Solving complex optimal control problems at no cost with PSOPT

This paper introduces PSOPT, an open source optimal control solver written in C++. PSOPT uses pseudospectral and local discretizations, sparse nonlinear programming, automatic differentiation, and it incorporates automatic scaling and mesh refinement facilities. The software is able to solve complex optimal control problems including multiple phases, delayed differential equations, nonlinear path constraints, interior point constraints, integral constraints, and free initial and/or final times. The software does not require any non-free platform to run, not even the operating system, as it is able to run under Linux. Additionally, the software generates plots as well as LATEX code so that its results can easily be included in publications. An illustrative example is provided.

The effect of nonlinearity in CO2 heating rates on the attribution of stratospheric ozone and temperature changes

An analysis of the attribution of past and future changes in stratospheric ozone and temperature to anthropogenic forcings is presented. The analysis is an extension of the study of Shepherd and Jonsson (2008) who analyzed chemistry-climate simulations from the Canadian Middle Atmosphere Model (CMAM) and attributed both past and future changes to changes in the external forcings, i.e. the abundances of ozone-depleting substances (ODS) and well-mixed greenhouse gases. The current study is based on a new CMAM dataset and includes two important changes. First, we account for the nonlinear radiative response to changes in CO2. It is shown that over centennial time scales the radiative response in the upper stratosphere to CO2 changes is significantly nonlinear and that failure to account for this effect leads to a significant error in the attribution. To our knowledge this nonlinearity has not been considered before in attribution analysis, including multiple linear regression studies. For the regression analysis presented here the nonlinearity was taken into account by using CO2 heating rate, rather than CO2 abundance, as the explanatory variable. This approach yields considerable corrections to the results of the previous study and can be recommended to other researchers. Second, an error in the way the CO2 forcing changes are implemented in the CMAM was corrected, which significantly affects the results for the recent past. As the radiation scheme, based on Fomichev et al. (1998), is used in several other models we provide some description of the problem and how it was fixed.

Estimation of optimal gravity wave parameters for climate models using data assimilation

There is a current need to constrain the parameters of gravity wave drag (GWD) schemes in climate models using observational information instead of tuning them subjectively. In this work, an inverse technique is developed using data assimilation principles to estimate gravity wave parameters. Because mostGWDschemes assume instantaneous vertical propagation of gravity waves within a column, observations in a single column can be used to formulate a one-dimensional assimilation problem to estimate the unknown parameters. We define a cost function that measures the differences between the unresolved drag inferred from observations (referred to here as the ‘observed’ GWD) and the GWD calculated with a parametrisation scheme. The geometry of the cost function presents some difficulties, including multiple minima and ill-conditioning because of the non-independence of the gravity wave parameters. To overcome these difficulties we propose a genetic algorithm to minimize the cost function, which provides a robust parameter estimation over a broad range of prescribed ‘true’ parameters. When real experiments using an independent estimate of the ‘observed’ GWD are performed, physically unrealistic values of the parameters can result due to the non-independence of the parameters. However, by constraining one of the parameters to lie within a physically realistic range, this degeneracy is broken and the other parameters are also found to lie within physically realistic ranges. This argues for the essential physical self-consistency of the gravity wave scheme. A much better fit to the observed GWD at high latitudes is obtained when the parameters are allowed to vary with latitude. However, a close fit can be obtained either in the upper or the lower part of the profiles, but not in both at the same time. This result is a consequence of assuming an isotropic launch spectrum. The changes of sign in theGWDfound in the tropical lower stratosphere, which are associated with part of the quasi-biennial oscillation forcing, cannot be captured by the parametrisation with optimal parameters.

European storminess and associated circulation weather types: future changes deduced from a multi-model ensemble of GCM simulations

