Modelling the heart: insights,failures and progress

Mathematical models of the heart have developed over a period of about 40 years. Cell types in all regions of the heart have been modelled and they are now being incorporated into anatomically detailed models of the whole organ. This combination is leading to the creation of the first 'virtual organ,' which is being used in drug discovery and testing, and in simulating the action of devices, such as cardiac defibrillators. Simulation is a necessary tool of analysis in attempting to understand biological complexity. We often learn as much from the failures as from the successes of mathematical models. It is the iterative interaction between experiment and simulation that is important. Examples are given where this process has been instrumental in some of the major advances in the field.     

Modelling multimodal expression of emotion in a virtual agent

Over the past few years we have been developing an expressive embodied conversational agent system. In particular, we have developed a model of multimodal behaviours that includes dynamism and complex facial expressions. The first feature refers to the qualitative execution of behaviours. Our model is based on perceptual studies and encompasses several parameters that modulate multimodal behaviours. The second feature, the model of complex expressions, follows a componential approach where a new expression is obtained by combining facial areas of other expressions. Lately we have been working on adding temporal dynamism to expressions. So far they have been designed statically, typically at their apex. Only full-blown expressions could be modelled. To overcome this limitation, we have defined a representation scheme that describes the temporal evolution of the expression of an emotion. It is no longer represented by a static definition but by a temporally ordered sequence of multimodal signals.     

Contesting the natural in Japan: Moral dilemmas and technologies of dying

The paper opens with a discussion about the recognition of whole-brain death as the end of life in North America in order to perform solid organ transplants. This situation is contrasted with Japan, where, despite no financial or technological restrictions, brain death is not recognized, and transplants from brain-dead bodies cannot be performed. The Japanese cultural debate over the past twenty-five years about the brain-death problem is presented, followed by an analysis of Japanese attitudes, towards technological intervention into what is taken to be the natural domain, together with a discussion of current Japanese attitudes towards death. This debate is interpreted as one aspect of a search for moral order in contemporary Japan, revealing ambivalence about self and other, Japan and the West, and tradition and modernity.Portions of this paper were first given as the inaugural Roger Allan Moore lecture series on Values and Medicine: Ethical, Religious and Cultural Perspectives, Harvard University, May 1992.     

Modelling the effects of dams on freshwater fish distributions in Hokkaido, Japan

1. We examined the effects of habitat fragmentation caused by dams on freshwater fish species using a database of 7848 fish presence/absence surveys, conducted between 1953–2003 in Hokkaido, Japan. 2. A series of generalised linear models showed that for 11 of 41 taxa examined, the probability of occurrence had been influenced either negatively (eight taxa) or positively (three taxa) by the presence of a dam downstream from their habitat. 3. Maps of modelled predictions revealed that dams had had widespread negative impacts on certain taxa, while for other taxa the impact was limited to specific basins. Two of the three taxa whose probability of occurrence was increased in areas above dams have long been transplanted into reservoirs in Japan. 4. For four of the eight taxa whose probability of occurrence was reduced above dams and all three taxa whose probability of occurrence increased above dams, the temporal length of habitat isolation (i.e. the number of years between dam construction and sampling) was also a significant predictor of the probability of occurrence. This pattern indicates that these taxa experienced a gradual rather than an instantaneous population impact as a result of dam construction. 5. The eight taxa whose probability of occurrence was reduced as a consequence of dams all exhibit migratory life cycles. Although migratory taxa are probably more susceptible to the negative effect of dams, we could not detect significant relationships between migration life histories and the effect of fragmentation by dams. 6. These analyses enable stream and fisheries managers to quantify the impacts of habitat fragmentation because of dams for individual species. The spatially explicit nature of our analyses also enables identification of the areas of the impact at broad geographical scales. Using our results, managers can take effective conservation and restoration measures to predict, mitigate or remove the impact of dams. For example, our results can be used to prioritise dams for removal or to predict losses of biodiversity and ecosystem services in advance of dam construction.     

Bioinspired actuation of the eyeballs of an android robotic face: concept and preliminary investigations

This paper describes the concept and preliminary investigations related to the development of simple bioinspired actuation mechanisms for the eyeballs of an android robotic face. Two design solutions for a one-degree-of-freedom mechanism are proposed and analytically studied according to linear models. Both of them are based on new contractile actuators made of electroactive polymers, employed as pseudomuscular devices. The actuators consist of dielectric elastomers and are capable of electrically driven linear contractions. The arrangement and the functionality of the actuators were conceived to mimic those of rectus-type human ocular muscles. Both the presented solutions rely on a couple of agonist-antagonist actuators, in order to enable bidirectional rotations of the eyeball around an axis. The two configurations basically differ in the presence/absence of pulleys, guiding tendon-like wires which connect the actuators to the eyeball. The influence on the system performances of both rest length and elastic modulus of the actuators was studied for both configurations. Geometrical constraints allow the configuration with pulleys to perform more than the other, despite a potential intrinsic superior efficacy of the latter. The paper describes also the assembly of a simple prototype version of the system and presents the results of preliminary tests. These permitted us to assess the feasibility of the proposed concept and suggested possible improvements.     

Modelling the population dynamics of the toxic dinoflagellate Alexandrium Tamarense in Hiroshima Bay, Japan

In the present study, a numerical model that simulates speciescompetition between the toxic dinoflagellate Alexandrium tamarenseand the non-toxic diatom Skeletonema costatum was constructedusing data from a number of experiments and field observations.In the model, not only vertical migration of swimming cellsbut also the encystment and excystment processes of A. tamarensewere taken into consideration. Sinking of S. costatum cellswas also considered. Both zooplankton and oysters, which areintensively cultured in this bay, feed on the phytoplanktonbut the contribution of grazing to the decrease in the celldensities of both species was small. The model predicts thatwhile sinking is one of the major processes that reduce thecell density of S. costatum, encystment of A. tamarense is acrucial process that determines the cessation of blooms of thisdinoflagellate. Advection and diffusion are also important physicalprocesses that affect, in positive and negative ways, the fluctuationof cell densities.     

