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Yoh Iwasa

Publications and source records attributed to Yoh Iwasa.

At least 55 records · Page 3Linked to original sources
PubMed2004

Estimating local interaction from spatiotemporal forest data, and Monte Carlo bias correction.

We point out a general problem in fitting continuous time spatially explicit models to a temporal sequence of spatial data observed at discrete times. To illustrate the problem, we examined the continuous time Markov model for forest gap dynamics. A forest is assumed to be apportioned into discrete cells (or sites) arranged in a regular square lattice. Each site is characterized as either a gap or a non-gap site according to the vegetation height of trees. The model incorporates the influence of neighboring sites on transition rate: transition rate from a non-gap to a gap site increases linearly with the number of neighbors that are currently in the gap state, and vice versa. We fitted the model to the spatiotemporal data of canopy height observed at the permanent plot in Barro Colorado Island (BCI). When we used the approximate maximum likelihood method to estimate the parameters of the model, the estimated transition rates included a large bias-in particular, the strength of interaction between nearby sites was underestimated. This bias originated from the assumption that each transition between two observation times is independent. The interaction between sites at local scale creates a long chain of transitions within a single census interval, which violates the independence of each transition. We show that a computer-intensive method, called Monte Carlo bias correction (MCBC), is very effective in removing the bias included in the estimate. The global and local gap densities measuring spatial aggregation of gap sites were computed from simulated and real gap dynamics to assess the model. When the approximate likelihood estimates were applied to the model, the predicted local gap density was clearly lower than the observed one. The use of MCBC estimates, suggesting a strong interaction between sites, improved this discrepancy.

Data Interpretation, Statistical↗
PubMed2004

Stochastic tunnels in evolutionary dynamics.

We study a situation that arises in the somatic evolution of cancer. Consider a finite population of replicating cells and a sequence of mutations: type 0 can mutate to type 1, which can mutate to type 2. There is no back mutation. We start with a homogeneous population of type 0. Mutants of type 1 emerge and either become extinct or reach fixation. In both cases, they can generate type 2, which also can become extinct or reach fixation. If mutation rates are small compared to the inverse of the population size, then the stochastic dynamics can be described by transitions between homogeneous populations. A "stochastic tunnel" arises, when the population moves from all 0 to all 2 without ever being all 1. We calculate the exact rate of stochastic tunneling for the case when type 1 is as fit as type 0 or less fit. Type 2 has the highest fitness. We discuss implications for the elimination of tumor suppressor genes and the activation of genetic instability. Although our theory is developed for cancer genetics, stochastic tunnels are general phenomena that could arise in many circumstances.

Cell Physiological Phenomena↗
PubMed2003

Evolutionary dynamics of escape from biomedical intervention.

Viruses, bacteria, eukaryotic parasites, cancer cells, agricultural pests and other inconvenient animates have an unfortunate tendency to escape from selection pressures that are meant to control them. Chemotherapy, anti-viral drugs or antibiotics fail because their targets do not hold still, but evolve resistance. A major problem in developing vaccines is that microbes evolve and escape from immune responses. The fundamental question is the following: if a genetically diverse population of replicating organisms is challenged with a selection pressure that has the potential to eradicate it, what is the probability that this population will produce escape mutants? Here, we use multi-type branching processes to describe the accumulation of mutants in independent lineages. We calculate escape dynamics for arbitrary mutation networks and fitness landscapes. Our theory shows how to estimate the probability of success or failure of biomedical intervention, such as drug treatment and vaccination, against rapidly evolving organisms.

Biological Evolution↗
PubMed2003

Somatic selection for and against cancer.

In multicellular organisms, cells cooperate within a well-defined developmental program. Cancer is a breakdown of such cooperation: cells mutate to phenotypes of uncoordinated proliferation. We study basic principles of the architecture of solid tissues that influence the rate of cancer initiation. In particular, we explore how somatic selection acts to prevent or to promote cancer. Cells with mutations in oncogenes or tumor suppressor genes often have increased proliferation rates. Somatic selection increases their abundance and thus enhances the risk of cancer. Many potentially harmful mutations, however, increase the probability of triggering apoptosis and, hence, initially lead to cells with reduced net proliferation rates. Such cells are eliminated by somatic selection, which therefore also works to reduce the risk of cancer. We show that a tissue organization into small compartments avoids the rapid spread of mutations in oncogenes and tumor suppressor genes, but promotes genetic instability. In small compartments, genetic instability, which confers a selective disadvantage for the cell, can spread by random drift. If both deleterious and advantageous mutations participate in tumor initiation, then we find an intermediate optimum for the compartment size.

