Chromatin immunoprecipitation (ChIP) methodology and readouts

The identification of direct nuclear hormone receptor gene targets provides clues to their contribution to both development and cancer progression. Until recently, the identification of such direct target genes has relied on a combination of expression analysis and in silico searches for consensus binding motifs in gene promoters. Consensus binding motifs for transcription factors are often defined using in vitro DNA binding strategies. Such in vitro strategies fail to account for the many factors that contribute significantly to target selection by transcription factors in cells beyond the recognition of these short consensus DNA sequences. These factors include DNA methylation, chromatin structure, posttranslational modifications of transcription factors, and the cooperative recruitment of transcription factor complexes. Chromatin immunoprecipitation (ChIP) provides a means of isolating transcription factor complexes in the context of endogenous chromatin, allowing the identification of direct transcription factor targets. ChIP can be combined with site-specific PCR for candidate binding sites or alternatively with cloning, genomic microarrays or more recently direct high throughput sequencing to identify novel genomic targets. The application of ChIP-based approaches has redefined consensus binding motifs for transcription factors and provided important insights into transcription factor biology.

Development of a Vehicle-Bridge-Soil Dynamic Interaction Model for Scour Damage Modelling

Damage detection in bridges using vibration-based methods is an area of growing research interest. Improved assessment
methodologies combined with state-of-the-art sensor technology are rapidly making these approaches applicable for real-world
structures. Applying these techniques to the detection and monitoring of scour around bridge foundations has remained
challenging; however this area has gained attraction in recent years. Several authors have investigated a range of methods but
there is still significant work required to achieve a rounded and widely applicable methodology to detect and monitor scour.This
paper presents a novel Vehicle-Bridge-Soil Dynamic Interaction (VBSDI) model which can be used to simulate the effect of scour
on an integral bridge. The model outputs dynamic signals which can be analysed to determine modal parameters and the variation
of these parameters with respect to scour can be examined.The key novelty of this model is that it is the first numerical model for
simulating scour that combines a realistic vehicle loadingmodel with a robust foundation soil responsemodel.This paper provides a
description of the model development and explains the mathematical theory underlying themodel. Finally a case study application
of the model using typical bridge, soil, and vehicle properties is provided.

Development of Seismic Fragility Functions for a Moment Resisting Reinforced Concrete Framed Structure

Understanding the seismic vulnerability of building structures is important for seismic engineers, building owners, risk insurers and governments. Seismic vulnerability defines a buildings predisposition to be damaged as a result of an earthquake of a given severity. There are two components to seismic risk; the seismic hazard and the exposure of the structural inventory to any given earthquake event. This paper demonstrates the development of fragility curves at different damage states using a detailed mechanical model of a moment resisting reinforced concrete structure typical of Southern Europe. The mechanical model consists of a complex three-dimensional finite element model of the reinforced concrete moment resisting frame structure and is used to define the damage states through pushover analysis. Fragility curves are also defined using the HAZUS macroseismic methodology and the Risk-UE macroseismic methodology. Comparison of the mechanically modelled and HAZUS fragility curve shows good agreement while the Risk-UE methodology shows reasonably poor agreement.