Single-cell analysis of TORC1 and PKA signalling during the budding yeast cell cycle:towards a holistic view of growth and division

Cell growth, characterized by the accumulation of biomass, and the cell division process, are fundamental for cell survival and reproduction. Classically, it was thought that cell growth was independent from the cell cycle, but recent studies showed that the activity of several processes related to biomass accumulation are dependent on the cell cycle phase. How the activity of these processes is coordinated with cell cycle progression is still unknown. In budding yeast, the two main regulators of cell growth are the evolutionarily conserved Target of Rapamycin Complex 1 (TORC1) and Protein Kinase A (PKA) pathways. Given that TORC1 and PKA are also known to interact with cell cycle machinery components, it is possible that they mediate the coordination of cell growth with the cell cycle. In this thesis we investigate the connections of TORC1 and PKA with the budding yeast cell cycle. By using single-cell analysis we revealed oscillations of TORC1 and PKA activity during the unperturbed budding yeast cell cycle, with a peak during G1 and minima at budding and in late mitosis. Furthermore, continuous inhibition of TORC1 or PKA decreases biomass accumulation and cell cycle progression both in G1 and during S/G2/M, and alters cell size both at budding and at the end of G2/M. Finally, changing the metabolic activity of the cell perturbs TORC1 and PKA cell-cycle dynamics and so do deletions of cell cycle machinery components showing that TORC1 and PKA mediate the interconnection of fundamental cellular processes such as metabolism, growth and cell cycle progression

On the mass transport by a Burgers velocity field

The mass transport by a Burgers velocity field is investigated in the framework of the theory of stochastic processes. Much attention is devoted to the limit of vanishing viscosity (inviscid limit) describing the "adhesion model" for the early stage of the evolution of the Universe. In particular the mathematical foundations for the ansatz currently used in the literature to compute the mass distribution in the inviscid limit are provided.Comment: 14 pages, Latex, revised version submitted to Physica

Novità e tendenze nel quadro normativo della finanza dei comuni: entrate tributarie e patto di stabilità

In the first part of the paper we present and discuss the new legislation, on both local taxes and the Internal Stability Pact, enacted in Italy between September 2006 and December 2007. The most important aspects concern: the “thawing” of the income surtax levied by local government; the introduction of “dynamic” allocation of funding from the personal income tax (Irpef) to guarantee municipalities an automatic source of income, and an earmarked tax to finance local investments; new rules on property rates (Ici) mainly intended to reduce taxation on the principal family home; the legalisation of the use of property development dues for financing current expenditure; the temporary halt to the switch from waste disposal tax (Tarsu) to charges for the same service (Tia); the new rules included in the Internal Stability Pact, passed as part of the 2007 Budget and partially relaxed by the 2008 Budget, which first and foremost replace expenditure with deficit as the main indicator of municipalities’ financial rectitude. In the second part we analyse the principles of the bill on fiscal federalism proposed by the Council of Ministers in August 2007, and discuss its expected effects on the financing of municipalities. We mainly refer to the problems of financial coordination between the different levels of government, and the fiscal autonomy of municipalities. We focus in particular on the problems involved in financing the national standard levels of service set for social and health services and long term-care, which are the responsibility of central government but are actually delivered by regional and local authorities.local taxation; intergovernmental financial coordination; fiscal federalism

Enforced generative patterns for the specification of the syntax and semantics of visual languages

This is the author’s version of a work that was accepted for publication in Journal of Visual Languages and Computing. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Visual Languages and Computing,19, 4 (2008) DO: 10.1016/j.jvlc.2008.04.004Selected Papers from IEEE Symposium on Visual Languages and Human Centric Computing 2007 (VL/HCC 2007)We present the new notion of enforced generative pattern, a structure that declares positive or negative conditions that must be satisfied by a model. Patterns are applied to transformation rules resulting in new rules that modify models according to the pattern specification. In the case of a negative pattern, an application condition is added to the rule. In the case of a positive one, the rule is modified to consider additional context in its left-hand side and to increase its effects. We have defined these patterns in an abstract setting, which enables their instantiation for different structures, like graphs, triple graphs and graph transformation rules. We apply the previous concepts to the specification of the syntax and semantics of visual languages. In particular, we show instantiations for: (i) graphs, with applications at the syntactical level; (ii) triple graphs, for the coordination of syntax and static semantics; and (iii) rules, for the incremental construction of execution rules. We present some examples that illustrate the usefulness of the combination of these three instantiations. In particular, we show the specification of environments for visual languages with token-holder semantics, discrete-event semantics and communication semantics.Work supported by the Spanish Ministry of Education and Science, projects MOSAIC (TSI2005-08225-C07-06) and MODUWEB (TIN2006-09678). We thank the referees for their detailed and useful com- ments, which helped us in improving the paper

