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At least 145 records · Page 8Linked to original sources

arXiv2011

Radiobiological investigations at tumor cell lines by exploiting chrono-biological aspects of chronological dose distributions

Using 31P-NMR spectroscopy the chronological behavior of the ATP-metabolism of the tumor spheroids C3H-MA, 9L-Gliome and the mono-layer L1210 has been analyzed via decrease of the β-peak. All three cell lines show characteristic periods, and a homeostatic control cannot be recognized. Essential components of these periods are circadian (i.e. one day), circa-semiseptan (i.e. 3.5 days) and circa-septan (i.e. one week). The determination of the survival fractions provides an optimum exploitation of radiation damages, when the ATP-concentration assumes a maximum value. This optimum is reached, when all three cycles exhibit the ATP maximum, which is only possible by accounting for the circa-septan rhythm. The goal of this study is to elaborate an optimal fractionation scheme with regard to the irradiation of tumors.

physics.med-ph↗

arXiv2011

The cellular dynamics of bone remodeling: a mathematical model

The mechanical properties of vertebrate bone are largely determined by a process which involves the complex interplay of three different cell types. This process is called {\it bone remodeling}, and occurs asynchronously at multiple sites in the mature skeleton. The cells involved are bone resorbing osteoclasts, bone matrix producing osteoblasts and mechanosensing osteocytes. These cells communicate with each other by means of autocrine and paracrine signaling factors and operate in complex entities, the so-called bone multicellular units (BMU). To investigate the BMU dynamics in silico, we develop a novel mathematical model resulting in a system of nonlinear partial differential equations with time delays. The model describes the osteoblast and osteoclast populations together with the dynamics of the key messenger molecule RANKL and its decoy receptor OPG. Scaling theory is used to address parameter sensitivity and predict the emergence of pathological remodeling regimes. The model is studied numerically in one and two space dimensions using finite difference schemes in space and explicit delay equation solvers in time. The computational results are in agreement with in vivo observations and provide new insights into the role of the RANKL/OPG pathway in the spatial regulation of bone remodeling.

q-bio.TO↗

arXiv2011

Non-invasive estimation of the metabolic heat production of breast tumors using digital infrared imaging

In this work the metabolic heat generated by breast tumors was estimated indirectly and noninvasively from digital infrared images and numerically simulating a simplified breast model and a cancerous tumor, this parameter can be of clinical importance since it has been related to the doubling volume's time and malignancy for that particular tumor. The results indicate that digital infrared imaging has the potential to estimate in a non-invasive way the malignancy of a tumor by calculating its metabolic heat generation from bioheat thermal transfer models.

physics.med-ph↗

arXiv2011

Propagating left/right asymmetry in the zebrafish embryo: one-dimensional model

During embryonic development in vertebrates, left-right (L/R) asymmetry is reliably generated by a conserved mechanism: a L/R asymmetric signal is transmitted from the embryonic node to other parts of the embryo by the L/R asymmetric expression and diffusion of the TGF-$β$ related proteins Nodal and Lefty via propagating gene expression fronts in the lateral plate mesoderm (LPM) and midline. In zebrafish embryos, Nodal and Lefty expression can only occur along 3 narrow stripes that express the co-receptor \emph{one-eyed pinhead} (oep): Nodal along stripes in the left and right LPM, and Lefty along the midline. In wild-type embryos, Nodal is only expressed in the left LPM but not the right, because of inhibition by Lefty from the midline; however, bilateral Nodal expression occurs in loss-of-handedness mutants. A two-dimensional model of the zebrafish embryo predicts this loss of L/R asymmetry in oep mutants \cite{henley-xu-burdine}. In this paper, we simplify this two-dimensional picture to a one-dimensional model of Nodal and Lefty front propagation along the oep-expressing stripes. We represent Nodal and Lefty production by step functions that turn on when a linear function of Nodal and Lefty densities crosses a threshold. We do a parameter exploration of front propagation behavior, and find the existence of \emph{pinned} intervals, along which the linear function underlying production is pinned to the threshold. Finally, we find parameter regimes for which spatially uniform oscillating solutions are possible.

