Paralog re-emergence: a novel, historically contingent mechanism in the evolution of antimicrobial resistance

Evolution of resistance to drugs and pesticides poses a serious threat to human health and agricultural production. CYP51 encodes the target site of azole fungicides, widely used clinically and in agriculture. Azole resistance can evolve due to point mutations or overexpression of CYP51, and previous studies have shown that fungicide-resistant alleles have arisen by de novo mutation. Paralogs CYP51A and CYP51B are found in filamentous ascomycetes, but CYP51A has been lost from multiple lineages. Here, we show that in the barley pathogen Rhynchosporium commune, re-emergence of CYP51A constitutes a novel mechanism for the evolution of resistance to azoles. Pyrosequencing analysis of historical barley leaf samples from a unique long-term experiment from 1892 to 2008 indicates that the majority of the R. commune population lacked CYP51A until 1985, after which the frequency of CYP51A rapidly increased. Functional analysis demonstrates that CYP51A retains the same substrate as CYP51B, but with different transcriptional regulation. Phylogenetic analyses show that the origin of CYP51A far predates azole use, and newly sequenced Rhynchosporium genomes show CYP51A persisting in the R. commune lineage rather than being regained by horizontal gene transfer; therefore, CYP51A re-emergence provides an example of adaptation to novel compounds by selection from standing genetic variation.

Proposal of a floating mechanism based on magnetic levitation method toward EEG-driven robotic system

We discussed a floating mechanism based on quasi-magnetic levitation method that can be attached at the endpoint of a robot arm in order to construct a novel redundant robot arm for producing compliant motions. The floating mechanism can be composed of magnets and a constraint mechanism such that the repelling force of the magnets floats the endpoint part of the mechanism stable for the guided motions. The analytical and experimental results show that the proposed floating mechanism can produce stable floating motions with small inertia and viscosity. The results also show that the proposed mechanism can detect small force applied to the endpoint part because the friction force of the mechanism is very small.

Using an individual-based model to select among alternative foraging strategies of woodpigeons: data support a memory-based model with a flocking mechanism

Population modelling is increasingly recognised as a useful tool for pesticide risk assessment. For vertebrates that may ingest pesticides with their food, such as woodpigeon (Columba palumbus), population models that simulate foraging behaviour explicitly can help predicting both exposure and population-level impact. Optimal foraging theory is often assumed to explain the individual-level decisions driving distributions of individuals in the field, but it may not adequately predict spatial and temporal characteristics of woodpigeon foraging because of the woodpigeons’ excellent memory, ability to fly long distances, and distinctive flocking behaviour. Here we present an individual-based model (IBM) of the woodpigeon. We used the model to predict distributions of foraging woodpigeons that use one of six alternative foraging strategies: optimal foraging, memory-based foraging and random foraging, each with or without flocking mechanisms. We used pattern-oriented modelling to determine which of the foraging strategies is best able to reproduce observed data patterns. Data used for model evaluation were gathered during a long-term woodpigeon study conducted between 1961 and 2004 and a radiotracking study conducted in 2003 and 2004, both in the UK, and are summarised here as three complex patterns: the distributions of foraging birds between vegetation types during the year, the number of fields visited daily by individuals, and the proportion of fields revisited by them on subsequent days. The model with a memory-based foraging strategy and a flocking mechanism was the only one to reproduce these three data patterns, and the optimal foraging model produced poor matches to all of them. The random foraging strategy reproduced two of the three patterns but was not able to guarantee population persistence. We conclude that with the memory-based foraging strategy including a flocking mechanism our model is realistic enough to estimate the potential exposure of woodpigeons to pesticides. We discuss how exposure can be linked to our model, and how the model could be used for risk assessment of pesticides, for example predicting exposure and effects in heterogeneous landscapes planted seasonally with a variety of crops, while accounting for differences in land use between landscapes.

IMF control of cusp proton emission intensity and dayside convection: implications for component and anti-parallel reconnection

