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At least 127 records · Page 7Linked to original sources

arXiv2011

Noise-assisted tumor-immune cells interaction

We consider a three-state model comprising tumor cells, effector cells and tumor detecting cells under the influence of noises. It is demonstrated that inevitable stochastic forces existing in all three cell species are able to suppress tumor cell growth completely. Whereas the deterministic model does not reveal a stable tumor-free state, the auto-correlated noise combined with cross-correlation functions can either lead to tumor dormant states, tumor progression as well as to an elimination of tumor cells. The auto-correlation function exhibits a finite correlation time $τ$ while the cross-correlation functions shows a white noise behavior. The evolution of each of the three kinds of cells leads to a multiplicative noise coupling. The model is investigated by means of a multivariate Fokker-Planck equation for small $τ$. The different behavior of the system is above all determined by the variation of the correlation time and the strength of the cross-correlation between tumor and tumor detecting cells. The theoretical model is based on a biological background discussed in detail and the results are tested using realistic parameters from experimental observations.

q-bio.TO↗

arXiv2011

Multiscale approach for bone remodeling simulation based on finite element and neural network computation

The aim of this paper is to develop a multiscale hierarchical hybrid model based on finite element analysis and neural network computation to link mesoscopic scale (trabecular network level) and macroscopic (whole bone level) to simulate bone remodelling process. Because whole bone simulation considering the 3D trabecular level is time consuming, the finite element calculation is performed at macroscopic level and a trained neural network are employed as numerical devices for substituting the finite element code needed for the mesoscale prediction. The bone mechanical properties are updated at macroscopic scale depending on the morphological organization at the mesoscopic computed by the trained neural network. The digital image-based modeling technique using m-CT and voxel finite element mesh is used to capture 2 mm3 Representative Volume Elements at mesoscale level in a femur head. The input data for the artificial neural network are a set of bone material parameters, boundary conditions and the applied stress. The output data is the updated bone properties and some trabecular bone factors. The presented approach, to our knowledge, is the first model incorporating both FE analysis and neural network computation to simulate the multilevel bone adaptation in rapid way.

physics.med-ph↗

arXiv2011

Collective Cell Migration: Leadership, Invasion and Segregation

A number of biological processes, such as embryo development, cancer metastasis or wound healing, rely on cells moving in concert. The mechanisms leading to the emergence of coordinated motion remain however largely unexplored. Although biomolecular signalling is known to be involved in most occurrences of collective migration, the role of physical and mechanical interactions has only been recently investigated. In this paper, a versatile framework for cell motility is implemented in-silico in order to study the minimal requirements for the coordination of a group of epithelial cells. We find that cell motility and cell-cell mechanical interactions are sufficient to generate a broad array of behaviours commonly observed in vitro and in vivo. Cell streaming, sheet migration and susceptibility to leader cells are examples of behaviours spontaneously emerging from these simple assumptions, which might explain why collective effects are so ubiquitous in nature. This analysis provides also new insights into cancer metastasis and cell sorting, suggesting in particular that collective invasion might result from an emerging coordination in a system where single cells are mechanically unable to invade.

q-bio.CB↗

arXiv2011

On drug transport after intravenous administration

A mathematical model of a drug transport after rapid injection is given. It takes into account three processes: - drug plasma protein binding in central compartment - transport processes between the central compartment and the peripheral compartment - elimination of a drug from the central compartment. .

q-bio.TO↗

arXiv2011

Reaction-Diffusion-Delay Model for EPO/TNF-$α$? Interaction in Articular Cartilage Lesion Abatement

