129 research outputs found

    Supporting Smart Home Scenarios Using OWL and SWRL Rules

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    Despite the pervasiveness of IoT domotic devices in the home automation landscape, their potential is still quite under-exploited due to the high heterogeneity and the scarce expressivity of the most commonly adopted scenario programming paradigms. The aim of this study is to show that Semantic Web technologies constitute a viable solution to tackle not only the interoperability issues, but also the overall programming complexity of modern IoT home automation scenarios. For this purpose, we developed a knowledge-based home automation system in which scenarios are the result of logical inferences over the IoT sensors data combined with formalised knowledge. In particular, we describe how the SWRL language can be employed to overcome the limitations of the well-known trigger-action paradigm. Through various experiments in three distinct scenarios, we demonstrated the feasibility of the proposed approach and its applicability in a standardised and validated context such as SARE

    FMAP: Distributed Cooperative Multi-Agent Planning

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    This paper proposes FMAP (Forward Multi-Agent Planning), a fully-distributed multi-agent planning method that integrates planning and coordination. Although FMAP is specifically aimed at solving problems that require cooperation among agents, the flexibility of the domain-independent planning model allows FMAP to tackle multi-agent planning tasks of any type. In FMAP, agents jointly explore the plan space by building up refinement plans through a complete and flexible forward-chaining partial-order planner. The search is guided by h D T G , a novel heuristic function that is based on the concepts of Domain Transition Graph and frontier state and is optimized to evaluate plans in distributed environments. Agents in FMAP apply an advanced privacy model that allows them to adequately keep private information while communicating only the data of the refinement plans that is relevant to each of the participating agents. Experimental results show that FMAP is a general-purpose approach that efficiently solves tightly-coupled domains that have specialized agents and cooperative goals as well as loosely-coupled problems. Specifically, the empirical evaluation shows that FMAP outperforms current MAP systems at solving complex planning tasks that are adapted from the International Planning Competition benchmarks.This work has been partly supported by the Spanish MICINN under projects Consolider Ingenio 2010 CSD2007-00022 and TIN2011-27652-C03-01, the Valencian Prometeo project II/2013/019, and the FPI-UPV scholarship granted to the first author by the Universitat Politecnica de Valencia.Torreño Lerma, A.; Onaindia De La Rivaherrera, E.; Sapena Vercher, O. (2014). FMAP: Distributed Cooperative Multi-Agent Planning. Applied Intelligence. 41(2):606-626. https://doi.org/10.1007/s10489-014-0540-2S606626412Benton J, Coles A, Coles A (2012) Temporal planning with preferences and time-dependent continuous costs. In: Proceedings of the 22nd international conference on automated planning and scheduling (ICAPS). AAAI, pp 2–10Borrajo D. (2013) Multi-agent planning by plan reuse. In: Proceedings of the 12th international conference on autonomous agents and multi-agent systems (AAMAS). IFAAMAS, pp 1141–1142Boutilier C, Brafman R (2001) Partial-order planning with concurrent interacting actions. J Artif Intell Res 14(105):136Brafman R, Domshlak C (2008) From one to many: planning for loosely coupled multi-agent systems. In: Proceedings of the 18th international conference on automated planning and scheduling (ICAPS). AAAI, pp 28–35Brenner M, Nebel B (2009) Continual planning and acting in dynamic multiagent environments. J Auton Agents Multiagent Syst 19(3):297–331Bresina J, Dearden R, Meuleau N, Ramakrishnan S, Smith D, Washington R (2002) Planning under continuous time and resource uncertainty: a challenge for AI. In: Proceedings of the 18th conference on uncertainty in artificial intelligence (UAI). Morgan Kaufmann, pp 77–84Cox J, Durfee E (2009) Efficient and distributable methods for solving the multiagent plan coordination problem. Multiagent Grid Syst 5(4):373–408Crosby M, Rovatsos M, Petrick R (2013) Automated agent decomposition for classical planning. In: Proceedings of the 23rd international conference on automated planning and scheduling (ICAPS). AAAI, pp 46–54Dimopoulos Y, Hashmi MA, Moraitis P (2012) μ-satplan: Multi-agent planning as satisfiability. Knowl-Based Syst 29:54–62Fikes R, Nilsson N (1971) STRIPS: a new approach to the application of theorem proving to problem solving. Artif