Scholarly publishing and argument in hyperspace

The World Wide Web is opening up access to documents and data for scholars. However it has not yet impacted on one of the primary activities in research: assessing new findings in the light of current knowledge and debating it with colleagues. The ClaiMaker system uses a directed graph model with similarities to hypertext, in which new ideas are published as nodes, which other contributors can build on or challenge in a variety of ways by linking to them. Nodes and links have semantic structure to facilitate the provision of specialist services for interrogating and visualizing the emerging network. By way of example, this paper is grounded in a ClaiMaker model to illustrate how new claims can be described in this structured way.

The development of a novel in vitro model suitable for the prediction of bioavailability

In vitro studies of drug absorption processes are undertaken to assess drug candidate or formulation suitability, mechanism investigation, and ultimately for the development of predictive models. This study included each of these approaches, with the aim of developing novel in vitro methods for inclusion in a drug absorption model. Two model analgesic drugs, ibuprofen and paracetamol, were selected. The study focused on three main areas, the interaction of the model drugs with co-administered antacids, the elucidation of the mechanisms responsible for the increased absorption rate observed in a novel paracetamol formulation and the development of novel ibuprofen tablet formulations containing alkalising excipients as dissolution promoters.Several novel dissolution methods were developed. A method to study the interaction of drug/excipient mixtures in the powder form was successfully used to select suitable dissolution enhancing exicipents. A method to study intrinsic dissolution rate using paddle apparatus was developed and used to study dissolution mechanisms. Methods to simulate stomach and intestine environments in terms of media composition and volume and drug/antacid doses were developed. Antacid addition greatly increased the dissolution of ibuprofen in the stomach model.Novel methods to measure drug permeability through rat stomach and intestine were developed, using sac methodology. The methods allowed direct comparison of the apparent permeability values obtained. Tissue stability, reproducibility and integrity was observed, with selectivity between paracellular and transcellular markers and hydrophilic and lipophilic compounds within an homologous series of beta-blockers.

A probabilistic model for trust and reputation

This paper concerns the problem of agent trust in an electronic market place. We maintain that agent trust involves making decisions under uncertainty and therefore the phenomenon should be modelled probabilistically. We therefore propose a probabilistic framework that models agent interactions as a Hidden Markov Model (HMM). The observations of the HMM are the interaction outcomes and the hidden state is the underlying probability of a good outcome. The task of deciding whether to interact with another agent reduces to probabilistic inference of the current state of that agent given all previous interaction outcomes. The model is extended to include a probabilistic reputation system which involves agents gathering opinions about other agents and fusing them with their own beliefs. Our system is fully probabilistic and hence delivers the following improvements with respect to previous work: (a) the model assumptions are faithfully translated into algorithms; our system is optimal under those assumptions, (b) It can account for agents whose behaviour is not static with time (c) it can estimate the rate with which an agent's behaviour changes. The system is shown to significantly outperform previous state-of-the-art methods in several numerical experiments. Copyright © 2010, International Foundation for Autonomous Agents and Multiagent Systems (www.ifaamas.org). All rights reserved.

Binocular interaction:Contrast matching and contrast discrimination are predicted by the same model

How do signals from the 2 eyes combine and interact? Our recent work has challenged earlier schemes in which monocular contrast signals are subject to square-law transduction followed by summation across eyes and binocular gain control. Much more successful was a new 'two-stage' model in which the initial transducer was almost linear and contrast gain control occurred both pre- and post-binocular summation. Here we extend that work by: (i) exploring the two-dimensional stimulus space (defined by left- and right-eye contrasts) more thoroughly, and (ii) performing contrast discrimination and contrast matching tasks for the same stimuli. Twenty-five base-stimuli made from 1 c/deg patches of horizontal grating, were defined by the factorial combination of 5 contrasts for the left eye (0.3-32%) with five contrasts for the right eye (0.3-32%). Other than in contrast, the gratings in the two eyes were identical. In a 2IFC discrimination task, the base-stimuli were masks (pedestals), where the contrast increment was presented to one eye only. In a matching task, the base-stimuli were standards to which observers matched the contrast of either a monocular or binocular test grating. In the model, discrimination depends on the local gradient of the observer's internal contrast-response function, while matching equates the magnitude (rather than gradient) of response to the test and standard. With all model parameters fixed by previous work, the two-stage model successfully predicted both the discrimination and the matching data and was much more successful than linear or quadratic binocular summation models. These results show that performance measures and perception (contrast discrimination and contrast matching) can be understood in the same theoretical framework for binocular contrast vision. © 2007 VSP.

