Significance of the dissociation of Dna2 by flap endonuclease 1 to Okazaki fragment processing in Saccharomyces cerevisiae

Okazaki fragments are initiated by short RNA/DNA primers, which are displaced into flap intermediates for processing. Flap endonuclease 1 (FEN1) and Dna2 are responsible for flap cleavage. Replication protein A (RPA)-bound flaps inhibit cleavage by FEN1 but stimulate Dna2, requiring that Dna2 cleaves prior to FEN1. Upon cleavage, Dna2 leaves a short flap, which is then cut by FEN1 forming a nick for ligation. Both enzymes require a flap with a free 5'-end for tracking to the cleavage sites. Previously, we demonstrated that FEN1 disengages the tracking mechanism of Dna2 to remove it from the flap. To determine why the disengagement mechanism evolved, we measured FEN1 dissociation of Dna2 on short RNA and DNA flaps, which occur during flap processing. Dna2 tracked onto these flaps but could not cleave, presenting a block to FEN1 entry. However, FEN1 disengaged these nonproductively bound Dna2 molecules, proceeding on to conduct proper cleavage. These results clarify the importance of disengagement. Additional results showed that flap substrate recognition and tracking by FEN1, as occur during fragment processing, are required for effective displacement of the flap-bound Dna2. Dna2 was recently shown to dissociate flap-bound RPA, independent of cleavage. Using a nuclease-defective Dna2 mutant, we reconstituted the sequential dissociation reactions in the proposed RPA/Dna2/FEN1 pathway showing that, even without cutting, Dna2 enables FEN1 to cleave RPA-coated flaps. In summary, RPA, Dna2, and FEN1 have evolved highly coordinated binding properties enabling one protein to succeed the next for proper and efficient Okazaki flap processing

A novel context ontology to facilitate interoperation of semantic services in environments with wearable devices

The LifeWear-Mobilized Lifestyle with Wearables (Lifewear) project attempts to create Ambient Intelligence (AmI) ecosystems by composing personalized services based on the user information, environmental conditions and reasoning outputs. Two of the most important benefits over traditional environments are 1) take advantage of wearable devices to get user information in a nonintrusive way and 2) integrate this information with other intelligent services and environmental sensors. This paper proposes a new ontology composed by the integration of users and services information, for semantically representing this information. Using an Enterprise Service Bus, this ontology is integrated in a semantic middleware to provide context-aware personalized and semantically annotated services, with discovery, composition and orchestration tasks. We show how these services support a real scenario proposed in the Lifewear project

A Rule-Based Contextual Reasoning Platform for Ambient Intelligence Environments

The special characteristics and requirements of intelligent environments impose several challenges to the reasoning processes of Ambient Intelligence systems. Such systems must enable heterogeneous entities operating in open and dynamic environments to collectively reason with imperfect context information. Previously we introduced Contextual Defeasible Logic (CDL) as a contextual reasoning model that addresses most of these challenges using the concepts of context, mappings and contextual preferences. In this paper, we present a platform integrating CDL with Kevoree, a component-based software framework for Dynamically Adaptive Systems. We explain how the capabilities of Kevoree are exploited to overcome several technical issues, such as communication, information exchange and detection, and explain how the reasoning methods may be further extended. We illustrate our approach with a running example from Ambient Assisted Living. © 2013 Springer-Verlag Berlin Heidelberg

OLAP queries context-aware recommender system

It becomes hard and tedious to easily obtain relevant decisional data in large data warehouses. In order to ease user exploration during on-line analytical processing analysis, recommender systems are developed. However some recommendations can be inappropriate (irrelevant queries or non-computable queries). To overcome these mismatches, we propose to integrate contextual data into the recommender system. In this paper, we provide (i) an indicator of obsolescence for OLAP queries and (ii) a context-aware recommender system based on a contextual post-filtering for OLAP queries

Addressing the evolution of automated user behaviour patterns by runtime model interpretation

