Sparse probability density function estimation using the minimum integrated square error

We develop a new sparse kernel density estimator using a forward constrained regression framework, within which the nonnegative and summing-to-unity constraints of the mixing weights can easily be satisfied. Our main contribution is to derive a recursive algorithm to select significant kernels one at time based on the minimum integrated square error (MISE) criterion for both the selection of kernels and the estimation of mixing weights. The proposed approach is simple to implement and the associated computational cost is very low. Specifically, the complexity of our algorithm is in the order of the number of training data N, which is much lower than the order of N2 offered by the best existing sparse kernel density estimators. Numerical examples are employed to demonstrate that the proposed approach is effective in constructing sparse kernel density estimators with comparable accuracy to those of the classical Parzen window estimate and other existing sparse kernel density estimators.

Use of synthetic CaV2.2 Ca2+ channel peptides to study presynaptic function

Small, synthetic peptides based on specific regions of voltage-gated Ca2+ channels (VGCCs) have been widely used to study Ca2+ channel function and have been instrumental in confirming the contribution of specific amino acid sequences to interactions with putative binding partners. In particular, peptides based on the Ca2+ channel Alpha Interaction Domain (AID) on the intracellular region connecting domains I and II (the I-II loop) and the SYNaptic PRotein INTerction (synprint) site on the II-III loop have been widely used. Emerging evidence suggests that such peptides may themselves possess inherent functionality, a property that may be exploitable for future drug design. Here, we review our recent work using synthetic Ca2+ channel peptides based on sequences within the CaV2.2 amino terminal and I-II loop, originally identified as molecular determinates for G protein modulation, and their effects on VGCC function. These CaV2.2 peptides act as inhibitory modules to decrease Ca2+ influx with direct effects on VGCC gating, ultimately leading to a reduction of synaptic transmission. CaV2.2 peptides also attenuate G protein modulation of VGCCs. Amino acid substitutions generate CaV2.2 peptides with increased or decreased inhibitory effects suggesting that synthetic peptides can be used to further probe VGCC function and, potentially, form the basis for novel therapeutic development.

Wave-activity conservation laws and stability theorems for semi-geostrophic dynamics: part 1. pseudomomentum-based theory

There exists a well-developed body of theory based on quasi-geostrophic (QG) dynamics that is central to our present understanding of large-scale atmospheric and oceanic dynamics. An important question is the extent to which this body of theory may generalize to more accurate dynamical models. As a first step in this process, we here generalize a set of theoretical results, concerning the evolution of disturbances to prescribed basic states, to semi-geostrophic (SG) dynamics. SG dynamics, like QG dynamics, is a Hamiltonian balanced model whose evolution is described by the material conservation of potential vorticity, together with an invertibility principle relating the potential vorticity to the advecting fields. SG dynamics has features that make it a good prototype for balanced models that are more accurate than QG dynamics. In the first part of this two-part study, we derive a pseudomomentum invariant for the SG equations, and use it to obtain: (i) linear and nonlinear generalized Charney–Stern theorems for disturbances to parallel flows; (ii) a finite-amplitude local conservation law for the invariant, obeying the group-velocity property in the WKB limit; and (iii) a wave-mean-flow interaction theorem consisting of generalized Eliassen–Palm flux diagnostics, an elliptic equation for the stream-function tendency, and a non-acceleration theorem. All these results are analogous to their QG forms. The pseudomomentum invariant – a conserved second-order disturbance quantity that is associated with zonal symmetry – is constructed using a variational principle in a similar manner to the QG calculations. Such an approach is possible when the equations of motion under the geostrophic momentum approximation are transformed to isentropic and geostrophic coordinates, in which the ageostrophic advection terms are no longer explicit. Symmetry-related wave-activity invariants such as the pseudomomentum then arise naturally from the Hamiltonian structure of the SG equations. We avoid use of the so-called ‘massless layer’ approach to the modelling of isentropic gradients at the lower boundary, preferring instead to incorporate explicitly those boundary contributions into the wave-activity and stability results. This makes the analogy with QG dynamics most transparent. This paper treats the f-plane Boussinesq form of SG dynamics, and its recent extension to β-plane, compressible flow by Magnusdottir & Schubert. In the limit of small Rossby number, the results reduce to their respective QG forms. Novel features particular to SG dynamics include apparently unnoticed lateral boundary stability criteria in (i), and the necessity of including additional zonal-mean eddy correlation terms besides the zonal-mean potential vorticity fluxes in the wave-mean-flow balance in (iii). In the companion paper, wave-activity conservation laws and stability theorems based on the SG form of the pseudoenergy are presented.

Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function

Within the healthy population, there is substantial, heritable, and interindividual variability in the platelet response. We explored whether a proportion of this variability could be accounted for by interindividual variation in gene expression. Through a correlative analysis of genome-wide platelet RNA expression data from 37 subjects representing the normal range of platelet responsiveness within a cohort of 500 subjects, we identified 63 genes in which transcript levels correlated with variation in the platelet response to adenosine diphosphate and/or the collagen-mimetic peptide, cross-linked collagen-related peptide. Many of these encode proteins with no reported function in platelets. An association study of 6 of the 63 genes in 4235 cases and 6379 controls showed a putative association with myocardial infarction for COMMD7 (COMM domain-containing protein 7) and a major deviation from the null hypo thesis for LRRFIP1 [leucine-rich repeat (in FLII) interacting protein 1]. Morpholino-based silencing in Danio rerio identified a modest role for commd7 and a significant effect for lrrfip1 as positive regulators of thrombus formation. Proteomic analysis of human platelet LRRFIP1-interacting proteins indicated that LRRFIP1 functions as a component of the platelet cytoskeleton, where it interacts with the actin-remodeling proteins Flightless-1 and Drebrin. Taken together, these data reveal novel proteins regulating the platelet response.

Identification of partial resetting using De as a function of illumination time

Modern age samples from various depositional environments were examined for signal resetting. For 19 modern aeolian/beach samples all De values obtained were View the MathML source, with ∼70% having View the MathML source. For 21 fluvial/colluvial samples, all De values were View the MathML source with ∼80% being View the MathML source. De as a function of illumination (OSL measurement) time (De(t)) plots were examined for all samples. Based on previous laboratory experiments, increases in De(t) were expected for partially reset samples, and constant De(t) for fully reset samples. All aeolian samples, both modern age and additional ‘young’ samples (<1000 years), showed constant (flat) De(t) while all modern, non-zero De, fluvial/colluvial samples showed increasing De(t). ‘Replacement plots’, where a regenerated signal is substituted for the natural, yielded constant (flat) De(t). These findings support strongly the use of De(t) as a method of identifying incomplete resetting in fluvial samples. Potential complicating factors, such as illumination (bleaching) spectrum, thermal instability and component composition are discussed and a series of internal checks on the applicability of the De(t) for each individual aliquot/grain level are outlined.

Endocannabinoids in neuroendopsychology: multiphasic control of mitochondrial function

The endocannabinoid system (ECS) is a construct based on the discovery of receptors that are modulated by the plant compound tetrahydrocannabinol and the subsequent identification of a family of nascent ligands, the 'endocannabinoids'. The function of the ECS is thus defined by modulation of these receptors-in particular, by two of the best-described ligands (2-arachidonyl glycerol and anandamide), and by their metabolic pathways. Endocannabinoids are released by cell stress, and promote both cell survival and death according to concentration. The ECS appears to shift the immune system towards a type 2 response, while maintaining a positive energy balance and reducing anxiety. It may therefore be important in resolution of injury and inflammation. Data suggest that the ECS could potentially modulate mitochondrial function by several different pathways; this may help explain its actions in the central nervous system. Dose-related control of mitochondrial function could therefore provide an insight into its role in health and disease, and why it might have its own pathology, and possibly, new therapeutic directions.

