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At least 325 records · Page 18Linked to original sources

arXiv2015

In silico tumor control induced via alternating immunostimulating and immunosuppressive phases

Despite recent advances in the field of Oncoimmunology, the success potential of immunomodulatory therapies against cancer remains to be elucidated. One of the reasons is the lack of understanding on the complex interplay between tumor growth dynamics and the associated immune system responses. Towards this goal, we consider a mathematical model of vascularized tumor growth and the corresponding effector cell recruitment dynamics. Bifurcation analysis allows for the exploration of model's dynamic behavior and the determination of these parameter regimes that result in immune-mediated tumor control. Here, we focus on a particular tumor evasion regime that involves tumor and effector cell concentration oscillations of slowly increasing and decreasing amplitude, respectively. Considering a temporal multiscale analysis, we derive an analytically tractable mapping of model solutions onto a weakly negatively damped harmonic oscillator. Based on our analysis, we propose a theory-driven intervention strategy involving immunostimulating and immunosuppressive phases to induce long-term tumor control.

q-bio.TO↗

arXiv2016

A Cahn--Hilliard--Darcy model for tumour growth with chemotaxis and active transport

Using basic thermodynamic principles we derive a Cahn--Hilliard--Darcy model for tumour growth including nutrient diffusion, chemotaxis, active transport, adhesion, apoptosis and proliferation. The model generalises earlier models and in particular includes active transport mechanisms which ensure thermodynamic consistency. We perform a formally matched asymptotic expansion and develop several sharp interface models. Some of them are classical and some are new which for example include a jump in the nutrient density at the interface. A linear stability analysis for a growing nucleus is performed and in particular the role of the new active transport term is analysed. Numerical computations are performed to study the influence of the active transport term for specific growth scenarios.

math.AP↗

arXiv2016

A two-runners model: optimization of running strategies according to the physiological parameters

In order to describe the velocity and the anaerobic energy of two runners competing against each other for middle-distance races, we present a mathematical model relying on an optimal control problem for a system of ordinary differential equations. The model is based on energy conservation and on Newton's second law: resistive forces, propulsive forces and variations in the maximal oxygen uptake are taken into account. The interaction between the runners provides a minimum for staying one meter behind one's competitor. We perform numerical simulations and show how a runner can win a race against someone stronger by taking advantage of staying behind, or how he can improve his personal record by running behind someone else. Our simulations show when it is the best time to overtake, depending on the difference between the athletes. Finally, we compare our numerical results with real data from the men's 1500 -- m finals of different competitions.

math.OC↗

arXiv2017

Active Tension Network model reveals an exotic mechanical state realized in epithelial tissues

It is now widely recognized that mechanical interactions between cells play a crucial role in epithelial morphogenesis, yet understanding the mechanisms through which stress and deformation affect cell behavior remains an open problem due to the complexity inherent in the mechanical behavior of cells and the difficulty of direct measurement of forces within tissues. Theoretical models can help by focusing experimental studies and by providing the framework for interpreting measurements. To that end, "vertex models" have introduced an approximation of epithelial cell mechanics based on a polygonal tiling representation of planar tissue. Here we formulate and analyze an Active Tension Network (ATN) model, which is based on the same polygonal representation of epithelial tissue geometry, but in addition i) assumes that mechanical balance is dominated by cortical tension and ii) introduces tension dependent local remodeling of the cortex, representing the active nature of cytoskeletal mechanics. The tension-dominance assumption has immediate implications for the geometry of cells, which we demonstrate to hold in certain types of Drosophila epithelial tissues. We demonstrate that stationary configurations of an ATN form a manifold with one degree of freedom per cell, corresponding to "isogonal" - i.e. angle preserving - deformations of cells, which dominate the dynamic response to perturbations. We show that isogonal modes account for approximately 90% of experimentally observed deformation of cells during the process of ventral furrow formation in Drosophila. Other interesting properties of our model include the exponential screening of mechanical stress and a negative Poisson ratio response to external uniaxial stress. We also provide a new approach to the problem of inferring local cortical tensions from the observed geometry of epithelial cells in a tissue

q-bio.TO↗

arXiv2015

Use of biogenic nanomaterials to improve the peritoneal dialysis technique: A Translational Research Perspective

