Accommodating repair actions into gas turbine prognostics

Elements of gas turbine degradation, such as compressor fouling, are recoverable through maintenance actions like compressor washing. These actions increase the usable engine life and optimise the performance of the gas turbine. However, these maintenance actions are performed by a separate organization to those undertaking fleet management operations, leading to significant uncertainty in the maintenance state of the asset. The uncertainty surrounding maintenance actions impacts prognostic efficacy. In this paper, we adopt Bayesian on-line change point detection to detect the compressor washing events. Then, the event detection information is used as an input to a prognostic algorithm, advising an update to the estimation of remaining useful life. To illustrate the capability of the approach, we demonstrated our on-line Bayesian change detection algorithms on synthetic and real aircraft engine service data, in order to identify the compressor washing events for a gas turbine and thus provide demonstrably improved prognosis

Parallel compensatory evolution stabilizes plasmids across the parasitism-mutualism continuum

Plasmids drive genomic diversity in bacteria via horizontal gene transfer [1 and 2]; nevertheless, explaining their survival in bacterial populations is challenging [3]. Theory predicts that irrespective of their net fitness effects, plasmids should be lost: when parasitic (costs outweigh benefits), plasmids should decline due to purifying selection [4, 5 and 6], yet under mutualism (benefits outweigh costs), selection favors the capture of beneficial accessory genes by the chromosome and loss of the costly plasmid backbone [4]. While compensatory evolution can enhance plasmid stability within populations [7, 8, 9, 10, 11, 12, 13, 14 and 15], the propensity for this to occur across the parasitism-mutualism continuum is unknown. We experimentally evolved Pseudomonas fluorescens and its mercury resistance mega-plasmid, pQBR103 [ 16], across an environment-mediated parasitism-mutualism continuum. Compensatory evolution stabilized plasmids by rapidly ameliorating the cost of plasmid carriage in all environments. Genomic analysis revealed that, in both parasitic and mutualistic treatments, evolution repeatedly targeted the gacA/gacS bacterial two-component global regulatory system while leaving the plasmid sequence intact. Deletion of either gacA or gacS was sufficient to completely ameliorate the cost of plasmid carriage. Mutation of gacA/gacS downregulated the expression of ∼17% of chromosomal and plasmid genes and appears to have relieved the translational demand imposed by the plasmid. Chromosomal capture of mercury resistance accompanied by plasmid loss occurred throughout the experiment but very rarely invaded to high frequency, suggesting that rapid compensatory evolution can limit this process. Compensatory evolution can explain the widespread occurrence of plasmids and allows bacteria to retain horizontally acquired plasmids even in environments where their accessory genes are not immediately useful

Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans

BACKGROUND: Systemic infections commonly cause sickness symptoms including psychomotor retardation. Inflammatory cytokines released during the innate immune response are implicated in the communication of peripheral inflammatory signals to the brain. METHODS: We used functional magnetic resonance brain imaging (fMRI) to investigate neural effects of peripheral inflammation following typhoid vaccination in 16 healthy men, using a double-blind, randomized, crossover-controlled design. RESULTS: Vaccination had no global effect on neurovascular coupling but markedly perturbed neural reactivity within substantia nigra during low-level visual stimulation. During a cognitive task, individuals in whom typhoid vaccination engendered higher levels of circulating interleukin-6 had significantly slower reaction time responses. Prolonged reaction times and larger interleukin-6 responses were associated with evoked neural activity within substantia nigra. CONCLUSIONS: Our findings provide mechanistic insights into the interaction between inflammatio

Bacteriophages limit the existence conditions for conjugative plasmids

Bacteriophages are a major cause of bacterial mortality and impose strong selection on natural bacterial populations, yet their effects on the dynamics of conjugative plasmids have rarely been tested. We combined experimental evolution, mathematical modeling, and individual-based simulations to explain how the ecological and population genetics effects of bacteriophages upon bacteria interact to determine the dynamics of conjugative plasmids and their persistence. The ecological effects of bacteriophages on bacteria are predicted to limit the existence conditions for conjugative plasmids, preventing persistence under weak selection for plasmid accessory traits. Experiments showed that phages drove faster extinction of plasmids in environments where the plasmid conferred no benefit, but they also revealed more complex effects of phages on plasmid dynamics under these conditions, specifically, the temporary maintenance of plasmids at fixation followed by rapid loss. We hypothesized that the population genetic effects of bacteriophages, specifically, selection for phage resistance mutations, may have caused this. Further mathematical modeling and individual-based simulations supported our hypothesis, showing that conjugative plasmids may hitchhike with phage resistance mutations in the bacterial chromosome

CATHEDRAL: A Fast and Effective Algorithm to Predict Folds and Domain Boundaries from Multidomain Protein Structures

We present CATHEDRAL, an iterative protocol for determining the location of previously observed protein folds in novel multidomain protein structures. CATHEDRAL builds on the features of a fast secondary-structure–based method (using graph theory) to locate known folds within a multidomain context and a residue-based, double-dynamic programming algorithm, which is used to align members of the target fold groups against the query protein structure to identify the closest relative and assign domain boundaries. To increase the fidelity of the assignments, a support vector machine is used to provide an optimal scoring scheme. Once a domain is verified, it is excised, and the search protocol is repeated in an iterative fashion until all recognisable domains have been identified. We have performed an initial benchmark of CATHEDRAL against other publicly available structure comparison methods using a consensus dataset of domains derived from the CATH and SCOP domain classifications. CATHEDRAL shows superior performance in fold recognition and alignment accuracy when compared with many equivalent methods. If a novel multidomain structure contains a known fold, CATHEDRAL will locate it in 90% of cases, with <1% false positives. For nearly 80% of assigned domains in a manually validated test set, the boundaries were correctly delineated within a tolerance of ten residues. For the remaining cases, previously classified domains were very remotely related to the query chain so that embellishments to the core of the fold caused significant differences in domain sizes and manual refinement of the boundaries was necessary. To put this performance in context, a well-established sequence method based on hidden Markov models was only able to detect 65% of domains, with 33% of the subsequent boundaries assigned within ten residues. Since, on average, 50% of newly determined protein structures contain more than one domain unit, and typically 90% or more of these domains are already classified in CATH, CATHEDRAL will considerably facilitate the automation of protein structure classification