Animals↗
PubMed2003

The linear process of somatic evolution.

Cancer is the consequence of an unwanted evolutionary process. Cells receive mutations that alter their phenotype. Especially dangerous are those mutations that increase the net reproductive rate of cells, thereby leading to neoplasia and later to cancer. The standard models of evolutionary dynamics consider well mixed populations of individuals in symmetric positions. Here we introduce a spatially explicit, asymmetric stochastic process that captures the essential architecture of evolutionary dynamics operating within tissues of multicellular organisms. The "linear process" has the property of cancelling out selective differences among cells yet retaining the protective function of apoptosis. This design can slow down the rate of somatic evolution dramatically and therefore delay the onset of cancer.

Animals↗
PubMed2003

Stripes, spots, or reversed spots in two-dimensional Turing systems.

Two-dimensional Turing models can generate stationary striped patterns or spotted patterns, and are used to explain the body pattern formation of animals. We studied the effects of the choice of reaction terms on pattern selection, i.e., which pattern is likely to be formed. We examined in detail a model with linear reaction terms and additional constraint terms that confine two variables within a finite range. In the one-dimensional model, a periodic stationary pattern can be formed only when the activator level is constrained both from below and from above. In the two-dimensional model, the relative distance of the equilibrium level of the activator between the upper and lower limitations determines the pattern selection. Striped patterns are produced when the equilibrium is equally distant from the upper and the lower limitations, but spotted patterns are produced when the equilibrium is clearly closer to one than to the other of two limitations. We then examined models with nonlinear reaction terms, including both activator-inhibitor and activator-depletion substrate type models; we attempted to explain the pattern selection of these nonlinear models based on the results of linear models with constraints. The distribution of the activator level is skewed positively and negatively for spotted patterns and reversed spotted patterns, respectively. In contrast, the skew of the distribution of the activator level was close to zero in the case of striped patterns. This observation provides a heuristic argument of how the location of the equilibrium between the constraints leads to pattern selection.

Animals↗
PubMed2003

Stochastic elimination of cancer cells.

Tissues of multicellular organisms consist of stem cells and differentiated cells. Stem cells divide to produce new stem cells or differentiated cells. Differentiated cells divide to produce new differentiated cells. We show that such a tissue design can reduce the rate of fixation of mutations that increase the net proliferation rate of cells. It has, however, no consequence for the rate of fixation of neutral mutations. We calculate the optimum relative abundance of stem cells that minimizes the rate of generating cancer cells. There is a critical fraction of stem cell divisions that is required for a stochastic elimination ('wash out') of cancer cells.

Animals↗
PubMed2003

Conservation effort and assessment of population size in fluctuating environments.

We consider optimal conservation strategies for endangered populations. We assume that the survival of the population is affected by unpredictable environmental fluctuation and can be improved by conservation effort. Furthermore, the exact value of the initial population size is assumed to be unknown. The conservation strategy involves two aspects: investment of assessment effort, to improve the estimate of the initial population size and investment of conservation effort. Both types of effort imply economic costs. The optimal management strategy is assumed to minimize the weighted sum of extinction probability and the economic cost of the conservation and the assessment effort. (1) We first analyse the optimal conservation effort when the current population size is known accurately. (2) Next, we consider the situation in which there is limited information (i.e. a cue) on population size. (3) We subsequently discuss the cases where the cue accuracy can be improved by assessment of the population. We study the optimal level of the assessment effort and discuss its dependence on various parameters.

Animals↗
PubMed2003

Optimal choice between feedforward and feedback control in gene expression to cope with unpredictable danger.

All organisms face risks of unpredictable danger caused by harmful physical environments, pathogens, parasites or predators. Organisms may have several alternative ways of coping with such dangers. These differ in cost, effectiveness and activation time. We study the conditions under which it is optimal to use different alternatives for damage control. As an example we consider a microbe (such as E. coli), which may experience heat shocks that cause denaturation of proteins in the cell. To restore the denatured proteins the organism produces heat-shock proteins (HSP). There are two different pathways for production of HSP. Some HSP are produced immediately after a heat shock (feedforward control), but additional HSP may be produced thereafter, stimulated by the presence of denatured proteins (feedback control). Feedforward is based solely on heat-shock intensity without accurate information on the resulting amount of denatured proteins. We examine the optimal combination of the two pathways that minimizes the sum of the damage caused by the presence of untreated denatured proteins and the production cost of HSP. The optimal response depends on the time delay for feedback control, the effectiveness of HSP in processing denatured proteins, the production cost of HSP, the severity of damage by denatured proteins and the probability distribution of the abundance of denatured protein conditional on heat-shock intensity. We find that feedforward control should always be used. Additional HSP may be produced by feedback control when the abundance of denatured protein is large whilst no feedback control should be used when it is small. All the HSP are produced by feedforward control when the maximum is close to the mean of denatured protein abundance conditional on the heat-shock intensity.

