995 resultados para 7140-216


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Mode of access: Internet.

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Mu ke ben. Kuang : 21.8 cm x 16 cm.

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Human cytochrome P450 (P450) 2D6 is an important enzyme involved in the metabolism of drugs, many of which are amines or contain other basic nitrogen atoms. Asp301 has generally been considered to be involved in electrostatic docking with the basic substrates, on the basis of previous modeling studies and site-directed mutagenesis. Substitution of Glu216 with a residue other than Asp strongly attenuated the binding of quinidine, bufuralol, and several other P450 2D6 ligands. Catalytic activity with the substrates bufuralol and 4-methoxyphenethylamine was strongly inhibited by neutral or basic mutations at Glu216 (>95%), to the same extent as the substitution of Asn at Asp301. Unlike the Asp301 mutants, the Gln216 mutant (E216Q) retained 40% enzyme efficiency with the substrate spirosulfonamide, devoid of basic nitrogen, suggesting that the substitutions at Glu216 affect binding of amine substrates more than other catalytic steps. Attempts to induce catalytic specificity toward new substrates by substitutions at Asp301 and Glu216 were unsuccessful. Collectively, the results provide evidence for electrostatic interaction of amine substrates with Glu216, and we propose that both of these acidic residues plus at least another residue(s) is (are) involved in binding the repertoire of P450 2D6 ligands.

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The next phase envisioned for the World Wide Web is automated ad-hoc interaction between intelligent agents, web services, databases and semantic web enabled applications. Although at present this appears to be a distant objective, there are practical steps that can be taken to advance the vision. We propose an extension to classical conceptual models to allow the definition of application components in terms of public standards and explicit semantics, thus building into web-based applications, the foundation for shared understanding and interoperability. The use of external definitions and the need to store outsourced type information internally, brings to light the issue of object identity in a global environment, where object instances may be identified by multiple externally controlled identification schemes. We illustrate how traditional conceptual models may be augmented to recognise and deal with multiple identities.

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This study aimed to identify the aptitudes required in allied health professionals working in three different service delivery models serving remote locations in Northern tropical Australia. Eighteen allied health professionals including," dietetics, diabetes educators, occupational therapy, physiotherapy, psychology, podiatry, social work and speech pathology participated in this exploratory study using a narrative approach. A range of aptitudes were identified and themed under the following headings: (1) being organized but flexible, (2) cooperation and mediation, (3) culturally aware and accepting communicators, (4) knowing the community (5) resourcefulness and resilience and (6) reflectivity. Limiting factors were also deduced. Three of the themes are discussed in this paper. The study found that allied health professionals working in remote settings identified as important personal attributes not necessarily valued in metropolitan settings. Recruitment processes and education programs need to recognize the importance of personal attributes as well as professional skills.

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People with intellectual disability are a relatively new but growing minority group within Australia's ageing population. Disability policies point to the equal right of people with disabilities to a quality of life similar to that of other citizens. Disability services are increasingly required to provide individualised and responsive services, irrespective of age, for people with lifelong disabilities. The present study explored the everyday lives of older people with intellectual disability in Victoria and Queensland, examining their experiences of using disability services and the ways in which services responded to their ageing. The aim of the study was to inform practice and service development for older people with intellectual disability. The findings suggest that services facilitate important social relationships with other service users and staff. Most older people had a sense of belonging and led busy but directionless lives in two disconnected worlds. Their lives were subject to significant external present-focused control. Yet, despite this, neither services nor family members took responsibility for ensuring their sense of continuity or supporting the development of plans about their future. The experiences described suggest an urgent need for, but significant challenges in the implementation of, holistic indivdualised planning similar to the UK concept of person-centred planning.