Intraperitoneal and catheter exit site infections are the most common complications associated with prolonged peritoneal dialysis (PD) therapy used for treating the patients with end stage renal failure (ESRF). Recurrent and persistent infections often cause inflammation of the peritoneum, a condition known as infectious peritonitis and to resolve the condition, patients require antibiotic treatment. However, if the treatment is delayed or if it fails due to antibiotic resistance, the peritonitis may lead to permanent malfunctioning of peritoneal membrane causing technique failure and transferring the patients to haemodialysis. Severe and prolonged peritonitis is not only the major cause of technique failure, it is also the leading cause of mortality and morbidity in PD patients. Therefore, there is an urgent need to improve the existing PD technique so that the frequency of PD associated infections could be reduced and infectious peritonitis episodes thereof during prolonged peritoneal dialysis. In this perspective, I highlight the possibility to improve the PD technique through the use of antimicrobial nanoparticles synthesized biologically.

physics.bio-ph↗

arXiv2015

Optical control of waves in a cardiac excitable medium

In nature, excitable reaction-diffusion systems found in diverse settings (e.g. chemical reactions, metal rust, yeast, amoeba, heart, brain) generate geometrically similar macroscopic waves(1,2). For the heart and brain, the spatiotemporal patterns formed by these excitation waves separate healthy from diseased states(1-3). Current electrical and pharmacological therapies for bioelectric disorders often lack the necessary spatiotemporal precision needed to control these patterns. Optical methodologies have the potential to overcome these limitations, but have only been demonstrated in simple systems, e.g. the Belousov-Zhabotinsky (BZ) chemical reaction4. Here we combine novel dye-free optical imaging with optogenetic actuation for dynamic control of cardiac excitation waves. We leverage patterned light to optically control emergent macroscopic properties of cardiac tissue: wave direction, wave speed, and spiral wave chirality. This all-optical approach offers a fundamentally new experimental platform for the study and control of pattern formation in complex biological excitable systems.

q-bio.TO↗

arXiv2015

Biomechanical conditions of walking

The development of rehabilitation training program for lower limb injury does not usually include gait pattern design. This paper introduced a gait pattern design by using equations (conditions of walking). Following the requirements of reducing force to the injured side to avoid further injury, we developed a lower limb gait pattern to shorten the stride length so as to reduce walking speed, to delay the stance phase of the uninjured side and to reduce step length of the uninjured side. This gait pattern was then verified by the practice of a rehabilitation training of an Achilles tendon rupture patient, whose two-year rehabilitation training (with 24 tests) has proven that this pattern worked as intended. This indicates that rehabilitation training program for lower limb injury can rest on biomechanical conditions of walking based on experimental evidence.

physics.med-ph↗

arXiv2015

Testing randomness for cancer risk

There are numerous stochastic models for cancer risk for a given tissue. Many rely on the following two hypotheses. 1. There is a fixed probability that a given cell division will eventually lead to a cancerous cell. 2. Cell divisions are nefarious or not independently of each other. We show that recent data on cancer risk and number of stem divisions is consistent with hypotheses 1 and 2.

q-bio.TO↗

arXiv2015

ERK/p38 MAPK inhibition reduces radio-resistance to pulsed proton beam in breast cancer stem cells cells

Recent studies have identified highly tumorigenic cells with stem cell-like characteristics in human cancers, termed cancer stem cells (CSCs). CSCs are resistant to conventional radiotherapy and chemotherapy owing to their high DNA repair ability and oncogene overexpression. However, the mechanisms regulating CSC radio-resistance, particularly proton beam resistance, remain unclear. We isolated CSCs from the breast cancer cell lines MCF-7 and MDA-MB-231, which expressed the characteristic breast CSC membrane protein markers CD44+/CD24-/low, and irradiated the CSCs with pulsed proton beams. We confirmed that CSCs are resistant to pulsed proton beams and showed that treatment with p38 and ERK inhibitors reduced CSC radioresistance. Based on these results, BCSC radio-resistance can be reduced during proton beam therapy by co-treatment with ERK1/2 or p38 inhibitors, representing a novel approach for breast cancer therapy.

q-bio.TO↗

arXiv2015

Variance-reduced simulation of stochastic agent-based models for tumor growth

We investigate a hybrid PDE/Monte Carlo technique for the variance reduced simulation of an agent-based multiscale model for tumor growth. The variance reduction is achieved by combining a simulation of the stochastic agent-based model on the microscopic scale with a deterministic solution of a simplified (coarse) partial differential equation (PDE) on the macroscopic scale as a control variable. We show that this technique is able to significantly reduce the variance with only the (limited) additional computational cost associated with the deterministic solution of the coarse PDE. We illustrate the performance with numerical experiments in different regimes, both in the avascular and vascular stage of tumor growth.

q-bio.QM↗

arXiv2016

CYP3A Mediated Ketamine Metabolism is Severely Impaired in Liver S9 Fractions from Aging Sprague Dawley Rats