Endocannabinoids, FOXO and the metabolic syndrome: redox, function and tipping point--the view from two systems

The endocannabinoid system (ECS) was only 'discovered' in the 1990s. Since then, many new ligands have been identified, as well as many new intracellular targets--ranging from the PPARs, to mitochondria, to lipid rafts. It was thought that blocking the CB-1 receptor might reverse obesity and the metabolic syndrome. This was based on the idea that the ECS was dysfunctional in these conditions. This has met with limited success. The reason may be that the ECS is a homeostatic system, which integrates energy seeking and storage behaviour with resistance to oxidative stress. It could be viewed as having thrifty actions. Thriftiness is an innate property of life, which is programmed to a set point by both environment and genetics, resulting in an epigenotype perfectly adapted to its environment. This thrifty set point can be modulated by hormetic stimuli, such as exercise, cold and plant micronutrients. We have proposed that the physiological and protective insulin resistance that underlies thriftiness encapsulates something called 'redox thriftiness', whereby insulin resistance is determined by the ability to resist oxidative stress. Modern man has removed most hormetic stimuli and replaced them with a calorific sedentary lifestyle, leading to increased risk of metabolic inflexibility. We suggest that there is a tipping point where lipotoxicity in adipose and hepatic cells induces mild inflammation, which switches thrifty insulin resistance to inflammation-driven insulin resistance. To understand this, we propose that the metabolic syndrome could be seen from the viewpoint of the ECS, the mitochondrion and the FOXO group of transcription factors. FOXO has many thrifty actions, including increasing insulin resistance and appetite, suppressing oxidative stress and shifting the organism towards using fatty acids. In concert with factors such as PGC-1, they also modify mitochondrial function and biogenesis. Hence, the ECS and FOXO may interact at many points; one of which may be via intracellular redox signalling. As cannabinoids have been shown to modulate reactive oxygen species production, it is possible that they can upregulate anti-oxidant defences. This suggests they may have an 'endohormetic' signalling function. The tipping point into the metabolic syndrome may be the result of a chronic lack of hormetic stimuli (in particular, physical activity), and thus, stimulus for PGC-1, with a resultant reduction in mitochondrial function and a reduced lipid capacitance. This, in the context of a positive calorie environment, will result in increased visceral adipose tissue volume, abnormal ectopic fat content and systemic inflammation. This would worsen the inflammatory-driven pathological insulin resistance and inability to deal with lipids. The resultant oxidative stress may therefore drive a compensatory anti-oxidative response epitomised by the ECS and FOXO. Thus, although blocking the ECS (e.g. via rimonabant) may induce temporary weight loss, it may compromise long-term stress resistance. Clues about how to modulate the system more safely are emerging from observations that some polyphenols, such as resveratrol and possibly, some phytocannabinoids, can modulate mitochondrial function and might improve resistance to a modern lifestyle.

Flavonoid inhibitory pharmacodynamics on platelet function in physiological environments

The complex relationship between flavonoid-based nutrition and cardiovascular disease may be dissected by understanding the activities of these compounds in biological systems. The aim of the present study was to explore a hierarchy for the importance of dietary flavonoids on cardiovascular health by examining the structural basis for inhibitory effects of common, dietary flavonoids (quercetin, apigenin, and naringenin) and the plasma metabolite, tamarixetin. Understanding flavonoid effects on platelets in vivo can be informed by investigations of the ability of these compounds to attenuate the function of these cells. Inhibition of platelet function in whole blood and plasma was structure-dependent. The order of potency was apigenin > tamarixetin > quercetin = naringenin indicating that in vivo, important functional groups are potentially a methylated B ring, and a non-hydroxylated, planar C ring. Apigenin and the methylated metabolite of quercetin, tamarixetin significantly reduced thrombus volume at concentrations (5 μM) that suggested their reported physiological levels (0.1-1 μM) may exert low levels of inhibition. Flavonoid interactions with erythrocytes, leukocytes and human serum albumin in whole blood reduce their inhibitory activities against platelet function. The diminished inhibitory activity of flavonoids that we observed in whole blood and plasma indicated that these interactions do not overcome the attenuating effects of these compounds. Furthermore, inhibition of platelet aggregation by flavonoids was enhanced with increases in exposure time, indicating the potential for measurable inhibitory effects during resident plasma times. We conclude that flavonoid structures may be a major influence of their activities in vivo with methylated metabolites and those of flavones being more potent than those of flavonols and flavanones.

