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Sample records for modeling multicellular systems

  1. Multiscale modeling of the dynamics of multicellular systems

    Science.gov (United States)

    Kosztin, Ioan

    2011-03-01

    Describing the biomechanical properties of cellular systems, regarded as complex highly viscoelastic materials, is a difficult problem of great conceptual and practical value. Here we present a novel approach, referred to as the Cellular Particle Dynamics (CPD) method, for: (i) quantitatively relating biomechanical properties at the cell level to those at the multicellular and tissue level, and (ii) describing and predicting the time evolution of multicellular systems that undergo biomechanical relaxations. In CPD cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through integration of their equations of motion. Cell and multicellular level biomechanical properties (e.g., viscosity, surface tension and shear modulus) are determined through the combined use of experiments and theory of continuum viscoelastic media. The same biomechanical properties are also ``measured'' computationally by employing the CPD method, the results being expressed in terms of CPD parameters. Once these parameters have been calibrated experimentally, the formalism provides a systematic framework to predict the time evolution of complex multicellular systems during shape-changing biomechanical transformations. By design, the CPD method is rather flexible and most suitable for multiscale modeling of multicellular system. The spatial level of detail of the system can be easily tuned by changing the number of CPs in a cell. Thus, CPD can be used equally well to describe both cell level processes (e.g., the adhesion of two cells) and tissue level processes (e.g., the formation of 3D constructs of millions of cells through bioprinting). Work supported by NSF [FIBR-0526854 and PHY-0957914

  2. Controllability in hybrid kinetic equations modeling nonequilibrium multicellular systems.

    Science.gov (United States)

    Bianca, Carlo

    2013-01-01

    This paper is concerned with the derivation of hybrid kinetic partial integrodifferential equations that can be proposed for the mathematical modeling of multicellular systems subjected to external force fields and characterized by nonconservative interactions. In order to prevent an uncontrolled time evolution of the moments of the solution, a control operator is introduced which is based on the Gaussian thermostat. Specifically, the analysis shows that the moments are solution of a Riccati-type differential equation.

  3. Collective dynamics of multicellular systems

    Indian Academy of Sciences (India)

    R Maithreye; C Suguna; Somdatta Sinha

    2011-11-01

    We have studied the collective behaviour of a one-dimensional ring of cells for conditions when the individual uncoupled cells show stable, bistable and oscillatory dynamics. We show that the global dynamics of this model multicellular system depends on the system size, coupling strength and the intrinsic dynamics of the cells. The intrinsic variability in dynamics of the constituent cells are suppressed to stable dynamics, or modified to intermittency under different conditions. This simple model study reveals that cell–cell communication, system size and intrinsic cellular dynamics can lead to evolution of collective dynamics in structured multicellular biological systems that is significantly different from its constituent single-cell behaviour.

  4. Multiscale mechanobiology: computational models for integrating molecules to multicellular systems.

    Science.gov (United States)

    Mak, Michael; Kim, Taeyoon; Zaman, Muhammad H; Kamm, Roger D

    2015-10-01

    Mechanical signals exist throughout the biological landscape. Across all scales, these signals, in the form of force, stiffness, and deformations, are generated and processed, resulting in an active mechanobiological circuit that controls many fundamental aspects of life, from protein unfolding and cytoskeletal remodeling to collective cell motions. The multiple scales and complex feedback involved present a challenge for fully understanding the nature of this circuit, particularly in development and disease in which it has been implicated. Computational models that accurately predict and are based on experimental data enable a means to integrate basic principles and explore fine details of mechanosensing and mechanotransduction in and across all levels of biological systems. Here we review recent advances in these models along with supporting and emerging experimental findings.

  5. Colloquium: Modeling the dynamics of multicellular systems: Application to tissue engineering

    Science.gov (United States)

    Kosztin, Ioan; Vunjak-Novakovic, Gordana; Forgacs, Gabor

    2012-10-01

    Tissue engineering is a rapidly evolving discipline that aims at building functional tissues to improve or replace damaged ones. To be successful in such an endeavor, ideally, the engineering of tissues should be based on the principles of developmental biology. Recent progress in developmental biology suggests that the formation of tissues from the composing cells is often guided by physical laws. Here a comprehensive computational-theoretical formalism is presented that is based on experimental input and incorporates biomechanical principles of developmental biology. The formalism is described and it is shown that it correctly reproduces and predicts the quantitative characteristics of the fundamental early developmental process of tissue fusion. Based on this finding, the formalism is then used toward the optimization of the fabrication of tubular multicellular constructs, such as a vascular graft, by bioprinting, a novel tissue engineering technology.

  6. Computational modeling of calcium signaling from the nanoscale to multicellular systems

    Science.gov (United States)

    Ullah, Ghanim

    Calcium signaling is one of the most important signaling mechanisms controlling e.g. the contraction of muscle cells, the release of neurotransmitter from neurons and astrocytes, transcription inside the nucleus and metabolic processes in liver and pancreas [8, 44, 36]. Due to the general importance in cell biology, Ca2+ signals of a variety of forms have been the subject of much recent experimental research. A recent and particularly powerful approach towards the understanding of Ca2+ signaling is the combination of highly resolved fluorescent imaging methods and detailed mathematical modeling. Models for Ca2+ signaling are probably the most advanced and realistic modes in all areas of biological physics. Hence theoretical predictions are quantitative in nature and allow direct comparison with experiments. Ca2+ signaling patterns exhibit a hierarchical structure varying from single-channel release events (10's of nanometers) to Ca2+ waves sweeping over entire organs like the liver to globally orchestrate the efficient release of enzymes [48]. This multi-scale organization renders it an ideal tool for studying basic concepts of pattern formation, especially since access to the most important experimental parameters is given. The aim of this dissertation is to develop mathematical models that quantitatively describe the characteristics of elementary Ca2+ elements (called Ca2+ -puffs) on the nano-scale as well as the organization of global waves and oscillations on the cell and organ scale. We used oocytes, eggs and astrocytes as model cells for our theoretical studies. Particularly on the microscopic scale we report significant progress in modeling Ca 2+ release events that are accurate in time course and spatial shape. Experimental investigations have revealed recently that Ca 2+ signaling differentiates during the development of oocytes into mature eggs. The fertilization specific Ca2+ signal in mature eggs is characterized by a fast rise of intracellular Ca2+ and

  7. Cellular Potts modeling of complex multicellular behaviors in tissue morphogenesis

    NARCIS (Netherlands)

    T. Hirashima (Tsuyoshi); E.G. Rens (Lisanne); R.M.H. Merks (Roeland)

    2017-01-01

    textabstractMathematical modeling is an essential approach for the understanding of complex multicellular behaviors in tissue morphogenesis. Here, we review the cellular Potts model (CPM; also known as the Glazier-Graner-Hogeweg model), an effective computational modeling framework. We discuss its

  8. Cellular Potts modeling of complex multicellular behaviors in tissue morphogenesis.

    Science.gov (United States)

    Hirashima, Tsuyoshi; Rens, Elisabeth G; Merks, Roeland M H

    2017-06-01

    Mathematical modeling is an essential approach for the understanding of complex multicellular behaviors in tissue morphogenesis. Here, we review the cellular Potts model (CPM; also known as the Glazier-Graner-Hogeweg model), an effective computational modeling framework. We discuss its usability for modeling complex developmental phenomena by examining four fundamental examples of tissue morphogenesis: (i) cell sorting, (ii) cyst formation, (iii) tube morphogenesis in kidney development, and (iv) blood vessel formation. The review provides an introduction for biologists for starting simulation analysis using the CPM framework. © 2017 Japanese Society of Developmental Biologists.

  9. Spatial self-organization in hybrid models of multicellular adhesion

    Science.gov (United States)

    Bonforti, Adriano; Duran-Nebreda, Salva; Montañez, Raúl; Solé, Ricard

    2016-10-01

    Spatial self-organization emerges in distributed systems exhibiting local interactions when nonlinearities and the appropriate propagation of signals are at work. These kinds of phenomena can be modeled with different frameworks, typically cellular automata or reaction-diffusion systems. A different class of dynamical processes involves the correlated movement of agents over space, which can be mediated through chemotactic movement or minimization of cell-cell interaction energy. A classic example of the latter is given by the formation of spatially segregated assemblies when cells display differential adhesion. Here, we consider a new class of dynamical models, involving cell adhesion among two stochastically exchangeable cell states as a minimal model capable of exhibiting well-defined, ordered spatial patterns. Our results suggest that a whole space of pattern-forming rules is hosted by the combination of physical differential adhesion and the value of probabilities modulating cell phenotypic switching, showing that Turing-like patterns can be obtained without resorting to reaction-diffusion processes. If the model is expanded allowing cells to proliferate and die in an environment where diffusible nutrient and toxic waste are at play, different phases are observed, characterized by regularly spaced patterns. The analysis of the parameter space reveals that certain phases reach higher population levels than other modes of organization. A detailed exploration of the mean-field theory is also presented. Finally, we let populations of cells with different adhesion matrices compete for reproduction, showing that, in our model, structural organization can improve the fitness of a given cell population. The implications of these results for ecological and evolutionary models of pattern formation and the emergence of multicellularity are outlined.

  10. Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation.

    Science.gov (United States)

    Murovec, Tomo; Sweeney, Daniel C; Latouche, Eduardo; Davalos, Rafael V; Brosseau, Christian

    2016-11-15

    Many approaches for studying the transmembrane potential (TMP) induced during the treatment of biological cells with pulsed electric fields have been reported. From the simple analytical models to more complex numerical models requiring significant computational resources, a gamut of methods have been used to recapitulate multicellular environments in silico. Cells have been modeled as simple shapes in two dimensions as well as more complex geometries attempting to replicate realistic cell shapes. In this study, we describe a method for extracting realistic cell morphologies from fluorescence microscopy images to generate the piecewise continuous mesh used to develop a finite element model in two dimensions. The preelectroporation TMP induced in tightly packed cells is analyzed for two sets of pulse parameters inspired by clinical irreversible electroporation treatments. We show that high-frequency bipolar pulse trains are better, and more homogeneously raise the TMP of tightly packed cells to a simulated electroporation threshold than conventional irreversible electroporation pulse trains, at the expense of larger applied potentials. Our results demonstrate the viability of our method and emphasize the importance of considering multicellular effects in the numerical models used for studying the response of biological tissues exposed to electric fields. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

    Science.gov (United States)

    McCune, Matthew; Kosztin, Ioan

    2013-03-01

    Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

  12. Predictive modeling of multicellular structure formation by using Cellular Particle Dynamics simulations

    Science.gov (United States)

    McCune, Matthew; Shafiee, Ashkan; Forgacs, Gabor; Kosztin, Ioan

    2014-03-01

    Cellular Particle Dynamics (CPD) is an effective computational method for describing and predicting the time evolution of biomechanical relaxation processes of multicellular systems. A typical example is the fusion of spheroidal bioink particles during post bioprinting structure formation. In CPD cells are modeled as an ensemble of cellular particles (CPs) that interact via short-range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through integration of their equations of motion. CPD was successfully applied to describe and predict the fusion of 3D tissue construct involving identical spherical aggregates. Here, we demonstrate that CPD can also predict tissue formation involving uneven spherical aggregates whose volumes decrease during the fusion process. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

  13. Sliding mode control for a three phase multicellular inverter dedicated to renewable energy systems

    Science.gov (United States)

    Hemici, K.; Zegaoui, A.; Djahbar, A.; Bokhtache, A. Aissa; Kessaissia, F. Z.; Allouache, H.; Mahmoudi, M. O.; Aillerie, M.

    2017-02-01

    In this paper, Sliding Mode controller has been sized to control multi-cell converters configured as a three-phase multicellular inverter. Unlike traditional inverters, multicellular inverters have the following advantages: lower switching frequency, high number of output levels, and less voltage constraints on the power switch. Significant performances are provided with this structure, which is constituted with flying capacitors. The main purpose of this paper is to present the model and generate commutation sliding-surfaces based on a Lyapunov function. The performed simulations point the efficiency of the proposed strategy with a three-phase multicellular inverters and allow to assess the performances and the robustness of the synthesized controller.

  14. Development of cell differentiation in the transition to multicellularity: a dynamical modeling approach

    Science.gov (United States)

    Mora Van Cauwelaert, Emilio; Arias Del Angel, Juan A.; Benítez, Mariana; Azpeitia, Eugenio M.

    2015-01-01

    Multicellularity has emerged and continues to emerge in a variety of lineages and under diverse environmental conditions. In order to attain individuality and integration, multicellular organisms must exhibit spatial cell differentiation, which in turn allows cell aggregates to robustly generate traits and behaviors at the multicellular level. Nevertheless, the mechanisms that may lead to the development of cellular differentiation and patterning in emerging multicellular organisms remain unclear. We briefly review two conceptual frameworks that have addressed this issue: the cooperation-defection framework and the dynamical patterning modules (DPMs) framework. Then, situating ourselves in the DPM formalism first put forward by S. A. Newman and collaborators, we state a hypothesis for cell differentiation and arrangement in cellular masses of emerging multicellular organisms. Our hypothesis is based on the role of the generic cell-to-cell communication and adhesion patterning mechanisms, which are two fundamental mechanisms for the evolution of multicellularity, and whose molecules seem to be well-conserved in extant multicellular organisms and their unicellular relatives. We review some fundamental ideas underlying this hypothesis and contrast them with empirical and theoretical evidence currently available. Next, we use a mathematical model to illustrate how the mechanisms and assumptions considered in the hypothesis we postulate may render stereotypical arrangements of differentiated cells in an emerging cellular aggregate and may contribute to the variation and recreation of multicellular phenotypes. Finally, we discuss the potential implications of our approach and compare them to those entailed by the cooperation-defection framework in the study of cell differentiation in the transition to multicellularity. PMID:26157427

  15. Kinetic Monte Carlo and Cellular Particle Dynamics Simulations of Multicellular Systems

    CERN Document Server

    Flenner, Elijah; Barz, Bogdan; Neagu, Adrian; Forgacs, Gabor; Kosztin, Ioan

    2011-01-01

    Computer modeling of multicellular systems has been a valuable tool for interpreting and guiding in vitro experiments relevant to embryonic morphogenesis, tumor growth, angiogenesis and, lately, structure formation following the printing of cell aggregates as bioink particles. Computer simulations based on Metropolis Monte Carlo (MMC) algorithms were successful in explaining and predicting the resulting stationary structures (corresponding to the lowest adhesion energy state). Here we introduce two alternatives to the MMC approach for modeling cellular motion and self-assembly: (1) a kinetic Monte Carlo (KMC), and (2) a cellular particle dynamics (CPD) method. Unlike MMC, both KMC and CPD methods are capable of simulating the dynamics of the cellular system in real time. In the KMC approach a transition rate is associated with possible rearrangements of the cellular system, and the corresponding time evolution is expressed in terms of these rates. In the CPD approach cells are modeled as interacting cellular ...

  16. Kinetic Monte Carlo and cellular particle dynamics simulations of multicellular systems

    Science.gov (United States)

    Flenner, Elijah; Janosi, Lorant; Barz, Bogdan; Neagu, Adrian; Forgacs, Gabor; Kosztin, Ioan

    2012-03-01

    Computer modeling of multicellular systems has been a valuable tool for interpreting and guiding in vitro experiments relevant to embryonic morphogenesis, tumor growth, angiogenesis and, lately, structure formation following the printing of cell aggregates as bioink particles. Here we formulate two computer simulation methods: (1) a kinetic Monte Carlo (KMC) and (2) a cellular particle dynamics (CPD) method, which are capable of describing and predicting the shape evolution in time of three-dimensional multicellular systems during their biomechanical relaxation. Our work is motivated by the need of developing quantitative methods for optimizing postprinting structure formation in bioprinting-assisted tissue engineering. The KMC and CPD model parameters are determined and calibrated by using an original computational-theoretical-experimental framework applied to the fusion of two spherical cell aggregates. The two methods are used to predict the (1) formation of a toroidal structure through fusion of spherical aggregates and (2) cell sorting within an aggregate formed by two types of cells with different adhesivities.

  17. Complex multicellular systems and immune competition: new paradigms looking for a mathematical theory.

    Science.gov (United States)

    Bellomo, Nicola; Forni, Guido

    2008-01-01

    This chapter deals with the modeling and simulation of large systems of interacting entities whose microscopic state includes not only geometrical and mechanical variables (typically position and velocity), but also biological functions or specific activities. The main issue looks at the development of a biological mathematical theory for multicellular systems. The first part is devoted to the derivation of mathematical structures to be properly used to model a variety of biological phenomena with special focus on immune competition. Then, some specific applications are proposed referring to the competition between neoplastic and immune cells. Finally, the last part is devoted to research perspectives towards the objective of developing a mathematical-biological theory. A critique is presented of what has already been achieved towards the above target and what is still missing with special focus on multiscale systems.

  18. Modeling collective & intelligent decision making of multi-cellular populations.

    Science.gov (United States)

    Shin, Yong-Jun; Mahrou, Bahareh

    2014-01-01

    In the presence of unpredictable disturbances and uncertainties, cells intelligently achieve their goals by sharing information via cell-cell communication and making collective decisions, which are more reliable compared to individual decisions. Inspired by adaptive sensor network algorithms studied in communication engineering, we propose that a multi-cellular adaptive network can convert unreliable decisions by individual cells into a more reliable cell-population decision. It is demonstrated using the effector T helper (a type of immune cell) population, which plays a critical role in initiating immune reactions in response to invading foreign agents (e.g., viruses, bacteria, etc.). While each individual cell follows a simple adaptation rule, it is the combined coordination among multiple cells that leads to the manifestation of "self-organizing" decision making via cell-cell communication.

  19. The cellular Ising model: a framework for phase transitions in multicellular environments.

    Science.gov (United States)

    Weber, Marc; Buceta, Javier

    2016-06-01

    Inspired by the Ising model, we introduce a gene regulatory network that induces a phase transition that coordinates robustly the behaviour of cell ensembles. The building blocks of the design are the so-called toggle switch interfaced with two quorum sensing modules, Las and Lux. We show that as a function of the transport rate of signalling molecules across the cell membrane the population undergoes a spontaneous symmetry breaking from cells individually switching their phenotypes to a global collective phenotypic organization. By characterizing the critical behaviour, we reveal some properties, such as phenotypic memory and hypersensitivity, with relevance in the field of synthetic biology. We argue that our results can be extrapolated to other multicellular systems and be a generic framework for collective decision-making processes. © 2016 The Author(s).

  20. Multicellular bacteria deploy the type VI secretion system to preemptively strike neighboring cells.

    Science.gov (United States)

    Alteri, Christopher J; Himpsl, Stephanie D; Pickens, Shannon R; Lindner, Jonathon R; Zora, Jonathan S; Miller, Jessa E; Arno, Peter D; Straight, Samuel W; Mobley, Harry L T

    2013-01-01

    The Type VI Secretion System (T6SS) functions in bacteria as a contractile nanomachine that punctures and delivers lethal effectors to a target cell. Virtually nothing is known about the lifestyle or physiology that dictates when bacteria normally produce their T6SS, which prevents a clear understanding of how bacteria benefit from its action in their natural habitat. Proteus mirabilis undergoes a characteristic developmental process to coordinate a multicellular swarming behavior and will discriminate itself from another Proteus isolate during swarming, resulting in a visible boundary termed a Dienes line. Using transposon mutagenesis, we discovered that this recognition phenomenon requires the lethal action of the T6SS. All mutants identified in the genetic screen had insertions within a single 33.5-kb region that encodes a T6SS and cognate Hcp-VrgG-linked effectors. The identified T6SS and primary effector operons were characterized by killing assays, by construction of additional mutants, by complementation, and by examining the activity of the type VI secretion system in real-time using live-cell microscopy on opposing swarms. We show that lethal T6SS-dependent activity occurs when a dominant strain infiltrates deeply beyond the boundary of the two swarms. Using this multicellular model, we found that social recognition in bacteria, underlying killing, and immunity to killing all require cell-cell contact, can be assigned to specific genes, and are dependent on the T6SS. The ability to survive a lethal T6SS attack equates to "recognition". In contrast to the current model of T6SS being an offensive or defensive weapon our findings support a preemptive mechanism by which an entire population indiscriminately uses the T6SS for contact-dependent delivery of effectors during its cooperative mode of growth.

  1. Multicellular bacteria deploy the type VI secretion system to preemptively strike neighboring cells.

    Directory of Open Access Journals (Sweden)

    Christopher J Alteri

    Full Text Available The Type VI Secretion System (T6SS functions in bacteria as a contractile nanomachine that punctures and delivers lethal effectors to a target cell. Virtually nothing is known about the lifestyle or physiology that dictates when bacteria normally produce their T6SS, which prevents a clear understanding of how bacteria benefit from its action in their natural habitat. Proteus mirabilis undergoes a characteristic developmental process to coordinate a multicellular swarming behavior and will discriminate itself from another Proteus isolate during swarming, resulting in a visible boundary termed a Dienes line. Using transposon mutagenesis, we discovered that this recognition phenomenon requires the lethal action of the T6SS. All mutants identified in the genetic screen had insertions within a single 33.5-kb region that encodes a T6SS and cognate Hcp-VrgG-linked effectors. The identified T6SS and primary effector operons were characterized by killing assays, by construction of additional mutants, by complementation, and by examining the activity of the type VI secretion system in real-time using live-cell microscopy on opposing swarms. We show that lethal T6SS-dependent activity occurs when a dominant strain infiltrates deeply beyond the boundary of the two swarms. Using this multicellular model, we found that social recognition in bacteria, underlying killing, and immunity to killing all require cell-cell contact, can be assigned to specific genes, and are dependent on the T6SS. The ability to survive a lethal T6SS attack equates to "recognition". In contrast to the current model of T6SS being an offensive or defensive weapon our findings support a preemptive mechanism by which an entire population indiscriminately uses the T6SS for contact-dependent delivery of effectors during its cooperative mode of growth.

  2. A software architecture for multi-cellular system simulations on graphics processing units.

    Science.gov (United States)

    Jeannin-Girardon, Anne; Ballet, Pascal; Rodin, Vincent

    2013-09-01

    The first aim of simulation in virtual environment is to help biologists to have a better understanding of the simulated system. The cost of such simulation is significantly reduced compared to that of in vivo simulation. However, the inherent complexity of biological system makes it hard to simulate these systems on non-parallel architectures: models might be made of sub-models and take several scales into account; the number of simulated entities may be quite large. Today, graphics cards are used for general purpose computing which has been made easier thanks to frameworks like CUDA or OpenCL. Parallelization of models may however not be easy: parallel computer programing skills are often required; several hardware architectures may be used to execute models. In this paper, we present the software architecture we built in order to implement various models able to simulate multi-cellular system. This architecture is modular and it implements data structures adapted for graphics processing units architectures. It allows efficient simulation of biological mechanisms.

  3. Bioelectrical Signals and Ion Channels in the Modeling of Multicellular Patterns and Cancer Biophysics.

    Science.gov (United States)

    Cervera, Javier; Alcaraz, Antonio; Mafe, Salvador

    2016-02-04

    Bioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects in small multicellular ensembles, ignoring slow diffusional processes. The spatio-temporal patterns obtained for the local map of cell electric potentials illustrate the normalization of regions with abnormal cell electrical states. The effects of intercellular coupling and blocking of specific channels on the electrical patterns are described. These patterns can regulate the electrically-induced redistribution of charged nanoparticles over small regions of a model tissue. The inclusion of bioelectrical signals provides new insights for the modeling of cancer biophysics because collective multicellular states show electrical coupling mechanisms that are not readily deduced from biochemical descriptions at the individual cell level.

  4. MicroRNA Intercellular Transfer and Bioelectrical Regulation of Model Multicellular Ensembles by the Gap Junction Connectivity.

    Science.gov (United States)

    Cervera, Javier; Meseguer, Salvador; Mafe, Salvador

    2017-08-17

    We have studied theoretically the microRNA (miRNA) intercellular transfer through voltage-gated gap junctions in terms of a biophysically grounded system of coupled differential equations. Instead of modeling a specific system, we use a general approach describing the interplay between the genetic mechanisms and the single-cell electric potentials. The dynamics of the multicellular ensemble are simulated under different conditions including spatially inhomogeneous transcription rates and local intercellular transfer of miRNAs. These processes result in spatiotemporal changes of miRNA, mRNA, and ion channel protein concentrations that eventually modify the bioelectrical states of small multicellular domains because of the ensemble average nature of the electrical potential. The simulations allow a qualitative understanding of the context-dependent nature of the effects observed when specific signaling molecules are transferred through gap junctions. The results suggest that an efficient miRNA intercellular transfer could permit the spatiotemporal control of small cellular domains by the conversion of single-cell genetic and bioelectric states into multicellular states regulated by the gap junction interconnectivity.

  5. A generic spatial-stochastic framework for quantifying noisy information flow in multicellular systems

    Science.gov (United States)

    Sokolowski, Thomas; Tkačik, Gašper

    Spatio-temporal protein signals play a crucial role in communicating information within and between cells. However, their ability to convey signals robustly is hampered by noise in gene regulation and biochemical transport, occuring at low copy numbers. While we increasingly understand distinct strategies of biochemical noise control, it remains unclear how nature orchestrates them to maximize information flow. Our recent work extends our information-theoretic framework for gene regulation to an explicitly spatial setting. We constructed a stochastic model enabling fast calculation of local means and variances in a spatially coupled gene regulatory system, which we use for rigorous quantification of information flow in an ensemble of units sensing a spatially distributed input and exchanging information via diffusion. By applying our framework to the paradigmatic Bcd-Hbk system in early fly development, we demonstrate that diffusive coupling can be of substantial benefit in encoding positional information, and uncover a novel optimal regulatory strategy relying on spatial coupling. Thanks to the generic methodology employed, our framework is universally applicable for realistic predictive modeling and data-driven inference of multicellular systems engaging in noisy communication. Institute of Science and Technology Austria, Am Campus 1, A-3400 Klosterneuburg, Austria.

  6. Scaling Laws and Design Principles for Multi-Cellular Wireless OFDMA Systems

    CERN Document Server

    Aggarwal, Rohit; Schniter, Philip

    2011-01-01

    In this paper, we consider the downlink of large-scale multi-cellular OFDMA-based networks and study performance bounds of the system as a function of the number of users $K$, the number of base-stations $B$, and the number of resource-blocks $N$. Here, a resource block is a collection of subcarriers such that all such collections, that are disjoint have associated independently fading channels. We derive novel upper and lower bounds on the sum-utility for a general spatial geometry of base stations, a truncated path loss model, and a variety of fading models (Rayleigh, Nakagami-$m$, Weibull, and LogNormal). We also establish the associated scaling laws and show that, in the special case of fixed number of resource blocks, a grid-based network of base stations, and Rayleigh-fading channels, the sum information capacity of the system scales as $\\Theta(B \\log\\log K/B)$ for extended networks, and as $O(B \\log\\log K)$ and $\\Omega(\\log \\log K)$ for dense networks. Interpreting these results, we develop some design...

  7. Application of GA in optimization of pore network models generated by multi-cellular growth algorithms

    Science.gov (United States)

    Jamshidi, Saeid; Boozarjomehry, Ramin Bozorgmehry; Pishvaie, Mahmoud Reza

    2009-10-01

    In pore network modeling, the void space of a rock sample is represented at the microscopic scale by a network of pores connected by throats. Construction of a reasonable representation of the geometry and topology of the pore space will lead to a reliable prediction of the properties of porous media. Recently, the theory of multi-cellular growth (or L-systems) has been used as a flexible tool for generation of pore network models which do not require any special information such as 2D SEM or 3D pore space images. In general, the networks generated by this method are irregular pore network models which are inherently closer to the complicated nature of the porous media rather than regular lattice networks. In this approach, the construction process is controlled only by the production rules that govern the development process of the network. In this study, genetic algorithm has been used to obtain the optimum values of the uncertain parameters of these production rules to build an appropriate irregular lattice network capable of the prediction of both static and hydraulic information of the target porous medium.

  8. Delineation of nuclear structures in 3D multicellular systems

    Energy Technology Data Exchange (ETDEWEB)

    2013-09-13

    A pipeline, implemented within the Insight Segmentation and Registration Toolkit (ITK) and The Visualization Toolkit (VTK) framework, to delineate each nucleus and to profile morphometric and colony organization. At an abstract level, our approach is an extension of a previously developed method for monolayer call structure models.

  9. On eukaryotic intelligence: signaling system's guidance in the evolution of multicellular organization.

    Science.gov (United States)

    Marijuán, Pedro C; del Moral, Raquel; Navarro, Jorge

    2013-10-01

    Communication with the environment is an essential characteristic of the living cell, even more when considering the origins and evolution of multicellularity. A number of changes and tinkering inventions were necessary in the evolutionary transition between prokaryotic and eukaryotic cells, which finally made possible the appearance of genuine multicellular organisms. In the study of this process, however, the transformations experimented by signaling systems themselves have been rarely object of analysis, obscured by other more conspicuous biological traits: incorporation of mitochondria, segregated nucleus, introns/exons, flagellum, membrane systems, etc. Herein a discussion of the main avenues of change from prokaryotic to eukaryotic signaling systems and a review of the signaling resources and strategies underlying multicellularity will be attempted. In the expansion of prokaryotic signaling systems, four main systemic resources were incorporated: molecular tools for detection of solutes, molecular tools for detection of solvent (Donnan effect), the apparatuses of cell-cycle control, and the combined system endocytosis/cytoskeleton. The multiple kinds of enlarged, mixed pathways that emerged made possible the eukaryotic revolution in morphological and physiological complexity. The massive incorporation of processing resources of electro-molecular nature, derived from the osmotic tools counteracting the Donnan effect, made also possible the organization of a computational tissue with huge information processing capabilities: the nervous system. In the central nervous systems of vertebrates, and particularly in humans, neurons have achieved both the highest level of molecular-signaling complexity and the highest degree of information-processing adaptability. Theoretically, it can be argued that there has been an accelerated pace of evolutionary change in eukaryotic signaling systems, beyond the other general novelties introduced by eukaryotic cells in their

  10. Connecting models to data in multiscale multicellular tissue simulations

    OpenAIRE

    2013-01-01

    System level biological behaviour typically arises from highly dynamic, strongly nonlinear, tightly coupled interactions between component processes occurring across multiple space and time scales. The interdependent nature of these processes often makes it difficult to apply standard mathematical techniques to separate out the scales, uncouple the physical processes or average over contributions from discrete components. To make rapid progress we need to address interoperability challenges: ...

  11. Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model

    DEFF Research Database (Denmark)

    Bendtsen, Kristian Moss; Juul, Jeppe Søgaard; Trusina, Ala

    2012-01-01

    DNA damages, as well as mutations, increase with age. It is believed that these result from increased genotoxic stress and decreased capacity for DNA repair. The two causes are not independent, DNA damage can, for example, through mutations, compromise the capacity for DNA repair, which in turn...... to DNA damage can undergo full repair, go apoptotic, or accumulate mutations thus reducing DNA repair capacity. Our model predicts that at the tissue level repair rate does not continuously decline with age, but instead has a characteristic extended period of high and non-declining DNA repair capacity...... of compromised cells, thus freeing the space for healthy peers. This finding might be a first step toward understanding why a mutation in single DNA repair protein (e.g. Wrn or Blm) is not buffered by other repair proteins and therefore, leads to severe ageing disorders...

