Cell entry by enveloped viruses: redox considerations for HIV and SARS-coronavirus

For enveloped viruses, genome entry into the target cell involves two major steps: virion binding to the cell-surface receptor and fusion of the virion and cell membranes. Virus-cell membrane fusion is mediated by the virus envelope complex, and its fusogenicity is the result of an active virus-cell interaction process that induces conformation changes within the envelope. For some viruses, such as influenza, exposure to an acidic milieu within the cell during the early steps of infection triggers the necessary structural changes. However, for other pathogens which are not exposed to such environmental stress, activation of fusogenicity can result from precise thiol/disulfide rearrangements mediated by either an endogenous redox autocatalytic isomerase or a cell-associated oxidoreductase. Study of the activation of HIV envelope fusogenicity has revealed new knowledge about how redox changes within a viral envelope trigger fusion. We discuss these findings and their implication for anti-HIV therapy. In addition, to compare and contrast the situation outlined for HIV with an enveloped virus that can fuse with the cell plasma membrane independent of the redox status of its envelope protein, we review parallel data obtained on SARS coronavirus entry.

The challenges of creating actionable knowledge: an action research perspective

Academia has a critical role in developing new knowledge which construction industry practitioners need to envision, undertake and sustain successful innovation. The new knowledge produced by academia, however, often does not satisfy the needs of practitioners. This unsatisfactory state of affairs is frequently taken to be the consequence of the cultural, motivational and operational differences between the two communities. Actionable knowledge is presented as a useful concept which can fuse the expectations, contributions and outputs of academia and practitioners. Within this context, action research is argued to be an appropriate methodology to develop successful actionable knowledge. Results from an action research project are given which provide researchers and practitioners greater understanding of the key factors that shape the degree to which action research produces actionable knowledge: change focus, collaboration capabilities and systematic process. The criteria intrinsic to Mode 2 research (Gibbons et al., 1994) are demonstrated to have utility in evidencing actionable knowledge. The implication for policy is that there is a need to develop and use appropriate actionable knowledge frameworks and measures to design funding calls, and to evaluate research proposals and outputs.

Knowledge-elicitation and data-mining: fusing human and industrial plant information

Knowledge-elicitation is a common technique used to produce rules about the operation of a plant from the knowledge that is available from human expertise. Similarly, data-mining is becoming a popular technique to extract rules from the data available from the operation of a plant. In the work reported here knowledge was required to enable the supervisory control of an aluminium hot strip mill by the determination of mill set-points. A method was developed to fuse knowledge-elicitation and data-mining to incorporate the best aspects of each technique, whilst avoiding known problems. Utilisation of the knowledge was through an expert system, which determined schedules of set-points and provided information to human operators. The results show that the method proposed in this paper was effective in producing rules for the on-line control of a complex industrial process. (C) 2005 Elsevier Ltd. All rights reserved.

Fusing data-mining and knowledge elicitation for the supervisory control of an aluminium plate mill

Knowledge-elicitation is a common technique used to produce rules about the operation of a plant from the knowledge that is available from human expertise. Similarly, data-mining is becoming a popular technique to extract rules from the data available from the operation of a plant. In the work reported here knowledge was required to enable the supervisory control of an aluminium hot strip mill by the determination of mill set-points. A method was developed to fuse knowledge-elicitation and data-mining to incorporate the best aspects of each technique, whilst avoiding known problems. Utilisation of the knowledge was through an expert system, which determined schedules of set-points and provided information to human operators. The results show that the method proposed in this paper was effective in producing rules for the on-line control of a complex industrial process.

Pre-CME onset fuses: do the STEREO heliospheric imagers hold the clues to the CME onset process?

Understanding the onset of coronal mass ejections (CMEs) is surely one of the holy grails of solar physics today. Inspection of data from the Heliospheric Imagers (HI), which are part of the SECCHI instrument suite aboard the two NASA STEREO spacecraft, appears to have revealed pre-eruption signatures which may provide valuable evidence for identifying the CME onset mechanism. Specifically, an examination of the HI images has revealed narrow rays comprised of a series of outward-propagating plasma blobs apparently forming near the edge of the streamer belt prior to many CME eruptions. In this pilot study, we inspect a limited dataset to explore the significance of this phenomenon, which we have termed a pre-CME ‘fuse’. Although, the enhanced expulsion of blobs may be consistent with an increase in the release of outward-propagating blobs from the streamers themselves, it could also be interpreted as evidence for interchange reconnection in the period leading to a CME onset. Indeed, it is argued that the latter could even have implications for the end-of-life of CMEs. Thus, the presence of these pre-CME fuses provides evidence that the CME onset mechanism is either related to streamer reconnection processes or the reconnection between closed field lines in the streamer belt and adjacent, open field lines. We investigate the nature of these fuses, including their timing and location with respect to CME launch sites, as well as their speed and topology.

Structural characterisation of bisintercalation in higher-order DNA at a junction-like quadruplex

We report the single-crystal X-ray structure for the complex of the bisacridine bis-(9-aminooctyl(2-(dimethylaminoethyl)acridine-4-carboxamide)) with the oligonucleotide d(CGTACG)2 to a resolution of 2.4 Å. Solution studies with closed circular DNA show this compound to be a bisintercalating threading agent, but so far we have no crystallographic or NMR structural data conforming to the model of contiguous intercalation within the same duplex. Here, with the hexameric duplex d(CGTACG), the DNA is observed to undergo a terminal cytosine base exchange to yield an unusual guanine quadruplex intercalation site through which the bisacridine threads its octamethylene linker to fuse two DNA duplexes. The 4-carboxamide side-chains form anchoring hydrogen-bonding interactions with guanine O6 atoms on each side of the quadruplex. This higher-order DNA structure provides insight into an unexpected property of bisintercalating threading agents, and suggests the idea of targeting such compounds specifically at four-way DNA junctions.

Multicamera trajectory analysis for semantic behaviour characterisation

In this paper we propose an innovative approach for behaviour recognition, from a multicamera environment, based on translating video activity into semantics. First, we fuse tracks from individual cameras through clustering employing soft computing techniques. Then, we introduce a higher-level module able to translate fused tracks into semantic information. With our proposed approach, we address the challenge set in PETS 2014 on recognising behaviours of interest around a parked vehicle, namely the abnormal behaviour of someone walking around the vehicle.