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The presence of debris in Earth's orbit poses a significant risk to human activity in outer space. This debris population continues to grow due to ground launches, loss of external parts from space ships, and uncontrollable collisions between objects. A computationally feasible continuum model for the growth of the debris population and its spatial distribution is therefore critical. Here we propose a diffusion-collision model for the evolution of debris density in Low-Earth Orbit (LEO) and its dependence on ground-launch policy. We parametrize this model and test it against data from publicly available object catalogs to examine timescales for uncontrolled growth. Finally, we consider sensible launch policies and cleanup strategies and how they reduce the future risk of collisions with active satellites or space ships.

Protein-protein interaction networks associated with diseases have gained prominence as an area of research. We investigate algebraic and topological indices for protein-protein interaction networks of 11 human cancers derived from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We find a strong correlation between relative automorphism group sizes and topological network complexities on the one hand and five year survival probabilities on the other hand. Moreover, we identify several protein families (e.g. PIK, ITG, AKT families) that are repeated motifs in many of the cancer pathways. Interestingly, these sources of symmetry are often central rather than peripheral. Our results can aide in identification of promising targets for anti-cancer drugs. Beyond that, we provide a unifying framework to study protein-protein interaction networks of families of related diseases (e.g. neurodegenerative diseases, viral diseases, substance abuse disorders)., Comment: 15 pages, 4 figures

We study packings of $n$ hard spheres of equal radius in the $d$-dimensional unit cube. We present a nonsmooth function whose local extrema are the radii of jammed packings (where no subset of spheres can be moved keeping all others fixed) and show that for a fixed number of spheres there are only finitely many radii of such jammed configurations. We propose an algorithm for the maximization of this maximal radius function and present examples for 5 - 8 disks in the unit square and 4 - 6 spheres in the unit cube. The method allows straightforward generalization to packings of spheres in other compact containers., Comment: 23 pages, 12 figures

Matrix tablets are drug delivery devices designed to release a drug in a controlled manner over an extended period of time. We develop a cellular automaton (CA) model for the dissolution and release of a water-soluble drug and excipient from a matrix tablet of water-insoluble polymer. Cells of the CA are occupied by drug, excipient, water or polymer and the CA updating rules simulate the dissolution of drug and excipient and the subsequent diffusion of the dissolved substances. In addition we simulate the possible fracture of brittle drug and excipient powders during the tablet compression and the melting of the polymer during a possible thermal curing process. Different stirring mechanisms that facilitate the transport of dissolved drug in the fluid in which the tablet is immersed are modeled in the water cells adjacent to the boundary of the tablet. We find that our simulations can reproduce experimental drug release profiles. Our simulation tool can be used to streamline the formulation and production of sustained release tablets., Comment: 15 pages, 9 figures

We propose a hybrid dynamical system approach to model the evolution of a pathogen that experiences different selective pressures according to a stochastic process. In every environment, the evolution of the pathogen is described by a version of the Fisher-Haldane-Wright equation while the switching between environments follows a Markov jump process. We investigate how the qualitative behavior of a simple single-host deterministic system changes when the stochastic switching process is added. In particular, we study the stability in probability of monomorphic equilibria. We prove that in a "constantly" fluctuating environment, the genotype with the highest mean fitness is asymptotically stable in probability. However, if the probability of host switching depends on the genotype composition of the population, polymorphism can be stably maintained. This is a corrected version of the paper that appeared in Mathematical Biosciences 240 (2012), p. 70-75. A corrigendum has appeared in the same journal., Comment: 15 pages, 4 figures

We propose a stochastic model that accounts for the growth, catastrophe and rescue processes of steady state microtubules assembled from MAP-free tubulin. Both experimentally and theoretically we study the perturbation of microtubule dynamic instability by S-methyl-D-DM1, a synthetic derivative of the microtubule-targeted agent maytansine and a potential anticancer agent. We find that to be an effective suppressor of microtubule dynamics a drug must primarily suppress the loss of GDP tubulin from the microtubule tip., Comment: 17 pages, 11 figures, to appear in Phys. Biol

We consider a linear size-structured population model with diffusion in the size-space. Individuals are recruited into the population at arbitrary sizes. The model is equipped with generalized Wentzell-Robin (or dynamic) boundary conditions. This allows modelling of "adhesion" at extremely small or large sizes. We establish existence and positivity of solutions by showing that solutions are governed by a positive quasicontractive semigroup of linear operators on the biologically relevant state space. This is carried out via establishing dissipativity of a suitably perturbed semigroup generator. We also show that solutions of the model exhibit balanced exponential growth, that is our model admits a finite dimensional global attractor. In case of strictly positive fertility we are able to establish that solutions in fact exhibit asynchronous exponential growth.

