Chuan Xue

A mathematical model of ischemic cutaneous wounds

Chronic wounds represent a major public health problem affecting 6.5 million people in the United States. Ischemia, primarily caused by peripheral artery diseases, represents a major complicating factor in cutaneous wound healing. In this work, we sought to develop a mathematical model of ischemic dermal wounds. The model consists of a coupled system of partial differential equations in the partially healed region, with the wound boundary as a free boundary. The extracellular matrix (ECM) is assumed to be viscoelastic, and the free boundary moves with the velocity of the ECM at the boundary. The model equations involve the concentration of oxygen, PDGF and VEGF, the densities of macrophages, fibroblasts, capillary tips and sprouts, and the density and velocity of the ECM. Simulations of the model demonstrate how ischemic conditions may limit macrophage recruitment to the wound-site and impair wound closure. The results are in general agreement with experimental findings.

Global small-data solutions of a two-dimensional chemotaxis system with rotational flux terms

We study non-negative solutions to the chemotaxis system under no-flux boundary conditions in a bounded planar convex domain with smooth boundary, where f and S are given parameter functions on Ω × [0, ∞)2 with values in [0, ∞) and ℝ2×2, respectively, which are assumed to satisfy certain regularity assumptions and growth restrictions. Systems of type (⋆), in the special case reducing to a version of the standard Keller–Segel system with signal consumption, have recently been proposed as a model for swimming bacteria near a surface, with the sensitivity tensor then given by , reflecting rotational chemotactic motion. It is shown that for any choice of suitably regular initial data (u0, v0) fulfilling a smallness condition on the norm of v0 in L∞(Ω), the corresponding initial-boundary value problem associated with (⋆) possesses a globally defined classical solution which is bounded. This result is achieved through the derivation of a series of a priori estimates involving an interpolation inequality of Gagliardo–Nirenberg type which appears to be new in this context. It is next proved that all corresponding solutions approach a spatially homogeneous steady state of the form (u, v) ≡ (μ, κ) in the large time limit, with μ := fΩu0 and some κ ≥ 0. A mild additional assumption on the positivity of f is shown to guarantee that κ = 0. Finally, numerical solutions are presented which suggest the occurrence of wave-like solution behavior.

A mathematical model for pancreatic cancer growth and treatments

Pancreatic cancer is one of the most deadly types of cancer and has extremely poor prognosis. This malignancy typically induces only limited cellular immune responses, the magnitude of which can increase with the number of encountered cancer cells. On the other hand, pancreatic cancer is highly effective at evading immune responses by inducing polarization of pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages, and promoting expansion of myeloid derived suppressor cells, which block the killing of cancer cells by cytotoxic T cells. These factors allow immune evasion to predominate, promoting metastasis and poor responsiveness to chemotherapies and immunotherapies. In this paper we develop a mathematical model of pancreatic cancer, and use it to qualitatively explain a variety of biomedical and clinical data. The model shows that drugs aimed at suppressing cancer growth are effective only if the immune induced cancer cell death lies within a specific range, that is, the immune system has a specific window of opportunity to effectively suppress cancer under treatment. The model results suggest that tumor growth rate is affected by complex feedback loops between the tumor cells, endothelial cells and the immune response. The relative strength of the different loops determines the cancer growth rate and its response to immunotherapy. The model could serve as a starting point to identify optimal nodes for intervention against pancreatic cancer.

Travelling waves in hyperbolic chemotaxis equations

Mathematical models of bacterial populations are often written as systems of partial differential equations for the densities of bacteria and concentrations of extracellular (signal) chemicals. This approach has been employed since the seminal work of Keller and Segel in the 1970s (Keller and Segel, J. Theor. Biol. 30:235–248, 1971). The system has been shown to permit travelling wave solutions which correspond to travelling band formation in bacterial colonies, yet only under specific criteria, such as a singularity in the chemotactic sensitivity function as the signal approaches zero. Such a singularity generates infinite macroscopic velocities which are biologically unrealistic. In this paper, we formulate a model that takes into consideration relevant details of the intracellular processes while avoiding the singularity in the chemotactic sensitivity. We prove the global existence of solutions and then show the existence of travelling wave solutions both numerically and analytically.

Travelling waves in hybrid chemotaxis models.

Hybrid models of chemotaxis combine agent-based models of cells with partial differential equation models of extracellular chemical signals. In this paper, travelling wave properties of hybrid models of bacterial chemotaxis are investigated. Bacteria are modelled using an agent-based (individual-based) approach with internal dynamics describing signal transduction. In addition to the chemotactic behaviour of the bacteria, the individual-based model also includes cell proliferation and death. Cells consume the extracellular nutrient field (chemoattractant), which is modelled using a partial differential equation. Mesoscopic and macroscopic equations representing the behaviour of the hybrid model are derived and the existence of travelling wave solutions for these models is established. It is shown that cell proliferation is necessary for the existence of non-transient (stationary) travelling waves in hybrid models. Additionally, a numerical comparison between the wave speeds of the continuum models and the hybrid models shows good agreement in the case of weak chemotaxis and qualitative agreement for the strong chemotaxis case. In the case of slow cell adaptation, we detect oscillating behaviour of the wave, which cannot be explained by mean-field approximations.

ANALYSIS OF A MATHEMATICAL MODEL OF ISCHEMIC CUTANEOUS WOUNDS

Chronic wounds represent a major public health problem affecting 6.5 million people in the United States. Ischemia represents a serious complicating factor in wound healing. In this paper we analyze a recently developed mathematical model of ischemic dermal wounds. The model consists of a coupled system of PDEs in the partially healed region, with the wound boundary as a free boundary. The extracellular matrix (ECM) is assumed to be viscoelastic, and the free boundary moves with the velocity of the ECM at the boundary of the open wound. The model equations involve the concentrations of oxygen, cytokines, and the densities of several types of cells. The ischemic level is represented by a parameter which appears in the boundary conditions,

A MATHEMATICAL MODEL FOR CHRONIC WOUNDS

0\leq\gamma<1

The Mathematical Analysis of Biological Aggregation and Dispersal: Progress, Problems and Perspectives

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Excitation and Adaptation in Bacteria-a Model Signal Transduction System that Controls Taxis and Spatial Pattern Formation

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From Individual to Collective Behavior of Unicellular Organisms: Recent Results and Open Problems

near 1 corresponds to extreme ischemia and