Defense Mechanisms↗
PubMed2003

Possibility of tissue separation caused by cell adhesion.

Adhesive molecules are suggested to play an important role when a single tissue is separated into two in developmental processes, illustrated by tissue-specific cadherins in the neural tube formation of amphibians. In this paper, we study the possibility for tissue separation to be carried out only by differential cell adhesion and random cell movement without any other morphogenetic mechanisms. We consider a two-dimensional regular triangular lattice filled with cells of three types (black, white, and gray). In the initial state, a cluster of black cells and a cluster of white cells are in contact and are surrounded by gray cells. Nearest-neighbor cells exchange their location at random, but the movement occurs faster if it increases the total adhesion. We considered separation to be successful if, in the final state, black cells and white cells kept their clusters but two clusters lost their direct contact with each other as gray cells are inserted between them. The maximum total adhesion (MTA) rule conjectures that the spatial pattern achieving maximum total adhesion might be that obtained in the final state. In the computer simulation, the runs for successful separation satisfied the condition predicted by the MTA rule. However, the condition for successful separation was more restricted than that predicted by the MTA rule. For some combinations of adhesions, it took an extremely long time to accomplish tissue separation. Finally, we discuss the role of homophilic adhesion molecules (such as cadherins) in the tissue separation processes, and show that the new expression of homophilic adhesion molecules cannot perform tissue separation without the change in other morphogenetic processes.

Animals↗
PubMed2003

Local regulation of homeostasis favors chromosomal instability.

Tissues of long-lived multicellular organisms have to maintain a constant number of functioning cells for many years. This process is called homeostasis. Homeostasis breaks down when cells emerge with mutations in tumor suppressor genes or oncogenes. Such mutated cells can have increased net rates of proliferation, which is increased somatic fitness. We show that the best protection against such mutations is achieved when homeostasis is regulated locally via small compartments. Small compartments, on the other hand, allow the accumulation of cells with reduced somatic fitness. Cells with mutations conferring genetic instability normally have a reduced somatic fitness because they have an increased probability of producing deleterious mutations or triggering apoptosis. Thus, small compartments protect against mutations in tumor suppressor genes or oncogenes but promote the emergence of genetic instability.

Cell Transformation, Neoplastic↗
PubMed2003

Difference in the retinal cone mosaic pattern between zebrafish and medaka: cell-rearrangement model.

In fish retina, four kinds of photoreceptor cells (or cones) are two-dimensionally arranged in a very regular manner, forming cone mosaics. Mosaic pattern differs between species--two typical patterns are "row mosaic" and "square mosaic", exemplified by the cone mosaics in zebrafish and in medaka, respectively. In this paper, we study a cell-rearrangement model. Cells with pre-fixed fate exchange their locations between nearest neighbors and form regular mosaic patterns spontaneously, if the adhesive force between nearest neighbors and between next-nearest neighbors depend on their cell types in an appropriate manner. The same model can produce both row and square mosaic patterns. However, if the cell-cell interaction is restricted to nearest neighbors only, the square mosaic (medaka pattern) cannot be generated, showing the importance of interaction between next-nearest neighbors. In determining whether row mosaic (zebrafish pattern) or square mosaic (medaka pattern) is to be formed, two shape factors are very important, which control the way adhesions in different geometric relations are combined. We also developed theoretical analysis of the parameter ranges for the row mosaic and the square mosaic to have higher total adhesion than alternative spatial patterns.

Animals↗
PubMed2003

Optimal conservation effort for a population in a stochastic environment.