  12. PhantomNet: Exploring Optimal Multicellular Multiple Antenna Systems

    Directory of Open Access Journals (Sweden)

    Foschini Gerard J

    2004-01-01

    Full Text Available We present a network framework for evaluating the theoretical performance limits of wireless data communication. We address the problem of providing the best possible service to new users joining the system without affecting existing users. Since, interference-wise, new users are required to be invisible to existing users, the network is dubbed PhantomNet. The novelty is the generality obtained in this context. Namely, we can deal with multiple users, multiple antennas, and multiple cells on both the uplink and the downlink. The solution for the uplink is effectively the same as for a single cell system since all the base stations (BSs simply amount to one composite BS with centralized processing. The optimum strategy, following directly from known results, is successive decoding (SD, where the new user is decoded before the existing users so that the new users' signal can be subtracted out to meet its invisibility requirement. Only the BS needs to modify its decoding scheme in the handling of new users, since existing users continue to transmit their data exactly as they did before the new arrivals. The downlink, even with the BSs operating as one composite BS, is more problematic. With multiple antennas at each BS site, the optimal coding scheme and the capacity region for this channel are unsolved problems. SD and dirty paper (DP are two schemes previously reported to achieve capacity in special cases. For PhantomNet, we show that DP coding at the BS is equal to or better than SD. The new user is encoded before the existing users so that the interference caused by his signal to existing users is known to the transmitter. Thus the BS modifies its encoding scheme to accommodate new users so that existing users continue to operate as before: they achieve the same rates as before and they decode their signal in precisely the same way as before. The solutions for the uplink and the downlink are particularly interesting in the way they exhibit a

  13. An Evo-Devo Perspective on Multicellular Development of Myxobacteria.

    Science.gov (United States)

    Arias Del Angel, Juan A; Escalante, Ana E; Martínez-Castilla, León Patricio; Benítez, Mariana

    2017-01-01

    The transition to multicellularity, recognized as one the major transitions in evolution, has occurred independently several times. While multicellular development has been extensively studied in zygotic organisms including plant and animal groups, just a few aggregative multicellular organisms have been employed as model organisms for the study of multicellularity. Studying different evolutionary origins and modes of multicellularity enables comparative analyses that can help identifying lineage-specific aspects of multicellular evolution and generic factors and mechanisms involved in the transition to multicellularity. Among aggregative multicellular organisms, myxobacteria are a valuable system to explore the particularities that aggregation confers to the evolution of multicellularity and mechanisms shared with clonal organisms. Moreover, myxobacteria species develop fruiting bodies displaying a range of morphological diversity. In this review, we aim to synthesize diverse lines of evidence regarding myxobacteria development and discuss them in the context of Evo-Devo concepts and approaches. First, we briefly describe the developmental processes in myxobacteria, present an updated comparative analysis of the genes involved in their developmental processes and discuss these and other lines of evidence in terms of co-option and developmental system drift, two concepts key to Evo-Devo studies. Next, as has been suggested from Evo-Devo approaches, we discuss how broad comparative studies and integration of diverse genetic, physicochemical, and environmental factors into experimental and theoretical models can further our understanding of myxobacterial development, phenotypic variation, and evolution. © 2017 Wiley Periodicals, Inc.

  14. A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids

    Energy Technology Data Exchange (ETDEWEB)

    Kaufman, N.; Bicher, H.I.; Hetzel, F.W.; Brown, M.

    1981-01-01

    We have characterized some of the physiology of multicellular spheroids of different sizes grown from Chinese hamster lung fibroblast (V79) cells. Among the parameters studied were oxygen tension distributions within the spheroid. This was achieved using ultramicroelectrodes with tip diameters of 1-5 mu and a perfusion system whereby environmental conditions such as flow, temperature, and chemical makeup of the milieu could be measured and controlled. Plateau pO/sup 2/ values of less than 10 mm Hg were consistently obtained from spheroids under various conditions. We were able to modify these distributions by use of indirect radiation sensitizer drugs such as mechlorethamine HCl (mustargen) at nontoxic doses. We have also made determinations of the inhibitory capacities of several other drugs on the respiration rate of constituent cells of multicellular spheroids in single-cell suspensions. We have concluded that there are indeed hypoxic cells in spheroids whose radioresistance may be modified by essentially nontoxic levels of indirect radiosensitizer drugs and that the system described shows great promise for screening agents which may modify radiation response.

  15. Growth of Entamoeba invadens in sediments with metabolically repressed bacteria leads to multicellularity and redefinition of the amoebic cell system.

    Science.gov (United States)

    Niculescu, Vladimir F

    2013-01-01

    Extracellular signaling and mechanisms of cell differentiation in Entamoeba are misunderstood. The main reason is the popular use of axenic media, which do not correspond to the natural habitats of Entamoeba. The axenic environment lacks the exogenous activators and repressors provided by natural habitats. Absent bacterial commensals understanding of the development of the amoebic cell system remains deficient. The present Aa(Sm) culture method using mixed sediments of antibiotically repressed Aerobacter aerogens and amoebae was developed to model in vitro extracellular signaling that induce multicellularity in cultures of E. invadens. Repressed oxygen consuming sediment bacteria supply E. invadens the hypoxic environment needed for differentiation and development. The amoebae themselves alter the environment by consuming the bacteria by phagocytosis thus reversing hypoxia. Exogenous activators are in this manner down regulated and suppressed. This feedback effect controls amoebic development and differentiation. Co-existing cell types and cell fractions with different life spans and cell cycle length could be identified. Aa(Sm) long term cultures contain continuous and non-continuous self renewing cell lines producing quiescent and terminally differentiated daughter cells (precysts) by asymmetric division. This culturing method helps to understand the intimate relationship between hypoxic environments and the multicellular behaviour of E. invadens and the interrelations existing between the distinct cell types.

  16. Collective chemotaxis through noisy multicellular gradient sensing

    CERN Document Server

    Varennes, Julien; Mugler, Andrew

    2016-01-01

    Collective cell migration in response to a chemical cue occurs in many biological processes such as morphogenesis and cancer metastasis. Clusters of migratory cells in these systems are capable of responding to gradients of less than 1% difference in chemical concentration across a cell length. Multicellular systems are extremely sensitive to their environment and while the limits to multicellular sensing are becoming known, how this information leads to coherent migration remains poorly understood. We develop a computational model of multicellular sensing and migration in which groups of cells collectively measure noisy chemical gradients. The output of the sensing process is coupled to individual cells polarization to model migratory behavior. Through the use of numerical simulations, we find that larger clusters of cells detect the gradient direction with higher precision and thus achieve stronger polarization bias, but larger clusters also induce more drag on collective motion. The trade-off between these...

  17. Realistic multi-cellular dosimetry for (177)Lu-labelled antibodies: model and application.

    Science.gov (United States)

    Marcatili, S; Pichard, A; Courteau, A; Ladjohounlou, R; Navarro-Teulon, I; Repetto-Llamazares, A; Heyerdahl, H; Dahle, J; Pouget, J P; Bardiès, M

    2016-10-07

    Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin(®), a novel (177)Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of (177)Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

  18. Realistic multi-cellular dosimetry for 177Lu-labelled antibodies: model and application

    Science.gov (United States)

    Marcatili, S.; Pichard, A.; Courteau, A.; Ladjohounlou, R.; Navarro-Teulon, I.; Repetto-Llamazares, A.; Heyerdahl, H.; Dahle, J.; Pouget, J. P.; Bardiès, M.

    2016-10-01

    Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin®, a novel 177Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of 177Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

  19. Designing a multicellular organotypic 3D liver model with a detachable, nanoscale polymeric Space of Disse.

    Science.gov (United States)

    Larkin, Adam L; Rodrigues, Richard R; Murali, T M; Rajagopalan, Padmavathy

    2013-11-01

    The design of in vitro models that mimic the stratified multicellular hepatic microenvironment continues to be challenging. Although several in vitro hepatic cultures have been shown to exhibit liver functions, their physiological relevance is limited due to significant deviation from in vivo cellular composition. We report the assembly of a novel three-dimensional (3D) organotypic liver model incorporating three different cell types (hepatocytes, liver sinusoidal endothelial cells, and Kupffer cells) and a polymeric interface that mimics the Space of Disse. The nanoscale interface is detachable, optically transparent, derived from self-assembled polyelectrolyte multilayers, and exhibits a Young's modulus similar to in vivo values for liver tissue. Only the 3D liver models simultaneously maintain hepatic phenotype and elicit proliferation, while achieving cellular ratios found in vivo. The nanoscale detachable polymeric interfaces can be modulated to mimic basement membranes that exhibit a wide range of physical properties. This facile approach offers a versatile new avenue in the assembly of engineered tissues. These results demonstrate the ability of the tri-cellular 3D cultures to serve as an organotypic hepatic model that elicits proliferation and maintenance of phenotype and in vivo-like cellular ratios.

  20. Integrative multicellular biological modeling: a case study of 3D epidermal development using GPU algorithms

    Directory of Open Access Journals (Sweden)

    Christley Scott

    2010-08-01

    Full Text Available Abstract Background Simulation of sophisticated biological models requires considerable computational power. These models typically integrate together numerous biological phenomena such as spatially-explicit heterogeneous cells, cell-cell interactions, cell-environment interactions and intracellular gene networks. The recent advent of programming for graphical processing units (GPU opens up the possibility of developing more integrative, detailed and predictive biological models while at the same time decreasing the computational cost to simulate those models. Results We construct a 3D model of epidermal development and provide a set of GPU algorithms that executes significantly faster than sequential central processing unit (CPU code. We provide a parallel implementation of the subcellular element method for individual cells residing in a lattice-free spatial environment. Each cell in our epidermal model includes an internal gene network, which integrates cellular interaction of Notch signaling together with environmental interaction of basement membrane adhesion, to specify cellular state and behaviors such as growth and division. We take a pedagogical approach to describing how modeling methods are efficiently implemented on the GPU including memory layout of data structures and functional decomposition. We discuss various programmatic issues and provide a set of design guidelines for GPU programming that are instructive to avoid common pitfalls as well as to extract performance from the GPU architecture. Conclusions We demonstrate that GPU algorithms represent a significant technological advance for the simulation of complex biological models. We further demonstrate with our epidermal model that the integration of multiple complex modeling methods for heterogeneous multicellular biological processes is both feasible and computationally tractable using this new technology. We hope that the provided algorithms and source code will be a

  1. Multicellular Tumor Spheroids as a Model for Assessing Delivery of Oligonucleotides in Three Dimensions

    Science.gov (United States)

    Carver, Kyle; Ming, Xin; Juliano, Rudolph L

    2014-01-01

    Oligonucleotides have shown promise in selectively manipulating gene expression in vitro, but that success has not translated to the clinic for cancer therapy. A potential reason for this is that cells behave differently in monolayer than in the three-dimensional tumor, resulting in limited penetration and distribution of oligonucleotides in the tumor. This may be especially true when oligonucleotides are associated with nanocarriers such as lipoplexes and polyplexes, commonly used delivery vehicles for oligonucleotides. The multicellular tumor spheroid (MCTS), a three-dimensional model that closely resembles small avascular tumors and micrometastases, has been utilized as an intermediate between monolayer culture and in vivo studies for the screening of small-molecule drugs. However, spheroids have been little used for the study of various oligonucleotide delivery formulations. Here, we have evaluated the uptake and efficacy of splice-switching antisense oligonucleotides using various delivery modalities in two- and three-dimensional culture models. We find that the size of the delivery agent dramatically influences penetration into the spheroid and thus the biological effect of the oligonucleotides. We hypothesize that the MCTS model will prove to be a useful tool in the future development of oligonucleotide delivery formulations. PMID:24618852

  2. Encapsulated multicellular tumor spheroids as a novel in vitro model to study small size tumors

    Directory of Open Access Journals (Sweden)

    Markvicheva Elena

    2003-01-01

    Full Text Available Presently multicellular tumor spheroids (MTS are being widely used in various aspects of tumor biology, including studies in biology and photodynamic therapy. The cellular organization of spheroids allows the recreation of in vivo small tumors much better than all common two-dimensional in vitro models. The cell encapsulation method could be proposed as a novel technique to quickly and easily prepare a large number of spheroids with narrow size distribution within a desirable diameter range. Moreover, the proposed technique for spheroid generation using encapsulated growing tumor cells could provide entirely new avenues to develop a novel spheroid co-culture model (for instance, the in vitro co-cultvation of tumor cells and monocytes, or epithelial cells, or fibroblasts etc. The current research was aimed at developing a simple and reliable method to encapsulate tumor cells and to cultivate them in vitro. In order to generate spheroids, MCF-7 cells were encapsulated and cultivated in 200 ml T-flasks in a 5% CO2 atmosphere at 37°C for 4-5 weeks. The cell proliferation was easily observed using a light microscope. The cells grew in aggregates increasing in size with time. The cell growth resulted in the formation of large cell clusters (spheroids which filled the whole microcapsule volume in 4-5 weeks.

  3. Generation model of positional values as cell operation during the development of multicellular organisms.

    Science.gov (United States)

    Ogawa, Ken-ichiro; Miyake, Yoshihiro

    2011-03-01

    Many conventional models have used the positional information hypothesis to explain each elementary process of morphogenesis during the development of multicellular organisms. Their models assume that the steady concentration patterns of morphogens formed in an extracellular environment have an important property of positional information, so-called "robustness". However, recent experiments reported that a steady morphogen pattern, the concentration gradient of the Bicoid protein, during early Drosophila embryonic development is not robust for embryo-to-embryo variability. These reports encourage a reconsideration of a long-standing problem in systematic cell differentiation: what is the entity of positional information for cells? And, what is the origin of the robust boundary of gene expression? To address these problems at a cellular level, in this article we pay attention to the re-generative phenomena that show another important property of positional information, "size invariance". In view of regenerative phenomena, we propose a new mathematical model to describe the generation mechanism of a spatial pattern of positional values. In this model, the positional values are defined as the values into which differentiable cells transform a spatial pattern providing positional information. The model is mathematically described as an associative algebra composed of various terms, each of which is the multiplication of some fundamental operators under the assumption that the operators are derived from the remarkable properties of cell differentiation on an amputation surface in regenerative phenomena. We apply this model to the concentration pattern of the Bicoid protein during the anterior-posterior axis formation in Drosophila, and consider the conditions needed to establish the robust boundary of the expression of the hunchback gene.

  4. The interplay between genetic and bioelectrical signaling permits a spatial regionalisation of membrane potentials in model multicellular ensembles.

    Science.gov (United States)

    Cervera, Javier; Meseguer, Salvador; Mafe, Salvador

    2016-10-12

    The single cell-centred approach emphasises ion channels as specific proteins that determine individual properties, disregarding their contribution to multicellular outcomes. We simulate the interplay between genetic and bioelectrical signals in non-excitable cells from the local single-cell level to the long range multicellular ensemble. The single-cell genetic regulation is based on mean-field kinetic equations involving the mRNA and protein concentrations. The transcription rate factor is assumed to depend on the absolute value of the cell potential, which is dictated by the voltage-gated cell ion channels and the intercellular gap junctions. The interplay between genetic and electrical signals may allow translating single-cell states into multicellular states which provide spatio-temporal information. The model results have clear implications for biological processes: (i) bioelectric signals can override slightly different genetic pre-patterns; (ii) ensembles of cells initially at the same potential can undergo an electrical regionalisation because of persistent genetic differences between adjacent spatial regions; and (iii) shifts in the normal cell electrical balance could trigger significant changes in the genetic regulation.

  5. Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian-Zheng, E-mail: wppzheng@126.com [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Zhu, Yu-Xia [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang [Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Meng, Yue-Zhong [State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou 510275 (China)

    2016-05-01

    In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose–lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. - Highlights: • Chitosan/collagen/alginate (CCA) scaffolds were fabricated by spray-spinning. • MCF-7 cells presented a multi-cellular tumor spheroid model (MCTS) in CCA scaffold. • MCTS in CCA possessed a more conservative phenotype of tumor than monolayer cells. • Anticancer drug screening in MCTS-CCA system is superior to 2D culture system.

  6. Cell models lead to understanding of multi-cellular morphogenesis consisting of successive self-construction of cells.

    Science.gov (United States)

    Honda, Hisao; Nagai, Tatsuzo

    2015-03-01

    Morphogenesis of multi-cellular organisms occurs through cell behaviours within a cell aggregate. Cell behaviours have been described using cell models involving equations of motion for cells. Cells in cell models construct shapes of the cell aggregate by themselves. Here, a history of cell models, the cell centre model and the vertex cell model, which we have constructed, are described. Furthermore, the application of these cell models is explained in detail. These cell models have been applied to transformation of cell aggregates to become spherical, formation of mammalian blastocysts and cell intercalation in elongating tissues. These are all elemental processes of morphogenesis and take place in succession during the whole developmental process. A chain of successive elemental processes leads to morphogenesis. Finally, we highlight that cell models are indispensable to understand the process whereby genes direct biological shapes.

  7. Overview: membrane traffic in multicellular systems: more than just a housekeeper.

    Science.gov (United States)

    Ohno, Hiroshi

    2006-06-01

    Membrane traffic is a fundamental cellular function by which molecules are transported between organelles in the post-Golgi network. Accumulating evidence supports the notion that membrane traffic is not only indispensable for normal cellular function and maintenance of cellular viability by playing housekeeping roles, but also critical for various functions characteristic of multicellular organisms. This Minireview series will focus on the latter aspects of membrane traffic. The topics discussed are: the pathophysiological impact of clathrin-associated adaptor protein (AP) complexes, the significance of membrane traffic in Alzheimer's disease, regulated exocytosis of insulin, secretory lysosomes in immune response, exosomes in physiology and pathology, viral and mammalian ubiquitin ligases modulating immune response, membrane traffic of bacterial toxins, and containment of bacterial infection by autophagy.

  8. NADPH oxidase: an enzyme for multicellularity?

    Science.gov (United States)

    Lalucque, Hervé; Silar, Philippe

    2003-01-01

    Multicellularity has evolved several times during the evolution of eukaryotes. One evolutionary pressure that permits multicellularity relates to the division of work, where one group of cells functions as nutrient providers and the other in specialized roles such as defence or reproduction. This requires signalling systems to ensure harmonious development of multicellular structures. Here, we show that NADPH oxidases are specifically present in organisms that differentiate multicellular structures during their life cycle and are absent from unicellular life forms. The biochemical properties of these enzymes make them ideal candidates for a role in intercellular signalling.

  9. A novel cell traction force microscopy to study multi-cellular system.

    Directory of Open Access Journals (Sweden)

    Xin Tang

    2014-06-01

    Full Text Available Traction forces exerted by adherent cells on their microenvironment can mediate many critical cellular functions. Accurate quantification of these forces is essential for mechanistic understanding of mechanotransduction. However, most existing methods of quantifying cellular forces are limited to single cells in isolation, whereas most physiological processes are inherently multi-cellular in nature where cell-cell and cell-microenvironment interactions determine the emergent properties of cell clusters. In the present study, a robust finite-element-method-based cell traction force microscopy technique is developed to estimate the traction forces produced by multiple isolated cells as well as cell clusters on soft substrates. The method accounts for the finite thickness of the substrate. Hence, cell cluster size can be larger than substrate thickness. The method allows computing the traction field from the substrate displacements within the cells' and clusters' boundaries. The displacement data outside these boundaries are not necessary. The utility of the method is demonstrated by computing the traction generated by multiple monkey kidney fibroblasts (MKF and human colon cancerous (HCT-8 cells in close proximity, as well as by large clusters. It is found that cells act as individual contractile groups within clusters for generating traction. There may be multiple of such groups in the cluster, or the entire cluster may behave a single group. Individual cells do not form dipoles, but serve as a conduit of force (transmission lines over long distances in the cluster. The cell-cell force can be either tensile or compressive depending on the cell-microenvironment interactions.

  10. A novel cell traction force microscopy to study multi-cellular system.

    Science.gov (United States)

    Tang, Xin; Tofangchi, Alireza; Anand, Sandeep V; Saif, Taher A

    2014-06-01

    Traction forces exerted by adherent cells on their microenvironment can mediate many critical cellular functions. Accurate quantification of these forces is essential for mechanistic understanding of mechanotransduction. However, most existing methods of quantifying cellular forces are limited to single cells in isolation, whereas most physiological processes are inherently multi-cellular in nature where cell-cell and cell-microenvironment interactions determine the emergent properties of cell clusters. In the present study, a robust finite-element-method-based cell traction force microscopy technique is developed to estimate the traction forces produced by multiple isolated cells as well as cell clusters on soft substrates. The method accounts for the finite thickness of the substrate. Hence, cell cluster size can be larger than substrate thickness. The method allows computing the traction field from the substrate displacements within the cells' and clusters' boundaries. The displacement data outside these boundaries are not necessary. The utility of the method is demonstrated by computing the traction generated by multiple monkey kidney fibroblasts (MKF) and human colon cancerous (HCT-8) cells in close proximity, as well as by large clusters. It is found that cells act as individual contractile groups within clusters for generating traction. There may be multiple of such groups in the cluster, or the entire cluster may behave a single group. Individual cells do not form dipoles, but serve as a conduit of force (transmission lines) over long distances in the cluster. The cell-cell force can be either tensile or compressive depending on the cell-microenvironment interactions.

  11. A stochastic multicellular model identifies biological watermarks from disorders in self-organized patterns of phyllotaxis

    Science.gov (United States)

    Refahi, Yassin; Brunoud, Géraldine; Farcot, Etienne; Jean-Marie, Alain; Pulkkinen, Minna; Vernoux, Teva; Godin, Christophe

    2016-01-01

    Exploration of developmental mechanisms classically relies on analysis of pattern regularities. Whether disorders induced by biological noise may carry information on building principles of developmental systems is an important debated question. Here, we addressed theoretically this question using phyllotaxis, the geometric arrangement of plant aerial organs, as a model system. Phyllotaxis arises from reiterative organogenesis driven by lateral inhibitions at the shoot apex. Motivated by recurrent observations of disorders in phyllotaxis patterns, we revisited in depth the classical deterministic view of phyllotaxis. We developed a stochastic model of primordia initiation at the shoot apex, integrating locality and stochasticity in the patterning system. This stochastic model recapitulates phyllotactic patterns, both regular and irregular, and makes quantitative predictions on the nature of disorders arising from noise. We further show that disorders in phyllotaxis instruct us on the parameters governing phyllotaxis dynamics, thus that disorders can reveal biological watermarks of developmental systems. DOI: http://dx.doi.org/10.7554/eLife.14093.001 PMID:27380805

  12. Stabilizing multicellularity through ratcheting

    Science.gov (United States)

    Libby, Eric; Conlin, Peter L.; Kerr, Ben; Ratcliff, William C.

    2016-01-01

    The evolutionary transition to multicellularity probably began with the formation of simple undifferentiated cellular groups. Such groups evolve readily in diverse lineages of extant unicellular taxa, suggesting that there are few genetic barriers to this first key step. This may act as a double-edged sword: labile transitions between unicellular and multicellular states may facilitate the evolution of simple multicellularity, but reversion to a unicellular state may inhibit the evolution of increased complexity. In this paper, we examine how multicellular adaptations can act as evolutionary ‘ratchets’, limiting the potential for reversion to unicellularity. We consider a nascent multicellular lineage growing in an environment that varies between favouring multicellularity and favouring unicellularity. The first type of ratcheting mutations increase cell-level fitness in a multicellular context but are costly in a single-celled context, reducing the fitness of revertants. The second type of ratcheting mutations directly decrease the probability that a mutation will result in reversion (either as a pleiotropic consequence or via direct modification of switch rates). We show that both types of ratcheting mutations act to stabilize the multicellular state. We also identify synergistic effects between the two types of ratcheting mutations in which the presence of one creates the selective conditions favouring the other. Ratcheting mutations may play a key role in diverse evolutionary transitions in individuality, sustaining selection on the new higher-level organism by constraining evolutionary reversion. This article is part of the themed issue ‘The major synthetic evolutionary transitions’. PMID:27431522

  13. Composition and abstraction of logical regulatory modules: application to multicellular systems.

    Science.gov (United States)

    Mendes, Nuno D; Lang, Frédéric; Le Cornec, Yves-Stan; Mateescu, Radu; Batt, Gregory; Chaouiya, Claudine

    2013-03-15

    Logical (Boolean or multi-valued) modelling is widely used to study regulatory or signalling networks. Even though these discrete models constitute a coarse, yet useful, abstraction of reality, the analysis of large networks faces a classical combinatorial problem. Here, we propose to take advantage of the intrinsic modularity of inter-cellular networks to set up a compositional procedure that enables a significant reduction of the dynamics, yet preserving the reachability of stable states. To that end, we rely on process algebras, a well-established computational technique for the specification and verification of interacting systems. We develop a novel compositional approach to support the logical modelling of interconnected cellular networks. First, we formalize the concept of logical regulatory modules and their composition. Then, we make this framework operational by transposing the composition of logical modules into a process algebra framework. Importantly, the combination of incremental composition, abstraction and minimization using an appropriate equivalence relation (here the safety equivalence) yields huge reductions of the dynamics. We illustrate the potential of this approach with two case-studies: the Segment-Polarity and the Delta-Notch modules.

  14. 3D pulmospheres serve as a personalized and predictive multicellular model for assessment of antifibrotic drugs

    Science.gov (United States)

    Surolia, Ranu; Li, Fu Jun; Wang, Zheng; Li, Huashi; Liu, Gang; Zhou, Yong; Luckhardt, Tracy; Bae, Sejong; Liu, Rui-ming; de Andrade, Joao; Thannickal, Victor J.; Antony, Veena B.

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fatal progressive fibrotic lung disease characterized by the presence of invasive myofibroblasts in the lung. Currently, there are only two FDA-approved drugs (pirfenidone and nintedanib) for the treatment of IPF. There are no defined criteria to guide specific drug therapy. New methodologies are needed not only to predict personalized drug therapy, but also to screen novel molecules that are on the horizon for treatment of IPF. We have developed a model system that exploits the invasive phenotype of IPF lung tissue. This ex vivo 3D model uses lung tissue from patients to develop pulmospheres. Pulmospheres are 3D spheroids composed of cells derived exclusively from primary lung biopsies and inclusive of lung cell types reflective of those in situ, in the patient. We tested the pulmospheres of 20 subjects with IPF and 9 control subjects to evaluate the responsiveness of individual patients to antifibrotic drugs. Clinical parameters and outcomes were also followed in the same patients. Our results suggest that pulmospheres simulate the microenvironment in the lung and serve as a personalized and predictive model for assessing responsiveness to antifibrotic drugs in patients with IPF. PMID:28138565

  15. Multi-cellular logistics of collective cell migration.

    Directory of Open Access Journals (Sweden)

    Masataka Yamao

    Full Text Available During development, the formation of biological networks (such as organs and neuronal networks is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes "collective migration," whereas strong noise from non-migratory cells causes "dispersive migration." Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems.

  16. A BABCOCK–LEIGHTON SOLAR DYNAMO MODEL WITH MULTI-CELLULAR MERIDIONAL CIRCULATION IN ADVECTION- AND DIFFUSION-DOMINATED REGIMES

    Energy Technology Data Exchange (ETDEWEB)

    Belucz, Bernadett; Forgács-Dajka, Emese [Eötvös University, Department of Astronomy, 1518 Budapest, Pf. 32 (Hungary); Dikpati, Mausumi, E-mail: bbelucz@astro.elte.hu, E-mail: dikpati@ucar.edu [High Altitude Observatory, National Center for Atmospheric Research, 3080 Center Green, Boulder, CO 80307-3000 (United States)

    2015-06-20

    Babcock–Leighton type-solar dynamo models with single-celled meridional circulation are successful in reproducing many solar cycle features. Recent observations and theoretical models of meridional circulation do not indicate a single-celled flow pattern. We examine the role of complex multi-cellular circulation patterns in a Babcock–Leighton solar dynamo in advection- and diffusion-dominated regimes. We show from simulations that the presence of a weak, second, high-latitude reverse cell speeds up the cycle and slightly enhances the poleward branch in the butterfly diagram, whereas the presence of a second cell in depth reverses the tilt of the butterfly wing to an antisolar type. A butterfly diagram constructed from the middle of convection zone yields a solar-like pattern, but this may be difficult to realize in the Sun because of magnetic buoyancy effects. Each of the above cases behaves similarly in higher and lower magnetic diffusivity regimes. However, our dynamo with a meridional circulation containing four cells in latitude behaves distinctly differently in the two regimes, producing solar-like butterfly diagrams with fast cycles in the higher diffusivity regime, and complex branches in butterfly diagrams in the lower diffusivity regime. We also find that dynamo solutions for a four-celled pattern, two in radius and two in latitude, prefer to quickly relax to quadrupolar parity if the bottom flow speed is strong enough, of similar order of magnitude as the surface flow speed.

  17. A Babcock-Leighton solar dynamo model with multi-cellular meridional circulation in advection- and diffusion-dominated regimes

    CERN Document Server

    Belucz, Bernadett; Forgacs-Dajka, Emese

    2015-01-01

    Babcock-Leighton type solar dynamo models with single-celled meridional circulation are successful in reproducing many solar cycle features. Recent observations and theoretical models of meridional circulation do not indicate a single-celled flow pattern. We examine the role of complex multi-cellular circulation patterns in a Babcock-Leighton solar dynamo in advection- and diffusion-dominated regimes. We show from simulations that presence of a weak, second, high-latitude reverse cell speeds up the cycle and slightly enhances the poleward branch in butterfly diagram, whereas the presence of a second cell in depth reverses the tilt of butterfly wing to an anti-solar type. A butterfly diagram constructed from middle of convection zone yields a solar-like pattern, but this may be difficult to realize in the Sun because of magnetic buoyancy effects. Each of the above cases behaves similarly in higher and lower magnetic diffusivity regimes. However, our dynamo with a meridional circulation containing four cells in...

  18. Construction of 3D multicellular microfluidic chip for an in vitro skin model.

    Science.gov (United States)

    Lee, Sojin; Jin, Seon-Pil; Kim, Yeon Kyung; Sung, Gun Yong; Chung, Jin Ho; Sung, Jong Hwan

    2017-06-01

    Current in vitro skin models do not recapitulate the complex architecture and functions of the skin tissue. In particular, on-chip construction of an in vitro model comprising the epidermis and dermis layer with vascular structure for mass transport has not been reported yet. In this study, we aim to develop a microfluidic, three-dimensional (3D) skin chip with fluidic channels using PDMS and hydrogels. Mass transport within the collagen hydrogel matrix was verified with fluorescent model molecules, and a transport-reaction model of oxygen and glucose inside the skin chip was developed to aid the design of the microfluidic skin chip. Comparison of viabilities of dermal fibroblasts and HaCaT cultured in the chip with various culture conditions revealed that the presence of flow plays a crucial role in maintaining the viability, and both cells were viable after 10 days of air exposure culture. Our 3D skin chip with vascular structures can be a valuable in vitro model for reproducing the interaction between different components of the skin tissue, and thus work as a more physiologically realistic platform for testing skin reaction to cosmetic products and drugs.

  19. The organotypic multicellular spheroid is a relevant three-dimensional model to study adenovirus replication and penetration in human tumors in vitro.

    Science.gov (United States)

    Grill, Jacques; Lamfers, Martine L M; van Beusechem, Victor W; Dirven, Clemens M; Pherai, D Shareen; Kater, Mathijs; Van der Valk, Paul; Vogels, Ronald; Vandertop, W Peter; Pinedo, Herbert M; Curiel, David T; Gerritsen, Winald R

    2002-11-01

    The use of adenoviruses for gene transfer and as oncolytic agents is currently receiving widespread attention. As specific constraints to adenovirus distribution and spread cannot be studied in cell cultures, there is a need for an in vitro three-dimensional (3D) model mimicking the in vivo biology of tumors. We studied the interactions between tumor and adenoviruses using multicellular spheroids grown from primary brain tumor material. Using beta-galactosidase and luciferase reporter genes expressed by replication-defective adenoviruses, we showed that infection was restricted to the first layer of cells. Using a replication-competent adenovirus expressing the luciferase gene, we showed that transgene expression in the spheroid was considerably enhanced and that viral spreading deep into the 3D structure took place. In addition, a tetrazolium salt-based metabolic assay could be used to compare the oncolytic activity of different concentrations of replication-competent adenoviruses. We can conclude that organotypic spheroids offer a versatile in vitro system for studying distribution, spread, and oncolysis by adenoviruses in a clinically relevant model.

  20. Semiotic scaffolding of multicellularity

    DEFF Research Database (Denmark)

    Hoffmeyer, Jesper

    2015-01-01

    semiotic scaffoldings had to be invented in order to prevent this. While a unicellular self may go on to live practically forever, the multicellular self most often must run through an individuation process ending in the death of the individual. Due to basic differences in cells of plants, fungi...... of fertilization and thereby the need for a whole new set of elaborate semiotic scaffoldings. Multicellularity also opened the door to the formation symbiotic relations where cells with different genomes might collaborate or at least coexist inside the same body. All in all multicellularity led to an enormous...... diversification both of morphology space and the space of sensomotoric elaborations. New means for scaffolding of this expansion and diversification of possible life forms into functional patterns called for a corresponding growth in the space of semiotic tools (chemical processes, heat, light, sound, volatile...

