Global Guidance for Local Generalization in Model Checking

SMT-based model checkers, especially IC3-style ones, are currently the most effective techniques for verification of infinite state systems. They infer global inductive invariants via local reasoning about a single step of the transition relation of a system, while employing SMT-based procedures, such as interpolation, to mitigate the limitations of local reasoning and allow for better generalization. Unfortunately, these mitigations intertwine model checking with heuristics of the underlying SMT-solver, negatively affecting stability of model checking. In this paper, we propose to tackle the limitations of locality in a systematic manner. We introduce explicit global guidance into the local reasoning performed by IC3-style algorithms. To this end, we extend the SMT-IC3 paradigm with three novel rules, designed to mitigate fundamental sources of failure that stem from locality. We instantiate these rules for the theory of Linear Integer Arithmetic and implement them on top of Spacer solver in Z3. Our empirical results show that GSpacer, Spacer extended with global guidance, is significantly more effective than both Spacer and sole global reasoning, and, furthermore, is insensitive to interpolation

Global Guidance for Local Generalization in Model Checking

SMT-based model checkers, especially IC3-style ones, are currently the most effective techniques for verification of infinite state systems. They infer global inductive invariants via local reasoning about a single step of the transition relation of a system, while employing SMT-based procedures, such as interpolation, to mitigate the limitations of local reasoning and allow for better generalization. Unfortunately, these mitigations intertwine model checking with heuristics of the underlying SMT-solver, negatively affecting stability of model checking. In this paper, we propose to tackle the limitations of locality in a systematic manner. We introduce explicit global guidance into the local reasoning performed by IC3-style algorithms. To this end, we extend the SMT-IC3 paradigm with three novel rules, designed to mitigate fundamental sources of failure that stem from locality. We instantiate these rules for the theory of Linear Integer Arithmetic and implement them on top of SPACER solver in Z3. Our empirical results show that GSPACER, SPACER extended with global guidance, is significantly more effective than both SPACER and sole global reasoning, and, furthermore, is insensitive to interpolation.Comment: Published in CAV 202

High-confidence glycosome proteome for procyclic form <em>Trypanosoma brucei</em> by epitope-tag organelle enrichment and SILAC proteomics

The glycosome of the pathogenic African trypanosome Trypanosoma brucei is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed

ATG24 represses autophagy and differentiation and is essential for homeostasy of the flagellar pocket in trypanosoma brucei

We have previously identified homologs for nearly half of the approximately 30 known yeast Atg's in the genome database of the human sleeping sickness parasite Trypanosoma brucei. So far, only a few of these homologs have their role in autophagy experimentally confirmed. Among the candidates was the ortholog of Atg24 that is involved in pexophagy in yeast. In T. brucei, the peroxisome-like organelles named glycosomes harbor core metabolic processes, especially glycolysis. In the autotrophic yeast, autophagy is essential for adaptation to different nutritional environments by participating in the renewal of the peroxisome population. We hypothesized that autophagic turnover of the parasite's glycosomes plays a role in differentiation during its life cycle, which demands adaptation to different host environments and associated dramatic changes in nutritional conditions. We therefore characterized T. brucei ATG24, the T. brucei ortholog of yeast Atg24 and mammalian SNX4, and found it to have a regulatory role in autophagy and differentiation as well as endocytic trafficking. ATG24 partially localized on endocytic membranes where it was recruited via PI3-kinase III/VPS34. ATG24 silencing severely impaired receptor-mediated endocytosis of transferrin, but not adsorptive uptake of a lectin, and caused a major enlargement of the flagellar pocket. ATG24 silencing approximately doubled the number of autophagosomes, suggesting a role in repressing autophagy, and strongly accelerated differentiation, in accordance with a role of autophagy in parasite differentiation. Overexpression of the two isoforms of T. brucei ATG8 fused to GFP slowed down differentiation, possibly by a dominant-negative effect. This was overcome by ATG24 depletion, further supporting its regulatory role

Substitution Électrophile Aliphatique II. Influence de l'effet stérique dans la bromo et l'iododemétallation de dérivés alcoylés de l'étain (1)

The rates of the reactions of tetraalkyltins (R4Sn) with bromine in dimethylformamide and acetic acid solutions and with iodine in acetic acid are found to depend on steric effects (kMe> kEt > knPr), caused by the R3Sn leaving group. Trialkyltin bromides (R3SnBr) are cleaved by bromine in acetic acid in a reactivity sequence (kMe knPr) which is best explained by an increasing importance of inductive effects. Copyright © 1962 Wiley‐VCH Verlag GmbH & Co. KGaA, WeinheimSCOPUS: ar.jinfo:eu-repo/semantics/publishe