Intell 2(3):189–208Gerevini A, Haslum P, Long D, Saetti A, Dimopoulos Y (2009) Deterministic planning in the fifth international planning competition: PDDL3 and experimental evaluation of the planners. Artif Intell 173(5-6):619–668Ghallab M, Nau D, Traverso P (2004) Automated planning. Theory and practice. Morgan KaufmannGünay A, Yolum P (2013) Constraint satisfaction as a tool for modeling and checking feasibility of multiagent commitments. Appl Intell 39(3):489–509Helmert M (2004) A planning heuristic based on causal graph analysis. In: Proceedings of the 14th international conference on automated planning and scheduling ICAPS. AAAI, pp 161–170Hoffmann J, Nebel B (2001) The FF planning system: fast planning generation through heuristic search. J Artif Intell Res 14:253–302Jannach D, Zanker M (2013) Modeling and solving distributed configuration problems: a CSP-based approach. IEEE Trans Knowl Data Eng 25(3):603–618Jonsson A, Rovatsos M (2011) Scaling up multiagent planning: a best-response approach. In: Proceedings of the 21st international conference on automated planning and scheduling (ICAPS). AAAI, pp 114–121Kala R, Warwick K (2014) Dynamic distributed lanes: motion planning for multiple autonomous vehicles. Appl Intell:1–22Koehler J, Ottiger D (2002) An AI-based approach to destination control in elevators. AI Mag 23(3):59–78Kovacs DL (2011) Complete BNF description of PDDL3.1. Technical reportvan der Krogt R (2009) Quantifying privacy in multiagent planning. Multiagent Grid Syst 5(4):451–469Kvarnström J (2011) Planning for loosely coupled agents using partial order forward-chaining. In: Proceedings of the 21st international conference on automated planning and scheduling (ICAPS). AAAI, pp 138–145Lesser V, Decker K, Wagner T, Carver N, Garvey A, Horling B, Neiman D, Podorozhny R, Prasad M, Raja A et al (2004) Evolution of the GPGP/TAEMS domain-independent coordination framework. Auton Agents Multi-Agent Syst 9(1–2):87–143Long D, Fox M (2003) The 3rd international planning competition: results and analysis. J Artif Intell Res 20:1–59Nissim R, Brafman R, Domshlak C (2010) A general, fully distributed multi-agent planning algorithm. In: Proceedings of the 9th international conference on autonomous agents and multiagent systems (AAMAS). IFAAMAS, pp 1323–1330O’Brien P, Nicol R (1998) FIPA - towards a standard for software agents. BT Tech J 16(3):51–59Öztürk P, Rossland K, Gundersen O (2010) A multiagent framework for coordinated parallel problem solving. Appl Intell 33(2):132–143Pal A, Tiwari R, Shukla A (2013) Communication constraints multi-agent territory exploration task. Appl Intell 38(3):357–383Richter S, Westphal M (2010) The LAMA planner: guiding cost-based anytime planning with landmarks. J Artif Intell Res 39(1):127–177de la Rosa T, García-Olaya A, Borrajo D (2013) A case-based approach to heuristic planning. Appl Intell 39(1):184–201Sapena O, Onaindia E (2008) Planning in highly dynamic environments: an anytime approach for planning under time constraints. Appl Intell 29(1):90–109Sapena O, Onaindia E, Garrido A, Arangú M (2008) A distributed CSP approach for collaborative planning systems. Eng Appl Artif Intell 21(5):698–709Serrano E, Such J, Botía J, García-Fornes A (2013) Strategies for avoiding preference profiling in agent-based e-commerce environments. Appl Intell:1–16Smith D, Frank J, Jónsson A (2000) Bridging the gap between planning and scheduling. Knowl Eng Rev 15(1):47–83Such J, García-Fornes A, Espinosa A, Bellver J (2012) Magentix2: a privacy-enhancing agent platform. Eng Appl Artif Intell:96–109Tonino H, Bos A, de Weerdt M, Witteveen C (2002) Plan coordination by revision in collective agent based systems. Artif Intell 142(2):121–145Torreño A, Onaindia E, Sapena O (2012) An approach to multi-agent planning with incomplete information. In: Proceedings of the 20th European conference on artificial intelligence (ECAI), vol 242. IOS Press, pp 762–767Torreño A, Onaindia E, Sapena O (2014) A flexible coupling approach to multi-agent planning under incomplete information. Knowl Inf Syst 38(1):141–178Van Der Krogt R, De Weerdt M (2005) Plan repair as an extension of planning. In: Proceedings of the 15th international conference on automated planning and scheduling (ICAPS). AAAI, pp 161–170de Weerdt M, Clement B (2009) Introduction to planning in multiagent systems. Multiagent Grid Syst 5(4):345– 355Yokoo M, Durfee E, Ishida T, Kuwabara K (1998) The distributed constraint satisfaction problem: formalization and algorithms. IEEE Trans Knowl Data Eng 10(5):673–685Zhang J, Nguyen X, Kowalczyk R (2007) Graph-based multi-agent replanning algorithm. In: Proceedings of the 6th international joint conference conference on autonomous agents and multiagent systems (AAMAS). IFAAMAS, pp 798–80

