A System of Interaction and Structure

This paper introduces a logical system, called BV, which extends multiplicative linear logic by a non-commutative self-dual logical operator. This extension is particularly challenging for the sequent calculus, and so far it is not achieved therein. It becomes very natural in a new formalism, called the calculus of structures, which is the main contribution of this work. Structures are formulae submitted to certain equational laws typical of sequents. The calculus of structures is obtained by generalising the sequent calculus in such a way that a new top-down symmetry of derivations is observed, and it employs inference rules that rewrite inside structures at any depth. These properties, in addition to allow the design of BV, yield a modular proof of cut elimination.Comment: This is the authoritative version of the article, with readable pictures, in colour, also available at . (The published version contains errors introduced by the editorial processing.) Web site for Deep Inference and the Calculus of Structures at <http://alessio.guglielmi.name/res/cos

Ecumenical modal logic

The discussion about how to put together Gentzen's systems for classical and intuitionistic logic in a single unified system is back in fashion. Indeed, recently Prawitz and others have been discussing the so called Ecumenical Systems, where connectives from these logics can co-exist in peace. In Prawitz' system, the classical logician and the intuitionistic logician would share the universal quantifier, conjunction, negation, and the constant for the absurd, but they would each have their own existential quantifier, disjunction, and implication, with different meanings. Prawitz' main idea is that these different meanings are given by a semantical framework that can be accepted by both parties. In a recent work, Ecumenical sequent calculi and a nested system were presented, and some very interesting proof theoretical properties of the systems were established. In this work we extend Prawitz' Ecumenical idea to alethic K-modalities

Towards a Combinatorial Proof Theory

International audienceThe main part of a classical combinatorial proof is a skew fi-bration, which precisely captures the behavior of weakening and contraction. Relaxing the presence of these two rules leads to certain substruc-tural logics and substructural proof theory. In this paper we investigate what happens if we replace the skew fibration by other kinds of graph homomorphism. This leads us to new logics and proof systems that we call combinatorial

On the Length of Medial-Switch-Mix Derivations

International audienceSwitch and medial are two inference rules that play a central role in many deep inference proof systems. In specific proof systems, the mix rule may also be present. In this paper we show that the maximal length of a derivation using only the inference rules for switch, medial, and mix, modulo associativity and commutativity of the two binary con-nectives involved, is quadratic in the size of the formula at the conclusion of the derivation. This shows, at the same time, the termination of the rewrite system

Adaptation of plasminogen activator sequences to known protease structures

AbstractThe sequences of urokinase (UK) and tissue-type plasminogen activator (TPA) were aligned with those of chymotrypsin, trypsin, and elastase according to their ‘structurally conserved regions’. In spite of its trypsin-like specificity UK was model-built on the basis of the chymotrypsin structure because of a corresponding disulfide pattern. The extra disulfide bond falls to cysteines 50 and 111d. Insertions can easily be accommodated at the surface. As they occur similarly in both, UK and TPA, a role in plasminogen recognition may be possible. Of the functional positions known to be involved in substrate or inhibitor binding, Asp 97, Lys 143 and Arg 217 (Leu in TPA) may contribute to plasminogen activating specificity. PTI binding may in part be impaired by structural differences at the edge of the binding pocket

PPP2R5C couples hepatic glucose and lipid homeostasis

In mammals, the liver plays a central role in maintaining carbohydrate and lipid homeostasis by acting both as a major source and a major sink of glucose and lipids. In particular, when dietary carbohydrates are in excess, the liver converts them to lipids via de novo lipogenesis. The molecular checkpoints regulating the balance between carbohydrate and lipid homeostasis, however, are not fully understood. Here we identify PPP2R5C, a regulatory subunit of PP2A, as a novel modulator of liver metabolism in postprandial physiology. Inactivation of PPP2R5C in isolated hepatocytes leads to increased glucose uptake and increased de novo lipogenesis. These phenotypes are reiterated in vivo, where hepatocyte specific PPP2R5C knockdown yields mice with improved systemic glucose tolerance and insulin sensitivity, but elevated circulating triglyceride levels. We show that modulation of PPP2R5C levels leads to alterations in AMPK and SREBP-1 activity. We find that hepatic levels of PPP2R5C are elevated in human diabetic patients, and correlate with obesity and insulin resistance in these subjects. In sum, our data suggest that hepatic PPP2R5C represents an important factor in the functional wiring of energy metabolism and the maintenance of a metabolically healthy state

Eleven strategies for making reproducible research and open science training the norm at research institutions

Reproducible research and open science practices have the potential to accelerate scientific progress by allowing others to reuse research outputs, and by promoting rigorous research that is more likely to yield trustworthy results. However, these practices are uncommon in many fields, so there is a clear need for training that helps and encourages researchers to integrate reproducible research and open science practices into their daily work. Here, we outline eleven strategies for making training in these practices the norm at research institutions. The strategies, which emerged from a virtual brainstorming event organized in collaboration with the German Reproducibility Network, are concentrated in three areas: (i) adapting research assessment criteria and program requirements; (ii) training; (iii) building communities. We provide a brief overview of each strategy, offer tips for implementation, and provide links to resources. We also highlight the importance of allocating resources and monitoring impact. Our goal is to encourage researchers - in their roles as scientists, supervisors, mentors, instructors, and members of curriculum, hiring or evaluation committees - to think creatively about the many ways they can promote reproducible research and open science practices in their institutions