Detection of bifurcations in noisy coupled systems from multiple time series

This is the final version of the article. Available from AIP Publishing via the DOI in this record.We generalize a method of detecting an approaching bifurcation in a time series of a noisy system from the special case of one dynamical variable to multiple dynamical variables. For a system described by a stochastic differential equation consisting of an autonomous deterministic part with one dynamical variable and an additive white noise term, small perturbations away from the system's fixed point will decay slower the closer the system is to a bifurcation. This phenomenon is known as critical slowing down and all such systems exhibit this decay-type behaviour. However, when the deterministic part has multiple coupled dynamical variables, the possible dynamics can be much richer, exhibiting oscillatory and chaotic behaviour. In our generalization to the multi-variable case, we find additional indicators to decay rate, such as frequency of oscillation. In the case of approaching a homoclinic bifurcation, there is no change in decay rate but there is a decrease in frequency of oscillations. The expanded method therefore adds extra tools to help detect and classify approaching bifurcations given multiple time series, where the underlying dynamics are not fully known. Our generalisation also allows bifurcation detection to be applied spatially if one treats each spatial location as a new dynamical variable. One may then determine the unstable spatial mode(s). This is also something that has not been possible with the single variable method. The method is applicable to any set of time series regardless of its origin, but may be particularly useful when anticipating abrupt changes in the multi-dimensional climate system.The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under Grant Agreement No. 603864 (HELIX). We thank Jan Sieber for help in identifying the case studies and useful comments on an early draft of the manuscript

Ion channels as insecticide targets.

Published onlineJournal ArticleIon channels remain the primary target of most of the small molecule insecticides. This review examines how the subunit composition of heterologously expressed receptors determines their insecticide-specific pharmacology and how the pharmacology of expressed receptors differs from those found in the insect nervous system. We find that the insecticide-specific pharmacology of some receptors, like that containing subunits of the Rdl encoded GABA receptor, can be reconstituted with very few of the naturally occurring subunits expressed. In contrast, workers have struggled even to express functional insect nicotinic acetylcholine receptors (nAChRs), and work has therefore often relied upon the expression of vertebrate receptor subunits in their place. We also examine the extent to which insecticide-resistance-associated mutations, such as those in the para encoded voltage-gated sodium channel, can reveal details of insecticide-binding sites and mode of action. In particular, we examine whether mutations are present in the insecticide-binding site and/or at sites that allosterically affect the drug preferred conformation of the receptor. We also discuss the ryanodine receptor as a target for the recently developed diamides. Finally, we examine the lethality of the genes encoding these receptor subunits and discuss how this might determine the degree of conservation of the resistance-associated mutations found

Biology Extended 1A

Exam paper (Supplementary) for second semeste

Investigating the molecular mechanisms of organophosphate and pyrethroid resistance in the fall armyworm Spodoptera frugiperda.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tThe fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain) or lambda-cyhalothrin (PYR strain) were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE) and pyrethroid (voltage-gated sodium channel, VGSC) target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS). These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results provide evidence that both target-site and metabolic mechanisms underlie the resistance of S. frugiperda to pyrethroids and organophosphates.BBSRCNational Council for Scientific and Technological Development of Brazi

PCR-based detection of Plasmodium in Anopheles mosquitoes: a comparison of a new high-throughput assay with existing methods.