Modelling the Evolution of Traits in a Two-Sex Population,with an Application to Grandmothering

We present a mathematical simplification for the evolutionary dynamics of a heritable trait within a two-sex population. This trait is assumed to control the timing of sex-specific life-history events, such as the age of sexual maturity and end of female fertility, and each sex has a distinct fitness trade-off associated with the trait. We provide a formula for the fitness landscape of the population and show a natural extension of the result to an arbitrary number of heritable traits. Our method can be viewed as a dynamical systems generalisation of the Price equation to include two sexes, age structure and multiple traits. We use this formula to examine the effect of grandmothering, whereby post-fertile females subsidise their daughter’s fertility by provisioning grandchildren. Grandmothering can drive a shift towards increasingly male-biased mating sex ratios due to a post-fertile life stage in females, while male fertility continues to older ages. Our fitness landscapes show a net increase in fitness for both males and females at longer lifespans, and as a result, we find that grandmothering alone provides an evolutionary trajectory to higher longevities.     

Molecular technologies in parasitology, with an emphasis on genomic approaches for investigating parasitic nematodes

In the last years, there have been substantial and rapid technological advances in the areas of genomics and genetics. These advances provide unique opportunities for exploring parasite development and reproduction at the molecular level and offer prospects for developing novel methods for the diagnosis and control of parasitism. The present keynote address illustrates the importance and impact of 'targeted' genomic studies of parasites in the wake of this technological revolution.     

The technologies and politics of delusion: an interview with artist Rod Dickinson

Artist Rod Dickinson’s work engages in a highly intelligent and provocative manner with the conditions of mediation and delusion that appear in the brain in a vat scenario. Over the last decade he has put together an impressive body of work about the apparatuses of social and informational control with which we are surrounded, involving an eclectic range of subject matter, including crop circles, Jim Jones and the suicides at the People’s Temple in Guyana, Stanley Milgram’s ‘Obedience to authority’ experiments, and James Tilly Matthews’ imaginary ‘Air loom’, an eighteenth-century mind-influencing device. He is now involved in a number of projects, including a recreation of the Waco siege and a piece based on Joseph Conrad’s The secret agent. In this conversation with Charlie Gere he discusses questions of social control, brainwashing, truth, and knowledge in relation to his work.     

Multilevel Modelling with Spatial Interaction Effects with Application to an Emerging Land Market in Beijing,China

This paper develops a methodology for extending multilevel modelling to incorporate spatial interaction effects. The motivation is that classic multilevel models are not specifically spatial. Lower level units may be nested into higher level ones based on a geographical hierarchy (or a membership structure—for example, census zones into regions) but the actual locations of the units and the distances between them are not directly considered: what matters is the groupings but not how close together any two units are within those groupings. As a consequence, spatial interaction effects are neither modelled nor measured, confounding group effects (understood as some sort of contextual effect that acts ‘top down’ upon members of a group) with proximity effects (some sort of joint dependency that emerges between neighbours). To deal with this, we incorporate spatial simultaneous autoregressive processes into both the outcome variable and the higher level residuals. To assess the performance of the proposed method and the classic multilevel model, a series of Monte Carlo simulations are conducted. The results show that the proposed method performs well in retrieving the true model parameters whereas the classic multilevel model provides biased and inefficient parameter estimation in the presence of spatial interactions. An important implication of the study is to be cautious of an apparent neighbourhood effect in terms of both its magnitude and statistical significance if spatial interaction effects at a lower level are suspected. Applying the new approach to a two-level land price data set for Beijing, China, we find significant spatial interactions at both the land parcel and district levels.     

Does chloroquine, an antimalarial drug, affect autophagy in Tetrahymena pyriformis?

The effect of chloroquine (CQ) on autophagy was studied in starved Tetrahymena pyriformis. When a proliferating Tetrahymena culture is transferred to a starvation medium, autophagy commences although cells most advanced in the cell cycle will divide. The drug was added to 1-h starved cells at different pH values because CQ affects pH dependently. The CQ concentration blocking all cell divisions was determined as the lowest toxic, but sublethal, concentration. Hence, the highest tolerated concentrations at pH 6.8, 7.1, and 7.7 were 1.0, 0.3, and 0.03 mM CQ, respectively. Lower CQ concentrations had a dose-dependent effect on cell increment and higher concentrations induced cell mortality. Rates of cell motility and decreases in cell volume were affected by the drug, while the capacity for endocytosis was unaffected in low concentrations but affected dose dependently in high concentrations. Light microscopically, all drug-treated cells contained small refractive bodies, but in toxic concentrations they also contained conspicuously large vacuoles. After 1 h and 4 h in CQ, fine structure analysis showed autophagosomes with electron-dense material in cells in tolerated concentrations and of enlarged size, but decreased number, in toxic concentrations. The contents of autophagosomes revealed cell organelles in different stages of disintegration. The conclusion is that the drug enhances autophagy in Tetrahymena in a pH-, dose-, and time-dependent manner.     

Actomyosin contractility and buckling of microtubules in nucleation,growth and disassembling of focal adhesions

Biomechanics and Modeling in Mechanobiology - Building up and maintenance of cytoskeletal structure in living cells are force-dependent processes involving a dynamic chain of polymerization and...