Relationships between plant traits and climate in the Mediterranean region: an analysis based on pollen data

Question: What are the correlations between the degree of drought stress and temperature, and the adoption of specific adaptive strategies by plants in the Mediterranean region? Location: 602 sites across the Mediterranean region. Method: We considered 12 plant morphological and phenological traits, and measured their abundance at the sites as trait scores obtained from pollen percentages. We conducted stepwise regression analyses of trait scores as a function of plant available moisture (α) and winter temperature (MTCO). Results: Patterns in the abundance for the plant traits we considered are clearly determined by α, MTCO or a combination of both. In addition, trends in leaf size, texture, thickness, pubescence and aromatic leaves and other plant level traits such as thorniness and aphylly, vary according to the life form (tree, shrub, forb), the leaf type (broad, needle) and phenology (evergreen, summer-green). Conclusions: Despite conducting this study based on pollen data we have identified ecologically plausible trends in the abundance of traits along climatic gradients. Plant traits other than the usual life form, leaf type and leaf phenology carry strong climatic signals. Generally, combinations of plant traits are more climatically diagnostic than individual traits. The qualitative and quantitative relationships between plant traits and climate parameters established here will help to provide an improved basis for modelling the impact of climate changes on vegetation and form a starting point for a global analysis of pollen-climate relationships

PDFOS: PDF estimation based over-sampling for imbalanced two-class problems

This contribution proposes a novel probability density function (PDF) estimation based over-sampling (PDFOS) approach for two-class imbalanced classification problems. The classical Parzen-window kernel function is adopted to estimate the PDF of the positive class. Then according to the estimated PDF, synthetic instances are generated as the additional training data. The essential concept is to re-balance the class distribution of the original imbalanced data set under the principle that synthetic data sample follows the same statistical properties. Based on the over-sampled training data, the radial basis function (RBF) classifier is constructed by applying the orthogonal forward selection procedure, in which the classifier’s structure and the parameters of RBF kernels are determined using a particle swarm optimisation algorithm based on the criterion of minimising the leave-one-out misclassification rate. The effectiveness of the proposed PDFOS approach is demonstrated by the empirical study on several imbalanced data sets.

Adaptive nonlinear equalizer using a mixture of gaussians based on-line density estimator

This paper introduces a new adaptive nonlinear equalizer relying on a radial basis function (RBF) model, which is designed based on the minimum bit error rate (MBER) criterion, in the system setting of the intersymbol interference channel plus a co-channel interference. Our proposed algorithm is referred to as the on-line mixture of Gaussians estimator aided MBER (OMG-MBER) equalizer. Specifically, a mixture of Gaussians based probability density function (PDF) estimator is used to model the PDF of the decision variable, for which a novel on-line PDF update algorithm is derived to track the incoming data. With the aid of this novel on-line mixture of Gaussians based sample-by-sample updated PDF estimator, our adaptive nonlinear equalizer is capable of updating its equalizer’s parameters sample by sample to aim directly at minimizing the RBF nonlinear equalizer’s achievable bit error rate (BER). The proposed OMG-MBER equalizer significantly outperforms the existing on-line nonlinear MBER equalizer, known as the least bit error rate equalizer, in terms of both the convergence speed and the achievable BER, as is confirmed in our simulation study

Televised Whorf: cognitive restructuring in advanced foreign language learners as a function of audio-visual media exposure

The encoding of goal-oriented motion events varies across different languages. Speakers of languages without grammatical aspect (e.g., Swedish) tend to mention motion endpoints when describing events, e.g., “two nuns walk to a house,”, and attach importance to event endpoints when matching scenes from memory. Speakers of aspect languages (e.g., English), on the other hand, are more prone to direct attention to the ongoingness of motion events, which is reflected both in their event descriptions, e.g., “two nuns are walking.”, and in their non-verbal similarity judgements. This study examines to what extent native speakers of Swedish (n = 82) with English as a foreign language (FL) restructure their categorisation of goal-oriented motion as a function of their English proficiency and experience with the English language (e.g., exposure, learning). Seventeen monolingual native English speakers from the United Kingdom (UK) were engaged for comparison purposes. Data on motion event cognition were collected through a memory-based triads matching task, in which a target scene with an intermediate degree of endpoint orientation was matched with two alternative scenes with low and high degrees of endpoint orientation, respectively. Results showed that the preference among the Swedish speakers of L2 English to base their similarity judgements on ongoingness rather than event endpoints was correlated with their use of English in their everyday lives, such that those who often watched television in English approximated the ongoingness preference of the English native speakers. These findings suggest that event cognition patterns may be restructured through the exposure to FL audio-visual media. The results thus add to the emerging picture that learning a new language entails learning new ways of observing and reasoning about reality.