The final publication is available at Springer via http://dx.doi.org/10.1007/s10270-013-0371-3The use of high-level abstraction models can facilitate and improve not only system development but also runtime system evolution. This is the idea of this work, in which behavioural models created at design time are also used at runtime to evolve system behaviour. These behavioural models describe the routine tasks that users want to be automated by the system. However, users¿ needs may change after system deployment, and the routine tasks automated by the system must evolve to adapt to these changes. To facilitate this evolution, the automation of the specified routine tasks is achieved by directly interpreting the models at runtime. This turns models into the primary means to understand and interact with the system behaviour associated with the routine tasks as well as to execute and modify it. Thus, we provide tools to allow the adaptation of this behaviour by modifying the models at runtime. This means that the system behaviour evolution is performed by using high-level abstractions and avoiding the costs and risks associated with shutting down and restarting the system.This work has been developed with the support of MICINN, under the project EVERYWARE TIN2010-18011, and the support of the Christian Doppler Forschungsgesellschaft and the BMWFJ, Austria.Serral Asensio, E.; Valderas Aranda, PJ.; Pelechano Ferragud, V. (2013). Addressing the evolution of automated user behaviour patterns by runtime model interpretation. Software and Systems Modeling. https://doi.org/10.1007/s10270-013-0371-3SWeiser, M.: The computer of the 21st century. Sci. Am. 265, 66–75 (1991)Serral, E., Valderas, P., Pelechano, V.: Context-adaptive coordination of pervasive services by interpreting models during runtime. Comput. J. 56(1), 87–114 (2013)Ajila, S.A., Alam, S.: Using a formal language constructs for software model evolution. In: Third IEEE International Conference on Semantic Computing (IEEE-ICSC 2009). Berkeley, CA, USA, pp. 390–395 (2009)Bennett, K., Rajlich, V.: Software Maintenance and Evolution: A Roadmap. In: 22nd International Conference on Software Engineering (ICSE 2000). Limerick, Ireland, pp. 75–87 (2000)Mens, T.: The ERCIM working group on software evolution: the past and the future. In: Proceedings of the Joint International and Annual ERCIM Workshops on Principles of Software Evolution (IWPSE) and Software Evolution (Evol) Workshops. ACM (2009)Mens, T., Wermelinger, M., Ducasse, S., Demeyer, S., Hirschfeld, R.: Challenges in software evolution. In: Report of the ChaSE 2005 Workshop Organised by the ERCIM Working Group on Software Evolution. IWPSE-05. Lisbon, Portugal, pp. 13–22 (2005)Hirschfeld, R., Kawamura, K., Berndt, H.: Dynamic service adaptation for runtime system extensions. In: Wireless On-Demand Network Systems, pp. 227–240. Springer, Berlin, Heidelberg, Madonna di Campiglio, Italy (2004)Lientz, B.P., Swanson, E.B.: Software maintenance management: a study of the maintenance of computer applications software in 487 data processing organizations. Addison-Wesley, Reading, MA (1980)Buckley, J., Mens, T., Zenger, M., Rashid, A., Kniesel, G.: Towards a taxonomy of software change. J. Softw. Maint. Evolut. Res. Pract. 17(5), 309–332 (2003)Hardian, B., Indulska, J., Henricksen, K.: Balancing autonomy and user control in context-aware systems—a survey. In: CoMoRea, IEEE PerCom Workshops 2006. (2006)Biegel, G., Cahill, V.: A framework for developing mobile, context-aware applications. In: The 2nd IEEE Conference on Pervasive Computing and Communication (PerCom), pp. 361–365 (2004)Hofer, T., Schwinger, W., Pichler, M., Leonhartsberger, G., Altmann, J.: Context-awareness on mobile devices—the hydrogen approach. In: The 36th Annual Hawaii International Conference on System Sciences, pp. 292–302 (2002)Dey, A.K.: Understanding and using context. Pers. Ubiquitous Comput. 5(1), 4–7 (2001)Sheng, Q.Z., Benatallah, B.: ContextUML: a UML-based modelling language for model-driven development of context-aware web services. In: Proceedings of the International Conference on Mobile, Business (ICMB’05). pp. 206–212 (2005)Henricksen, K., Indulska, J.: A software engineering framework for context-aware pervasive computing. In: Proceedings of the Second IEEE Annual Conference on Pervasive Computing and Communications (PerCom 2004), pp. 77–86. IEEE, Orlando, FL, USA (2004)Baldauf, M., Dustdar, S., Rosenberg, F.: A survey on context-aware systems. Int. J. Ad Hoc Ubiquitous Comput. 