QRAT+: Generalizing QRAT by a More Powerful QBF Redundancy Property

The QRAT (quantified resolution asymmetric tautology) proof system simulates virtually all inference rules applied in state of the art quantified Boolean formula (QBF) reasoning tools. It consists of rules to rewrite a QBF by adding and deleting clauses and universal literals that have a certain redundancy property. To check for this redundancy property in QRAT, propositional unit propagation (UP) is applied to the quantifier free, i.e., propositional part of the QBF. We generalize the redundancy property in the QRAT system by QBF specific UP (QUP). QUP extends UP by the universal reduction operation to eliminate universal literals from clauses. We apply QUP to an abstraction of the QBF where certain universal quantifiers are converted into existential ones. This way, we obtain a generalization of QRAT we call QRAT+. The redundancy property in QRAT+ based on QUP is more powerful than the one in QRAT based on UP. We report on proof theoretical improvements and experimental results to illustrate the benefits of QRAT+ for QBF preprocessing.Comment: preprint of a paper to be published at IJCAR 2018, LNCS, Springer, including appendi

Evaluating QBF Solvers: Quantifier Alternations Matter

We present an experimental study of the effects of quantifier alternations on the evaluation of quantified Boolean formula (QBF) solvers. The number of quantifier alternations in a QBF in prenex conjunctive normal form (PCNF) is directly related to the theoretical hardness of the respective QBF satisfiability problem in the polynomial hierarchy. We show empirically that the performance of solvers based on different solving paradigms substantially varies depending on the numbers of alternations in PCNFs. In related theoretical work, quantifier alternations have become the focus of understanding the strengths and weaknesses of various QBF proof systems implemented in solvers. Our results motivate the development of methods to evaluate orthogonal solving paradigms by taking quantifier alternations into account. This is necessary to showcase the broad range of existing QBF solving paradigms for practical QBF applications. Moreover, we highlight the potential of combining different approaches and QBF proof systems in solvers.Comment: preprint of a paper to be published at CP 2018, LNCS, Springer, including appendi

DepQBF 6.0: A Search-Based QBF Solver Beyond Traditional QCDCL

We present the latest major release version 6.0 of the quantified Boolean formula (QBF) solver DepQBF, which is based on QCDCL. QCDCL is an extension of the conflict-driven clause learning (CDCL) paradigm implemented in state of the art propositional satisfiability (SAT) solvers. The Q-resolution calculus (QRES) is a QBF proof system which underlies QCDCL. QCDCL solvers can produce QRES proofs of QBFs in prenex conjunctive normal form (PCNF) as a byproduct of the solving process. In contrast to traditional QCDCL based on QRES, DepQBF 6.0 implements a variant of QCDCL which is based on a generalization of QRES. This generalization is due to a set of additional axioms and leaves the original Q-resolution rules unchanged. The generalization of QRES enables QCDCL to potentially produce exponentially shorter proofs than the traditional variant. We present an overview of the features implemented in DepQBF and report on experimental results which demonstrate the effectiveness of generalized QRES in QCDCL.Comment: 12 pages + appendix; to appear in the proceedings of CADE-26, LNCS, Springer, 201

Shortening QBF Proofs with Dependency Schemes

We provide the first proof complexity results for QBF dependency calculi. By showing that the reflexive resolution path dependency scheme admits exponentially shorter Q-resolution proofs on a known family of instances, we answer a question first posed by Slivovsky and Szeider in 2014 [30]. Further, we conceive a method of QBF solving in which dependency recomputation is utilised as a form of inprocessing. Formalising this notion, we introduce a new calculus in which a dependency scheme is applied dynamically. We demonstrate the further potential of this approach beyond that of the existing static system with an exponential separation

Genomics and proteomics approaches to the study of cancer-stroma interactions

<p>Abstract</p> <p>Background</p> <p>The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.</p> <p>Methods</p> <p>The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.</p> <p>Results</p> <p>We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (<it>ARID4A</it>, <it>CALR</it>, <it>GNB2L1</it>, <it>RNF10</it>, <it>SQSTM1</it>, <it>USP9X</it>) were validated by real time PCR.</p> <p>Conclusions</p> <p>A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.</p

Involvement of cholecystokinin in baseline and post-prandial whole body insulin

The objective of the study was to investigate the role of cholecystokinin (CCK) on the food-induced insulin sensitization phenomenon in healthy Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats. Whole body insulin sensitivity determined by hyperinsulinaemic euglycaemic glucose clamping and the rapid insulin sensitivity test served as endpoints. Determinations were done in both fasted and re-fed animals. The involvement of CCK in post-prandial insulin sensitization was assessed by using proglumide, a CCK receptor blocker, by assessment of hypothalamic CCK-1/CCK-2 receptor expression by rt-PCR technique and by plasma insulin immunoreactivity determinations by means of radioimmunoassay as pharmacological, genetic and analytical approaches, respectively. The body weight of the OLETF rats and the amount of food consumed much exceeded those seen with LETO rats. The post-prandial increase in insulin sensitivity was marked in LETO, but not in OLETF rats. Intravenous proglumide attenuated post-prandial insulin sensitivity in LETO rats, with no effect in OLETF rats. Nevertheless, baseline insulin sensitivity was much lower in OLETF than in LETO rats. Treatment with rosiglitazone increased baseline insulin sensitivity of OLETF rats and evoked an increase in CCK-1 receptor gene expression in LETO rats. The results provide evidence for the involvement of CCK receptors in adjustment of both fasting and post-prandial insulin sensitivity. The data obtained with OLETF rats strongly suggest the predominant role of CCK-1 receptor