When the path is never shortest: a reality check on shortest path biocomputation

Shortest path problems are a touchstone for evaluating the computing performance and functional range of novel computing substrates. Much has been published in recent years regarding the use of biocomputers to solve minimal path problems such as route optimisation and labyrinth navigation, but their outputs are typically difficult to reproduce and somewhat abstract in nature, suggesting that both experimental design and analysis in the field require standardising. This chapter details laboratory experimental data which probe the path finding process in two single-celled protistic model organisms, Physarum polycephalum and Paramecium caudatum, comprising a shortest path problem and labyrinth navigation, respectively. The results presented illustrate several of the key difficulties that are encountered in categorising biological behaviours in the language of computing, including biological variability, non-halting operations and adverse reactions to experimental stimuli. It is concluded that neither organism examined are able to efficiently or reproducibly solve shortest path problems in the specific experimental conditions that were tested. Data presented are contextualised with biological theory and design principles for maximising the usefulness of experimental biocomputer prototypes.Comment: To appear in: Adamatzky, A (Ed.) Shortest path solvers. From software to wetware. Springer, 201

Identification of KIF3A as a Novel Candidate Gene for Childhood Asthma Using RNA Expression and Population Allelic Frequencies Differences

Asthma is a chronic inflammatory disease with a strong genetic predisposition. A major challenge for candidate gene association studies in asthma is the selection of biologically relevant genes.Using epithelial RNA expression arrays, HapMap allele frequency variation, and the literature, we identified six possible candidate susceptibility genes for childhood asthma including ADCY2, DNAH5, KIF3A, PDE4B, PLAU, SPRR2B. To evaluate these genes, we compared the genotypes of 194 predominantly tagging SNPs in 790 asthmatic, allergic and non-allergic children. We found that SNPs in all six genes were nominally associated with asthma (p<0.05) in our discovery cohort and in three independent cohorts at either the SNP or gene level (p<0.05). Further, we determined that our selection approach was superior to random selection of genes either differentially expressed in asthmatics compared to controls (p = 0.0049) or selected based on the literature alone (p = 0.0049), substantiating the validity of our gene selection approach. Importantly, we observed that 7 of 9 SNPs in the KIF3A gene more than doubled the odds of asthma (OR = 2.3, p<0.0001) and increased the odds of allergic disease (OR = 1.8, p<0.008). Our data indicate that KIF3A rs7737031 (T-allele) has an asthma population attributable risk of 18.5%. The association between KIF3A rs7737031 and asthma was validated in 3 independent populations, further substantiating the validity of our gene selection approach.Our study demonstrates that KIF3A, a member of the kinesin superfamily of microtubule associated motors that are important in the transport of protein complexes within cilia, is a novel candidate gene for childhood asthma. Polymorphisms in KIF3A may in part be responsible for poor mucus and/or allergen clearance from the airways. Furthermore, our study provides a promising framework for the identification and evaluation of novel candidate susceptibility genes

AdaptFlow: Protocol-based Medical Treatment Using Adaptive Workflows

Objectives: In many medical domains investigator-initiated clinical trials are used to introduce new treatments and hence act as implementations of guideline-based therapies. Trial protocols contain detailed instructions to conduct the therapy and additionally specify reactions to exceptional situations (for instance an infection or a toxicity). To increase quality in health care and raise the number of patients treated according to trial protocols, a consultation system is needed that supports the handling of the complex trial therapy processes efficiently. Our objective was to design and evaluate a consultation system that should 1) observe the status of the therapies currently being applied, 2) offer automatic recognition of exceptional situations and appropriate decision support and 3) provide an automatic adaptation of affected therapy processes to handle exceptional situations. Methods: We applied a hybrid approach that combines process support for the timely and efficient execution of the therapy processes as offered by workflow management systems with a knowledge and rule base and a mechanism for dynamic workflow adaptation to change running therapy processes if induced by changed patient condition. Results and Conclusions: This approach has been implemented in the AdaptFlow prototype. We performed several evaluation studies on the practicability of the approach and the usefulness of the system. These studies show that the AdaptFlow prototype offers adequate support for the execution of real-world investigator-initiated trial protocols and is able to handle a large number of exceptions

Reference Materials for Measuring the Size of Nanoparticles

This article discusses the requirements for reference materials (RMs) for measuring the size of nanoparticles (NPs). Such RMs can be used for instrument calibration, statistical quality control or interlaboratory comparisons. They can come in the form of suspensions, powders or matrix-embedded materials [i.e. NPs integrated in a natural matrix (e.g., food, soil, or sludge)]. At present, uncertainty about the most suitable form of material, the most relevant measurands and the most useful metrological-traceability statement inhibits the production of NP RMs. In addition, the lack of validated methods and qualified laboratories to produce NP RMs present formidable challenges. Metal, inorganic and organic NPs are available, but most of them are intended to be laboratory chemicals. With the exception of latex materials, certified RMs are not available, although some metrology institutes have started to develop such materials for colloidal gold and silica particles.JRC.DG.D.2-Reference material

