The work is devoted to the analysis of cell population dynamics where cells make a choice between differentiation and apoptosis. This choice is based on the values of intracellular proteins whose concentrations are described by a system of ordinary differential equations with bistable dynamics. Intracellular regulation and cell fate are controlled by the extracellular regulation through the number

A predator-prey model is used to investigate the interactions between phages and bacteria by considering the lytic and lysogenic life cycles of phages and the prophage induction. We provide answers to the following conflictual research questions: (1) what are conditions under which the presence of phages can purify a bacterial infected environment? (2) Can the presence of phages triggers virulent bacterial

In this paper, we study a single serotype transmission model of dengue to determine the optimal vaccination age for Dengvaxia. The transmission dynamics are modelled with an age-dependent force of infection. The force of infection for each serotype is derived from the serological profile of dengue in Brazil without serotype distinction and from serotype-specific reported cases. The risk due to an infection

Nearly all life forms require iron to survive and function. Microorganisms utilize a number of mechanisms to acquire iron including the production of siderophores, which are organic compounds that combine with ferric iron into forms that are easily absorbed by the microorganism. There has been significant experimental investigation into the role, distribution and function of siderophores in fungi but

Inflammation is now known to play a significant role in tumour growth and progression. It is also difficult to adequately quantify systemic inflammation and the resulting localized effects in cancer. Here, we use experimental data to infer the possible contributions of inflammation in a mouse model of cancer. The model is validated by predicting tumour growth under anti-inflammatory treatments, and

An accurate characterization of soft biological tissue properties is essential for a realistic simulation of surgical procedures. Unconfined uniaxial compression tests with specimens affixed to the fixtures are often performed to characterize the stress-stretch curves of soft biological tissues, with which the material parameters can be obtained. However, the constrained boundary condition causes non-uniform

Acute lymphoblastic leukaemia (ALL) is associated with a compromised myeloid system. Understanding the state of granulopoiesis in a patient during treatment, places the clinician in an advantageous position. Mathematical models are aids able to present the clinician with insight into the behaviour of myeloid-derived leucocytes. The main objective of this investigation was to determine whether a proposed

Swelling pressure in the interstitial fluid within the pores of cartilage tissue is known to have a significant effect on the rheology of cartilage tissue. The swelling pressure varies rapidly within thin regions inside pores known as Debye layers, caused by the presence of fixed charge, as observed in cartilage. Tissue level calculation of cartilage deformation therefore requires resolution of three

We present a mathematical model to study the influence of a lipid reservoir, seen experimentally, at the lid margin on the formation and relaxation of the tear film during a partial blink. Applying the lubrication limit, we derive two coupled non-linear partial differential equations characterizing the evolution of the aqueous tear fluid and the covering insoluble lipid concentration. Departing from

In food webs, fishery can play the role of top predator, competing thus with other top predators for valuable food resources. In this view, it has been claimed in fisheries management that culling of top predators can be a means to improve fishery yield. To investigate this hypothesis, we use theoretical population models to assess in a multispecies context how fishery yield from target species harvest

Tissue level cardiac electrophysiology is usually modelled by the bidomain equations, or the monodomain simplification of the bidomain equations. One assumption made when deriving the bidomain equations is that both the intracellular and extracellular spaces are in electrical equilibrium. This assumption neglects the disturbance of this equilibrium in thin regions close to the cell membrane known as

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

We develop and analyse a mathematical model of tumour-immune interaction that explicitly incorporates heterogeneity in tumour cell cycle duration by using a distributed delay differential equation. We derive a necessary and sufficient condition for local stability of the cancer-free equilibrium in which the amount of tumour-immune interaction completely characterizes disease progression. Consistent

Ailments of the bladder are often treated via intravesical delivery-direct application of therapeutic into the bladder through a catheter. This technique is employed hundreds of thousands of times every year, but protocol development has largely been limited to empirical determination. Furthermore, the numerical analyses of intravesical delivery performed to date have been restricted to static geometries

Lineage switches are genetic regulatory motifs that govern and maintain the commitment of a developing cell to a particular cell fate. A canonical example of a lineage switch is the pair of transcription factors PU.1 and GATA-1, of which the former is affiliated with the myeloid and the latter with the erythroid lineage within the haematopoietic system. On a molecular level, PU.1 and GATA-1 positively

