306 research outputs found

    Reasoning about context in uncertain pervasive computing environments

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    Context-awareness is a key to enabling intelligent adaptation in pervasive computing applications that need to cope with dynamic and uncertain environments. Addressing uncertainty is one of the major issues in context-based situation modeling and reasoning approaches. Uncertainty can be caused by inaccuracy, ambiguity or incompleteness of sensed context. However, there is another aspect of uncertainty that is associated with human concepts and real-world situations. In this paper we propose and validate a Fuzzy Situation Inference (FSI) technique that is able to represent uncertain situations and reflect delta changes of context in the situation inference results. The FSI model integrates fuzzy logic principles into the Context Spaces (CS) model, a formal and general context reasoning and modeling technique for pervasive computing environments. The strengths of fuzzy logic for modeling and reasoning of imperfect context and vague situations are combined with the CS model's underlying theoretical basis for supporting context-aware pervasive computing scenarios. An implementation and evaluation of the FSI model are presented to highlight the benefits of the FSI technique for context reasoning under uncertainty</p

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

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    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

    Thawing the Frozen Heart: Turning to Antonio Machado to Overcome the Silence in \u3cem\u3eEl corazón helado\u3c/em\u3e by Almudena Grandes

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    In an attempt to demonstrate Spain\u27s obligation to recover its ignored historic memory, Almudena Grandes evokes the poetry of a man whose past itself has been manipulated, misused and partially forgotten: the great poet Antonio Machado. In this study I examine the use of the famous two Spain imagery from Machado\u27s Españolito as a tool for subverting many erroneous concepts about the war that, according to Grandes, are still prevalent in Spanish society. I also examine how this two Spain conflict demonstrates the crossroads that faces the third generation of Spaniards after the Civil War: that of collectively remaining in silence or turning openly to the past. To capture this conflict Grandes uses images of water and ice as symbols of the fluidity (or lack of fluidity) of time, images similarly used by Machado throughout much of his poetry. As Ãlvaro, the protagonist, progressively discovers the past his father had so desperately tried to hide, his heart breaks free of the ice that had surrounded his life. His example demonstrates the actions that Grandes desires for a society that still suffers from the effects of the prevailing historic ignorance: that of turning to the past for a foundation on which to build. By evoking Machado´s name and exploring similar imageries, Grandes not only strengthens him as a defender of the Republic but suggests that the only way for Spain to become normal again is to turn to the Republic and its ideals and build upon what they started and what has been overlooked since the Civil War

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

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    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

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

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    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

    DNA2 drives processing and restart of reversed replication forks in human cells

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    Accurate processing of stalled or damaged DNA replication forks is paramount to genomic integrity and recent work points to replication fork reversal and restart as a central mechanism to ensuring high-fidelity DNA replication. Here, we identify a novel DNA2- and WRN-dependent mechanism of reversed replication fork processing and restart after prolonged genotoxic stress. The human DNA2 nuclease and WRN ATPase activities functionally interact to degrade reversed replication forks with a 5'-to-3' polarity and promote replication restart, thus preventing aberrant processing of unresolved replication intermediates. Unexpectedly, EXO1, MRE11, and CtIP are not involved in the same mechanism of reversed fork processing, whereas human RECQ1 limits DNA2 activity by preventing extensive nascent strand degradation. RAD51 depletion antagonizes this mechanism, presumably by preventing reversed fork formation. These studies define a new mechanism for maintaining genome integrity tightly controlled by specific nucleolytic activities and central homologous recombination factors

    Spinal manipulation and mobilisation among infants, children, and adolescents: an international Delphi survey of expert physiotherapists

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    Objective: The aim of this study was to establish international consensus regarding the use of spinal manipulation and mobilisation among infants, children, and adolescents among expert international physiotherapists. Methods: Twenty-six international expert physiotherapists in manual therapy and paediatrics voluntarily participated in a 3-Round Delphi survey to reach a consensus via direct electronic mail solicitation using Qualtrics®. Consensus was defined a-priori as ≥75% agreement on all items with the same ranking of agreement or disagreement. Round 1 identified impairments and conditions where spinal mobilisation and manipulation might be utilised. In Rounds 2 and 3, panelists agreed or disagreed using a 4-point Likert scale. Results: Eleven physiotherapists from seven countries representing five continents completed all three Delphi rounds. Consensus regarding spinal mobilisation or manipulation included: Manipulation is not recommended: (1) for infants across all conditions, impairments, and spinal levels; and (2) for children and adolescents across most conditions and spinal levels. Manipulation may be recommended for adolescents to treat spinal region-specific joint hypomobility (thoracic, lumbar), and pain (thoracic). Mobilisation may be recommended for children and adolescents with hypomobility, joint pain, muscle/myofascial pain, or stiffness at all spinal levels.Conclusion: Consensus revealed spinal manipulation should not be performed on infants regardless of condition, impairment, or spinal level. Additionally, the panel agreed that manipulation may be recommended only for adolescents to treat joint pain and joint hypomobility (limited to thoracic and/or lumbar levels). Spinal mobilisation may be recommended for joint hypomobility, joint pain, muscle/myofascial pain, and muscle/myofascial stiffness at all spinal levels among children and adolescents.</p

    Perceived factors and barriers affecting physiotherapists’ decision to use spinal manipulation and mobilisation among infants, children, and adolescents: an international survey

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    Objective: To identify factors and barriers, which affect the utilisation of spinal manipulation and mobilisation among infants, children, and adolescents. Methods: Twenty-six international expert physiotherapists in manual therapy and paediatrics were invited to participate in a Delphi investigation using QualtricsⓇ. In Round-1 physiotherapists selected from a list of factors and barriers affecting their decision to use spinal manipulation and mobilisation in the paediatric population and had opportunity to add to the list. Round-2 asked respondents to select as many factors and barriers that they agreed with, resulting in a frequency count. The subset of responses to questions around barriers and facilitators are the focus of this study. Results: Twelve physiotherapists completed both rounds of the survey. Medical diagnosis, mechanism of injury, patient presentation, tolerance to handling, and therapist’s knowledge of techniques were the dominant deciding factors to use spinal manipulation and mobilisation among infants, children, and adolescents across spinal levels. More than 90% of the respondents selected manipulation as inappropriate among infants as their top barrier. Additional dominant barriers to using spinal manipulation among infants and children identified by ≥ 75% of the respondents included fear of injuring the patient, fear of litigation, lack of communication, lack of evidence, lack of guardian consent, and precision of the examination to inform clinical reasoning. Conclusion: This international survey provides much needed insight regarding the factors and barriers physiotherapists should consider when contemplating the utilisation of spinal mobilisation and manipulation in the paediatric population.</p

    OLAP queries context-aware recommender system

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    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

    A Rule-Based Contextual Reasoning Platform for Ambient Intelligence Environments

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    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
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