We investigate steady states of a quasilinear first order hyperbolic partial integro-differential equation. The model describes the evolution of a hierarchical structured population with distributed states at birth. Hierarchical size-structured models describe the dynamics of populations when individuals experience size-specific environment. This is the case for example in a population where individuals exhibit cannibalistic behavior and the chance to become prey (or to attack) depends on the individual's size. The other distinctive feature of the model is that individuals are recruited into the population at arbitrary size. This amounts to an infinite rank integral operator describing the recruitment process. First we establish conditions for the existence of a positive steady state of the model. Our method uses a fixed point result of nonlinear maps in conical shells of Banach spaces. Then we study stability properties of steady states for the special case of a separable growth rate using results from the theory of positive operators on Banach lattices., Comment: to appear in Discrete and Continuous Dynamical Systems - Series B

Motivated by a problem arising from pharmaceutical science [B. Baeumer et al., Discr. Contin. Dyn. Sys. B 12], we study random walks on the contact graph of a bidisperse random sphere packing. For a random walk on the unweighted graph that terminates in a specified target set, we compare the number of steps and the total euclidean length of the walk. We find a linear relationship between the two metrics with a proportionality constant that can be calculated from the edge length probabilities of the contact graph., Comment: 9 pages, 4 figures

We introduce and investigate a series of models for an infection of a diplodiploid host species by the bacterial endosymbiont \textit{Wolbachia}. The continuous models are characterized by partial vertical transmission, cytoplasmic incompatibility and fitness costs associated with the infection. A particular aspect of interest is competitions between mutually incompatible strains. We further introduce an age-structured model that takes into account different fertility and mortality rates at different stages of the life cycle of the individuals. With only a few parameters, the ordinary differential equation models exhibit already interesting dynamics and can be used to predict criteria under which a strain of bacteria is able to invade a population. Interestingly, but not surprisingly, the age-structured model shows significant differences concerning the existence and stability of equilibrium solutions compared to the unstructured model., Comment: 24 pages, 6 figures, revised and expanded

In this work we introduce and analyze a linear size-structured population model with infinite states-at-birth. We model the dynamics of a population in which individuals have two distinct life-stages: an "active" phase when individuals grow, reproduce and die and a second "resting" phase when individuals only grow. Transition between these two phases depends on individuals' size. First we show that the problem is governed by a positive quasicontractive semigroup on the biologically relevant state space. Then we investigate, in the framework of the spectral theory of linear operators, the asymptotic behavior of solutions of the model. We prove that the associated semigroup has, under biologically plausible assumptions, the property of asynchronous exponential growth., Comment: 1 figure, to appear in Positivity

Motivated by structured parasite populations in aquaculture we consider a class of size-structured population models, where individuals may be recruited into the population with distributed states at birth. The mathematical model which describes the evolution of such a population is a first-order nonlinear partial integro-differential equation of hyperbolic type. First, we use positive perturbation arguments and utilise results from the spectral theory of semigroups to establish conditions for the existence of a positive equilibrium solution of our model. Then, we formulate conditions that guarantee that the linearised system is governed by a positive quasicontraction semigroup on the biologically relevant state space. We also show that the governing linear semigroup is eventually compact, hence growth properties of the semigroup are determined by the spectrum of its generator. In the case of a separable fertility function, we deduce a characteristic equation, and investigate the stability of equilibrium solutions in the general case using positive perturbation arguments., Comment: to appear in Mathematical Modelling of Natural Phenomena

