Propositionalisation of multiple sequence alignments using probabilistic models

Multiple sequence alignments play a central role in Bioinformatics. Most alignment representations are designed to facilitate knowledge extraction by human experts. Additionally statistical models like Profile Hidden Markov Models are used as representations. They offer the advantage to provide sound, probabilistic scores. The basic idea we present in this paper is to use the structure of a Profile Hidden Markov Model for propositionalisation. This way we get a simple, extendable representation of multiple sequence alignments which facilitates further analysis by Machine Learning algorighms

PIRATE: A Remotely Operable Telescope for Research and Education

This thesis introduces PIRATE, a remotely operable telescope facility for use in research and education, constructed from off-the-shelf hardware, operated by the Open University. It focuses on the PIRATE Mark 1 and PIRATE Mark 1.5 phases of operation; the telescope facility has been in the Mark 2 phase since September 2011. Situated at the Observatori Astronomic de Mallorca, PIRATE is currently used to follow up potential transiting extrasolar planet candidates produced by the SuperWASP North experiment, as well as to hunt for novae in M31 and other nearby galaxies. It is operated by a mixture of commercially available software and proprietary software. In this thesis I discuss the hardware and its characterisation, problems with performing precision time-series photometry when using a German Equatorial Mount, and the PIRATE pipeline developed to assist with the fast and effective production of results from the follow-up observations of potential transiting extrasolar planets. I then go on to discuss the logistics of the follow-up program, and present the results from the PIRATE Mark 1 and 1.5 follow-up data, followed by the results from observational work on known transiting systems (such as WASP-12b). A discussion of areas for improvement and possible avenues for future work concludes the thesis

General description of quasi-adiabatic dynamical phenomena near exceptional points

The appearance of so-called exceptional points in the complex spectra of non-Hermitian systems is often associated with phenomena that contradict our physical intuition. One example of particular interest is the state-exchange process predicted for an adiabatic encircling of an exceptional point. In this work we analyse this and related processes for the generic system of two coupled oscillator modes with loss or gain. We identify a characteristic system evolution consisting of periods of quasi-stationarity interrupted by abrupt non-adiabatic transitions, and we present a qualitative and quantitative description of this switching behaviour by connecting the problem to the phenomenon of stability loss delay. This approach makes accurate predictions for the breakdown of the adiabatic theorem as well as the occurrence of chiral behavior observed previously in this context, and provides a general framework to model and understand quasi-adiabatic dynamical effects in non-Hermitian systems.Comment: Main text: 9 pages; 5 figures. Appendix: 4 pages; 1 figur

An efficient algorithm for the parallel solution of high-dimensional differential equations

The study of high-dimensional differential equations is challenging and difficult due to the analytical and computational intractability. Here, we improve the speed of waveform relaxation (WR), a method to simulate high-dimensional differential-algebraic equations. This new method termed adaptive waveform relaxation (AWR) is tested on a communication network example. Further we propose different heuristics for computing graph partitions tailored to adaptive waveform relaxation. We find that AWR coupled with appropriate graph partitioning methods provides a speedup by a factor between 3 and 16

PIRATE - the piCETL Astronomical Telescope Explorer

We have set up PIRATE, a remotely operable 35 cm astronomical telescope in a robotic dome at the Observatori Astronomic de Mallorca, to pilot the realtime use of a telescope by distance-leaning students from their home. Remote access software, webpages and course materials for third level Open University students were developed. The experience from the first cohort of students of a 10 week-long project based on PIRATE demonstrates the success of the PIRATE concept for teaching practical science at a distance, and highlights the benefits distance learning students draw from a stimulating framework that facilitates group working

Genome and Plasmid Sequences of Escherichia coli KV7, an Extended-Spectrum β-Lactamase Isolate Derived from Feces of a Healthy Pig.

