Sensorimotor experience enhances automatic imitation of robotic action

Recent research in cognitive neuroscience has found that observation of human actions activates the ‘mirror system’ and provokes automatic imitation to a greater extent than observation of non-biological movements. The present study investigated whether this human bias depends primarily on phylogenetic or ontogenetic factors by examining the effects of sensorimotor experience on automatic imitation of non-biological robotic, stimuli. Automatic imitation of human and robotic action stimuli was assessed before and after training. During these test sessions, participants were required to execute a pre-specified response (e.g. to open their hand) while observing a human or robotic hand making a compatible (opening) or incompatible (closing) movement. During training, participants executed opening and closing hand actions while observing compatible (group CT) or incompatible movements (group IT) of a robotic hand. Compatible, but not incompatible, training increased automatic imitation of robotic stimuli (speed of responding on compatible trials, compared with incompatible trials) and abolished the human bias observed at pre-test. These findings suggest that the development of the mirror system depends on sensorimotor experience, and that, in our species, it is biased in favour of human action stimuli because these are more abundant than non-biological action stimuli in typical developmental environments.

On wave action and phase in the non-canonical Hamiltonian formulation

The long time–evolution of disturbances to slowly–varying solutions of partial differential equations is subject to the adiabatic invariance of the wave action. Generally, this approximate conservation law is obtained under the assumption that the partial differential equations are derived from a variational principle or have a canonical Hamiltonian structure. Here, the wave action conservation is examined for equations that possess a non–canonical (Poisson) Hamiltonian structure. The linear evolution of disturbances in the form of slowly varying wavetrains is studied using a WKB expansion. The properties of the original Hamiltonian system strongly constrain the linear equations that are derived, and this is shown to lead to the adiabatic invariance of a wave action. The connection between this (approximate) invariance and the (exact) conservation laws of pseudo–energy and pseudomomentum that exist when the basic solution is exactly time and space independent is discussed. An evolution equation for the slowly varying phase of the wavetrain is also derived and related to Berry's phase.

Conservation strategy maps: a tool to facilitate biodiversity action planning illustrated using the heath fritillary butterfly

1. The UK Biodiversity Action Plan (UKBAP) identifies invertebrate species in danger of national extinction. For many of these species, targets for recovery specify the number of populations that should exist by a specific future date but offer no procedure to plan strategically to achieve the target for any species. 2. Here we describe techniques based upon geographic information systems (GIS) that produce conservation strategy maps (CSM) to assist with achieving recovery targets based on all available and relevant information. 3. The heath fritillary Mellicta athalia is a UKBAP species used here to illustrate the use of CSM. A phase 1 habitat survey was used to identify habitat polygons across the county of Kent, UK. These were systematically filtered using relevant habitat, botanical and autecological data to identify seven types of polygon, including those with extant colonies or in the vicinity of extant colonies, areas managed for conservation but without colonies, and polygons that had the appropriate habitat structure and may therefore be suitable for reintroduction. 4. Five clusters of polygons of interest were found across the study area. The CSM of two of them are illustrated here: the Blean Wood complex, which contains the existing colonies of heath fritillary in Kent, and the Orlestone Forest complex, which offers opportunities for reintroduction. 5. Synthesis and applications. Although the CSM concept is illustrated here for the UK, we suggest that CSM could be part of species conservation programmes throughout the world. CSM are dynamic and should be stored in electronic format, preferably on the world-wide web, so that they can be easily viewed and updated. CSM can be used to illustrate opportunities and to develop strategies with scientists and non-scientists, enabling the engagement of all communities in a conservation programme. CSM for different years can be presented to illustrate the progress of a plan or to provide continuous feedback on how a field scenario develops.

Extinction processes in hotspots of avian biodiversity and the targeting of pre-emptive conservation action

Hot spots of endemism are regarded as important global sites for conservation as they are rich in threatened endemic species and currently experiencing extensive habitat loss. Targeting pre-emptive conservation action to sites that are currently relatively intact but which would be vulnerable to particular human activities if they occurred in the future is, however, also valuable but has received less attention. Here, we address this issue by using data on Endemic Bird Areas (EBAs). First, we identify the ecological factors that affect extinction risk in the face of particular human activities, and then use these insights to identify EBAs that should be priorities for pre-emptive conservation action. Threatened endemic species in EBAs are significantly more likely to be habitat specialists or relatively large-bodied than non-threatened species, when compared across avian families. Increasing habitat loss causes a significant increase in extinction risk among habitat specialists, but we found no evidence to suggest that the presence of alien species/human exploitation causes a significant increase in extinction risk among large-bodied species. This suggests that these particular human activities are contributing to high extinction risk among habitat specialists, but not among large-bodied species. Based on these analyses, we identify 39 EBAs containing 570 species (24% of the total in EBAs) that are not currently threatened with severe habitat loss, but would be ecologically vulnerable to future habitat loss should it occur. We show that these sites tend to be poorly represented in existing priority setting exercises involving hot spots, suggesting that vulnerability must be explicitly included within these exercises if such sites are to be adequately protected.

