Weak memory models using event structures

National audienceIn this article, we investigate a denotational semantics based on event structures for a very simple imperative and concurrent programming language. The model incorporates behaviours of weak memory models such as reordering of instructions and non-locality. Our model can then be used to define a function from programs to their possible outcomes that can be used to give a formal semantics to a processor or a programming language. Most of the semantic ideas come from game semantics and its recent development based on event structures, but taking advantage of the first-order setting, we present in this paper a self-contained simplification of these ideas

Thin Games with Symmetry and Concurrent Hyland-Ong Games

We build a cartesian closed category, called Cho, based on event structures. It allows an interpretation of higher-order stateful concurrent programs that is refined and precise: on the one hand it is conservative with respect to standard Hyland-Ong games when interpreting purely functional programs as innocent strategies, while on the other hand it is much more expressive. The interpretation of programs constructs compositionally a representation of their execution that exhibits causal dependencies and remembers the points of non-deterministic branching.The construction is in two stages. First, we build a compact closed category Tcg. It is a variant of Rideau and Winskel's category CG, with the difference that games and strategies in Tcg are equipped with symmetry to express that certain events are essentially the same. This is analogous to the underlying category of AJM games enriching simple games with an equivalence relations on plays. Building on this category, we construct the cartesian closed category Cho as having as objects the standard arenas of Hyland-Ong games, with strategies, represented by certain events structures, playing on games with symmetry obtained as expanded forms of these arenas.To illustrate and give an operational light on these constructions, we interpret (a close variant of) Idealized Parallel Algol in Cho

Undecidability of Equality in the Free Locally Cartesian Closed Category (Extended version)

We show that a version of Martin-L\"of type theory with an extensional identity type former I, a unit type N1 , Sigma-types, Pi-types, and a base type is a free category with families (supporting these type formers) both in a 1- and a 2-categorical sense. It follows that the underlying category of contexts is a free locally cartesian closed category in a 2-categorical sense because of a previously proved biequivalence. We show that equality in this category is undecidable by reducing it to the undecidability of convertibility in combinatory logic. Essentially the same construction also shows a slightly strengthened form of the result that equality in extensional Martin-L\"of type theory with one universe is undecidable

Observably Deterministic Concurrent Strategies and Intensional Full Abstraction for Parallel-or

International audienceAlthough Plotkin's parallel-or is inherently deterministic, it has a non-deterministic interpretation in games based on (prime) event structures-in which an event has a unique causal history-because they do not directly support disjunctive causality. General event structures can express disjunctive causality and have a more permissive notion of determinism, but do not support hiding. We show that (structures equivalent to) deterministic general event structures do support hiding, and construct a new category of games based on them with a deterministic interpretation of aPCFpor, an affine variant of PCF extended with parallel-or. We then exploit this deterministic interpretation to give a relaxed notion of determinism (observable determinism) on the plain event structures model. Putting this together with our previously introduced concurrent notions of well-bracketing and innocence, we obtain an intensionally fully abstract model of aPCFpor

Games and Strategies as Event Structures.

In 2011, Rideau and Winskel introduced concurrent games and strategies as event structures, generalizing prior work on causal formulations of games. In this paper we give a detailed, self-contained and slightly-updated account of the results of Rideau and Winskel: a notion of pre-strategy based on event structures; a characterisation of those pre-strategies (deemed strategies) which are preserved by composition with a copycat strategy; and the construction of a bicategory of these strategies. Furthermore, we prove that the corresponding category has a compact closed structure, and hence forms the basis for the semantics of concurrent higher-order computation

Physiologically Based Pharmacokinetic Modelling of Cytochrome P450 2C9-Related Tolbutamide Drug Interactions with Sulfaphenazole and Tasisulam

