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At least 217 records · Page 12Linked to original sources

arXiv2012

Automated Image Analysis of Hodgkin lymphoma

Hodgkin lymphoma is an unusual type of lymphoma, arising from malignant B-cells. Morphological and immunohistochemical features of malignant cells and their distribution differ from other cancer types. Based on systematic tissue image analysis, computer-aided exploration can provide new insights into Hodgkin lymphoma pathology. In this paper, we report results from an image analysis of CD30 immunostained Hodgkin lymphoma tissue section images. To the best of our knowledge, this is the first systematic application of image analysis to a set of tissue sections of Hodgkin lymphoma. We have implemented an automatic procedure to handle and explore image data in Aperio's SVS format. We use pre-processing approaches on a down-scaled image to separate the image objects from the background. Then, we apply a supervised classification method to assign pixels to predefined classes. Our pre-processing method is able to separate the tissue content of images from the image background. We analyzed three immunohistologically defined groups, non-lymphoma and the two most common forms of Hodgkin lymphoma, nodular sclerosis and mixed cellularity type. We found that nodular sclerosis and non-lymphoma images exhibit different amounts of CD30 stain, whereas mixed cellularity type exhibits a large variance and overlaps with the other groups. The results can be seen as a first step to computationally identify tumor regions in the images. This allows us to focus on these regions when performing computationally expensive tasks like object detection in the high-resolution image.

q-bio.TO↗

arXiv2012

Qualitative Modelling via Constraint Programming: Past, Present and Future

Qualitative modelling is a technique integrating the fields of theoretical computer science, artificial intelligence and the physical and biological sciences. The aim is to be able to model the behaviour of systems without estimating parameter values and fixing the exact quantitative dynamics. Traditional applications are the study of the dynamics of physical and biological systems at a higher level of abstraction than that obtained by estimation of numerical parameter values for a fixed quantitative model. Qualitative modelling has been studied and implemented to varying degrees of sophistication in Petri nets, process calculi and constraint programming. In this paper we reflect on the strengths and weaknesses of existing frameworks, we demonstrate how recent advances in constraint programming can be leveraged to produce high quality qualitative models, and we describe the advances in theory and technology that would be needed to make constraint programming the best option for scientific investigation in the broadest sense.

cs.CE↗

arXiv2012

Time in the cell: a plausible role for the plasma membrane

All cells must keep time to consistently perform vital biological functions. To that end, the coupling and interrelatedness of diverse subsecond events in the complex cellular environment, such as protein folding or translation rates, cannot simply result from the chance convergence of the inherent chemical properties of these phenomena, but may instead be synchronized through a cell-wide pacemaking mechanism. Picosecond vibrations of lipid membranes may play a role in such a mechanism.

q-bio.SC↗

arXiv2012

Cellular compartments cause multistability in biochemical reaction networks and allow cells to process more information

Many biological, physical, and social interactions have a particular dependence on where they take place. In living cells, protein movement between the nucleus and cytoplasm affects cellular response (i.e., proteins must be present in the nucleus to regulate their target genes). Here we use recent developments from dynamical systems and chemical reaction network theory to identify and characterize the key-role of the spatial organization of eukaryotic cells in cellular information processing. In particular the existence of distinct compartments plays a pivotal role in whether a system is capable of multistationarity (multiple response states), and is thus directly linked to the amount of information that the signaling molecules can represent in the nucleus. Multistationarity provides a mechanism for switching between different response states in cell signaling systems and enables multiple outcomes for cellular-decision making. We find that introducing species localization can alter the capacity for multistationarity and mathematically demonstrate that shuttling confers flexibility for and greater control of the emergence of an all-or-none response.

q-bio.MN↗

arXiv2012

One lump or two?

We investigate methods for modelling metabolism within populations of cells. Typically one represents the interaction of a cloned population of cells with their environment as though it were one large cell. The question is as to whether any dynamics are lost by this assumption, and as to whether it might be more appropriate to instead model each cell individually. We show that it is sufficient to model at an intermediate level of granularity, representing the population as two interacting lumps of tissue.

q-bio.QM↗

arXiv2012

The 'Swiss cheese' instability of bacterial biofilms

We demonstrate a novel pattern that results in bacterial biofilms as a result of the competition between hydrodynamic forces and adhesion forces. After the passage of an air plug, the break up of the residual thin liquid film scrapes and rearranges bacteria on the surface, such that a Swiss cheese pattern of holes is left in the residual biofilm.