We present single-contig assemblies for Escherichia coli strain KV7 (serotype O27, phylogenetic group D) and its six plasmids, isolated from a healthy pig, as determined by PacBio RS II and Illumina MiSeq sequencing. The chromosome of 4,997,475 bp and G+C content of 50.75% harbored 4,540 protein-encoding genes

Dynamic optical coherence tomography of blood vessels in cutaneous melanoma — correlation with histology, immunohistochemistry and dermoscopy

Dermoscopy adds important information to the assessment of cutaneous melanoma, but the risk of progression is predicted by histologic parameters and therefore requires surgery and histopathologic preparation. Neo-vascularization is crucial for tumor progression and worsens prognosis. The aim of this study was the in vivo evaluation of blood vessel patterns in melanoma with dynamic optical coherence tomography (D-OCT) and the correlation with dermoscopic and histologic malignancy parameters for the risk assessment of melanoma. In D-OCT vessel patterns, shape, distribution and presence/type of branching of 49 melanomas were evaluated in vivo at three depths and correlated with the same patterns in dermoscopy and with histologic parameters after excision. In D-OCT, blood vessel density and atypical shapes (coils and serpiginous vessels) increased with higher tumor stage. The histologic parameters ulceration and Hmb45- and Ki67-positivity increased, whereas regression, inflammation and PD-L1-positivity decreased with risk. CD31, VEGF and Podoplanin correlated with D-OCT vasculature findings. B-RAF mutation status had no influence. Due to pigment overlay and the summation effect, the vessel evaluation in dermoscopy and D-OCT did not correlate well. In summary, atypical vessel patterns in melanoma correlate with histologic parameters for risk for metastases. Tumor vasculature can be noninvasively assessed using D-OCT before surgery

PITX2 Modulates Atrial Membrane Potential and the Antiarrhythmic Effects of Sodium-Channel Blockers.

BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs. METHODS: LA PITX2 messenger ribonucleic acid (mRNA) levels were measured in 95 patients undergoing thoracoscopic AF ablation. The effects of flecainide, a sodium (Na(+))-channel blocker, and d,l-sotalol, a potassium channel blocker, were studied in littermate mice with normal and reduced Pitx2c mRNA by electrophysiological study, optical mapping, and patch clamp studies. PITX2-dependent mechanisms of antiarrhythmic drug action were studied in human embryonic kidney (HEK) cells expressing human Na channels and by modeling human action potentials. RESULTS: Flecainide 1 μmol/l was more effective in suppressing atrial arrhythmias in atria with reduced Pitx2c mRNA levels (Pitx2c(+/-)). Resting membrane potential was more depolarized in Pitx2c(+/-) atria, and TWIK-related acid-sensitive K(+) channel 2 (TASK-2) gene and protein expression were decreased. This resulted in enhanced post-repolarization refractoriness and more effective Na-channel inhibition. Defined holding potentials eliminated differences in flecainide's effects between wild-type and Pitx2c(+/-) atrial cardiomyocytes. More positive holding potentials replicated the increased effectiveness of flecainide in blocking human Nav1.5 channels in HEK293 cells. Computer modeling reproduced an enhanced effectiveness of Na-channel block when resting membrane potential was slightly depolarized. CONCLUSIONS: PITX2 mRNA modulates atrial resting membrane potential and thereby alters the effectiveness of Na-channel blockers. PITX2 and ion channels regulating the resting membrane potential may provide novel targets for antiarrhythmic drug development and companion therapeutics in AF

Muscle strength mediates the relationship between mitochondrial energetics and walking performance

Skeletal muscle mitochondrial oxidative capacity declines with age and negatively affects walking performance, but the mechanism for this association is not fully clear. We tested the hypothesis that impaired oxidative capacity affects muscle performance and, through this mechanism, has a negative effect on walking speed. Muscle mitochondrial oxidative capacity was measured by in vivo phosphorus magnetic resonance spectroscopy as the postexercise phosphocreatine resynthesis rate, kPCr , in 326 participants (154 men), aged 24-97 years (mean 71), in the Baltimore Longitudinal Study of Aging. Muscle strength and quality were determined by knee extension isokinetic strength, and the ratio of knee extension strength to thigh muscle cross-sectional area derived from computed topography, respectively. Four walking tasks were evaluated: a usual pace over 6 m and for 150 s, and a rapid pace over 6 m and 400 m. In multivariate linear regression analyses, kPCr was associated with muscle strength (β = 0.140, P = 0.007) and muscle quality (β = 0.127, P = 0.022), independent of age, sex, height, and weight; muscle strength was also a significant independent correlate of walking speed (P < 0.02 for all tasks) and in a formal mediation analysis significantly attenuated the association between kPCr and three of four walking tasks (18-29% reduction in β for kPCr ). This is the first demonstration in human adults that mitochondrial function affects muscle strength and that inefficiency in muscle bioenergetics partially accounts for differences in mobility through this mechanism