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Mathematical Medicine and Biology: a Journal of the IMA

Bronwyn H Bradshaw-Hajek, Philip Broadbridge
The evolution of calcium fertilisation waves on the cortex of amphibian eggs can be described by a nonlinear reaction-diffusion process on the surface of a sphere. Here, we use the nonclassical symmetry technique to find an exact analytic solution that describes the evolution of the calcium concentration. The solutions presented compare well with published experimental results. The analytic solution can be used to give insight into the processes governing the fertilisation wave, such as the flow of calcium ions from the sperm entry point...
February 15, 2019: Mathematical Medicine and Biology: a Journal of the IMA
Travis B Thompson, Beatrice M Riviere, Matthew G Knepley
Edema, also termed oedema, is a generalized medical condition associated with an abnormal aggregation of fluid in a tissue matrix. In the intestine, excessive edema can lead to serious health complications associated with reduced motility. A $7.5\%$ solution of hypertonic saline (HS) has been hypothesized as an effective means to reduce the effects of edema following surgery or injury. However, detailed clinical edema experiments can be difficult to implement, or costly, in practice. In this manuscript we introduce an implicit in time discontinuous Galerkin method with novel adaptations for modeling edema in the 3D layered physiology of the intestine...
February 5, 2019: Mathematical Medicine and Biology: a Journal of the IMA
Zenab Alrikaby
We propose a simple model of lac operon that describes the expression of B-galactosidase from lac Z gene in Escherichia coli, through the interaction among several identical mRNA. Our goal is to explore the complex dynamics (i.e. the oscillation phenomenon) of this architecture mediated by this interaction. This model was theoretically and numerically investigated using distributed time delay. We considered the average delay as a bifurcation parameter and the nonlinear degradation rate as a control parameter...
December 28, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Thuy T T Le, Felix Jost, Thomas Raupach, Jakob Zierk, Manfred Rauh, Meinolf Suttorp, Martin Stanulla, Markus Metzler, Sebastian Sager
Acute lymphoblastic leukemia is the most common malignancy in childhood and requires prolonged oral maintenance chemotherapy to prevent disease relapse after remission induction with intensive intravenous chemotherapy. In maintenance therapy, drug doses of 6-mercaptopurine (6-MP) and methotrexate (MTX) are adjusted to achieve sustained antileukemic activity without excessive myelosuppression. However, uncertainty exists regarding timing and extent of drug dose responses and optimal dose adaptation strategies...
October 24, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Lucia Carichino, Sarah D Olson
Changes in calcium concentration along the sperm flagellum regulate sperm motility and hyperactivation, characterized by an increased flagellar bend amplitude and beat asymmetry, enabling the sperm to reach and penetrate the ovum (egg). The signalling pathways by which calcium increases within the flagellum are well established. However, the exact mechanisms of how calcium regulates flagellar bending are still under investigation. We extend our previous model of planar flagellar bending by developing a fluid-structure interaction model that couples the 3D motion of the flagellum in a viscous Newtonian fluid with the evolving calcium concentration...
October 16, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Miller Cerón Gómez, Hyun Mo Yang
We develop a mathematical model to describe the role of antibody-dependent enhancement (ADE) in heterologous secondary infections, assuming that antibodies specific to primary dengue virus (DENV) infection are being produced by immunological memory. The model has a virus-free equilibrium (VFE) and a unique virus-presence equilibrium (VPE). VFE is asymptotically stable when VPE is unstable; and unstable, otherwise. Additionally, there is an asymptotic attractor (not a fixed point) due to the fact that the model assumes unbounded increase in memory cells...
October 9, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Angela M Jarrett, Meghan J Bloom, Wesley Godfrey, Anum K Syed, David A Ekrut, Lauren I Ehrlich, Thomas E Yankeelov, Anna G Sorace
The goal of this study is to develop an integrated, mathematical-experimental approach for understanding the interactions between the immune system and the effects of trastuzumab on breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2+). A system of coupled, ordinary differential equations was constructed to describe the temporal changes in tumour growth, along with intratumoural changes in the immune response, vascularity, necrosis and hypoxia. The mathematical model is calibrated with serially acquired experimental data of tumour volume, vascularity, necrosis and hypoxia obtained from either imaging or histology from a murine model of HER2+ breast cancer...