2(4), 263–277 (2007)Ye, J., Coyle, L., Dobson, S., Nixon, P.: Ontology-based models in pervasive computing systems. Knowl. Eng. Rev. 22(4), 315–347 (2007)Chen, H., Finin, T., Joshi, A.: An ontology for context-aware pervasive computing environments. Special Issue on Ontologies for Distributed Systems. Knowl. Eng. Rev. 18(3), 197–207 (2004)Welty, C., McGuinness, D.L.: OWL Web Ontology Language Guide. vol. W3C Recomm. W3C Recommendation 10 Feb 2004 (2004)Shepherd, A.: HTA as a framework for task analysis. Ergonomics 41, 1537–1552 (1998)Serral, E., Valderas, P., Pelechano, V.: Towards the model driven development of context-aware pervasive systems. Special Issue on Context Modelling, Reasoning and Management. PMC 6(2), 254–280 (2010)Serral, E.: Automating Routine Tasks in Smart Environments. A Context-aware Model-driven Approach, Technical University of Valencia (2011)Mellor, S.J., Balcer, M.J.: Executable UML: A Foundation for Model Driven Architecture. Addison-Wesley, Indianapolis (2002)Muñoz, J., Ferragud, D.V.P.: Model Driven Development of Pervasive Systems. Building a Software Factory. Universidad Politécnica de Valencia, Valencia (2008)Juric, M.B., Sarang, P.: Business Process Execution Language for Web Services: BPEL and BPEL4WS (2006)Loke, S.W., Smanchat, S., Ling, S., Indrawan, M.: Formal mirror models: an approach to just-in-time reasoning for device ecologies. Int. J. Smart Home 2(1), 15–32 (2008)Code Generation conference. http://www.codegeneration.net/cg2010/ (2010)Guy, M.: Report 2: API Good Practice Good practice for provision of and consuming APIs. UKOLN (2009)Bloch, J.: How to design a good API and why it matters. pp. 506–507 (2005)Sirin, E., Parsia, B., Grau, B.C., Kalyanpur, A., Katz, Y.: Pellet: A practical OWL-DL reasoner. J. Web Semant. 5(2), 51–53 (2007)Bernstein, P.: Multiversion concurrency control—theory and algorithms. ACM Trans. Database Syst. 8(4), 465–484 (1983)Cooper, S., Dann, W., Pausch, R.: Alice: a 3-D tool for introductory programming concepts. J. Comput. Sci. Coll. 15, 107–116 (2000)Pérez, F., Valderas, P.: Allowing end-users to actively participate within the elicitation of pervasive system requirements through immediate visualization. In: Fourth International Workshop on Requirements Engineering Visualization (REV), pp. 31–40. IEEE, Atlanta, Georgia, USA (2009)Lieberman, H., Paternó, F., Wulf, V.: End User Development. Springer, Dordrecht (2006)Nielsen, J.: Usability Engineering. Morgan Kaufmann Publishers Inc, San Francisco (1993)Van Welie, M., Trætteberg, H.: Interaction Patterns in User, Interfaces. pp. 13–16 (2000)Galitz, W.O.: The Essential Guide to User Interface Design: An Introduction to GUI Design Principles and Techniques. Wiley, New York (2002)Kitchenham, B., Pickard, L., Pfleeger, S.L.: Case studies for method and tool evaluation. Softw. IEEE 12(4), 52–62 (1995)Wohlin, C., Runeson, P., Höst, M., Ohlsson, M.C., Regnell, B., Wesslén, A.: Experimentation in Software Engineering. Springer, Berlin (2012)Jones, J.V.: Applied software measurement: assuring productivity & quality (2nd ed’97). McGraw-Hill, New York (1997)Strang, T., Linnhoff-Popien, C.: A context modeling survey. In: First International Workshop on Advanced Context Modelling, Reasoning And Management at UbiComp (2004)Lewis, J.R.: Psychometric Evaluation of an After-Scenario Questionnaire for Computer Usability Studies? The ASQ. SIGCHI Bulletin (1991)Cook, D.J., Youngblood, M., Heierman, I.I.I.E.O., Gopalratnam, K., Rao, S., Litvin, A., Khawaja, F.: MavHome: An Agent-based Smart Home. In: First IEEE International Conference on Pervasive Computing and, Communications (PerCom’03), pp. 521–524 (2003)Hagras, H., Callaghan, V., Colley, M., Clarke, G., Pounds-Cornish, A., Duman, H.: Creating an ambient-intelligence environment using embedded agents. IEEE Intell. Syst. 19(6), 12–20 (2004)Rashidi, P., Cook, D.J.: Keeping the resident in the loop: adapting the smart home to the user. IEEE Trans. Syst. Man Cybern. 