Marine ecosystem models for earth systems applications: the MarQUEST experience

The MarQUEST (Marine Biogeochemistry and Ecosystem Modelling Initiative in QUEST) project was established to develop improved descriptions of marine biogeochemistry, suited for the next generation of Earth system models. We review progress in these areas providing insight on the advances that have been made as well as identifying remaining key outstanding gaps for the development of the marine component of next generation Earth system models. The following issues are discussed and where appropriate results are presented; the choice of model structure, scaling processes from physiology to functional types, the ecosystem model sensitivity to changes in the physical environment, the role of the coastal ocean and new methods for the evaluation and comparison of ecosystem and biogeochemistry models. We make recommendations as to where future investment in marine ecosystem modelling should be focused, highlighting a generic software framework for model development, improved hydrodynamic models, and better parameterisation of new and existing models, reanalysis tools and ensemble simulations. The final challenge is to ensure that experimental/observational scientists are stakeholders in the models and vice versa.

Data assimilation for marine monitoring and prediction: The MERCATOR operational assimilation systems and the MERSEA developments

During the past 15 years, a number of initiatives have been undertaken at national level to develop ocean forecasting systems operating at regional and/or global scales. The co-ordination between these efforts has been organized internationally through the Global Ocean Data Assimilation Experiment (GODAE). The French MERCATOR project is one of the leading participants in GODAE. The MERCATOR systems routinely assimilate a variety of observations such as multi-satellite altimeter data, sea-surface temperature and in situ temperature and salinity profiles, focusing on high-resolution scales of the ocean dynamics. The assimilation strategy in MERCATOR is based on a hierarchy of methods of increasing sophistication including optimal interpolation, Kalman filtering and variational methods, which are progressively deployed through the Syst`eme d’Assimilation MERCATOR (SAM) series. SAM-1 is based on a reduced-order optimal interpolation which can be operated using ‘altimetry-only’ or ‘multi-data’ set-ups; it relies on the concept of separability, assuming that the correlations can be separated into a product of horizontal and vertical contributions. The second release, SAM-2, is being developed to include new features from the singular evolutive extended Kalman (SEEK) filter, such as three-dimensional, multivariate error modes and adaptivity schemes. The third one, SAM-3, considers variational methods such as the incremental four-dimensional variational algorithm. Most operational forecasting systems evaluated during GODAE are based on least-squares statistical estimation assuming Gaussian errors. In the framework of the EU MERSEA (Marine EnviRonment and Security for the European Area) project, research is being conducted to prepare the next-generation operational ocean monitoring and forecasting systems. The research effort will explore nonlinear assimilation formulations to overcome limitations of the current systems. This paper provides an overview of the developments conducted in MERSEA with the SEEK filter, the Ensemble Kalman filter and the sequential importance re-sampling filter.

CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation

The clonal expansion of antigen-specific CD8+ T cells in response to microbial infections is essential for adaptive immunity. Although IL-2 has been considered to be primarily responsible for this process, quantitatively normal expansion occurs in the absence of IL-2 receptor signaling. Here, we show that ligating CD27 on CD8+ T cells that have been stimulated through the T cell receptor causes their expansion in the absence of IL-2 by mediating two distinct cellular processes: enhancing cell cycling and promoting cell survival by maintaining the expression of IL-7 receptor alpha. This pathway for clonal expansion of the CD8+ T cell is not associated with the development of a capacity either for production of IFN-gamma or for cytotoxic T lymphocyte function and, therefore, is uncoupled from differentiation. Furthermore, ligating CD27 increases the threshold concentration at which IL-2 induces IFN-gamma-producing capability by the CD8+ T cell, suggesting that CD27 signaling may suppress effector differentiation. Finally, CD8+ T cells that have been stimulated by the TCR/CD27 pathway maintain their capacity for subsequent expansion and effector differentiation in response to a viral challenge in vivo. Thus, the TCR/CD27 pathway enables the CD8+ T cell to replicate by a process of self-renewal, which may contribute to the continuous generation of new effector CD8+ T cells in persistent viral infections.

Population genetic models can be used to study the evolution of the interacting behaviours of parents and their progeny

An example of the evolution of the interacting behaviours of parents and progeny is studied using iterative equations linking the frequencies of the gametes produced by the progeny to the frequencies of the gametes in the parental generation. This population genetics approach shows that a model in which both behaviours are determined by a single locus can lead to a stable equilibrium in which the two behaviours continue to segregate. A model in which the behaviours are determined by genes at two separate loci leads eventually to fixation of the alleles at both loci but this can take many generations of selection. Models of the type described in this paper will be needed to understand the evolution of complex behaviour when genomic or experimental information is available about the genetic determinants of behaviour and the selective values of different genomes. (c) 2007 Elsevier Inc. All rights reserved.

