Verification of Ptime reducibility for system F terms via Dual Light Affine Logic.

Proceedings of Computer Science Logic 2006 (CSL'06), volume 4207 of Lecture Notes in Computer Science, pp.150-166. � SpringerIn a previous work we introduced Dual Light Affine Logic (DLAL) ([BaillotTerui04]) as a variant of Light Linear Logic suitable for guaranteeing complexity properties on lambda-calculus terms: all typable terms can be evaluated in polynomial time and all Ptime functions can be represented. In the present work we address the problem of typing lambda-terms in second-order DLAL. For that we give a procedure which, starting with a term typed in system F, finds all possible ways to decorate it into a DLAL typed term. We show that our procedure can be run in time polynomial in the size of the original Church typed system F term

Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders:Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients

RIPK1 is a master regulator of inflammatory signaling and cell death and increased RIPK1 activity is observed in human diseases, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). RIPK1 inhibition has been shown to protect against cell death in a range of preclinical cellular and animal models of diseases. SAR443060 (previously DNL747) is a selective, orally bioavailable, central nervous system (CNS)-penetrant, small-molecule, reversible inhibitor of RIPK1. In three early-stage clinical trials in healthy subjects and patients with AD or ALS (NCT03757325 and NCT03757351), SAR443060 distributed into the cerebrospinal fluid (CSF) after oral administration and demonstrated robust peripheral target engagement as measured by a reduction in phosphorylation of RIPK1 at serine 166 (pRIPK1) in human peripheral blood mononuclear cells compared to baseline. RIPK1 inhibition was generally safe and well-tolerated in healthy volunteers and patients with AD or ALS. Taken together, the distribution into the CSF after oral administration, the peripheral proof-of-mechanism, and the safety profile of RIPK1 inhibition to date, suggest that therapeutic modulation of RIPK1 in the CNS is possible, conferring potential therapeutic promise for AD and ALS, as well as other neurodegenerative conditions. However, SAR443060 development was discontinued due to long-term nonclinical toxicology findings, although these nonclinical toxicology signals were not observed in the short duration dosing in any of the three early-stage clinical trials. The dose-limiting toxicities observed for SAR443060 preclinically have not been reported for other RIPK1-inhibitors, suggesting that these toxicities are compound-specific (related to SAR443060) rather than RIPK1 pathway-specific

Typage et réduction optimale pour le lambda dans des variantes de la logique linéaire pour la complexité implicite

Le lambda-calcul a été introduit pour étudier les fonctions mathématiques d un point de vue calculatoire. Il a ensuite servi de fondement au développement des langages de prgrammation fonctionnels. Savoir si il existe une méthode prouvablement la plus e cace pour réduire les lambda-termes, et connaître la complexité intrinsèque de cette opération en général sont toujours des questions ouvertes. Dans cette thèse, nous utilisons les outils du typage, de l inférence de type, de la Logique linéaire et de la Réduction optimale pour explorer ces questions. Nous présentons un algorithme d inférence de type pour Dual light a ne logic (dlal), un système de type qui caractérise la classe de complexité polynomiale. L algorithme prend en entrée un lambda-terme typé dans le système F et renvoie un typage dans dlal si il en existe un. Une implémentation est fournie. Puis, nous étendons un système de type fondé sur Elementary a ne logic avec du sous-typage, a n d automatiser le placement des cœrcicions. Nous montrons que le sous-typage capture bien les cœrcicions, et nous donnons un algorithme d inférence complet pour ce système étendu. En n, nous adaptons l algorithme de Réduction optimale de Lamping pour les lambda-termes typables dans Soft linear logic (sll), une logique qui caractérise le temps polynomial. Nous montrons qu une borne polynomiale existe pour tous les graphes de partage ainsi réduits, et que les lambda termes typables dans sll sont réduits correctement.Lambda-calculus has been introduced to study the mathematical functions from a computational point of view. It has then been used as a basis for the design of functional programming languages. Knowing whether there exists a provably most e cient method to reduce lambda-terms, and evaluate the complexity of this operation in general are still open questions. In this thesis, we use the tools of typing, of Linear logic, of type inference and of Optimal reduction to explore those questions. We present a type inference algorithm for Dual light a ne logic (dlal), a type system which characterises the polynomial time complexity class. The algorithm takes in input a system F typed lambda-term, and outputs a typing in dlal if there exists one. An implementation is provided. Then, we extend a type system based on Elementary a ne logic with subtyping, in order to automatise the cœrcions placement. We show that subtyping captures indeed the cœrcions, and we give a fully- edged type inference algorithm for this extended system. Finally, we adapt Lamping s Optimal reduction algorithm to the lambdaterms typable in Soft linear logic (sll), also characterising polynomial time. We prove a complexity bound on the reduction of any Sharing graph, and that lambda-terms typable in sll can be correctly reduced with our ad-hoc Optimal reduction algorithm.PARIS13-BU Sciences (930792102) / SudocSudocFranceF

Verification of Ptime Reducibility for system F Terms: Type Inference in Dual Light Affine Logic

In a previous work Baillot and Terui introduced Dual light affine logic(DLAL) as a variant of Light linear logic suitable for guaranteeing complexityproperties on lambda calculus terms: all typable terms can be evaluated inpolynomial time by beta reduction and all Ptime functions can be represented.In the present work we address the problem of typing lambda-terms insecond-order DLAL. For that we give a procedure which, starting with a termtyped in system F, determines whether it is typable in DLAL and outputs aconcrete typing if there exists any. We show that our procedure can be run intime polynomial in the size of the original Church typed system F term.Comment: 32 pages, 8 figure

Synthèse et caractérisation d'une série de bis‐9,9′(thio‐9‐acridinyl)‐α,ω‐alcanes

Une méthode rapide de préparation de composés diacridiniques soufrés pontés en position 9,9′, est décrite. Le pontage est réalisé par des dihalogénoalcanes en utilisant la catalyse en transfert de phase. Les caractéristiques physicochimiques de 61 composés, en particulier leurs paramètres de rmn du 1H et du 13C, sont présentées. Copyright © 1986 Journal of Heterocyclic ChemistrySCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

A change in the fingertip contact area induces an illusory displacement of the finger

Moscatelli A, Bianchi M, Serio A, et al. A change in the fingertip contact area induces an illusory displacement of the finger. In: Proceedings of the EuroHaptics Society Meeting. Springer; 2014