Ants find the shortest path: a mathematical proof

In the most basic application of Ant Colony Optimization (ACO), a set of artificial ants find the shortest path between a source and a destination. Ants deposit pheromone on paths they take, preferring paths that have more pheromone on them. Since shorter paths are traversed faster, more pheromone accumulates on them in a given time, attracting more ants and leading to reinforcement of the pheromone trail on shorter paths. This is a positive feedback process that can also cause trails to persist on longer paths, even when a shorter path becomes available. To counteract this persistence on a longer path, ACO algorithms employ remedial measures, such as using negative feedback in the form of uniform evaporation on all paths. Obtaining high performance in ACO algorithms typically requires fine tuning several parameters that govern pheromone deposition and removal. This paper proposes a new ACO algorithm, called EigenAnt, for finding the shortest path between a source and a destination, based on selective pheromone removal that occurs only on the path that is actually chosen for each trip. We prove that the shortest path is the only stable equilibrium for EigenAnt, which means that it is maintained for arbitrary initial pheromone concentrations on paths, and even when path lengths change with time. The EigenAnt algorithm uses only two parameters and does not require them to be finely tuned. Simulations that illustrate these properties are provided.     

Host bromeliads and their associated frog species: Further considerations on the importance of species interactions for conservation

Bromeliads constitute a good example of symbiosis with organisms that spend their entire life cycle inside the plants, and often depend on them to breed. The bromeliads benefit from this interaction by increasing their nutrients intake. Conservation efforts tend to focus on a single endangered species, but in symbiotic associations, the viability of one species depends on that of the other. Based on IUCN criteria, any species that depends on another to complete its life cycle should be assigned a conservation status equivalent to that of the host taxon, where appropriate. We gathered published plus fieldwork data on the frog-bromeliad mutualism and compiled a checklist of 99 bromeligenous frogs species associated to 69 bromeliad hosts, and found threatened bromeliads hosting non-threatened frogs. We found that 62% bromeligenous frogs inhabit unspecified bromeliads. Finally, we propose strategies for improving understanding and conservation of the frog-bromeliad mutualism.     

Metapopulations of moths on islands: a test of two contrasting models

1. We describe a generalized mainland-island metapopulation model which includes migration among the island populations. We test model predictions with quantitative data on more than 200 species of moths in two contrasting networks of small islands. The data include a direct measure of migration rate, based on trapping of moths on rocky skerries with no local populations of the vast majority of species.
2. We predicted that moths which are strong fliers but uncommon on the islands have a higher incidence on scattered islands than on islands in a group, because the latter 'compete' for immigrants from the mainland. In contrast, we predicted that weakly flying species with potentially large local populations on the islands occur more frequently on islands in a group due to enhanced colonization rate.
3. Both predicted patterns were observed. Island occupancy increased significantly with the number of individuals caught on the rocky skerries, which is our measure of migration rate from the mainland, supporting the basic assumption that the species occur on the islands in a balance between colonizations and extinctions.
4. These results demonstrate that the moth metapopulations on islands represent a mixture of Levins's and mainland-island metapopulations, and that the mixture is different for different species in the same landscape.     

Human embryonic stem cell research: why the discarded-created-distinction cannot be based on the potentiality argument

Discussions about the use and derivation of pluripotent human embryonic stem cells are a stumbling block in developing public policy on stem cell research. On the one hand there is a broad consensus on the benefits of these cells for science and biomedicine; on the other hand there is the controversial issue of killing human embryos. I will focus on the compromise position that accepts research on spare embryos, but not on research embryos ('discarded-created-distinction', from now on d-c-d). I will point out that this viewpoint is hard to maintain. The main focus is that the 'revealed beliefs' of its defenders are inconsistent with their 'professed beliefs', more specifically with their main argument, i.e. the potentiality argument. I will point out that (1) the defenders of d-c-d actually grant a relative moral status to the human embryo, (2) this moral status is dependent on internal and external criteria of potentiality, (3) potentiality seen as a variable value that also depends on external criteria cannot justify d-c-d, and (4) an approach to human embryonic stem cell-research that would also allow the use of research embryos is more compatible with the feelings, attitudes and values of those who currently defend d-c-d and, therefore, could lead to a broader consensus and to actions that alleviate individual human suffering.     