  1. A pilot-scale floating closed culture system for the multicellular cyanobacterium Arthrospira platensis NIES-39.

    Science.gov (United States)

    Toyoshima, Masakazu; Aikawa, Shimpei; Yamagishi, Takahiro; Kondo, Akihiko; Kawai, Hiroshi

    Microalgae are considered to be efficient bio-resources for biofuels and bio-based chemicals because they generally have high productivity. The filamentous cyanobacterium Arthrospira (Spirulina) platensis has been widely used for food, feed, and nutrient supplements and is usually cultivated in open ponds. In order to extend the surface area for growing this alga, we designed a pilot-scale floating closed culture system for cultivating A. platensis on open water and compared the growth and quality of the alga harvested at both subtropical and temperate regions. The biomass productivity of A. platensis NIES-39 was ca. 9 g dry biomass m(-2) day(-1) in summer at Awaji Island (warm temperature region) and ca. 10 and 6 g dry biomass m(-2) day(-1) in autumn and winter, respectively, at Ishigaki Island, (subtropical region) in Japan. If seawater can be used for culture media, culture cost can be reduced; therefore, we examined the influence of seawater salt concentrations on the growth of A. platensis NIES-39. Growth rates of A. platensis NIES-39 in diluted seawater with enrichment of 2.5 g L(-1) NaNO3, 0.01 g L(-1) FeSO4·7H2O, and 0.08 g L(-1) Na2EDTA were considerably lower than SOT medium, but the biomass productivity (dry weight) was comparable to SOT medium. This is explained by the heavier cell weight of the alga grown in modified seawater media compared to the alga grown in SOT medium. Furthermore, A. platensis grown in modified seawater-based medium exhibited self-flocculation and had more loosely coiled trichomes.

  2. The simplest integrated multicellular organism unveiled.

    Directory of Open Access Journals (Sweden)

    Yoko Arakaki

    Full Text Available Volvocine green algae represent the "evolutionary time machine" model lineage for studying multicellularity, because they encompass the whole range of evolutionary transition of multicellularity from unicellular Chlamydomonas to >500-celled Volvox. Multicellular volvocalean species including Gonium pectorale and Volvox carteri generally have several common morphological features to survive as integrated multicellular organisms such as "rotational asymmetry of cells" so that the cells become components of the individual and "cytoplasmic bridges between protoplasts in developing embryos" to maintain the species-specific form of the multicellular individual before secretion of new extracellular matrix (ECM. However, these morphological features have not been studied in the four-celled colonial volvocine species Tetrabaena socialis that is positioned in the most basal lineage within the colonial or multicellular volvocine greens. Here we established synchronous cultures of T. socialis and carried out immunofluorescence microscopic and ultrastructural observations to elucidate these two morphological attributes. Based on immunofluorescence microscopy, four cells of the mature T. socialis colony were identical in morphology but had rotational asymmetry in arrangement of microtubular rootlets and separation of basal bodies like G. pectorale and V. carteri. Ultrastructural observations clearly confirmed the presence of cytoplasmic bridges between protoplasts in developing embryos of T. socialis even after the formation of new flagella in each daughter protoplast within the parental ECM. Therefore, these two morphological attributes might have evolved in the common four-celled ancestor of the colonial volvocine algae and contributed to the further increase in cell number and complexity of the multicellular individuals of this model lineage. T. socialis is one of the simplest integrated multicellular organisms in which four identical cells constitute the

  3. A 3D self-organizing multicellular epidermis model of barrier formation and hydration with realistic cell morphology based on EPISIM

    Science.gov (United States)

    Sütterlin, Thomas; Tsingos, Erika; Bensaci, Jalil; Stamatas, Georgios N.; Grabe, Niels

    2017-01-01

    The epidermis and the stratum corneum (SC) as its outermost layer have evolved to protect the body from evaporative water loss to the environment. To morphologically represent the extremely flattened cells of the SC - and thereby the epidermal barrier - in a multicellular computational model, we developed a 3D biomechanical model (BM) based on ellipsoid cell shapes. We integrated the BM in the multicellular modelling and simulation platform EPISIM. We created a cell behavioural model (CBM) with EPISIM encompassing regulatory feedback loops between the epidermal barrier, water loss to the environment, and water and calcium flow within the tissue. This CBM allows a small number of stem cells to initiate self-organizing epidermal stratification, yielding the spontaneous emergence of water and calcium gradients comparable to experimental data. We find that the 3D in silico epidermis attains homeostasis most quickly at high ambient humidity, and once in homeostasis the epidermal barrier robustly buffers changes in humidity. Our model yields an in silico epidermis with a previously unattained realistic morphology, whose cell neighbour topology is validated with experimental data obtained from in vivo images. This work paves the way to computationally investigate how an impaired SC barrier precipitates disease. PMID:28262741

  4. Quantitative multivariate analysis of dynamic multicellular morphogenic trajectories.

    Science.gov (United States)

    White, Douglas E; Sylvester, Jonathan B; Levario, Thomas J; Lu, Hang; Streelman, J Todd; McDevitt, Todd C; Kemp, Melissa L

    2015-07-01

    Interrogating fundamental cell biology principles that govern tissue morphogenesis is critical to better understanding of developmental biology and engineering novel multicellular systems. Recently, functional micro-tissues derived from pluripotent embryonic stem cell (ESC) aggregates have provided novel platforms for experimental investigation; however elucidating the factors directing emergent spatial phenotypic patterns remains a significant challenge. Computational modelling techniques offer a unique complementary approach to probe mechanisms regulating morphogenic processes and provide a wealth of spatio-temporal data, but quantitative analysis of simulations and comparison to experimental data is extremely difficult. Quantitative descriptions of spatial phenomena across multiple systems and scales would enable unprecedented comparisons of computational simulations with experimental systems, thereby leveraging the inherent power of computational methods to interrogate the mechanisms governing emergent properties of multicellular biology. To address these challenges, we developed a portable pattern recognition pipeline consisting of: the conversion of cellular images into networks, extraction of novel features via network analysis, and generation of morphogenic trajectories. This novel methodology enabled the quantitative description of morphogenic pattern trajectories that could be compared across diverse systems: computational modelling of multicellular structures, differentiation of stem cell aggregates, and gastrulation of cichlid fish. Moreover, this method identified novel spatio-temporal features associated with different stages of embryo gastrulation, and elucidated a complex paracrine mechanism capable of explaining spatiotemporal pattern kinetic differences in ESC aggregates of different sizes.

  5. Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening.

    Science.gov (United States)

    Wang, Jian-Zheng; Zhu, Yu-Xia; Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang; Meng, Yue-Zhong

    2016-05-01

    In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose-lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system.

  6. Drosophila melanogaster--the model organism of choice for the complex biology of multi-cellular organisms

    Science.gov (United States)

    Beckingham, Kathleen M.; Armstrong, J. Douglas; Texada, Michael J.; Munjaal, Ravi; Baker, Dean A.

    2005-01-01

    Drosophila melanogaster has been intensely studied for almost 100 years. The sophisticated array of genetic and molecular tools that have evolved for analysis of gene function in this organism are unique. Further, Drosophila is a complex multi-cellular organism in which many aspects of development and behavior parallel those in human beings. These combined advantages have permitted research in Drosophila to make seminal contributions to the understanding of fundamental biological processes and ensure that Drosophila will continue to provide unique insights in the genomic era. An overview of the genetic methodologies available in Drosophila is given here, together with examples of outstanding recent contributions of Drosophila to our understanding of cell and organismal biology. The growing contribution of Drosophila to our knowledge of gravity-related responses is addressed.

  7. Drosophila melanogaster--the model organism of choice for the complex biology of multi-cellular organisms

    Science.gov (United States)

    Beckingham, Kathleen M.; Armstrong, J. Douglas; Texada, Michael J.; Munjaal, Ravi; Baker, Dean A.

    2005-01-01

    Drosophila melanogaster has been intensely studied for almost 100 years. The sophisticated array of genetic and molecular tools that have evolved for analysis of gene function in this organism are unique. Further, Drosophila is a complex multi-cellular organism in which many aspects of development and behavior parallel those in human beings. These combined advantages have permitted research in Drosophila to make seminal contributions to the understanding of fundamental biological processes and ensure that Drosophila will continue to provide unique insights in the genomic era. An overview of the genetic methodologies available in Drosophila is given here, together with examples of outstanding recent contributions of Drosophila to our understanding of cell and organismal biology. The growing contribution of Drosophila to our knowledge of gravity-related responses is addressed.

  8. Multicellular computing using conjugation for wiring.

    Science.gov (United States)

    Goñi-Moreno, Angel; Amos, Martyn; de la Cruz, Fernando

    2013-01-01

    Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal "re-programming" and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a "computation" is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the "wiring" between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing

  9. Photoluminescent carbon nanotubes interrogate the permeability of multicellular tumor spheroids

    Science.gov (United States)

    Shah, Janki; Roxbury, Daniel; Paknejad, Navid; Heller, Daniel A.

    2015-01-01

    Nanomaterials have been extensively investigated for cancer drug delivery and imaging applications. Nanoparticles that show promise in two-dimensional cell culture systems often fail in more complex environments, possibly due to the lack of penetration in dense, three-dimensional structures. Multicellular tumor spheroids are an emerging model system to investigate interactions of nanoparticles with 3D in vitro cell culture environments. Using the intrinsic near-infrared emission of semiconducting carbon nanotubes to optically reconstruct their localization within a three-dimensional volume, we resolved the relative permeability of two different multicellular tumor spheroids. Nanotube photoluminescence revealed that nanotubes rapidly internalized into MCF-7 breast cancer cell-derived spheroids, whereas they exhibited little penetration into spheroids derived from SK-136, a cell line that we developed from murine liver cancer. Characterization of the spheroids by electron microscopy and immunohistochemistry revealed large differences in the extracellular matrix and interstitial spacing, which correlated directly with nanotube penetration. This platform portends a new approach to characterize the permeability of living multicellular environments. PMID:26456974

  10. Combined exposure of diesel exhaust particles and respirable Soufrière Hills volcanic ash causes a (pro-)inflammatory response in an in vitro multicellular epithelial tissue barrier model

    Science.gov (United States)

    Tomašek, Ines; Horwell, Claire J.; Damby, David; Barošová, Hana; Geers, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara; Clift, Martin J. D.

    2016-01-01

    three cell types of the multicellular system was observed by SEM.ConclusionsCombined exposure of respirable Soufrière Hills VA with DEP causes a (pro-)inflammatory effect in an advanced in vitro multicellular model of the epithelial airway barrier. This finding suggests that the combined exposure to volcanic and urban particulate matter should be further investigated in order to deduce the potential human health hazard, especially how it may influence the respiratory function of susceptible individuals (i.e. with pre-existing lung diseases) in the population.

  11. Differential superiority of heavy charged-particle irradiation to x-rays: Studies on biological effectivenes and side effect mechanisms in multicellular tumor and normal tissue models

    Directory of Open Access Journals (Sweden)

    Stefan eWalenta

    2016-02-01

    Full Text Available This review is focused on the radiobiology of carbon ions compared to x-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review deals with radiation-induced cell migration and mucositis.Multicellular spheroids (MCS from V79 hamster cells were irradiated with x-rays or carbon ions under ambient or restricted oxygen supply conditions. Oxygen enhancement ratios (OER were 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. A relative biological effectiveness (RBE of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M, and a dose-dependent massive induction of apoptosis. Clinically relevant doses (3 Gy of x-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in 1 integrin expression. Unlike with particles, the photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor (EGFR and AKT-ERK1/2 pathway. Comparing the gene toxicity of x-rays with that of particles using the gamma-H2AX technique in organotypic cultures of the oral mucosa, the superior effectiveness of heavy ions was confirmed by a two-fold higher number of foci per nucleus. Pro-inflammatory signs, however, were similar for both treatment modalities, e. g., the activation of NFkappaB, and the release of IL

  12. Detecting tree-like multicellular life on extrasolar planets.

    Science.gov (United States)

    Doughty, Christopher E; Wolf, Adam

    2010-11-01

    Over the next two decades, NASA and ESA are planning a series of space-based observatories to find Earth-like planets and determine whether life exists on these planets. Previous studies have assessed the likelihood of detecting life through signs of biogenic gases in the atmosphere or a red edge. Biogenic gases and the red edge could be signs of either single-celled or multicellular life. In this study, we propose a technique with which to determine whether tree-like multicellular life exists on extrasolar planets. For multicellular photosynthetic organisms on Earth, competition for light and the need to transport water and nutrients has led to a tree-like body plan characterized by hierarchical branching networks. This design results in a distinct bidirectional reflectance distribution function (BRDF) that causes differing reflectance at different sun/view geometries. BRDF arises from the changing visibility of the shadows cast by objects, and the presence of tree-like structures is clearly distinguishable from flat ground with the same reflectance spectrum. We examined whether the BRDF could detect the existence of tree-like structures on an extrasolar planet by using changes in planetary albedo as a planet orbits its star. We used a semi-empirical BRDF model to simulate vegetation reflectance at different planetary phase angles and both simulated and real cloud cover to calculate disk and rotation-averaged planetary albedo for a vegetated and non-vegetated planet with abundant liquid water. We found that even if the entire planetary albedo were rendered to a single pixel, the rate of increase of albedo as a planet approaches full illumination would be comparatively greater on a vegetated planet than on a non-vegetated planet. Depending on how accurately planetary cloud cover can be resolved and the capabilities of the coronagraph to resolve exoplanets, this technique could theoretically detect tree-like multicellular life on exoplanets in 50 stellar systems.

  13. Communication theory and multicellular biology.

    Science.gov (United States)

    Mian, I S; Rose, C

    2011-04-01

    In this Perspective, we propose that communication theory--a field of mathematics concerned with the problems of signal transmission, reception and processing--provides a new quantitative lens for investigating multicellular biology, ancient and modern. What underpins the cohesive organisation and collective behaviour of multicellular ecosystems such as microbial colonies and communities (microbiomes) and multicellular organisms such as plants and animals, whether built of simple tissue layers (sponges) or of complex differentiated cells arranged in tissues and organs (members of the 35 or so phyla of the subkingdom Metazoa)? How do mammalian tissues and organs develop, maintain their architecture, become subverted in disease, and decline with age? How did single-celled organisms coalesce to produce many-celled forms that evolved and diversified into the varied multicellular organisms in existence today? Some answers can be found in the blueprints or recipes encoded in (epi)genomes, yet others lie in the generic physical properties of biological matter such as the ability of cell aggregates to attain a certain complexity in size, shape, and pattern. We suggest that Lasswell's maxim "Who says what to whom in what channel with what effect" provides a foundation for understanding not only the emergence and evolution of multicellularity, but also the assembly and sculpting of multicellular ecosystems and many-celled structures, whether of natural or human-engineered origin. We explore how the abstraction of communication theory as an organising principle for multicellular biology could be realised. We highlight the inherent ability of communication theory to be blind to molecular and/or genetic mechanisms. We describe selected applications that analyse the physics of communication and use energy efficiency as a central tenet. Whilst communication theory has and could contribute to understanding a myriad of problems in biology, investigations of multicellular biology

  14. Role of multicellular aggregates in biofilm formation

    DEFF Research Database (Denmark)

    Kragh, Kasper N.; Hutchison, Jaime B.; Melaugh, Gavin;

    2016-01-01

    response, may add to this ecological benefit. Our findings suggest that current models of biofilm formation should be reconsidered to incorporate the role of aggregates in biofilm initiation.IMPORTANCE During the past decades, there has been a consensus around the model of development of a biofilm......In traditional models of in vitro biofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However......, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process. This makes it likely that biofilms are often seeded by aggregates and single cells, yet how these aggregates impact biofilm...

  15. Epigenetics decouples mutational from environmental robustness. Did it also facilitate multicellularity?

    Directory of Open Access Journals (Sweden)

    Saurabh Gombar

    2014-03-01

    Full Text Available The evolution of ever increasing complex life forms has required innovations at the molecular level in order to overcome existing barriers. For example, evolving processes for cell differentiation, such as epigenetic mechanisms, facilitated the transition to multicellularity. At the same time, studies using gene regulatory network models, and corroborated in single-celled model organisms, have shown that mutational robustness and environmental robustness are correlated. Such correlation may constitute a barrier to the evolution of multicellularity since cell differentiation requires sensitivity to cues in the internal environment during development. To investigate how this barrier might be overcome, we used a gene regulatory network model which includes epigenetic control based on the mechanism of histone modification via Polycomb Group Proteins, which evolved in tandem with the transition to multicellularity. Incorporating the Polycomb mechanism allowed decoupling of mutational and environmental robustness, thus allowing the system to be simultaneously robust to mutations while increasing sensitivity to the environment. In turn, this decoupling facilitated cell differentiation which we tested by evaluating the capacity of the system for producing novel output states in response to altered initial conditions. In the absence of the Polycomb mechanism, the system was frequently incapable of adding new states, whereas with the Polycomb mechanism successful addition of new states was nearly certain. The Polycomb mechanism, which dynamically reshapes the network structure during development as a function of expression dynamics, decouples mutational and environmental robustness, thus providing a necessary step in the evolution of multicellularity.

  16. Simulating growth dynamics and radiation response of avascular tumour spheroids-model validation in the case of an EMT6/Ro multicellular spheroid.

    Science.gov (United States)

    Zacharaki, Evangelia I; Stamatakos, Georgios S; Nikita, Konstantina S; Uzunoglu, Nikolaos K

    2004-12-01

    The goal of this paper is to provide both the basic scientist and the clinician with an advanced computational tool for performing in silico experiments aiming at supporting the process of biological optimisation of radiation therapy. Improved understanding and description of malignant tumour dynamics is an additional intermediate objective. To this end an advanced three-dimensional (3D) Monte-Carlo simulation model of both the avascular development of multicellular tumour spheroids and their response to radiation therapy is presented. The model is based upon a number of fundamental biological principles such as the transition between the cell cycle phases, the diffusion of oxygen and nutrients and the cell survival probabilities following irradiation. Efficient algorithms describing tumour expansion and shrinkage are proposed and applied. The output of the biosimulation model is introduced into the (3D) visualisation package AVS-Express, which performs the visualisation of both the external surface and the internal structure of the dynamically evolving tumour based on volume or surface rendering techniques. Both the numerical stability and the statistical behaviour of the simulation model have been studied and evaluated for the case of EMT6/Ro spheroids. Predicted histological structure and tumour growth rates have been shown to be in agreement with published experimental data. Furthermore, the underlying structure of the tumour spheroid as well as its response to irradiation satisfactorily agrees with laboratory experience.

  17. Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models

    Science.gov (United States)

    Walenta, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during 12C+6 irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral mucosa, the

  18. Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models.

    Science.gov (United States)

    Walenta, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, (12)C(+6) in the plateau region, and (12)C(+6) in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during (12)C(+6) irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral

  19. Role of multicellular aggregates in biofilm formation

    DEFF Research Database (Denmark)

    Kragh, Kasper N.; Hutchison, Jaime B.; Melaugh, Gavin

    2016-01-01

    In traditional models of in vitro biofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However......, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process. This makes it likely that biofilms are often seeded by aggregates and single cells, yet how these aggregates impact biofilm...... initiation and development is not known. Here we use a combination of experimental and computational approaches to determine the relative fitness of single cells and preformed aggregates during early development of Pseudomonas aeruginosa biofilms. We find that the relative fitness of aggregates depends...

  20. Communication shapes sensory response in multicellular networks.

    Science.gov (United States)

    Potter, Garrett D; Byrd, Tommy A; Mugler, Andrew; Sun, Bo

    2016-09-13

    Collective sensing by interacting cells is observed in a variety of biological systems, and yet, a quantitative understanding of how sensory information is collectively encoded is lacking. Here, we investigate the ATP-induced calcium dynamics of monolayers of fibroblast cells that communicate via gap junctions. Combining experiments and stochastic modeling, we find that increasing the ATP stimulus increases the propensity for calcium oscillations, despite large cell-to-cell variability. The model further predicts that the oscillation propensity increases with not only the stimulus, but also the cell density due to increased communication. Experiments confirm this prediction, showing that cell density modulates the collective sensory response. We further implicate cell-cell communication by coculturing the fibroblasts with cancer cells, which we show act as "defects" in the communication network, thereby reducing the oscillation propensity. These results suggest that multicellular networks sit at a point in parameter space where cell-cell communication has a significant effect on the sensory response, allowing cells to simultaneously respond to a sensory input and the presence of neighbors.

  1. Weakly coupled map lattice models for multicellular patterning and collective normalization of abnormal single-cell states

    Science.gov (United States)

    García-Morales, Vladimir; Manzanares, José A.; Mafe, Salvador

    2017-04-01

    We present a weakly coupled map lattice model for patterning that explores the effects exerted by weakening the local dynamic rules on model biological and artificial networks composed of two-state building blocks (cells). To this end, we use two cellular automata models based on (i) a smooth majority rule (model I) and (ii) a set of rules similar to those of Conway's Game of Life (model II). The normal and abnormal cell states evolve according to local rules that are modulated by a parameter κ . This parameter quantifies the effective weakening of the prescribed rules due to the limited coupling of each cell to its neighborhood and can be experimentally controlled by appropriate external agents. The emergent spatiotemporal maps of single-cell states should be of significance for positional information processes as well as for intercellular communication in tumorigenesis, where the collective normalization of abnormal single-cell states by a predominantly normal neighborhood may be crucial.

  2. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources

    Science.gov (United States)

    Lippmann, Ethan S.; Al-Ahmad, Abraham; Azarin, Samira M.; Palecek, Sean P.; Shusta, Eric V.

    2014-02-01

    Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm2). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.

  3. Ellipsoid Segmentation Model for Analyzing Light-Attenuated 3D Confocal Image Stacks of Fluorescent Multi-Cellular Spheroids.

    Directory of Open Access Journals (Sweden)

    Michaël Barbier

    Full Text Available In oncology, two-dimensional in-vitro culture models are the standard test beds for the discovery and development of cancer treatments, but in the last decades, evidence emerged that such models have low predictive value for clinical efficacy. Therefore they are increasingly complemented by more physiologically relevant 3D models, such as spheroid micro-tumor cultures. If suitable fluorescent labels are applied, confocal 3D image stacks can characterize the structure of such volumetric cultures and, for example, cell proliferation. However, several issues hamper accurate analysis. In particular, signal attenuation within the tissue of the spheroids prevents the acquisition of a complete image for spheroids over 100 micrometers in diameter. And quantitative analysis of large 3D image data sets is challenging, creating a need for methods which can be applied to large-scale experiments and account for impeding factors. We present a robust, computationally inexpensive 2.5D method for the segmentation of spheroid cultures and for counting proliferating cells within them. The spheroids are assumed to be approximately ellipsoid in shape. They are identified from information present in the Maximum Intensity Projection (MIP and the corresponding height view, also known as Z-buffer. It alerts the user when potential bias-introducing factors cannot be compensated for and includes a compensation for signal attenuation.

  4. Organotypic Culture of Breast Tumor Explants as a Multicellular System for the Screening of Natural Compounds with Antineoplastic Potential

    Science.gov (United States)

    Carranza-Torres, Irma Edith; Guzmán-Delgado, Nancy Elena; Coronado-Martínez, Consuelo; Bañuelos-García, José Inocente; Viveros-Valdez, Ezequiel; Morán-Martínez, Javier; Carranza-Rosales, Pilar

    2015-01-01

    Breast cancer is the leading cause of death in women worldwide. The search for novel compounds with antitumor activity, with less adverse effects and higher efficacy, and the development of methods to evaluate their toxicity is an area of intense research. In this study we implemented the preparation and culture of breast tumor explants, which were obtained from precision-cut breast tumor slices. In order to validate the model we are proposing to screen antineoplastic effect of natural compounds, we selected caffeic acid, ursolic acid, and rosmarinic acid. Using the Krumdieck tissue slicer, precision-cut tissue slices were prepared from breast cancer samples; from these slices, 4 mm explants were obtained and incubated with the selected compounds. Viability was assessed by Alamar Blue assay, LDH release, and histopathological criteria. Results showed that the viability of the explants cultured in the presence of paclitaxel (positive control) decreased significantly (P < 0.05); however, tumor samples responded differently to each compound. When the explants were coincubated with paclitaxel and compounds, a synergic effect was observed. This study shows that ex vivo culture of breast cancer explants offers a suitable alternative model for evaluating natural or synthetic compounds with antitumor properties within the complex microenvironment of the tumor. PMID:26075250

  5. Organotypic Culture of Breast Tumor Explants as a Multicellular System for the Screening of Natural Compounds with Antineoplastic Potential

    Directory of Open Access Journals (Sweden)

    Irma Edith Carranza-Torres

    2015-01-01

    Full Text Available Breast cancer is the leading cause of death in women worldwide. The search for novel compounds with antitumor activity, with less adverse effects and higher efficacy, and the development of methods to evaluate their toxicity is an area of ​​intense research. In this study we implemented the preparation and culture of breast tumor explants, which were obtained from precision-cut breast tumor slices. In order to validate the model we are proposing to screen antineoplastic effect of natural compounds, we selected caffeic acid, ursolic acid, and rosmarinic acid. Using the Krumdieck tissue slicer, precision-cut tissue slices were prepared from breast cancer samples; from these slices, 4 mm explants were obtained and incubated with the selected compounds. Viability was assessed by Alamar Blue assay, LDH release, and histopathological criteria. Results showed that the viability of the explants cultured in the presence of paclitaxel (positive control decreased significantly (P<0.05; however, tumor samples responded differently to each compound. When the explants were coincubated with paclitaxel and compounds, a synergic effect was observed. This study shows that ex vivo culture of breast cancer explants offers a suitable alternative model for evaluating natural or synthetic compounds with antitumor properties within the complex microenvironment of the tumor.

  6. The roles and regulation of multicellular rosette structures during morphogenesis

    Science.gov (United States)

    Harding, Molly J.; McGraw, Hillary F.; Nechiporuk, Alex

    2014-01-01

    Multicellular rosettes have recently been appreciated as important cellular intermediates that are observed during the formation of diverse organ systems. These rosettes are polarized, transient epithelial structures that sometimes recapitulate the form of the adult organ. Rosette formation has been studied in various developmental contexts, such as in the zebrafish lateral line primordium, the vertebrate pancreas, the Drosophila epithelium and retina, as well as in the adult neural stem cell niche. These studies have revealed that the cytoskeletal rearrangements responsible for rosette formation appear to be conserved. By contrast, the extracellular cues that trigger these rearrangements in vivo are less well understood and are more diverse. Here, we review recent studies of the genetic regulation and cellular transitions involved in rosette formation. We discuss and compare specific models for rosette formation and highlight outstanding questions in the field. PMID:24961796

  7. Sensitivity analysis of FBMC-based multi-cellular networks to synchronization errors and HPA nonlinearities

    Science.gov (United States)

    Elmaroud, Brahim; Faqihi, Ahmed; Aboutajdine, Driss

    2017-01-01

    In this paper, we study the performance of asynchronous and nonlinear FBMC-based multi-cellular networks. The considered system includes a reference mobile perfectly synchronized with its reference base station (BS) and K interfering BSs. Both synchronization errors and high-power amplifier (HPA) distortions will be considered and a theoretical analysis of the interference signal will be conducted. On the basis of this analysis, we will derive an accurate expression of signal-to-noise-plus-interference ratio (SINR) and bit error rate (BER) in the presence of a frequency-selective channel. In order to reduce the computational complexity of the BER expression, we applied an interesting lemma based on the moment generating function of the interference power. Finally, the proposed model is evaluated through computer simulations which show a high sensitivity of the asynchronous FBMC-based multi-cellular network to HPA nonlinear distortions.

  8. Evolution of SET-domain protein families in the unicellular and multicellular Ascomycota fungi

    Directory of Open Access Journals (Sweden)

    Moriyama Etsuko N

    2008-07-01

    Full Text Available Abstract Background The evolution of multicellularity is accompanied by the occurrence of differentiated tissues, of organismal developmental programs, and of mechanisms keeping the balance between proliferation and differentiation. Initially, the SET-domain proteins were associated exclusively with regulation of developmental genes in metazoa. However, finding of SET-domain genes in the unicellular yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe suggested that SET-domain proteins regulate a much broader variety of biological programs. Intuitively, it is expected that the numbers, types, and biochemical specificity of SET-domain proteins of multicellular versus unicellular forms would reflect the differences in their biology. However, comparisons across the unicellular and multicellular domains of life are complicated by the lack of knowledge of the ancestral SET-domain genes. Even within the crown group, different biological systems might use the epigenetic 'code' differently, adapting it to organism-specific needs. Simplifying the model, we undertook a systematic phylogenetic analysis of one monophyletic fungal group (Ascomycetes containing unicellular yeasts, Saccharomycotina (hemiascomycetes, and a filamentous fungal group, Pezizomycotina (euascomycetes. Results Systematic analysis of the SET-domain genes across an entire eukaryotic phylum has outlined clear distinctions in the SET-domain gene collections in the unicellular and in the multicellular (filamentous relatives; diversification of SET-domain gene families has increased further with the expansion and elaboration of multicellularity in animal and plant systems. We found several ascomycota-specific SET-domain gene groups; each was unique to either Saccharomycotina or Pezizomycotina fungi. Our analysis revealed that the numbers and types of SET-domain genes in the Saccharomycotina did not reflect the habitats, pathogenicity, mechanisms of sexuality, or the ability to

  9. The origin of multicellularity in cyanobacteria

    Science.gov (United States)

    2011-01-01

    Background Cyanobacteria are one of the oldest and morphologically most diverse prokaryotic phyla on our planet. The early development of an oxygen-containing atmosphere approximately 2.45 - 2.22 billion years ago is attributed to the photosynthetic activity of cyanobacteria. Furthermore, they are one of the few prokaryotic phyla where multicellularity has evolved. Understanding when and how multicellularity evolved in these ancient organisms would provide fundamental information on the early history of life and further our knowledge of complex life forms. Results We conducted and compared phylogenetic analyses of 16S rDNA sequences from a large sample of taxa representing the morphological and genetic diversity of cyanobacteria. We reconstructed ancestral character states on 10,000 phylogenetic trees. The results suggest that the majority of extant cyanobacteria descend from multicellular ancestors. Reversals to unicellularity occurred at least 5 times. Multicellularity was established again at least once within a single-celled clade. Comparison to the fossil record supports an early origin of multicellularity, possibly as early as the "Great Oxygenation Event" that occurred 2.45 - 2.22 billion years ago. Conclusions The results indicate that a multicellular morphotype evolved early in the cyanobacterial lineage and was regained at least once after a previous loss. Most of the morphological diversity exhibited in cyanobacteria today —including the majority of single-celled species— arose from ancient multicellular lineages. Multicellularity could have conferred a considerable advantage for exploring new niches and hence facilitated the diversification of new lineages. PMID:21320320

  10. Antimicrobial peptides of multicellular organisms

    Science.gov (United States)

    Zasloff, Michael

    2002-01-01

    Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?

  11. The Multiple Origins of Complex Multicellularity

    Science.gov (United States)

    Knoll, Andrew H.

    2011-05-01

    Simple multicellularity has evolved numerous times within the Eukarya, but complex multicellular organisms belong to only six clades: animals, embryophytic land plants, florideophyte red algae, laminarialean brown algae, and two groups of fungi. Phylogeny and genomics suggest a generalized trajectory for the evolution of complex multicellularity, beginning with the co-optation of existing genes for adhesion. Molecular channels to facilitate cell-cell transfer of nutrients and signaling molecules appear to be critical, as this trait occurs in all complex multicellular organisms but few others. Proliferation of gene families for transcription factors and cell signals accompany the key functional innovation of complex multicellular clades: differentiated cells and tissues for the bulk transport of oxygen, nutrients, and molecular signals that enable organisms to circumvent the physical limitations of diffusion. The fossil records of animals and plants document key stages of this trajectory.