Ketamine is widely used in veterinary medicine and in medicine. Ketamine is metabolized to its active metabolite norketamine principally by liver CYP3A. Drug metabolism alterations during aging have severe consequences particularly in anesthesiology and very few studies on older animals were conducted for ketamine. The objective of the present study is to assess the influence of aging on CYP3A metabolism of ketamine. Liver S9 fractions from 3, 6, 12 and 18 month old male Sprague Dawley rats were prepared and Michaelis-Menten parameters were determined for primary metabolic pathways. The derived maximum enzyme velocity (i.e. Vmax) suggests a rapid saturation of the CYP3A enzyme active sites in liver S9 fractions of 18-month old rats. Observed Vmax for Liver S9 fractions from 3, 6 and 12 month old male Sprague Dawley rats were 2.39 (+-0.23), 2.61 (+-0.18), and 2.07 (+-0.07) respectively compared to 0.68 (+-0.02) for Liver S9 fractions from 18 month old male Sprague Dawley rats. Interestingly, we observed a 6 to 7 fold change in the derived Km when comparing Liver S9 fractions from 18 month old male Sprague Dawley rats with Liver S9 fractions from younger rats. Our results suggest that rat CYP3A enzyme undergoes conformational changes with age particularly in our geriatric group (e.g. 18 month rats) leading significant decrease in the rate of formation of norketamine. Moreover, our results strongly suggest a severe impairment of CYP3A ketamine mediated metabolism.

q-bio.SC↗

arXiv2015

Visualization techniques for the developing chicken heart

We present a geometric surface parameterization algorithm and several visualization techniques adapted to the problem of understanding the 4D peristaltic-like motion of the outflow tract (OFT) in an embryonic chick heart. We illustrated the techniques using data from hearts under normal conditions (four embryos), and hearts in which blood flow conditions are altered through OFT banding (four embryos). The overall goal is to create quantitative measures of the temporal heart-shape change both within a single subject and between multiple subjects. These measures will help elucidate how altering hemodynamic conditions changes the shape and motion of the OFT walls, which in turn influence the stresses and strains on the developing heart, causing it to develop differently. We take advantage of the tubular shape and periodic motion of the OFT to produce successively lower dimensional visualizations of the cardiac motion (e.g. curvature, volume, and cross-section) over time, and quantifications of such visualizations.

cs.GR↗

arXiv2015

Assessing Measures of Atrial Fibrillation Clustering via Stochastic Models of Episode Recurrence and Disease Progression

Atrial fibrillation (AF) is a leading cause of morbidity and mortality. AF prevalence increases with age, which is attributed to pathophysiological changes that aid AF initiation and perpetuation. Current state-of-the-art models are only capable of simulating short periods of atrial activity at high spatial resolution, whilst the majority of clinical recordings are based on infrequent temporal datasets of limited spatial resolution. Being able to estimate disease progression informed by both modelling and clinical data would be of significant interest. In addition an analysis of the temporal distribution of recorded fibrillation episodes AF density can provide insights into recurrence patterns. We present an initial analysis of the AF density measure using a simplified idealised stochastic model of a binary time series representing AF episodes. The future aim of this work is to develop robust clinical measures of progression which will be tested on models that generate long-term synthetic data. These measures would then be of clinical interest in deciding treatment strategies.

q-bio.TO↗

arXiv2015

Mathematical Modelling of Heart Rate Changes in the Mouse

The CVS is composed of numerous interacting and dynamically regulated physiological subsystems which each generate measurable periodic components such that the CVS can itself be presented as a system of weakly coupled oscillators. The interactions between these oscillators generate a chaotic blood pressure waveform signal, where periods of apparent rhythmicity are punctuated by asynchronous behaviour. It is this variability which seems to characterise the normal state. We used a standard experimental data set for the purposes of analysis and modelling. Arterial blood pressure waveform data was collected from conscious mice instrumented with radiotelemetry devices over $24$ hours, at a $100$ Hz and $1$ kHz time base. During a $24$ hour period, these mice display diurnal variation leading to changes in the cardiovascular waveform. We undertook preliminary analysis of our data using Fourier transforms and subsequently applied a series of both linear and nonlinear mathematical approaches in parallel. We provide a minimalistic linear and nonlinear coupled oscillator model and employed spectral and Hilbert analysis as well as a phase plane analysis. This provides a route to a three way synergistic investigation of the original blood pressure data by a combination of physiological experiments, data analysis viz. Fourier and Hilbert transforms and attractor reconstructions, and numerical solutions of linear and nonlinear coupled oscillator models. We believe that a minimal model of coupled oscillator models that quantitatively describes the complex physiological data could be developed via such a method. Further investigations of each of these techniques will be explored in separate publications.