    A flexible coupling approach to multi-agent planning under incomplete information

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    The final publication is available at Springer via http://dx.doi.org/10.1007/s10115-012-0569-7Multi-agent planning (MAP) approaches are typically oriented at solving loosely coupled problems, being ineffective to deal with more complex, strongly related problems. In most cases, agents work under complete information, building complete knowledge bases. The present article introduces a general-purpose MAP framework designed to tackle problems of any coupling levels under incomplete information. Agents in our MAP model are partially unaware of the information managed by the rest of agents and share only the critical information that affects other agents, thus maintaining a distributed vision of the task. Agents solve MAP tasks through the adoption of an iterative refinement planning procedure that uses single-agent planning technology. In particular, agents will devise refinements through the partial-order planning paradigm, a flexible framework to build refinement plans leaving unsolved details that will be gradually completed by means of new refinements. Our proposal is supported with the implementation of a fully operative MAP system and we show various experiments when running our system over different types of MAP problems, from the most strongly related to the most loosely coupled.This work has been partly supported by the Spanish MICINN under projects Consolider Ingenio 2010 CSD2007-00022 and TIN2011-27652-C03-01, and the Valencian Prometeo project 2008/051.Torreño Lerma, A.; Onaindia De La Rivaherrera, E.; Sapena Vercher, O. (2014). A flexible coupling approach to multi-agent planning under incomplete information. Knowledge and Information Systems. 38:141-178. https://doi.org/10.1007/s10115-012-0569-7S14117838Argente E, Botti V, Carrascosa C, Giret A, Julian V, Rebollo M (2011) An abstract architecture for virtual organizations: the THOMAS approach. Knowl Inf Syst 29(2):379–403Barrett A, Weld DS (1994) Partial-order planning: evaluating possible efficiency gains. Artif Intell 67(1):71–112Belesiotis A, Rovatsos M, Rahwan I (2010) Agreeing on plans through iterated disputes. In: Proceedings of the 9th international conference on autonomous agents and multiagent systems. pp 765–772Bellifemine F, Poggi A, Rimassa G (2001) JADE: a FIPA2000 compliant agent development environment. In: Proceedings of the 5th international conference on autonomous agents (AAMAS). ACM, pp 216–217Blum A, Furst ML (1997) Fast planning through planning graph analysis. Artif Intell 90(1–2):281–300Boutilier C, Brafman R (2001) Partial-order planning with concurrent interacting actions. J Artif Intell Res 14(105):136Brafman R, Domshlak C (2008) From one to many: planning for loosely coupled multi-agent systems. In: Proceedings of the 18th international conference on automated planning and scheduling (ICAPS). pp 28–35Brenner M, Nebel B (2009) Continual planning and acting in dynamic multiagent environments. J Auton Agents Multiag Syst 19(3):297–331Coles A, Coles A, Fox M, Long D (2010) Forward-chaining partial-order planning. In: Proceedings of the 20th international conference on automated planning and scheduling (ICAPS). pp 42–49Coles A, Fox M, Long D, Smith A (2008) Teaching forward-chaining planning with JavaFF. In: Colloquium on AI education, 23rd AAAI conference on artificial intelligenceCox J, Durfee E, Bartold T (2005) A distributed framework for solving the multiagent plan coordination problem. In: Proceedings of the 4th international joint conference on autonomous agents and multiagent systems (AAMAS). ACM, pp 821–827de Weerdt M, Clement B (2009) Introduction to planning in multiagent systems. Multiag Grid Syst 5(4):345–355Decker K, Lesser VR (1992) Generalizing the partial global planning algorithm. Int J Coop Inf Syst 2(2):319–346desJardins M, Durfee E, Ortiz C, Wolverton M (1999) A survey of research in distributed continual planning. AI Mag 20(4):13–22Doshi P (2007) On the role of interactive epistemology in multiagent planning. In: Artificial intelligence and, pattern recognition. pp 208–213Dréo J, Savéant P, Schoenauer M, Vidal V (2011) Divide-and-evolve: the marriage of descartes and darwin. In: Proceedings of the 7th international planning competition (IPC). Freiburg, GermanyDurfee EH (2001) Distributed problem solving and planning. In: Multi-agents systems and applications: selected tutorial papers from the 9th ECCAI advanced course (ACAI) and agentLink’s third European agent systems summer school (EASSS), vol LNAI 2086. Springer, pp 118–149Durfee EH, Lesser V (1991) Partial global planning: a coordination framework for distributed hypothesis formation. IEEE Trans Syst Man Cybern Special Issue Distrib Sens Netw 21(5):1167–1183Ephrati E, Rosenschein JS (1996) Deriving consensus in multiagent systems. Artif Intell 87(1–2):21–74Fikes R, Nilsson N (1971) STRIPS: a new approach to the application of theorem proving to problem solving. Artif Intell 2(3):189–208Fogués R, Alberola J, Such J, Espinosa A, Garcia-Fornes A (2010) Towards dynamic agent interaction support in open multiagent systems. In: Proceedings of the 2010 conference on artificial intelligence research and development: proceedings of the 13th international conference of the Catalan association for artificial intelligence’. IOS Press, pp 89–98Gerevini A, Long D (2006) Preferences and soft constraints in PDDL3. In: ICAPS workshop on planning with preferences and soft constraints, vol 6. Citeseer, pp 46–53Ghallab M, Howe A, Knoblock C, McDermott D, Ram A, Veloso M, Weld D, Wilkins D (1998) PDDL-the Planning Domain Definition Language. In: AIPS-98 planning committeeGmytrasiewicz P, Doshi P (2005) A framework for sequential planning in multi-agent settings. J Artif Intell Res 24:49–79Haslum P, Jonsson P (1999) Some results on the complexity of planning with incomplete information. In: Proceedings of the 5th European conference on, planning (ECP). pp 308–318Helmert M (2006) The fast downward planning system. J Artif Intell Res 26(1):191–246Hoffmann J, Nebel B (2001) The FF planning system: fast planning generation through heuristic search. J Artif Intell Res 14:253–302Jonsson A, Rovatsos M (2011) Scaling up multiagent planning: a best-response approach. In: Proceedings of the 21st international conference on automated planning and scheduling (ICAPS). AAAI, pp 114–121Kambhampati S (1997) Refinement planning as a unifying framework for plan synthesis. AI Mag 18(2):67–97Kaminka GA, Pynadath DV, Tambe M (2002) Monitoring teams by overhearing: a multi-agent plan-recognition approach. J Artif Intell Res 17:83–135Kone M, Shimazu A, Nakajima T (2000) The state of the art in agent communication languages. Knowl Inf Syst 2(3):259–284Kovacs DL (2011) Complete BNF description of PDDL3.1. Technical reportKraus S (1997) Beliefs, time and incomplete information in multiple encounter negotiations among autonomous agents. Ann Math Artif Intell 20(1–4):111–159Kumar A, Zilberstein S, Toussaint M (2011) Scalable multiagent planning using probabilistic inference. In: Proceedings of the 22nd international joint conference on artificial intelligence (IJCAI)’. Barcelona, Spain, pp 2140–2146Kvarnström J. (2011) Planning for loosely coupled agents using partial order forward-chaining. In: Proceedings of the 21st international conference on automated planning and scheduling (ICAPS). AAAI, pp 138–145Lesser V, Decker K, Wagner T, Carver N, Garvey A, Horling B, Neiman D, Podorozhny R, Prasad M, Raja A et al (2004) Evolution of the GPGP/TAEMS domain-independent coordination framework. Auton Agents Multi Agent Syst 9(1):87–143Lipovetzky N, Geffner H (2011) Searching for plans with carefully designed probes. In: Proceedings of the 21th international conference on automated planning and scheduling (ICAPS)Micacchi C, Cohen R (2008) A framework for simulating real-time multi-agent systems. Knowl Inf Syst 17(2):135–166Nguyen N, Katarzyniak R (2009) Actions and social interactions in multi-agent systems. Knowl Inf Syst 18(2):133–136Nguyen X, Kambhampati S (2001) Reviving partial order planning. In: Proceedings of the 17th international joint conference on artificial intelligence (IJCAI). Morgan Kaufmann, pp 459–464Nissim R, Brafman R, Domshlak C (2010) A general, fully distributed multi-agent planning algorithm. In: Proceedings of the 9th international conference on autonomous agents and multiagent systems (AAMAS). pp 1323–1330Pajares S, Onaindia E (2012) Defeasible argumentation for multi-agent planning in ambient intelligence applications. In: Proceedings of the 11th international conference on autonomous agents and multiagent systems (AAMAS) pp 509–516Paolucci M, Shehory O, Sycara K, Kalp D, Pannu A (2000) A planning component for RETSINA agents. Intelligent Agents VI. Agent Theories Architectures, and Languages pp 147–161Parsons S, Sierra C, Jennings N (1998) Agents that reason and negotiate by arguing. J Logic Comput 8(3):261Penberthy J, Weld D (1992) UCPOP: a sound, complete, partial order planner for ADL. In: Proceedings of the 3rd international conference on principles of knowledge representation and reasoning (KR). Morgan Kaufmann, pp 103–114Richter S, Westphal M (2010) The LAMA planner: guiding cost-based anytime planning with landmarks. J Artif Intell Res 39(1):127–177Sycara K, Pannu A (1998) The RETSINA multiagent system (video session): towards integrating planning, execution and information gathering. In: Proceedings of the 2nd international conference on autonomous agents (Agents). ACM, pp 350–351Tambe M (1997) Towards flexible teamwork. J Artif Intell Res 7:83–124Tang Y, Norman T, Parsons S (2010) A model for integrating dialogue and the execution of joint plans. Argumentation in multi-agent systems, pp 60–78Tonino H, Bos A, de Weerdt M, Witteveen C (2002) Plan coordination by revision in collective agent based systems. Artif Intell 142(2):121–145Van Der Krogt R, De Weerdt M (2005), Plan repair as an extension of planning. In: Proceedings of the 15th international conference on automated planning and scheduling (ICAPS). pp 161–170Weld D (1994) An introduction to least commitment planning. AI Mag 15(4):27Weld D (1999) Recent advances in AI planning. AI Mag 20(2):93–123Wilkins D, Myers K (1998) A multiagent planning architecture. In: Proceedings of the 4th international conference on artificial intelligence planning systems (AIPS), pp 154–162Wu F, Zilberstein S, Chen X (2011) Online planning for multi-agent systems with bounded communication. Artif Intell 175(2):487–511Younes H, Simmons R (2003) VHPOP: versatile heuristic partial order planner. J Artif Intell Res 20: 405–430Zhang J, Nguyen X, Kowalczyk R (2007) Graph-based multi-agent replanning algorithm. In: Proceedings of the 6th conference on autonomous agents and multiagent systems (AAMAS