A mathematical model of foraging in a dynamic environment by trail-laying Argentine ants

Ants live in dynamically changing environments, where food sources become depleted and alternative sources appear. Yet most mathematical models of ant foraging assume that the ants' foraging environment is static. Here we describe a mathematical model of ant foraging in a dynamic environment. Our model attempts to explain recent empirical data on dynamic foraging in the Argentine ant Linepithema humile (Mayr). The ants are able to find the shortest path in a Towers of Hanoi maze, a complex network containing 32,768 alternative paths, even when the maze is altered dynamically. We modify existing models developed to explain ant foraging in static environments, to elucidate what possible mechanisms allow the ants to quickly adapt to changes in their foraging environment. Our results suggest that navigation of individual ants based on a combination of one pheromone deposited during foraging and directional information enables the ants to adapt their foraging trails and recreates the experimental results.14 page(s

AdaptFlow: Protocol-based Medical Treatment Using Adaptive Workflows

Objectives: In many medical domains investigator-initiated clinical trials are used to introduce new treatments and hence act as implementations of guideline-based therapies. Trial protocols contain detailed instructions to conduct the therapy and additionally specify reactions to exceptional situations (for instance an infection or a toxicity). To increase quality in health care and raise the number of patients treated according to trial protocols, a consultation system is needed that supports the handling of the complex trial therapy processes efficiently. Our objective was to design and evaluate a consultation system that should 1) observe the status of the therapies currently being applied, 2) offer automatic recognition of exceptional situations and appropriate decision support and 3) provide an automatic adaptation of affected therapy processes to handle exceptional situations. Methods: We applied a hybrid approach that combines process support for the timely and efficient execution of the therapy processes as offered by workflow management systems with a knowledge and rule base and a mechanism for dynamic workflow adaptation to change running therapy processes if induced by changed patient condition. Results and Conclusions: This approach has been implemented in the AdaptFlow prototype. We performed several evaluation studies on the practicability of the approach and the usefulness of the system. These studies show that the AdaptFlow prototype offers adequate support for the execution of real-world investigator-initiated trial protocols and is able to handle a large number of exceptions

Identification and characterization of organic nanoparticles in food

Interest in nanoparticles (NPs) has increased explosively over the past two decades. Using NPs, high loadings of vitamins and health-benefit actives can be achieved in food, and stable flavors as well as natural food-coloring dispersions can be developed. Detection and characterization of NPs are essential in understanding the benefits as well as the potential risks of the application of such materials in food. While many such applications are described in the literature, methods for detection and characterization of such particles are lacking. Organic NPs suitable for application in food are lipid-, protein- or polysaccharide-based particles, and this review describes current analytical techniques that are used, or could be used, for identification and characterization of such particles in food products. We divide the analytical approaches into four sections: sample preparation; separation; imaging; and, characterization. We discuss techniques and reported applications for NPs or otherwise related particle compounds. The results of this investigation show that, for a successful characterization of NPs in food, at least some kind of sample preparation will be required. While a simple sample preparation may be satisfactory for imaging techniques for known analytes, for other techniques, a further separation using chromatography, field-flow fractionation or ion-mobility separation is necessary. Subsequently, photon-correlation spectroscopy and especially mass spectrometry techniques as matrix-assisted laser desorption/ionization combined with time-of-flight mass spectrometry, seem suitable techniques for characterizing a wide variety of organic NPs

Identification and characterization of organic nanoparticles in food

Interest in nanoparticles (NPs) has increased explosively over the past two decades. Using NPs, high loadings of vitamins and health-benefit actives can be achieved in food, and stable flavors as well as natural food-coloring dispersions can be developed. Detection and characterization of NPs are essential in understanding the benefits as well as the potential risks of the application of such materials in food. While many such applications are described in the literature, methods for detection and characterization of such particles are lacking. Organic NPs suitable for application in food are lipid-, protein- or polysaccharide-based particles, and this review describes current analytical techniques that are used, or could be used, for identification and characterization of such particles in food products. We divide the analytical approaches into four sections: sample preparation; separation; imaging; and, characterization. We discuss techniques and reported applications for NPs or otherwise related particle compounds. The results of this investigation show that, for a successful characterization of NPs in food, at least some kind of sample preparation will be required. While a simple sample preparation may be satisfactory for imaging techniques for known analytes, for other techniques, a further separation using chromatography, field-flow fractionation or ion-mobility separation is necessary. Subsequently, photon-correlation spectroscopy and especially mass spectrometry techniques as matrix-assisted laser desorption/ionization combined with time-of-flight mass spectrometry, seem suitable techniques for characterizing a wide variety of organic NPs