Injuries to articular cartilage result in the development of lesions that form on the surface of the cartilage. Such lesions are associated with articular cartilage degeneration and osteoarthritis. The typical injury response often causes collateral damage, primarily an effect of inflammation, which results in the spread of lesions beyond the region where the initial injury occurs. We present a minimal mathematical model based on known mechanisms to investigate the spread and abatement of such lesions. In particular we represent the "balancing act" between pro-inflammatory and anti-inflammatory cytokines that is hypothesized to be a principal mechanism in the expansion properties of cartilage damage during the typical injury response. We present preliminary results of in vitro studies that confirm the anti-inflammatory activities of the cytokine erythropoietin (EPO). We assume that the diffusion of cytokines determine the spatial behaviour of injury response and lesion expansion so that a reaction-diffusion system involving chemical species and chondrocyte cell state population densities is a natural way to represent cartilage injury response. We present computational results using the mathematical model showing that our representation is successful in capturing much of the interesting spatial behaviour of injury associated lesion development and abatement in articular cartilage. Further, we discuss the use of this model to study the possibility of using EPO as a therapy for reducing the amount of inflammation induced collateral damage to cartilage during the typical injury response. The mathematical model presented herein suggests that not only are anti-inflammatory cytokines, such as EPO necessary to prevent chondrocytes signaled by pro-inflammatory cytokines from entering apoptosis, they may also influence how chondrocytes respond to signaling by pro-inflammatory cytokines.

q-bio.TO↗

arXiv2011

On inconsistencies in passive pharmacokinetics

Some inconsistencies in the passive pharmacokinetics has been observed many years ago. It is possible these inconsistencies result from the lack of proper evolution equations. In this communication, this possibility is illustrated on the example of an evolution equation for an one compartment model.

q-bio.QM↗

arXiv2011

Questing for an optimal, universal viral agent for oncolytic virotherapy

One of the most promising strategies to treat cancer is attacking it with viruses designed to exploit specific altered pathways. Here, the effects of oncolytic virotherapy on tumors having compact, papillary and disconnected morphologies are investigated through computer simulations of a multiscale model coupling macroscopic reaction diffusion equations for the nutrients with microscopic stochastic rules for the actions of individual cells and viruses. The interaction among viruses and tumor cells involves cell infection, intracellular virus replication and release of new viruses in the tissue after cell lysis. The evolution in time of both viral load and cancer cell population, as well as the probabilities for tumor eradication were evaluated for a range of multiplicities of infection, viral entries and burst sizes. It was found that in immunosuppressed hosts, the antitumor efficacy of a virus is primarily determined by its entry efficiency, its replicative capacity within the tumor, and its ability to spread over the tissue. However, the optimal traits for oncolytic viruses depends critically on the tumor growth dynamics and do not necessarily include rapid replication, cytolysis and spreading currently assumed as necessary conditions to a successful therapeutic outcome. Our findings have potential implications on the design of new vectors for the viral therapy of cancer.

physics.bio-ph↗

arXiv2011

Psoriasis as a consequence of incorporation of beta-streptococci into the microbiocenosis of highly permeable intestines (a pathogenic concept)

A review of recent investigations into pathogenesis of psoriasis summarizing data on the relationship between the presence β-streptococci in the organism and the cutaneous immune reaction. Results of the studies on gastrointestinal pathology in psoriatic patients are presented. The authors propose a hypothesis that advocates the primary origin of psoriatic gastrointestinal pathology and secondary nature of skin manifestations. A chronic plaque psoriasis model is developed on the basis of the assumption on the key role of two psorafactors, i.e. hyperpermeability of intestinal walls for certain proteins and incorporation of beta-streptococci in the microbiocenosis of intestinal mucosa. The validity of the model is confirmed by the results of practical clinical work.

q-bio.TO↗

arXiv2011

Photon Trajectory in the Human Cornea

In this article, we follow the trajectory of a photon in the human cornea. Prior to experimental evidence of the cornea's gradient refractive index (GRIN) nature, schematic eye models used a constant or average as the corneal refractive index. A few recent models respect the intra-corneal GRIN, but are based on the paraxial approximation, and thereby have limited validity in peripheral visual field analysis and non-paraxial photon tracking. Here, we introduce the Trajectron algorithm. It uses a closed form solution of the ray equation of constant axial GRIN media, and evaluates over piece-wise constant GRIN. Using Trajectron, we present the first quantitative demonstration of non-paraxial intra-corneal light-bending phenomena. This demonstration has significant implications in the development of refractive surgery algorithms.

