We describe a 'reactor-diffusion' mechanism for precartilage condensation based on recent experiments on chondrogenesis in the early vertebrate limb and additional hypotheses. Cellular differentiation of mesenchymal cells into subtypes with different fibroblast growth factor (FGF) receptors occurs in the presence of spatio-temporal variations of FGFs and transforming growth factor-betas (TGF-βs). One class of differentiated cells produces elevated quantities of the extracellular matrix protein fibronectin, which initiates adhesion-mediated preskeletal mesenchymal condensation. The same class of cells also produces an FGFdependent laterally acting inhibitor that keeps condensations from expanding beyond a critical size. We show that this 'reactor-diffusion' mechanism leads naturally to patterning consistent with skeletal form, and describe simulations of spatio-temporal distribution of these differentiated cell types and the TGF-β and inhibitor concentrations in the developing limb bud.

It is shown that the problem of designing a two-reflector system transforming a plane wave front with given intensity into an output plane front with prescribed output intensity can be formulated and solved as the Monge-Kantorovich mass transfer problem 1 .where P d is the map ofΩ onT d and J is the Jacobian, is the expansion ratio and it measures the expansion of a tube of rays due to the two reflections [5]. It is assumed that both R 1 and R 2 are perfect reflectors and no energy is lost in the transformation process. Consequently, the corresponding relation between the input intensity I on Ω and output intensity L on T d is given by(1)The "two-reflector" problem that needs to be solved by designers of optical systems consists in determining the reflectors R 1 and R 2 so that all of the properties of the two-reflector system above hold for prescribed in advance domains Ω, T and positive integrable functions I(x), x ∈ Ω, and L(p), p ∈ T ;

We present COMPUCELL3D, a software framework for three-dimensional simulation of morphogenesis in different organisms. COMPUCELL3D employs biologically relevant models for cell clustering, growth, and interaction with chemical fields. COMPUCELL3D uses design patterns for speed, efficient memory management, extensibility, and flexibility to allow an almost unlimited variety of simulations. We have verified COMPUCELL3D by building a model of growth and skeletal pattern formation in the avian (chicken) limb bud. Binaries and source code are available, along with documentation and input files for sample simulations, at http:// compucell.sourceforge.net.

In this paper we present the foundation of a unified, object-oriented, three-dimensional biomodelling environment, which allows us to integrate multiple submodels at scales from subcellular to those of tissues and organs. Our current implementation combines a modified discrete model from statistical mechanics, the Cellular Potts Model, with a continuum reaction-diffusion model and a state automaton with well-defined conditions for cell differentiation transitions to model genetic regulation. This environment allows us to rapidly and compactly create computational models of a class of complex-developmental phenomena. To illustrate model development, we simulate a simplified version of the formation of the skeletal pattern in a growing embryonic vertebrate limb.

The cellular Potts model (CPM) has been used for simulating various biological phenomena such as differential adhesion, fruiting body formation of the slime mold Dictyostelium discoideum, angiogenesis, cancer invasion, chondrogenesis in embryonic vertebrate limbs, and many others. We derive a continuous limit of a discrete one-dimensional CPM with the chemotactic interactions between cells in the form of a Fokker-Planck equation for the evolution of the cell probability density function. This equation is then reduced to the classical macroscopic Keller-Segel model. In particular, all coefficients of the Keller-Segel model are obtained from parameters of the CPM. Theoretical results are verified numerically by comparing Monte Carlo simulations for the CPM with numerics for the Keller-Segel model.

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To gain performance, developers often build scientific applications in procedural languages, such as C or Fortran, which unfortunately reduces flexibility. To address this imbalance, the authors present CompuCell3D, a multitiered, flexible, and scalable problem-solving environment for morphogenesis simulations that's written in C++ using object-oriented design patterns.How the 3D development, or morphogenesis, of multicellular organisms arises from a singlecelled fertilized zygote with a 1D genome is still a challenge in postgenomic biology. But by treating cells with a phenomenological approach that ignores much of the detail of intracellular biochemistry, we can reduce multiple complex biochemical interactions to a small set of behaviors such as movement, division, death, differentiation, shape changes, and cell-cell communication. To tackle these sorts of problems, researchers often use problem-solving environments (PSEs) because they let users focus on particular domains of expertise without requiring knowledge of low-level modules. A molecular modeling PSE, for example, lets chemists transparently set up simulations of various systems at different temperatures, pressures, and so on, whereas an ecosystem PSE lets ecologists set up environments and add entities, organisms, and evolutionary models.