BlogForever D2.6: Data Extraction Methodology

This report outlines an inquiry into the area of web data extraction, conducted within the context of blog preservation. The report reviews theoretical advances and practical developments for implementing data extraction. The inquiry is extended through an experiment that demonstrates the effectiveness and feasibility of implementing some of the suggested approaches. More specifically, the report discusses an approach based on unsupervised machine learning that employs the RSS feeds and HTML representations of blogs. It outlines the possibilities of extracting semantics available in blogs and demonstrates the benefits of exploiting available standards such as microformats and microdata. The report proceeds to propose a methodology for extracting and processing blog data to further inform the design and development of the BlogForever platform

An antibody raised against a pathogenic serpin variant induces mutant-like behaviour in the wild-type protein

A monoclonal antibody (mAb) that binds to a transient intermediate may act as a catalyst for the corresponding reaction; here we show this principle can extend on a macro molecular scale to the induction of mutant-like oligomerization in a wild-type protein. Using the common pathogenic E342K (Z) variant of α1-antitrypsin as antigen-whose native state is susceptible to the formation of a proto-oligomeric intermediate-we have produced a mAb (5E3) that increases the rate of oligomerization of the wild-type (M) variant. Employing ELISA, gel shift, thermal stability and FRET time-course experiments, we show that mAb5E3 does not bind to the native state of α1-antitrypsin, but recognizes a cryptic epitope in the vicinity of the post-helix A loop and strand 4C that is revealed upon transition to the polymerization intermediate, and which persists in the ensuing oligomer. This epitope is not shared by loop-inserted monomeric conformations. We show the increased amenity to polymerization by either the pathogenic E342K mutation or the binding of mAb5E3 occurs without affecting the energetic barrier to polymerization. As mAb5E3 also does not alter the relative stability of the monomer to intermediate, it acts in a manner similar to the E342K mutant, by facilitating the conformational interchange between these two states

Nature of the spin-glass phase at experimental length scales

We present a massive equilibrium simulation of the three-dimensional Ising spin glass at low temperatures. The Janus special-purpose computer has allowed us to equilibrate, using parallel tempering, L=32 lattices down to T=0.64 Tc. We demonstrate the relevance of equilibrium finite-size simulations to understand experimental non-equilibrium spin glasses in the thermodynamical limit by establishing a time-length dictionary. We conclude that non-equilibrium experiments performed on a time scale of one hour can be matched with equilibrium results on L=110 lattices. A detailed investigation of the probability distribution functions of the spin and link overlap, as well as of their correlation functions, shows that Replica Symmetry Breaking is the appropriate theoretical framework for the physically relevant length scales. Besides, we improve over existing methodologies to ensure equilibration in parallel tempering simulations.Comment: 48 pages, 19 postscript figures, 9 tables. Version accepted for publication in the Journal of Statistical Mechanic

Thermodynamic glass transition in a spin glass without time-reversal symmetry

Spin glasses are a longstanding model for the sluggish dynamics that appears at the glass transition. However, spin glasses differ from structural glasses for a crucial feature: they enjoy a time reversal symmetry. This symmetry can be broken by applying an external magnetic field, but embarrassingly little is known about the critical behaviour of a spin glass in a field. In this context, the space dimension is crucial. Simulations are easier to interpret in a large number of dimensions, but one must work below the upper critical dimension (i.e., in d<6) in order for results to have relevance for experiments. Here we show conclusive evidence for the presence of a phase transition in a four-dimensional spin glass in a field. Two ingredients were crucial for this achievement: massive numerical simulations were carried out on the Janus special-purpose computer, and a new and powerful finite-size scaling method.Comment: 10 pages, 6 figure

Optimizing street mobility through a netlogo simulation environment

The routes and streets make it possible to drive and travel through the cities, but unfortunately traffic and particularly congestion leads to drivers losing time while traveling from one place to another, because of the time it takes to transit on the roads, in addition to waiting times by traffic lights. This research introduces the extension of an agent-oriented system aimed at reducing driver waiting times at a street intersection. The simulation environment was implemented in NetLogo, which allowed comparison of the impact of Smart traffic light use versus a fixed-time traffic light

Janus II: a new generation application-driven computer for spin-system simulations