39(5), 949–959 (2009)Webb, G.I., Pazzani, M.J., Billsus, D.: Machine learning for user modeling. User model. User-Adapt Interact. 11(1–2), 19–29 (2001)Valiant, L.G.: A theory of the learnable. Commun. ACM 27(11), 1134–1142 (1984)Serral, E., Valderas, P., Pelechano, V.: (2011) Improving the cold-start problem in user task automation by using models at runtime. In: Information Systems Development, pp. 671–683. (2011)García-Herranz, M., Haya, P.A., Esquivel, A., Montoro, G., Alamán, X.: Easing the smart home: semi-automatic adaptation in perceptive environments. J. Univers. Comput. Sci. 14(9), 1529–1544 (2008)Henricksen, K., Indulska, J., Rakotonirainy, A.: Using context and preferences to implement self-adapting pervasive computing applications. Sofw. Pract. Exp. 36(11–12), 1307–1330 (2006)Johnson, P.: Tasks and situations: considerations for models and design principles in human computer interaction, pp. 1199–1204. HCI International. Munich, Germany (1999)Cook, D.J., Das, S.K.: Smart environments: technologies, protocols, and applications, vol. 43. Wiley-Interscience, New York (2005)Paternò, F.: ConcurTaskTrees: an Engineered approach to model-based design of interactive systems. In: The Handbook of Analysis for Human-Computer Interaction, pp. 483–500 (2002)Pribeanu, C., Limbourg, Q., Vanderdonckt1, J.: Task modelling for context-sensitive user interfaces. In: Interactive Systems: Design, Specification, and Verification (DSV-IS), pp. 49–68. Springer, Berlin, Heidelberg 2001, Glasgow, Scotland, UK (2001)Souchon, N., Limbourg, Q., Vanderdonckt., J.: Task modelling in multiple contexts of use. In: Interactive Systems: Design, Specification, and Verification (DSV-IS), pp. 59–73 (2002)Huang, R., Cao, Q., Zhou, J., Sun, D., Su, Q.: Context-aware active task discovery for pervasive computing. In: International Conference on Computer Science and Software Engineering, pp. 463–466. IEEE, Wuhan, China (2008)Sousa, J.P., Poladian, V., Garlan, D., Schmerl, B.: Task-based adaptation for ubiquitous computing. IEEE Trans. Syst. Man Cybern. 36(3), 328–340 (2006)Masuoka, R., Parsia, B., Labrou, Y.: Task Computing—The Semantic Web Meets Pervasive Computing. In: 2nd International Semantic Web Conference on the Semantic Web (ISWC 2003), pp. 866–881. vol. LNCS 2870. Sanibel Island, FL, USA (2003)Oreizy, P., Gorlick, M.M., Taylor, R.N., Heimbigner, D., Johnson, G., Medvidovic, N., Quilici, A., Rosenblum, D.S., Wolf, A.L.: An architecture-based approach to self-adaptive software. IEEE Intell. Syst. Their Appl. 14(3), 54–62 (1999)Floch, J., Hallsteinsen, S., Stav, E., Eliassen, F., Lund, K., Gjørven, E.: Using Architecture Models for Runtime Adaptability. IEEE Software. 23(2), 62–70 (2006)Morin, B., Jézéquel, J.-M., Fleurey, F., Solberg, A.: Models at runtime to support dynamic adaptation. IEEE Comput. Soc. pp. 46–53 (2009)Cetina, C., Giner, P., Fons, J., Pelechano, V.: Using feature models for developing self-configuring smart homes. In: Fifth International Conference on Autonomic and Autonomous Systems, pp. 179–188. IEEE, Valencia, Spain (2009)Garlan, D., Schmerl, B.: Using architectural models at runtime: research challenges. In: Proceedings of the European Workshop on Software Architectures, pp. 200–205. Springer, Berlin, Heidelberg, St Andrews, UK (2004)Blumendorf, M., Lehmann, G., Feuerstack, S., Albayrak, S.: Executable models for human-computer interaction. In: Interactive Systems, Design, Specification, and Verification Workshop (DSV-IS 2008), pp. 238–251. Springer Berlin Heidelberg, Kingston, Canada (2008)Ballagny, C., Hameurlain, N., Barbier, F.: MOCAS: a state-based component model for self-adaptation. In: Third IEEE International Conference on Self-Adaptive and Self-Organizing Systems, pp. 206–215. IEEE, San Francisco, California (2009)Amoui, M., Derakhshanmanesh, M., Ebert, J., Tahvildari, L.: Achieving dynamic adaptation via management and interpretation of runtime models. J. Syst. Softw. 85(12), 2720–2737 (2012)Blair, G., Bencomo, N., France, R.B.: [email protected]. IEEE Comput. 42, 22–27 (2009)Zhang, J., Cheng, B.H.C.: Model based development of dynamically adaptive software. In: International Conference on Software Engineering (ICSE’06), pp. 371–380. ACM, Shanghai, China (2006