physics.optics↗

arXiv2012

Model of pathogenesis of psoriasis. Part 1. Systemic psoriatic process

Analytical study of results of experimental and theoretical works on pathogenesis of psoriatic disease was conducted. Psoriasis is dermal implication of systemic psoriatic process (SPP). New SPP model explaining results of clinical and laboratory experiments was formulated. According to Y-model there are two main factors: hyperpermeability of small intestine for bacterial products and colonization of its walls by Gram+ bacteria (incl. psoriagenic bacteria PsB) and Gram(-) TLR4-active bacteria. Inside SPP there is a vicious cycle which is supported by disturbance of production and-or circulation of bile acids. SPP central subprocess is PAMP-nemia, namely chronic kPAMP-load on blood phagocytes (neutrophiles, monocytes and dendritic cells). The load results in increase of blood kPAMP level. The major key PAMP (kPAMP) are LPS and PG (incl. PG-Y - peptidoglycan of psoriagenic bacteria). Chronically increased kPAMP-load possibly provides tolerization of some neutrophils Neu, monocytes Mo and dendritic cells DC in blood flow. The chemostatus of tolerized blood Neu-T in process of their aging changes similarly to chemostatus nonactivated Neu and, hence, they carry endocytosed content from blood flow into the bone marrow. Chemostatuses of tolerized Mo-T and DC-T are similar to nonactivated ones. So they don't bring endocytosed content to lymph nodes or spleen and remain in blood. Tolerized phagocytes degrade endocytosed fragments of bacterial products containing kPAMP slowly and incompletely, Tolerized phagocytes appeared to be (PG-Y)-carriers are named by R-phagocytes and are designated as Neu-R, Mo-R and DC-R. SPP severity predetermines possibility of psoriasis initialization and maintenance because Mo-R and DC-R along with normal Mo and DC participate in homeostatic and inflammatory renewal of pool of dermal macrophages and DC of non-resident origin. Part 2 - arXiv:1201.2900

q-bio.TO↗

arXiv2011

New mathematical model for fluid-glucose-albumin transport in peritoneal dialysis

A mathematical model for fluid transport in peritoneal dialysis is constructed. The model is based on a three-component nonlinear system of two-dimensional partial differential equations for fluid, glucose and albumin transport with the relevant boundary and initial conditions. Non-constant steady-state solutions of the model are studied. The restrictions on the parameters arising in the model are established with the aim to obtain exact formulae for the non-constant steady-state solutions. As the result, the exact formulae for the fluid fluxes from blood to tissue and across the tissue were constructed together with two linear autonomous ODEs for glucose and albumin concentrations. The analytical results were checked for their applicability for the description of fluid-glucose-albumin transport during peritoneal dialysis.

math.AP↗

arXiv2011

Gap Junctions: The Claymore for Cancerous Cells

Introduction: Gap junctions play an important role in the cell proliferation in mammalian cells as well as carcinogenesis. However, there are controversial issues about their role in cancer pathogenesis. This study was designed to evaluate genotoxicity and cytotoxicity of Carbenoxolone (CBX) as a prototype of inter-cellular gap junction blocker in MCF7 and BT20 human breast cancer cells. Methods: The MCF7and BT20 human breast cancer cell lines were cultivated, and treated at designated confluency with different doses of CBX. Cellular cytotoxicity was examined using standard colorimetric assay associated with cell viability tests. Gene expression evaluation was carried out using real time polymerase chain reaction (PCR). Results: MCF7 and BT20 cells were significantly affected by CBX in a dose dependent manner in cell viability assays. Despite varying expression of genes, down regulation of pro- and anti-apoptotic genes was observed in these cells. Conclusion: Based upon this investigation, it can be concluded that CBX could affect both low and high proliferative types of breast cancer cell lines and disproportionate down regulation of both pre- and anti-apoptotic genes may be related to interacting biomolecules, perhaps via gap junctions.

q-bio.BM↗

arXiv2011

Psoriasis as a consequence of incorporation of beta-streptococci into the microbiocenosis of highly permeable intestines (a pathogenic concept). Russian edition