Cost function for sub-agent elements in multi-agent energy management system

Distributed generation plays a key role in reducing CO2 emissions and losses in transmission of power. However, due to the nature of renewable resources, distributed generation requires suitable control strategies to assure reliability and optimality for the grid. Multi-agent systems are perfect candidates for providing distributed control of distributed generation stations as well as providing reliability and flexibility for the grid integration. The proposed multi-agent energy management system consists of single-type agents who control one or more gird entities, which are represented as generic sub-agent elements. The agent applies one control algorithm across all elements and uses a cost function to evaluate the suitability of the element as a supplier. The behavior set by the agent's user defines which parameters of an element have greater weight in the cost function, which allows the user to specify the preference on suppliers dynamically. This study shows the ability of the multi-agent energy management system to select suppliers according to the selection behavior given by the user. The optimality of the supplier for the required demand is ensured by the cost function based on the parameters of the element.

A radial basis function network classifier to maximise leave-one-out mutual information

tWe develop an orthogonal forward selection (OFS) approach to construct radial basis function (RBF)network classifiers for two-class problems. Our approach integrates several concepts in probabilisticmodelling, including cross validation, mutual information and Bayesian hyperparameter fitting. At eachstage of the OFS procedure, one model term is selected by maximising the leave-one-out mutual infor-mation (LOOMI) between the classifier’s predicted class labels and the true class labels. We derive theformula of LOOMI within the OFS framework so that the LOOMI can be evaluated efficiently for modelterm selection. Furthermore, a Bayesian procedure of hyperparameter fitting is also integrated into theeach stage of the OFS to infer the l2-norm based local regularisation parameter from the data. Since eachforward stage is effectively fitting of a one-variable model, this task is very fast. The classifier construc-tion procedure is automatically terminated without the need of using additional stopping criterion toyield very sparse RBF classifiers with excellent classification generalisation performance, which is par-ticular useful for the noisy data sets with highly overlapping class distribution. A number of benchmarkexamples are employed to demonstrate the effectiveness of our proposed approach.

Aircraft-based observations of air–sea turbulent fluxes around the British Isles

Observations of turbulent fluxes of momentum, heat and moisture from low-level aircraft data are presented. Fluxes are calculated using the eddy covariance technique from flight legs typically ∼40 m above the sea surface. Over 400 runs of 2 min (∼12 km) from 26 flights are evaluated. Flight legs are mainly from around the British Isles although a small number are from around Iceland and Norway. Sea-surface temperature (SST) observations from two on-board sensors (the ARIES interferometer and a Heimann radiometer) and a satellite-based analysis (OSTIA) are used to determine an improved SST estimate. Most of the observations are from moderate to strong wind speed conditions, the latter being a regime short of validation data for the bulk flux algorithms that are necessary for numerical weather prediction and climate models. Observations from both statically stable and unstable atmospheric boundary-layer conditions are presented. There is a particular focus on several flights made as part of the DIAMET (Diabatic influence on mesoscale structures in extratropical storms) project. Observed neutral exchange coefficients are in the same range as previous studies, although higher for the momentum coefficient, and are broadly consistent with the COARE 3.0 bulk flux algorithm, as well as the surface exchange schemes used in the ECMWF and Met Office models. Examining the results as a function of aircraft heading shows higher fluxes and exchange coefficients in the across-wind direction, compared to along-wind (although this comparison is limited by the relatively small number of along-wind legs). A multi-resolution spectral decomposition technique demonstrates a lengthening of spatial scales in along-wind variances in along-wind legs, implying the boundary-layer eddies are elongated in the along-wind direction. The along-wind runs may not be able to adequately capture the full range of turbulent exchange that is occurring because elongation places the largest eddies outside of the run length.