q-bio.TO↗

arXiv2011

An electromagnetic model for biological tissue

This essay is a recapitulation of an earlier Kramers-Kronig analysis of biological tissue, published in 2010, "Kramers-Kronig analysis of biological skin". The intent is to both complement and bolster the antecedent analysis by furnishing supplemental clarification on the electromagnetic model employed and provide further technical details. Biological tissue is modeled a dielectric embedded in a conductor, which necessitates using both a quotient and product subspace to form a complete topological cover space. Discerning a suitable quotient enables decisive separation of tissue's dielectric behavior from excess conductivity. The residual dielectric behavior revealed conforms with expectations based upon electromagnetic theory and those commonly held for dielectric materials. An appreciation for conflicting experimental absorption measurements spanning the optical spectrum, reported for biological skin, engenders conceptualizing a damage dependent attenuation coefficient. Lastly, descriptive codes are provided for numerical algorithms implemented in the original analysis.

q-bio.TO↗

arXiv2024

The Fundamental Theorem of Phyllotaxis revisited

Jean's `Fundamental Theorem of Phyllotaxis' (\emph{Phyllotaxis: a systematic study in Plant Morphogenesis}, CUP 1994) describes the relationship between the count numbers of observed spirals in cylindrical lattices and the horizontal angle between vertically successive spots in the lattice. It is indeed fundamental to observational studies of phyllotactic counts, and especially to the evaluation of hypotheses about the origin of Fibonacci structure within lattices. Unfortunately the textbook version of the theorem is incomplete in that it is incorrect for an important special case. This paper provides a complete statement and proof of the Theorem.

q-bio.TO↗

arXiv2012

Mechanobiological regulation of bone remodeling -- Theoretical development of a coupled systems biology-micromechanical approach

Bone remodeling involves the coordinated removal of bone by osteoclasts and addition of bone by osteoblasts, a process that is modulated by the prevailing mechanical environment. In this paper a fully coupled model of bone remodeling is developed, based on coupling a bone cell population model with a micromechanical homogenization scheme of bone stiffness. While the former model considers biochemical regulatory mechanisms between bone cells such as the RANK-RANKL-OPG pathway and action of TGF-β, the latter model allows for accurate upscaling of the mechanical properties of bone. Importantly, we consider bone remodeling as being controlled proportionally to the microscopic strain energy density, on the observation scale where the sensing of the mechanical loading takes place, estimated by means of continuum micromechanics-based strain concentration. This approach allows to address two fundamental questions of bone biology: (i) How do biochemical changes influence bone remodeling and so affect the composition and mechanical properties of bone? and (ii) What mechanisms are responsible for mechanoregulation of bone remodeling? Numerical studies highlight the conceptual advantage of this new approach compared to conventional phenomenological models. It is demonstrated that the proposed model is able to simulate changes of the bone constituent volume fractions that are in qualitative agreement with experimental observations for osteoporotic and disuse syndromes.

q-bio.TO↗

arXiv2012

Bridging the gap between the micro- and the macro-world of tumors

At present it is still quite difficult to match the vast knowledge on the behavior of individual tumor cells with macroscopic measurements on clinical tumors. On the modeling side, we already know how to deal with many molecular pathways and cellular events, using systems of differential equations and other modeling tools, and ideally, we should be able to extend such a mathematical description up to the level of large tumor masses. An extended model should thus help us forecast the behavior of large tumors from our basic knowledge of microscopic processes. Unfortunately, the complexity of these processes makes it very difficult -- probably impossible -- to develop comprehensive analytical models. We try to bridge the gap with a simulation program which is based on basic biochemical and biophysical processes -- thereby building an effective computational model -- and in this paper we describe its structure, endeavoring to make the description sufficiently detailed and yet understandable.