Microtubules are a major component of the cytoskeleton distinguished by highly dynamic behavior both in vitro and in vivo. We propose a general mathematical model that accounts for the growth, catastrophe, rescue and nucleation processes in the polymerization of microtubules from tubulin dimers. Our model is an extension of various mathematical models developed earlier formulated in order to capture and unify the various aspects of tubulin polymerization including the dynamic instability, growth of microtubules to saturation, time-localized periods of nucleation and depolymerization as well as synchronized oscillations exhibited by microtubules under various experimental conditions. Our model, while attempting to use a minimal number of adjustable parameters, covers a broad range of behaviors and has predictive features discussed in the paper. We have analyzed the resultant behaviors of the microtubules changing each of the parameter values at a time and observing the emergence of various dynamical regimes., Comment: 25 pages, 12 figures

In this paper we develop two mathematical models to predict the release kinetics of a water soluble drug from a polymer/excipient matrix tablet. The first of our models consists of a random walk on a weighted graph, where the vertices of the graph represent particles of drug, excipient and polymer, respectively. The graph itself is the contact graph of a multidisperse random sphere packing. The second model describes the dissolution and the subsequent diffusion of the active drug out of a porous matrix using a system of partial differential equations. The predictions of both models show good qualitative agreement with experimental release curves. The models will provide tools for designing better controlled release devices., Comment: 17 pages, 7 figures; Elaborated at the first Workshop on the Application of Mathematics to Problems in Biomedicine, December 17-19, 2007 at the University of Otago in Dunedin, New Zealand

In this paper we consider chemotherapy in a spatial model of tumor growth. The model, which is of reaction-diffusion type, takes into account the complex interactions between the tumor and surrounding stromal cells by including densities of endothelial cells and the extra-cellular matrix. When no treatment is applied the model reproduces the typical dynamics of early tumor growth. The initially avascular tumor reaches a diffusion limited size of the order of millimeters and initiates angiogenesis through the release of vascular endothelial growth factor (VEGF) secreted by hypoxic cells in the core of the tumor. This stimulates endothelial cells to migrate towards the tumor and establishes a nutrient supply sufficient for sustained invasion. To this model we apply cytostatic treatment in the form of a VEGF-inhibitor, which reduces the proliferation and chemotaxis of endothelial cells. This treatment has the capability to reduce tumor mass, but more importantly, we were able to determine that inhibition of endothelial cell proliferation is the more important of the two cellular functions targeted by the drug. Further, we considered the application of a cytotoxic drug that targets proliferating tumor cells. The drug was treated as a diffusible substance entering the tissue from the blood vessels. Our results show that depending on the characteristics of the drug it can either reduce the tumor mass significantly or in fact accelerate the growth rate of the tumor. This result seems to be due to complicated interplay between the stromal and tumor cell types and highlights the importance of considering chemotherapy in a spatial context., Comment: revised version, 25 pages, 9 figures, minor misprints corrected

Mesenchymal motion describes the movement of cells in biological tissues formed by fiber networks. An important example is the migration of tumor cells through collagen networks during the process of metastasis formation. We investigate the mesenchymal motion model proposed by T. Hillen (J. Math. Biol. 53:585-616, 2006) in higher dimensions. We formulate the problem as an evolution equation in a Banach space of measure-valued functions and use methods from semigroup theory to show the global existence of classical solutions. We investigate steady states of the model and show that patterns of network type exist as steady states. For the case of constant fiber distribution, we find an explicit solution and we prove the convergence to the parabolic limit., Comment: 26 pages, 4 figures, revised and expanded version; to appear in Discr. Contin. Dyn. Sys. Ser. B

Transforming growth factor (TGF) $\beta$ is known to have properties of both a tumor suppressor and a tumor promoter. While it inhibits cell proliferation, it also increases cell motility and decreases cell--cell adhesion. Coupling mathematical modeling and experiments, we investigate the growth and motility of oncogene--expressing human mammary epithelial cells under exposure to TGF--$\beta$. We use a version of the well--known Fisher--Kolmogorov equation, and prescribe a procedure for its parametrization. We quantify the simultaneous effects of TGF--$\beta$ to increase the tendency of individual cells and cell clusters to move randomly and to decrease overall population growth. We demonstrate that in experiments with TGF--$\beta$ treated cells \textit{in vitro}, TGF--$\beta$ increases cell motility by a factor of 2 and decreases cell proliferation by a factor of 1/2 in comparison with untreated cells., Comment: 15 pages, 4 figures; to appear in Computational and Mathematical Methods in Medicine