Interaction of quinolone antibiotics with the human intestinal CACO-2 cell model

The transport of a group of quinolone antibiotics across the human intestinal model, Caco-2 cells, was investigated. It was found that the transport of the quinolones generally correlated with the lipophilicity of the compounds, indicating the passive diffusional transcellular processes were involved. However, it was observed that the transport in both directions apical-to-basolateral and basolateral-to-apical was not equivalent, and polarised transport occurred. For all the quinolones studied except, BMS-284756-01, it was found that the basolateral-to-apical transport was significantly greater than the apical-to-basolateral transport. This finding suggested that the quinolones underwent a process of active secretion. The pKas and logPs for the quinolones were determined using potentiometric titrations. The measured logP values were compared with those determined using theoretical methods. The theoretical methods for calculating logP including the Moriguchi method correlated poorly with the measured logP values. Further investigations revealed that there may be an active transporter involved in the apical-to-basolateral transport of quinolones as well. This mechanism was sensitive to competing quinolones, but, it was unaffected by the metabolic inhibitor combination of sodium azide (15mM) with 2-deoxy-D-glucose (50mM). The basolateral-to-apical transport of quinolones was found to be sensitive to inhibition by a number of different inhibitors. The metabolic inhibitors, sodium azide (15mM) with 2-deoxy-D-glucose (50mM) and 2,4-dinitrophenol (1mM), were able to reduce the basolateral-to-apical transport of quinolones. A reduction in temperature from 37°C to 2°C caused an 80-fold decrease in the transport of gatifloxacin in both directions, however, this effect was not sufficient to abolish the greater basolateral-to-apical secretion. As with apical-to-basolateral transport, it was found that quinolones competed with gatifloxacin for basolateral-to-apical transport, both ofloxacin (100μM) and norfloxacin (100μM) significantly (P<0.003) decreased the basolateral-to-apical transport of gatifloxacin; however, ciprofloxacin (100μM and 300μM) had no effect. A number of inhibitors of various transport systems were also investigated. It was found that the anion transport inhibitor, probenecid (100 μM) had a significant inhibitory effect on the basolateral-to-apical transport of ciprofloxacin (P=0.039), while the cation transport inhibitor cimetidine (100μM and 500μM) had no effect. The organic anion exchange inhibitor 4,4'diisothiocyanostilbene-2-2' -disulphonic acid DIDS (400μM) also had a significant inhibitory effect (P=O.O 13). The PgP inhibitor and anion exchange inhibitor verapamil (400Mμ) was able to completely abolish the basolateral-to-apical secretion of gatifloxacin and bring it into line with the apical-to-basolateral flux. In conclusion, the apical-to-basolateral and basolateral-toapical transport of quinolones involved an active component. The basolateral-to-apical secretion was abolished by a verapamil (400μM), a bisubstrate for PgP and the anion transporter.

A four-factor user interaction model for content-based image retrieval

In order to bridge the “Semantic gap”, a number of relevance feedback (RF) mechanisms have been applied to content-based image retrieval (CBIR). However current RF techniques in most existing CBIR systems still lack satisfactory user interaction although some work has been done to improve the interaction as well as the search accuracy. In this paper, we propose a four-factor user interaction model and investigate its effects on CBIR by an empirical evaluation. Whilst the model was developed for our research purposes, we believe the model could be adapted to any content-based search system.

The development of a computer simulation model of the interaction between the supply and usage of major components in car assembly you use in stock control

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Integration of a graph-based model indexer in commercial modelling tools

Softeam has over 20 years of experience providing UML-based modelling solutions, such as its Modelio modelling tool, and its Constellation enterprise model management and collaboration environment. Due to the increasing number and size of the models used by Softeam’s clients, Softeam joined the MONDO FP7 EU research project, which worked on solutions for these scalability challenges and produced the Hawk model indexer among other results. This paper presents the technical details and several case studies on the integration of Hawk into Softeam’s toolset. The first case study measured the performance of Hawk’s Modelio support using varying amounts of memory for the Neo4j backend. In another case study, Hawk was integrated into Constellation to provide scalable global querying of model repositories. Finally, the combination of Hawk and the Epsilon Generation Language was compared against Modelio for document generation: for the largest model, Hawk was two orders of magnitude faster.