September 19, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Shi Chen, Suzanne Lenhart, Judy D Day, Chihoon Lee, Michael Dulin, Cristina Lanzas
Queueing theory studies the properties of waiting queues and has been applied to investigate direct host-to-host transmitted disease dynamics, but its potential in modelling environmentally transmitted pathogens has not been fully explored. In this study, we provide a flexible and customizable queueing theory modelling framework with three major subroutines to study the in-hospital contact processes between environments and hosts and potential nosocomial pathogen transfer, where environments are servers and hosts are customers...
September 11, 2018: Mathematical Medicine and Biology: a Journal of the IMA
V S K Manem, A Dhawan
In the past few years, proton therapy has taken the centre stage in treating various tumour types. The primary contribution of this study is to investigate the tumour control probability (TCP), relapse time and the corresponding secondary cancer risks induced by proton beam radiation therapy. We incorporate tumour relapse kinetics into the TCP framework and calculate the associated second cancer risks. To calculate proton therapy-induced secondary cancer induction, we used the well-known biologically motivated mathematical model, initiation-inactivation-proliferation formalism...
September 11, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Atanaska Dobreva, Ralf Paus, N G Cogan
Alopecia areata (AA) is a CD8$^{+}$ T cell-dependent autoimmune disease that disrupts the constantly repeating cyclic transformations of hair follicles (HFs). Among the three main HF cycle stages-growth (anagen), regression (catagen) and relative quiescence (telogen)-only anagen HFs are attacked and thereby forced to prematurely enter into catagen, thus shortening active hair growth substantially. After having previously modelled the dynamics of immune system components critically involved in the disease development (Dobreva et al...
September 11, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Jennifer H Tweedy, Jan O Pralits, Rodolfo Repetto, Paolo Soleri
Flow in the aqueous humour that fills the anterior chamber of the eye occurs in response to the production and drainage of the aqueous humour, and also due to buoyancy effects produced by thermal gradients. Phakic intraocular lenses are manufactured lenses that are surgically inserted in the eyes of patients to correct refractive errors. Their presence has a dramatic effect on the circulation of the aqueous humour, resulting a very different flow in the anterior chamber, the effects of which have not been extensively investigated...
September 11, 2018: Mathematical Medicine and Biology: a Journal of the IMA
J E F Green, J P Whiteley, J M Oliver, H M Byrne, S L Waters
We develop a continuum model for the aggregation of cells cultured in a nutrient-rich medium in a culture well. We consider a 2D geometry, representing a vertical slice through the culture well, and assume that the cell layer depth is small compared with the typical lengthscale of the culture well. We adopt a continuum mechanics approach, treating the cells and culture medium as a two-phase mixture. Specifically, the cells and culture medium are treated as fluids. Additionally, the cell phase can generate forces in response to environmental cues, which include the concentration of a chemoattractant that is produced by the cells within the culture medium...
September 11, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Benjamin Engelhardt, Janine Holze, Christina Elliott, George S Baillie, Maik Kschischo, Holger Fröhlich
The muscarinic M$_{2}$ receptor is a prominent member of the GPCR family and strongly involved in heart diseases. Recently published experimental work explored the cellular response to iperoxo-induced M$_{2}$ receptor stimulation in Chinese hamster ovary (CHO) cells. To better understand these responses, we modelled and analysed the muscarinic M$_{2}$ receptor-dependent signalling pathway combined with relevant secondary messenger molecules using mass action. In our literature-based joint signalling and secondary messenger model, all binding and phosphorylation events are explicitly taken into account in order to enable subsequent stoichiometric matrix analysis...
