Adenovirus-mediated transfer of a gene encoding acyloxyacyl hydrolase (AOAH) into mice increases tissue and plasma AOAH activity

Although the host response to gram-negative bacterial infection follows largely from the interactions of bacterial lipopolysaccharides (LPS or endotoxin) with host cells, little information is available concerning the mechanisms by which the host eliminates or detoxifies LPS. Acyloxyacyl hydrolase (AOAH) is an enzyme, found in phagocytic cells, that catalyzes the enzymatic deacylation of the lipid A moiety of LPS. Enzymatically deacylated LPS is much less potent than LPS at inducing responses in human cells, and it can antagonize the ability of LPS to activate human macrophages, neutrophils, and endothelial cells. Despite these observations, the physiologic role of LPS deacylation remains undefined. To investigate the ability of AOAH to carry out LPS deacylation in vivo, we produced a recombinant adenovirus carrying a gene encoding AOAH (Ad.CMV-AOAH) and employed this vector to elicit transient overexpression of AOAH in mice. Mice infected with Ad.CMV-AOAH expressed high levels of the enzyme in plasma, liver, spleen, and kidney. Although adenovirus-induced hepatitis reduced hepatic uptake of intravenously injected [H-3]LPS, animals expressing the transgene deacylated a larger fraction of the [3H]LPS taken up by their livers than did mice infected with a control adenovirus. These studies indicate that AOAH can catalyze the deacylation of LPS in vivo, and they provide evidence that the rates of hepatic LPS uptake and deacylation are not closely linked

Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-inflammatory agents in a rat model of antigen-induced arthritis

INTRODUCTION: Previously, secretory phospholipase A(2 )(sPLA(2)) inhibition has been used as an adjunct to conventional rheumatoid arthritis therapy in human clinical trials without significant improvement of arthritic pathology. In this study, we compared the efficacy of a potent and orally active group IIa secretory phospholipase A(2 )inhibitor (sPLA(2)I) to conventional anti-arthritic agents; infliximab, leflunomide and prednisolone, in a rat model of antigen-induced arthritis. METHODS: Initially, to establish efficacy and dose-response, rats were orally dosed with the sPLA(2)I (1 and 5 mg/kg) two days prior to arthritis induction, and then daily throughout the 14-day study period. In the second trial, rats were orally dosed with the sPLA(2)I (5 and 10 mg/kg/day) beginning two days after the induction of arthritis, at the peak of joint swelling. Separate groups of rats were also dosed with the tumour necrosis factor-alpha (TNF-α) inhibitor infliximab (single 3 mg/kg i.v. injection), leflunomide (10 mg/kg/day, oral) or prednisolone (1 mg/kg/day, oral) at this same time point and used as comparative treatments. RESULTS: In the pathology prevention trial, both 1 and 5 mg/kg dose groups of sPLA(2)I demonstrated a significant reduction in joint swelling and gait disturbances; however, only the higher 5 mg/kg dose resulted in significantly reduced histopathology scores. In the post-induction trial, rats dosed with sPLA(2)I showed a significant improvement in joint swelling and gait scoring, whereas none of the conventional therapeutics achieved a significant decrease in both of these two disease markers. Histopathological scoring at the end-point of the study demonstrated significantly reduced median scores in rats treated with 10 mg/kg sPLA(2)I and leflunomide. CONCLUSIONS: The results from this study suggest a pathogenic role for sPLA(2 )enzymes in this model of arthritis in rats, and the potential clinical utility of sPLA(2 )inhibition as a safer, and more effective, alternative to conventional anti-arthritic therapeutics

Non-linearity and spatial resolution in a cellular automaton model of a small upland basin

International audienceThe continuing development of computational fluid dynamics is allowing the high resolution study of hydraulic and sediment transport processes but, due to computational complexities, these are rarely applied to areas larger than a reach. Existing approaches, based upon linked cross sections, can give a quasi two-dimensional view, effectively simulating sediment transport for a single river reach. However, a basin represents a whole discrete dynamic system within which channel, floodplain and slope processes operate over a wide range of space and time scales. Here, a cellular automaton (CA) approach has been used to overcome some of these difficulties, in which the landscape is represented as a series of fixed size cells. For every model iteration, each cell acts only in relation to the influence of its immediate neighbours in accordance with appropriate rules. The model presented here takes approximations of existing flow and sediment transport equations, and integrates them, together with slope and floodplain approximations, within a cellular automaton framework. This method has been applied to the basin of Cam Gill Beck (4.2 km2 ) above Starbotton, upper Wharfedale, a tributary of the River Wharfe, North Yorkshire, UK. This approach provides, for the first time, a workable model of the whole basin at a 1 m resolution. Preliminary results show the evolution of bars, braids, terraces and alluvial fans which are similar to those observed in the field, and examples of large and small scale non-linear behaviour which may have considerable implications for future models

Religious Vehicle Stickers in Nigeria: a discourse of identity, faith and social vision