We study the optimal conservation effort for a population in a fluctuating environment. The survivorship of a population is affected by unpredictable environmental fluctuation (noise) and can be improved by conservation effort accompanied by a cost. The optimal effort level is the one that minimizes the total cost, defined as the weighted sum of the population extinction risk and the economic cost of conservation effort. The optimal effort depends on the variance and the probability distribution of the noise, the relative importance of the population's survival vs. the economic cost, the effectiveness of conservation effort, and the time scope over which we optimize. The analysis of dynamic programming illustrates that the choice of extinction risk function greatly affects the optimal effort level. The conservation effort level that is the best solution of a multiple-year optimization may be higher than that for the corresponding single-year optimization, if the population is relatively safe. However, the conservation level for the multiple-year optimization becomes lower than for the single-year optimization if the population is endangered. In a similar manner, the optimal conservation effort level for the problem with a short time scope is either higher or lower than that for the problem with a long time scope, depending on the extinction risk of the population. Next, for each parameter of the model, we define five different sensitivities of extinction probability or of the total cost. We then study the mean increase in the total cost caused by the uncertainty of parameters. To achieve the best conservation result, we need to invest the limited research effort to the parameter with the largest effect to the optimal effort level, rather than to those with large impacts on the extinction probability or on the total cost. The recommended policy should depend critically on the choice of the criterion to optimize, which shows the importance of theoretical study of the relationship in performing proper decision making in conservation practice.

Animals↗
PubMed2003

Origin of directionality in the fish stripe pattern.

The formation of stripe patterns in animal skin has been explained by the reaction-diffusion (RD) system, a hypothetical chemical reaction proposed by A. Turing. Although animal stripes usually have directionality, the RD model alone cannot explain how the direction is specified. To investigate the mechanism regulating the direction of stripes, we studied stripe pattern formation in two species of Genicanthus during sexual conversion. These species share almost identical morphologic properties, except for their stripe direction. In both species, spots transiently arise at random positions and then combine and rearrange to form directional stripes. Computational analysis has shown that diffusion anisotropy is very effective at specifying the direction of stripes formed by the RD system. Model simulations reproduce the transient dynamics of directional pattern formation observed in fish as well as the resulting stripes. In cases where the magnitude and direction of diffusion anisotropy of the substances are identical, the resulting stripes are not directional. However, if they differ, stripes become directional. As only a small difference in anisotropy is required for this effect, any kind of structure with directional conformation might cause a marked change in stripe direction. Scales are the most likely candidate structure for generating anisotropic interactions in skin.

Animals↗
PubMed2003

Incomplete mixing promotes species coexistence in a lottery model with permanent spatial heterogeneity.

For many marine organisms, the population dynamics in multiple habitats are affected by migration of planktonic larvae. We herein examine the effect of incomplete larval mixing on the condition for species coexistence. The system consists of two heterogeneous habitats, each composed of a number of sites occupied by adults of two species. Larvae produced in a habitat form a pool and migrate to the pool of the other habitat. When an adult dies, the vacant site becomes occupied by an individual randomly chosen from the larval pool. We study (1). the invasibility of a inferior species which has no advantage in either habitats, (2). the dynamics when larval migration and competition among adults are symmetric between habitats, and (3). the case with unidirectional migration. The coexistence of competitors is more likely to occur when larval migration is weak.

Algorithms↗
PubMed2003

Extinction risk to bird populations caused by DDT exposure.

The impact of toxic chemicals on wild animals and plants can be quantified in terms of the enhanced risk of population extinction. To illustrate a method for doing this, we estimated such impact for two bird species: herring gull (Larus argentatus) in Long Island, NY, and sparrowhawk (Accipiter nisus) in eastern England, when they were exposed to DDT (p,p(')-dichlorodiphenyltrichloroethane) and its metabolites (called DDTs). The method we used is based on a formula of the mean time to population extinction derived for a stochastic differential equation (the canonical model). The intrinsic rate of natural population growth was estimated from an exponentially growing population, and the intensity of the environmental fluctuation was estimated from the magnitude of population size fluctuation. The effect of exposure to DDTs in reducing the population growth rate was evaluated based on an age-structured population model, by assuming that age-specific fertility is density-dependent and sensitive to DDTs exposure, but age-specific survivorship is not. The results are expressed in terms of the risk equivalent--the decrease in carrying capacity K that causes the same enhancement of extinction risk as chemical exposure at a given level. The risk equivalent can be used in mitigation banking.

Animals↗
PubMed2003

Environmental risk evaluation of chemicals: achievements of the project and seeds for future--development of metrics for evaluating risks.

Achievements of the research project entitled "Establishment of a scientific framework for the management of toxicity of chemicals based on environmental risk-benefit analysis" supported by the JST were introduced and reviewed, focusing on the development of the methodology for estimating risks; human health risks and ecological risks. The usefulness of loss of life expectancy as a metric for evaluating cancer and noncancer risks was demonstrated. To evaluate ecological risks, three metrics, 1/T, logT and T, developed based on the mean extinction time (T) of species were proposed. Then, their implication and feasibility were examined in terms of what ecological system should be conserved and how easily people can understand the implications of metrics. Protocols for estimating human health risks and ecological risks are illustrated.

Animals↗