Enforcing QVT-R with mu-calculus and games

Abstract. QVT-R is the standard Object Management Group bidi-rectional transformation language. In previous work, we gave a precise game-theoretic semantics for the checkonly semantics of QVT-R trans-formations, including the recursive invocation of relations which is al-lowed and used, but not defined, by the QVT standard. In this paper, we take up the problem of enforce semantics, where the standard at-tempts formality, but at crucial points lapses into English. We show that our previous semantics can be extended to enforce mode, giving a precise semantics taking the standard into account.

Implementing QVT-R bidirectional model transformations using alloy

QVT Relations (QVT-R) is the standard language proposed by the OMG to specify bidirectional model transformations. Unfortunately, in part due to ambiguities and omissions in the original semantics, acceptance and development of effective tool support has been slow. Recently, the checking semantics of QVT-R has been clarified and formalized. In this paper we propose a QVT-R tool that complies to such semantics. Unlike any other existing tool, it also supports meta-models enriched with OCL constraints (thus avoiding returning ill-formed models), and proposes an alternative enforcement semantics that works according to the simple and predictable “principle of least change”. The implementation is based on an embedding of both QVT-R transformations and UML class diagrams (annotated with OCL) in Alloy, a lightweight formal specification language with support for automatic model finding via SAT solving.Fundação para a Ciência e a Tecnologi

From coinductive proofs to exact real arithmetic: theory and applications

Based on a new coinductive characterization of continuous functions we extract certified programs for exact real number computation from constructive proofs. The extracted programs construct and combine exact real number algorithms with respect to the binary signed digit representation of real numbers. The data type corresponding to the coinductive definition of continuous functions consists of finitely branching non-wellfounded trees describing when the algorithm writes and reads digits. We discuss several examples including the extraction of programs for polynomials up to degree two and the definite integral of continuous maps

Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement

Background: Whole-exome sequencing has identified the causes of several Mendelian diseases by analyzing multiple unrelated cases, but it is more challenging to resolve the cause of extremely rare and suspected Mendelian diseases from individual families. We identified a family quartet with two children, both affected with a previously unreported disease, characterized by progressive muscular weakness and cardiomyopathy, with normal intelligence. During the course of the study, we identified one additional unrelated patient with a comparable phenotype. Methods: We performed whole-genome sequencing (Complete Genomics platform), whole-exome sequencing (Agilent SureSelect exon capture and Illumina Genome Analyzer II platform), SNP genotyping (Illumina HumanHap550 SNP array) and Sanger sequencing on blood samples, as well as RNA-Seq (Illumina HiSeq platform) on transformed lymphoblastoid cell lines. Results: From whole-genome sequence data, we identified RBCK1, a gene encoding an E3 ubiquitin-protein ligase, as the most likely candidate gene, with two protein-truncating mutations in probands in the first family. However, exome data failed to nominate RBCK1 as a candidate gene, due to poor regional coverage. Sanger sequencing identified a private homozygous splice variant in RBCK1 in the proband in the second family, yet SNP genotyping revealed a 1.2Mb copy-neutral region of homozygosity covering RBCK1. RNA-Seq confirmed aberrant splicing of RBCK1 transcripts, resulting in truncated protein products. Conclusions: While the exact mechanism by which these mutations cause disease is unknown, our study represents an example of how the combined use of whole-genome DNA and RNA sequencing can identify a disease-predisposing gene for a novel and extremely rare Mendelian disease

Thalamic inputs to dorsomedial striatum are involved in inhibitory control: evidence from the five-choice serial reaction time task in rats

Rationale Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. Objectives Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats. Methods The 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively. Results We found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field. Conclusions These results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control

Automata for true concurrency properties

We present an automata-theoretic framework for the model checking of true concurrency properties. These are specified in a fixpoint logic, corresponding to history-preserving bisimilarity, capable of describing events in computations and their dependencies. The models of the logic are event structures or any formalism which can be given a causal semantics, like Petri nets. Given a formula and an event structure satisfying suitable regularity conditions we show how to construct a parity tree automaton whose language is non-empty if and only if the event structure satisfies the formula. The automaton, due to the nature of event structure models, is usually infinite. We discuss how it can be quotiented to an equivalent finite automaton, where emptiness can be checked effectively. In order to show the applicability of the approach, we discuss how it instantiates to finite safe Petri nets. As a proof of concept we provide a model checking tool implementing the technique

Association Analysis of Type 2 Diabetes Loci in Type 1 Diabetes

OBJECTIVE—To search for a possible association of type 1 diabetes with 10 validated type 2 diabetes loci, i.e., PPARG, KCNJ11, WFS1, HNF1B, IDE/HHEX, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2, and FTO/RPGRIP1L

Egg shape in the Common Guillemot Uria aalge and Brunnich’s Guillemot U. lomvia: not a rolling matter?

The adaptive significance of avian egg shape is poorly understood, and has been studied only in those species producing pyriform (pear-shaped, or pointed) eggs: waders and guillemots (murres) Uria spp., albeit to a limited extent. In the latter, it is widely believed that the pyriform shape has evolved to minimise their likelihood of rolling off a cliff ledge: the idea being that the more pointed the egg, the narrower the arc in which it rolls, and the less likely it is it will fall from a cliff ledge. Previous research also claimed that the rolling trajectory—the diameter of the arc they describe—of Common Guillemot U. aalge eggs is influenced not only by its shape but also by its mass, with heavier (i.e. larger) eggs describing a wider arc than lighter eggs. The finding that both shape and mass determined the rolling trajectory of Common Guillemot eggs (the shape–mass hypothesis) was used to explain the apparent anomaly that Bru¨nnich’s Guillemot U. lomvia produce eggs that are less pointed, yet breed on narrower ledges than Common Guillemots. They are able to do this, it was suggested, because Bru¨nnich’s Guillemot eggs are smaller and lighter in mass than those of Common Guillemots. However, since some populations of Bru¨nnich’s Guillemots produce eggs that are as large or larger than those of some Common Guillemot populations, the shape–mass hypothesis predicts that that (1) larger (i.e. heavier) eggs of both guillemot species will be more pyriform (pointed) in shape, and (2) that eggs of the two species of same mass should be similarly pointed. We tested these predictions and found: (1) only a weak, positive association between egg volume and pointedness in both guillemot species (\3% of the variation in egg shape explained by egg volume), and (2) no evidence that eggs of the two species of similar mass were more similar in shape: regardless of their mass, Brunnich’s Guillemot eggs were less pointed than Common Guillemot eggs. Overall, our results call into question the long-held belief that protection from rolling is the main selective factor driving guillemot egg shape

Limits to Poisson's ratio in isotropic materials - general result for arbitrary deformation

The lower bound usually cited for Poisson's ratio {\nu} is -1, derived from the relationship between {\nu} and the bulk and shear moduli. From consideration of the longitudinal and biaxial moduli, we recently determined that the lower bound on {\nu} for isotropic materials is actually 1/5, a value also consistent with experimental measurements on real materials. Herein we generalize this result, first by analyzing expressions for {\nu} in terms of six common elastic constants, and then by considering arbitrary strains. The results corroborate the prior finding that 1/5 <= {\nu} for linear elasticity to be applicable.Comment: 15 pages, 3 figures, 1 tabl