In vivo regulation of the Vi antigen in Salmonella and induction of immune responses with an in vivo-inducible promoter.

Salmonella enterica serovar Typhi, the agent of typhoid fever in humans, expresses the surface Vi polysaccharide antigen that contributes to virulence. However, Vi expression can also be detrimental to some key steps of S. Typhi infectivity, for example, invasion, and Vi is the target of protective immune responses. We used a strain of S. Typhimurium carrying the whole Salmonella pathogenicity island 7 (SPI-7) to monitor in vivo Vi expression within phagocytic cells of mice at different times after systemic infection. We also tested whether it is possible to modulate Vi expression via the use of in vivo-inducible promoters and whether this would trigger anti-Vi antibodies through the use of Vi-expressing live bacteria. Our results show that Vi expression in the liver and spleen is downregulated with the progression of infection and that the Vi-negative population of bacteria becomes prevalent by day 4 postinfection. Furthermore, we showed that replacing the natural tviA promoter with the promoter of the SPI-2 gene ssaG resulted in sustained Vi expression in the tissues. Intravenous or oral infection of mice with a strain of S. Typhimurium expressing Vi under the control of the ssaG promoter triggered detectable levels of all IgG subclasses specific for Vi. Our work highlights that Vi is downregulated in vivo and provides proof of principle that it is possible to generate a live attenuated vaccine that induces Vi-specific antibodies after single oral administration.

Mapping the conceptual design activity of interdisciplinary teams

The conceptual design phase of any project is, by its very nature, a vibrant, creative and dynamic period. It can also be disorganized with much backtracking accompanying the exchange of information between design team members. The transfer of information, ideas and opinion is critical to the development of concepts and as such, rather than being recognized as merely a component of conceptual design activity, it needs to be understood and, ultimately, managed. This paper describes an experimental workshop involving fifteen design professionals in which conceptual design activity was tracked, and subsequently mapped, in order to test and validate a tentative design framework (phase and activity model). The nature of the design progression of the various teams is captured and analyzed, allowing a number of conclusions to be drawn regarding both the iterative nature of this phase of design and how teams of professionals actually design together.

The night purging of a two-storey atrium building

We examine the fluid mechanics of night purging in a two-storey naturally ventilated atrium building. We develop a mathematical model of a simplified atrium building and focus on the rate at which warm air purges from each storey and the atrium by displacement ventilation into a still cool night environment of a constant temperature. To develop a first insight into how the geometry of the building influences the rate at which warm air purges from each storey via the atrium we neglect heat exchange with the fabric (so there is no thermal buffering) and furthermore assume that the warm air layers in each storey and the atrium are of uniform temperature. The plumes of warm air that rise from the storeys into the atrium, causing the atrium to fill with warm air, have a very strong influence on the night purge. Modelling these as axisymmetric turbulent plumes, we identify three forms of purging behaviour. Each purge is characterised by five key times identified in the progression of the night purge and physical rationale for these differing behaviours is given. An interface velocity deficit and volumetric purge deficit are introduced as measures of the efficiency of a night purge. © 2010 Elsevier Ltd.

Modelling failure of composite specimens with defects under compression loading

Composite structures exhibit many different failure mechanisms, but attempts to model composite failure frequently make a priori assumptions about the mechanism by which failure will occur. Wang et al. [1] conducted compressive tests on four configurations of composite specimen manufactured with out-of-plane waviness created by ply-drop defects. There were significantly different failures for each case. Detailed finite element models of these experiments were developed which include competing failure mechanisms. The model predictions correlate well with experimental results-both qualitatively (location of failure and shape of failed specimen) and quantitatively (failure load). The models are used to identify the progression of failure during the compressive tests, determine the critical failure mechanism for each configuration, and investigate the effect of cohesive parameters upon specimen strength. This modelling approach which includes multiple competing failure mechanisms can be applied to predict failure in situations where the failure mechanism is not known in advance. © 2013 Elsevier Ltd. All rights reserved.

Decadal persistence of cycles in lava lake motion at Erebus volcano, Antarctica

Studies of Erebus volcano's active lava lake have shown that many of its observable properties (gas composition, surface motion and radiant heat output) exhibit cyclic behaviour with a period of ~10 min. We investigate the multi-year progression of the cycles in surface motion of the lake using an extended (but intermittent) dataset of thermal infrared images collected by the Mount Erebus Volcano Observatory between 2004 and 2011. Cycles with a period of ~5-18 min are found to be a persistent feature of the lake's behaviour and no obvious long-term change is observed despite variations in lake level and surface area. The times at which gas bubbles arrive at the lake's surface are found to be random with respect to the phase of the motion cycles, suggesting that the remarkable behaviour of the lake is governed by magma exchange rather than an intermittent flux of gases from the underlying magma reservoir. © 2014 The Authors.