We study a brightening of the Lyman-alpha emission in the cusp which occurred in response to a short-lived southward turning of the interplanetary magnetic field (IMF) during a period of strongly enhanced solar wind plasma concentration. The cusp proton emission is detected using the SI-12 channel of the FUV imager on the IMAGE spacecraft. Analysis of the IMF observations recorded by the ACE and Wind spacecraft reveals that the assumption of a constant propagation lag from the upstream spacecraft to the Earth is not adequate for these high time-resolution studies. The variations of the southward IMF component observed by ACE and Wind allow for the calculation of the ACE-to-Earth lag as a function of time. Application of the derived propagation delays reveals that the intensity of the cusp emission varied systematically with the IMF clock angle, the relationship being particularly striking when the intensity is normalised to allow for the variation in the upstream solar wind proton concentration. The latitude of the cusp migrated equatorward while the lagged IMF pointed southward, confirming the lag calculation and indicating ongoing magnetopause reconnection. Dayside convection, as monitored by the SuperDARN network of radars, responded rapidly to the IMF changes but lagged behind the cusp proton emission response: this is shown to be as predicted by the model of flow excitation by Cowley and Lockwood (1992). We use the numerical cusp ion precipitation model of Lockwood and Davis (1996), along with modelled Lyman-_ emission efficiency and the SI-12 instrument response, to investigate the effect of the sheath field clock angle on the acceleration of ions on crossing the dayside magnetopause. This modelling reveals that the emission commences on each reconnected field line 2–2.5min after it is opened and peaks 3–5 min after it is opened. We discuss how comparison of the Lyman-alpha intensities with oxygen emissions observed simultaneously by the SI-13 channel of the FUV instrument offers an opportunity to test whether or not the clock angle dependence is consistent with the “component” or the “anti-parallel” reconnection hypothesis.

Towards a parallel computationally efficient approach to scaling up data stream classification

Advances in hardware technologies allow to capture and process data in real-time and the resulting high throughput data streams require novel data mining approaches. The research area of Data Stream Mining (DSM) is developing data mining algorithms that allow us to analyse these continuous streams of data in real-time. The creation and real-time adaption of classification models from data streams is one of the most challenging DSM tasks. Current classifiers for streaming data address this problem by using incremental learning algorithms. However, even so these algorithms are fast, they are challenged by high velocity data streams, where data instances are incoming at a fast rate. This is problematic if the applications desire that there is no or only a very little delay between changes in the patterns of the stream and absorption of these patterns by the classifier. Problems of scalability to Big Data of traditional data mining algorithms for static (non streaming) datasets have been addressed through the development of parallel classifiers. However, there is very little work on the parallelisation of data stream classification techniques. In this paper we investigate K-Nearest Neighbours (KNN) as the basis for a real-time adaptive and parallel methodology for scalable data stream classification tasks.

Friction in mid-latitude cyclones: an Ekman-PV mechanism

The mechanism by which the atmospheric boundary layer reduces the intensity of mid-latitude cyclones is investigated. It is demonstrated that two alternative theories, Ekman pumping and the baroclinic potential vorticity (PV) mechanism, in fact act in union to maximize the spin-down. Ekman pumping aids the ventilation of PV from the boundary layer, and shapes the resulting PV anomaly into one of increased static stability. PV inversion techniques are used to demonstrate how this anomaly reduces the coupling between the upper- and lower-levels within the cyclone, reducing the growth rate.

Increased dietary α-linolenic acid has sex-specific effects upon eicosapentaenoic acid status in humans: re-examination of data from a randomised, placebo-controlled, parallel study

Background: There is a metabolic pathway by which mammals can convert the omega-3 (n-3) essential fatty acid α-linolenic acid (ALA) into longer-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). As far as we know there are currently no studies that have specifically examined sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans, although acute studies with isotope-labelled ALA identified that women have a significantly greater capacity to synthesise EPA and DHA from ALA compared to men. Findings: Available data from a placebo-controlled, randomised study were re-examined to identify whether there are sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans. There was a significant difference between sexes in the response to increased dietary ALA, with women having a significantly greater increase in the EPA content of plasma phospholipids (mean +2.0% of total fatty acids) after six months of an ALA-rich diet compared to men (mean +0.7%, P = 0.039). Age and BMI were identified as predictors of response to dietary ALA among women. Conclusions: Women show a greater increase in circulating EPA than men during increased dietary ALA consumption. Further understanding of individual variation in the response to dietary ALA could inform nutrition advice, with recommendations being specifically tailored according to habitual diet, sex, age and BMI.

Investigating music tempo as a feedback mechanism for closed-loop BCI control

The feedback mechanism used in a brain-computer interface (BCI) forms an integral part of the closed-loop learning process required for successful operation of a BCI. However, ultimate success of the BCI may be dependent upon the modality of the feedback used. This study explores the use of music tempo as a feedback mechanism in BCI and compares it to the more commonly used visual feedback mechanism. Three different feedback modalities are compared for a kinaesthetic motor imagery BCI: visual, auditory via music tempo, and a combined visual and auditory feedback modality. Visual feedback is provided via the position, on the y-axis, of a moving ball. In the music feedback condition, the tempo of a piece of continuously generated music is dynamically adjusted via a novel music-generation method. All the feedback mechanisms allowed users to learn to control the BCI. However, users were not able to maintain as stable control with the music tempo feedback condition as they could in the visual feedback and combined conditions. Additionally, the combined condition exhibited significantly less inter-user variability, suggesting that multi-modal feedback may lead to more robust results. Finally, common spatial patterns are used to identify participant-specific spatial filters for each of the feedback modalities. The mean optimal spatial filter obtained for the music feedback condition is observed to be more diffuse and weaker than the mean spatial filters obtained for the visual and combined feedback conditions.