September 11, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Alfonso Sepúlveda-Gálvez, Jesús Agustín Badillo-Corona, Isaac Chairez
Mathematical modelling applied to biological systems allows for the inferring of changes in the dynamic behaviour of organisms associated with variations in the environment. Models based on ordinary differential equations are most commonly used because of their ability to describe the mechanisms of biological systems such as transcription. The disadvantage of using this approach is that there is a large number of parameters involved and that it is difficult to obtain them experimentally. This study presents an algorithm to obtain a finite-time parameter characterization of the model used to describe changes in the metabolic behaviour of Escherichia coli associated with environmental changes...
September 11, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Sevnaz Nourollahi, Archis Ghate, Minsun Kim
The goal in external beam radiotherapy (EBRT) for cancer is to maximize damage to the tumour while limiting toxic effects on the organs-at-risk. EBRT can be delivered via different modalities such as photons, protons and neutrons. The choice of an optimal modality depends on the anatomy of the irradiated area and the relative physical and biological properties of the modalities under consideration. There is no single universally dominant modality. We present the first-ever mathematical formulation of the optimal modality selection problem...
September 6, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Andrew L Krause, Dmitry Beliaev, Robert A Van Gorder, Sarah L Waters
A contemporary procedure to grow artificial tissue is to seed cells onto a porous biomaterial scaffold and culture it within a perfusion bioreactor to facilitate the transport of nutrients to growing cells. Typical models of cell growth for tissue engineering applications make use of spatially homogeneous or spatially continuous equations to model cell growth, flow of culture medium, nutrient transport and their interactions. The network structure of the physical porous scaffold is often incorporated through parameters in these models, either phenomenologically or through techniques like mathematical homogenization...
August 10, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Bruno Buonomo, Rossella Della Marca, Alberto d'Onofrio
Hesitancy and refusal of vaccines preventing childhood diseases are spreading due to 'pseudo-rational' behaviours: parents overweigh real and imaginary side effects of vaccines. Nonetheless, the 'Public Health System' (PHS) may enact public campaigns to favour vaccine uptake. To determine the optimal time profiles for such campaigns, we apply the optimal control theory to an extension of the susceptible-infectious-removed (SIR)-based behavioural vaccination model by d'Onofrio et al. (2012, PLoS ONE, 7, e45653)...
July 27, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Wenjing Zhang, Sophia Jang, Colleen B Jonsson, Linda J S Allen
Inflammatory responses to an infection from a zoonotic pathogen, such as avian influenza viruses, hantaviruses and some coronaviruses, are distinctly different in their natural reservoir versus human host. While not as well studied in the natural reservoirs, the pro-inflammatory response and viral replication appear controlled and show no obvious pathology. In contrast, infection in humans results in an initial high viral load marked by an aggressive pro-inflammatory response known as a cytokine storm. The key difference in the course of the infection between the reservoir and human host is the inflammatory response...
June 29, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Artur C Fassoni, Hyun M Yang
Tumorigenesis has been described as a multistep process, where each step is associated with a genetic alteration, in the direction to progressively transform a normal cell and its descendants into a malignant tumour. Into this work, we propose a mathematical model for cancer onset and development, considering three populations: normal, premalignant and cancer cells. The model takes into account three hallmarks of cancer: self-sufficiency on growth signals, insensibility to anti-growth signals and evading apoptosis...
June 27, 2018: Mathematical Medicine and Biology: a Journal of the IMA
Miquel Gomez, Francisco Maduell
Kinetic modelling in haemodialysis is usually based upon the resolution of volume-defined compartment models. The interaction among these compartments is described by purely diffusive processes. In this paper we present an alternative kinetic model for uremic toxins in post-dilutional haemodiafiltration treatments by means of a unidimensional diffusion equation. A wide range of solutes such as urea, creatinine, $\beta _{2}$-microglobulin, myoglobin and prolactin were studied by imposing appropriate boundary and initial conditions in a virtual [0,1] domain...
June 15, 2018: Mathematical Medicine and Biology: a Journal of the IMA
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