Mapping Protein-DNA Interactions Using ChIP-exo and Illumina-Based Sequencing

Chromatin immunoprecipitation (ChIP) provides a means of enriching DNA associated with transcription factors, histone modifications, and indeed any other proteins for which suitably characterized antibodies are available. Over the years, sequence detection has progressed from quantitative real-time PCR and Southern blotting to microarrays (ChIP-chip) and now high-throughput sequencing (ChIP-seq). This progression has vastly increased the sequence coverage and data volumes generated. This in turn has enabled informaticians to predict the identity of multi-protein complexes on DNA based on the overrepresentation of sequence motifs in DNA enriched by ChIP with a single antibody against a single protein. In the course of the development of high-throughput sequencing, little has changed in the ChIP methodology until recently. In the last three years, a number of modifications have been made to the ChIP protocol with the goal of enhancing the sensitivity of the method and further reducing the levels of nonspecific background sequences in ChIPped samples. In this chapter, we provide a brief commentary on these methodological changes and describe a detailed ChIP-exo method able to generate narrower peaks and greater peak coverage from ChIPped material.

Aerodynamic optimization using Adjoint methods and parametric CAD models

This paper describes an implementation of a method capable of integrating parametric, feature based, CAD models based on commercial software (CATIA) with the SU2 software framework. To exploit the adjoint based methods for aerodynamic optimisation within the SU2, a formulation to obtain geometric sensitivities directly from the commercial CAD parameterisation is introduced, enabling the calculation of gradients with respect to CAD based design variables. To assess the accuracy and efficiency of the alternative approach, two aerodynamic optimisation problems are investigated: an inviscid, 3D, problem with multiple constraints, and a 2D high-lift aerofoil, viscous problem without any constraints. Initial results show the new parameterisation obtaining reliable optimums, with similar levels of performance of the software native parameterisations. In the final paper, details of computing CAD sensitivities will be provided, including accuracy as well as linking geometric sensitivities to aerodynamic objective functions and constraints; the impact in the robustness of the overall method will be assessed and alternative parameterisations will be included.

Using Computational Significance and Resilience in System Software Stacks.:Keynote Talk

This talk explores how the runtime system and operating system can leverage metrics that express the significance and resilience of application components in order to reduce the energy footprint of parallel applications. We will explore in particular how software can tolerate and indeed exploit higher error rates in future processors and memory technologies that may operate outside their safe margins.

A framework for experimental determination of localised vertical pedestrian forces on full-scale structures using wireless attitude and heading reference systems

A major weakness among loading models for pedestrians walking on flexible structures proposed in recent years is the various uncorroborated assumptions made in their development. This applies to spatio-temporal characteristics of pedestrian loading and the nature of multi-object interactions. To alleviate this problem, a framework for the determination of localised pedestrian forces on full-scale structures is presented using a wireless attitude and heading reference systems (AHRS). An AHRS comprises a triad of tri-axial accelerometers, gyroscopes and magnetometers managed by a dedicated data processing unit, allowing motion in three-dimensional space to be reconstructed. A pedestrian loading model based on a single point inertial measurement from an AHRS is derived and shown to perform well against benchmark data collected on an instrumented treadmill. Unlike other models, the current model does not take any predefined form nor does it require any extrapolations as to the timing and amplitude of pedestrian loading. In order to assess correctly the influence of the moving pedestrian on behaviour of a structure, an algorithm for tracking the point of application of pedestrian force is developed based on data from a single AHRS attached to a foot. A set of controlled walking tests with a single pedestrian is conducted on a real footbridge for validation purposes. A remarkably good match between the measured and simulated bridge response is found, indeed confirming applicability of the proposed framework.

Continuous statistical modelling for rapid detection of adulteration of extra virgin olive oil using mid infrared and Raman spectroscopic data

The main objective of this work was to develop a novel dimensionality reduction technique as a part of an integrated pattern recognition solution capable of identifying adulterants such as hazelnut oil in extra virgin olive oil at low percentages based on spectroscopic chemical fingerprints. A novel Continuous Locality Preserving Projections (CLPP) technique is proposed which allows the modelling of the continuous nature of the produced in-house admixtures as data series instead of discrete points. The maintenance of the continuous structure of the data manifold enables the better visualisation of this examined classification problem and facilitates the more accurate utilisation of the manifold for detecting the adulterants. The performance of the proposed technique is validated with two different spectroscopic techniques (Raman and Fourier transform infrared, FT-IR). In all cases studied, CLPP accompanied by k-Nearest Neighbors (kNN) algorithm was found to outperform any other state-of-the-art pattern recognition techniques.