A parallel formulation for the simulation of a generic branch predictor

A parallel formulation for the simulation of a branch prediction algorithm is presented. This parallel formulation identifies independent tasks in the algorithm which can be executed concurrently. The parallel implementation is based on the multithreading model and two parallel programming platforms: pthreads and Cilk++. Improvement in execution performance by up to 7 times is observed for a generic 2-bit predictor in a 12-core multiprocessor system.

A mechanism of internal decadal atlantic ocean variability in a high-resolution coupled climate model

The North Atlantic Ocean subpolar gyre (NA SPG) is an important region for initialising decadal climate forecasts. Climate model simulations and palaeo climate reconstructions have indicated that this region could also exhibit large, internally generated variability on decadal timescales. Understanding these modes of variability, their consistency across models, and the conditions in which they exist, is clearly important for improving the skill of decadal predictions — particularly when these predictions are made with the same underlying climate models. Here we describe and analyse a mode of internal variability in the NA SPG in a state-of-the-art, high resolution, coupled climate model. This mode has a period of 17 years and explains 15–30% of the annual variance in related ocean indices. It arises due to the advection of heat content anomalies around the NA SPG. Anomalous circulation drives the variability in the southern half of the NA SPG, whilst mean circulation and anomalous temperatures are important in the northern half. A negative feedback between Labrador Sea temperatures/densities and those in the North Atlantic Current is identified, which allows for the phase reversal. The atmosphere is found to act as a positive feedback on to this mode via the North Atlantic Oscillation which itself exhibits a spectral peak at 17 years. Decadal ocean density changes associated with this mode are driven by variations in temperature, rather than salinity — a point which models often disagree on and which we suggest may affect the veracity of the underlying assumptions of anomaly-assimilating decadal prediction methodologies.

Unpacking the mechanism by which psychological ownership manifests at the level of the individual: a dynamic model of identity and self

Increasing prominence of the psychological ownership (PO) construct in management studies raises questions about how PO manifests at the level of the individual. In this article, we unpack the mechanism by which individuals use PO to express aspects of their identity and explore how PO manifestations can display congruence as well as incongruence between layers of self. As a conceptual foundation, we develop a dynamic model of individual identity that differentiates between four layers of self, namely, the “core self,” “learned self,” “lived self,” and “perceived self.” We then bring identity and PO literatures together to suggest a framework of PO manifestation and expression viewed through the lens of the four presented layers of self. In exploring our framework, we develop a number of propositions that lay the foundation for future empirical and conceptual work and discuss implications for theory and practice.

Syk-dependent phosphorylation of CLEC-2: a novel mechanism of hem-immunoreceptor tyrosine-based activation motif signalling

The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors.

Revisiting the ‘Venturi effect’ in passage ventilation between two non-parallel buildings

A recent study conducted by Blocken et al. (Numerical study on the existence of the Venturi effect in passages between perpendicular buildings. Journal of Engineering Mechanics, 2008,134: 1021-1028) challenged the popular view of the existence of the ‘Venturi effect’ in building passages as the wind is exposed to an open boundary. The present research extends the work of Blocken et al. (2008a) into a more general setup with the building orientation varying from 0° to 180° using CFD simulations. Our results reveal that the passage flow is mainly determined by the combination of corner streams. It is also shown that converging passages have a higher wind-blocking effect compared to diverging passages, explained by a lower wind speed and higher drag coefficient. Fluxes on the top plane of the passage volume reverse from outflow to inflow in the cases of α=135°, 150° and 165°. A simple mathematical expression to explain the relationship between the flux ratio and the geometric parameters has been developed to aid wind design in an urban neighborhood. In addition, a converging passage with α=15° is recommended for urban wind design in cold and temperate climates since the passage flow changes smoothly and a relatively lower wind speed is expected compared with that where there are no buildings. While for the high-density urban area in (sub)tropical climates such as Hong Kong where there is a desire for more wind, a diverging passage with α=150° is a better choice to promote ventilation at the pedestrian level.