  12. The multicellularity genes of dictyostelid social amoebas.

    Science.gov (United States)

    Glöckner, Gernot; Lawal, Hajara M; Felder, Marius; Singh, Reema; Singer, Gail; Weijer, Cornelis J; Schaap, Pauline

    2016-06-30

    The evolution of multicellularity enabled specialization of cells, but required novel signalling mechanisms for regulating cell differentiation. Early multicellular organisms are mostly extinct and the origins of these mechanisms are unknown. Here using comparative genome and transcriptome analysis across eight uni- and multicellular amoebozoan genomes, we find that 80% of proteins essential for the development of multicellular Dictyostelia are already present in their unicellular relatives. This set is enriched in cytosolic and nuclear proteins, and protein kinases. The remaining 20%, unique to Dictyostelia, mostly consists of extracellularly exposed and secreted proteins, with roles in sensing and recognition, while several genes for synthesis of signals that induce cell-type specialization were acquired by lateral gene transfer. Across Dictyostelia, changes in gene expression correspond more strongly with phenotypic innovation than changes in protein functional domains. We conclude that the transition to multicellularity required novel signals and sensors rather than novel signal processing mechanisms.

  13. Bacterial Ventures into Multicellularity: Collectivism through Individuality.

    Science.gov (United States)

    van Vliet, Simon; Ackermann, Martin

    2015-06-01

    Multicellular eukaryotes can perform functions that exceed the possibilities of an individual cell. These functions emerge through interactions between differentiated cells that are precisely arranged in space. Bacteria also form multicellular collectives that consist of differentiated but genetically identical cells. How does the functionality of these collectives depend on the spatial arrangement of the differentiated bacteria? In a previous issue of PLOS Biology, van Gestel and colleagues reported an elegant example of how the spatial arrangement of differentiated cells gives rise to collective behavior in Bacillus subtilus colonies, further demonstrating the similarity of bacterial collectives to higher multicellular organisms.

  14. Bacterial Ventures into Multicellularity: Collectivism through Individuality.

    Directory of Open Access Journals (Sweden)

    Simon van Vliet

    2015-06-01

    Full Text Available Multicellular eukaryotes can perform functions that exceed the possibilities of an individual cell. These functions emerge through interactions between differentiated cells that are precisely arranged in space. Bacteria also form multicellular collectives that consist of differentiated but genetically identical cells. How does the functionality of these collectives depend on the spatial arrangement of the differentiated bacteria? In a previous issue of PLOS Biology, van Gestel and colleagues reported an elegant example of how the spatial arrangement of differentiated cells gives rise to collective behavior in Bacillus subtilus colonies, further demonstrating the similarity of bacterial collectives to higher multicellular organisms.

  15. Myxobacteria, Polarity, and Multicellular Morphogenesis

    Science.gov (United States)

    Kaiser, Dale; Robinson, Mark; Kroos, Lee

    2010-01-01

    Myxobacteria are renowned for the ability to sporulate within fruiting bodies whose shapes are species-specific. The capacity to build those multicellular structures arises from the ability of M. xanthus to organize high cell-density swarms, in which the cells tend to be aligned with each other while constantly in motion. The intrinsic polarity of rod-shaped cells lays the foundation, and each cell uses two polar engines for gliding on surfaces. It sprouts retractile type IV pili from the leading cell pole and secretes capsular polysaccharide through nozzles from the trailing pole. Regularly periodic reversal of the gliding direction was found to be required for swarming. Those reversals are generated by a G-protein switch which is driven by a sharply tuned oscillator. Starvation induces fruiting body development, and systematic reductions in the reversal frequency are necessary for the cells to aggregate rather than continue to swarm. Developmental gene expression is regulated by a network that is connected to the suppression of reversals. PMID:20610548

  16. The Evolution of Multicellular Plants and Animals.

    Science.gov (United States)

    Valentine, James W.

    1978-01-01

    Traces the evolution of unicellular organisms to the multi-cellular plants and animals in existence today. Major events are depicted in a geologic timetable. Organisms, extinct and recent, are classified by taxonomic group. (MA)

  17. The origin of multicellularity in cyanobacteria

    OpenAIRE

    Antonelli Alexandre; Schirrmeister Bettina E; Bagheri Homayoun C

    2011-01-01

    Abstract Background Cyanobacteria are one of the oldest and morphologically most diverse prokaryotic phyla on our planet. The early development of an oxygen-containing atmosphere approximately 2.45 - 2.22 billion years ago is attributed to the photosynthetic activity of cyanobacteria. Furthermore, they are one of the few prokaryotic phyla where multicellularity has evolved. Understanding when and how multicellularity evolved in these ancient organisms would provide fundamental information on ...

  18. The origin of multicellularity in cyanobacteria

    Directory of Open Access Journals (Sweden)

    Antonelli Alexandre

    2011-02-01

    Full Text Available Abstract Background Cyanobacteria are one of the oldest and morphologically most diverse prokaryotic phyla on our planet. The early development of an oxygen-containing atmosphere approximately 2.45 - 2.22 billion years ago is attributed to the photosynthetic activity of cyanobacteria. Furthermore, they are one of the few prokaryotic phyla where multicellularity has evolved. Understanding when and how multicellularity evolved in these ancient organisms would provide fundamental information on the early history of life and further our knowledge of complex life forms. Results We conducted and compared phylogenetic analyses of 16S rDNA sequences from a large sample of taxa representing the morphological and genetic diversity of cyanobacteria. We reconstructed ancestral character states on 10,000 phylogenetic trees. The results suggest that the majority of extant cyanobacteria descend from multicellular ancestors. Reversals to unicellularity occurred at least 5 times. Multicellularity was established again at least once within a single-celled clade. Comparison to the fossil record supports an early origin of multicellularity, possibly as early as the "Great Oxygenation Event" that occurred 2.45 - 2.22 billion years ago. Conclusions The results indicate that a multicellular morphotype evolved early in the cyanobacterial lineage and was regained at least once after a previous loss. Most of the morphological diversity exhibited in cyanobacteria today —including the majority of single-celled species— arose from ancient multicellular lineages. Multicellularity could have conferred a considerable advantage for exploring new niches and hence facilitated the diversification of new lineages.

  19. Robust Multi-Cellular Developmental Design

    CERN Document Server

    Devert, Alexandre; Schoenauer, Marc

    2007-01-01

    This paper introduces a continuous model for Multi-cellular Developmental Design. The cells are fixed on a 2D grid and exchange "chemicals" with their neighbors during the growth process. The quantity of chemicals that a cell produces, as well as the differentiation value of the cell in the phenotype, are controlled by a Neural Network (the genotype) that takes as inputs the chemicals produced by the neighboring cells at the previous time step. In the proposed model, the number of iterations of the growth process is not pre-determined, but emerges during evolution: only organisms for which the growth process stabilizes give a phenotype (the stable state), others are declared nonviable. The optimization of the controller is done using the NEAT algorithm, that optimizes both the topology and the weights of the Neural Networks. Though each cell only receives local information from its neighbors, the experimental results of the proposed approach on the 'flags' problems (the phenotype must match a given 2D pattern...

  20. A multicellular view of cytokinesis in epithelial tissue.

    Science.gov (United States)

    Herszterg, Sophie; Pinheiro, Diana; Bellaïche, Yohanns

    2014-05-01

    The study of cytokinesis in single-cell systems provided a wealth of knowledge on the molecular and biophysical mechanisms controlling daughter cell separation. In this review, we outline recent advances in the understanding of cytokinesis in epithelial tissues. These findings provide evidence for how the cytokinetic machinery adapts to a multicellular context and how the cytokinetic machinery is itself exploited by the tissue for the preservation of tissue function and architecture during proliferation. We propose that cytokinesis in epithelia should be viewed as a multicellular process, whereby the biochemical and mechanical interactions between the dividing cell and its neighbors are essential for successful daughter cell separation while defining epithelial tissue organization and preserving tissue integrity.

  1. Phase transitions in the multi-cellular regulatory behavior of pancreatic islet excitability.

    Directory of Open Access Journals (Sweden)

    Thomas H Hraha

    2014-09-01

    Full Text Available The pancreatic islets of Langerhans are multicellular micro-organs integral to maintaining glucose homeostasis through secretion of the hormone insulin. β-cells within the islet exist as a highly coupled electrical network which coordinates electrical activity and insulin release at high glucose, but leads to global suppression at basal glucose. Despite its importance, how network dynamics generate this emergent binary on/off behavior remains to be elucidated. Previous work has suggested that a small threshold of quiescent cells is able to suppress the entire network. By modeling the islet as a Boolean network, we predicted a phase-transition between globally active and inactive states would emerge near this threshold number of cells, indicative of critical behavior. This was tested using islets with an inducible-expression mutation which renders defined numbers of cells electrically inactive, together with pharmacological modulation of electrical activity. This was combined with real-time imaging of intracellular free-calcium activity [Ca2+]i and measurement of physiological parameters in mice. As the number of inexcitable cells was increased beyond ∼15%, a phase-transition in islet activity occurred, switching from globally active wild-type behavior to global quiescence. This phase-transition was also seen in insulin secretion and blood glucose, indicating physiological impact. This behavior was reproduced in a multicellular dynamical model suggesting critical behavior in the islet may obey general properties of coupled heterogeneous networks. This study represents the first detailed explanation for how the islet facilitates inhibitory activity in spite of a heterogeneous cell population, as well as the role this plays in diabetes and its reversal. We further explain how islets utilize this critical behavior to leverage cellular heterogeneity and coordinate a robust insulin response with high dynamic range. These findings also give new

  2. Optical signature of multicellular tumor spheroid using index-mismatch-induced spherical aberrations

    Science.gov (United States)

    Le Corre, G.; Weiss, P.; Ducommun, B.; Lorenzo, C.

    2014-02-01

    The development of new cancer treatments and the early prediction of their therapeutic potential are often made difficult by the lack of predictive pharmacological models. The 3D multicellular tumor spheroid (MCTS) model offers a level of complexity that recapitulates the three-dimensional organization of a tumor and appears to be fairly predictive of therapeutic efficiency. The use of spheroids in large-scale automated screening was recently reported to link the power of a high throughput analysis to the predictability of a 3D cell model. The spheroid has a radial symmetry; this simple geometry allows establishing a direct correlation between structure and function. The outmost layers of MCTS are composed of proliferating cells and form structurally uniform domain with an approximate thickness of 100 microns. The innermost layers are composed of quiescent cells. Finally, cells in the center of the spheroid can form a necrotic core. This latest region is structurally heterogeneous and is poorly characterized. These features make the spheroid a model of choice and a paradigm to study the optical properties of various epithelial tissues. In this study, we used an in-vitro optical technique for label-free characterization of multicellular systems based on the index- mismatch induced spherical aberrations. We achieve to monitor and characterize the optical properties of MCTS. This new and original approach might be of major interest for the development of innovative screening strategies dedicated to the identification of anticancer drugs.

  3. "Hypothesis for the Modern RNA World": A pervasive Non-coding RNA-Based Genetic Regulation is a Prerequisite for the Emergence of Multicellular Complexity

    Science.gov (United States)

    Lozada-Chávez, Irma; Stadler, Peter F.; Prohaska, Sonja J.

    2011-12-01

    The transitions to multicellularity mark the most pivotal and distinctive events in life's history on Earth. Although several transitions to "simple" multicellularity (SM) have been recorded in both bacterial and eukaryotic clades, transitions to complex multicellularity (CM) have only happened a few times in eukaryotes. A large number of cell types (associated with large body size), increased energy consumption per gene expressed, and an increment of non-protein-coding DNA positively correlate with CM. These three factors can indeed be understood as the causes and consequences of the regulation of gene expression. Here, we discuss how a vast expansion of non-protein-coding RNA (ncRNAs) regulators rather than large numbers of novel protein regulators can easily contribute to the emergence of CM. We also propose that the evolutionary advantage of RNA-based gene regulation derives from the robustness of the RNA structure that makes it easy to combine genetic drift with functional exploration. We describe a model which aims to explain how the evolutionary dynamic of ncRNAs becomes dominated by the accessibility of advantageous mutations to innovate regulation in complex multicellular organisms. The information and models discussed here outline the hypothesis that pervasive ncRNA-based regulatory systems, only capable of being expanded and explored in higher eukaryotes, are prerequisite to complex multicellularity. Thereby, regulatory RNA molecules in Eukarya have allowed intensification of morphological complexity by stabilizing critical phenotypes and controlling developmental precision. Although the origin of RNA on early Earth is still controversial, it is becoming clear that once RNA emerged into a protocellular system, its relevance within the evolution of biological systems has been greater than we previously thought.

  4. MULTICELLULAR-MEDIATED EXPRESSION OF P-GP AND MRP AND RELATIONSHIP WITH CELL CYCLE PROFILES IN HUMAN OVARIAN CANCER SK-OV-3ip1 MULTICELLULAR AGGREGATES

    Institute of Scientific and Technical Information of China (English)

    陈建利; 丰有吉; 张琴

    2001-01-01

    To investigate the expression of P-glycoprotein (P-gp) and multidrug resistance- associated protein (MRP) and the relationship with cell cycle profiles in ovarian cancer SK-OV-3ip1 multicellular aggregates. Methods: Liquid overlay system was employed to obtain multicellular aggregates. Expression of P-gp and MRP was detected with flow cytometry (FCM). Outer, intermediate and inner cells from multicellular aggregates were collected by layer-trypsinized method. Cell cycle profiles were also analyzed by FCM. Results: Compared with control cells, no expression of P-gp and MRP was detected in monolyer cells (P=0.128 and P=0.604), but expression of P-gp and MRP in aggregate cells was significantly elevated (P<0.01). P-gp expression in every layer cells was also obviously increased (P<0.01). Furthermore, P-gp expression in every layer cells was also obviously increased (P=0.071). Tendency to increased G0-G1 phase and reduced S phase cells existed from outer through intermediate to inner layers in multicellular aggregates but with no statistical difference. Cell percentages in G2-M phase also had no difference. However, compared with monolayer cells, cells in G0-G1 phase increased and cells in S and G2-M phases lowered significantly in every layer and in the whole multicellular aggregates. Expression elevation of P-gp and MRP was consistent with increased G0-G1 percentage in aggregate cells. Conclusion: Expression of P-gp and MRP increases in cells of SK-OV-3ip1 multicellular aggregates and is consistent with increased G0-G1 percentage, which implies the possible relationship between them and the possible role in multicellular-mediated drug resistance.

  5. Bacterial biofilms: prokaryotic adventures in multicellularity

    DEFF Research Database (Denmark)

    Webb, J.S.; Givskov, Michael Christian; Kjelleberg, S.

    2003-01-01

    The development of bacterial biofilms includes both the initial social behavior of undifferentiated cells, as well as cell death and differentiation in the mature biofilm, and displays several striking similarities with higher organisms. Recent advances in the field provide new insight...... into differentiation and cell death events in bacterial biofilm development and propose that biofilms have an unexpected level of multicellularity....

  6. Performance Analysis of Downlink Based Multi-Cellular Systems in Rayleigh Fading%Rayleigh信道下的多小区下行链路性能分析

    Institute of Scientific and Technical Information of China (English)

    邹应全; 赵睿; 杨绿溪

    2011-01-01

    针对存在来自相邻蜂窝小区的同信道、不同功率信道干扰的单用户下行链路场景,分析了基站和用户均为单天线时的系统性能.系统模型为两个基站、两个用户,基站与用户均为单天线.在期望信号和干扰信号均为Rayleigh分布时,运用基于概率密度函数性能分析法推导了系统中断概率;基于瞬时信干噪比(SINR)的推导,并对瞬时误符号率(SER)取平均的方法推导了平均误符号率(ASER)的闭合表达式和用户的接收SINR的n阶矩;根据用户接收平均SINR的n阶矩表达式,推导并分析了用户接收平均SINR的衰落量(AF)性能.计算机仿真了在不同干扰功率下多小区系统的中断概率、ASER的性能以及AF性能.仿真结果表明:单小区和多小区系统的中断概率、ASER和AF的解析曲线均与数值仿真结果一致.系统性能随着干扰基站功率的降低而提升,系统性能随发送功率的增加增益明显.%In this paper, we analyzed the performance of the multi-cell downlink system in the presence of unequal power cochannel interference from the other cells. We adopt the system model composed with two cells and two users, which all equipped with one antenna, While the desired and interfering signals all in the presence of Rayleigh fading channel. First, the closed form expression of system outage prohability is derived by using performance analysis method based on probability density function ( PDF) . Second, by deriving the instantaneous signal to noise plus interference ratio( SINR) and averaging the instantaneous symbol error ratio ( SER) , average symbol error ratio ( ASER) and n order moments of user's receiving SINR are evaluated. Last, an exact closed-form expression of the Averaging fading (AF) of averaging SINR is derived by using the expression of SINR. Computer simulated the outage probability,ASER and AF performance of the system with the different power of interference cell, while the system

  7. Micro-trichome as a class I homeodomain-leucine zipper gene regulates multicellular trichome development in Cucumis sativus.

    Science.gov (United States)

    Zhao, Jun-Long; Pan, Jun-Song; Guan, Yuan; Zhang, Wei-Wei; Bie, Bei-Bei; Wang, Yun-Li; He, Huan-Le; Lian, Hong-Li; Cai, Run

    2015-11-01

    Plant trichomes serve as a highly suitable model for investigating cell differentiation at the single-cell level. The regulatory genes involved in unicellular trichome development in Arabidopsis thaliana have been intensively studied, but genes regulating multicellular trichome development in plants remain unclear. Here, we characterized Cucumis sativus (cucumber) trichomes as representative multicellular and unbranched structures, and identified Micro-trichome (Mict), using map-based cloning in an F2 segregating population of 7,936 individuals generated from a spontaneous mict mutant. In mict plants, trichomes in both leaves and fruits, are small, poorly developed, and denser than in the wild type. Sequence analysis revealed that a 2,649-bp genomic deletion, spanning the first and second exons, occurred in a plant-specific class I homeodomain-leucine zipper gene. Tissue-specific expression analysis indicated that Mict is strongly expressed in the trichome cells. Transcriptome profiling identified potential targets of Mict including putative homologs of genes known in other systems to regulate trichome development, meristem determinacy, and hormone responsiveness. Phylogenic analysis charted the relationships among putative homologs in angiosperms. Our paper represents initial steps toward understanding the development of multicellular trichomes.

  8. The Gonium pectorale genome demonstrates co-option of cell cycle regulation during the evolution of multicellularity

    Science.gov (United States)

    Hanschen, Erik R.; Marriage, Tara N.; Ferris, Patrick J.; Hamaji, Takashi; Toyoda, Atsushi; Fujiyama, Asao; Neme, Rafik; Noguchi, Hideki; Minakuchi, Yohei; Suzuki, Masahiro; Kawai-Toyooka, Hiroko; Smith, David R.; Sparks, Halle; Anderson, Jaden; Bakarić, Robert; Luria, Victor; Karger, Amir; Kirschner, Marc W.; Durand, Pierre M.; Michod, Richard E.; Nozaki, Hisayoshi; Olson, Bradley J. S. C.

    2016-01-01

    The transition to multicellularity has occurred numerous times in all domains of life, yet its initial steps are poorly understood. The volvocine green algae are a tractable system for understanding the genetic basis of multicellularity including the initial formation of cooperative cell groups. Here we report the genome sequence of the undifferentiated colonial alga, Gonium pectorale, where group formation evolved by co-option of the retinoblastoma cell cycle regulatory pathway. Significantly, expression of the Gonium retinoblastoma cell cycle regulator in unicellular Chlamydomonas causes it to become colonial. The presence of these changes in undifferentiated Gonium indicates extensive group-level adaptation during the initial step in the evolution of multicellularity. These results emphasize an early and formative step in the evolution of multicellularity, the evolution of cell cycle regulation, one that may shed light on the evolutionary history of other multicellular innovations and evolutionary transitions. PMID:27102219

  9. The Gonium pectorale genome demonstrates co-option of cell cycle regulation during the evolution of multicellularity.

    Science.gov (United States)

    Hanschen, Erik R; Marriage, Tara N; Ferris, Patrick J; Hamaji, Takashi; Toyoda, Atsushi; Fujiyama, Asao; Neme, Rafik; Noguchi, Hideki; Minakuchi, Yohei; Suzuki, Masahiro; Kawai-Toyooka, Hiroko; Smith, David R; Sparks, Halle; Anderson, Jaden; Bakarić, Robert; Luria, Victor; Karger, Amir; Kirschner, Marc W; Durand, Pierre M; Michod, Richard E; Nozaki, Hisayoshi; Olson, Bradley J S C

    2016-04-22

    The transition to multicellularity has occurred numerous times in all domains of life, yet its initial steps are poorly understood. The volvocine green algae are a tractable system for understanding the genetic basis of multicellularity including the initial formation of cooperative cell groups. Here we report the genome sequence of the undifferentiated colonial alga, Gonium pectorale, where group formation evolved by co-option of the retinoblastoma cell cycle regulatory pathway. Significantly, expression of the Gonium retinoblastoma cell cycle regulator in unicellular Chlamydomonas causes it to become colonial. The presence of these changes in undifferentiated Gonium indicates extensive group-level adaptation during the initial step in the evolution of multicellularity. These results emphasize an early and formative step in the evolution of multicellularity, the evolution of cell cycle regulation, one that may shed light on the evolutionary history of other multicellular innovations and evolutionary transitions.

  10. From cat's eyes to disjoint multicellular natural convection flow in tall tilted cavities

    Energy Technology Data Exchange (ETDEWEB)

    Nicolas, Alfredo, E-mail: anc@xanum.uam.mx [Depto. Matematicas, 3er Piso Ed. AT-Diego Bricio, UAM-I, 09340 Mexico D.F. (Mexico); Baez, Elsa [Depto. Matematicas Aplicadas y Sistemas, UAM-C, 01120 Mexico D.F. (Mexico); Bermudez, Blanca [Facultad de C. de la Computacion, BUAP, 72570 Puebla, Pue. (Mexico)

    2011-07-11

    Numerical results of two-dimensional natural convection problems, in air-filled tall cavities, are reported to study the change of the cat's eyes flow as some parameters vary, the aspect ratio A and the angle of inclination φ of the cavity, with the Rayleigh number Ra mostly fixed; explicitly, the range of the variation is given by 12≤A≤20 and 0{sup o}≤φ≤270{sup o}; about Ra=1.1x10{sup 4}. A novelty contribution of this work is the transition from the cat's eyes changes, as A varies, to a disjoint multicellular flow, as φ varies. These flows may be modeled by the unsteady Boussinesq approximation in stream function and vorticity variables which is solved with a fixed point iterative process applied to the nonlinear elliptic system that results after time discretization. The validation of the results relies on mesh size and time-step independence studies. -- Highlights: → Fixed point iterative method for solving symmetric linear elliptic problems. → Robust method to study effects as aspect ratio and angle of inclination vary. → Interest on the dynamics and evolution of the fluid flow and on heat transfer. → Study of transition from cat's eyes instability to a disjoint multicellular flow.

  11. Computational model of tumor growth for cell line MCF7 of multicellular sheroids; Modelo computacional de crecimiento tumoral para la linea celular MCF7 de esferoides multicelulares

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz-Arrebola, S.; Tornero-Lopez, A. M.; Guirado, D.; Aranda, M.; Villalobos, M.; Lallena, A. M.

    2013-07-01

    The ultimate goal is a computational model that will allow us to overcome the ethical constraints that exist for the realization of certain clinical trials, since putting up compromise the quality of treating real patients. Thus, for the study of important problems of Oncology, perhaps the last resort is the virtual simulation of the effects of certain forms of therapy. (Author)

  12. What can we learn from the toughest animals of the Earth? Water bears (tardigrades) as multicellular model organisms in order to perform scientific preparations for lunar exploration

    Science.gov (United States)

    Guidetti, Roberto; Rizzo, Angela Maria; Altiero, Tiziana; Rebecchi, Lorena

    2012-12-01

    Space missions of long duration required a series of preliminary experiments on living organisms, validated by a substantial phase of ground simulation experiments, in the field of micro- and inter-mediate gravities, radiobiology, and, for planetary explorations, related to risks deriving from regolith and dust exposure. In this review, we present the tardigrades, whose characteristics that recommend them as an emerging model for space biology. They are microscopic animals but are characterized by a complex structural organization similar to that of larger animals; they can be cultured in lab in small facilities, having small size; they are able to produce clonal lineages by means of parthenogenesis; they can completely suspend their metabolism when entering in dormant states (anhydrobiosis induced by dehydration and cryobiosis induced by freezing); desiccated anhydrobiotic tardigrades are able to withstand chemical and physical extremes, but a large tolerance is showed also by active animals; they can be stored in dry state for many years without loss of viability. Tardigrades have already been exposed to space stressors on Low Earth Orbit several times. The relevance of ground-based and space studies on tardigrades rests on the presumption that results could suggest strategies to protect organisms, also humans, when exposed to the space and lunar environments.

  13. Structural Performance of Light Weight Multicellular FRP Composite Bridge Deck Using Finite Element Analysis

    Institute of Scientific and Technical Information of China (English)

    Woraphot Prachasaree; Pongsak Sookmanee

    2012-01-01

    Fiber reinforced polymer (FRP) composite materials having advantages such as higher strength to weight than conventional engineering materials,non-corrosiveness and modularization,which should help engineers to obtain more efficient and cost effective structural materials and systems.Currently,FRP composites are becoming more popular in civil engineering applications.The objectives of this research are to study performance and behavior of light weight multi-cellular FRP composite bridge decks (both module and system levels) under various loading conditions through finite element modeling,and to validate analytical response of FRP composite bridge decks with data from laboratory evaluations.The relative deflection,equivalent flexural rigidity,failure load (mode) and load distribution factors (LDF) based on FE results have been compared with experimental data and discussed in detail.The finite element results showing good correlations with experimental data are presented in this work.

  14. Emergent patterns of growth controlled by multicellular form and mechanics

    Science.gov (United States)

    Nelson, Celeste M.; Jean, Ronald P.; Tan, John L.; Liu, Wendy F.; Sniadecki, Nathan J.; Spector, Alexander A.; Chen, Christopher S.

    2005-01-01

    Spatial patterns of cellular growth generate mechanical stresses that help to push, fold, expand, and deform tissues into their specific forms. Genetic factors are thought to specify patterns of growth and other behaviors to drive morphogenesis. Here, we show that tissue form itself can feed back to regulate patterns of proliferation. Using microfabrication to control the organization of sheets of cells, we demonstrated the emergence of stable patterns of proliferative foci. Regions of concentrated growth corresponded to regions of high tractional stress generated within the sheet, as predicted by a finite-element model of multicellular mechanics and measured directly by using a micromechanical force sensor array. Inhibiting actomyosin-based tension or cadherin-mediated connections between cells disrupted the spatial pattern of proliferation. These findings demonstrate the existence of patterns of mechanical forces that originate from the contraction of cells, emerge from their multicellular organization, and result in patterns of growth. Thus, tissue form is not only a consequence but also an active regulator of tissue growth. PMID:16049098

  15. Quantification of DNA synthesis in multicellular organisms by a combined DAPI and BrdU technique.

    Science.gov (United States)

    Knobloch, Jürgen; Kunz, Werner; Grevelding, Christoph G

    2002-12-01

    The development of a novel method to detect and quantify mitotic activity in multicellular organisms is reported. The method is based on the combinatorial use of 4',6-diamidino-2-phenylindole (DAPI) as a dye for the specific staining of DNA and the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) as a marker for DNA synthesis. It is shown that on nitrocellulose filters, the amount of DNA can be determined by DAPI as a prerequisite for the subsequent quantification of mitotic activity by BrdU. As a model system to prove the applicability of this technique, the blood fluke Schistosoma mansoni has been used. It is demonstrated that the DNA synthesis rate is higher in adult female schistosomes than in adult males. Furthermore, dimethyl sulfoxide, a widely used solvent for many mitogens and inhibitors of mitosis, has no influence on mitotic activity in adult schistosomes.

  16. From cat's eyes to disjoint multicellular natural convection flow in tall tilted cavities

    Science.gov (United States)

    Nicolás, Alfredo; Báez, Elsa; Bermúdez, Blanca

    2011-07-01

    Numerical results of two-dimensional natural convection problems, in air-filled tall cavities, are reported to study the change of the cat's eyes flow as some parameters vary, the aspect ratio A and the angle of inclination ϕ of the cavity, with the Rayleigh number Ra mostly fixed; explicitly, the range of the variation is given by 12⩽A⩽20 and 0°⩽ϕ⩽270°; about Ra=1.1×10. A novelty contribution of this work is the transition from the cat's eyes changes, as A varies, to a disjoint multicellular flow, as ϕ varies. These flows may be modeled by the unsteady Boussinesq approximation in stream function and vorticity variables which is solved with a fixed point iterative process applied to the nonlinear elliptic system that results after time discretization. The validation of the results relies on mesh size and time-step independence studies.

  17. Collective Calcium Signaling of Defective Multicellular Networks

    Science.gov (United States)

    Potter, Garrett; Sun, Bo

    2015-03-01

    A communicating multicellular network processes environmental cues into collective cellular dynamics. We have previously demonstrated that, when excited by extracellular ATP, fibroblast monolayers generate correlated calcium dynamics modulated by both the stimuli and gap junction communication between the cells. However, just as a well-connected neural network may be compromised by abnormal neurons, a tissue monolayer can also be defective with cancer cells, which typically have down regulated gap junctions. To understand the collective cellular dynamics in a defective multicellular network we have studied the calcium signaling of co-cultured breast cancer cells and fibroblast cells in various concentrations of ATP delivered through microfluidic devices. Our results demonstrate that cancer cells respond faster, generate singular spikes, and are more synchronous across all stimuli concentrations. Additionally, fibroblast cells exhibit persistent calcium oscillations that increase in regularity with greater stimuli. To interpret these results we quantitatively analyzed the immunostaining of purigenic receptors and gap junction channels. The results confirm our hypothesis that collective dynamics are mainly determined by the availability of gap junction communications.

  18. MultiCellDS: a standard and a community for sharing multicellular data

    NARCIS (Netherlands)

    Friedman, S.H. (Samuel); Anderson, A.R.A. (Alexander); Bortz, D.M. (David); Fletcher, A.G. (Alexander; Frieboes, H.B. (Herman); Ghaffarizadeh, A. (Ahmadreza ); Grimes, D.R. (Robert); Hawkins-Daarud, A. (Andrea); Hoehme, S. (Stefan); Juarez, E.F. (Edwin); Kesselman, K. (Karl); R.M.H. Merks (Roeland); Mumenthaler, S.M. (Shannon); Newton, P.K. (Paul); Norton, K.-A. (Kerri-Ann); Rawat, R. (Rishi); Rockne, R.C. (Russell); Ruderman, D. (Daniel); Scott, J. (Jacob); Sindi, S.S. (Suzanne); Sparks, J.L. (Jessica); Swanson, K. (Kristin); Agus, D.B. (David); Macklin, P. (Paul)

    2016-01-01

    textabstractCell biology is increasingly focused on cellular heterogeneity and multicellular systems. To make the fullest use of experimental, clinical, and computational efforts, we need standardized data formats, community-curated "public data libraries", and tools to combine and analyze shared

  19. The Role of Functional Amyloids in Multicellular Growth and Development of Gram-Positive Bacteria

    DEFF Research Database (Denmark)

    Dragoš, Anna; Kovács, Ákos T.; Claessen, Dennis

    2017-01-01

    in the two distant Gram-positive bacteria, Streptomyces coelicolor and Bacillus subtilis. We describe how amyloid fibrils contribute to a multitude of developmental processes in each of these systems, including multicellular growth and community development. Despite this variety of tasks, we know...

  20. ARTIFICIAL IMMUNE ALGORITHM OF MULTICELLULAR GROUP AND ITS CONVERGENCE

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To find out more extrema simultaneously including global optimum and multiple local optima existed in multi-modal functions. Methods Germinal center is the generator and selector of high-affinity B cells, a multicellular group's artificial immune algorithm was proposed based on the germinal center reaction mechanism of natural immune systems. Main steps of the algorithm were given, including hyper-mutation, selection, memory, similarity suppression and recruitment of B cells and the convergence of it was proved. Results The algorithm has been tested to optimize various multi-modal functions, and the simulation results show that the artificial immune algorithm proposed here can find multiple extremum of these functions with lower computational cost. Conclusion The algorithm is valid and can converge on the satisfactory solution set D with probability 1 and approach to global solution and many local optimal solutions existed.