Behavioral responses of the whitebacked planthopperSogatella furcifera (Homoptera: Delphacidae) on rice plants whose odors have been masked

In a two-choice test, moreS. furcifera females settled more often on exposed plants than on parafilm-masked ones, regardless of the susceptibility of rice varieties. This indicates that rice volatiles play an important role in the insect's short-range orientation to its host. The fact that more insects settled on exposed resistant Rathu Heenati (RHT) than to masked susceptible Taichung Native 1 (TN1) suggests that there must be certain common volatiles released by both varieties. Few females landed on masked plants of either RHT or TN1. This implies that the insect could not recognize at a distance that a plant was resistant or susceptible without olfactory stimuli.S. furcifera excreted less honeydew on masked plants than on exposed ones for both varieties and more on masked TN1 than on exposed RHT. The electronic monitoring of feeding behavior demonstrates that the insect made more frequent probes and had shorter phloem ingestion durations on exposed RHT than on exposed TN1 and on masked RHT than on masked TN1. Moreover, the insect had longer phloem ingestion durations on masked TN1 than on exposed RHT. These results suggest that volatile chemicals given off by resistant RHT plants have a negative effect on feeding.     

Risk assessment: the importance of genetic polymorphisms in man

Spontaneous mutation was greatly increased in a localized region of the chromosome of Haemophilus influenzae, but not at other loci, by a nov gene mutation called novC that increased DNA supercoiling. Another nov gene mutation, called novD, decreased spontaneous mutation in the same localized region and depressed DNA supercoiling. Both mutations, which code for the gyrase B subunit, have been cloned, and the cloned versions also altered mutagenesis and supercoiling in a similar fashion as the two mutations on the chromosome, although novC on the plasmid caused somewhat less mutation than on the chromosome. We postulate that the effects of the gyrase B mutations on the chromosome result from their effects on supercoiling because of increased gyrase near its site of production. The fact that the novC on a plasmid does not cause mutagenesis except in the same localized region that is altered by this mutation on the chromosome, is difficult to explain. One possibility is that there is a complex of proteins in this region which is necessary for the effects on supercoiling and thus, also on mutagenesis.     

Why Are Product Prices in Online Markets Not Converging?

Why are product prices in online markets dispersed in spite of very small search costs? To address this question, we construct a unique dataset from a Japanese price comparison site, which records price quotes offered by e-retailers as well as customers’ clicks on products, which occur when they proceed to purchase the product. The novelty of our approach is that we seek to extract useful information on the source of price dispersion from the shape of price distributions rather than focusing merely on the standard deviation or the coefficient of variation of prices, as previous studies have done. We find that the distribution of prices retailers quote for a particular product at a particular point in time (divided by the lowest price) follows an exponential distribution, showing the presence of substantial price dispersion. For example, 20 percent of all retailers quote prices that are more than 50 percent higher than the lowest price. Next, comparing the probability that customers click on a retailer with a particular rank and the probability that retailers post prices at a particular rank, we show that both decline exponentially with price rank and that the exponents associated with the probabilities are quite close. This suggests that the reason why some retailers set prices at a level substantially higher than the lowest price is that they know that some customers will choose them even at that high price. Based on these findings, we hypothesize that price dispersion in online markets stems from heterogeneity in customers’ preferences over retailers; that is, customers choose a set of candidate retailers based on their preferences, which are heterogeneous across customers, and then pick a particular retailer among the candidates based on the price ranking.     

Culture of large vessel endothelial cells on floating collagen gels promotes a phenotype characteristic of endothelium in vivo

The vascular endothelium in vivo is a remarkably quiescent cell layer that displays a highly differentiated and tissue-specific phenotype. Once established in culture, endothelial cells (EC) are phenotypically different from their in situ counterparts, displaying altered gene expression, increased mitotic index, and decreased cell density. To determine whether manipulating the microenvironment of cells in vitro would lead to a more differentiated phenotype, we cultured bovine aortic EC on floating collagen gels. EC cultured to confluence on floating gels for 24 or 48 hr display mitotic indices nearly identical to those of quiescent endothelium in vivo, nearly two log orders lower than that of EC cultured to confluence on plastic, and cell density on floating gels also resembles that observed for endothelium in vivo. Culture of EC on floating gels leads to decreased expression of platelet-derived growth factor-B, fibronectin, and fibronectin isoform ED-B, and increased levels of connexin40, relative to cells cultured on plastic. We conclude that culture of bovine aortic EC under standard culture conditions results in a phenotype reminiscent of development and/or wound healing, and that culturing them on a floating collagen gel leads to a more differentiated phenotype, reminiscent of that observed for large vessel EC in vivo.     

