An experimental validation of the fatigue damaging events extracted using the wavelet bump extraction (WBE) algorithm

This paper describes an experimental validation of the fatigue damaging events that were identified and extracted using a wavelet-based fatigue data editing technique. This technique, known as the Wavelet Bump Extraction (WBE) algorithm, is specifically designed to summarise a long record of fatigue variable amplitude (VA) loading whilst preserving the original load cycle sequence. Using WBE the fatigue damaging events were identified and extracted in order to produce a mission signal. In order to validate the effectiveness of WBE in practical applications a VA road load time history that was measured on a road vehicle suspension arm was taken as a case study. Uniaxial fatigue tests were performed using the original signal, the WBE mission signal and the individual WBE extracted segments. A mirror polished specimen of SAE 1042 steel was tested using a servo-hydraulic machine. The fatigue lives measured for these VA loadings were then compared to the fatigue lives calculated from a VA strain loading fatigue damage model. The results show a good fatigue life correlation at the coefficient of 0.98 between the prediction and experiment. For the road load time history considered, the WBE mission signal was found to be only 40% the time duration of the original time history while maintaining 60% of the fatigue damage according to analytical calculation and 87% according to experimental testing

Bump extraction algorithm for variable amplitude fatigue loading

This paper presents the development of a fatigue mission synthesis algorithm, called Wavelet Bump Extraction (WBE), for summarising long records of fatigue road load data. This algorithm is used to extract fatigue damaging events or bumps in the record that cause the majority of the fatigue damage, whilst preserving the load cycle sequences. Bumps are identified from characteristic frequency bands in the load spectrum using the 12th order Daubechies wavelet. The bumps are combined to produce a mission signal which has equivalent signal statistics and fatigue damage to the original signal. The WBE accuracy has been evaluated by observing the cycle sequence effects of the bump loadings. The WBE was compared with the time domain fatigue data editing method, so that the effectiveness of WBE can be verified. Using WBE, a substantial compression of the load-time history could be achieved for the purpose of accelerated fatigue tests in the automotive industry

e-MERLIN 21 cm constraints on the mass-loss rates of OB stars in Cyg OB2

We present e-MERLIN 21 cm (L-band) observations of single luminous OB stars in the Cygnus OB2 association, from the Cyg OB2 Radio Survey Legacy programme. The radio observations potentially offer the most straightforward, least model-dependent, determinations of mass-loss rates, and can be used to help resolve current discrepancies in mass-loss rates via clumped and structured hot star winds. We report here that the 21 cm flux densities of O3 to O6 supergiant and giant stars are less than ∼70 μJy. These fluxes may be translated to ‘smooth’ wind mass-loss upper limits of ∼4.4–4.8 × 10−6 M⊙ yr −1 for O3 supergiants and ≲2.9 × 10−6 M⊙ yr −1 for B0 to B1 supergiants. The first ever resolved 21 cm detections of the hypergiant (and luminous blue variable candidate) Cyg OB2 #12 are discussed; for multiple observations separated by 14 d, we detect an ∼69 per cent increase in its flux density. Our constraints on the upper limits for the mass-loss rates of evolved OB stars in Cyg OB2 support the model that the inner wind region close to the stellar surface (where Hα forms) is more clumped than the very extended geometric region sampled by our radio observations

Complement C3 variant and the risk of age-related macular degeneration

Background: Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis.Methods: We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls.Results: The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9 x 10(sup -5)) and the Scottish group (244 cases and 351 controls, P=5.0 x 10(sup -5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%.Conclusions: Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease

Software Lock Mass by Two-Dimensional Minimization of Peptide Mass Errors

Mass accuracy is a key parameter in proteomic experiments, improving specificity, and success rates of peptide identification. Advances in instrumentation now make it possible to routinely obtain high resolution data in proteomic experiments. To compensate for drifts in instrument calibration, a compound of known mass is often employed. This ‘lock mass’ provides an internal mass standard in every spectrum. Here we take advantage of the complexity of typical peptide mixtures in proteomics to eliminate the requirement for a physical lock mass. We find that mass scale drift is primarily a function of the m/z and the elution time dimensions. Using a subset of high confidence peptide identifications from a first pass database search, which effectively substitute for the lock mass, we set up a global mathematical minimization problem. We perform a simultaneous fit in two dimensions using a function whose parameterization is automatically adjusted to the complexity of the analyzed peptide mixture. Mass deviation of the high confidence peptides from their calculated values is then minimized globally as a function of both m/z value and elution time. The resulting recalibration function performs equal or better than adding a lock mass from laboratory air to LTQ-Orbitrap spectra. This ‘software lock mass’ drastically improves mass accuracy compared with mass measurement without lock mass (up to 10-fold), with none of the experimental cost of a physical lock mass, and it integrated into the freely available MaxQuant analysis pipeline (www.maxquant.org)

Predictive validity of the UK clinical aptitude test in the final years of medical school:a prospective cohort study

Peer reviewedPublisher PD

Semantic distillation: a method for clustering objects by their contextual specificity

Techniques for data-mining, latent semantic analysis, contextual search of databases, etc. have long ago been developed by computer scientists working on information retrieval (IR). Experimental scientists, from all disciplines, having to analyse large collections of raw experimental data (astronomical, physical, biological, etc.) have developed powerful methods for their statistical analysis and for clustering, categorising, and classifying objects. Finally, physicists have developed a theory of quantum measurement, unifying the logical, algebraic, and probabilistic aspects of queries into a single formalism. The purpose of this paper is twofold: first to show that when formulated at an abstract level, problems from IR, from statistical data analysis, and from physical measurement theories are very similar and hence can profitably be cross-fertilised, and, secondly, to propose a novel method of fuzzy hierarchical clustering, termed \textit{semantic distillation} -- strongly inspired from the theory of quantum measurement --, we developed to analyse raw data coming from various types of experiments on DNA arrays. We illustrate the method by analysing DNA arrays experiments and clustering the genes of the array according to their specificity.Comment: Accepted for publication in Studies in Computational Intelligence, Springer-Verla

Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus

Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) research in particular, improved methods for predicting this cross-protection are critical for predicting the severity of outbreaks within endemic settings where multiple serotypes and subtypes commonly co-circulate, as well as for deciding whether appropriate vaccine(s) exist and how much they could mitigate the effects of any outbreak. To identify antigenic relationships and their predictors, we used linear mixed effects models to account for variation in pairwise cross-neutralization titres using only viral sequences and structural data. We identified those substitutions in surface-exposed structural proteins that are correlates of loss of cross-reactivity. These allowed prediction of both the best vaccine match for any single virus and the breadth of coverage of new vaccine candidates from their capsid sequences as effectively as or better than serology. Sub-sequences chosen by the model-building process all contained sites that are known epitopes on other serotypes. Furthermore, for the SAT1 serotype, for which epitopes have never previously been identified, we provide strong evidence - by controlling for phylogenetic structure - for the presence of three epitopes across a panel of viruses and quantify the relative significance of some individual residues in determining cross-neutralization. Identifying and quantifying the importance of sites that predict viral strain cross-reactivity not just for single viruses but across entire serotypes can help in the design of vaccines with better targeting and broader coverage. These techniques can be generalized to any infectious agents where cross-reactivity assays have been carried out. As the parameterization uses pre-existing datasets, this approach quickly and cheaply increases both our understanding of antigenic relationships and our power to control disease