Action following the discovery of a global association between the whole genome and adverse event risk in a clinical drug-development programme

Observation of adverse drug reactions during drug development can cause closure of the whole programme. However, if association between the genotype and the risk of an adverse event is discovered, then it might suffice to exclude patients of certain genotypes from future recruitment. Various sequential and non-sequential procedures are available to identify an association between the whole genome, or at least a portion of it, and the incidence of adverse events. In this paper we start with a suspected association between the genotype and the risk of an adverse event and suppose that the genetic subgroups with elevated risk can be identified. Our focus is determination of whether the patients identified as being at risk should be excluded from further studies of the drug. We propose using a utility function to? determine the appropriate action, taking into account the relative costs of suffering an adverse reaction and of failing to alleviate the patient's disease. Two illustrative examples are presented, one comparing patients who suffer from an adverse event with contemporary patients who do not, and the other making use of a reference control group. We also illustrate two classification methods, LASSO and CART, for identifying patients at risk, but we stress that any appropriate classification method could be used in conjunction with the proposed utility function. Our emphasis is on determining the action to take rather than on providing definitive evidence of an association. Copyright (C) 2008 John Wiley & Sons, Ltd.

Non-genomic signalling of the retinoic X receptor through inhibition of Gq signalling in human platelets

Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxisome proliferator-activated receptor (PPAR) gamma, PPARbeta, and the glucocorticoid receptor have all been found active in human platelets. Human platelets express RXRalpha and RXRbeta. RXR ligands inhibit platelet aggregation and TXA(2) release to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular calcium release. We propose that RXR ligands may have beneficial clinical actions through inhibition of platelet activation. Furthermore, our results demonstrate a novel nongenomic mode for nuclear receptor action and a functional cross-talk between G-protein and nuclear receptor signaling families.

Extinction processes in hot spots of avian biodiversity and the targeting of pre-emptive conservation action

Hot spots of endemism are regarded as important global sites for conservation as they are rich in threatened endemic species and currently experiencing extensive habitat loss. Targeting pre-emptive conservation action to sites that are currently relatively intact but which would be vulnerable to particular human activities if they occurred in the future is, however, also valuable but has received less attention. Here, we address this issue by using data on Endemic Bird Areas (EBAs). First, we identify the ecological factors that affect extinction risk in the face of particular human activities, and then use these insights to identify EBAs that should be priorities for pre-emptive conservation action. Threatened endemic species in EBAs are significantly more likely to be habitat specialists or relatively large-bodied than non-threatened species, when compared across avian families. Increasing habitat loss causes a significant increase in extinction risk among habitat specialists, but we found no evidence to suggest that the presence of alien species/human exploitation causes a significant increase in extinction risk among large-bodied species. This suggests that these particular human activities are contributing to high extinction risk among habitat specialists, but not among large-bodied species. Based on these analyses, we identify 39 EBAs containing 570 species (24% of the total in EBAs) that are not currently threatened with severe habitat loss, but would be ecologically vulnerable to future habitat loss should it occur. We show that these sites tend to be poorly represented in existing priority setting exercises involving hot spots, suggesting that vulnerability must be explicitly included within these exercises if such sites are to be adequately protected.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit vascular smooth muscle cell proliferation via differential effects on the cell cycle

