494 research outputs found

    An object-oriented organic architecture for next generation intelligent reconfigurable mobile networks

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    Next generation mobile networks have great potential in providing personalised and effcient quality of service by using re-confgurable platforms. The foundation is the concept of software radio where both the mobile terminal and the serving network can be re-configurable. This approach becomes more effective when combined with historic-based prediction strategies that enable the system to learn about application behaviour and predict its resource consumption. We extend that concept by proposing the use of an object-oriented intelligent decision making architecture, which supports general and large-scale applications. The proposed architecture applies the principles of business intelligence and data warehousing, together with the concept of organic viable systems. The architecture is applied to the CAST (Configurable radio with Advanced Software Technology) platform

    Intelligent reconfiguration of large mobile networks using complex organic distributed architecture

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    This paper presents a possible solution to the intelligent evolution of mobile systems using a Complex Organic Distributed Architecture (CODA), which supports intelligent reconfiguration of all system components. A key feature of this architecture is the deployment of multiple warehouses. The warehouses store data in a variety of ways depending on the type of intelligence required. On Line Analytical Processing (OLAP) software is used to monitor and control data in the system. An effective system of filters and wrappers ensures that data is secure. A system of feedback loops ensures that information travels through the system quickly and effectively

    Influences on academics' approaches to development: voices from below

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    The purpose of this qualitative case study research was to explore faculty-based academics’ views on what influences their behaviours and attitudes towards their development. Informed by critical realist ontology, the data collection was carried out through narrative interviews with academics in two contrasting English Universities. Findings, or areas for reflection, have emerged about the constraints and enablements academics perceive in respect of their professional development. In particular, themes such as the significance of professional status; misaligned initiatives and priorities; the influence of supportive networks; and emergent personal, individual concerns have surfaced. The conclusion is drawn that the significance of agency raises the importance of responding to the ‘voices from below’

    Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair and p53.

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    The antitumor prodrug Temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (EC 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bi-functional analogs are reported and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bi-functional congener as optimized for potency, MGMT-independence and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development and their improved in vitro activity validates the principles on which they were designed

    Academic freedom in Europe: time for a Magna Charta?

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    This paper is a preliminary attempt to establish a working definition of academic freedom for the European Union states. The paper details why such a definition is required for the European Union and then examines some of the difficulties of defining academic freedom. By drawing upon experience of the legal difficulties beset by the concept in the USA and building on previous analyses of constitutional and legislative protection for academic freedom, and of legal regulations concerning institutional governance and academic tenure, a working definition of academic freedom is then derived. The resultant definition which, it is suggested, could form the basis for a European Magna Charta Libertatis Academicae, goes beyond traditional discussions of academic freedom by specifying not only the rights inherent in the concept but also its accompanying duties, necessary limitations and safeguards. The paper concludes with proposals for how the definition might be tested and carried forward

    The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch

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    The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with Ssubstitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T) as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening

    Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

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    Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

    Development and measurement properties of the AxEL (attitude toward education and advice for low-back-pain) questionnaire

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    Introduction: Clinician time and resources may be underutilised if the treatment they offer does not match patient expectations and attitudes. We developed a questionnaire (AxEL-Q) to guide clinicians toward elements of first-line care that are pertinent to their patients with low back pain. Methods: We used guidance from the COSMIN consortium to develop the questionnaire and evaluated it in a sample of people with low back pain of any duration. Participants were recruited from the community, were over 18 years and fluent in English. Statements that represented first-line care were identified. Semantic scales were used to measure attitude towards these statements. These items were combined to develop the questionnaire draft. Construct validity was evaluated with exploratory factor analysis and hypotheses testing, comparing to the Back Beliefs Questionnaire and modified Pain Self-Efficacy Questionnaire. Reliability was evaluated and floor and ceiling effects calculated. Results: We recruited 345 participants, and had complete data for analysis for 313 participants. The questionnaire draft was reduced to a 3-Factor questionnaire through exploratory factor analysis. Factor 1 comprised 9 items and evaluated Attitude toward staying active, Factor 2 comprised 4 items and evaluated Attitude toward low back pain being rarely caused by a serious health problem, Factor 3 comprised 4 items and evaluated Attitude toward not needing to know the cause of back pain to manage it effectively. There was a strong inverse association between each factor and the Back Beliefs Questionnaire and a moderate positive association with the modified Pain Self-Efficacy Questionnaire. Each independent factor demonstrated acceptable internal consistency; Cronbach α Factor 1 = 0.92, Factor 2 = 0.91, Factor 3 = 0.90 and adequate interclass correlation coefficients; Factor 1 = 0.71, Factor 2 = 0.73, Factor 3 = 0.79. Conclusion: This study demonstrates acceptable construct validity and reliability of the AxEL-Q, providing clinicians with an insight into the likelihood of patients following first-line care at the outset
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