A range of possible changes in the frequency and characteristics of European wind storms under future climate conditions was investigated on the basis of a multi-model ensemble of 9 coupled global climate model (GCM) simulations for the 20th and 21st centuries following the IPCC SRES A1B scenario. A multi-model approach allowed an estimation of the (un)certainties of the climate change signals. General changes in large-scale atmospheric flow were analysed, the occurrence of wind storms was quantified, and atmospheric features associated with wind storm events were considered. Identified storm days were investigated according to atmospheric circulation, associated pressure patterns, cyclone tracks and wind speed patterns. Validation against reanalysis data revealed that the GCMs are in general capable of realistically reproducing characteristics of European circulation weather types (CWTs) and wind storms. Results are given with respect to frequency of occurrence, storm-associated flow conditions, cyclone tracks and specific wind speed patterns. Under anthropogenic climate change conditions (SRES A1B scenario), increased frequency of westerly flow during winter is detected over the central European investigation area. In the ensemble mean, the number of detected wind storm days increases between 19 and 33% for 2 different measures of storminess, only 1 GCM revealed less storm days. The increased number of storm days detected in most models is disproportionately high compared to the related CWT changes. The mean intensity of cyclones associated with storm days in the ensemble mean increases by about 10 (±10)% in the Eastern Atlantic, near the British Isles and in the North Sea. Accordingly, wind speeds associated with storm events increase significantly by about 5 (±5)% over large parts of central Europe, mainly on days with westerly flow. The basic conclusions of this work remain valid if different ensemble contructions are considered, leaving out an outlier model or including multiple runs of one particular model.

Introducing "ecoputation": a universal systems design process

A universal systems design process is specified, tested in a case study and evaluated. It links English narratives to numbers using a categorical language framework with mathematical mappings taking the place of conjunctions and numbers. The framework is a ring of English narrative words between 1 (option) and 360 (capital); beyond 360 the ring cycles again to 1. English narratives are shown to correspond to the field of fractional numbers. The process can enable the development, presentation and communication of complex narrative policy information among communities of any scale, on a software implementation known as the "ecoputer". The information is more accessible and comprehensive than that in conventional decision support, because: (1) it is expressed in narrative language; and (2) the narratives are expressed as compounds of words within the framework. Hence option generation is made more effective than in conventional decision support processes including Multiple Criteria Decision Analysis, Life Cycle Assessment and Cost-Benefit Analysis.The case study is of a participatory workshop in UK bioenergy project objectives and criteria, at which attributes were elicited in environmental, economic and social systems. From the attributes, the framework was used to derive consequences at a range of levels of precision; these are compared with the project objectives and criteria as set out in the Case for Support. The design process is to be supported by a social information manipulation, storage and retrieval system for numeric and verbal narratives attached to the "ecoputer". The "ecoputer" will have an integrated verbal and numeric operating system. Novel design source code language will assist the development of narrative policy. The utility of the program, including in the transition to sustainable development and in applications at both community micro-scale and policy macro-scale, is discussed from public, stakeholder, corporate, Governmental and regulatory perspectives.

Platelet 12-lipoxygenase activation via glycoprotein VI: involvement of multiple signaling pathways in agonist control of H(P)ETE synthesis

Lipoxygenases (LOX) contribute to vascular disease and inflammation through generation of bioactive lipids, including 12-hydro(pero xyeicosatetraenoic acid (12-H(P)ETE). The physiological mechanisms that acutely control LOX product generation in mammalian cells are uncharacterized. Human platelets that contain a 12-LOX isoform (p12-LOX) were used to define pathways that activate H(P)ETE synthesis in the vasculature. Collagen and collagen-related peptide (CRP) (1 to 10 g/mL) acutely induced platelet 12-H(P)ETE synthesis. This implicated the collagen receptor glycoprotein VI (GPVI), which signals via the immunoreceptor-based activatory motif (ITAM)- containing FcR chain. Conversely, thrombin only activated at high concentrations ( 0.2 U/mL), whereas U46619 and ADP alone were ineffective. Collagen or CRP-stimulated 12-H(P)ETE generation was inhibited by staurosporine, PP2, wortmannin, BAPTA/AM, EGTA, and L-655238, implicating src-tyrosine kinases, PI3-kinase, Ca2 mobilization, and p12-LOX translocation. In contrast, protein kinase C (PKC) inhibition potentiated 12-H(P)ETE generation. Finally, activation of the immunoreceptor tyrosine-based inhibitory motif (ITIM)– containing platelet endothelial cell adhesion molecule (PECAM-1) inhibited p12-LOX product generation. This study characterizes a receptor-dependent pathway for 12-H(P)ETE synthesis via the collagen receptor GPVI, which is negatively regulated by PECAM-1 and PKC, and demonstrates a novel link between immune receptor signaling and lipid mediator generation in the vasculature. (Circ Res. 2004;94:1598-1605.)