Published onlineComparative StudyEvaluation StudiesJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: Detection of the four malaria-causing Plasmodium species (Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae) within their mosquito hosts is an essential component of vector control programmes. Several PCR protocols have been developed for this purpose. Many of these methods, while sensitive, require multiple PCR reactions to detect and discriminate all four Plasmodium species. In this study a new high-throughput assay was developed and compared with three previously described PCR techniques. METHODS: A new assay based on TaqMan SNP genotyping was developed to detect all four Plasmodium species and discriminate P. falciparum from P. vivax, P. ovale and P. malariae. The sensitivity and the specificity of the new assay was compared to three alternative PCR approaches and to microscopic dissection of salivary glands in a blind trial of 96 single insect samples that included artificially infected Anopheles stephensi mosquitoes. The performance of the assays was then compared using more than 450 field-collected specimens that had been stored on silica gel, in ethanol or in isopropanol. RESULTS: The TaqMan assay was found to be highly specific when using Plasmodium genomic DNA as template. Tests of analytical sensitivity and the results of the blind trial showed the TaqMan assay to be the most sensitive of the four methods followed by the 'gold standard' nested PCR approach and the results generated using these two methods were in good concordance. The sensitivity of the other two methods and their agreement with the nested PCR and TaqMan approaches varied considerably. In trials using field collected specimens two of the methods (including the nested protocol) showed a high degree of non-specific amplification when using DNA derived from mosquitoes stored in ethanol or isopropanol. The TaqMan method appeared unaffected when using the same samples. CONCLUSION: This study describes a new high-throughput TaqMan assay that very effectively detects the four Plasmodium species that cause malaria in humans and discriminates the most deadly species, P. falciparum, from the others. This method is at least as sensitive and specific as the gold standard nested PCR approach and because it has no requirement for post-PCR processing is cheaper, simpler and more rapid to run. In addition this method is not inhibited by the storage of mosquito specimens by drying or in ethanol or isopropanol.BBSRCInnovative Vector Control Consortiu

Abrupt Climate Change in an Oscillating World.

This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.The notion that small changes can have large consequences in the climate or ecosystems has become popular as the concept of tipping points. Typically, tipping points are thought to arise from a loss of stability of an equilibrium when external conditions are slowly varied. However, this appealingly simple view puts us on the wrong foot for understanding a range of abrupt transitions in the climate or ecosystems because complex environmental systems are never in equilibrium. In particular, they are forced by diurnal variations, the seasons, Milankovitch cycles and internal climate oscillations. Here we show how abrupt and sometimes even irreversible change may be evoked by even small shifts in the amplitude or time scale of such environmental oscillations. By using model simulations and reconciling evidence from previous studies we illustrate how these phenomena can be relevant for ecosystems and elements of the climate system including terrestrial ecosystems, Arctic sea ice and monsoons. Although the systems we address are very different and span a broad range of time scales, the phenomena can be understood in a common framework that can help clarify and unify the interpretation of abrupt shifts in the Earth system.This work was carried out under the program of the Netherlands Earth System Science Centre (NESSC), financially supported by the Ministry of Education, Culture and Science (OCW). We are grateful to Chris Huntingford for his constructive comments that helped us to improve the manuscript. We would also like to acknowledge Michel Crucifix, Henk Dijkstra, and Peter Cox for their helpful comments. S.B. is eternally grateful to Nina Engelhardt and the University of Edinburgh for the inspiring working conditions

Identification of the main malaria vectors in the Anopheles gambiae species complex using a TaqMan real-time PCR assay

Background: The Anopheles gambiae sensu lato species complex comprises seven sibling species of mosquitoes that are morphologically indistinguishable. Rapid identification of the two main species which vector malaria, Anopheles arabiensis and An. gambiae sensu stricto, from the non-vector species Anopheles quadriannulatus is often required as part of vector control programmes. Currently the most widely used method for species identification is a multiplex PCR protocol that targets species specific differences in ribosomal DNA sequences. While this assay has proved to be reasonably robust in many studies, additional steps are required post-PCR making it time consuming. Recently, a high-throughput assay based on TaqMan single nucleotide polymorphism genotyping that detects and discriminates An. gambiae s.s and An. arabiensis has been reported. Methods: A new TaqMan assay was developed that distinguishes between the main malaria vectors (An. Arabiensis and An. gambiae s.s.) and the non-vector An. quadriannulatus after it was found that the existing TaqMan assay incorrectly identified An. quadriannulatus, An. merus and An. melas as An. gambiae s.s. The performance of this new TaqMan assay was compared against the existing TaqMan assay and the standard PCR method in a blind species identification trial of over 450 samples using field collected specimens from a total of 13 countries in Sub-Saharan Africa. Results: The standard PCR method was found to be specific with a low number of incorrect scores (<1%), however when compared to the TaqMan assays it showed a significantly higher number of failed reactions (15%). Both the new vector-specific TaqMan assay and the exisiting TaqMan showed a very low number of incorrectly identified samples (0 and 0.54%) and failed reactions (1.25% and 2.96%). In tests of analytical sensitivity the new TaqMan assay showed a very low detection threshold and can consequently be used on a single leg from a fresh or silica-dried mosquito without the need to first extract DNA. Conclusion: This study describes a rapid and sensitive assay that very effectively identifies the two main malaria vectors of the An. gambiae species complex from the non-vector sibling species. The method is based on TaqMan SNP genotyping and can be used to screen single legs from dried specimens. In regions where An. merus/melas/ bwambae, vectors with restricted distributions, are not present it can be used alone to discriminate vector from non-vector or in combination with the Walker TaqMan assay to distinguish An. arabiensis and An. gambiae s.s