  1. Molecular recognition between glyconectins as an adhesion self-assembly pathway to multicellularity.

    Science.gov (United States)

    Misevic, Gradimir N; Guerardel, Yann; Sumanovski, Lazar T; Slomianny, Marie-Christine; Demarty, Maurice; Ripoll, Camille; Karamanos, Yannis; Maes, Emmanuel; Popescu, Octavian; Strecker, Gerard

    2004-04-01

    The appearance of multicellular forms of life has been tightly coupled to the ability of an organism to retain its own anatomical integrity and to distinguish self from non-self. Large glycoconjugates, which make up the outermost cell surface layer of all Metazoans, are the primary candidates for the primordial adhesion and recognition functions in biological self-assembly systems. Atomic force microscopy experiments demonstrated that the binding strength between a single pair of Porifera cell surface glyconectin 1 glycoconjugates from Microciona prolifera can hold the weight of 1600 cells, proving their adhesion functions. Here, measurement of molecular self-recognition of glyconectins (GNs) purified from three Porifera species was used as an experimental model for primordial xenogeneic self/non-self discrimination. Physicochemical and biochemical characterization of the three glyconectins, their glycans, and peptides using gel electrophoresis, ultracentrifugation, NMR, mass spectrometry, glycosaminoglycan-degrading enzyme treatment, amino acid and carbohydrate analyses, and peptide mapping showed that GNs define a new family of proteoglycan-like molecules exhibiting species-specific structures with complex and repetitive acidic carbohydrate motives different from the classical proteoglycans and mucins. In functional self-assembly color-coded bead, cell, and blotting assays, glyconectins displayed species-specific recognition and adhesion. Affinity-purified monospecific polyclonal antibodies prepared against GN1, -2, and -3 glycans selectively inhibited cell adhesion of the respective sponge species. These results together with species-specific coaggregation of GN carbohydrate-coated beads with cells showed that GN glycans are functional in cell recognition and adhesion. The specificity of carbohydrate-mediated homophilic GN interactions in Porifera approaches the binding selectivity of the evolutionarily advanced immunoglobulin superfamily. Xenoselectivity of

  2. Gene silencing pathways found in the green alga Volvox carteri reveal insights into evolution and origins of small RNA systems in plants

    NARCIS (Netherlands)

    Dueck, Anne; Evers, Maurits; Henz, Stefan R.; Unger, Katharina; Eichner, Norbert; Merkl, Rainer; Berezikov, Eugene; Engelmann, Julia C.; Weigel, Detlef; Wenzl, Stephan; Meister, Gunter

    2016-01-01

    Background: Volvox carteri (V. carteri) is a multicellular green alga used as model system for the evolution of multicellularity. So far, the contribution of small RNA pathways to these phenomena is not understood. Thus, we have sequenced V. carteri Argonaute 3 (VcAGO3)-associated small RNAs from

  3. Transitioning from multi-phase to single-phase microfluidics for long-term culture and treatment of multicellular spheroids.

    Science.gov (United States)

    McMillan, Kay S; Boyd, Marie; Zagnoni, Michele

    2016-09-21

    When compared to methodologies based on low adhesion or hanging drop plates, droplet microfluidics offers several advantages for the formation and culture of multicellular spheroids, such as the potential for higher throughput screening and the use of reduced cell numbers, whilst providing increased stability for plate handling. However, a drawback of the technology is its characteristic compartmentalisation which limits the nutrients available to cells within an emulsion and poses challenges to the exchange of the encapsulated solution, often resulting in short-term cell culture and/or viability issues. The aim of this study was to develop a multi-purpose microfluidic platform that combines the high-throughput characteristics of multi-phase flows with that of ease of perfusion typical of single-phase microfluidics. We developed a versatile system to upscale the formation and long-term culture of multicellular spheroids for testing anticancer treatments, creating an array of fluidically addressable, compact spheroids that could be cultured in either medium or within a gel scaffold. The work provides proof-of-concept results for using this system to test both chemo- and radio-therapeutic protocols using in vitro 3D cancer models.

  4. MULTICELLULAR-MEDIATED RESISTANCE TO CISPLATIN AND TAXOL IN HUMAN OVARIAN CANCER SK-OV-3IP1 MULTICELLULAR AGGREGATES

    Institute of Scientific and Technical Information of China (English)

    陈建利; 丰有吉; 张琴

    2002-01-01

    Objective: To investigate the chemosensitivity of ovarian cancer SK-OV-3ip1 multicellular aggregates (MCA) to cisplatin and taxol and to explore the possible mechanisms. Methods: Liquid overlay system was employed to obtain MCA. We detected the resistance using trypan blue exclusion testing, clonogenic assay, cell cycle profiles and apoptosis with flow cytometry (FCM). Results: After cisplatin exposure, MCA cells showed nearly equal cell viability with monolayer cells (P=0.05). After 40(M cisplatin exposure for 12 h, no clone ((50 cells) was formed, but more viable cells attached to the bottom of 24-well plate in MCA group than monolayer. Furthermore, apoptosis rate and cell cycle profiles with FCM had no significant change between MCA and monolayer cells. After taxol exposure, however, trypan blue exclusion testing demonstrated higher cell viability in MCA cells (P=0.003) and higher clone formation rate in 100-cell group than monolayer cells (0.01multicellular-mediated inhibition of apoptosis can partially account for the resistance.

  5. Transcriptional profiling of a yeast colony provides new insight into the heterogeneity of multicellular fungal communities.

    Science.gov (United States)

    Traven, Ana; Jänicke, Amrei; Harrison, Paul; Swaminathan, Angavai; Seemann, Torsten; Beilharz, Traude H

    2012-01-01

    Understanding multicellular fungal structures is important for designing better strategies against human fungal pathogens. For example, the ability to form multicellular biofilms is a key virulence property of the yeast Candida albicans. C. albicans biofilms form on indwelling medical devices and are drug resistant, causing serious infections in hospital settings. Multicellular fungal communities are heterogeneous, consisting of cells experiencing different environments. Heterogeneity is likely important for the phenotypic characteristics of communities, yet it is poorly understood. Here we used colonies of the yeast Saccharomyces cerevisiae as a model fungal multicellular structure. We fractionated the outside colony layers from the cells in the center by FACS, using a Cit1-GFP marker expressed exclusively on the outside. Transcriptomics analysis of the two subpopulations revealed that the outside colony layers are actively growing by fermentative metabolism, while the cells residing on the inside are in a resting state and experience changes to mitochondrial activity. Our data shows several parallels with C. albicans biofilms providing insight into the contributions of heterogeneity to biofilm phenotypes. Hallmarks of C. albicans biofilms - the expression of ribosome and translation functions and activation of glycolysis and ergosterol biosynthesis occur on the outside of colonies, while expression of genes associates with sulfur assimilation is observed in the colony center. Cell wall restructuring occurs in biofilms, and cell wall functions are enriched in both fractions: the outside cells display enrichment of cell wall biosynthesis enzymes and cell wall proteins, while the inside cells express cell wall degrading enzymes. Our study also suggests that noncoding transcription and posttranscriptional mRNA regulation play important roles during growth of yeast in colonies, setting the scene for investigating these pathways in the development of multicellular

  6. Transcriptional profiling of a yeast colony provides new insight into the heterogeneity of multicellular fungal communities.

    Directory of Open Access Journals (Sweden)

    Ana Traven

    Full Text Available Understanding multicellular fungal structures is important for designing better strategies against human fungal pathogens. For example, the ability to form multicellular biofilms is a key virulence property of the yeast Candida albicans. C. albicans biofilms form on indwelling medical devices and are drug resistant, causing serious infections in hospital settings. Multicellular fungal communities are heterogeneous, consisting of cells experiencing different environments. Heterogeneity is likely important for the phenotypic characteristics of communities, yet it is poorly understood. Here we used colonies of the yeast Saccharomyces cerevisiae as a model fungal multicellular structure. We fractionated the outside colony layers from the cells in the center by FACS, using a Cit1-GFP marker expressed exclusively on the outside. Transcriptomics analysis of the two subpopulations revealed that the outside colony layers are actively growing by fermentative metabolism, while the cells residing on the inside are in a resting state and experience changes to mitochondrial activity. Our data shows several parallels with C. albicans biofilms providing insight into the contributions of heterogeneity to biofilm phenotypes. Hallmarks of C. albicans biofilms - the expression of ribosome and translation functions and activation of glycolysis and ergosterol biosynthesis occur on the outside of colonies, while expression of genes associates with sulfur assimilation is observed in the colony center. Cell wall restructuring occurs in biofilms, and cell wall functions are enriched in both fractions: the outside cells display enrichment of cell wall biosynthesis enzymes and cell wall proteins, while the inside cells express cell wall degrading enzymes. Our study also suggests that noncoding transcription and posttranscriptional mRNA regulation play important roles during growth of yeast in colonies, setting the scene for investigating these pathways in the development

  7. Asymmetric segregation of damaged cellular components in spatially structured multicellular organisms.

    Directory of Open Access Journals (Sweden)

    Charlotte Strandkvist

    Full Text Available The asymmetric distribution of damaged cellular components has been observed in species ranging from fission yeast to humans. To study the potential advantages of damage segregation, we have developed a mathematical model describing ageing mammalian tissue, that is, a multicellular system of somatic cells that do not rejuvenate at cell division. To illustrate the applicability of the model, we specifically consider damage incurred by mutations to mitochondrial DNA, which are thought to be implicated in the mammalian ageing process. We show analytically that the asymmetric distribution of damaged cellular components reduces the overall damage level and increases the longevity of the cell population. Motivated by the experimental reports of damage segregation in human embryonic stem cells, dividing symmetrically with respect to cell-fate, we extend the model to consider spatially structured systems of cells. Imposing spatial structure reduces, but does not eliminate, the advantage of asymmetric division over symmetric division. The results suggest that damage partitioning could be a common strategy for reducing the accumulation of damage in a wider range of cell types than previously thought.

  8. Measuring collective behaviour of multicellular ensembles: role of space–time scales

    Indian Academy of Sciences (India)

    S Rajesh; Somdatta Sinha

    2008-06-01

    Living systems are spectacular examples of spatiotemporally organized structures. During the development of complex organization there is dynamic equilibrium between the local and global processes acting at the intra- and intercellular levels in multiple space and time scales. Although in modelling studies such spatiotemporal systems can be described by different space–time scales and at many organizational levels, the experimental quantities measured and predictions useful for practical applications are at a macroscopic (coarser or averaged) level/scale; these are limited by the resolution of the measuring method and experimental protocol. In this work, we address whether the spatiotemporal collective dynamics exhibited by a multiscale system can discriminate between, or be borne out by, the coarse-grained and averaged measurements done at different spatial and temporal scales. Using a simple model of a ring of cells, we show that measurements of both spatial and spatiotemporal average behaviour in this multicellular ensemble can mask the variety of collective dynamics observed at other space–time scales, and exhibit completely different behaviours. Such outcomes of measurements can lead to incomplete and incorrect understanding of physiological functions and pathogenesis in multicell ensembles.

  9. Model Systems

    Directory of Open Access Journals (Sweden)

    Francisco Rodríguez-Trelles

    1998-12-01

    Full Text Available Current efforts to study the biological effects of global change have focused on ecological responses, particularly shifts in species ranges. Mostly ignored are microevolutionary changes. Genetic changes may be at least as important as ecological ones in determining species' responses. In addition, such changes may be a sensitive indicator of global changes that will provide different information than that provided by range shifts. We discuss potential candidate systems to use in such monitoring programs. Studies of Drosophila subobscura suggest that its chromosomal inversion polymorphisms are responding to global warming. Drosophila inversion polymorphisms can be useful indicators of the effects of climate change on populations and ecosystems. Other species also hold the potential to become important indicators of global change. Such studies might significantly influence ecosystem conservation policies and research priorities.

  10. Computational implementation of a tunable multicellular memory circuit for engineered eukaryotic consortia

    Directory of Open Access Journals (Sweden)

    Josep eSardanyés

    2015-10-01

    Full Text Available Cells are complex machines capable of processing information by means of an entangled network ofmolecular interactions. A crucial component of these decision-making systems is the presence of memoryand this is also a specially relevant target of engineered synthetic systems. A classic example of memorydevices is a 1-bit memory element known as the flip-flop. Such system can be in principle designed usinga single-cell implementation, but a direct mapping between standard circuit design and a living circuitcan be cumbersome. Here we present a novel computational implementation of a 1-bit memory deviceusing a reliable multicellular design able to behave as a set-reset flip-flop that could be implemented inyeast cells. The dynamics of the proposed synthetic circuit is investigated with a mathematical modelusing biologically-meaningful parameters. The circuit is shown to behave as a flip-flop in a wide range ofparameter values. The repression strength for the NOT logics is shown to be crucial to obtain a goodflip-flop signal. Our model also shows that the circuit can be externally tuned to achieve different memorystates and dynamics, such as persistent and transient memory. We have characterised the parameterdomains for robust memory storage and retrieval as well as the corresponding time response dynamics.

  11. The green seaweed Ulva: A model system to study morphogenesis

    Directory of Open Access Journals (Sweden)

    Thomas eWichard

    2015-02-01

    Full Text Available Green macroalgae, mostly represented by the Ulvophyceae, the main multicellular branch of the Chlorophyceae, constitute important primary producers of marine and brackish coastal ecosystems. Ulva or sea lettuce species are some of the most abundant representatives, being ubiquitous in coastal benthic communities around the world. Nonetheless the genus also remains largely understudied. This review highlights Ulva as an exciting novel model organism for studies of algal growth, development and morphogenesis as well as mutualistic interactions. The key reasons that Ulva is potentially such a good model system are: (i patterns of Ulva development can drive ecologically important events, such as the increasing number of green tides observed worldwide as a result of eutrophication of coastal waters, (ii Ulva growth is symbiotic, with proper development requiring close association with bacterial epiphytes, (iii Ulva is extremely developmentally plastic, which can shed light on the transition from simple to complex multicellularity and (iv Ulva will provide additional information about the evolution of the green lineage.

  12. Noise-plasticity correlations of gene expression in the multicellular organism Arabidopsis thaliana.

    Science.gov (United States)

    Hirao, Koudai; Nagano, Atsushi J; Awazu, Akinori

    2015-12-21

    Gene expression levels exhibit stochastic variations among genetically identical organisms under the same environmental conditions (called gene expression "noise" or phenotype "fluctuation"). In yeast and Escherichia coli, positive correlations have been found between such gene expression noise and "plasticity" with environmental variations. To determine the universality of such correlations in both unicellular and multicellular organisms, we focused on the relationships between gene expression "noise" and "plasticity" in Arabidopsis thaliana, a multicellular model organism. In recent studies on yeast and E. coli, only some gene groups with specific properties of promoter architecture, average expression levels, and functions exhibited strong noise-plasticity correlations. However, we found strong noise-plasticity correlations for most gene groups in Arabidopsis; additionally, promoter architecture, functional essentiality of genes, and circadian rhythm appeared to have only a weak influence on the correlation strength. The differences in the characteristics of noise-plasticity correlations may result from three-dimensional chromosomal structures and/or circadian rhythm.

  13. Multicellularity in green algae: Upsizing in a walled complex.

    Directory of Open Access Journals (Sweden)

    David S. Domozych

    2014-11-01

    Full Text Available Modern green algae constitute a large and diverse taxonomic assemblage that encompasses many multicellular phenotypes including colonial, filamentous and parenchymatous forms. In all multicellular green algae, each cell is surrounded by an extracellular matrix, most often in the form of a cell wall. Volvocalean taxa like Volvox have an elaborate, gel-like, hydroxyproline rich glycoprotein covering that contains the cells of the colony. In ulvophytes, uronic acid-rich and sulfated polysaccharides are the likely adhesion agents that maintain the multicellular habit. Charophytes also produce polysaccharide-rich cell walls and in late divergent taxa, pectin plays a critical role in cell-adhesion in the multicellular complex. Cell walls are products of coordinated interaction of membrane trafficking, cytoskeletal dynamics and the cell’s signal transduction machinery responding both to precise internal clocks and external environmental cues. Most often, these activities must be synchronized with the secretion, deposition and remodeling of the polymers of the extracellular matrix. Rapid advances in molecular genetics, cell biology and cell wall biochemistry of green algae will soon provide new insights into the evolution and subcellular processes leading to multicellularity.

  14. Multicellularity in green algae: upsizing in a walled complex.

    Science.gov (United States)

    Domozych, David S; Domozych, Catherine E

    2014-01-01

    Modern green algae constitute a large and diverse taxonomic assemblage that encompasses many multicellular phenotypes including colonial, filamentous, and parenchymatous forms. In all multicellular green algae, each cell is surrounded by an extracellular matrix (ECM), most often in the form of a cell wall. Volvocalean taxa like Volvox have an elaborate, gel-like, hydroxyproline rich glycoprotein covering that contains the cells of the colony. In "ulvophytes," uronic acid-rich and sulfated polysaccharides are the likely adhesion agents that maintain the multicellular habit. Charophytes also produce polysaccharide-rich cell walls and in late divergent taxa, pectin plays a critical role in cell adhesion in the multicellular complex. Cell walls are products of coordinated interaction of membrane trafficking, cytoskeletal dynamics and the cell's signal transduction machinery responding both to precise internal clocks and external environmental cues. Most often, these activities must be synchronized with the secretion, deposition and remodeling of the polymers of the ECM. Rapid advances in molecular genetics, cell biology and cell wall biochemistry of green algae will soon provide new insights into the evolution and subcellular processes leading to multicellularity.

  15. Bacterial Stigmergy: An Organising Principle of Multicellular Collective Behaviours of Bacteria

    Directory of Open Access Journals (Sweden)

    Erin S. Gloag

    2015-01-01

    Full Text Available The self-organisation of collective behaviours often manifests as dramatic patterns of emergent large-scale order. This is true for relatively “simple” entities such as microbial communities and robot “swarms,” through to more complex self-organised systems such as those displayed by social insects, migrating herds, and many human activities. The principle of stigmergy describes those self-organised phenomena that emerge as a consequence of indirect communication between individuals of the group through the generation of persistent cues in the environment. Interestingly, despite numerous examples of multicellular behaviours of bacteria, the principle of stigmergy has yet to become an accepted theoretical framework that describes how bacterial collectives self-organise. Here we review some examples of multicellular bacterial behaviours in the context of stigmergy with the aim of bringing this powerful and elegant self-organisation principle to the attention of the microbial research community.

  16. A conceptual framework for the evolutionary origins of multicellularity

    Science.gov (United States)

    Libby, Eric; Rainey, Paul B.

    2013-06-01

    The evolution of multicellular organisms from unicellular counterparts involved a transition in Darwinian individuality from single cells to groups. A particular challenge is to understand the nature of the earliest groups, the causes of their evolution, and the opportunities for emergence of Darwinian properties. Here we outline a conceptual framework based on a logical set of possible pathways for evolution of the simplest self-replicating groups. Central to these pathways is the recognition of a finite number of routes by which genetic information can be transmitted between individual cells and groups. We describe the form and organization of each primordial group state and consider factors affecting persistence and evolution of the nascent multicellular forms. Implications arising from our conceptual framework become apparent when attempting to partition fitness effects at individual and group levels. These are discussed with reference to the evolutionary emergence of individuality and its manifestation in extant multicellular life—including those of marginal Darwinian status.

  17. Cell motility dynamics: a novel segmentation algorithm to quantify multi-cellular bright field microscopy images.

    Directory of Open Access Journals (Sweden)

    Assaf Zaritsky

    Full Text Available Confocal microscopy analysis of fluorescence and morphology is becoming the standard tool in cell biology and molecular imaging. Accurate quantification algorithms are required to enhance the understanding of different biological phenomena. We present a novel approach based on image-segmentation of multi-cellular regions in bright field images demonstrating enhanced quantitative analyses and better understanding of cell motility. We present MultiCellSeg, a segmentation algorithm to separate between multi-cellular and background regions for bright field images, which is based on classification of local patches within an image: a cascade of Support Vector Machines (SVMs is applied using basic image features. Post processing includes additional classification and graph-cut segmentation to reclassify erroneous regions and refine the segmentation. This approach leads to a parameter-free and robust algorithm. Comparison to an alternative algorithm on wound healing assay images demonstrates its superiority. The proposed approach was used to evaluate common cell migration models such as wound healing and scatter assay. It was applied to quantify the acceleration effect of Hepatocyte growth factor/scatter factor (HGF/SF on healing rate in a time lapse confocal microscopy wound healing assay and demonstrated that the healing rate is linear in both treated and untreated cells, and that HGF/SF accelerates the healing rate by approximately two-fold. A novel fully automated, accurate, zero-parameters method to classify and score scatter-assay images was developed and demonstrated that multi-cellular texture is an excellent descriptor to measure HGF/SF-induced cell scattering. We show that exploitation of textural information from differential interference contrast (DIC images on the multi-cellular level can prove beneficial for the analyses of wound healing and scatter assays. The proposed approach is generic and can be used alone or alongside traditional

  18. Directing three-dimensional multicellular morphogenesis by self-organization of vascular mesenchymal cells in hyaluronic acid hydrogels.

    Science.gov (United States)

    Zhu, Xiaolu; Gojgini, Shiva; Chen, Ting-Hsuan; Fei, Peng; Dong, Siyan; Ho, Chih-Ming; Segura, Tatiana

    2017-01-01

    Physical scaffolds are useful for supporting cells to form three-dimensional (3D) tissue. However, it is non-trivial to develop a scheme that can robustly guide cells to self-organize into a tissue with the desired 3D spatial structures. To achieve this goal, the rational regulation of cellular self-organization in 3D extracellular matrix (ECM) such as hydrogel is needed. In this study, we integrated the Turing reaction-diffusion mechanism with the self-organization process of cells and produced multicellular 3D structures with the desired configurations in a rational manner. By optimizing the components of the hydrogel and applying exogenous morphogens, a variety of multicellular 3D architectures composed of multipotent vascular mesenchymal cells (VMCs) were formed inside hyaluronic acid (HA) hydrogels. These 3D architectures could mimic the features of trabecular bones and multicellular nodules. Based on the Turing reaction-diffusion instability of morphogens and cells, a theoretical model was proposed to predict the variations observed in 3D multicellular structures in response to exogenous factors. It enabled the feasibility to obtain diverse types of 3D multicellular structures by addition of Noggin and/or BMP2. The morphological consistency between the simulation prediction and experimental results probably revealed a Turing-type mechanism underlying the 3D self-organization of VMCs in HA hydrogels. Our study has provided new ways to create a variety of self-organized 3D multicellular architectures for regenerating biomaterial and tissues in a Turing mechanism-based approach.

  19. Is the periplasm continuous in filamentous multicellular cyanobacteria?

    Science.gov (United States)

    Flores, Enrique; Herrero, Antonia; Wolk, C Peter; Maldener, Iris

    2006-10-01

    Filamentous, heterocyst-forming cyanobacteria are multicellular organisms in which individual cells exchange nutrients and, presumably, regulatory molecules. Unknown mechanisms underlie this exchange. Classical electron microscopy shows that filamentous cyanobacteria bear a Gram-negative cell wall comprising a peptidoglycan layer and an outer membrane that are external to the cytoplasmic membrane, and that the outer membrane appears to be continuous along the filament of cells. This implies that the periplasmic space between the cytoplasmic and outer membranes might also be continuous. We propose that a continuous periplasm could constitute a communication conduit for the transfer of compounds, which is essential for the performance of these bacteria as multicellular organisms.

  20. Transcriptome profiling of trichome-less reveals genes associated with multicellular trichome development in Cucumis sativus.

    Science.gov (United States)

    Zhao, Jun-Long; Wang, Yun-Li; Yao, Dan-Qing; Zhu, Wen-Ying; Chen, Long; He, Huan-Le; Pan, Jun-Song; Cai, Run

    2015-10-01

    Trichomes on plants, similar to fine hairs on animal and human bodies, play important roles in plant survival and development. They also represent a useful model for the study of cell differentiation. Although the regulatory gene network of unicellular trichome development in Arabidopsis thaliana has been well studied, the genes that regulate multicellular trichome development remain unclear. We confirmed that Cucumis sativus (cucumber) trichomes are multicellular and unbranched, but identified a spontaneous mutant, trichome-less (tril), which presented a completely glabrous phenotype. We compared the transcriptome profilings of the tril mutant and wild type using the Illumina HiSeq 2000 sequencing technology. A total of 991 genes exhibited differential expression: 518 were up-regulated and 473 were down-regulated. We further identified 62 differentially expressed genes that encoded crucial transcription factors and were subdivided into seven categories: homeodomain, MADS, MYB, and WRKY domains, ethylene-responsive, zinc finger, and other transcription factor genes. We further analyzed the tissue-expression profiles of two candidate genes, GLABRA2-like and ATHB51-like, using qRT-PCR and found that these two genes were specifically expressed in the epidermis and trichomes, respectively. These results and the tril mutant provide useful tools to study the molecular networks associated with multicellular trichome development.

  1. How to make a synthetic multicellular computer.

    Science.gov (United States)

    Macia, Javier; Sole, Ricard

    2014-01-01

    Biological systems perform computations at multiple scales and they do so in a robust way. Engineering metaphors have often been used in order to provide a rationale for modeling cellular and molecular computing networks and as the basis for their synthetic design. However, a major constraint in this mapping between electronic and wet computational circuits is the wiring problem. Although wires are identical within electronic devices, they must be different when using synthetic biology designs. Moreover, in most cases the designed molecular systems cannot be reused for other functions. A new approximation allows us to simplify the problem by using synthetic cellular consortia where the output of the computation is distributed over multiple engineered cells. By evolving circuits in silico, we can obtain the minimal sets of Boolean units required to solve the given problem at the lowest cost using cellular consortia. Our analysis reveals that the basic set of logic units is typically non-standard. Among the most common units, the so called inverted IMPLIES (N-Implies) appears to be one of the most important elements along with the NOT and AND functions. Although NOR and NAND gates are widely used in electronics, evolved circuits based on combinations of these gates are rare, thus suggesting that the strategy of combining the same basic logic gates might be inappropriate in order to easily implement synthetic computational constructs. The implications for future synthetic designs, the general view of synthetic biology as a standard engineering domain, as well as potencial drawbacks are outlined.

  2. The Evolution of Aggregative Multicellularity and Cell-Cell Communication in the Dictyostelia.

    Science.gov (United States)

    Du, Qingyou; Kawabe, Yoshinori; Schilde, Christina; Chen, Zhi-Hui; Schaap, Pauline

    2015-11-20

    Aggregative multicellularity, resulting in formation of a spore-bearing fruiting body, evolved at least six times independently amongst both eukaryotes and prokaryotes. Amongst eukaryotes, this form of multicellularity is mainly studied in the social amoeba Dictyostelium discoideum. In this review, we summarise trends in the evolution of cell-type specialisation and behavioural complexity in the four major groups of Dictyostelia. We describe the cell-cell communication systems that control the developmental programme of D. discoideum, highlighting the central role of cAMP in the regulation of cell movement and cell differentiation. Comparative genomic studies showed that the proteins involved in cAMP signalling are deeply conserved across Dictyostelia and their unicellular amoebozoan ancestors. Comparative functional analysis revealed that cAMP signalling in D. discoideum originated from a second messenger role in amoebozoan encystation. We highlight some molecular changes in cAMP signalling genes that were responsible for the novel roles of cAMP in multicellular development.

  3. Continuous system modeling

    Science.gov (United States)

    Cellier, Francois E.

    1991-01-01

    A comprehensive and systematic introduction is presented for the concepts associated with 'modeling', involving the transition from a physical system down to an abstract description of that system in the form of a set of differential and/or difference equations, and basing its treatment of modeling on the mathematics of dynamical systems. Attention is given to the principles of passive electrical circuit modeling, planar mechanical systems modeling, hierarchical modular modeling of continuous systems, and bond-graph modeling. Also discussed are modeling in equilibrium thermodynamics, population dynamics, and system dynamics, inductive reasoning, artificial neural networks, and automated model synthesis.

  4. Regulated aggregative multicellularity in a close unicellular relative of metazoa

    Science.gov (United States)

    Sebé-Pedrós, Arnau; Irimia, Manuel; del Campo, Javier; Parra-Acero, Helena; Russ, Carsten; Nusbaum, Chad; Blencowe, Benjamin J; Ruiz-Trillo, Iñaki

    2013-01-01

    The evolution of metazoans from their unicellular ancestors was one of the most important events in the history of life. However, the cellular and genetic changes that ultimately led to the evolution of multicellularity are not known. In this study, we describe an aggregative multicellular stage in the protist Capsaspora owczarzaki, a close unicellular relative of metazoans. Remarkably, transition to the aggregative stage is associated with significant upregulation of orthologs of genes known to establish multicellularity and tissue architecture in metazoans. We further observe transitions in regulated alternative splicing during the C. owczarzaki life cycle, including the deployment of an exon network associated with signaling, a feature of splicing regulation so far only observed in metazoans. Our results reveal the existence of a highly regulated aggregative stage in C. owczarzaki and further suggest that features of aggregative behavior in an ancestral protist may had been co-opted to develop some multicellular properties currently seen in metazoans. DOI: http://dx.doi.org/10.7554/eLife.01287.001 PMID:24368732

  5. Computation Modeling of Limb-bud Dysmorphogenesis: Predicting Cellular Dynamics and Key Events in Developmental Toxicity with a Multicellular Systems Model (FutureToxII)

    Science.gov (United States)

    Congenital limb malformations are among the most frequent malformation occurs in humans, with a frequency of about 1 in 500 to 1 in 1000 human live births. ToxCast is profiling the bioactivity of thousands of chemicals based on high-throughput (HTS) and computational methods that...

  6. The coevolution of cooperation and dispersal in social groups and its implications for the emergence of multicellularity

    Directory of Open Access Journals (Sweden)

    Hochberg Michael E

    2008-08-01

    Full Text Available Abstract Background Recent work on the complexity of life highlights the roles played by evolutionary forces at different levels of individuality. One of the central puzzles in explaining transitions in individuality for entities ranging from complex cells, to multicellular organisms and societies, is how different autonomous units relinquish control over their functions to others in the group. In addition to the necessity of reducing conflict over effecting specialized tasks, differentiating groups must control the exploitation of the commons, or else be out-competed by more fit groups. Results We propose that two forms of conflict – access to resources within groups and representation in germ line – may be resolved in tandem through individual and group-level selective effects. Specifically, we employ an optimization model to show the conditions under which different within-group social behaviors (cooperators producing a public good or cheaters exploiting the public good may be selected to disperse, thereby not affecting the commons and functioning as germ line. We find that partial or complete dispersal specialization of cheaters is a general outcome. The propensity for cheaters to disperse is highest with intermediate benefit:cost ratios of cooperative acts and with high relatedness. An examination of a range of real biological systems tends to support our theory, although additional study is required to provide robust tests. Conclusion We suggest that trait linkage between dispersal and cheating should be operative regardless of whether groups ever achieve higher levels of individuality, because individual selection will always tend to increase exploitation, and stronger group structure will tend to increase overall cooperation through kin selected benefits. Cheater specialization as dispersers offers simultaneous solutions to the evolution of cooperation in social groups and the origin of specialization of germ and soma in

  7. Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation

    Science.gov (United States)

    Xu, Wen-Hong; Han, Min; Dong, Qi; Fu, Zhi-Xuan; Diao, Yuan-Yuan; Liu, Hai; Xu, Jing; Jiang, Hong-Liang; Zhang, Su-Zhan; Zheng, Shu; Gao, Jian-Qing; Wei, Qi-Chun

    2012-01-01

    Background The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line. Methods A novel composite doxorubicin-loaded micelle consisting of polyethylene glycolpolycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems. Results Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are radiosensitive, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher radiosensitivity for the composite micelles loaded with doxorubicin than for free doxorubicin. Conclusion Our composite doxorubicin-loaded micelle was demonstrated to have radiosensitization. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer. PMID:22679376

  8. A Novel Multiparametric Drug-Scoring Method for High-Throughput Screening of 3D Multicellular Tumor Spheroids Using the Celigo Image Cytometer.