    A randomised controlled trial evaluating family mediated exercise (FAME) therapy following stroke

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    <p>Abstract</p> <p>Background</p> <p>Stroke is a leading cause of disability among adults worldwide. Evidence suggests that increased duration of exercise therapy following stroke has a positive impact on functional outcome following stroke. The main objective of this randomised controlled trial is to evaluate the impact of additional family assisted exercise therapy in people with acute stroke.</p> <p>Methods/Design</p> <p>A prospective multi-centre single blind randomised controlled trial will be conducted. Forty patients with acute stroke will be randomised into either an experimental or control group. The experimental group will receive routine therapy and additional lower limb exercise therapy in the form of family assisted exercises. The control group will receive routine therapy with no additional formal input from their family members. Participants will be assessed at baseline, post intervention and followed up at three months using a series of standardised outcome measures. A secondary aim of the project is to evaluate the impact of the family mediated exercise programme on the person with stroke and the individual(s) assisting in the delivery of exercises using a qualitative methodology. The study has gained ethical approval from the Research Ethics Committees of each of the clinical sites involved in the study.</p> <p>Discussion</p> <p>This study will evaluate a structured programme of exercises that can be delivered to people with stroke by their 'family members/friends'. Given that the progressive increase in the population of older people is likely to lead to an increased prevalence of stroke in the future, it is important to reduce the burden of this illness on the individual, the family and society. Family mediated exercises can maximise the carry over outside formal physiotherapy sessions, giving patients the opportunity for informal practice.</p> <p>Trial Registration</p> <p>The protocol for this study is registered with the US NIH Clinical trials registry (NCT00666744)</p