Abnormal vascular smooth muscle cell (VSMC) proliferation plays an important role in the pathogenesis of both atherosclerosis and restenosis. Recent studies suggest that high-dose salicylates, in addition to inhibiting cyclooxygenase activity, exert an antiproliferative effect on VSMC growth both in-vitro and in-vivo. However, whether all non-steroidal anti-inflammatory drugs (NSAIDs) exert similar anti proliferative effects on VSMCs, and do so via a common mechanism of action, remains to be shown. In this study, we demonstrate that the NSAIDs aspirin, sodium salicylate, diclofenac, ibuprofen, indometacin and sulindac induce a dose-dependent inhibition of proliferation in rat A10 VSMCs in the absence of significant cytotoxicity. Flow cytometric analyses showed that exposure of A10 cells to diclofenac, indometacin, ibuprofen and sulindac, in the presence of the mitotic inhibitor, nocodazole, led to a significant G0/G1 arrest. In contrast, the salicylates failed to induce a significant G1 arrest since flow cytometry profiles were not significantly different from control cells. Cyclin A levels were elevated, and hyperphosphorylated p107 was present at significant levels, in salicylate-treated A10 cells, consistent with a post-G1/S block, whereas cyclin A levels were low, and hypophosphorylated p107 was the dominant form, in cells treated with other NSAIDs consistent with a G1 arrest. The ubiquitously expressed cyclin-dependent kinase (CDK) inhibitors, p21 and p27, were increased in all NSAID-treated cells. Our results suggest that diclofenac, indometacin, ibuprofen and sulindac inhibit VSMC proliferation by arresting the cell cycle in the G1 phase, whereas the growth inhibitory effect of salicylates probably affects the late S and/or G2/M phases. Irrespective of mechanism, our results suggest that NSAIDs might be of benefit in the treatment of certain vasculoproliferative disorders.

Conservation strategy maps: a tool to facilitate biodiversity action planning illustrated using the heath fritillary butterfly

1. The UK Biodiversity Action Plan (UKBAP) identifies invertebrate species in danger of national extinction. For many of these species, targets for recovery specify the number of populations that should exist by a specific future date but offer no procedure to plan strategically to achieve the target for any species. 2. Here we describe techniques based upon geographic information systems (GIS) that produce conservation strategy maps (CSM) to assist with achieving recovery targets based on all available and relevant information. 3. The heath fritillary Mellicta athalia is a UKBAP species used here to illustrate the use of CSM. A phase 1 habitat survey was used to identify habitat polygons across the county of Kent, UK. These were systematically filtered using relevant habitat, botanical and autecological data to identify seven types of polygon, including those with extant colonies or in the vicinity of extant colonies, areas managed for conservation but without colonies, and polygons that had the appropriate habitat structure and may therefore be suitable for reintroduction. 4. Five clusters of polygons of interest were found across the study area. The CSM of two of them are illustrated here: the Blean Wood complex, which contains the existing colonies of heath fritillary in Kent, and the Orlestone Forest complex, which offers opportunities for reintroduction. 5. Synthesis and applications. Although the CSM concept is illustrated here for the UK, we suggest that CSM could be part of species conservation programmes throughout the world. CSM are dynamic and should be stored in electronic format, preferably on the world-wide web, so that they can be easily viewed and updated. CSM can be used to illustrate opportunities and to develop strategies with scientists and non-scientists, enabling the engagement of all communities in a conservation programme. CSM for different years can be presented to illustrate the progress of a plan or to provide continuous feedback on how a field scenario develops.

Inhibition of vascular smooth muscle cell proliferation by non-steroidal anti-inflammatory drugs

Abnormal vascular smooth muscle cell (VSMC) proliferation is known to play an important role in the pathogenesis of atherosclerosis, restenosis and instent stenosis. Recent studies suggest that salicylates, in addition to inhibiting cyclooxygenase activity, exert an antiproliferative effect on VSMC growth both in vitro and in vivo. However, whether all non-steroidal anti-inflammatory drugs (NSAID) exert similar antiproliferative effects on VSMCs, and do so via a common mechanism of action, remains unknown. In the present study, we demonstrated that the NSAIDs, aspirin, ibuprofen and sulindac induced a dose-dependent inhibition of proliferation in rat A10 VSMCs (IC50 = 1666 mumol/L, 937 mumol/L and 520 mumol/L, respectively). These drugs did not show significant cytotoxic effects as determined by LDH release assay, even at the highest concentrations tested (aspirin, 5000 mumol/L; ibuprofen, 2500 mumol/L; and sulindac, 1000 mumol/L). Flow cytometric analyses showed that a 48 h exposure of A10 VSMCs to ibuprofen (1000 mumol/L) and sulindac (750 mumol/L) led to a significant G1 arrest (from 68.7 +/- 2.0% of cells in G1 to 76.6 +/- 2.2% and 75.8 +/- 2.2%, respectively, p < 0.05). In contrast, aspirin (2500 mumol/L) failed to induce a significant G1 arrest (68.1 +/- 5.2%). Clearer evidence of a G1 block was obtained by treatment of cells with the mitotic inhibitor, nocodazole (40 ng/ml), for the final 24 h of the experiment. Under these conditions, aspirin still failed to induce a G1 arrest (from 25.9 +/- 10.9% of cells in G1 to 19.6 +/- 2.3%) whereas ibuprofen and sulindac led to a significant accumulation of cells in G1(51.8% +/- 17.2% and 54.1% +/- 10.6%, respectively, p < 0.05). These results indicate that ibuprofen and sulindac inhibit VSMC proliferation by arresting the cell cycle in the G1 phase whereas the effect of aspirin appears to be independent of any special phase of the cell cycle. Irrespective of mechanism, our results suggest that NSAIDs might be of benefit to the treatment of vascular proliferative disorders.