physics.bio-ph↗

arXiv2012

Discrete modelling of bacterial conjugation dynamics

In bacterial populations, cells are able to cooperate in order to yield complex collective functionalities. Interest in population-level cellular behaviour is increasing, due to both our expanding knowledge of the underlying biological principles, and the growing range of possible applications for engineered microbial consortia. Researchers in the field of synthetic biology - the application of engineering principles to living systems - have, for example, recently shown how useful decision-making circuits may be distributed across a bacterial population. The ability of cells to interact through small signalling molecules (a mechanism known as it quorum sensing) is the basis for the majority of existing engineered systems. However, horizontal gene transfer (or conjugation) offers the possibility of cells exchanging messages (using DNA) that are much more information-rich. The potential of engineering this conjugation mechanism to suit specific goals will guide future developments in this area. Motivated by a lack of computational models for examining the specific dynamics of conjugation, we present a simulation framework for its further study. We present an agent-based model for conjugation dynamics, with realistic handling of physical forces. Our framework combines the management of intercellular interactions together with simulation of intracellular genetic networks, to provide a general-purpose platform. We validate our simulations against existing experimental data, and then demonstrate how the emergent mixing patterns of multi-strain populations can affect conjugation dynamics. Our model of conjugation, based on a probability distribution, may be easily tuned to correspond to the behaviour of different cell types. Simulation code and movies are available at http://code.google.com/p/discus/.

cs.MA↗

arXiv2012

Emergence of Self-Organized Amoeboid Movement in a Multi-Agent Approximation of Physarum polycephalum

The giant single-celled slime mould Physarum polycephalum exhibits complex morphological adaptation and amoeboid movement as it forages for food and may be seen as a minimal example of complex robotic behaviour. Swarm computation has previously been used to explore how spatiotemporal complexity can emerge from, and be distributed within, simple component parts and their interactions. Using a particle based swarm approach we explore the question of how to generate collective amoeboid movement from simple non-oscillatory component parts in a model of P. polycephalum. The model collective behaves as a cohesive and deformable virtual material, approximating the local coupling within the plasmodium matrix. The collective generates de-novo and complex oscillatory patterns from simple local interactions. The origin of this motor behaviour is distributed within the collective rendering is morphologically adaptive, amenable to external influence, and robust to simulated environmental insult. We show how to gain external influence over the collective movement by simulated chemo-attraction (pulling towards nutrient stimuli) and simulated light irradiation hazards (pushing from stimuli). The amorphous and distributed properties of the collective are demonstrated by cleaving it into two independent entities and fusing two separate entities to form a single device, thus enabling it to traverse narrow, separate or tortuous paths. We conclude by summarising the contribution of the model to swarm based robotics and soft-bodied modular robotics and discuss the future potential of such material approaches to the field.

cs.MA↗

arXiv2012

Biomembranes report

In this report, we analyse and simulate a chemotaxis model given by a system of stochastic reaction-diffusion equations posed on an evolving surface.

q-bio.CB↗

arXiv2012

Anergy in self-directed B lymphocytes from a statistical mechanics perspective

The ability of the adaptive immune system to discriminate between self and non-self mainly stems from the ontogenic clonal-deletion of lymphocytes expressing strong binding affinity with self-peptides. However, some self-directed lymphocytes may evade selection and still be harmless due to a mechanism called clonal anergy. As for B lymphocytes, two major explanations for anergy developed over three decades: according to "Varela theory", it stems from a proper orchestration of the whole B-repertoire, in such a way that self-reactive clones, due to intensive interactions and feed-back from other clones, display more inertia to mount a response. On the other hand, according to the `two-signal model", which has prevailed nowadays, self-reacting cells are not stimulated by helper lymphocytes and the absence of such signaling yields anergy. The first result we present, achieved through disordered statistical mechanics, shows that helper cells do not prompt the activation and proliferation of a certain sub-group of B cells, which turn out to be just those broadly interacting, hence it merges the two approaches as a whole (in particular, Varela theory is then contained into the two-signal model). As a second result, we outline a minimal topological architecture for the B-world, where highly connected clones are self-directed as a natural consequence of an ontogenetic learning; this provides a mathematical framework to Varela perspective. As a consequence of these two achievements, clonal deletion and clonal anergy can be seen as two inter-playing aspects of the same phenomenon too.

physics.bio-ph↗

arXiv2012

Network-level dynamics of diffusively coupled cells

We study molecular dynamics within populations of diffusively coupled cells under the assumption of fast diffusive exchange. As a technical tool, we propose conditions on boundedness and ultimate boundedness for systems with a singular perturbation, which extend the classical asymptotic stability results for singularly perturbed systems. Based on these results, we show that with common models of intracellular dynamics, the cell population is coordinated in the sense that all cells converge close to a common equilibrium point. We then study a more specific example of coupled cells which behave as bistable switches, where the intracellular dynamics are such that cells may be in one of two equilibrium points. Here, we find that the whole population is bistable in the sense that it converges to a population state where either all cells are close to the one equilibrium point, or all cells are close to the other equilibrium point. Finally, we discuss applications of these results for the robustness of cellular decision making in coupled populations.

q-bio.CB↗

arXiv2013

Negative-feedback self-regulation contributes to robust and high-fidelity transmembrane signal transduction

We present a minimal motif model for transmembrane cell signaling. The model assumes signaling events taking place in spatially distributed nanoclusters regulated by a birth/death dynamics. The combination of these spatio-temporal aspects can be modulated to provide a robust and high-fidelity response behavior without invoking sophisticated modeling of the signaling process as a sequence of cascade reactions and fine-tuned parameters. Our results show that the fact that the distributed signaling events take place in nanoclusters with a finite lifetime regulated by local production is sufficient to obtain a robust and high-fidelity response.