q-bio.TO↗

arXiv2012

Model of pathogenesis of psoriasis. Part 2. Local processes

Analytical research of results of experimental and theoretical studies on pathogenesis of psoriatic disease is carried out. The new model of pathogenesis - skin reaction to systemic psoriatic process SPP is formulated. ... Psoriatic inflammation is regarded as a reaction of the skin immune system to activity of Mo-R and DC-R involved in derma from blood flow. They contain Y-antigen and, getting to derma, can be transformed in mature maDC-Y and present this antigen to Y-specific T-lymphocytes as well as activate them. Y-antigen is a part of the interpeptide bridge IB-Y. Therefore, the skin immune system can incorrectly interpret Y-antigen presentation as a sign of external PsB-infection and switch one of mechanisms of protection against bacterial infection - epidermal hyperproliferation. Psoriatic plaque can be initiated only during action of local inflammatory process LP2 in derma causing not only innate, but also adaptive response. In particular, it is possible at LP2(IN) - open trauma of derma or at LP2(HPV) - HPV-carriage of keratinocytes. The level of Y-priming (presence and concentration of Y-specific T-lymphocytes in prepsoriatic derma and in lymph nodes) also determines possibility of psoriatic plaque initiation. Existence and severity of psoriatic plaque is determined by intensity of Y-antigen income into derma (inside Mo-R and DC-R). ... Severity of plaque is aggravated by LP2-inflammation if it persists after this plaque initiation. New Mo-T, DC-T (incl. Mo-R, DC-R) and Y-specific T-lymphocytes are constantly attracted into plaques from blood flow, and so support vicious cycles. Only at decrease of SPP severity, these vicious cycles weaken and natural remission of plaques takes place, up to their complete disappearance. The detailed analysis comparing the new model of pathogenesis with five other previously published models is carried out. Part 1. arXiv:1110.0584

q-bio.CB↗

arXiv2012

Immunity to Plasmodium knowlesi H strain malaria in olive baboons

Malaria disease is a major global health and economic development threat. It results in approximately 2.7 million deaths annually. There is currently no vaccine that has been licensed for use against malaria. Studies in animal models, especially non-human primates can lead to the revelation of possible immunological mechanisms that can lead to protection or predisposition of the host to malaria. Plasmodium knowlesi, a simian and human malaria parasite, is an attractive experimental parasite for malaria research since it can infect olive baboons (Papio anubis), non-human primates that have similar host-pathogen interactions to humans. This study was carried out to determine host immunological profiles provoked in olive baboons during the course of an infection with Plasmodium knowlesi. A total of eight adult baboons were intravenously inoculated with overnight cultured blood stage P. knowlesi H strain parasites. Five of these baboons became acutely infected while the other three became chronically infected. The immunological basis of this dual outcome of the infection was determined by measuring circulating cytokine (T helper 1 and T helper 2) and antibody (immunoglobulin G and immunoglobulin M) responses elicited in the infected baboons on a weekly basis by Enzyme Linked Immunosorbent Assay (ELISA) for up to six weeks post infection. Generated data for the first time indicated that acute P. knowlesi malaria is accompanied by increased concentrations of interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha) and IL 6 and reduced levels of circulating interleukin 10 (IL 10), IL 4, IL 12, immunoglobulin G (IgG) and IgM in the baboon host. These results are largely agreeable with data from human studies, thereby increasing the relevance of the olive baboon - P. knowlesi experimental infection system for future malaria studies.

q-bio.CB↗

arXiv2012

Velocity distribution of neutral particles ejected from biological material under ultra short laser radiation

Neutral particles ejected from biological material under ultra short laser ablation have been investigated by laser post-ionization time-of-flight mass spectrometry. It could be shown, that beside ionized species, a substantial amount of neutral particles is ejected. A temporal study of the ablation plume is carried out by recording neutral particle time-of- flight mass spectra as a function of delay time between the ablation and post-ionization pulse. Close the ablation threshold, the mechanism of ejection is found to be of predominantely mechanical nature, driven by the relaxation of the laser-induced pressure. In this regime of stress confinement, the ejection results in very broad velocity distributions and extremely low velocities.

physics.bio-ph↗

arXiv2012

Neural network prediction of load from the morphology of trabecular bone

Bone adaptation models are often solved in the forward direction, meaning that the response of bone to a given set of loads is determined by running a bone tissue adaptation model. The model is generally solved using a numerical technique such as the finite element model. Conversely, one may be interested in the loads that have resulted in a given state of bone. This is the inverse of the former problem. Even though the inverse problem has several applications, it has not received as much attention as the forward problem, partly because solving the inverse problem is more difficult. A nonlinear system identification technique is needed for solving the inverse problem. In this study, we use artificial neural networks for prediction of tissue adaptation loads from a given density distribution of trabecular bone. It is shown that the proposed method can successfully identify the loading parameters from the density distribution of the tissue. Two important challenges for all load prediction algorithms are the non-uniqueness of the solution of the inverse problem and the inaccuracies in the measurement of the morphology of the tissue. Both challenges are studied, and it is shown that the load prediction technique proposed in this paper can overcome both.