Rapid compensatory evolution promotes the survival of conjugative plasmids

Conjugative plasmids play a vital role in bacterial adaptation through horizontal gene transfer. Explaining how plasmids persist in host populations however is difficult, given the high costs often associated with plasmid carriage. Compensatory evolution to ameliorate this cost can rescue plasmids from extinction. In a recently published study we showed that compensatory evolution repeatedly targeted the same bacterial regulatory system, GacA/GacS, in populations of plasmid-carrying bacteria evolving across a range of selective environments. Mutations in these genes arose rapidly and completely eliminated the cost of plasmid carriage. Here we extend our analysis using an individual based model to explore the dynamics of compensatory evolution in this system. We show that mutations which ameliorate the cost of plasmid carriage can prevent both the loss of plasmids from the population and the fixation of accessory traits on the bacterial chromosome. We discuss how dependent the outcome of compensatory evolution is on the strength and availability of such mutations and the rate at which beneficial accessory traits integrate on the host chromosome

Effectiveness of an educational intervention for general practice teams to deliver problem focused therapy for insomnia: pilot cluster randomised trial

Introduction Sleep problems are common leading to physical and psychosocial morbidity and impaired quality of life. Sufferers often seek help from primary care and receive advice or hypnotic drugs which are ineffective long term. Cognitive behavioural therapy for insomnia (CBTi) is effective but is not widely used in general practice. We conducted a pilot study to test procedures and collect information in preparation for a larger definitive trial to measure effectiveness and cost-effectiveness of an educational intervention for general practitioners and primary care nurses a to deliver problem focused therapy to adults Methods This was a pilot cluster randomised controlled trial. General practices were randomised to an educational intervention (2x2 hours) for problem focused therapy which comprised assessment (of secondary causes, severity and using sleep diaries) and modified CBTi compared with usual care (sleep hygiene advice and hypnotic drugs). We recruited patients with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety and Pittsburgh Sleep Quality Index (PSQI≥4). The primary outcome was PSQI and secondary outcomes including Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Beck Depression Inventory and PSYCHLOPS were measured at 0, 4, 8 and 13 weeks. Intervention fidelity was evaluated using telephone interviews of participating practitioners and patients. Results Out of 64 participants recruited, 37 completed the trial. Analysis was conducted masked to treatment allocation. We used a mixed effects model to test for overall change and whether the intervention affected the rate of change over time. There was significant dropout during the pilot study, mainly due to delays in recruitment. We detected neither an overall change over time (PSQI score increase per week 0.06 (95%CI -0.03 to 0.16) nor differential change between intervention and control groups 0.10 (-0.03 to 0.23) although the study was not powered to detect such a change. Conclusion This pilot study confirmed that it was feasible to undertake a trial of education for primary care clinicians to deliver problem focused therapy for insomnia in general practice but also exposed problems with study recruitment, dropout, and intervention fidelity which should be addressed in the design of a full trial

Population genetic structure and direct observations reveal sex-reversed patterns of dispersal in a cooperative bird.

Sex-biased dispersal is pervasive and has diverse evolutionary implications, but the fundamental drivers of dispersal sex biases remain unresolved. This is due in part to limited diversity within taxonomic groups in the direction of dispersal sex biases, which leaves hypothesis testing critically dependent upon identifying rare reversals of taxonomic norms. Here, we use a combination of observational and genetic data to demonstrate a rare reversal of the avian sex bias in dispersal in the cooperatively breeding white-browed sparrow weaver (Plocepasser mahali). Direct observations revealed that (i) natal philopatry was rare, with both sexes typically dispersing locally to breed, and (ii), unusually for birds, males bred at significantly greater distances from their natal group than females. Population genetic analyses confirmed these patterns, as (i) corrected Assignment index (AIc), FST tests and isolation-by-distance metrics were all indicative of longer dispersal distances among males than females, and (ii) spatial autocorrelation analysis indicated stronger within-group genetic structure among females than males. Examining the spatial scale of extra-group mating highlighted that the resulting 'sperm dispersal' could have acted in concert with individual dispersal to generate these genetic patterns, but gamete dispersal alone cannot account entirely for the sex differences in genetic structure observed. That leading hypotheses for the evolution of dispersal sex biases cannot readily account for these sex-reversed patterns of dispersal in white-browed sparrow weavers highlights the continued need for attention to alternative explanations for this enigmatic phenomenon. We highlight the potential importance of sex differences in the distances over which dispersal opportunities can be detected

BALANCE VARIABILITY DURING THE PYRAMID EXECUTION IN ACROBATIC GYMNASTICS

The objective of this study was to analyse the relationship between intra-trial variability in balance scores obtained via a force platform and acrobatic gymnasts’ pyramid scores provided by a qualified and experienced judge. Twelve acrobatic gymnasts grouped in pairs performed five successful straddle lever pyramids on two force platforms with one foot on each platform. The variability of path length of the centre of pressure of each foot was examined to analyse the balance of the pyramid. The variability of path length was negatively correlated with pyramid score in both legs, non-preferred (rho = -0.706 [very large]) and preferred leg (rho = -0.530 [large]). The results suggest a relationship between intra-trial variability and pyramid performance