Statistical indicators of Arctic sea-ice stability-prospects and limitations

This is the final version of the article. Available from the European Geosciences Union via the DOI in this record.We examine the relationship between the mean and the variability of Arctic sea-ice coverage and volume in a large range of climates from globally ice-covered to globally ice-free conditions. Using a hierarchy of two column models and several comprehensive Earth system models, we consolidate the results of earlier studies and show that mechanisms found in simple models also dominate the interannual variability of Arctic sea ice in complex models. In contrast to predictions based on very idealised dynamical systems, we find a consistent and robust decrease of variance and autocorrelation of sea-ice volume before summer sea ice is lost. We attribute this to the fact that thinner ice can adjust more quickly to perturbations. Thereafter, the autocorrelation increases, mainly because it becomes dominated by the ocean water's large heat capacity when the ice-free season becomes longer. We show that these changes are robust to the nature and origin of climate variability in the models and do not depend on whether Arctic sea-ice loss occurs abruptly or irreversibly. We also show that our climate is changing too rapidly to detect reliable changes in autocorrelation of annual time series. Based on these results, the prospects of detecting statistical early warning signals before an abrupt sea-ice loss at a "tipping point" seem very limited. However, the robust relation between state and variability can be useful to build simple stochastic climate models and to make inferences about past and future sea-ice variability from only short observations or reconstructions.This work was carried out under the programme of the Netherlands Earth System Science Centre (NESSC), financially supported by the Ministry of Education, Culture and Science (OCW). We also acknowledge the World Climate Research Programme’s Working Group on Coupled Modelling, which is responsible for CMIP, and we thank the climate modelling groups for producing and making available their model output. We thank Vasilis Dakos for helping to apply his early warnings R package and Chao Li for making available the MPI-ESM model output. S. B. gratefully acknowledges Arie Staal for his fruitful and revealing approaches to savour scientific achievements. We are also indebted to Till Wagner and Ian Eisenman for their valuable comments and their very amiable and cooperative spirit. Finally, we acknowledge two anonymous reviewers who helped us to improve the manuscript

The theory of international business: the role of economic models

This paper reviews the scope for economic modelling in international business studies. It argues for multi-level theory based on classic internalisation theory. It present a systems approach that encompasses both firm-level and industry-level analysis

Mitigating agency risk between investors and ventures’ managers

The general management literature has long focused on the agency risks involved in the relationship between general managers and shareholders. Shareholders can deploy contractual and non-contractual mechanisms to reduce these inefficiencies. This study examines - based on a broad international sample of investment contracts - how the use of contractual and non-contractual mechanisms is related to the degree of risks associated with the venture’s development stage as well as how these practices differ across countries. Hypotheses are tested using a proprietary dataset of 265 hand-collected investment contracts associated with ventures in the U.S., Israel and nine European countries. Findings suggest that the use of mitigating contractual and non-contractual mechanisms is related to the degree of agency risks, and that these practices vary across countries. This study draws implications for how investors can best deploy their capital in different institutional settings whilst nurturing their relationships with managers and entrepreneurs