q-bio.TO↗

arXiv2012

Simulating Organogenesis in COMSOL

Organogenesis is a tightly regulated process that has been studied experimentally for decades. Computational models can help to integrate available knowledge and to better understand the underlying regulatory logic. We are currently studying mechanistic models for the development of limbs, lungs, kidneys, and bone. We have tested a number of alternative methods to solve our spatio- temporal differential equation models of reaction-diffusion type on growing domains of realistic shape, among them finite elements in COMSOL Multiphysics. Given the large number of variables (up to fifteen), the sharp domain boundaries, the travelling wave character of some solutions, and the stiffness of the reactions we are facing numerous numerical challenges. To test new ideas efficiently we have developed a strategy to optimize simulation times in COMSOL.

q-bio.TO↗

arXiv2012

Fibonacci numbers in phyllotaxis : a simple model

A simple model is presented which explains the occurrence of high order Fibonacci number parastichies in asteracae flowers by two distinct steps. First low order parastichies result from the fact that a new floret, at its appearance is repelled by two former ones, then, in order to accommodate for the increase of the radius, parastichies numbers have to evolve and can do it only by applying the Fibonacci recurrence formula.

cond-mat.soft↗

arXiv2012

Estimating the age of renal tumors

We present a Bayesian method for estimating the age of a renal tumor given its size. We use a model of tumor growth based on published data from observations of untreated tumors. We find, for example, that the median age of a 5 cm tumor is 20 years, with interquartile range 16-23 and 90% confidence interval 11-30 years.

stat.AP↗

arXiv2012

Hypoxic Cell Waves around Necrotic Cores in Glioblastoma: A Biomathematical Model and its Therapeutic Implications

Glioblastoma is a rapidly evolving high-grade astrocytoma that is distinguished pathologically from lower grade gliomas by the presence of necrosis and microvascular hiperplasia. Necrotic areas are typically surrounded by hypercellular regions known as "pseudopalisades" originated by local tumor vessel occlusions that induce collective cellular migration events. This leads to the formation of waves of tumor cells actively migrating away from central hypoxia. We present a mathematical model that incorporates the interplay among two tumor cell phenotypes, a necrotic core and the oxygen distribution. Our simulations reveal the formation of a traveling wave of tumor cells that reproduces the observed histologic patterns of pseudopalisades. Additional simulations of the model equations show that preventing the collapse of tumor microvessels leads to slower glioma invasion, a fact that might be exploited for therapeutic purposes.

q-bio.QM↗

arXiv2012

Reconstruction of the 3D structure and developmental history of plant cells and tissues

Modern spatial microscopy has provided developmental biology with powerful research tools. However, the recent significant technological breakthroughs have inevitably led to technical "bottlenecks" for the application of the new procedures to other tasks. We have developed a protocol for the 3D reconstruction of plant organelles and tissues from stacks of two-dimensional images obtained by means of a wide range of electron transmission and light microscopy. This protocol can be applied to a large set of primary data: live, fixed or even paleobotanical material. For tissue reconstruction, we have also developed a protocol of cell lineage tracing based on the geometrical properties of plant cells. For the tissue sample consisting of $n$ cells, this approach allows the reconstruction of up to $n-1$ cell divisions from the previous cell generations. Our protocol complements the limitations of clonal analysis and recent real-time approaches of lineage tracing. It works well in the case of tissues with directed and non-directed growth. Using these protocols, the subcellular relations between the complex surface of plastids with stromules and mitochondria in the tuber parenchyma cells in \textit{Corydalis bracteata} have been revealed. Moreover, for the embryo ($n=17$) and the seedling shoot apex ($n=208$) of \textit{Calla palustris}, the cellular architecture and full cell genealogy of up to 15 cell generations have been reconstructed. Three relatively independent cell lineages with stem cells located at the surface of the shoot apex have been found. The possibility of using a wide range of software, including open-source projects, is discussed.

q-bio.QM↗

arXiv2012

An Analysis of the Methods Employed for Breast Cancer Diagnosis

Breast cancer research over the last decade has been tremendous. The ground breaking innovations and novel methods help in the early detection, in setting the stages of the therapy and in assessing the response of the patient to the treatment. The prediction of the recurrent cancer is also crucial for the survival of the patient. This paper studies various techniques used for the diagnosis of breast cancer. Different methods are explored for their merits and de-merits for the diagnosis of breast lesion. Some of the methods are yet unproven but the studies look very encouraging. It was found that the recent use of the combination of Artificial Neural Networks in most of the instances gives accurate results for the diagnosis of breast cancer and their use can also be extended to other diseases.

cs.NE↗