Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements

Glypican (GPC)-3 inhibits cell proliferation and regulates cell survival during development. This action is demonstrated by GPC3 loss-of-function mutations in humans and mice. Here, we show that the GPC3 core protein is processed by a furinlike convertase. This processing is essential for GPC3 modulating Wnt signaling and cell survival in vitro and for supporting embryonic cell movements in zebrafish. The processed GPC3 core protein is necessary and sufficient for the cell-specific induction of apoptosis, but in vitro effects on canonical and noncanonical Wnt signaling additionally require substitution of the core protein with heparan sulfate. Wnt 5A physically associates only with processed GPC3, and only a form of GPC3 that can be processed by a convertase is able to rescue epiboly and convergence/extension movements in GPC3 morphant embryos. Our data imply that the Simpson–Golabi–Behmel syndrome may in part result from a loss of GPC3 controls on Wnt signaling, and suggest that this function requires the cooperation of both the protein and the heparan sulfate moieties of the proteoglycan

MiniSAT(ID) for satisfiability checking and constraint solving

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Model expansion in the presence of function symbols using constraint programming

The traditional approach to model expansion (generating models of a logic theory extending a partial structure) is to reduce the theory to a propositional language and apply a search algorithm to the resulting theory. Function symbols are typically replaced by predicate symbols representing the graph of the function, an operation that blows up the reduced theory.In this paper, we present an improved approach to handle function symbols in a ground-and-solve methodology, building on ideas from Constraint Programming.We do so in the context of FO(.)^IDP, the knowledge representation language that extends First-Order logic with, among others, inductive definitions, arithmetic and aggregates.A model expansion algorithm is developed, consisting of(i) a grounding algorithm for FO(.)^IDP that is parametrized by the function symbols the are allowed to occur in the reduced theory, and (ii) a search algorithm for unrestricted, ground FO(.)^IDP. The ideas are implemented within the IDP knowledge-base system and experimental evaluation shows that both more compact groundings and improved search performance are obtained.status: publishe

Symmetry propagation: Improved dynamic symmetry breaking in SAT

For constraint programming, many well performing dynamic symmetry breaking techniques have been devised. For propositional satisfiability solving, dynamic symmetry breaking is still either slower or less general than static symmetry breaking. This paper presents Symmetry Propagation, which is an improvement to Lightweight Dynamic Symmetry Breaking, a dynamic symmetry breaking approach from CP. Symmetry Propagation uses any given symmetry as a propagator, and as a result is a general symmetry breaking technique. Experiments with an implementation in the SAT solver Minisat show that on many benchmarks, Symmetry Propagation outperforms the state-of-the-art static symmetry breaking method Shatter.This is a presentation about the Symmetry Propagation algorithm, given by Chris Mears at the SymCon 2012 conference in Québec City.status: publishe

Predicate Logic as a Modeling Language: The IDP System

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Simulating dynamic systems using linear time calculus theories

Dynamic systems play a central role in fields such as planning, verification, and databases. Fragmented throughout these fields, we find a multitude of languages to formally specify dynamic systems and a multitude of systems to reason on such specifications. Often, such systems are bound to one specific language and one specific inference task. It is troublesome that performing several inference tasks on the same knowledge requires translations of your specification to other languages. In this paper we study whether it is possible to perform a broad set of well-studied inference tasks on one specification. More concretely, we extend IDP3 with several inferences from fields concerned with dynamic specifications.status: publishe