q-bio.TO↗

arXiv2015

Tumor-induced neoneurogenesis and perineural tumor growth: a mathematical approach

Primary tumors infrequently lead to demise of cancer patients; instead, mortality and a significant degree of morbidity result from the growth of secondary tumors in distant organs (metastasis). It is well-known that malignant tumors induce the formation of a lymphatic and a blood vascular network around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as \emph{neoneurogenesis}; in fact, recent studies have demonstrated that tumors initiate their own innervation. However, the relationship between tumor progression and the nervous system is still poorly understood. This process is most likely regulated by a multitude of factors in the tumor-nerve microenvironment and it is therefore important to study the interactions between the nervous system and tumor cells through mathematical/computational modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a (simple) system of differential equations. The model confirms the experimental observations that a tumor is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor (NGF) and axon guidance molecules (AGMs) are recorded in the presence of a tumor. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumor development and spread, indicating a mutually beneficial relationship between tumor cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumor growth and dissemination.

q-bio.TO↗

arXiv2015

Modelling afferent nerve responses to bladder filling

A sensation of fullness in the bladder is a regular experience, yet the mechanisms that act to generate this sensation remain poorly understood. This is an important issue because of the clinical problems that can result when this system does not function properly. The aim of the study group activity was to develop mathematical models that describe the mechanics of bladder filling, and how stretch modulates the firing rate of afferent nerves. Several models were developed, which were qualitatively consistent with experimental data obtained from a mouse model.

q-bio.TO↗

arXiv2018

The high osmotic pressure in a lens fiber as a driving force for the development of senile cortical cataract

In lens cataract, the clouding change in lens leads to a decline of transparency of part of the lens. There are three types of senile cataract: cortical cataract, nuclear cataract, and posterior/anterior sub-capsular cataract. The most common senile cataract is cortical cataract. For understanding cortical cataract, the pathology and the causing factors in cortical cataract are analyzed. The clouding change in senile cortical cataract begins from the edge of the lens and develops progressively to lens centre. The pathology of clouding change in cortical cataract is characterized by disruption of some lens fibers, swelling of some other fibers, and deposition of water between fibers. Based on the property of a lens fiber, we propose here a hypothesis on the mechanism of development of senile cortical cataract. I. Cortical cataract is triggered by disruption of a cortical lens fiber as a result of injury. The disrupted fiber will release water and crystallin proteins. II. Neighbor fibers can absorb this water due to high intracellular osmotic pressure (IOP) and become swollen. Swelling makes a fiber be stiff and have increased risk to disrupt when it is curved during the accommodation of the lens. These fibers will release water again when they disrupt, and the water will make more local fibers swelling. In this way, the local fibers become swollen and then disrupt successively. III. The successive swellings and disruptions of local fibers result in enlargement of a clouding change in lens. Since the fibers on the outer part of lens cortex have higher risk to be injured than that in the inner part, a clouding change starts from the edge of the lens. In conclusion, the progressive development of senile cortical cataract is a result of successive swellings and disruptions of local lens fibers, and this is driven by the high IOP in a lens fiber.

q-bio.TO↗

arXiv2015

Canine Olfactory Differentiation of Cancer: A Review of the Literature

Numerous studies have attempted to demonstrate the olfactory ability of canines to detect several common cancer types from human bodily fluids, breath and tissue. Canines have been reported to detect bladder cancer (sensitivity of 0.63-0.73 and specificity of 0.64-0.92) and prostate cancer (sensitivity of 0.91-0.99 and specificity of 0.91-0.97) from urine; breast cancer (sensitivity of 0.88 and specificity of 0.98) and lung cancer (sensitivity 0.56-0.99 and specificity of 8.30-0.99) on breath and colorectal cancer from stools (sensitivity of 0.91-0.97 and specificity of 0.97-0.99). The quoted figures of sensitivity and specificity across differing studies demonstrate that in many cases results are variable from study to study; this raises questions about the reproducibility of methodology and study design which we have identified herein. Furthermore in some studies the controls used have resulted in differentiation of samples which are of limited use for clinical diagnosis. These studies provide some evidence that cancer gives rise to different volatile organic compounds (VOCs) compared to healthy samples. Whilst canine detection may be unsuitable for clinical implementation they can, at least, provide inspiration for more traditional laboratory investigations.

q-bio.TO↗