9 resultados para ILL requests
em Cambridge University Engineering Department Publications Database
Resumo:
During product development, engineering designers raise several information requests that make them search through human and documentary sources. This paper reports research to characterise, in detail, these requests for designers working in a major aerospace engineering company. The research found that at a high level, a distinction can be made between requests to acquire information and to process information. The former are raised to access design and domain information. The latter, instead, are formed to define designs. For researchers, this study extends existing knowledge of information requests by characterising key differences in their nature and explaining how they are used in the design process. For practitioners, these findings can be used as a basis to understand the diverseness of information requests and how to channel efforts to support designers in information seeking. In particular, the research indicates that a strategy to support designers should enable the development of engineering communities that share information effectively and the introduction of techniques that facilitate the documentation of information. © 2012 Springer-Verlag London Limited.
Resumo:
BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.