q-bio.CB↗

arXiv2013

Finite Volume Model to Study Calcium Diffusion in Neuron Involving JRYR, JSERCA and JLEAK

Calcium dynamics is the highly responsible for intracellular electrical (action potential) and chemical (neurotransmitter) signaling in neuron cell. The Mathematical modeling of calcium dynamics in neurons lead to the reaction diffusion equation which involves the parameters like diffusion coefficient, free calcium, bound calcium, buffers and bound buffer. Here the parameters like receptors, serca and leak are also incorporated in the model. Appropriate boundary conditions have been framed based on biophysical conditions of the problem. The finite volume method has been employed to obtain the solution. The computer program has been developed using MATLAB 7.11 for the entire problem to compute Ca2+ profiles and study the relationships among various parameters.

q-bio.CB↗

arXiv2013

Virtual-organism toy-model as a tool to develop bioinformatics approaches of Systems Biology for medical-target discovery

Systems Biology has emerged in the last years as a new holistic approach based on the global understanding of cells instead of only being focused on their individual parts (genes or proteins), to better understand the complexity of human cells. Since the Systems Biology still does not provide the most accurate answers to our questions due to the complexity of cells and the limited quality of available information to perform a good gene/protein map analysis, we have created simpler models to ensure easier analysis of the map that represents the human cell. Therefore, a virtual organism has been designed according to the main physiological rules for humans in order to replicate the human organism and its vital functions. This toy model was constructed by defining the topology of its genes/proteins and the biological functions associated to it. There are several examples of these toy models that emulate natural processes to perform analysis of the virtual life in order to design the best strategy to understand real life. The strategy applied in this study combines topological and functional analysis integrating the knowledge about the relative position of a node among the others in the map with the conclusions generated by mathematical models that reproduce functional data of the virtual organism. Our results demonstrate that the combination of both strategies allows better understanding of our virtual organism even with the lower input of information needed and therefore it can be a potential tool to better understand the real life.

q-bio.MN↗

arXiv2013

In vitro investigation of the effects of X- rays carried by a photon beam upon the cell cycle progression in Vero cells

The effects of the X-rays carried out in a photon beam produced by a medical linear particle accelerator on the progression of the cell cycle in normal cells Vero were evaluated by flow cytometric mean. The evaluation of the consequences of 1 and 3 Gy irradiation upon cell cycle development was performed after 96 and 120 hours from the exposure moment, in order to register the late effects of irradiation. As compared with the control group (sham exposed) the treated cells with the dose of 1 Gy have shown an increase of the frequency of cells blocked in S and G2/M stages and also of the apoptotic cells at 96 hours from the treatment. After another 24 hours, the frequency of the blocked cells in S and G2/M has decreased. The response of the 96 hours cell cultures to 3 Gy treatment was faster, as suggested by the increased number of apoptotic cells and by reduced frequency of the arrested cells in S and G2/M. The blockage of Vero cells in different phases of the cell-cycle and the presence of active repairing systems reveals the reduced risk of the malignant transformation of the exposed normal cells and could offer an enhanced cell protection to another damaging agents.

q-bio.TO↗

arXiv2013

The effects of nutrient chemotaxis on bacterial aggregation patterns with non-linear degenerate cross diffusion

This paper introduces a reaction-diffusion-chemotaxis model for bacterial aggregation patterns on the surface of thin agar plates. It is based on the non-linear degenerate cross diffusion model proposed by Kawasaki et al. (J. of Theor. Biol. 188(2) 1997) and it includes a suitable nutrient chemotactic term compatible with such type of diffusion. High resolution numerical simulations using Graphic Processing Units (GPUs) of the new model are presented, showing that the chemotactic term enhances the velocity of propagation of the colony envelope for dense-branching morphologies. In addition, the chemotaxis seems to stabilize the formation of branches in the soft-agar, low-nutrient regime. An asymptotic estimation predicts the growth velocity of the colony envelope as a function of both the nutrient concentration and the chemotactic sensitivity. For fixed nutrient concentrations, the growth velocity is an increasing function of the chemotactic sensitivity.

q-bio.CB↗

arXiv2013

Cell Migration Model with Multiple Chemical Compasses

A simple model is proposed that describes the various morphodynamic principles of migrating cells from polar to amoeboidal motions. The model equation is derived using competing internal cellular compass variables and symmetries of the system. Fixed points for the $N = 2$ system are closely investigated to clarify how the competition among polaritors explains the observed morphodynamics. Response behaviors of cell--to--signal stimuli are also investigated. This model will be useful for classifying high-dimensional cell motions and investigating collective cellular behaviors.

q-bio.CB↗

arXiv2013

Mechanotaxis and cell motility

We propose a mechanism of cell motility which is based on contraction and does not require protrusion. The contraction driven translocation of a cell is due to internal flow of the cytoskeleton generated by molecular motors. Each motor contributes to the stress field and simultaneously undergoes biased random motion in the direction of a higher value of this stress. In this way active cross-linkers use passive actin network as a medium through which they interact and self-organize. The model exhibits motility initiation pattern similar to the one observed in experiments on keratocytes.

physics.bio-ph↗