This study focuses on analysing the ways in which vehicle stickers construct individual and group identities, people’s religious faith and social vision in the context of religious assumptions and practices in Nigeria. Data comprise 73 vehicle stickers collected in Lagos and Ota, between 2006 and 2007 and are analysed within the framework of the post-structuralist model of discourse analysis which views discourse as a product of a complex system of social and institutional practices that sustain its continuous existence (Derrida, 1982; Fairclough, 1989, 1992, 1995; Foucault, 1972, 1981). Results show that through stickers people define their individual and group identities within religious institutional practices. And as a means of group identification, they guarantee social security and privileges. In constructing social vision the stickers help mould the individual aspiration about a future which transcends the present. Significantly, stickers in the data also reveal the tension between Islam and Christianity and the struggle to propagate one above the other. KEY WORDS: assumption, discourse, discursive, practices, religion, stickers

Business process re-engineering to digitalise quality control checks for reducing physical waste and resource use in a food company

Quality control is an essential element of manufacturing operations that reduces product defects and provides excellent products of the right specifications to the end consumer. Industry 4.0 solutions, such as digitalisation, along with lean manufacturing tools, may support quality control operations. This paper presents a case study of a food company wherein quality control checks were optimised using business process re-engineering to reduce physical waste and resource usage. Following close analysis of the company’s pack-house operations, it was proposed to adopt elements of Industry 4.0 by digitalising the quality control process. Implementing such a solution led to a reduction in the time needed to complete recorded checks, an increase in the time the pack-house quality control team spends with packers on the production lines, and the facilitation of defects identification. It also ensured that the product met the customers’ specifications and reduced the likelihood of rejection at the customers’ depot. The new system also enabled monitoring of each line in real-time and gathering of additional information faster and more accurately. This article proves how employing lean principles in combination with Industry 4.0 technologies can lead to savings in resources and a reduction in waste, which leads to improvements in operational efficiency

Historic Spatial Patterns of Storm-Driven Compound Events in UK Estuaries

Compound estuarine flooding is driven by extreme sea-levels and river discharge occurring concurrently, or in close succession, and threatens low-lying coastal regions worldwide. We hypothesise that these drivers of flooding rarely occur independently and co-operate at sub-daily timescales. This research aimed to identify regions and individual estuaries within Britain susceptible to storm-driven compound events, using 27 tide gauges linked to 126 river gauges covering a 30-year record. Five methods were evaluated, based on daily mean, daily maximum, and instantaneous 15-min discharge data to identify extremes in the river records, with corresponding skew surges identified within a ‘storm window’ based on average hydrograph duration. The durations, relative timings, and overlap of these extreme events were also calculated. Dependence between extreme skew surge and river discharge in Britain displayed a clear east–west split, with gauges on the west coast showing stronger correlations up to 0.33. Interpreting dependence based on correlation alone can be misleading and should be considered alongside number of historic extreme events. The analyses identified 46 gauges, notably the Rivers Lune and Orchy, where there has been the greatest chance and most occurrences of river-sea extremes coinciding, and where these events readily overlapped one another. Our results were sensitive to the analysis method used. Most notably, daily mean discharge underestimated peaks in the record and did not accurately capture likelihood of compound events in 68% of estuaries. This has implications for future flood risk in Britain, whereby studies should capture sub-daily timescale and concurrent sea-fluvial climatology to support long-term flood management plans

Tapes, transcripts and trials:The routine contamination of police interview evidence

This article addresses a serious, but currently unacknowledged, problem of evidential consistency regarding police-suspect interview evidence. It sheds light on flaws in current criminal procedure through the lens of linguistics, focusing on key stages of currently accepted practice which fly in the face of what linguists have long known about language. It demonstrates that, in stark contrast to the strict principles of preservation applied to physical evidence, interview data go through significant transformation between their creation in the interview room and their presentation in the courtroom, especially through changes in format between written and spoken text. It argues that, despite the safeguards provided by PACE 1984, there is nonetheless a level of routine distortion and contamination unintentionally built in to the current system of presenting police interviews as evidence in England & Wales

Conversation acts in task-oriented spoken dialogue

A linguistic form\u27s compositional, timeless meaning can be surrounded or even contradicted by various social, aesthetic, or analogistic companion meanings. This paper addresses a series of problems in the structure of spoken language discourse, including turn-taking and grounding. It views these processes as composed of fine-grained actions, which resemble speech acts both in resulting from a computational mechanism of planning and in having a rich relationship to the specific linguistic features which serve to indicate their presence. The resulting notion of Conversation Acts is more general than speech act theory, encompassing not only the traditional speech acts but turn-taking, grounding, and higher-level argumentation acts as well. Furthermore, the traditional speech acts in this scheme become fully joint actions, whose successful performance requires full listener participation. This paper presents a detailed analysis of spoken language dialogue. It shows the role of each class of conversation acts in discourse structure, and discusses how members of each class can be recognized in conversation. Conversation acts, it will be seen, better account for the success of conversation than speech act theory alone