    Science.gov (United States)

    Cribbes, Scott; Kessel, Sarah; McMenemy, Scott; Qiu, Jean; Chan, Leo Li-Ying

    2017-01-01

    Three-dimensional (3D) tumor models have been increasingly used to investigate and characterize cancer drug compounds. The ability to perform high-throughput screening of 3D multicellular tumor spheroids (MCTS) can highly improve the efficiency and cost-effectiveness of discovering potential cancer drug candidates. Previously, the Celigo Image Cytometer has demonstrated a novel method for high-throughput screening of 3D multicellular tumor spheroids. In this work, we employed the Celigo Image Cytometer to examine the effects of 14 cancer drug compounds on 3D MCTS of the glioblastoma cell line U87MG in 384-well plates. Using parameters such as MCTS diameter and invasion area, growth and invasion were monitored for 9 and 3 d, respectively. Furthermore, fluorescent staining with calcein AM, propidium iodide, Hoechst 33342, and caspase 3/7 was performed at day 9 posttreatment to measure viability and apoptosis. Using the kinetic and endpoint data generated, we created a novel multiparametric drug-scoring system for 3D MCTS that can be used to identify and classify potential drug candidates earlier in the drug discovery process. Furthermore, the combination of quantitative and qualitative image data can be used to delineate differences between drugs that induce cytotoxic and cytostatic effects. The 3D MCTS-based multiparametric scoring method described here can provide an alternative screening method to better qualify tested drug compounds.

  9. The Role of Functional Amyloids in Multicellular Growth and Development of Gram-Positive Bacteria.

    Science.gov (United States)

    Dragoš, Anna; Kovács, Ákos T; Claessen, Dennis

    2017-08-07

    Amyloid fibrils play pivotal roles in all domains of life. In bacteria, these fibrillar structures are often part of an extracellular matrix that surrounds the producing organism and thereby provides protection to harsh environmental conditions. Here, we discuss the role of amyloid fibrils in the two distant Gram-positive bacteria, Streptomyces coelicolor and Bacillus subtilis. We describe how amyloid fibrils contribute to a multitude of developmental processes in each of these systems, including multicellular growth and community development. Despite this variety of tasks, we know surprisingly little about how their assembly is organized to fulfill all these roles.

  10. Image analysis of self-organized multicellular patterns

    Directory of Open Access Journals (Sweden)

    Thies Christian

    2016-09-01

    Full Text Available Analysis of multicellular patterns is required to understand tissue organizational processes. By using a multi-scale object oriented image processing method, the spatial information of cells can be extracted automatically. Instead of manual segmentation or indirect measurements, such as general distribution of contrast or flow, the orientation and distribution of individual cells is extracted for quantitative analysis. Relevant objects are identified by feature queries and no low-level knowledge of image processing is required.

  11. Stress Clamp Experiments on Multicellular Tumor Spheroids

    CERN Document Server

    Montel, Fabien; Elgeti, Jens; Malaquin, Laurent; Basan, Markus; Risler, Thomas; Cabane, Bernard; Vignjevic, Danijela; Prost, Jacques; Cappello, Giovanni; Joanny, Jean-François; 10.1103/PhysRevLett.107.188102

    2011-01-01

    The precise role of the microenvironment on tumor growth is poorly understood. Whereas the tumor is in constant competition with the surrounding tissue, little is known about the mechanics of this interaction. Using a novel experimental procedure, we study quantitatively the effect of an applied mechanical stress on the long-term growth of a spheroid cell aggregate. We observe that a stress of 10 kPa is sufficient to drastically reduce growth by inhibition of cell proliferation mainly in the core of the spheroid. We compare the results to a simple numerical model developed to describe the role of mechanics in cancer progression.

  12. Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression.

    Science.gov (United States)

    Barbone, Dario; Cheung, Priscilla; Battula, Sailaja; Busacca, Sara; Gray, Steven G; Longley, Daniel B; Bueno, Raphael; Sugarbaker, David J; Fennell, Dean A; Broaddus, V Courtney

    2012-01-01

    When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies.

  13. Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression.

    Directory of Open Access Journals (Sweden)

    Dario Barbone

    Full Text Available When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies.

  14. Modelling Railway Interlocking Systems

    DEFF Research Database (Denmark)

    Lindegaard, Morten Peter; Viuf, P.; Haxthausen, Anne Elisabeth

    2000-01-01

    In this report we present a model of interlocking systems, and describe how the model may be validated by simulation. Station topologies are modelled by graphs in which the nodes denote track segments, and the edges denote connectivity for train traÆc. Points and signals are modelled by annotatio...

  15. Complex Polarity: Building Multicellular Tissues Through Apical Membrane Traffic.

    Science.gov (United States)

    Román-Fernández, Alvaro; Bryant, David M

    2016-12-01

    The formation of distinct subdomains of the cell surface is crucial for multicellular organism development. The most striking example of this is apical-basal polarization. What is much less appreciated is that underpinning an asymmetric cell surface is an equally dramatic intracellular endosome rearrangement. Here, we review the interplay between classical cell polarity proteins and membrane trafficking pathways, and discuss how this marriage gives rise to cell polarization. We focus on those mechanisms that regulate apical polarization, as this is providing a number of insights into how membrane traffic and polarity are regulated at the tissue level. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Multicellular behavior in bacteria: communication, cooperation, competition and cheating.

    Science.gov (United States)

    Dunny, Gary M; Brickman, Timothy J; Dworkin, Martin

    2008-04-01

    The sociobiology of bacteria, largely unappreciated and ignored by the microbiology research community two decades ago is now a major research area, catalyzed to a significant degree by studies of communication and cooperative behavior among the myxobacteria and in quorum sensing (QS) and biofilm formation by pseudomonads and other microbes. Recently, the topic of multicellular cooperative behaviors among bacteria has been increasingly considered in the context of evolutionary biology. Here we discuss the significance of two recent studies of the phenomenon of "cheating" mutants and their exploitation of cooperating microbial populations of Pseudomonas aeruginosa.

  17. A Multicellular Approach Forms a Significant Amount of Tissue-Engineered Small Intestine in the Mouse

    Science.gov (United States)

    Sala, Frédéric G.; Matthews, Jamil A.; Speer, Allison L.; Torashima, Yasuhiro; Barthel, Erik R.

    2011-01-01

    Tissue-engineered small intestine (TESI) has successfully been used to rescue Lewis rats after massive small bowel resection. In this study, we transitioned the technique to a mouse model, allowing investigation of the processes involved during TESI formation through the transgenic tools available in this species. This is a necessary step toward applying the technique to human therapy. Multicellular organoid units were derived from small intestines of transgenic mice and transplanted within the abdomen on biodegradable polymers. Immunofluorescence staining was used to characterize the cellular processes during TESI formation. We demonstrate the preservation of Lgr5- and DcamKl1-positive cells, two putative intestinal stem cell populations, in proximity to their niche mesenchymal cells, the intestinal subepithelial myofibroblasts (ISEMFs), at the time of implantation. Maintenance of the relationship between ISEMF and crypt epithelium is observed during the growth of TESI. The engineered small intestine has an epithelium containing a differentiated epithelium next to an innervated muscularis. Lineage tracing demonstrates that all the essential components, including epithelium, muscularis, nerves, and some of the blood vessels, are of donor origin. This multicellular approach provides the necessary cell population to regenerate large amounts of intestinal tissue that could be used to treat short bowel syndrome. PMID:21395443

  18. Inter-cell interference mitigation in multi-cellular visible light communications.

    Science.gov (United States)

    Jung, Sun-Young; Kwon, Do-Hoon; Yang, Se-Hoon; Han, Sang-Kook

    2016-04-18

    Inter-cell interference hinders multi-cellular optical wireless communication to support various applications. We proposed and experimentally demonstrated a multicarrier-based cell partitioning scheme, combined with frequency reuse, which could be effective in optical communications although it is inefficient in RF wireless communications. For multicarrier-based cell partitioning, Orthogonal frequency division multiplexing-based multiple access (OFDMA) was employed to accommodate multi-cellular optical wireless communications without a large guard band between adjacent cells and without additional RF components. Moreover, we employed filter bank-based multicarrier (FBMC) to mitigate inter-cell interference generated in OFDMA-based cell partitioning due to asynchronous signals originated from RF path difference. By using FBMC-based cell partitioning, inter-cell interference could be effectively mitigated as well as capacity and spectral efficiency were improved about 1.5 times compared to those of OFDMA. Because no cyclic prefix (CP) is required in FBMC, the improvement factor could be increased if there is a large RF path difference between lighting cells. Moreover, it could be a stronger solution when many neighboring cells exist causing large interference. The proposed multicarrier-based cell partitioning combined with FBMC will effectively support visible light communication (VLC)-based localization-based services (LBS) and indoor positioning system by transparently providing trilateration-based positioning method.

  19. RssAB signaling coordinates early development of surface multicellularity in Serratia marcescens.

    Directory of Open Access Journals (Sweden)

    Yu-Huan Tsai

    Full Text Available Bacteria can coordinate several multicellular behaviors in response to environmental changes. Among these, swarming and biofilm formation have attracted significant attention for their correlation with bacterial pathogenicity. However, little is known about when and where the signaling occurs to trigger either swarming or biofilm formation. We have previously identified an RssAB two-component system involved in the regulation of swarming motility and biofilm formation in Serratia marcescens. Here we monitored the RssAB signaling status within single cells by tracing the location of the translational fusion protein EGFP-RssB following development of swarming or biofilm formation. RssAB signaling is specifically activated before surface migration in swarming development and during the early stage of biofilm formation. The activation results in the release of RssB from its cognate inner membrane sensor kinase, RssA, to the cytoplasm where the downstream gene promoters are located. Such dynamic localization of RssB requires phosphorylation of this regulator. By revealing the temporal activation of RssAB signaling following development of surface multicellular behavior, our findings contribute to an improved understanding of how bacteria coordinate their lifestyle on a surface.

  20. Noise-induced effects on multicellular biopacemaker spontaneous activity: Differences between weak and strong pacemaker cells

    Science.gov (United States)

    Aghighi, Alireza; Comtois, Philippe

    2017-09-01

    Self-organization of spontaneous activity of a network of active elements is important to the general theory of reaction-diffusion systems as well as for pacemaking activity to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes, consisting of resting and pacemaker cells, exhibit spontaneous activation of their electrical activity. Similarly, one proposed approach to the development of biopacemakers as an alternative to electronic pacemakers for cardiac therapy is based on heterogeneous cardiac cells with resting and spontaneously beating phenotypes. However, the combined effect of pacemaker characteristics, density, and spatial distribution of the pacemaker cells on spontaneous activity is unknown. Using a simple stochastic pattern formation algorithm, we previously showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of pacemaker cells. In this study, we show that this behavior is dependent on the pacemaker cell characteristics, with weaker pacemaker cells requiring higher density and larger clusters to sustain multicellular activity. These multicellular structures also demonstrated an increased sensitivity to voltage noise that favored spontaneous activity at lower density while increasing temporal variation in the period of activity. This information will help researchers overcome the current limitations of biopacemakers.

  1. SNAREing the basis of multicellularity: consequences of protein family expansion during evolution.

    Science.gov (United States)

    Kloepper, Tobias H; Kienle, C Nickias; Fasshauer, Dirk

    2008-09-01

    Vesicle trafficking between intracellular compartments of eukaryotic cells is mediated by conserved protein machineries. In each trafficking step, fusion of the vesicle with the acceptor membrane is driven by a set of distinctive soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins that assemble into tight 4-helix bundle complexes between the fusing membranes. During evolution, about 20 primordial SNARE types were modified independently in different eukaryotic lineages by episodes of duplication and diversification. Here we show that 2 major changes in the SNARE repertoire occurred in the evolution of animals, each reflecting a main overhaul of the endomembrane system. In addition, we found several lineage-specific losses of distinct SNAREs, particularly in nematodes and platyhelminthes. The first major transformation took place during the transition to multicellularity. The primary event that occurred during this transformation was an increase in the numbers of endosomal SNAREs, but the SNARE-related factor lethal giant larvae also emerged. Apparently, enhanced endosomal sorting capabilities were an advantage for early multicellular animals. The second major transformation during the rise of vertebrates resulted in a robust expansion of the secretory set of SNAREs, which may have helped develop a more versatile secretory apparatus.

  2. Characterization of the rdar morphotype, a multicellular behaviour in Enterobacteriaceae.

    Science.gov (United States)

    Römling, U

    2005-06-01

    The rdar morphotype, a multicellular behaviour of Salmonella enterica and Escherichia coli is characterized by the expression of the adhesive extracellular matrix components cellulose and curli fimbriae. The response regulator CsgD, which transcriptionally activates the biosynthesis of the exopolysaccharide cellulose and curli, also transforms cell physiology to the multicellular state. However, the only role of CsgD in cellulose biosynthesis is the activation of AdrA, a GGDEF domain protein that mediates production of the allosteric activator cyclic-di-(3'-5')guanylic acid (c-di-GMP). In S. enterica serovar Typhimurium a regulatory network consisting of 19 GGDEF/EAL domain-containing proteins tightly controls the concentration of c-di-GMP. c-di-GMP not only regulates the expression of cellulose, but also stimulates expression of adhesive curli and represses various modes of motility. Functions of characterized GGDEF and EAL domain proteins, as well as database searches, point to a global role for c-di-GMP as a novel secondary messenger that regulates a variety of cellular functions in response to diverse environmental stimuli already in the deepest roots of the prokaryotes.

  3. Selected System Models

    Science.gov (United States)

    Schmidt-Eisenlohr, F.; Puñal, O.; Klagges, K.; Kirsche, M.

    Apart from the general issue of modeling the channel, the PHY and the MAC of wireless networks, there are specific modeling assumptions that are considered for different systems. In this chapter we consider three specific wireless standards and highlight modeling options for them. These are IEEE 802.11 (as example for wireless local area networks), IEEE 802.16 (as example for wireless metropolitan networks) and IEEE 802.15 (as example for body area networks). Each section on these three systems discusses also at the end a set of model implementations that are available today.

  4. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  5. Multiscale Cloud System Modeling

    Science.gov (United States)

    Tao, Wei-Kuo; Moncrieff, Mitchell W.

    2009-01-01

    The central theme of this paper is to describe how cloud system resolving models (CRMs) of grid spacing approximately 1 km have been applied to various important problems in atmospheric science across a wide range of spatial and temporal scales and how these applications relate to other modeling approaches. A long-standing problem concerns the representation of organized precipitating convective cloud systems in weather and climate models. Since CRMs resolve the mesoscale to large scales of motion (i.e., 10 km to global) they explicitly address the cloud system problem. By explicitly representing organized convection, CRMs bypass restrictive assumptions associated with convective parameterization such as the scale gap between cumulus and large-scale motion. Dynamical models provide insight into the physical mechanisms involved with scale interaction and convective organization. Multiscale CRMs simulate convective cloud systems in computational domains up to global and have been applied in place of contemporary convective parameterizations in global models. Multiscale CRMs pose a new challenge for model validation, which is met in an integrated approach involving CRMs, operational prediction systems, observational measurements, and dynamical models in a new international project: the Year of Tropical Convection, which has an emphasis on organized tropical convection and its global effects.

  6. How 5000 independent rowers coordinate their strokes in order to row into the sunlight: Phototaxis in the multicellular green alga Volvox

    Directory of Open Access Journals (Sweden)

    Matsunaga Shigeru

    2010-07-01

    gravitational forces. Under our conditions, V. rousseletii spheroids showed no negative phototaxis. Conclusions On the basis of our results, we developed a mechanistic model that predicts the phototactic behavior in V. rousseletii. The model involves photoresponses, periodically changing light conditions, morphological polarity, rotation of the spheroid, two modes of flagellar beating, and the impact of gravity. Our results also indicate how recently evolved multicellular organisms adapted the phototactic capabilities of their unicellular ancestors to multicellular life.

  7. Control of multicellular development by the physically interacting deneddylases DEN1/DenA and COP9 signalosome.

    Directory of Open Access Journals (Sweden)

    Martin Christmann

    Full Text Available Deneddylases remove the ubiquitin-like protein Nedd8 from modified proteins. An increased deneddylase activity has been associated with various human cancers. In contrast, we show here that a mutant strain of the model fungus Aspergillus nidulans deficient in two deneddylases is viable but can only grow as a filament and is highly impaired for multicellular development. The DEN1/DenA and the COP9 signalosome (CSN deneddylases physically interact in A. nidulans as well as in human cells, and CSN targets DEN1/DenA for protein degradation. Fungal development responds to light and requires both deneddylases for an appropriate light reaction. In contrast to CSN, which is necessary for sexual development, DEN1/DenA is required for asexual development. The CSN-DEN1/DenA interaction that affects DEN1/DenA protein levels presumably balances cellular deneddylase activity. A deneddylase disequilibrium impairs multicellular development and suggests that control of deneddylase activity is important for multicellular development.

  8. Protein transfection study using multicellular tumor spheroids of human hepatoma Huh-7 cells.

    Directory of Open Access Journals (Sweden)

    Takuma Kato

    Full Text Available Several protein transfection reagents are commercially available and are powerful tools for elucidating function of a protein in a cell. Here we described protein transfection studies of the commercially available reagents, Pro-DeliverIN, Xfect, and TuboFect, using Huh-7 multicellular tumor spheroid (MCTS as a three-dimensional in vitro tumor model. A cellular uptake study using specific endocytosis inhibitors revealed that each reagent was internalized into Huh-7 MCTS by different mechanisms, which were the same as monolayer cultured Huh-7 cells. A certain amount of Pro-DeliverIN and Xfect was uptaken by Huh-7 cells through caveolae-mediated endocytosis, which may lead to transcytosis through the surface-first layered cells of MCTS. The results presented here will help in the choice and use of protein transfection reagents for evaluating anti-tumor therapeutic proteins against MCTS models.

  9. Dynamic Systems Modeling

    Directory of Open Access Journals (Sweden)

    Sorin Dan ŞANDOR

    2003-01-01

    Full Text Available System Dynamics was introduced by Jay W. Forrester in the 1960s. Since then the methodology was adopted in many areas of natural or social sciences. This article tries to present briefly how this methodology works, both as Systems Thinking and as Modelling with Vensim computer software.

  10. Synthetic multicellular oscillatory systems: controlling protein dynamics with genetic circuits

    Energy Technology Data Exchange (ETDEWEB)

    Koseska, Aneta [Interdisciplinary Center for Dynamics of Complex Systems, University of Potsdam, D-14469 Potsdam (Germany); Volkov, Evgenii [Department of Theoretical Physics, Lebedev Physical Institute, Leninskii 53, Moscow (Russian Federation); Kurths, Juergen, E-mail: akoseska@uni-potsdam.de [Institute of Physics, Humboldt University Berlin, D-10099 Berlin (Germany)

    2011-10-15

    Synthetic biology is a relatively new research discipline that combines standard biology approaches with the constructive nature of engineering. Thus, recent efforts in the field of synthetic biology have given a perspective to consider cells as 'programmable matter'. Here, we address the possibility of using synthetic circuits to control protein dynamics. In particular, we show how intercellular communication and stochasticity can be used to manipulate the dynamical behavior of a population of coupled synthetic units and, in this manner, finely tune the expression of specific proteins of interest, e.g. in large bioreactors.

  11. Modeling Sustainable Food Systems

    Science.gov (United States)

    Allen, Thomas; Prosperi, Paolo

    2016-05-01

    The processes underlying environmental, economic, and social unsustainability derive in part from the food system. Building sustainable food systems has become a predominating endeavor aiming to redirect our food systems and policies towards better-adjusted goals and improved societal welfare. Food systems are complex social-ecological systems involving multiple interactions between human and natural components. Policy needs to encourage public perception of humanity and nature as interdependent and interacting. The systemic nature of these interdependencies and interactions calls for systems approaches and integrated assessment tools. Identifying and modeling the intrinsic properties of the food system that will ensure its essential outcomes are maintained or enhanced over time and across generations, will help organizations and governmental institutions to track progress towards sustainability, and set policies that encourage positive transformations. This paper proposes a conceptual model that articulates crucial vulnerability and resilience factors to global environmental and socio-economic changes, postulating specific food and nutrition security issues as priority outcomes of food systems. By acknowledging the systemic nature of sustainability, this approach allows consideration of causal factor dynamics. In a stepwise approach, a logical application is schematized for three Mediterranean countries, namely Spain, France, and Italy.

  12. Sorodiplophrys stercorea: Another Novel Lineage of Sorocarpic Multicellularity.

    Science.gov (United States)

    Tice, Alexander K; Silberman, Jeffrey D; Walthall, Austin C; Le, Khoa N D; Spiegel, Frederick W; Brown, Matthew W

    2016-09-01

    Sorodiplophrys stercorea is a sorocarpic organism that utilizes filose pseudopodia for locomotion and absorptive nutrition. It has traditionally been considered to be a member of the Labyrinthulae based on its morphology. Its closest relatives were thought to be species in the taxon Diplophrys. Since the genus Diplophrys has been shown to be paraphyletic and S. stercorea has pseudopodia similar to some members of Rhizaria, we examined its relationship with other eukaryotes. We obtained four isolates from the dung of cow and horse, brought each into monoeukaryotic culture, and sequenced their SSU rRNA gene for phylogenetic analysis. All our isolates were shown to form a monophyletic group in the Labyrinthulae, nested in the Amphifiloidea clade. Our results demonstrate that Sorodiplophrys is more closely related to species of the genus Amphifila than to Diplophrys and represents an additional independent origin of sorocarpic multicellularity among eukaryotes. This study represents the first confirmed sorocarpic lifestyle in the Stramenopiles.

  13. Multicellular rosette formation links planar cell polarity to tissue morphogenesis.

    Science.gov (United States)

    Blankenship, J Todd; Backovic, Stephanie T; Sanny, Justina S P; Weitz, Ori; Zallen, Jennifer A

    2006-10-01

    Elongation of the body axis is accompanied by the assembly of a polarized cytoarchitecture that provides the basis for directional cell behavior. We find that planar polarity in the Drosophila embryo is established through a sequential enrichment of actin-myosin cables and adherens junction proteins in complementary surface domains. F-actin accumulation at AP interfaces represents the first break in planar symmetry and occurs independently of proper junctional protein distribution at DV interfaces. Polarized cells engage in a novel program of locally coordinated behavior to generate multicellular rosette structures that form and resolve in a directional fashion. Actin-myosin structures align across multiple cells during rosette formation, and adherens junction proteins assemble in a stepwise fashion during rosette resolution. Patterning genes essential for axis elongation selectively affect the frequency and directionality of rosette formation. We propose that the generation of higher-order rosette structures links local cell interactions to global tissue reorganization during morphogenesis.

  14. Three dimensional multi-cellular muscle-like tissue engineering in perfusion-based bioreactors.

    Science.gov (United States)

    Cerino, Giulia; Gaudiello, Emanuele; Grussenmeyer, Thomas; Melly, Ludovic; Massai, Diana; Banfi, Andrea; Martin, Ivan; Eckstein, Friedrich; Grapow, Martin; Marsano, Anna

    2016-01-01

    Conventional tissue engineering strategies often rely on the use of a single progenitor cell source to engineer in vitro biological models; however, multi-cellular environments can better resemble the complexity of native tissues. Previous described co-culture models used skeletal myoblasts, as parenchymal cell source, and mesenchymal or endothelial cells, as stromal component. Here, we propose instead the use of adipose tissue-derived stromal vascular fraction cells, which include both mesenchymal and endothelial cells, to better resemble the native stroma. Percentage of serum supplementation is one of the crucial parameters to steer skeletal myoblasts toward either proliferation (20%) or differentiation (5%) in two-dimensional culture conditions. On the contrary, three-dimensional (3D) skeletal myoblast culture often simply adopts the serum content used in monolayer, without taking into account the new cell environment. When considering 3D cultures of mm-thick engineered tissues, homogeneous and sufficient oxygen supply is paramount to avoid formation of necrotic cores. Perfusion-based bioreactor culture can significantly improve the oxygen access to the cells, enhancing the viability and the contractility of the engineered tissues. In this study, we first investigated the influence of different serum supplementations on the skeletal myoblast ability to proliferate and differentiate during 3D perfusion-based culture. We tested percentages of serum promoting monolayer skeletal myoblast-proliferation (20%) and differentiation (5%) and suitable for stromal cell culture (10%) with a view to identify the most suitable condition for the subsequent co-culture. The 10% serum medium composition resulted in the highest number of mature myotubes and construct functionality. Co-culture with stromal vascular fraction cells at 10% serum also supported the skeletal myoblast differentiation and maturation, hence providing a functional engineered 3D muscle model that resembles

  15. Nascent multicellular life and the emergence of individuality

    Indian Academy of Sciences (India)

    Silvia De Monte; Paul B Rainey

    2014-04-01

    The evolution of multicellular organisms from unicellular ancestors involves a shift in the level at which selection operates. It is usual to think about this shift in terms of the emergence of traits that cause heritable differences in reproductive output at the level of nascent collectives. Defining these traits and the causes of their origin lies at the heart of understanding the evolution of multicellular life. In working toward a mechanistic, take-nothing-for-granted account, we begin by recognizing that the standard Lewontin formulation of properties necessary and sufficient for evolution by natural selection does not necessarily encompass Darwinian evolution in primitive collectives where parent-offspring relationships may have been poorly defined. This, we suggest, limits the ability to conceptualize and capture the earliest manifestations of Darwinian properties. By way of solution we propose a relaxed interpretation of Lewontin’s conditions and present these in the form of a set of necessary requirements for evolution by natural selection based upon the establishment of genealogical connections between recurrences of collectives. With emphasis on genealogy – as opposed to reproduction – it is possible to conceive selection acting on collectives prior to any manifestation of heritable variance in fitness. Such possibility draws attention to the evolutionary emergence of traits that strengthen causal relationships between recurrences – traits likely to underpin the emergence of forms of multiplication that establish parent-offspring relationships. Application of this framework to collectives of marginal status, particularly those whose recurrence is not defined by genealogy, makes clear that change at the level of collectives need not arise from selection acting at the higher level. We conclude by outlining applicability of our framework to loosely defined collectives of cells, such as those comprising the slugs of social amoeba and microbes that

  16. Calcium inhibits bap-dependent multicellular behavior in Staphylococcus aureus.

    Science.gov (United States)

    Arrizubieta, María Jesús; Toledo-Arana, Alejandro; Amorena, Beatriz; Penadés, José R; Lasa, Iñigo

    2004-11-01

    Bap (biofilm-associated protein) is a 254-kDa staphylococcal surface protein implicated in formation of biofilms by staphylococci isolated from chronic mastitis infections. The presence of potential EF-hand motifs in the amino acid sequence of Bap prompted us to investigate the effect of calcium on the multicellular behavior of Bap-expressing staphylococci. We found that addition of millimolar amounts of calcium to the growth media inhibited intercellular adhesion of and biofilm formation by Bap-positive strain V329. Addition of manganese, but not addition of magnesium, also inhibited biofilm formation, whereas bacterial aggregation in liquid media was greatly enhanced by metal-chelating agents. In contrast, calcium or chelating agents had virtually no effect on the aggregation of Bap-deficient strain M556. The biofilm elicited by insertion of bap into the chromosome of a biofilm-negative strain exhibited a similar dependence on the calcium concentration, indicating that the observed calcium inhibition was an inherent property of the Bap-mediated biofilms. Site-directed mutagenesis of two of the putative EF-hand domains resulted in a mutant strain that was capable of forming a biofilm but whose biofilm was not inhibited by calcium. Our results indicate that Bap binds Ca2+ with low affinity and that Ca2+ binding renders the protein noncompetent for biofilm formation and for intercellular adhesion. The fact that calcium inhibition of Bap-mediated multicellular behavior takes place in vitro at concentrations similar to those found in milk serum supports the possibility that this inhibition is relevant to the pathogenesis and/or epidemiology of the bacteria in the mastitis process.

  17. Green algae and the origins of multicellularity in the plant kingdom.

    Science.gov (United States)

    Umen, James G

    2014-10-16

    The green lineage of chlorophyte algae and streptophytes form a large and diverse clade with multiple independent transitions to produce multicellular and/or macroscopically complex organization. In this review, I focus on two of the best-studied multicellular groups of green algae: charophytes and volvocines. Charophyte algae are the closest relatives of land plants and encompass the transition from unicellularity to simple multicellularity. Many of the innovations present in land plants have their roots in the cell and developmental biology of charophyte algae. Volvocine algae evolved an independent route to multicellularity that is captured by a graded series of increasing cell-type specialization and developmental complexity. The study of volvocine algae has provided unprecedented insights into the innovations required to achieve multicellularity.

  18. Modeling Complex Systems

    CERN Document Server

    Boccara, Nino

    2010-01-01

    Modeling Complex Systems, 2nd Edition, explores the process of modeling complex systems, providing examples from such diverse fields as ecology, epidemiology, sociology, seismology, and economics. It illustrates how models of complex systems are built and provides indispensable mathematical tools for studying their dynamics. This vital introductory text is useful for advanced undergraduate students in various scientific disciplines, and serves as an important reference book for graduate students and young researchers. This enhanced second edition includes: . -recent research results and bibliographic references -extra footnotes which provide biographical information on cited scientists who have made significant contributions to the field -new and improved worked-out examples to aid a student’s comprehension of the content -exercises to challenge the reader and complement the material Nino Boccara is also the author of Essentials of Mathematica: With Applications to Mathematics and Physics (Springer, 2007).

  19. A new, fast and semi-automated size determination method (SASDM for studying multicellular tumor spheroids

    Directory of Open Access Journals (Sweden)

    Lindhe Örjan

    2005-11-01

    Full Text Available Abstract Background Considering the width and importance of using Multicellular Tumor Spheroids (MTS in oncology research, size determination of MTSs by an accurate and fast method is essential. In the present study an effective, fast and semi-automated method, SASDM, was developed to determinate the size of MTSs. The method was applied and tested in MTSs of three different cell-lines. Frozen section autoradiography and Hemotoxylin Eosin (H&E staining was used for further confirmation. Results SASDM was shown to be effective, user-friendly, and time efficient, and to be more precise than the traditional methods and it was applicable for MTSs of different cell-lines. Furthermore, the results of image analysis showed high correspondence to the results of autoradiography and staining. Conclusion The combination of assessment of metabolic condition and image analysis in MTSs provides a good model to evaluate the effect of various anti-cancer treatments.

  20. A new, fast and semi-automated size determination method (SASDM) for studying multicellular tumor spheroids

    Science.gov (United States)

    Monazzam, Azita; Razifar, Pasha; Lindhe, Örjan; Josephsson, Raymond; Långström, Bengt; Bergström, Mats

    2005-01-01

    Background Considering the width and importance of using Multicellular Tumor Spheroids (MTS) in oncology research, size determination of MTSs by an accurate and fast method is essential. In the present study an effective, fast and semi-automated method, SASDM, was developed to determinate the size of MTSs. The method was applied and tested in MTSs of three different cell-lines. Frozen section autoradiography and Hemotoxylin Eosin (H&E) staining was used for further confirmation. Results SASDM was shown to be effective, user-friendly, and time efficient, and to be more precise than the traditional methods and it was applicable for MTSs of different cell-lines. Furthermore, the results of image analysis showed high correspondence to the results of autoradiography and staining. Conclusion The combination of assessment of metabolic condition and image analysis in MTSs provides a good model to evaluate the effect of various anti-cancer treatments. PMID:16283948

  1. A new, fast and semi-automated size determination method (SASDM) for studying multicellular tumor spheroids.

    Science.gov (United States)

    Monazzam, Azita; Razifar, Pasha; Lindhe, Orjan; Josephsson, Raymond; Långström, Bengt; Bergström, Mats

    2005-11-14

    Considering the width and importance of using Multicellular Tumor Spheroids (MTS) in oncology research, size determination of MTSs by an accurate and fast method is essential. In the present study an effective, fast and semi-automated method, SASDM, was developed to determinate the size of MTSs. The method was applied and tested in MTSs of three different cell-lines. Frozen section autoradiography and Hemotoxylin Eosin (H&E) staining was used for further confirmation. SASDM was shown to be effective, user-friendly, and time efficient, and to be more precise than the traditional methods and it was applicable for MTSs of different cell-lines. Furthermore, the results of image analysis showed high correspondence to the results of autoradiography and staining. The combination of assessment of metabolic condition and image analysis in MTSs provides a good model to evaluate the effect of various anti-cancer treatments.