A review of recent investigations into pathogenesis of psoriasis summarizing data on the relationship between the presence beta-streptococci in the organism and the cutaneous immune reaction. Results of the studies on gastrointestinal pathology in psoriatic patients are presented. The authors propose a hypothesis that advocates the primary origin of psoriatic gastrointestinal pathology and secondary nature of skin manifestations. A chronic plaque psoriasis model is developed on the basis of the assumption on the key role of two psorafactors, i.e. hyperpermeability of intestinal walls for certain proteins and incorporation of beta-streptococci in the microbiocenosis of intestinal mucosa. The validity of the model is confirmed by the results of practical clinical work.

q-bio.TO↗

arXiv2011

Prospects of using Antagonist Histamine H2-Receptor (Cimetidinum) as Adjuvant for Melanoma Biotherapy Treatment

Improvement of anti-tumor biotherapy effectiveness by modification of immune response with histamine H2 receptor Cimetidinum (CM) was studied using the experimental murine model of B16 F10 melanoma in vivo. It is shown that skin melanoma biotherapy by antitumor whole-cell GM-CSF-producing vaccine with the addition of CM (in dose of 25 mg/kg, daily for 5 days) increases preventive effects of vaccination. 33 % of mice did not have tumor growth within 60 days of observation. Average life span of animals exceeded those of the control group up to 68 %. Using CM-combined bio-chemotherapy doesn't improve therapeutic effect, however in the case of a monotherapeutic approach tendency for increased average life-time and decreased metastatic processes in mice with the developed tumors was noticed. Aquired data provides expediency to study the further application of CM as adjuvant for skin melanoma vaccinotherapy, and also the necessity to verify the immune status of an organism against the complex bio-chemotherapy.

q-bio.TO↗

arXiv2011

Pattern formation in auxin flux

The plant hormone auxin is fundamental for plant growth, and its spatial distribution in plant tissues is critical for plant morphogenesis. We consider a leading model of the polar auxin flux, and study in full detail the stability of the possible equilibrium configurations. We show that the critical states of the auxin transport process are composed of basic building blocks, which are isolated in a background of auxin depleted cells, and are not geometrically regular in general. The same model was considered recently through a continuous limit and a coupling to the von Karman equations, to model the interplay of biochemistry and mechanics during plant growth. Our conclusions might be of interest in this setting, since, for example, we establish the existence of Lyapunov functions for the auxin flux, proving in this way the convergence of pure transport processes toward the set of critical configurations.

q-bio.TO↗

arXiv2011

A Physiologically-Based Flow Network Model for Hepatic Drug Elimination I: Regular Lattice Lobule Model

We develop a physiologically-based lattice model for the transport and metabolism of drugs in the functional unit of the liver, called the lobule. In contrast to earlier studies, we have emphasized the dominant role of convection in well-vascularized tissue with a given structure. Estimates of convective, diffusive and reaction contributions are given. We have compared drug concentration levels observed exiting the lobule with their predicted detailed distribution inside the lobule, assuming that most often the former is accessible information while the latter is not.

physics.bio-ph↗

arXiv2011

Dinamics of HPV Infection among Women with Cervical Lesions

A total of 293 women treated at Tomsk Cancer Research Institute were examined. HPV type 16 had the highest incidence rate (45.0%) followed by HPV 31-17,0%, HPV 56/33-15,0%, HPV 51/18/52-13,0%, HPV 58/35/39/45-7,0%, HPV 59-5,0%. Persistent infection was detected in 35.7% of primarily HPV-positive cases (10 out of 28 patients), mainly in cervical cancer patients. Total number of primarily HPV-positive and HPV-negative patients with cervical cancer was 95.0% and 5.0%, respectively. The corresponding values after the complex treatment were 35.0% and 65.0%, respectively, pointing to the treatment efficiency.

q-bio.TO↗

arXiv2011

Polarization Theory of Motivations, Emotions and Attention

A new theory of motivations, emotions and attention is suggested, considering them as functions of sensory systems. The theory connects neurophysiological mechanisms of mental phenomena with the change of metabolic and functional state of perceptive neurons, which is reflected in the degree of polarization of a cell membrane.

q-bio.NC↗