A Formalization of the Theorem of Existence of First-Order Most General Unifiers

This work presents a formalization of the theorem of existence of most general unifiers in first-order signatures in the higher-order proof assistant PVS. The distinguishing feature of this formalization is that it remains close to the textbook proofs that are based on proving the correctness of the well-known Robinson's first-order unification algorithm. The formalization was applied inside a PVS development for term rewriting systems that provides a complete formalization of the Knuth-Bendix Critical Pair theorem, among other relevant theorems of the theory of rewriting. In addition, the formalization methodology has been proved of practical use in order to verify the correctness of unification algorithms in the style of the original Robinson's unification algorithm.Comment: In Proceedings LSFA 2011, arXiv:1203.542

Disarming Pseudomonas aeruginosa Virulence by the Inhibitory Action of 1,10-Phenanthroline-5,6-Dione- Based Compounds: Elastase B (LasB) as a Chemotherapeutic Target

negative pathogen Pseudomonas aeruginosa, and this enzyme orchestrates several physiopathological events during bacteria-host interplays. LasB is considered to be a potential target for the development of an innovative chemotherapeutic approach, especially against multidrug-resistant strains. Recently, our group showed that 1,10-phenanthroline-5,6-dione (phendione), [Ag(phendione)2]ClO4 (Ag-phendione) and [Cu(phendione)3](ClO4)2.4H2O (Cu-phendione) had anti-P. aeruginosa action against both planktonic- and biofilm-growing cells. In the present work, we have evaluated the effects of these compounds on the (i) interaction with the lasB active site using in silico approaches, (ii) lasB proteolytic activity by using a specific fluorogenic peptide substrate, (iii) lasB gene expression by real time-polymerase chain reaction, (iv) lasB protein secretion by immunoblotting, (v) ability to block the damages induced by lasB on a monolayer of lung epithelial cells, and (vi) survivability of Galleria mellonella larvae after being challenged with purified lasB and lasB-rich bacterial secretions. Molecular docking analyses revealed that phendione and its Ag+ and Cu2+ complexes were able to interact with the amino acids forming the active site of lasB, particularly Cu-phendione which exhibited the most favorable interaction energy parameters. Additionally, the test compounds were effective inhibitors of lasB activity, blocking the in vitro cleavage of the peptide substrate, aminobenzyl-Ala-Gly-Leu-Ala-p-nitrobenzylamide, with Cu- phendione having the best inhibitory action (Ki = 90 nM). Treating living bacteria with a sub-inhibitory concentration (1/2 × MIC value) of the test compounds caused a significant reduction in the expression of the lasB gene as well as its mature protein production/secretion. Further, Ag-phendione and Cu-phendione offered protective rg 1 August 2019 | Volume 10 | Article 1701 1,10-Phenanthroline-5,6-Dione-Based Compounds: As Anti-Virulence Drugs action for lung epithelial cells, reducing the A549 monolayer damage by approximately 32 and 42%, respectively. Interestingly, Cu-phendione mitigated the toxic effect of both purified lasB molecules and lasB-containing bacterial secretions in the in vivo model, increasing the survival time of G. mellonella larvae. Collectively, these data reinforce the concept of lasB being a veritable therapeutic target and phendione-based compounds (mainly Cu-phendione) being prospective anti-virulence drugs against P. aeruginosa

In vitro and in vivo safety evaluation of Dipteryx alata Vogel extract

<p>Abstract</p> <p>Background</p> <p><it>Dipteryx alata </it>Vogel popularly known as "baru" is an important commercial leguminous tree species from the Brazilian Cerrado, which possess medicinal properties, besides its fruits consumption by animals and humans. The use of the "naturally occurring plants" as herbal remedies and foods mainly from leaves, seeds, flowers and roots of plants or extracts require precautions before ensuring these are safe and efficacious. The objective of this study was to evaluate the safety of <it>D. alata </it>barks extract.</p> <p>Methods</p> <p>Vegetal drugs of <it>D. alata </it>barks were submitted to quality control assays and further to the safety assays under 1) <it>in vitro </it>parameter by <it>Salmonella </it>(Ames) mutagenicity, and 2) <it>in vivo </it>parameter on the pregnancy of rats.</p> <p>Results</p> <p>The extract was non-mutagenic to any of the assessed strains TA97a, TA98, TA100 and TA102 even after metabolic activation (+S9). All <it>in vivo </it>parameters (reproductive ability evaluation, physical development of rat offsprings, and neurobehavioral development assays) showed no changes related to control group.</p> <p>Conclusion</p> <p><it>D. alata </it>barks extract is neither mutagenic by the Ames test nor toxic in the pregnancy of rats, with no physical-neurobehavioral consequences on the rat offsprings development.</p

A PVS Theory for Term Rewriting Systems

AbstractA theory, called trs, for Term Rewriting Systems in the theorem Prover PVS is described. This theory is built on the PVS libraries for finite sequences and sets and a previously developed PVS theory named ars for Abstract Reduction Systems which was built on the PVS libraries for sets. Theories for dealing with the structure of terms, for replacements and substitutions jointly with ars allow for adequate specifications of notions of term rewriting such as critical pairs and formalization of elaborated criteria from the theory of Term Rewriting Systems such as the Knuth-Bendix Critical Pair Theorem. On the other hand, ars specifies definitions and notions such as reduction, confluence and normal forms as well as non basic concepts such as Noetherianity

Formal verification of an optimal air traffic conflict resolution and recovery algorithm

Highly accurate positioning systems and new broadcasting technology have enabled air traffic management concepts where the responsibility for aircraft separation resides on pilots rather than on air traffic controllers. The Formal Methods Group at the National Institute of Aerospace and NASA Langley Research Center has proposed and formally verified an algorithm, called KB3D, for distributed three dimensional conflict resolution. KB3D computes resolution maneuvers where only one component of the velocity vector, i.e., ground speed, vertical speed, or heading, is modified. Although these maneuvers are simple to implement by a pilot, they are not necessarily optimal from a geometrical point of view. In general, optimal resolutions require the combination of all the components of the velocity vector. In this paper, we propose a two dimensional version of KB3D, which we call KB2D, that computes resolution maneuvers that are optimal with respect to ground speed and heading changes. The algorithm has been mechanically verified in the Prototype Verification System (PVS). The verification relies on algebraic proof techniques for the manipulation of the geometrical concepts relevant to the algorithm as well as standard deductive techniques available in PVS

Geometrical Specification using Dependent Types in PVS

Abstract. We point out the importance of the use of the refined dependent types available in the proof assistant PVS for the correct specification of a geometrical approach to solve the problem of air traffic conflict detection and resolution (between two aircrafts in mid air). A correct PVS specification which completely solves this problem giving a triplet which consists of 〈escape trajectory, recovery trajectory, switching time 〉 and whose first component allows exclusively changes in a unique of the parameters ground speed, heading and vertical speed is partially extended in such a way that the formulated escape maneuvers may combine changes in two of these parameters: ground speed and heading

Doença de Hodgkin do sigmoide: relato de caso Hodgkin´s Disease of sigmoid: a case report

Doença de Hodgkin no cólon é uma afecção rara. Relata-se um caso de Doença de Hodgkin extranodal com acometimento de sigmoide, cuja confirmação diagnóstica somente foi realizada após a cirurgia de ressecção tumoral e estudo imunohistoquímico.<br>Hodgkin disease of the colon is rare. We report a case of extranodal Hodgkin's disease involving the sigmoid which diagnosis was confirmed only after tumor resection and immunohistochemical study