Optimal foraging when regulating intake of multiple nutrients

There is growing evidence that, rather than maximizing energy intake subject to constraints, many animals attempt to regulate intake of multiple nutrients independently. In the complex diets of animals such as herbivores, the consumption of nutritionally imbalanced foods is sometimes inevitable, forcing trade-offs between eating too much of nutrients present in the foods in relative excess against too little of those in deficit. Such situations are not adequately represented in existing formulations of foraging theory. Here we provide the necessary theory to fit this case, using an approach that combines state-space models of nutrition with Tilman's models of resource exploitation (Tilman 1982, Resource Competition and Community Structure, Princeton: Princeton University Press). Our approach was to construct a smooth fitness landscape over nutrient space, centred on a 'target' intake at which no fitness cost is incurred, and this leads to a natural classification of the simple possible fitness landscapes based on Taylor series approximations of landscape shape. We next examined how needs for multiple nutrients can be assessed experimentally using direct measures of animal performance as the common currency, so that the nutritional strategies of animals can be mapped on to the performance surface, including the position of regulated points of intake and points of nutrient balance when fed suboptimal foods. We surveyed published data and conducted an experiment to map out the performance landscape of a generalist leaf-feeding caterpillar, Spodoptera littoralis. (C) 2004 Tire Association for the Study of Animal Behaviour. Poblished by Elsevier Ltd. All rights reserved.

Flavonoids and brain health: multiple effects underpinned by common mechanisms

The neuroprotective actions of dietary flavonoids involve a number of effects within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. This multiplicity of effects appears to be underpinned by two processes. Firstly, they interact with important neuronal signalling cascades leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and differentiation. These interactions include selective actions on a number of protein kinase and lipid kinase signalling cascades, most notably the PI3K/Akt and MAP kinase pathways which regulate pro-survival transcription factors and gene expression. Secondly, they induce peripheral and cerebral vascular blood flow in a manner which may lead to the induction of angiogenesis, and new nerve cell growth in the hippocampus. Therefore, the consumption of flavonoid-rich foods, such as berries and cocoa, throughout life holds a potential to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance.

Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway

Background: The regulation of platelet function by pharmacological agents that modulate platelet signaling haspharmacolo proven a successful approach to the prevention of thrombosis. A variety of molecules present in the diet have been shown to inhibit platelet activation, including the antioxidant quercetin. Objectives: In this report we investigate the molecular mechanisms through which quercetin inhibits collagen-stimulated platelet aggregation. Methods: The effect of quercetin on platelet aggregation, intracellular calcium release, whole cell tyrosine phosphorylation and intracellular signaling events including tyrosine phosphorylation and kinase activity of proteins involved in the collagen-stimulated glycoprotein (GP) signaling pathway were investigated. Results: We report that quercetin inhibits collagen-stimulated whole cell protein tyrosine phosphorylation and intracellular mobilization of calcium, in a concentration-dependent manner. Quercetin was also found to inhibit various events in signaling generated by the collagen receptor GPVI. This includes collagen-stimulated tyrosine phosphorylation of the Fc receptor gamma-chain, Syk, LAT and phospholipase Cgamma2. Inhibition of phosphorylation of the Fc receptor gamma-chain suggests that quercetin inhibits early signaling events following stimulation of platelets with collagen. The activity of the kinases that phosphorylate the Fc receptor gamma-chain, Fyn and Lyn, as well as the tyrosine kinase Syk and phosphoinositide 3-kinase was also inhibited by quercetin in a concentration-dependent manner, both in whole cells and in isolation. Conclusions: The present results provide a molecular basis for the inhibition by quercetin of collagen-stimulated platelet activation, through inhibition of multiple components of the GPVI signaling pathway, and may begin to explain the proposed health benefits of high quercetin intake.

Clustering techniques applied to multiple-models structures

In this work a method for building multiple-model structures is presented. A clustering algorithm that uses data from the system is employed to define the architecture of the multiple-model, including the size of the region covered by each model, and the number of models. A heating ventilation and air conditioning system is used as a testbed of the proposed method.

Dimension and coverage of multiple-models structures using clustering techniques

In this work a method for building multiple-model structures is presented. A clustering algorithm that uses data from the system is employed to define the architecture of the multiple-model, including the size of the region covered by each model, and the number of models. A heating ventilation and air conditioning system is used as a testbed of the proposed method.