Action observation and robotic agents: learning and anthropomorphism

The ‘action observation network’ (AON), which is thought to translate observed actions into motor codes required for their execution, is biologically tuned: it responds more to observation of human, than non-human, movement. This biological specificity has been taken to support the hypothesis that the AON underlies various social functions, such as theory of mind and action understanding, and that, when it is active during observation of non-human agents like humanoid robots, it is a sign of ascription of human mental states to these agents. This review will outline evidence for biological tuning in the AON, examining the features which generate it, and concluding that there is evidence for tuning to both the form and kinematic profile of observed movements, and little evidence for tuning to belief about stimulus identity. It will propose that a likely reason for biological tuning is that human actions, relative to non-biological movements, have been observed more frequently while executing corresponding actions. If the associative hypothesis of the AON is correct, and the network indeed supports social functioning, sensorimotor experience with non-human agents may help us to predict, and therefore interpret, their movements.

Production, hidden action, and the payment system

In this paper, we study a model economy that examines the optimal intraday rate. In Freeman’s (1996) paper, he shows that the efficient allocation can be implemented by adopting a policy in which the intraday rate is zero. We modify the production set and show that such a model economy can account for the non-uniform distribution of settlements within a day. In addition, by modifying both the consumption set and the production set, we show that the central bank may be able to implement the planner’s allocation with a positive intraday interest rate.

Measures of observation impact in non-Gaussian data assimilation

ABSTRACT Non-Gaussian/non-linear data assimilation is becoming an increasingly important area of research in the Geosciences as the resolution and non-linearity of models are increased and more and more non-linear observation operators are being used. In this study, we look at the effect of relaxing the assumption of a Gaussian prior on the impact of observations within the data assimilation system. Three different measures of observation impact are studied: the sensitivity of the posterior mean to the observations, mutual information and relative entropy. The sensitivity of the posterior mean is derived analytically when the prior is modelled by a simplified Gaussian mixture and the observation errors are Gaussian. It is found that the sensitivity is a strong function of the value of the observation and proportional to the posterior variance. Similarly, relative entropy is found to be a strong function of the value of the observation. However, the errors in estimating these two measures using a Gaussian approximation to the prior can differ significantly. This hampers conclusions about the effect of the non-Gaussian prior on observation impact. Mutual information does not depend on the value of the observation and is seen to be close to its Gaussian approximation. These findings are illustrated with the particle filter applied to the Lorenz ’63 system. This article is concluded with a discussion of the appropriateness of these measures of observation impact for different situations.

Molecular mechanisms of oestrogen action on growth of human breast cancer cells in culture

Growth responses to oestrogen can be reproducibly obtained using a selection of oestrogen-receptor-containing human breast cancer cell lines, and molecular mechanisms have been shown to include modulation to growth factor/receptor/signalling pathways, cell-cycle proteins, apoptosis, differentiation, adhesion, motility and migration. Considerable progress has been made in understanding the molecular basis of oestrogen action on gene expression through the ligand-activated transcription factors human oestrogen receptor α (ERα) and ERβ and the resulting effects on global gene expression patterns, but the full profile of coordination of the alterations, which brings about changes in cell growth through genomic and non-genomic mechanisms remain to be fully elucidated. Oestrogen regulation of cell growth involves a complex cross-talk between oestrogen receptor and growth factor signalling pathways such that inhibition of one pathway may lead to stimulation of another, which may explain the remarkable ability of human breast cancer cells to escape from any mode of imposed growth inhibition be it oestrogen deprivation or administration of antioestrogen. Although studies on cell growth have focused to date on the effects of physiological oestrogens, many hundreds of environmental chemicals with oestrogenic properties have now been measured in the human breast. Whether or not the weight of evidence eventually establishes any causal link of complex mixtures of environmental oestrogenic chemicals with breast cancer, the presence of so many oestrogenic chemicals in the breast must influence resulting oestrogenic responses, and the impact of this additional oestrogenic burden needs to be taken into account in future studies on growth regulation of human breast cancer cells.