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

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

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

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

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

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

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

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 susce

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

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

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

We develop a mathematical model of information transmission across the biological neural network of the human brain. The overall function of the brain consists of the emergent processes resulting from the spread of information through the neural network. The capacity of the brain is therefore related to the rate at which it can transmit information through the neural network. The particular transmission

Understanding the impact of pathogen exposure on the within-host dynamics and its outcome in terms of infectiousness is a key issue to better understand and control the infection spread. Most experimental and modelling studies tackling this issue looked at the impact of the exposure dose on the infection probability and pathogen load, very few on the within-host immune response. Our aim was to explore

Staphylococcus aureus infections are a growing concern worldwide due to the increasing number of strains that exhibit antibiotic resistance. Recent studies have indicated that some percentage of people carry the bacteria in the nasal cavity and therefore are at a higher risk of subsequent, and more serious, infections in other parts of the body. However, individuals carrying the infection can be classified

Intra-tumour phenotypic heterogeneity limits accuracy of clinical diagnostics and hampers the efficiency of anti-cancer therapies. Dealing with this cellular heterogeneity requires adequate understanding of its sources, which is extremely difficult, as phenotypes of tumour cells integrate hardwired (epi)mutational differences with the dynamic responses to microenvironmental cues. The later comes in

Evaporation is a recognized contributor to tear film thinning and tear breakup (TBU). Recently, a different type of TBU is observed, where TBU happens under or around a thick area of lipid within a second after a blink. The thick lipid corresponds to a glob. Evaporation alone is too slow to offer a complete explanation of this breakup. It has been argued that the major reason of this rapid tear film

We address a non-linear programming problem to find the optimal scheme of dose fractionation in cancer radiotherapy. Using the LQ model to represent the response to radiation of tumour and normal tissues, we formulate a constrained non-linear optimization problem in terms of the variables number and sizes of the dose fractions. Quadratic constraints are imposed to guarantee that the damages to the

Cells adhere to each other and to the extracellular matrix (ECM) through protein molecules on the surface of the cells. The breaking and forming of adhesive bonds, a process critical in cancer invasion and metastasis, can be influenced by the mutation of cancer cells. In this paper, we develop a nonlocal mathematical model describing cancer cell invasion and movement as a result of integrin-controlled

DNA double strand breaks (DSBs) are the most lethal lesions of DNA induced by ionizing radiation, industrial chemicals and a wide variety of drugs used in chemotherapy. In the context of DNA damage response system modelling, uncertainty may arise in several ways such as number of induced DSBs, kinetic rates and measurement error in observable quantities. Therefore, using the stochastic approaches is

Recent in vivo experiments have illustrated the importance of understanding the haemodynamics of heart morphogenesis. In particular, ventricular trabeculation is governed by a delicate interaction between haemodynamic forces, myocardial activity, and morphogen gradients, all of which are coupled to genetic regulatory networks. The underlying haemodynamics at the stage of development in which the trabeculae

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

This article is about numerical control of HIV propagation. The contribution of the article is threefold: first, a novel model of HIV propagation is proposed; second, the methods from numerical optimal control are successfully applied to the developed model to compute optimal control profiles; finally, the computed results are applied to the real problem yielding important and practically relevant

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

The anterior chamber (AC) and posterior chamber (PC) of the eye are connected through the pupil and are filled with aqueous humour. The aqueous flows from the posterior to the AC at an approximately constant rate, and the intraocular pressure is governed by this rate and the resistance to aqueous outflow. In some patients the iris and lens come into contact, leading to pressure build-up in the PC,

We study the systems of partial differential equations with diffusion that model the dynamics of infectious diseases without life-time immunity, in particular the cases of cholera from Wang & Wang (2015, J. Biol. Dyn., 9, 233-261) and avian influenza from Vaidya et al. (2012, Discrete Contin. Dyn. Syst. Ser. B, 17, 2829-2848). In both works, similarly to all others in the literature on various models

Calcium has two important roles in haemodialysis. It participates in the activation of blood coagulation and calcium intakes have a major impact on patient mineral and bone metabolism. The aim of this article is to propose a mathematical model for calcium ions concentration in a dialyzer during haemodialysis using a citrate dialysate. The model is composed of two elements. The first describes the flows