This paper describes the architecture, the development and the implementation of Janus II, a new generation application-driven number cruncher optimized for Monte Carlo simulations of spin systems (mainly spin glasses). This domain of computational physics is a recognized grand challenge of high-performance computing: the resources necessary to study in detail theoretical models that can make contact with experimental data are by far beyond those available using commodity computer systems. On the other hand, several specific features of the associated algorithms suggest that unconventional computer architectures, which can be implemented with available electronics technologies, may lead to order of magnitude increases in performance, reducing to acceptable values on human scales the time needed to carry out simulation campaigns that would take centuries on commercially available machines. Janus II is one such machine, recently developed and commissioned, that builds upon and improves on the successful JANUS machine, which has been used for physics since 2008 and is still in operation today. This paper describes in detail the motivations behind the project, the computational requirements, the architecture and the implementation of this new machine and compares its expected performances with those of currently available commercial systems.Comment: 28 pages, 6 figure

The three dimensional Ising spin glass in an external magnetic field: the role of the silent majority

We perform equilibrium parallel-tempering simulations of the 3D Ising Edwards-Anderson spin glass in a field. A traditional analysis shows no signs of a phase transition. Yet, we encounter dramatic fluctuations in the behaviour of the model: Averages over all the data only describe the behaviour of a small fraction of it. Therefore we develop a new approach to study the equilibrium behaviour of the system, by classifying the measurements as a function of a conditioning variate. We propose a finite-size scaling analysis based on the probability distribution function of the conditioning variate, which may accelerate the convergence to the thermodynamic limit. In this way, we find a non-trivial spectrum of behaviours, where a part of the measurements behaves as the average, while the majority of them shows signs of scale invariance. As a result, we can estimate the temperature interval where the phase transition in a field ought to lie, if it exists. Although this would-be critical regime is unreachable with present resources, the numerical challenge is finally well posed.Comment: 42 pages, 19 figures. Minor changes and added figure (results unchanged

Embelin binds to human neuroserpin and impairs its polymerisation

Neuroserpin (NS) is a serpin inhibitor of tissue plasminogen activator (tPA) in the brain. The polymerisation of NS pathologic mutants is responsible for a genetic dementia known as familial encephalopathy with neuroserpin inclusion bodies (FENIB). So far, a pharmacological treatment of FENIB, i.e. an inhibitor of NS polymerisation, remains an unmet challenge. Here, we present a biophysical characterisation of the effects caused by embelin (EMB a small natural compound) on NS conformers and NS polymerisation. EMB destabilises all known NS conformers, specifically binding to NS molecules with a 1:1 NS:EMB molar ratio without unfolding the NS fold. In particular, NS polymers disaggregate in the presence of EMB, and their formation is prevented. The NS/EMB complex does not inhibit tPA proteolytic activity. Both effects are pharmacologically relevant: firstly by inhibiting the NS polymerisation associated to FENIB, and secondly by potentially antagonizing metastatic processes facilitated by NS activity in the brain

The bovine foot skin microbiota is associated with host genotype and the development of infectious digital dermatitis lesions

Abstract Background Bovine Digital Dermatitis (BDD) is a prevalent infectious disease, causing painful foot skin lesions and lameness in cattle. We describe herein the bovine foot skin microbiota and its associations with BDD using 16S rRNA gene amplicon and shotgun metagenomic sequencing on samples from 259 dairy cows from three UK dairy farms. Results We show evidence of dysbiosis, and differences in taxonomy and functional profiles in the bovine foot skin microbiome of clinically healthy animals that subsequently develop BDD lesions, compared to those that do not. Our results suggest that taxonomical and functional differences together with alterations in ecological interactions between bacteria in the normal foot skin microbiome may predispose an animal to develop BDD lesions. Using genome-wide association and regional heritability mapping approaches, we provide first evidence for interactions between host genotype and certain members of the foot skin microbiota. We show the existence of significant genetic variation in the relative abundance of Treponema spp. and Peptoclostridium spp. and identify regions in the bovine genome that explain a significant proportion of this variation. Conclusions Collectively this work shows early changes in taxonomic and functional profiles of the bovine foot-skin microbiota in clinically healthy animals which are associated with subsequent development of BDD and could be relevant to prevention of disease. The description of host genetic control of members of the foot skin microbiota, combined with the association of the latter with BDD development offer new insights into a complex relationship that can be exploited in selective breeding programmes. </jats:sec