Evaluation of agri-environmental and forestry schemes with multiple objectives

The evaluation of EU policy in the area of rural land use management often encounters problems of multiple and poorly articulated objectives. Agri-environmental policy has a range of aims, including natural resource protection, biodiversity conservation and the protection and enhancement of landscape quality. Forestry policy, in addition to production and environmental objectives, increasingly has social aims, including enhancement of human health and wellbeing, lifelong learning, and the cultural and amenity value of the landscape. Many of these aims are intangible, making them hard to define and quantify. This article describes two approaches for dealing with such situations, both of which rely on substantial participation by stakeholders. The first is the Agri-Environment Footprint Index, a form of multi-criteria participatory approach. The other, applied here to forestry, has been the development of ‘multi-purpose’ approaches to evaluation, which respond to the diverse needs of stakeholders through the use of mixed methods and a broad suite of indicators, selected through a participatory process. Each makes use of case studies and involves stakeholders in the evaluation process, thereby enhancing their commitment to the programmes and increasing their sustainability. Both also demonstrate more ‘holistic’ approaches to evaluation than the formal methods prescribed in the EU Common Monitoring and Evaluation Framework.

Organocatalytic enantioselective construction of nitrocyclohexanes containing multiple chiral centres via a cascade reaction

The stereoselective construction of complex molecules with multiple stereogenicity in a single step represents an extremely useful, but challenging approach to complexity in chemical synthesis. The development of organocatalytic cascade processes has proven useful in these studies, but reports where four or more stereocentres are created in a single step from just two achiral reagents are rare. Herein we report the development of a novel asymmetric domino Michael-Michael reaction between nitrohex-4-enoates and nitro-olefins to generate cyclohexanes of high complexity, including one with a quaternary centre, and one with five contiguous stereocentres. This methodology provides access to a range of useful nitrocyclohexane derivatives, including a novel class of a-lycorane-like structures.

Exposure of Escherichia coli and Salmonella enterica serovar Typhimurium to triclosan induces a species-specific response, including drug detoxification

Objectives: The use of triclosan within various environments has been linked to the development of multiple drug resistance (MDR) through the increased expression of efflux pumps such as AcrAB-ToIC. In this work, we investigate the effect of triclosan exposure in order to ascertain the response of two species to the presence of this widely used biocide. Methods: The transcriptomes of Salmonella enterica serovar Typhimurium SL1344 and Escherichia coli K-12 MG1655 after exposure to the MIC of triclosan (0.12 mg/L) were determined in microarray experiments. Phenotypic validation of the transcriptomic data included RT-PCR, ability to form a biofilm and motility assays. Results: Despite important differences in the triclosan-dependent transcriptomes of the two species, increased expression of efflux pump component genes was seen in both. Increased expression of soxS was observed in Salmonella Typhimurium, however, within E. coli, decreased expression was seen. Expression of fabBAGI in Salmonella Typhimurium was decreased, whereas in E. coli expression of fabABFH was increased. Increased expression of ompR and genes within this regulon (e.g. ompC, csgD and ssrA) was seen in the transcriptome of Salmonella Typhimurium. An unexpected response of E. coli was the differential expression of genes within operons involved in iron homeostasis; these included fhu, fep and ent. Conclusions: These data indicate that whilst a core response to triclosan exposure exists, the differential transcriptome of each species was different. This suggests that E. coli K-12 should not be considered the paradigm for the Enterobacteriaceae when exploring the effects of antimicrobial agents.

Multiple routes to mammalian diversity

The radiation of the mammals provides a 165-million-year test case for evolutionary theories of how species occupy and then fill ecological niches. It is widely assumed that species often diverge rapidly early in their evolution, and that this is followed by a longer, drawn-out period of slower evolutionary fine-tuning as natural selection fits organisms into an increasingly occupied niche space1,2. But recent studies have hinted that the process may not be so simple3–5. Here we apply statistical methods that automatically detect temporal shifts in the rate of evolution through time to a comprehensive mammalian phylogeny6 and data set7 of body sizes of 3,185 extant species. Unexpectedly, the majority of mammal species, including two of the most speciose orders (Rodentia and Chiroptera), have no history of substantial and sustained increases in the rates of evolution. Instead, a subset of the mammals has experienced an explosive increase (between 10- and 52-fold) in the rate of evolution along the single branch leading to the common ancestor of their monophyletic group (for example Chiroptera), followed by a quick return to lower or background levels. The remaining species are a taxonomically diverse assemblage showing a significant, sustained increase or decrease in their rates of evolution. These results necessarily decouple morphological diversification from speciation and suggest that the processes that give rise to the morphological diversity of a class of animals are far more free to vary than previously considered. Niches do not seem to fill up, and diversity seems to arise whenever, wherever and at whatever rate it is advantageous.