We consider extensions to previous models for patient level nosocomial infection in several ways, provide a specification of the likelihoods for these new models, specify new update steps required for stochastic integration, and provide programs that implement these methods to obtain parameter estimates and model choice statistics. Previous susceptible-infected models are extended to allow for a latent

Fluorescein is perhaps the most commonly used substance to visualize tear film thickness and dynamics; better understanding of this process aids understanding of dry eye syndrome which afflicts millions of people. We study a mathematical model for tear film flow, evaporation, solutal transport and fluorescence over the exposed ocular surface during the interblink. Transport of the fluorescein ion by

Using a popular vertex-based model to describe a spatially disordered planar epithelial monolayer, we examine the relationship between cell shape and mechanical stress at the cell and tissue level. Deriving expressions for stress tensors starting from an energetic formulation of the model, we show that the principal axes of stress for an individual cell align with the principal axes of shape, and we

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.

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

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

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

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

The immune system has many adaptive and dynamic components that are regulated to ensure appropriate, precise and rapid response to a foreign pathogen. A delayed or inadequate immune response can lead to prolonged disease, while an excessive or under-regulated response can lead to autoimmunity. The cytokine, interleukin-2 (IL-2) and its receptor IL-2R play an important role in maintaining this balance

We report the results of some recent experiments to visualize tear film dynamics. We then study a mathematical model for tear film thinning and tear film breakup (TBU), a term from the ocular surface literature. The thinning is driven by an imposed tear film thinning rate which is input from in vivo measurements. Solutes representing osmolarity and fluorescein are included in the model. Osmolarity

As technological improvements continue to infiltrate and impact medical practice, it has become possible to non-invasively collect dense physiological time series data from individual patients in real time. These advances continue to improve physicians' ability to detect and to treat infections early. One important benefit of early detection and treatment of nascent infections is that it leads to earlier

Cross-reactive T cell responses induced by a primary dengue virus infection may contribute to increased disease severity following heterologous infections with a different virus serotype in a phenomenon known as the original antigenic sin. In this study, we developed and analyzed in-host models of T cell responses to primary and secondary dengue virus infections that considered the effect of T cell

The tumour control probability (TCP) is the probability that a treatment regimen of radiation therapy (RT) eradicates all tumour cells in a given tissue. To decrease the toxic effects on healthy cells, RT is usually delivered over a period of weeks in a series of fractions. This allows tumour cells to repair sublethal damage (RSD) caused by radiation. In this article, we introduce a stochastic model

We present a two-phase model of platelet aggregation in coronary-artery-sized blood vessels. The model tracks the number densities of three platelet populations as well as the concentration of a platelet activating chemical. Through the formation of elastic bonds, activated platelets can cohere with one another to form a platelet thrombus. Bound platelets in a thrombus move in a velocity field different

This article studies a vehicle routing problem with environmental constraints that are motivated by the requirements for sustainable urban transport. The empirical research presents a fleet planning problem that takes into consideration both minimum cost vehicle routes and minimum pollution. The problem is formulated as a mixed integer linear programming model and experimentally validated using data

We propose a discrete in continuous mathematical model describing the in vitro growth process of biophsy-derived mammalian cardiac progenitor cells growing as clusters in the form of spheres (Cardiospheres). The approach is hybrid: discrete at cellular scale and continuous at molecular level. In the present model, cells are subject to the self-organizing collective dynamics mechanism and, additionally

T lymphoblastic lymphoma (T-LBL) is a rare type of lymphoma with a good prognosis with a remission rate of 85%. Patients can be completely cured or can relapse during or after a 2-year treatment. Relapses usually occur early after the remission of the acute phase. The median time of relapse is equal to 1 year, after the occurrence of complete remission (range 0.2-5.9 years) (Uyttebroeck et al., 2008)

This article generalizes the existing minimal model of the hypothalamic-pituitary-adrenal (HPA) axis in a realistic way, by including memory terms: distributed time delays, on one hand and fractional-order derivatives, on the other hand. The existence of a unique equilibrium point of the mathematical models is proved and a local stability analysis is undertaken for the system with general distributed