Generation of anti-complement "prodrugs": cleavable reagents for specific delivery of complement regulators to disease sites

Expression of biologically active molecules as fusion proteins with antibody Fc can substantially extend the plasma half-life of the active agent but may also influence function. We have previously generated a number of fusion proteins comprising a complement regulator coupled to Fc and shown that the hybrid molecule has a long plasma half-life and retains biological activity. However, several of the fusion proteins generated had substantially reduced biological activity when compared with the native regulator or regulator released from the Fc following papain cleavage. We have taken advantage of this finding to engineer a prodrug with low complement regulatory activity that is cleaved at sites of inflammation to release active regulator. Two model prodrugs, comprising, respectively, the four short consensus repeats of human decay accelerating factor (CD55) linked to IgG4 Fc and the three NH2-terminal short consensus repeats of human decay accelerating factor linked to IgG2 Fc have been developed. In each, specific cleavage sites for matrix metalloproteinases and/or aggrecanases have been incorporated between the complement regulator and the Fc. These prodrugs have markedly decreased complement inhibitory activity when compared with the parent regulator in vitro. Exposure of the prodrugs to the relevant enzymes, either purified, or in supernatants of cytokine-stimulated chondrocytes or in synovial fluid, efficiently cleaved the prodrug, releasing active regulator. Such agents, having negligible systemic effects but active at sites of inflammation, represent a paradigm for the next generation of anti-C therapeutics.

The influence of larval density, food availability and habitat longevity on the life history and population growth rate of the midge Chironomus riparius

Despite long-standing interest in the forms and mechanisms of density dependence, these are still imperfectly understood. However, in a constant environment an increase in density must reduce per capita resource availability, which in turn leads to reduced survival, fecundity and somatic growth rate. Here we report two population experiments examining the density dependent responses under controlled conditions of an important indicator species, Chironomus riparius. The first experiment was run for 35 weeks and was started at low density with replicate populations being fed three different rations. Increased ration reduced generation time and increased population growth rate (pgr) but had no effect on survival, fecundity and female body weight in the first generation. In the second generation there was a six-fold increase in generation time, presumably due to the greatly reduced per capita resource availability as the estimated initial densities of the second generation were 300 times greater than the first. Juvenile survival to emergence, fecundity, adult body weight and pgr declined by 90%, 75%, 35% and 99%, respectively. These large between-generation effects may have obscured the effects of the threefold variation in ration, as only survival to emergence significantly increased with ration in the second generation. These results suggest that some chironomid larvae survive a reduction in resource availability by growing more slowly. In the ephemeral habitats sometimes occupied by C. riparius, the effects of population density may depend crucially on the longevity of the environment. A second experiment was therefore performed to measure pgr from six different starting densities over an eight-week period. The relationship between pgr and density was concave, viewed from above. At densities above 16 larvae per cm(2), less than 1% of the population emerged and no offspring were produced. Under the conditions of experiment 2 - an 8-week habitat lifespan carrying capacity was estimated as 8 larvae per cm(2).

Specificity grafting of human antibody frameworks selected from a phage display library: generation of a highly stable humanized anti-CD22 single-chain Fv fragment

A prerequisite for the enrichment of antibodies screened from phage display libraries is their stable expression on a phage during multiple selection rounds. Thus, if stringent panning procedures are employed, selection is simultaneously driven by antigen affinity, stability and solubility. To take advantage of robust pre-selected scaffolds of such molecules, we grafted single-chain Fv (scFv) antibodies, previously isolated from a human phage display library after multiple rounds of in vitro panning on tumor cells, with the specificity of the clinically established murine monoclonal anti-CD22 antibody RFB4. We show that a panel of grafted scFvs retained the specificity of the murine monoclonal antibody, bound to the target antigen with high affinity (6.4-9.6 nM), and exhibited exceptional biophysical stability with retention of 89-93% of the initial binding activity after 6 days of incubation in human serum at 37degreesC. Selection of stable human scaffolds with high sequence identity to both the human germline and the rodent frameworks required only a small number of murine residues to be retained within the human frameworks in order to maintain the structural integrity of the antigen binding site. We expect this approach may be applicable for the rapid generation of highly stable humanized antibodies with low immunogenic potential.

1,3-Dipolar cycloadditions to unsymmetrical ketone-derived chiral stabilized azomethine ylides: strategies for the synthesis of highly substituted amino acids

We report herein, the first generation of unsymmetrical ketone-derived chiral stabilized azomethine ylides. Intrairiolecular and intermolecular cycloaddition strategies have been utilized to synthesize both an enantiornerically pure bicyclic proline derivative and an enantionierically pure beta-hydroxy-alpha-amino acid.

Exploring context-awareness in the construction logistics services delivery

Managing a construction project supply chain effectively and efficiently is extremely difficult due to involvement of numerous sectors that are supported by ineffective communication system. An efficient construction supply chain system ensures the delivery of materials and other services to construction site while minimising costs and rewarding all sectors based on value added to the supply chain. The advancement of information, communication and wireless technologies is driving construction companies to deploy supply chain management strategies to seek better outputs. As part of the emerging wireless technologies, contextaware computing capability represents the next generation of ICT to the construction services. Conceptually, context-awareness could be integrated with Web Services in order to ensure the delivery of pertinent information to construction site and enhance construction supply chain collaboration. An initial study has indicated that this integrated system has the potential of serving and improving the construction services delivery through access to context-specific data, information and services on as-needed basis.

Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise

Recent brain imaging studies using functional magnetic resonance imaging (fMRI) have implicated insula and anterior cingulate cortices in the empathic response to another's pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices) during meditation (versus rest). During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ), and right posterior superior temporal sulcus (pSTS) in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in response to emotional stimuli.

Random number generation as an index of controlled processing

Random number generation (RNG) is a functionally complex process that is highly controlled and therefore dependent on Baddeley's central executive. This study addresses this issue by investigating whether key predictions from this framework are compatible with empirical data. In Experiment 1, the effect of increasing task demands by increasing the rate of the paced generation was comprehensively examined. As expected, faster rates affected performance negatively because central resources were increasingly depleted. Next, the effects of participants' exposure were manipulated in Experiment 2 by providing increasing amounts of practice on the task. There was no improvement over 10 practice trials, suggesting that the high level of strategic control required by the task was constant and not amenable to any automatization gain with repeated exposure. Together, the results demonstrate that RNG performance is a highly controlled and demanding process sensitive to additional demands on central resources (Experiment 1) and is unaffected by repeated performance or practice (Experiment 2). These features render the easily administered RNG task an ideal and robust index of executive function that is highly suitable for repeated clinical use.

Using the web graph to influence application behaviour

The Web's link structure (termed the Web Graph) is a richly connected set of Web pages. Current applications use this graph for indexing and information retrieval purposes. In contrast the relationship between Web Graph and application is reversed by letting the structure of the Web Graph influence the behaviour of an application. Presents a novel Web crawling agent, AlienBot, the output of which is orthogonally coupled to the enemy generation strategy of a computer game. The Web Graph guides AlienBot, causing it to generate a stochastic process. Shows the effectiveness of such unorthodox coupling to both the playability of the game and the heuristics of the Web crawler. In addition, presents the results of the sample of Web pages collected by the crawling process. In particular, shows: how AlienBot was able to identify the power law inherent in the link structure of the Web; that 61.74 per cent of Web pages use some form of scripting technology; that the size of the Web can be estimated at just over 5.2 billion pages; and that less than 7 per cent of Web pages fully comply with some variant of (X)HTML.

An analysis on the performance of the forward and return interaction channels in DVB-RCS

The next generation consumer level interactive services require reliable and constant communication for both mobile and static users. The Digital Video Broadcasting ( DVB) group has exploited the rapidly increasing satellite technology for the provision of interactive services and launched a standard called Digital Video Broadcast through Return Channel Satellite (DYB-RCS). DVB-RCS relies on DVB-Satellite (DVB-S) for the provision of forward channel. The Digital Signal processing (DSP) implemented in the satellite channel adapter block of these standards use powerful channel coding and modulation techniques. The investigation is concentrated towards the Forward Error Correction (FEC) of the satellite channel adapter block, which will help in determining, how the technology copes with the varying channel conditions and user requirements(1).

Anticoagulant resistance in Norway rats (Rattus norvegicus Berk.) in Kent - a VKORC1 single nucleotide polymorphism, tyrosine139phenylalanine, new to the UK

A sample of 10 Norway rats (Rattus norvegicus) was taken for DNA resistance testing from an agricultural site in Kent where applications of the anticoagulant rodenticide bromadiolone had been unsuccessful. All animals tested were homozygous for the single nucleotide VKORC1 polymorphism tyrosine139phenylalanine, or Y139F. This is a common resistance mutation found extensively in France and Belgium but not previously in the UK. Y139F confers a significant level of resistance to first-generation anticoagulants, such as chlorophacinone, and to the second-generation compound bromadiolone. Another compound widely used in the UK, difenacoum, is also thought to be partially resisted by rats which carry Y139F. A silent VKORC1 mutation was also found in all rats tested. The presence of a third important VKORC1 mutation which confers resistance to anticoagulant rodenticides in widespread use in the UK, the others being Y139C and L120Q, further threatens the ability of pest control practitioners to deliver effective rodent control.

Blood-clotting response tests for resistance to diphacinone and chlorophacinone in the Norway rat (Rattus norvegicus Berk.)

Resistance baselines were obtained for the first generation anticoagulant rodenticides chlorophacinone and diphacinone using laboratory, caesarian-derived Norway rats (Rattus norvegicus) as the susceptible strain and the blood clotting response test method. The ED99 estimates for a quantal response were: chlorophacinone, males 0.86 mg kg−1, females 1.03 mg kg−1; diphacinone, males 1.26 mg kg−1, females 1.60 mg kg−1. The dose-response data also showed that chlorophacinone was significantly (p<0.0001) more potent than diphacinone for both male and female rats, and that male rats were more susceptible than females to both compounds (p<0.002). The ED99 doses were then given to groups of five male and five female rats of the Welsh and Hampshire warfarin-resistant strains. Twenty-four hours later, prothrombin times were slightly elevated in both strains but all the animals were classified as resistant to the two compounds, indicating cross-resistance from warfarin to diphacinone and chlorophacinone. When rats of the two resistant strains were fed for six consecutive days on baits containing either diphacinone or chlorophacinone, many animals survived, indicating that their resistance might enable them to survive treatments with these compounds in the field.