Triple patterns: Compact specifications for the generation of operational triple graph grammar rules

Proceedings of the Sixth International Workshop on Graph Transformation and Visual Modeling Techniques (GT-VMT 2007)Triple Graph Grammars (TGGs) allow the specification of high-level rules modelling the synchronized creation of elements in two graphs related through a correspondence graph. Low-level operational rules are then derived to manipulate concrete graphs. However, TGG rules may become unnecessarily verbose when elements have to be replicated from one graph to the other, and their actual derivation cannot exploit the presence of reoccurring patterns. Moreover they do not take advantage from situations in which a normal creation grammar for one of the graphs exists, from which TGG operational rules can be derived to build the other graph. We present an approach to generating TGG operational rules from normal ones, reducing the information needed to derive them, through the definition of Triple Patterns, a high-level, compact, declarative, and visual notation for the description of admissible structures in a triple graph. Patterns can be expressed with respect to classes defined in a meta-model, and instantiated with derived classes at the model level, thus exploiting the inheritance hierarchies. The application of the generated rules results into the (synchronized or batch) creation of the structures specified in the patterns. We illustrate these concepts by showing their application to the synchronized incremental construction of visual models and of their semantics.This work has been partially sponsored by the Spanish Ministry of Education and Science with projects MOSAIC (TSI2005-08225-C07-06) and MODUWEB (TIN 2006-09678), and the EC’s Human Potential Programme under contract HPRN-CT-2002-00275, SegraVis. The authors gratefully thank the referees for their useful suggestion

Towards a Formal Notion of Interaction Pattern

Proceedings of: IEEE Symposium on Visual Languages and Human-Centric Computing (VL/HCC 2010). Leganés-Madrid, Spain 21-25 Septemeber 2010.While interaction patterns are becoming widespread in the field of interface design, their definitions do not enjoy a common standard yet, as is for software patterns. Moreover, patterns are developed for diverse design aspects, reflecting the complexity of the field. As a consequence, research on formalization of interaction patterns is not developed, and few attempts have been made to extend techniques developed for design pattern formalization. We show here how an extension to our recent approach to pattern formalization can be usefully employed to formalize some classes of interaction patterns, to express relations among them, and to detect conflicts.Work funded by the Spanish Ministry of Science and Innovation through mobility grants JC2009-00015 and PR2009-0019, project TIN2008-02081 (METEORIC) and the R&D programme of the Madrid Community, project S2009/TIC-1650 (e-Madrid).Publicad

Action patterns for the incremental specification of the execution semantics of visual languages

Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works. P. Bottoni, J. de Lara, and E. Guerra, "Action Patterns for the Incremental Specification of the Execution Semantics of Visual Languages", IEEE Symposium on Visual Languages and Human-Centric Computing, 2007. VL/HCC 2007,Coeur d'Alene, ID, 2007, pp. 163-170We present a new approach - based on graph transformation - to incremental specification of the operational (execution) semantics of visual languages. The approach combines editing rules with two meta-models: one to define the concrete syntax and one for the static semantics. We introduce the notion of action patterns, defining basic actions (e.g. consuming or producing a token in transition-based semantics), in a way similar to graph transformation rules. The application of action patterns to a static semantics editing rule produces a meta-rule, to be paired with the firing of the corresponding syntactic rule to incrementally build an execution rule. An execution rule is thus tailored to any active element (e.g. a transition in a Petri net model) in the model. Examples from Petri nets, state automata and workflow languages illustrate these ideas.Work sponsored by the EC with contract HPRN-CT-2002-00275, SegraVis, and the Spanish Ministry of Science and Education, projects MD2 (TIC200303654) and MOSAIC (TSI2005-08225-C07-06