Background and Objectives: Cytochrome P450 2C9 (CYP2C9) is involved in the biotransformation of many commonly used drugs, and significant drug interactions have been reported for CYP2C9 substrates. Previously published physiologically based pharmacokinetic (PBPK) models of tolbutamide are based on an assumption that its metabolic clearance is exclusively through CYP2C9; however, many studies indicate that CYP2C9 metabolism is only responsible for 80–90% of the total clearance. Therefore, these models are not useful for predicting the magnitude of CYP2C9 drug–drug interactions (DDIs). This paper describes the development and verification of SimCYP-based PBPK models that accurately describe the human pharmacokinetics of tolbutamide when dosed alone or in combination with the CYP2C9 inhibitors sulfaphenazole and tasisulam. Methods: A PBPK model was optimized in SimCYP for tolbutamide as a CYP2C9 substrate, based on published in vitro and clinical data. This model was verified to replicate the magnitude of DDI reported with sulfaphenazole and was further applied to simulate the DDI with tasisulam, a small molecule investigated for the treatment of cancer. A clinical study (CT registration # NCT01185548) was conducted in patients with cancer to assess the pharmacokinetic interaction of tasisulum with tolbutamide. A PBPK model was built for tasisulam, and the clinical study design was replicated using the optimized tolbutamide model. Results: The optimized tolbutamide model accurately predicted the magnitude of tolbutamide AUC increase (5.3–6.2-fold) reported for sulfaphenazole. Furthermore, the PBPK simulations in a healthy volunteer population adequately predicted the increase in plasma exposure of tolbutamide in patients with cancer (predicted AUC ratio = 4.7–5.4; measured mean AUC ratio = 5.7). Conclusions: This optimized tolbutamide PBPK model was verified with two strong CYP2C9 inhibitors and can be applied to the prediction of CYP2C9 interactions for novel inhibitors. Furthermore, this work highlights the utility of mechanistic models in navigating the challenges in conducting clinical pharmacology studies in cancer patients

Structures concurrentes en sémantique des jeux

Game semantics is an effective tool to study and model abstractly programming languages from a mathematical point of view, by keeping enough concrete information on the structure of programs but yet leaving aside superfluous details. During my PhD thesis, I worked on merging game semantics with event structures to propose truly concurrent denotational models of higher-order concurrent languages. In the first part, I build a model based on this merge, retaining enough information about the behaviour of programs to interpret adequately a large variety of concurrent programming languages for various notions of convergence. The construction of this model is based on the introduction of symmetry to prove that the model is indeed in a cartesian-closed category. In the second part, I propose a generalization, in this setting, of innocence and well-bracketing, key notions in game semantics to understand the computational effects, and thusly closing openproblems of game semantics about concurrent and nondeterministic innocence.In the last part, I propose an interpretation in this model of concurrent languages with weak shared memory, one of the first works of denotational semantics for these kinds of languages. Althoughtheoretical, these models are compositional and based on partial orders, and thus could permit scaling verification of concurrent programs (an important problem of the domain).La sémantique des jeux permet l'étude et la modélisation abstraite des langages de programmation d'un point de vue mathématique, en gardant assez d'informations concrètes sur la structure des programmes, mais en laissant de côté les détails superflus. Durant mon doctorat, j'ai travaillé sur l'association de la sémantique des jeux avec les structures d'événements pour proposer des modèles dénotationnels vraiment concurrents de langages concurrents d'ordresupérieur. Dans un premier temps, je construis un modèle réalisant cette association, qui retient suffisamment d'informations sur le comportement des programmes pour interpréter adéquatement une grande variété de langages concurrents et non déterministes pour des notions fines de convergences. La construction de ce modèle se base surl'introduction de symétrie afin d'établir que le modèle forme une catégorie cartésienne fermée. Dans un second temps, je propose une généralisation dans ce cadre des notions d'innocence et de bon parenthésage, essentielles en sémantiquedes jeux pour comprendre les effets calculatoires, et résolvant ainsi des problèmes ouverts de la sémantique des jeux concernant l'innocence concurrente et non-déterministe. Dans un dernier temps je propose une interprétation dans ce modèle, de langages concurrents avec mémoire faible, un des premiers travaux de sémantique dénotationnelle pour ce type de langages. Bien que théoriques, ces modèles sont compositionnels et basés sur des ordres partiels, et donc pourraient permettre de faire passer la vérification de programmes concurrents à l'échelle (une problématique importante du domaine)

La stratégie de la fourchette

National audienceDans cet article, on se propose d'utiliser les développements récentsde sémantique des jeux basés sur des ordres partiels pour donner unesémantique dénotationnelle à une primitive de concurrence inspirée del'appel système UNIX fork. Cet appel système, lors de son invocation,duplique le contexte d'exécution de son programme, et renvoie deuxentiers distincts permettant au programme de savoir dans quelle dentde la fourche il se trouve.La première contribution de cet article est de donner une sémantiqueopérationnelle faisant droit au parfum opérateur de contrôle de cetteprimitive qui manipule le contexte d'exécution. La secondecontribution de ce papier est l'élaboration d'une sémantique des jeux« vraiment concurrente » qui donne une représentation fine del'exécution du langage.Cette sémantique des jeux est prouvée correcte vis-à-vis de lasémantique opérationnelle et permet de faire un premier pas vers lamodélisation de comportements concurrents complexes en utilisant lesjeux concurrents