A Dynamic Contextual Change Management Application for Real Time Decision-Making Support

Decision making is a fundamental process within organizations for many reasons. It is indeed involved at all levels (new product decisions, management and marketing decisions, etc.) and has a direct impact on companies’ efficiency and effectiveness. Many researches are conducted to enhance the decision-making process by proposing decision support systems where the most frequent challenge is the change management. Indeed, all businesses operate within an environment that is subject to constant changes (like new customers’ needs and requirements, organisational and technological changes, changes in key information used to derive decisions, etc.). These changes have a major impact on the quality and accuracy of the proposed decision if they are not detected and propagated, at the right time, during the decision-making process. The present work attempts to resolve this challenge by proposing a dynamic change management technique that allows three tasks to be automatically performed. First, continuously detect changes and note them. Second, retrieve from the detected changes those that are related to the decision rules. Finally, propagate them by computing the new value of the decision rule. The proposal has been fully implemented and tested in the supervision process of gas network exploitation.projet FUI Gontran

RPA and PCNA suppress formation of large deletion errors by yeast DNA polymerase δ

In fulfilling its biosynthetic roles in nuclear replication and in several types of repair, DNA polymerase δ (pol δ) is assisted by replication protein A (RPA), the single-stranded DNA-binding protein complex, and by the processivity clamp proliferating cell nuclear antigen (PCNA). Here we report the effects of these accessory proteins on the fidelity of DNA synthesis in vitro by yeast pol δ. We show that when RPA and PCNA are included in reactions containing pol δ, rates for single base errors are similar to those generated by pol δ alone, indicating that pol δ itself is by far the prime determinant of fidelity for single base errors. However, the rate of deleting multiple nucleotides between directly repeated sequences is reduced by ∼10-fold in the presence of either RPA or PCNA, and by ≥90-fold when both proteins are present. We suggest that PCNA and RPA suppress large deletion errors by preventing the primer terminus at a repeat from fraying and/or from relocating and annealing to a downstream repeat. Strong suppression of deletions by PCNA and RPA suggests that they may contribute to the high replication fidelity needed to stably maintain eukaryotic genomes that contain abundant repetitive sequences

Insights into the mechanism of Rad51 recombinase from the structure and properties of a filament interface mutant

Rad51 protein promotes homologous recombination in eukaryotes. Recombination activities are activated by Rad51 filament assembly on ssDNA. Previous studies of yeast Rad51 showed that His352 occupies an important position at the filament interface, where it could relay signals between subunits and active sites. To investigate, we characterized yeast Rad51 H352A and H352Y mutants, and solved the structure of H352Y. H352A forms catalytically competent but salt-labile complexes on ssDNA. In contrast, H352Y forms salt-resistant complexes on ssDNA, but is defective in nucleotide exchange, RPA displacement and strand exchange with full-length DNA substrates. The 2.5 Å crystal structure of H352Y reveals a right-handed helical filament in a high-pitch (130 Å) conformation with P61 symmetry. The catalytic core and dimer interface regions of H352Y closely resemble those of DNA-bound Escherichia coli RecA protein. The H352Y mutation stabilizes Phe187 from the adjacent subunit in a position that interferes with the γ-phosphate-binding site of the Walker A motif/P-loop, potentially explaining the limited catalysis observed. Comparison of Rad51 H352Y, RecA–DNA and related structures reveals that the presence of bound DNA correlates with the isomerization of a conserved cis peptide near Walker B to the trans configuration, which appears to prime the catalytic glutamate residue for ATP hydrolysis

Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.

Inherited mutations in human PALB2 are associated with a predisposition to breast and pancreatic cancers. PALB2's tumor-suppressing effect is thought to be based on its ability to facilitate BRCA2's function in homologous recombination. However, the biochemical properties of PALB2 are unknown. Here we show that human PALB2 binds DNA, preferentially D-loop structures, and directly interacts with the RAD51 recombinase to stimulate strand invasion, a vital step of homologous recombination. This stimulation occurs through reinforcing biochemical mechanisms, as PALB2 alleviates inhibition by RPA and stabilizes the RAD51 filament. Moreover, PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion. Finally, we show that PALB2-deficient cells are sensitive to PARP inhibitors. Our studies provide the first biochemical insights into PALB2's function with piBRCA2 as a mediator of homologous recombination in DNA double-strand break repair