PackHelix: a tool for helix-sheet packing during protein structure prediction

The three‐dimensional structure of a protein is organized around the packing of its secondary structure elements. Predicting the topology and constructing the geometry of structural motifs involving α‐helices and/or β‐strands are therefore key steps for accurate prediction of protein structure. While many efforts have focused on how to pack helices and on how to sample exhaustively the topologies and geometries of multiple strands forming a β‐sheet in a protein, there has been little progress on generating native‐like packings of helices on sheets. We describe a method that can generate the packing of multiple helices on a given β‐sheet for αβα sandwich type protein folds. This method mines the results of a statistical analysis of the conformations of αβ₂ motifs in protein structures to provide input values for the geometric attributes of the packing of a helix on a sheet. It then proceeds with a geometric builder that generates multiple arrangements of the helices on the sheet of interest by sampling through these values and performing consistency checks that guarantee proper loop geometry between the helices and the strands, minimal number of collisions between the helices, and proper formation of a hydrophobic core. The method is implemented as a module of ProteinShop. Our results show that it produces structures that are within 4–6 Å RMSD of the native one, regardless of the number of helices that need to be packed, though this number may increase if the protein has several helices between two consecutive strands in the sequence that pack on the sheet formed by these two strands. Proteins 2011; Published 2011 Wiley‐Liss, Inc.     

Effects of biological invasions on forest carbon sequestration

There has been a rapidly developing literature on the effects of some of the major drivers of global change on carbon (C) sequestration, particularly carbon dioxide (CO₂) enrichment, land use change, nitrogen (N) deposition and climate change. However, remarkably little attention has been given to one major global change driver, namely biological invasions. This is despite growing evidence that invasive species can dramatically alter a range of aboveground and belowground ecosystem processes, including those that affect C sequestration. In this review, we assess the evidence for the impacts of biological invaders on forest C stocks and C sequestration by biological invaders. We first present case studies that highlight a range of invader impacts on C sequestration in forest ecosystems, and draw on examples that involve invasive primary producers, decomposers, herbivores, plant pathogens, mutualists and predators. We then develop a conceptual framework for assessing the effects of invasive species on C sequestration impacts more generally, by identifying the features of biological invaders and invaded ecosystems that are thought to most strongly regulate C in forests. Finally we assess the implications of managing invasive species on C sequestration. An important principle that emerges from this review is that the direct effects of invaders on forest C are often smaller and shorter‐term than their indirect effects caused by altered nutrient availability, primary productivity or species composition, all of which regulate long‐term C pools and fluxes. This review provides a conceptual basis for improving our general understanding of biological invaders on ecosystem C, but also points to a paucity of primary data that are needed to determine the quantitative effects of invaders on ecosystem processes that drive C sequestration.     

Membrane effects of ethanol: bulk lipid versus lipid domains

It has been well-established that ethanol fluidizes the bulk lipid of membranes and that this effect may alter cell function and be involved in ethanol sensitivity and tolerance. This hypothesis has been supported in several studies, however, there is also a considerable amount of data that do not support such an explanation, e.g., direct effect of ethanol on proteins, other membrane acting drugs, temperature effects, effects of ethanol on aged membranes and inconsistent effects of chronic ethanol consumption on lipid content. This review examined the bulk membrane fluidization hypothesis in light of those data and proposed a modification of the bulk membrane hypothesis that is based on recent data that show that ethanol and other alcohols have a specific effect on the structural properties of different membrane domains. This specific effect of ethanol is discussed within the context of how changes in fluidity of domains may alter membrane function.     

Xkid, a chromokinesin required for chromosome alignment on the metaphase plate

Metaphase chromosome alignment is a key step of animal cell mitosis. The molecular mechanism leading to this equatorial positioning is still not fully understood. Forces exerted at kinetochores and on chromosome arms drive chromosome movements that culminate in their alignment on the metaphase plate. In this paper, we show that Xkid, a kinesin-like protein localized on chromosome arms, plays an essential role in metaphase chromosome alignment and in its maintenance. We propose that Xkid is responsible for the polar ejection forces acting on chromosome arms. Our results show that these forces are essential to ensure that kinetochores and chromosome arms align on a narrow equatorial plate during metaphase, a prerequisite for proper chromosome segregation.     