  2. Molecular Regulation of the Mitosis/Meiosis Decision in Multicellular Organisms

    Science.gov (United States)

    Kimble, Judith

    2011-01-01

    A major step in the journey from germline stem cell to differentiated gamete is the decision to leave the mitotic cell cycle and begin progression through the meiotic cell cycle. Over the past decade, molecular regulators of the mitosis/meiosis decision have been discovered in most of the major model multicellular organisms. Historically, the mitosis/meiosis decision has been closely linked with controls of germline self-renewal and the sperm/egg decision, especially in nematodes and mice. Molecular explanations of those linkages clarify our understanding of this fundamental germ cell decision, and unifying themes have begun to emerge. Although the complete circuitry of the decision is not known in any organism, the recent advances promise to impact key issues in human reproduction and agriculture. PMID:21646377

  3. Droplet-based microfluidic platforms for the encapsulation and screening of Mammalian cells and multicellular organisms.

    Science.gov (United States)

    Clausell-Tormos, Jenifer; Lieber, Diana; Baret, Jean-Christophe; El-Harrak, Abdeslam; Miller, Oliver J; Frenz, Lucas; Blouwolff, Joshua; Humphry, Katherine J; Köster, Sarah; Duan, Honey; Holtze, Christian; Weitz, David A; Griffiths, Andrew D; Merten, Christoph A

    2008-05-01

    High-throughput, cell-based assays require small sample volumes to reduce assay costs and to allow for rapid sample manipulation. However, further miniaturization of conventional microtiter plate technology is problematic due to evaporation and capillary action. To overcome these limitations, we describe droplet-based microfluidic platforms in which cells are grown in aqueous microcompartments separated by an inert perfluorocarbon carrier oil. Synthesis of biocompatible surfactants and identification of gas-permeable storage systems allowed human cells, and even a multicellular organism (C. elegans), to survive and proliferate within the microcompartments for several days. Microcompartments containing single cells could be reinjected into a microfluidic device after incubation to measure expression of a reporter gene. This should open the way for high-throughput, cell-based screening that can use >1000-fold smaller assay volumes and has approximately 500x higher throughput than conventional microtiter plate assays.

  4. Distributed generation systems model

    Energy Technology Data Exchange (ETDEWEB)

    Barklund, C.R.

    1994-12-31

    A slide presentation is given on a distributed generation systems model developed at the Idaho National Engineering Laboratory, and its application to a situation within the Idaho Power Company`s service territory. The objectives of the work were to develop a screening model for distributed generation alternatives, to develop a better understanding of distributed generation as a utility resource, and to further INEL`s understanding of utility concerns in implementing technological change.

  5. Modeling the earth system

    Energy Technology Data Exchange (ETDEWEB)

    Ojima, D. [ed.

    1992-12-31

    The 1990 Global Change Institute (GCI) on Earth System Modeling is the third of a series organized by the Office for Interdisciplinary Earth Studies to look in depth at particular issues critical to developing a better understanding of the earth system. The 1990 GCI on Earth System Modeling was organized around three themes: defining critical gaps in the knowledge of the earth system, developing simplified working models, and validating comprehensive system models. This book is divided into three sections that reflect these themes. Each section begins with a set of background papers offering a brief tutorial on the subject, followed by working group reports developed during the institute. These reports summarize the joint ideas and recommendations of the participants and bring to bear the interdisciplinary perspective that imbued the institute. Since the conclusion of the 1990 Global Change Institute, research programs, nationally and internationally, have moved forward to implement a number of the recommendations made at the institute, and many of the participants have maintained collegial interactions to develop research projects addressing the needs identified during the two weeks in Snowmass.

  6. Development of Three-Dimensional Multicellular Tissue-Like Constructs for Mutational Analysis Using Macroporous Microcarriers

    Science.gov (United States)

    Jordan, Jacqueline A.; Fraga, Denise N.; Gonda, Steve R.

    2002-01-01

    A three-dimensional (3-D), tissue-like model was developed for the genotoxic assessment of space environment. In previous experiments, we found that culturing mammalian cells in a NASA-designed bioreactor, using Cytodex-3 beads as a scaffold, generated 3-D multicellular spheroids. In an effort to generate scaffold-free spheroids, we developed a new 3-D tissue-like model by coculturing fibroblast and epithelial cell in a NASA bioreactor using macroporous Cultispher-S(TradeMark) microcarriers. Big Blue(Registered Trademark) Rat 2(Lambda) fibroblasts, genetically engineered to contain multiple copies (>60 copies/cell) of the Lac I target gene, were cocultured with radio-sensitive human epithelial cells, H184F5. Over an 8-day period, samples were periodically examined by microscopy and histology to confirm cell attachment, growth, and viability. Immunohistochemistry and western analysis were used to evaluate the expression of specific cytoskeletal and adhesion proteins. Key cell culture parameters (glucose, pH, and lactate concentrations) were monitored daily. Controls were two-dimensional mono layers of fibroblast or epithelial cells cultured in T-flasks. Analysis of 3-D spheroids from the bioreactor suggests fibroblast cells attached to and completely covered the bead surface and inner channels by day 3 in the bioreactor. Treatment of the 3-day spheroids with dispase II dissolved the Cultisphers(TradeMark) and produced multicellular, bead-less constructs. Immunohistochemistry confirmed the presence of vi.mentin, cytokeratin and E-cadherin in treated spheroids. Examination of the dispase II treated spheroids with transmission electron microscopy (TEM) also showed the presence of desmosomes. These results suggest that the controlled enzymatic degradation of an artificial matrix in the low shear environment of the NASA-designed bioreactor can produce 3-D tissue-like spheroids. 2

  7. A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking.

    Science.gov (United States)

    Pârvu, Ovidiu; Gilbert, David

    2016-01-01

    Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour

  8. Dynamical patterning modules: a "pattern language" for development and evolution of multicellular form.

    Science.gov (United States)

    Newman, Stuart A; Bhat, Ramray

    2009-01-01

    This article considers the role played by a core set of "dynamical patterning modules" (DPMs) in the origination, development and evolution of complex organisms. These consist of the products of a subset of the genes of what has come to be known as the "developmental-genetic toolkit" in association with physical processes they mobilize. The physical processes are those characteristic of chemically and mechanically excitable mesoscopic systems like cell aggregates: cohesion, viscoelasticity, diffusion, spatiotemporal heterogeneity based on activator-inhibitor interaction, and multistable and oscillatory dynamics. We focus on the emergence of the Metazoa, and show how toolkit gene products and pathways that pre-existed the metazoans acquired novel morphogenetic functions simply by virtue of the change in scale and context inherent to multicellularity. We propose that DPMs, acting singly and in combination with each other, constitute a "pattern language" capable of generating all metazoan body plans and organ forms. This concept implies that the multicellular organisms of the late Precambrian-early Cambrian were phenotypically plastic, fluently exploring morphospace in a fashion decoupled from both function-based selection and genotypic change. The relatively stable developmental trajectories and morphological phenotypes of modern organisms, then, are considered to be products of stabilizing selection. This perspective solves the apparent "molecular homology-analogy paradox," whereby widely divergent modern animal types utilize the same molecular toolkit during development, but it does so by inverting the neo-Darwinian principle that phenotypic disparity was generated over long periods of time in concert with, and in proportion to genotypic change.

  9. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2009-01-01

    This third volume completes the Work Mechanical Systems, Classical Models. The first two volumes dealt with particle dynamics and with discrete and continuous mechanical systems. The present volume studies analytical mechanics. Topics like Lagrangian and Hamiltonian mechanics, the Hamilton-Jacobi method, and a study of systems with separate variables are thoroughly discussed. Also included are variational principles and canonical transformations, integral invariants and exterior differential calculus, and particular attention is given to non-holonomic mechanical systems. The author explains in detail all important aspects of the science of mechanics, regarded as a natural science, and shows how they are useful in understanding important natural phenomena and solving problems of interest in applied and engineering sciences. Professor Teodorescu has spent more than fifty years as a Professor of Mechanics at the University of Bucharest and this book relies on the extensive literature on the subject as well as th...

  10. Synergistic cooperation promotes multicellular performance and unicellular free-rider persistence.

    Science.gov (United States)

    Driscoll, William W; Travisano, Michael

    2017-06-05

    The evolution of multicellular life requires cooperation among cells, which can be undermined by intra-group selection for selfishness. Theory predicts that selection to avoid non-cooperators limits social interactions among non-relatives, yet previous evolution experiments suggest that intra-group conflict is an outcome, rather than a driver, of incipient multicellular life cycles. Here we report the evolution of multicellularity via two distinct mechanisms of group formation in the unicellular budding yeast Kluyveromyces lactis. Cells remain permanently attached following mitosis, giving rise to clonal clusters (staying together); clusters then reversibly assemble into social groups (coming together). Coming together amplifies the benefits of multicellularity and allows social clusters to collectively outperform solitary clusters. However, cooperation among non-relatives also permits fast-growing unicellular lineages to 'free-ride' during selection for increased size. Cooperation and competition for the benefits of multicellularity promote the stable coexistence of unicellular and multicellular genotypes, underscoring the importance of social and ecological context during the transition to multicellularity.

  11. NEP systems model

    Science.gov (United States)

    George, Jeffrey A.

    A new nuclear electric propulsion (NEP) systems analysis code is discussed. The new code is modular and consists of a driver code and various subsystem models. The code models five different subsystems: (1) reactor/shield; (2) power conversion; (3) heat rejection; (4) power management and distribution (PMAD); and (5) thrusters. The code optimizes for the following design criteria: minimum mass; minimum radiator area; and low mass/low area. The code also optimizes the following parameters: separation distance; temperature ratio; pressure ratio; and transmission frequency. The discussion is presented in vugraph form.

  12. National Energy Modeling System

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, C.W. (Energy Information Administration, Washington, DC (United States))

    1993-01-01

    The Energy Information Administration is developing a new National Energy Modeling System to provide annual forecasts of energy supply, demand, and prices on a regional basis in the United States and, to a limited extent, in the rest of the world. The design for the system was based on a requirements analysis, a comparison of requirements with existing modeling capabilities, and a series of widely circulated issue papers defining the choices and tradeoffs for 13 key design decisions. An initial prototpye of the new NEMS was implemented in late 1992, with a more complete, operational version in 1993. NEMS is expected to provide EIA and other users with a greatly enhanced ability to illustrate quickly and effectively the effects of a wide range of energy policy proposals.

  13. Modeling Novo Nordisk Production Systems

    DEFF Research Database (Denmark)

    Miller, Thomas Dedenroth

    1997-01-01

    This report describes attributes of models and systems, and how models can be used for description of production systems. There are special attention on the 'Theory of Domains'.......This report describes attributes of models and systems, and how models can be used for description of production systems. There are special attention on the 'Theory of Domains'....

  14. Robust finite time observer design for multicellular converters

    Science.gov (United States)

    Defoort, Michael; Djemai, Mohamed; Floquet, Thierry; Perruquetti, Wilfrid

    2011-11-01

    In this article, a nonlinear finite time observer is designed for multicellular converters. The aim is to estimate the capacitor voltages by taking into account the hybrid behaviour of the converter. This article extends the validity of the strong Lyapunov function, proposed in Moreno and Osorio (Moreno, J., and Osorio, M. (2008), 'A Lyapunov Approach to Second Order Sliding Mode Controllers and Observers', in Proceedings of the IEEE Conference on Decision and Control, New Orleans, USA, pp. 2856-2861), in order to deeply study the reaching time estimation and robustness of the homogeneous finite time observer given in Perruquetti et al. (Perruquetti, W., Floquet, T., and Moulay, E. (2008), 'Finite Time Observers: Application to Secure Communication', IEEE Transactions on Automatic Control, 53, 356-360). The proposed approach enables the stabilisation of the observation errors in spite of the presence of perturbations and uncertainties. Some simulations and comparisons with the super-twisting sliding mode observer highlight the efficiency of the proposed strategy.

  15. System of systems modeling and analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, James E.; Anderson, Dennis James; Longsine, Dennis E. (Intera, Inc., Austin, TX); Shirah, Donald N.

    2005-01-01

    This report documents the results of an LDRD program entitled 'System of Systems Modeling and Analysis' that was conducted during FY 2003 and FY 2004. Systems that themselves consist of multiple systems (referred to here as System of Systems or SoS) introduce a level of complexity to systems performance analysis and optimization that is not readily addressable by existing capabilities. The objective of the 'System of Systems Modeling and Analysis' project was to develop an integrated modeling and simulation environment that addresses the complex SoS modeling and analysis needs. The approach to meeting this objective involved two key efforts. First, a static analysis approach, called state modeling, has been developed that is useful for analyzing the average performance of systems over defined use conditions. The state modeling capability supports analysis and optimization of multiple systems and multiple performance measures or measures of effectiveness. The second effort involves time simulation which represents every system in the simulation using an encapsulated state model (State Model Object or SMO). The time simulation can analyze any number of systems including cross-platform dependencies and a detailed treatment of the logistics required to support the systems in a defined mission.

  16. Observation of multicellular spinning behavior of Proteus mirabilis by atomic force microscopy and multifunctional microscopy.

    Science.gov (United States)

    Liu, Yanxia; Deng, Yuanxin; Luo, Shuxiu; Deng, Yu; Guo, Linming; Xu, Weiwei; Liu, Lei; Liu, Junkang

    2014-01-01

    This study aimed to observe the multicellular spinning behavior of Proteus mirabilis by atomic force microscopy (AFM) and multifunctional microscopy in order to understand the mechanism underlying this spinning movement and its biological significance. Multifunctional microscopy with charge-coupled device (CCD) and real-time AFM showed changes in cell structure and shape of P. mirabilis during multicellular spinning movement. Specifically, the morphological characteristics of P. mirabilis, multicellular spinning dynamics, and unique movement were observed. Our findings indicate that the multicellular spinning behavior of P. mirabilis may be used to collect nutrients, perform colonization, and squeeze out competitors. The movement characteristics of P. mirabilis are vital to the organism's biological adaptability to the surrounding environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Symplasmata are a clonal, conditional, and reversible type of bacterial multicellularity

    NARCIS (Netherlands)

    Tecon, R.; Leveau, Johan H. J.

    2016-01-01

    Microorganisms are capable of remarkable social behaviours, such as forming transient multicellular assemblages with properties and adaptive abilities exceeding those of individual cells. Here, we report on the formation and structure of genets known as symplasmata produced by Pantoea eucalypti

  18. Evolution of multicellularity coincided with increased diversification of cyanobacteria and the Great Oxidation Event

    Science.gov (United States)

    Schirrmeister, Bettina E.; de Vos, Jurriaan M.; Antonelli, Alexandre; Bagheri, Homayoun C.

    2013-01-01

    Cyanobacteria are among the most diverse prokaryotic phyla, with morphotypes ranging from unicellular to multicellular filamentous forms, including those able to terminally (i.e., irreversibly) differentiate in form and function. It has been suggested that cyanobacteria raised oxygen levels in the atmosphere around 2.45–2.32 billion y ago during the Great Oxidation Event (GOE), hence dramatically changing life on the planet. However, little is known about the temporal evolution of cyanobacterial lineages, and possible interplay between the origin of multicellularity, diversification of cyanobacteria, and the rise of atmospheric oxygen. We estimated divergence times of extant cyanobacterial lineages under Bayesian relaxed clocks for a dataset of 16S rRNA sequences representing the entire known diversity of this phylum. We tested whether the evolution of multicellularity overlaps with the GOE, and whether multicellularity is associated with significant shifts in diversification rates in cyanobacteria. Our results indicate an origin of cyanobacteria before the rise of atmospheric oxygen. The evolution of multicellular forms coincides with the onset of the GOE and an increase in diversification rates. These results suggest that multicellularity could have played a key role in triggering cyanobacterial evolution around the GOE. PMID:23319632

  19. High Capacity Downlink Transmission with MIMO Interference Subspace Rejection in Multicellular CDMA Networks

    Directory of Open Access Journals (Sweden)

    Henrik Hansen

    2004-05-01

    Full Text Available We proposed recently a new technique for multiuser detection in CDMA networks, denoted by interference subspace rejection (ISR, and evaluated its performance on the uplink. This paper extends its application to the downlink (DL. On the DL, the information about the interference is sparse, for example, spreading factor (SF and modulation of interferers may not be known, which makes the task much more challenging. We present three new ISR variants which require no prior knowledge of interfering users. The new solutions are applicable to MIMO systems and can accommodate any modulation, coding, SF, and connection type. We propose a new code allocation scheme denoted by DACCA which significantly reduces the complexity of our solution at the receiving mobile. We present estimates of user capacities and data rates attainable under practically reasonable conditions regarding interferences identified and suppressed in a multicellular interference-limited system. We show that the system capacity increases linearly with the number of antennas despite the existence of interference. Our new DL multiuser receiver consistently provides an Erlang capacity gain of at least 3 db over the single-user detector.

  20. Cyclooxygenase-2 inhibitor is a robust enhancer of anticancer agents against hepatocellular carcinoma multicellular spheroids

    Directory of Open Access Journals (Sweden)

    Cui J

    2014-02-01

    Full Text Available Jie Cui,1,2 Ya-Huan Guo,3 Hong-Yi Zhang,4 Li-Li Jiang,1 Jie-Qun Ma,1 Wen-Juan Wang,1 Min-Cong Wang,1 Cheng-Cheng Yang,1 Ke-Jun Nan,1 Li-Ping Song5 1Department of Oncology, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, 2Department of Oncology, Yan'an University Affiliated Hospital, Yan'an, 3Department of Oncology, Shaanxi Province Cancer Hospital, Xi'an, 4Department of Urology, Yan'an University Affiliated Hospital, Yan'an, 5Department of Radiotherapy, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, People's Republic of China Purpose: Celecoxib, an inhibitor of cyclooxygenase-2 (COX2, was investigated for enhancement of chemotherapeutic efficacy in cancer clinical trials. This study aimed to determine whether celecoxib combined with 5-fluorouracil or sorafenib or gefitinib is beneficial in HepG2 multicellular spheroids (MCSs, as well as elucidate the underlying mechanisms. Methods: The human hepatocellular carcinoma cell line HepG2 MCSs were used as in vitro models to investigate the effects of celecoxib combined with 5-fluorouracil or sorafenib or gefitinib treatment on cell growth, apoptosis, and signaling pathway. Results: MCSs showed resistance to drugs compared with monolayer cells. Celecoxib combined with 5-fluorouracil or sorafenib exhibited a synergistic action. Exposure to celecoxib (21.8 µmol/L plus 5-fluorouracil (8.1 × 10-3 g/L or sorafenib (4.4 µmol/L increased apoptosis but exerted no effect on COX2, phosphorylated epidermal growth-factor receptor (p-EGFR and phosphorylated (p-AKT expression. Gefitinib (5 µmol/L, which exhibits no growth-inhibition activity as a single agent, increased the inhibitory effect of celecoxib. Gefitinib (5 µmol/L plus celecoxib (21.8 µmol/L increased apoptosis. COX2, p-EGFR, and p-AKT were inhibited. Conclusion: Celecoxib combined with 5-fluorouracil or sorafenib or gefitinib may be superior to single-agent therapy in HepG2

  1. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  2. ECO-BIOLOGICAL SYSTEM MODELING

    Directory of Open Access Journals (Sweden)

    T. I. Burak

    2015-01-01

    Full Text Available The methodology for computer modeling of complex eco-biological models is presented in this paper. It is based on system approach of J. Forrester. Developed methodology is universal for complex ecological and biological systems. Modeling algorithm considers specialties of eco-biological systems and shows adequate and accurate results in practice. 

  3. The pre-Mendelian, pre-Darwinian world: Shifting relations between genetic and epigenetic mechanisms in early multicellular evolution

    Indian Academy of Sciences (India)

    Stuart A Newman

    2005-02-01

    The reliable dependence of many features of contemporary organisms on changes in gene content and activity is tied to the processes of Mendelian inheritance and Darwinian evolution. With regard to morphological characters, however, Mendelian inheritance is the exception rather than the rule, and neo-Darwinian mechanisms in any case do not account for the origination (as opposed to the inherited variation) of such characters. It is proposed, therefore, that multicellular organisms passed through a pre-Mendelian, pre-Darwinian phase, whereby cells, genes and gene products constituted complex systems with context-dependent, self-organizing morphogenetic capabilities. An example is provided of a plausible ‘core’ mechanism for the development of the vertebrate limb that is both inherently pattern forming and morphogenetically plastic. It is suggested that most complex multicellular structures originated from such systems. The notion that genes are privileged determinants of biological characters can only be sustained by neglecting questions of evolutionary origination and the evolution of developmental mechanisms.

  4. Generation of Multicellular Breast Cancer Tumor Spheroids: Comparison of Different Protocols.

    Science.gov (United States)

    Froehlich, Karolin; Haeger, Jan-Dirk; Heger, Julia; Pastuschek, Jana; Photini, Stella Mary; Yan, Yan; Lupp, Amelie; Pfarrer, Christiane; Mrowka, Ralf; Schleußner, Ekkehard; Markert, Udo R; Schmidt, André

    2016-12-01

    Multicellular tumor spheroids are widely used models in tumor research. Because of their three dimensional organization they can simulate avascular tumor areas comprising proliferative and necrotic cells. Nonetheless, protocols for spheroid generation are still inconsistent. Therefore, in this study the breast cancer cell lines MCF-7, MDA-MB-231 and SK-BR-3 have been used to compare different spheroid generation models including hanging drop, liquid overlay and suspension culture techniques, each under several conditions. Experimental approaches differed in cell numbers (400-10,000), media and additives (25 % methocel, 25 % methocel plus 1 % Matrigel, 3.5 % Matrigel). In total, 42 different experimental setups have been tested. Generation of spheroids was evaluated by light microscopy and the structural composition was assessed immunohistochemically by means of Ki-67, cleaved poly (ADP-ribose) polymerase (cPARP) and mucin-1 (MUC-1) expression. Although the tested cell lines diverged widely in their capacity of forming spheroids we recommend hanging drops supplemented with 25 % methocel as the most reliable and efficient method with regard to success of generation of uniform spheroids, costs, experimental complexity and time expenditure in the different cell lines. MCF-7 cells formed spheroids under almost all analyzed conditions, and MDA-MB-231 cells under only one protocol (liquid overlay technique, 3.5 % Matrigel), while SK-BR-3 did not under neither condition. Therefore, we outline specific methods and recommend the use of adapted and standardized spheroid generation protocols for each cell line.

  5. Rapid Generation of In Vitro Multicellular Spheroids for the Study of Monoclonal Antibody Therapy

    Directory of Open Access Journals (Sweden)

    Yen T. Phung, Dario Barbone, V. Courtney Broaddus, Mitchell Ho

    2011-01-01

    Full Text Available Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates and are difficult to study in vitro. Cells cultured as monolayers typically exhibit less resistance to therapy than those grown in vivo. Therefore, it is important to develop an alternative research model that better represents in vivo tumors. We have developed a protocol to produce multicellular spheroids, a simple and more relevant model of in vivo tumors that allows for further investigations of the microenvironmental effects on drug penetration and tumor cell killing. The protocol is used to produce in vitro three-dimensional tumor spheroids from established human cancer cell lines and primary cancer cells isolated from patients without the use of any extracellular components. To study the ability of tumor-targeting immunoconjugates to penetrate these tumor spheroids in vitro, we have used an immunotoxin targeting mesothelin, a surface protein expressed in malignant mesotheliomas. This method for producing consistent, reproducible 3D spheroids may allow for improved testing of novel monoclonal antibodies and other agents for their ability to penetrate solid tumors for cancer therapy.

  6. A multicellular spheroid array to realize spheroid formation, culture, and viability assay on a chip.

    Science.gov (United States)

    Torisawa, Yu-suke; Takagi, Airi; Nashimoto, Yuji; Yasukawa, Tomoyuki; Shiku, Hitoshi; Matsue, Tomokazu

    2007-01-01

    We describe a novel multicellular spheroid culture system that facilitates the easy preparation and culture of a spheroid microarray for the long-term monitoring of cellular activity. A spheroid culture device with an array of pyramid-like microholes was constructed in a silicon chip that was equipped with elastomeric microchannels. A cell suspension was introduced via the microfluidic channel into the microstructure that comprised silicon microholes and elastomeric microwells. A single spheroid can be formed and localized precisely within each microstructure. Since the culture medium could be replaced via the microchannels, a long-term culture (of approximately 2 weeks) is available on the chip. Measurement of albumin production in the hepatoma cell line (HepG2) showed that the liver-specific functions were maintained for 2 weeks. Based on the cellular respiratory activity, the cellular viability of the spheroid array on the chip was evaluated using scanning electrochemical microscopy. Responses to four different chemical stimulations were simultaneously detected on the same chip, thus demonstrating that each channel could be evaluated independently under various stimulation conditions. Our spheroid culture system facilitated the understanding of spheroid formation, culture, and viability assay on a single chip, thus functioning as a useful drug-screening device for cancer and liver cells.

  7. Imaging of bacterial multicellular behaviour in biofilms in liquid by atmospheric scanning electron microscopy

    Science.gov (United States)

    Sugimoto, Shinya; Okuda, Ken-ichi; Miyakawa, Reina; Sato, Mari; Arita-Morioka, Ken-ichi; Chiba, Akio; Yamanaka, Kunitoshi; Ogura, Teru; Mizunoe, Yoshimitsu; Sato, Chikara

    2016-01-01

    Biofilms are complex communities of microbes that attach to biotic or abiotic surfaces causing chronic infectious diseases. Within a biofilm, microbes are embedded in a self-produced soft extracellular matrix (ECM), which protects them from the host immune system and antibiotics. The nanoscale visualisation of delicate biofilms in liquid is challenging. Here, we develop atmospheric scanning electron microscopy (ASEM) to visualise Gram-positive and -negative bacterial biofilms immersed in aqueous solution. Biofilms cultured on electron-transparent film were directly imaged from below using the inverted SEM, allowing the formation of the region near the substrate to be studied at high resolution. We visualised intercellular nanostructures and the exocytosis of membrane vesicles, and linked the latter to the trafficking of cargos, including cytoplasmic proteins and the toxins hemolysin and coagulase. A thick dendritic nanotube network was observed between microbes, suggesting multicellular communication in biofilms. A universal immuno-labelling system was developed for biofilms and tested on various examples, including S. aureus biofilms. In the ECM, fine DNA and protein networks were visualised and the precise distribution of protein complexes was determined (e.g., straight curli, flagella, and excreted cytoplasmic molecular chaperones). Our observations provide structural insights into bacteria-substratum interactions, biofilm development and the internal microbe community. PMID:27180609

  8. Mathematical System Theory and System Modeling

    OpenAIRE

    1980-01-01

    Choosing models related effectively to the questions to be addressed is a central issue in the craft of systems analysis. Since the mathematical description the analyst chooses constrains the types of issues he candeal with, it is important for these models to be selected so as to yield limitations that are acceptable in view of the questions the systems analysis seeks to answer. In this paper, the author gives an overview of the central issues affecting the question of model choice. To ...

  9. The diversification of the LIM superclass at the base of the metazoa increased subcellular complexity and promoted multicellular specialization.

    Directory of Open Access Journals (Sweden)

    Bernard J Koch

    Full Text Available BACKGROUND: Throughout evolution, the LIM domain has been deployed in many different domain configurations, which has led to the formation of a large and distinct group of proteins. LIM proteins are involved in relaying stimuli received at the cell surface to the nucleus in order to regulate cell structure, motility, and division. Despite their fundamental roles in cellular processes and human disease, little is known about the evolution of the LIM superclass. RESULTS: We have identified and characterized all known LIM domain-containing proteins in six metazoans and three non-metazoans. In addition, we performed a phylogenetic analysis on all LIM domains and, in the process, have identified a number of novel non-LIM domains and motifs in each of these proteins. Based on these results, we have formalized a classification system for LIM proteins, provided reasonable timing for class and family origin events; and identified lineage-specific loss events. Our analysis is the first detailed description of the full set of LIM proteins from the non-bilaterian species examined in this study. CONCLUSION: Six of the 14 LIM classes originated in the stem lineage of the Metazoa. The expansion of the LIM superclass at the base of the Metazoa undoubtedly contributed to the increase in subcellular complexity required for the transition from a unicellular to multicellular lifestyle and, as such, was a critically important event in the history of animal multicellularity.

  10. Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids

    Directory of Open Access Journals (Sweden)

    Annkathrin Hornung

    2015-09-01

    Full Text Available Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT employing superparamagnetic iron oxide nanoparticles (SPION loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in the healthy tissue. For translation of nanomedicine from bench to bedside, nanoparticle-mediated effects have to be studied carefully. In this study, we compare the effect of SPION, unloaded or loaded with the cytotoxic drug mitoxantrone (MTO with the effect of free MTO, on the viability and proliferation of HT-29 cells within three-dimensional multicellular tumor spheroids. Fluorescence microscopy and flow cytometry showed that both free MTO, as well as SPION-loaded MTO (SPIONMTO are able to penetrate into tumor spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect cellular viability. Since SPIONMTO has herewith proven its effectivity also in complex multicellular tumor structures with its surrounding microenvironment, we conclude that it is a promising candidate for further use in magnetic drug targeting in vivo.

  11. Model Reduction of Hybrid Systems

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza

    systems are derived in this thesis. The results are used for output feedback control of switched nonlinear systems. Model reduction of piecewise affine systems is also studied in this thesis. The proposed method is based on the reduction of linear subsystems inside the polytopes. The methods which......High-Technological solutions of today are characterized by complex dynamical models. A lot of these models have inherent hybrid/switching structure. Hybrid/switched systems are powerful models for distributed embedded systems design where discrete controls are applied to continuous processes...... of hybrid systems, designing controllers and implementations is very high so that the use of these models is limited in applications where the size of the state space is large. To cope with complexity, model reduction is a powerful technique. This thesis presents methods for model reduction and stability...

  12. A Novel Computer-Assisted Approach to evaluate Multicellular Tumor Spheroid Invasion Assay

    Science.gov (United States)

    Cisneros Castillo, Liliana R.; Oancea, Andrei-Dumitru; Stüllein, Christian; Régnier-Vigouroux, Anne

    2016-10-01

    Multicellular tumor spheroids (MCTSs) embedded in a matrix are re-emerging as a powerful alternative to monolayer-based cultures. The primary information gained from a three-dimensional model is the invasiveness of treatment-exposed MCTSs through the acquisition of light microscopy images. The amount and complexity of the acquired data and the bias arisen by their manual analysis are disadvantages calling for an automated, high-throughput analysis. We present a universal algorithm we developed with the scope of being robust enough to handle images of various qualities and various invasion profiles. The novelty and strength of our algorithm lie in: the introduction of a multi-step segmentation flow, where each step is optimized for each specific MCTS area (core, halo, and periphery); the quantification through the density of the two-dimensional representation of a three-dimensional object. This latter offers a fine-granular differentiation of invasive profiles, facilitating a quantification independent of cell lines and experimental setups. Progression of density from the core towards the edges influences the resulting density map thus providing a measure no longer dependent on the sole area size of MCTS, but also on its invasiveness. In sum, we propose a new method in which the concept of quantification of MCTS invasion is completely re-thought.

  13. Recombination every day: abundant recombination in a virus during a single multi-cellular host infection.

    Directory of Open Access Journals (Sweden)

    Remy Froissart

    2005-03-01

    Full Text Available Viral recombination can dramatically impact evolution and epidemiology. In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur. While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking. This study fills this gap using the cauliflower mosaic virus as a model. We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses. The frequency of recombinant genomes was evaluated 21 d post-inoculation. On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus. Estimates of the recombination rate show that all regions of the genome are equally affected by this process. Assuming that ten viral replication cycles occurred during our experiment-based on data on the timing of coat protein detection-the per base and replication cycle recombination rate was on the order of 2 x 10(-5 to 4 x 10(-5. This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.

