Mechanisms of viral entry: sneaking in the front door

Recent developments in methods to study virus internalisation are providing clearer insights into mechanisms used by viruses to enter host cells. The use of dominant negative constructs, specific inhibitory drugs and RNAi to selectively prevent entry through particular pathways has provided evidence for the clathrin-mediated entry of hepatitis C virus (HCV) as well as the caveolar entry of Simian Virus 40. Moreover, the ability to image and track fluorescent-labelled virus particles in real-time has begun to challenge the classical plasma membrane entry mechanisms described for poliovirus and human immunodeficiency virus. This review will cover both well-documented entry mechanisms as well as more recent discoveries in the entry pathways of enveloped and non-enveloped viruses. This will include viruses which enter the cytosol directly at the plasma membrane and those which enter via endocytosis and traversal of internal membrane barrier(s). Recent developments in imaging and inhibition of entry pathways have provided insights into the ill-defined entry mechanism of HCV, bringing it to the forefront of viral entry research. Finally, as high-affinity receptors often define viral internalisation pathways, and tropism in vivo, host membrane proteins to which viral particles specifically bind will be discussed throughout

Railway-induced ground vibrations – a review of vehicle effects

This paper is a review of the effect of vehicle characteristics on ground- and track borne-vibrations from railways. It combines traditional theory with modern thinking and uses a range of numerical analysis and experimental results to provide a broad analysis of the subject area. First, the effect of different train types on vibration propagation is investigated. Then, despite not being the focus of this work, numerical approaches to vibration propagation modelling within the track and soil are briefly touched upon. Next an in-depth discussion is presented related to the evolution of numerical models, with analysis of the suitability of various modelling approaches for analysing vehicle effects. The differences between quasi-static and dynamic characteristics are also discussed with insights into defects such as wheel/rail irregularities. Additionally, as an appendix, a modest database of train types are presented along with detailed information related to their physical attributes. It is hoped that this information may provide assistance to future researchers attempting to simulate railway vehicle vibrations. It is concluded that train type and the contact conditions at the wheel/rail interface can be influential in the generation of vibration. Therefore, where possible, when using numerical approach, the vehicle should be modelled in detail. Additionally, it was found that there are a wide variety of modelling approaches capable of simulating train types effects. If non-linear behaviour needs to be included in the model, then time domain simulations are preferable, however if the system can be assumed linear then frequency domain simulations are suitable due to their reduced computational demand