Relating time progress and deadlines in hybrid systems

Time progress conditions in hybrid systems are usually specified in terms of invariants, predicates characterizing states where time can continuously progress, or in terms of deadline conditions, predicates characterizing states where time progress immediately stops. These specifications are each other's duals. The aim of this work is the study of relationships between general time progress conditions and these generated by using state predicates. It is shown that using deadline conditions or invariants allows to characterize all practically interesting time progress conditions. The study is performed by using a Galois connection between the corresponding lattices. We provide conditions for the connection to be a homomorphism and apply the results to the compositional description of hybrid system

Modeling urgency in timed systems

We define timed automata with deadlines (TAD) which are a class of timed automata where time progress conditions depend on deadlines associated with transitions. We show that using TAD makes urgency specification easier. We present the model of Petri nets with deadlines (PND), which are (1-safe) Petri nets extended with clocks exactly as TAD are extensions of automata. We compare PND with different classes of timed Petri nets (TPNs) and show that safe TPNs can be modeled as PND. Some applications to modeling systems and in particular to modeling multimedia documents are presente

A specification patterns system for discrete event systems analysis

As formal verification tools gain popularity, the problem arises of making them more accessible to engineers. A correct understanding of the logics used to express properties of a system's behavior is needed in order to guarantee that properties correctly encode the intent of the verification process. Writing appropriate properties, in a logic suitable for verification, is a skillful process. Errors in this step of the process can create serious problems since a false sense of safety is gained with the analysis. However, when compared to the effort put into developing and applying modeling languages, little attention has been devoted to the process of writing properties that accurately capture verification requirements. In this paper we illustrate how a collection of property patterns can help in simplifying the process of generating logical formulae from informally expressed requirements

AMPK activation protects against diet induced obesity through Ucp1-independent thermogenesis in subcutaneous white adipose tissue

Obesity results from a chronic imbalance between energy intake and energy output but remains difficult to prevent or treat in humans. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an important regulator of energy homeostasis1,2,3 and is a molecular target of drugs used for the treatment of metabolic diseases, including obesity4,5. Here we show that mice expressing a gain-of-function AMPK mutant6 display a change in morphology of subcutaneous white adipocytes that is reminiscent of browning. However, despite a dramatic increase in mitochondrial content, Ucp1 expression is undetectable in these adipocytes. In response to a high-fat diet (HFD), expression of skeletal muscle–associated genes is induced in subcutaneous white adipocytes from the gain-of-function AMPK mutant mice. Chronic genetic AMPK activation results in protection against diet-induced obesity due to an increase in whole-body energy expenditure, most probably because of a substantial increase in the oxygen consumption rate of white adipose tissue. These results suggest that AMPK activation enriches, or leads to the emergence of, a population of subcutaneous white adipocytes that produce heat via Ucp1-independent uncoupling of adenosine triphosphate (ATP) production on a HFD. Our findings indicate that AMPK activation specifically in adipose tissue may have therapeutic potential for the treatment of obesity

Assignment of PolyProline II Conformation and Analysis of Sequence – Structure Relationship

International audienceBACKGROUND: Secondary structures are elements of great importance in structural biology, biochemistry and bioinformatics. They are broadly composed of two repetitive structures namely α-helices and β-sheets, apart from turns, and the rest is associated to coil. These repetitive secondary structures have specific and conserved biophysical and geometric properties. PolyProline II (PPII) helix is yet another interesting repetitive structure which is less frequent and not usually associated with stabilizing interactions. Recent studies have shown that PPII frequency is higher than expected, and they could have an important role in protein - protein interactions. METHODOLOGY/PRINCIPAL FINDINGS: A major factor that limits the study of PPII is that its assignment cannot be carried out with the most commonly used secondary structure assignment methods (SSAMs). The purpose of this work is to propose a PPII assignment methodology that can be defined in the frame of DSSP secondary structure assignment. Considering the ambiguity in PPII assignments by different methods, a consensus assignment strategy was utilized. To define the most consensual rule of PPII assignment, three SSAMs that can assign PPII, were compared and analyzed. The assignment rule was defined to have a maximum coverage of all assignments made by these SSAMs. Not many constraints were added to the assignment and only PPII helices of at least 2 residues length are defined. CONCLUSIONS/SIGNIFICANCE: The simple rules designed in this study for characterizing PPII conformation, lead to the assignment of 5% of all amino as PPII. Sequence - structure relationships associated with PPII, defined by the different SSAMs, underline few striking differences. A specific study of amino acid preferences in their N and C-cap regions was carried out as their solvent accessibility and contact patterns. Thus the assignment of PPII can be coupled with DSSP and thus opens a simple way for further analysis in this field

Modelling Timeouts without Timelocks

We address the issue of modelling a simple timeout in timed automata. We argue that expression of the timeout in the UPPAAL timed automata model is unsatisfactory since when composed with a component behaviour, the timeout can generate timelocks. In response we consider an alternative timed automata framework - timed automata with deadlines. This framework has the property that timelocks cannot be created when composing automata in parallel. We explore a number of different options for reformulating the timeout in this framework and then we relate them