Predicting the effect of a point mutation on a protein fold: the villin and advillin headpieces and their Pro62Ala mutants

Homology modeling of unknown proteins is based on the assumption that highly similar sequences are likely to share the same fold. However, this does not provide any information on the stability of a given fold, which is ultimately determined by the subtle interplay of enthalpic and entropic contributions. Herein it is shown that ab initio atomistic simulations can be used to predict the effect of point mutations on the stability of a protein fold. The calculations indicate that the fold stabilities of two proteins of similar sequence and identical fold, the villin and advillin C-terminal headpiece fragments, are different and that the same P62A point mutation has a dramatic effect on the fold of villin but a minor one on that of advillin. These predictions were subsequently validated by NMR and CD experiments.     

Finite strain elastodynamics of intracranial saccular aneurysms.

Various investigators suggest that intracranial saccular aneurysms are dynamically unstable, that they resonate in response to pulsatile blood flow. This hypothesis is based on linearized analyses or experiments on rubber "models", however, and there is a need for a more critical examination. Toward this end, we (a) derive a new nonlinear equation of motion for a pulsating spherical aneurysm that is surrounded by cerebral spinal fluid and whose behavior is described by a Fung-type pseudostrain-energy function that fits data on human lesions, and (b) use methods of nonlinear dynamics to examine the stability of such lesions against perturbations to both in vivo and in vitro conditions. The numerical results suggest that this sub-class of lesions is dynamically stable. Moreover, with the exception of transients associated with initial perturbations, inertial effects appear to be insignificant for fundamental forcing frequencies less than 10 Hz and hence for typical physiologic and laboratory conditions. We submit, therefore, that further study of the mechanics of saccular aneurysms should be focused on quasi-static stress analyses that investigate the roles of lesion geometry and material properties, including growth and remodeling.     

A Few Bad Apples: A Model of Disease Influenced Agent Behaviour in a Heterogeneous Contact Environment

For diseases that infect humans or livestock, transmission dynamics are at least partially dependent on human activity and therefore human behaviour. However, the impact of human behaviour on disease transmission is relatively understudied, especially in the context of heterogeneous contact structures such as described by a social network. Here, we use a strategic game, coupled with a simple disease model, to investigate how strategic agent choices impact the spread of disease over a contact network. Using beliefs that are based on disease status and that build up over time, agents choose actions that stochastically determine disease spread on the network. An agent’s disease status is therefore a function of both his own and his neighbours actions. The effect of disease on agents is modelled by a heterogeneous payoff structure. We find that the combination of network shape and distribution of payoffs has a non-trivial impact on disease prevalence, even if the mean payoff remains the same. An important scenario occurs when a small percentage (called noncooperators) have little incentive to avoid disease. For diseases that are easily acquired when taking a risk, then even when good behavior can lead to disease eradication, a small increase in the percentage of noncooperators (less than 5%) can yield a large (up to 25%) increase in prevalence.     

On meta-analytic assessment of surrogate outcomes

We discuss the strengths and weaknesses of the meta-analytic approach to estimating the effect of a new treatment on a true clinical outcome measure, T, from the effect of treatment on a surrogate response, S. The meta-analytic approach (see Daniels and Hughes (1997) 16, 1965-1982) uses data from a series of previous studies of interventions similar to the new treatment. The data are used to estimate relationships between summary measures of treatment effects on T and S that can be used to infer the magnitude of the effect of the new treatment on T from its effects on S. We extend the class of models to cover a broad range of applications in which the parameters define features of the marginal distribution of (T, S). We present a new bootstrap procedure to allow for the variability in estimating the distribution that governs the between-study variation. Ignoring this variability can lead to confidence intervals that are much too narrow. The meta-analytic approach relies on quite different data and assumptions than procedures that depend, for example, on the conditional independence, at the individual level, of treatment and T, given S (see Prentice (1989) 8, 431-440). Meta-analytic calculations in this paper can be used to determine whether a new study, based only on S, will yield estimates of the treatment effect on T that are precise enough to be useful. Compared to direct measurement on T, the meta-analytic approach has a number of limitations, including likely serious loss of precision and difficulties in defining the class of previous studies to be used to predict the effects on T for a new intervention.     

