Automata-Based Software Model Checking of Hyperproperties

We develop model checking algorithms for Temporal Stream Logic (TSL) and Hyper Temporal Stream Logic (HyperTSL) modulo theories. TSL extends Linear Temporal Logic (LTL) with memory cells, functions and predicates, making it a convenient and expressive logic to reason over software and other systems with infinite data domains. HyperTSL further extends TSL to the specification of hyperproperties - properties that relate multiple system executions. As such, HyperTSL can express information flow policies like noninterference in software systems. We augment HyperTSL with theories, resulting in HyperTSL(T),and build on methods from LTL software verification to obtain model checking algorithms for TSL and HyperTSL(T). This results in a sound but necessarily incomplete algorithm for specifications contained in the forall*exists* fragment of HyperTSL(T). Our approach constitutes the first software model checking algorithm for temporal hyperproperties with quantifier alternations that does not rely on a finite-state abstraction

Oligonucleotide sequences for RT-qPCR.

<p>Oligonucleotide sequences for RT-qPCR.</p

Matrix conditions predict anti-viral properties of statins.

<p>LucUbiNeo-ET replicon cells growing on PAA gel supports (1–12 kPa: 1 kPa = soft; 12 kPa = stiff) were incubated with FLV for 72 hours. Effects on HCV replication were measured by luciferase assay (<b>A</b>). For the same settings cell viability was measured by MTT assay (<b>B</b>). LucUbiNeo-ET replicon cells were incubated with increasing concentrations of the Rho kinase inhibitor HA1100 alone or in combination with FLV at 5 µM for 72 hours. HCV replication was measured by luciferase reporter assay (<b>C</b>). Viability of LucUbiNeo-ET replicon cells was monitored for the same settings by MTT assay (<b>D</b>). Huh-5-15 replicon cells were incubated with FLV with or without coincubation with HA1100 for 6 hours. HCV replication (<b>E</b>) as well as HO-1 expression (<b>F</b>) was measured by RT-qPCR.</p

Statins promote HO-1 expression by reducing Bach1- and inducing KLF2- expression.

<p>Bach1 (<b>A</b>) and KLF2 (<b>B</b>) expression levels were measured in Huh-5-15 cells by real time RT-qPCR after 6 hours of statin incubation. LucUbiNeo-ET replicon cells were transfected with siRNA directed against KLF2 (siKLF2) or against a control gene (GFP; siControl) at [10 nM] (<b>C, D, E, F</b>). 24 hours after transfection expression of KLF2 and HO-1 was measured by RT-qPCR (<b>C</b>). Cells transfected with siRNA for 24 hours were further incubated with FLV for 24 hours. Expression of KLF2, HO-1 (<b>D</b>) <b>and HCV</b> (<b>E</b>) was measured by RT-qPCR, HCV replication was measured by luciferase reporter assay (<b>F</b>).</p

Inhibition of HCV in the infectious genotype 2a system.

<p>Huh-7.5 cells were transfected with the full length HCV clone JcR2a. HCV replication was measured by luciferase reporter assay after 72 hours of FLV incubation (<b>A</b>). Huh-7.5 cells were infected with the HCV genotype 2a strain JC1 and incubated with FLV or PRV for 24 hours. Viral replication was visualized by immunofluorescent staining of the HCV protein E2 (<b>B, upper pannel</b>). Cell viability was verified by bright field (BF) microscopy (<b>B, lower pannel</b>). Representative images pairs are shown.</p

Inhibition of HCV replication by statins in genotype 1b replicon cells.

<p>LucUbiNeo-ET replicon cells were incubated in the presence of fluvastatin (FLV), pravastatin (PRV), simvastatin (SMV), rosuvastatin (ROV) or atorvastatin (ATV) at the indicated concentrations for 24, 48 or 72 hours. (<b>A</b>) Expression of the LDL-receptor (LDLR) was measured by real time RT-qPCR after 48 h of statin incubation (<b>B–F</b>) Dose- and time-dependent inhibition of HCV replication caused by statins was measured by luciferase reporter assay. Statin mediated effects on cell proliferation were measured after 72 hours of incubation (<b>G</b>) and confirmed by Western Blot analysis (<b>H</b>).</p