efficiently. This fixes a known drawback of zonotopic methods, as used for reachability analysis for hybrid sys- tems as well as for invariant generation in abstract interpretation: intersection of zonotopes are not always zonotopes, and there is not even a best zonotopic over-approximation of the intersection. We describe some examples and an im- plementation of our method in the APRON library, and discuss some further in- teresting combinations of zonotopes with non-linear or non-convex domains such as quadratic templates and maxplus polyhedra

An Axiomatic Approach to Liveness for Differential Equations

This paper presents an approach for deductive liveness verification for ordinary differential equations (ODEs) with differential dynamic logic. Numerous subtleties complicate the generalization of well-known discrete liveness verification techniques, such as loop variants, to the continuous setting. For example, ODE solutions may blow up in finite time or their progress towards the goal may converge to zero. Our approach handles these subtleties by successively refining ODE liveness properties using ODE invariance properties which have a well-understood deductive proof theory. This approach is widely applicable: we survey several liveness arguments in the literature and derive them all as special instances of our axiomatic refinement approach. We also correct several soundness errors in the surveyed arguments, which further highlights the subtlety of ODE liveness reasoning and the utility of our deductive approach. The library of common refinement steps identified through our approach enables both the sound development and justification of new ODE liveness proof rules from our axioms.Comment: FM 2019: 23rd International Symposium on Formal Methods, Porto, Portugal, October 9-11, 201

Interval Slopes as Numerical Abstract Domain for Floating-Point Variables

The design of embedded control systems is mainly done with model-based tools such as Matlab/Simulink. Numerical simulation is the central technique of development and verification of such tools. Floating-point arithmetic, that is well-known to only provide approximated results, is omnipresent in this activity. In order to validate the behaviors of numerical simulations using abstract interpretation-based static analysis, we present, theoretically and with experiments, a new partially relational abstract domain dedicated to floating-point variables. It comes from interval expansion of non-linear functions using slopes and it is able to mimic all the behaviors of the floating-point arithmetic. Hence it is adapted to prove the absence of run-time errors or to analyze the numerical precision of embedded control systems

Synthesis of novel biocomposite powder for simultaneous removal of hazardous ciprofloxacin and methylene blue: Central composite design, kinetic and isotherm studies using Brouers-Sotolongo family models

Over the past decades, extensive efforts have been made to use biomass-based-materials for wastewater-treatment. The first purpose of this study was to develop and characterize regenerated-reed/reed-charcoal (RR-ChR), an enhanced biosorbent from Tunisian-reed (Phragmites-australis). The second aim was to assess and optimize the RR-ChR use for the removal of binary ciprofloxacin antibiotic (CIP) and methylene blue dye (MB), using Central Composite Design under Response Surface methodology. The third purpose was to explain the mechanisms involved in the biosorption-process. The study revealed that the highest removal-percentages (76.66 % for the CIP and 100 % for the MB) were obtained under optimum conditions: 1.55 g/L of adsorbent, 35 mg/L of CIP, 75 mg/L of MB, a pH of 10.42 and 115.28 min contact time. It showed that the CIP biosorption mechanism was described by Brouers–Sotolongo-fractal model, with regression-coefficient (R2) of 0.9994 and a Person’s Chi-square (X2) of 0.01. The Hill kinetic model better described the MB biosorption (R2 = 1 and X2 = 1.0E-4). The isotherm studies showed that the adsorbent surface was heterogeneous and the best nonlinear-fit was obtained with the Jovanovich (R2 = 0.9711), and Brouers–Sotolongo (R2 = 0.9723) models, for the CIP and MB adsorption, respectively. Finally, the RR-ChR lignocellulosic-biocomposite-powder could be adopted as efficient and cost-effective adsorbent

Drug Resistance in Eukaryotic Microorganisms

Eukaryotic microbial pathogens are major contributors to illness and death globally. Although much of their impact can be controlled by drug therapy as with prokaryotic microorganisms, the emergence of drug resistance has threatened these treatment efforts. Here, we discuss the challenges posed by eukaryotic microbial pathogens and how these are similar to, or differ from, the challenges of prokaryotic antibiotic resistance. The therapies used for several major eukaryotic microorganisms are then detailed, and the mechanisms that they have evolved to overcome these therapies are described. The rapid emergence of resistance and the restricted pipeline of new drug therapies pose considerable risks to global health and are particularly acute in the developing world. Nonetheless, we detail how the integration of new technology, biological understanding, epidemiology and evolutionary analysis can help sustain existing therapies, anticipate the emergence of resistance or optimize the deployment of new therapies

Heterologous expression of a novel drug transporter from the malaria parasite alters resistance to quinoline antimalarials

Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake. PF3D7_0629500-expressing cultures were also sensitized to related antimalarials; amodiaquine, mefloquine and particularly quinine. Drug sensitivity was reversed by introducing a SNP linked to CQ resistance in the parasite. Like Tat2p, PF3D7_0629500-dependent quinine hypersensitivity was suppressible with tryptophan, consistent with a common transport mechanism. A four-fold increase in quinine uptake by PF3D7_0629500 expressing cells was abolished by the resistance SNP. The parasite protein localised primarily to the yeast plasma membrane. Its expression varied between cells and this heterogeneity was used to show that high-expressing cell subpopulations were the most drug sensitive. The results reveal that the PF3D7_0629500 protein can determine the level of sensitivity to several major quinine-related antimalarials through an amino acid-inhibitable drug transport function. The potential clinical relevance is discussed

Robustness Analysis of Finite Precision Implementations

Abstract. A desirable property of control systems is robustness to inputs, when small perturbations of the inputs of a system will cause only small perturbations on outputs. This property should be maintained at the implementation level, where close inputs can lead to different execution paths. The problem becomes crucial for finite precision implementations, where any elementary computation is affected by an error. In this context, almost every test is potentially unstable, that is, for a given input, the finite precision and real numbers paths may differ. Still, state-of-the-art error analyses rely on the stable test hypothesis, yielding unsound error bounds when the conditional block is not robust to uncertainties. We propose a new abstract-interpretation based error analysis of finite precision implementations, which is sound in presence of unstable tests, by bounding the discontinuity error for path divergences. This gives a tractable analysis implemented in the FLUCTUAT analyzer.