Rising Publication Delays Inflate Journal Impact Factors

Journal impact factors have become an important criterion to judge the quality of scientific publications over the years, influencing the evaluation of institutions and individual researchers worldwide. However, they are also subject to a number of criticisms. Here we point out that the calculation of a journal’s impact factor is mainly based on the date of publication of its articles in print form, despite the fact that most journals now make their articles available online before that date. We analyze 61 neuroscience journals and show that delays between online and print publication of articles increased steadily over the last decade. Importantly, such a practice varies widely among journals, as some of them have no delays, while for others this period is longer than a year. Using a modified impact factor based on online rather than print publication dates, we demonstrate that online-to-print delays can artificially raise a journal’s impact factor, and that this inflation is greater for longer publication lags. We also show that correcting the effect of publication delay on impact factors changes journal rankings based on this metric. We thus suggest that indexing of articles in citation databases and calculation of citation metrics should be based on the date of an article’s online appearance, rather than on that of its publication in print.     

Conditional survival as a selection strategy to identify plant-inducible genes of Pseudomonas syringae

A novel strategy termed habitat-inducible rescue of survival (HIRS) was developed to identify genes of Pseudomonas syringae that are induced during growth on bean leaves. This strategy is based on the complementation of metXW, two cotranscribed genes that are necessary for methionine biosynthesis and required for survival of P. syringae on bean leaves exposed to conditions of low humidity. We constructed a promoter trap vector, pTrap, containing a promoterless version of the wild-type P. syringae metXW genes. Only with an active promoter fused to metXW on pTrap did this plasmid restore methionine prototrophy to the P. syringae metXW mutant B7MX89 and survival of this strain on bean leaves. To test this method, a partial library of P. syringae genomic DNA was constructed in pTrap and a total of 1,400 B7MX89 pTrap clones were subjected to HIRS selection on bean leaves. This resulted in the enrichment of five clones, each with a unique RsaI restriction pattern of their DNA insert. Sequence analysis of these clones revealed those P. syringae genes for which putative plant-inducible activity could be assigned. Promoter activity experiments with a gfp reporter gene revealed that these plant-inducible gene promoters had very low levels of expression in minimal medium. Based on green fluorescent protein fluorescence levels, it appears that many P. syringae genes have relatively low expression levels and that the metXW HIRS strategy is a sensitive method to detect weakly expressed P. syringae genes that are active on plants. Furthermore, we found that protected sites on the leaf surface provided a higher level of enrichment for P. syringae expressing metXW than exposed sites. Thus, the metXW HIRS strategy should lead to the identification of P. syringae genes that are expressed primarily in these areas on the leaf.     

The distribution of cell surface proteins on spreading cells. Comparison of theory with experiment.

Bretscher (1983) has shown that on uniformly spread giant HeLa cells, the receptors for low density lipoprotein (LDL) and transferrin are concentrated toward the periphery of the cells. To explain these nonuniform distributions, he proposed that on giant HeLa cells, recycling receptors return to the cell surface at the cell's leading edge. Since the distribution of coated pits on these cells is uniform, Bretscher and Thomson (1983) proposed that there is a bulk membrane flow toward the cell centers. Here we present a mathematical model that allows us to predict the distribution of cell surface proteins on a thin circular cell, when exocytosis occurs at the cell periphery and endocytosis occurs uniformly over the cell surface. We show that on such a cell, a bulk membrane flow will be generated, whose average velocity is zero at the cell center and increases linearly with the distance from the cell center. Our model predicts that proteins that aggregate in coated pits will have concentrations that are maximal at the cell periphery. We fit our theory to the data of Bretscher and Thomson (1983) on the distribution of ferritin receptors for the following cases: the receptors move by diffusion alone; they move by bulk membrane flow alone; they move by a combination of diffusion and bulk membrane flow. From our fits we show that tau m greater than 3.5 tau p, where tau m and tau p are the lifetimes of the membrane and the ferritin receptor on the cell surface, and that tau pD less than 6.9 X 10(-7) cm2, where D is the ferritin receptor diffusion coefficient. Surprisingly, we obtain the best fits to the data when we neglect membrane flow. Our model predicts that for proteins that are excluded from coated pits, the protein concentration will be Gaussian, being maximal at the cell center and decreasing with the distance from the cell center. If on giant HeLa cells a protein with such a distribution could be found, it would strongly support Bretcher's proposal that there is an inward membrane flow.