    Competitive Benchmarking: An IS Research Approach to Address Wicked Problems with Big Data and Analytics

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    Wicked problems like sustainable energy and financial market stability are societal challenges that arise from complex socio-technical systems in which numerous social, economic, political, and technical factors interact. Understanding and mitigating them requires research methods that scale beyond the traditional areas of inquiry of Information Systems (IS) “individuals, organizations, and markets” and that deliver solutions in addition to insights. We describe an approach to address these challenges through Competitive Benchmarking (CB), a novel research method that helps interdisciplinary research communities to tackle complex challenges of societal scale by using different types of data from a variety of sources such as usage data from customers, production patterns from producers, public policy and regulatory constraints, etc. for a given instantiation. Further, the CB platform generates data that can be used to improve operational strategies and judge the effectiveness of regulatory regimes and policies. We describe our experience applying CB to the sustainable energy challenge in the Power Trading Agent Competition (Power TAC) in which more than a dozen research groups from around the world jointly devise, benchmark, and improve IS-based solutions

    Biological Characterisation of Haliclona (?gellius) sp.: Sponge and Associated Microorganisms

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    We have characterised the northern Pacific undescribed sponge Haliclona (?gellius) sp. based on rDNA of the sponge and its associated microorganisms. The sponge is closely related to Amphimedon queenslandica from the Great Barrier Reef as the near-complete 18S rDNA sequences of both sponges were identical. The microbial fingerprint of three specimens harvested at different times and of a transplanted specimen was compared to identify stably associated microorganisms. Most bacterial phyla were detected in each sample, but only a few bacterial species were determined to be stably associated with the sponge. A sponge-specific β- and γ-Proteobacterium were abundant clones and both of them were present in three of the four specimens analysed. In addition, a Planctomycete and a Crenarchaea were detected in all sponge individuals. Both were closely related to operational taxonomic units that have been found in other sponges, but not exclusively in sponges. Interestingly, also a number of clones that are closely related to intracellular symbionts from insects and amoeba were detected

    Process Mining for Six Sigma

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    Process mining offers a set of techniques for gaining data-based insights into business processes from event logs. The literature acknowledges the potential benefits of using process mining techniques in Six Sigma-based process improvement initiatives. However, a guideline that is explicitly dedicated on how process mining can be systematically used in Six Sigma initiatives is lacking. To address this gap, the Process Mining for Six Sigma (PMSS) guideline has been developed to support organizations in systematically using process mining techniques aligned with the DMAIC (Define-Measure-Analyze-Improve-Control) model of Six Sigma. Following a design science research methodology, PMSS and its tool support have been developed iteratively in close collaboration with experts in Six Sigma and process mining, and evaluated by means of focus groups, demonstrations and interviews with industry experts. The results of the evaluations indicate that PMSS is useful as a guideline to support Six Sigma-based process improvement activities. It offers a structured guideline for practitioners by extending the DMAIC-based standard operating procedure. PMSS can help increasing the efficiency and effectiveness of Six Sigma-based process improving efforts. This work extends the body of knowledge in the fields of process mining and Six Sigma, and helps closing the gap between them. Hence, it contributes to the broad field of quality management

    Serendipitous alkylation of a Plk1 ligand uncovers a new binding channel

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    We obtained unanticipated synthetic byproducts from alkylation of the δ[superscript 1] nitrogen (N3) of the histidine imidazole ring of the polo-like kinase-1 (Plk1) polo-box domain (PBD)-binding peptide PLHSpT. For the highest-affinity byproduct, bearing a C[subscript 6]H[subscript 5](CH[subscript 2])[subscript 8]– group, a Plk1 PBD cocrystal structure revealed a new binding channel that had previously been occluded. An N-terminal PEGylated version of this peptide containing a hydrolytically stable phosphothreonyl residue (pT) bound the Plk1 PBD with affinity equal to that of the non-PEGylated parent but showed markedly less interaction with the PBDs of the two closely related proteins Plk2 and Plk3. Treatment of cultured cells with this PEGylated peptide resulted in delocalization of Plk1 from centrosomes and kinetochores and in chromosome misalignment that effectively induced mitotic block and apoptotic cell death. This work provides insights that might advance efforts to develop Plk1 PBD-binding inhibitors as potential Plk1-specific anticancer agents.National Institutes of Health (U.S.) (Grant GM60594)National Institutes of Health (U.S.) (Grant GM68762)National Institutes of Health (U.S.) (Grant CA112967

    Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

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    OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)
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