Pattern-based Rewriting through Abstraction

Fundamenta Informaticae, vol. 144, no. 2, pp. 109-160, 2016, Copyright 2016, with permission from IOS PressModel-based development relies on models in different phases for different purposes, with modelling patterns being used to document and gather knowledge about good practices in specific domains, to analyse the quality of existing designs, and to guide the construction and refactoring of models. Providing a formal basis for the use of patterns would also support their integration with existing approaches to model transformation. To this end, we turn to the commonly used, in this context, machinery of graph transformations and provide an algebraic-categorical formalization of modelling patterns, which can express variability and required/forbidden application contexts. This allows the definition of transformation rules having patterns in left and right-hand sides, which can be used to express refactorings towards patterns, change the use of one pattern by a different one, or switch between pattern variants. A key element in our proposal is the use of operations to abstract models into patterns, so that they can be manipulated by pattern rules, thus leading to a rewriting mechanism for classes of graphs described by patterns and not just individual graphs. The proposal is illustrated with examples in object-oriented software design patterns and enterprise architecture patterns, but can be applied to any other domain where patterns are used for modelling.This work has been partially supported by the Spanish Ministry of Economy and Competitivity with projects Go-Lite (TIN2011-24139) and Flexor (TIN2014-52129-R), the Madrid Region with project SICOMORO (S2013/ICE-3006), and the EU commission with project MONDO (FP7-ICT-2013-10, #611125)

Action patterns for the incremental specification of the execution semantics of visual languages

Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works. P. Bottoni, J. de Lara, and E. Guerra, "Action Patterns for the Incremental Specification of the Execution Semantics of Visual Languages", IEEE Symposium on Visual Languages and Human-Centric Computing, 2007. VL/HCC 2007,Coeur d'Alene, ID, 2007, pp. 163-170We present a new approach - based on graph transformation - to incremental specification of the operational (execution) semantics of visual languages. The approach combines editing rules with two meta-models: one to define the concrete syntax and one for the static semantics. We introduce the notion of action patterns, defining basic actions (e.g. consuming or producing a token in transition-based semantics), in a way similar to graph transformation rules. The application of action patterns to a static semantics editing rule produces a meta-rule, to be paired with the firing of the corresponding syntactic rule to incrementally build an execution rule. An execution rule is thus tailored to any active element (e.g. a transition in a Petri net model) in the model. Examples from Petri nets, state automata and workflow languages illustrate these ideas.Work sponsored by the EC with contract HPRN-CT-2002-00275, SegraVis, and the Spanish Ministry of Science and Education, projects MD2 (TIC200303654) and MOSAIC (TSI2005-08225-C07-06

A Language-Independent and Formal Approach to Pattern-Based Modelling with Support for Composition and Analysis

Context: Patterns are used in different disciplines as a way to record expert knowledge for problem solving in specific areas. Their systematic use in Software Engineering promotes quality, standardization, reusability and maintainability of software artefacts. The full realisation of their power is however hindered by the lack of a standard formalization of the notion of pattern. Objective: Our goal is to provide a language-independent formalization of the notion of pattern, so that it allows its application to different modelling languages and tools, as well as generic methods to enable pattern discovery, instantiation, composition, and conflict analysis. Method: For this purpose, we present a new visual and formal, language-independent approach to the specification of patterns. The approach is formulated in a general way, based on graphs and category theory, and allows the specification of patterns in terms of (nested) variable submodels, constraints on their allowed variance, and inter-pattern synchronization across several diagrams (e.g. class and sequence diagrams for UML design patterns). Results: We provide a formal notion of pattern satisfaction by models and propose mechanisms to suggest model transformations so that models become consistent with the patterns. We define methods for pattern composition, and conflict analysis. We illustrate our proposal on UML design patterns, and discuss its generality and applicability on different types of patterns, e.g. workflow patterns, enterprise integration patterns and interaction patterns. Conclusion: The approach has proven to be powerful enough to formalize patterns from different domains, providing methods to analyse conflicts and dependencies that usually are expressed only in textual form. Its language independence makes it suitable for integration in meta-modelling tools and for use in Model-Driven Engineering.This work has been supported by the Visiting Professor Programmes of ‘‘Sapienza” University of Rome and its Department of Computer Science, the R&D program of the Community of Madrid (S2009/TIC-1650, project ‘‘e-Madrid”), the CAM-UC3M project ‘‘EXPLORE” (CCG08-UC3M/TIC-4487), as well as by the Spanish Ministry of Science and Innovation, under project ‘‘METEORIC” (TIN2008-02081), and mobility Grants JC2009-00015 and PR2009-0019.Publicad