  14. Modelling on fuzzy control systems

    Institute of Scientific and Technical Information of China (English)

    LI; Hongxing(李洪兴); WANG; Jiayin(王加银); MIAO; Zhihong(苗志宏)

    2002-01-01

    A kind of modelling method for fuzzy control systems is first proposed here, which is calledmodelling method based on fuzzy inference (MMFI). It should be regarded as the third modelling method thatis different from two well-known modelling methods, that is, the first modelling method, mechanism modellingmethod (MMM), and the second modelling method, system identification modelling method (SlMM). Thismethod can, based on the interpolation mechanism on fuzzy logic system, transfer a group of fuzzy inferencerules describing a practice system into a kind of nonlinear differential equation with variable coefficients, calledHX equations, so that the mathematical model of the system can be obtained. This means that we solve thedifficult problem of how to get a model represented as differential equations on a complicated or fuzzy controlsystem.

  15. Energy System Modeling with REopt

    Energy Technology Data Exchange (ETDEWEB)

    Simpkins, Travis; Anderson, Kate; Cutler, Dylan; Olis, Dan; Elgqvist, Emma; DiOrio, Nick; Walker, Andy

    2016-07-15

    This poster details how REopt - NREL's software modeling platform for energy systems integration and optimization - can help to model energy systems. Some benefits of modeling with REopt include optimizing behind the meter storage for cost and resiliency, optimizing lab testing, optimizing dispatch of utility scale storage, and quantifying renewable energy impact on outage survivability.

  16. Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device

    Science.gov (United States)

    Ayuso, Jose M.; Basheer, Haneen A.; Monge, Rosa; Sánchez-Álvarez, Pablo; Doblaré, Manuel; Shnyder, Steven D.; Vinader, Victoria; Afarinkia, Kamyar

    2015-01-01

    We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it. PMID:26444904

  17. Modeling soft interface dominated systems

    NARCIS (Netherlands)

    Lamorgese, A.; Mauri, R.; Sagis, L.M.C.

    2017-01-01

    The two main continuum frameworks used for modeling the dynamics of soft multiphase systems are the Gibbs dividing surface model, and the diffuse interface model. In the former the interface is modeled as a two dimensional surface, and excess properties such as a surface density, or surface energy

  18. Validation of systems biology models

    NARCIS (Netherlands)

    Hasdemir, D.

    2015-01-01

    The paradigm shift from qualitative to quantitative analysis of biological systems brought a substantial number of modeling approaches to the stage of molecular biology research. These include but certainly are not limited to nonlinear kinetic models, static network models and models obtained by the

  19. Modeling of deterministic chaotic systems

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Y. [Department of Physics and Astronomy and Department of Mathematics, The University of Kansas, Lawrence, Kansas 66045 (United States); Grebogi, C. [Institute for Plasma Research, University of Maryland, College Park, Maryland 20742 (United States); Grebogi, C.; Kurths, J. [Department of Physics and Astrophysics, Universitaet Potsdam, Postfach 601553, D-14415 Potsdam (Germany)

    1999-03-01

    The success of deterministic modeling of a physical system relies on whether the solution of the model would approximate the dynamics of the actual system. When the system is chaotic, situations can arise where periodic orbits embedded in the chaotic set have distinct number of unstable directions and, as a consequence, no model of the system produces reasonably long trajectories that are realized by nature. We argue and present physical examples indicating that, in such a case, though the model is deterministic and low dimensional, statistical quantities can still be reliably computed. {copyright} {ital 1999} {ital The American Physical Society}

  20. Modelling of wastewater systems

    DEFF Research Database (Denmark)

    Bechmann, Henrik

    In this thesis, models of pollution fluxes in the inlet to 2 Danish wastewater treatment plants (WWTPs) as well as of suspended solids (SS) concentrations in the aeration tanks of an alternating WWTP and in the effluent from the aeration tanks are developed. The latter model is furthermore used...

  1. Modelling Epistemic Systems

    CERN Document Server

    Martins, Andre C R

    2012-01-01

    In this Chapter, I will explore the use of modeling in order to understand how Science works. I will discuss the modeling of scientific communities, providing a general, non-comprehensive overview of existing models, with a focus on the use of the tools of Agent-Based Modeling and Opinion Dynamics. A special attention will be paid to models inspired by a Bayesian formalism of Opinion Dynamics. The objective of this exploration is to better understand the effect that different conditions might have on the reliability of the opinions of a scientific community. We will see that, by using artificial worlds as exploring grounds, we can prevent some epistemological problems with the definition of truth and obtain insights on the conditions that might cause the quest for more reliable knowledge to fail.

  2. From Numeric Models to Granular System Modeling

    Directory of Open Access Journals (Sweden)

    Witold Pedrycz

    2015-03-01

    To make this study self-contained, we briefly recall the key concepts of granular computing and demonstrate how this conceptual framework and its algorithmic fundamentals give rise to granular models. We discuss several representative formal setups used in describing and processing information granules including fuzzy sets, rough sets, and interval calculus. Key architectures of models dwell upon relationships among information granules. We demonstrate how information granularity and its optimization can be regarded as an important design asset to be exploited in system modeling and giving rise to granular models. With this regard, an important category of rule-based models along with their granular enrichments is studied in detail.

  3. Pluralistic Modeling of Complex Systems

    CERN Document Server

    Helbing, Dirk

    2010-01-01

    The modeling of complex systems such as ecological or socio-economic systems can be very challenging. Although various modeling approaches exist, they are generally not compatible and mutually consistent, and empirical data often do not allow one to decide what model is the right one, the best one, or most appropriate one. Moreover, as the recent financial and economic crisis shows, relying on a single, idealized model can be very costly. This contribution tries to shed new light on problems that arise when complex systems are modeled. While the arguments can be transferred to many different systems, the related scientific challenges are illustrated for social, economic, and traffic systems. The contribution discusses issues that are sometimes overlooked and tries to overcome some frequent misunderstandings and controversies of the past. At the same time, it is highlighted how some long-standing scientific puzzles may be solved by considering non-linear models of heterogeneous agents with spatio-temporal inte...

  4. The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity.

    Science.gov (United States)

    Sundaram, Meera V; Buechner, Matthew

    2016-05-01

    The excretory system of the nematode Caenorhabditis elegans is a superb model of tubular organogenesis involving a minimum of cells. The system consists of just three unicellular tubes (canal, duct, and pore), a secretory gland, and two associated neurons. Just as in more complex organs, cells of the excretory system must first adopt specific identities and then coordinate diverse processes to form tubes of appropriate topology, shape, connectivity, and physiological function. The unicellular topology of excretory tubes, their varied and sometimes complex shapes, and the dynamic reprogramming of cell identity and remodeling of tube connectivity that occur during larval development are particularly fascinating features of this organ. The physiological roles of the excretory system in osmoregulation and other aspects of the animal's life cycle are only beginning to be explored. The cellular mechanisms and molecular pathways used to build and shape excretory tubes appear similar to those used in both unicellular and multicellular tubes in more complex organs, such as the vertebrate vascular system and kidney, making this simple organ system a useful model for understanding disease processes.

  5. Integrated Modeling Systems

    Science.gov (United States)

    1989-01-01

    American Economic Review , 71:1 (March 1981). 181 J.M. Jones and F. Zufryden. "Adding Explanatory Variables to a Consumer Purchase Behavior Model: An...McCall. "An Operational Measure of Liquidity," The American Economic Review , 761 (March 1986). WMSI Working Paper 329. 212 Nelson, R., R. Sarin, and R

  6. Robust Disaster Recovery System Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Highly security-critical system should possess features of continuous service. We present a new Robust Disaster Recovery System Model (RDRSM). Through strengthening the ability of safe communications, RDRSM guarantees the secure and reliable command on disaster recovery. Its self-supervision capability can monitor the integrality and security of disaster recovery system itself. By 2D and 3D real-time visible platform provided by GIS, GPS and RS, the model makes the using, management and maintenance of disaster recovery system easier. RDRSM possesses predominant features of security, robustness and controllability. And it can be applied to highly security-critical environments such as E-government and bank. Conducted by RDRSM, an important E-government disaster recovery system has been constructed successfully. The feasibility of this model is verified by practice. We especially emphasize the significance of some components of the model, such as risk assessment, disaster recovery planning, system supervision and robust communication support.

  7. Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Oud, B.; Guadalupe-Medina, V.; Nijkamp, J.F.; De Ridder, D.; Pronk, J.T.; Van Maris, A.J.A.; Daran, J.G.

    2013-01-01

    Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to

  8. Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Oud, B.; Guadalupe-Medina, V.; Nijkamp, J.F.; De Ridder, D.; Pronk, J.T.; Van Maris, A.J.A.; Daran, J.G.

    2013-01-01

    Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to mani

  9. Trichome-related mutants provide a new perspective on the multicellular trichome initiation and development in cucumber (Cucumis sativus. L

    Directory of Open Access Journals (Sweden)

    Xingwang Liu

    2016-08-01

    Full Text Available Trichomes are specialized epidermal cells located in aerial parts of plants that function in plant defense against biotic and abiotic stresses. The simple unicellular trichomes of Arabidopsis serve as an excellent model to study the molecular mechanism of cell differentiation and pattern formation in plants. Loss-of-function mutations in Arabidopsis thaliana have suggested that the core genes GL1 (which encodes a MYB transcription factor and TTG1 (which encodes a WD40 repeat-containing protein are important for the initiation and spacing of leaf trichomes, while for normal trichome initiation, the genes GL3 and EGL3 (which encode a bHLH protein are needed. However, the positive regulatory genes involved in multicellular trichrome development in cucumber remain unclear. This review focuses on the phenotype of mutants (csgl3, tril, tbh, mict and csgl1 with disturbed trichomes in cucumber and then infers which gene(s play key roles in trichome initiation and development in those mutants. Evidence indicates that MICT, TBH and CsGL1 are allelic with alternative splicing. CsGL3 and TRIL are allelic and override the effect of TBH, MICT and CsGL1 on the regulation of multicellular trichome development; and affect trichome initiation. CsGL3, TRIL, MICT, TBH and CsGL1 encode HD-Zip proteins with different subfamilies. Genetic and molecular analyses have revealed that CsGL3, TRIL, MICT, TBH and CsGL1 are responsible for the differentiation of epidermal cells and the development of trichomes. Based on current knowledge, a positive regulator pathway model for trichome development in cucumber was proposed and compared to a model in Arabidopsis. These data suggest that trichome development in cucumber may differ from that in Arabidopsis.

  10. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2007-01-01

    All phenomena in nature are characterized by motion; this is an essential property of matter, having infinitely many aspects. Motion can be mechanical, physical, chemical or biological, leading to various sciences of nature, mechanics being one of them. Mechanics deals with the objective laws of mechanical motion of bodies, the simplest form of motion. In the study of a science of nature mathematics plays an important role. Mechanics is the first science of nature which was expressed in terms of mathematics by considering various mathematical models, associated to phenomena of the surrounding nature. Thus, its development was influenced by the use of a strong mathematical tool; on the other hand, we must observe that mechanics also influenced the introduction and the development of many mathematical notions. In this respect, the guideline of the present book is precisely the mathematical model of mechanics. A special accent is put on the solving methodology as well as on the mathematical tools used; vectors, ...

  11. Processing and characterization of multi-cellular monolithic bioceramics for bone regenerative scaffolds

    Science.gov (United States)

    Ari-Wahjoedi, Bambang; Ginta, Turnad Lenggo; Parman, Setyamartana; Abustaman, Mohd Zikri Ahmad

    2014-10-01

    Multicellular monolithic ceramic body is a ceramic material which has many gas or liquid passages partitioned by thin walls throughout the bulk material. There are many currently known advanced industrial applications of multicellular ceramics structures i.e. as supports for various catalysts, electrode support structure for solid oxide fuel cells, refractories, electric/electronic materials, aerospace vehicle re-entry heat shields and biomaterials for dental as well as orthopaedic implants by naming only a few. Multicellular ceramic bodies are usually made of ceramic phases such as mullite, cordierite, aluminum titanate or pure oxides such as silica, zirconia and alumina. What make alumina ceramics is excellent for the above functions are the intrinsic properties of alumina which are hard, wear resistant, excellent dielectric properties, resists strong acid and alkali attacks at elevated temperatures, good thermal conductivities, high strength and stiffness as well as biocompatible. In this work the processing technology leading to truly multicellular monolithic alumina ceramic bodies and their characterization are reported. Ceramic slip with 66 wt.% solid loading was found to be optimum as impregnant to the polyurethane foam template. Mullitic ceramic composite of alumina-sodium alumino disilicate-Leucite-like phases with bulk and true densities of 0.852 and 1.241 g cm-3 respectively, pore linear density of ±35 cm-1, linear and bulk volume shrinkages of 7-16% and 32 vol.% were obtained. The compressive strength and elastic modulus of the bioceramics are ≈0.5-1.0 and ≈20 MPa respectively.

  12. Sponge cell reaggregation: Cellular structure and morphogenetic potencies of multicellular aggregates.

    Science.gov (United States)

    Lavrov, Andrey I; Kosevich, Igor A

    2016-02-01

    Sponges (phylum Porifera) are one of the most ancient extant multicellular animals and can provide valuable insights into origin and early evolution of Metazoa. High plasticity of cell differentiations and anatomical structure is characteristic feature of sponges. Present study deals with sponge cell reaggregation after dissociation as the most outstanding case of sponge plasticity. Dynamic of cell reaggregation and structure of multicellular aggregates of three demosponge species (Halichondria panicea (Pallas, 1766), Haliclona aquaeductus (Sсhmidt, 1862), and Halisarca dujardinii Johnston, 1842) were studied. Sponge tissue dissociation was performed mechanically. Resulting cell suspensions were cultured at 8-10°C for at least 5 days. Structure of multicellular aggregates was studied by light, transmission and scanning electron microscopy. Studied species share common stages of cell reaggregation-primary multicellular aggregates, early-stage primmorphs and primmorphs, but the rate of reaggregation varies considerably among species. Only cells of H. dujardinii are able to reconstruct functional and viable sponge after primmorphs formation. Sponge reconstruction in this species occurs due to active cell locomotion. Development of H. aquaeductus and H. panicea cells ceases at the stages of early primmorphs and primmorphs, respectively. Development of aggregates of these species is most likely arrested due to immobility of the majority of cells inside them. However, the inability of certain sponge species to reconstruct functional and viable individuals during cell reaggregation may be not a permanent species-specific characteristic, but depends on various factors, including the stage of the life cycle and experimental conditions.

  13. Small regulatory RNAs control the multi-cellular adhesive lifestyle of Escherichia coli

    DEFF Research Database (Denmark)

    Jørgensen, Mikkel Girke; Nielsen, Jesper Sejrup; Boysen, Anders

    2012-01-01

    Small regulatory RNA molecules have recently been recognized as important regulatory elements of developmental processes in both eukaryotes and bacteria. We here describe a striking example in Escherichia coli that can switch between a single-cell motile lifestyle and a multi-cellular, sessile...

  14. Experimental evolution reveals that high relatedness protects multicellular cooperation from cheaters

    NARCIS (Netherlands)

    Bastiaans, Eric; Debets, Alfons J.M.; Aanen, Duur K.

    2016-01-01

    In multicellular organisms, there is a potential risk that cheating mutants gain access to the germline. Development from a single-celled zygote resets relatedness among cells to its maximum value each generation, which should accomplish segregation of cheating mutants from non-cheaters and

  15. Studies of Catalytic Model Systems

    DEFF Research Database (Denmark)

    Holse, Christian

    The overall topic of this thesis is within the field of catalysis, were model systems of different complexity have been studied utilizing a multipurpose Ultra High Vacuum chamber (UHV). The thesis falls in two different parts. First a simple model system in the form of a ruthenium single crystal...... is investigated. Second the development of a complex Cu/ZnO nanoparticle model system is described and gas-induced dynamical changes in the model system is investigated. The ruthenium crystal serves as an extremely simple model for studying CO dissociation which is the rate limiting step of the methanation...... process. The Ru(0 1 54) surface is studied by means of Scanning Tunneling Microscopy (STM), Temperature Programmed Desoprtion (TPD), and Oxygen Titration (OT) experiments. Real space evidence of periodic features on every second monatomic step is observed via STM when the a clean ruthenium surface...

  16. Relocatable Coastal Modeling System

    Science.gov (United States)

    2016-06-07

    These relationships are stored on a variable-resolution grid (illustrated in figure 1b below) with sampling of 1 degree in deep water (and in data...version is referred to as MODAS2.1, which is now operational at NAVO. The NOMADS interface is being replaced by a system-independent, web -based version...inside the user’s web browser plus Perl CGI scripts which ran on a webserver. This permitted the user to run MODAS (and POM and other modules as they are

  17. Hydronic distribution system computer model

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, J.W.; Strasser, J.J.

    1994-10-01

    A computer model of a hot-water boiler and its associated hydronic thermal distribution loop has been developed at Brookhaven National Laboratory (BNL). It is intended to be incorporated as a submodel in a comprehensive model of residential-scale thermal distribution systems developed at Lawrence Berkeley. This will give the combined model the capability of modeling forced-air and hydronic distribution systems in the same house using the same supporting software. This report describes the development of the BNL hydronics model, initial results and internal consistency checks, and its intended relationship to the LBL model. A method of interacting with the LBL model that does not require physical integration of the two codes is described. This will provide capability now, with reduced up-front cost, as long as the number of runs required is not large.

  18. Data management system performance modeling

    Science.gov (United States)

    Kiser, Larry M.

    1993-01-01

    This paper discusses analytical techniques that have been used to gain a better understanding of the Space Station Freedom's (SSF's) Data Management System (DMS). The DMS is a complex, distributed, real-time computer system that has been redesigned numerous times. The implications of these redesigns have not been fully analyzed. This paper discusses the advantages and disadvantages for static analytical techniques such as Rate Monotonic Analysis (RMA) and also provides a rationale for dynamic modeling. Factors such as system architecture, processor utilization, bus architecture, queuing, etc. are well suited for analysis with a dynamic model. The significance of performance measures for a real-time system are discussed.

  19. BSim: an agent-based tool for modeling bacterial populations in systems and synthetic biology.

    Directory of Open Access Journals (Sweden)

    Thomas E Gorochowski

    Full Text Available Large-scale collective behaviors such as synchronization and coordination spontaneously arise in many bacterial populations. With systems biology attempting to understand these phenomena, and synthetic biology opening up the possibility of engineering them for our own benefit, there is growing interest in how bacterial populations are best modeled. Here we introduce BSim, a highly flexible agent-based computational tool for analyzing the relationships between single-cell dynamics and population level features. BSim includes reference implementations of many bacterial traits to enable the quick development of new models partially built from existing ones. Unlike existing modeling tools, BSim fully considers spatial aspects of a model allowing for the description of intricate micro-scale structures, enabling the modeling of bacterial behavior in more realistic three-dimensional, complex environments. The new opportunities that BSim opens are illustrated through several diverse examples covering: spatial multicellular computing, modeling complex environments, population dynamics of the lac operon, and the synchronization of genetic oscillators. BSim is open source software that is freely available from http://bsim-bccs.sf.net and distributed under the Open Source Initiative (OSI recognized MIT license. Developer documentation and a wide range of example simulations are also available from the website. BSim requires Java version 1.6 or higher.

  20. National Energy Outlook Modelling System

    Energy Technology Data Exchange (ETDEWEB)

    Volkers, C.M. [ECN Policy Studies, Petten (Netherlands)

    2013-12-15

    For over 20 years, the Energy research Centre of the Netherlands (ECN) has been developing the National Energy Outlook Modelling System (NEOMS) for Energy projections and policy evaluations. NEOMS enables 12 energy models of ECN to exchange data and produce consistent and detailed results.

  1. ABSTRACT MODELS FOR SYSTEM VIRTUALIZATION

    Directory of Open Access Journals (Sweden)

    M. G. Koveshnikov

    2015-05-01

    Full Text Available The paper is dedicated to issues of system objects securing (system files and user system or application configuration files against unauthorized access including denial of service attacks. We have suggested the method and developed abstract system virtualization models, which are used toresearch attack scenarios for different virtualization modes. Estimation for system tools virtualization technology effectiveness is given. Suggested technology is based on redirection of access requests to system objects shared among access subjects. Whole and partial system virtualization modes have been modeled. The difference between them is the following: in the whole virtualization mode all copies of access system objects are created whereon subjects’ requests are redirected including corresponding application objects;in the partial virtualization mode corresponding copies are created only for part of a system, for example, only system objects for applications. Alternative solutions effectiveness is valued relating to different attack scenarios. We consider proprietary and approved technical solution which implements system virtualization method for Microsoft Windows OS family. Administrative simplicity and capabilities of correspondingly designed system objects security tools are illustrated on this example. Practical significance of the suggested security method has been confirmed.

  2. Aerodynamic and Mechanical System Modelling

    DEFF Research Database (Denmark)

    Jørgensen, Martin Felix

    This thesis deals with mechanical multibody-systems applied to the drivetrain of a 500 kW wind turbine. Particular focus has been on gearbox modelling of wind turbines. The main part of the present project involved programming multibody systems to investigate the connection between forces, moments...

  3. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...

  4. An extensible analysable system model

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, Rene Rydhof

    2008-01-01

    , this does not hold for real physical systems. Approaches such as threat modelling try to target the formalisation of the real-world domain, but still are far from the rigid techniques available in security research. Many currently available approaches to assurance of critical infrastructure security...... allows for easy development of analyses for the abstracted systems. We briefly present one application of our approach, namely the analysis of systems for potential insider threats....

  5. Modeling Multi-Level Systems

    CERN Document Server

    Iordache, Octavian

    2011-01-01

    This book is devoted to modeling of multi-level complex systems, a challenging domain for engineers, researchers and entrepreneurs, confronted with the transition from learning and adaptability to evolvability and autonomy for technologies, devices and problem solving methods. Chapter 1 introduces the multi-scale and multi-level systems and highlights their presence in different domains of science and technology. Methodologies as, random systems, non-Archimedean analysis, category theory and specific techniques as model categorification and integrative closure, are presented in chapter 2. Chapters 3 and 4 describe polystochastic models, PSM, and their developments. Categorical formulation of integrative closure offers the general PSM framework which serves as a flexible guideline for a large variety of multi-level modeling problems. Focusing on chemical engineering, pharmaceutical and environmental case studies, the chapters 5 to 8 analyze mixing, turbulent dispersion and entropy production for multi-scale sy...

  6. Distribution system modeling and analysis

    CERN Document Server

    Kersting, William H

    2002-01-01

    For decades, distribution engineers did not have the sophisticated tools developed for analyzing transmission systems-often they had only their instincts. Things have changed, and we now have computer programs that allow engineers to simulate, analyze, and optimize distribution systems. Powerful as these programs are, however, without a real understanding of the operating characteristics of a distribution system, engineers using the programs can easily make serious errors in their designs and operating procedures.Distribution System Modeling and Analysis helps prevent those errors. It gives re

  7. Stirling Engine Dynamic System Modeling

    Science.gov (United States)

    Nakis, Christopher G.

    2004-01-01

    The Thermo-Mechanical systems branch at the Glenn Research Center focuses a large amount time on Stirling engines. These engines will be used on missions where solar power is inefficient, especially in deep space. I work with Tim Regan and Ed Lewandowski who are currently developing and validating a mathematical model for the Stirling engines. This model incorporates all aspects of the system including, mechanical, electrical and thermodynamic components. Modeling is done through Simplorer, a program capable of running simulations of the model. Once created and then proven to be accurate, a model is used for developing new ideas for engine design. My largest specific project involves varying key parameters in the model and quantifying the results. This can all be done relatively trouble-free with the help of Simplorer. Once the model is complete, Simplorer will do all the necessary calculations. The more complicated part of this project is determining which parameters to vary. Finding key parameters depends on the potential for a value to be independently altered in the design. For example, a change in one dimension may lead to a proportional change to the rest of the model, and no real progress is made. Also, the ability for a changed value to have a substantial impact on the outputs of the system is important. Results will be condensed into graphs and tables with the purpose of better communication and understanding of the data. With the changing of these parameters, a more optimal design can be created without having to purchase or build any models. Also, hours and hours of results can be simulated in minutes. In the long run, using mathematical models can save time and money. Along with this project, I have many other smaller assignments throughout the summer. My main goal is to assist in the processes of model development, validation and testing.

  8. Kinetic Modeling of Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Resat, Haluk; Petzold, Linda; Pettigrew, Michel F.

    2009-04-21

    The dynamics of how its constituent components interact define the spatio-temporal response of a natural system to stimuli. Modeling the kinetics of the processes that represent a biophysical system has long been pursued with the aim of improving our understanding of the studied system. Due to the unique properties of biological systems, in addition to the usual difficulties faced in modeling the dynamics of physical or chemical systems, biological simulations encounter difficulties that result from intrinsic multiscale and stochastic nature of the biological processes. This chapter discusses the implications for simulation of models involving interacting species with very low copy numbers, which often occur in biological systems and give rise to significant relative fluctuations. The conditions necessitating the use of stochastic kinetic simulation methods and the mathematical foundations of the stochastic simulation algorithms are presented. How the well-organized structural hierarchies often seen in biological systems can lead to multiscale problems, and possible ways to address the encountered computational difficulties are discussed. We present the details of the existing kinetic simulation methods, and discuss their strengths and shortcomings. A list of the publicly available kinetic simulation tools and our reflections for future prospects are also provided.

  9. Large Scale Tissue Morphogenesis Simulation on Heterogenous Systems Based on a Flexible Biomechanical Cell Model.

    Science.gov (United States)

    Jeannin-Girardon, Anne; Ballet, Pascal; Rodin, Vincent

    2015-01-01

    The complexity of biological tissue morphogenesis makes in silico simulations of such system very interesting in order to gain a better understanding of the underlying mechanisms ruling the development of multicellular tissues. This complexity is mainly due to two elements: firstly, biological tissues comprise a large amount of cells; secondly, these cells exhibit complex interactions and behaviors. To address these two issues, we propose two tools: the first one is a virtual cell model that comprise two main elements: firstly, a mechanical structure (membrane, cytoskeleton, and cortex) and secondly, the main behaviors exhibited by biological cells, i.e., mitosis, growth, differentiation, molecule consumption, and production as well as the consideration of the physical constraints issued from the environment. An artificial chemistry is also included in the model. This virtual cell model is coupled to an agent-based formalism. The second tool is a simulator that relies on the OpenCL framework. It allows efficient parallel simulations on heterogenous devices such as micro-processors or graphics processors. We present two case studies validating the implementation of our model in our simulator: cellular proliferation controlled by cell signalling and limb growth in a virtual organism.

  10. Surface chemistry-mediated penetration and gold nanorod thermotherapy in multicellular tumor spheroids

    Science.gov (United States)

    Jin, Shubin; Ma, Xiaowei; Ma, Huili; Zheng, Kaiyuan; Liu, Juan; Hou, Shuai; Meng, Jie; Wang, Paul C.; Wu, Xiaochun; Liang, Xing-Jie

    2012-12-01

    We investigated the penetration and thermotherapy efficiency of different surface coated gold nanorods (Au NRs) in multicellular tumor spheroids. The current data show that negatively charged Au NRs, other than positively charged Au NRs, can penetrate deep into the tumor spheroids and achieve a significant thermal therapeutic benefit.We investigated the penetration and thermotherapy efficiency of different surface coated gold nanorods (Au NRs) in multicellular tumor spheroids. The current data show that negatively charged Au NRs, other than positively charged Au NRs, can penetrate deep into the tumor spheroids and achieve a significant thermal therapeutic benefit. Electronic supplementary information (ESI) available: Materials and methods section. See DOI: 10.1039/c2nr31877f

  11. The Dynamic Regulatory Genome of Capsaspora and the Origin of Animal Multicellularity.

    Science.gov (United States)

    Sebé-Pedrós, Arnau; Ballaré, Cecilia; Parra-Acero, Helena; Chiva, Cristina; Tena, Juan J; Sabidó, Eduard; Gómez-Skarmeta, José Luis; Di Croce, Luciano; Ruiz-Trillo, Iñaki

    2016-05-19

    The unicellular ancestor of animals had a complex repertoire of genes linked to multicellular processes. This suggests that changes in the regulatory genome, rather than in gene innovation, were key to the origin of animals. Here, we carry out multiple functional genomic assays in Capsaspora owczarzaki, the unicellular relative of animals with the largest known gene repertoire for transcriptional regulation. We show that changing chromatin states, differential lincRNA expression, and dynamic cis-regulatory sites are associated with life cycle transitions in Capsaspora. Moreover, we demonstrate conservation of animal developmental transcription-factor networks and extensive network interconnection in this premetazoan organism. In contrast, however, Capsaspora lacks animal promoter types, and its regulatory sites are small, proximal, and lack signatures of animal enhancers. Overall, our results indicate that the emergence of animal multicellularity was linked to a major shift in genome cis-regulatory complexity, most notably the appearance of distal enhancer regulation.

  12. Executive Information Systems' Multidimensional Models

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Executive Information Systems are design to improve the quality of strategic level of management in organization through a new type of technology and several techniques for extracting, transforming, processing, integrating and presenting data in such a way that the organizational knowledge filters can easily associate with this data and turn it into information for the organization. These technologies are known as Business Intelligence Tools. But in order to build analytic reports for Executive Information Systems (EIS in an organization we need to design a multidimensional model based on the business model from the organization. This paper presents some multidimensional models that can be used in EIS development and propose a new model that is suitable for strategic business requests.

  13. Numerical Modeling of Microelectrochemical Systems

    DEFF Research Database (Denmark)

    Adesokan, Bolaji James

    for the reactants in the bulk electrolyte that are traveling waves. The first paper presents the mathematical model which describes an electrochemical system and simulates an electroanalytical technique called cyclic voltammetry. The model is governed by a system of advection–diffusion equations with a nonlinear...... reaction term at the boundary. We investigate the effect of flow rates, scan rates, and concentration on the cyclic voltammetry. We establish that high flow rates lead to the reduced hysteresis in the cyclic voltammetry curves and increasing scan rates lead to more pronounced current peaks. The final part...... of the paper shows that the response current in a cyclic voltammetry increases proportionally to the electrolyte concentration. In the second paper we present an experiment of an electrochemical system in a microfluidc system and compare the result to the numerical solutions. We investigate how the position...

  14. Processing and characterization of multi-cellular monolithic bioceramics for bone regenerative scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Ari-Wahjoedi, Bambang, E-mail: bambang-ariwahjoedi@petronas.com.my [Department of Fundamental and Applied Sciences, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tronoh, Perak Darul Ridzuan (Malaysia); Centre for Intelligent Signal and Imaging Research, Universiti Teknologi PETRONAS, Bandar Seri Iskandar (Malaysia); Ginta, Turnad Lenggo [Department of Mechanical Engineering, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tronoh, Perak Darul Ridzuan (Malaysia); Centre for Intelligent Signal and Imaging Research, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tro (Malaysia); Parman, Setyamartana [Department of Mechanical Engineering, Universiti Teknologi PETRONAS, Bandar Seri Iskandar, 31750 Tronoh, Perak Darul Ridzuan (Malaysia); Abustaman, Mohd Zikri Ahmad [Kebabangan Petroleum Operating Company Sdn Bhd, Lvl. 52, Tower 2, PETRONAS Twin Towers, KLCC, 50088 Kuala Lumpur (Malaysia)

    2014-10-24

    Multicellular monolithic ceramic body is a ceramic material which has many gas or liquid passages partitioned by thin walls throughout the bulk material. There are many currently known advanced industrial applications of multicellular ceramics structures i.e. as supports for various catalysts, electrode support structure for solid oxide fuel cells, refractories, electric/electronic materials, aerospace vehicle re-entry heat shields and biomaterials for dental as well as orthopaedic implants by naming only a few. Multicellular ceramic bodies are usually made of ceramic phases such as mullite, cordierite, aluminum titanate or pure oxides such as silica, zirconia and alumina. What make alumina ceramics is excellent for the above functions are the intrinsic properties of alumina which are hard, wear resistant, excellent dielectric properties, resists strong acid and alkali attacks at elevated temperatures, good thermal conductivities, high strength and stiffness as well as biocompatible. In this work the processing technology leading to truly multicellular monolithic alumina ceramic bodies and their characterization are reported. Ceramic slip with 66 wt.% solid loading was found to be optimum as impregnant to the polyurethane foam template. Mullitic ceramic composite of alumina-sodium alumino disilicate-Leucite-like phases with bulk and true densities of 0.852 and 1.241 g cm{sup −3} respectively, pore linear density of ±35 cm{sup −1}, linear and bulk volume shrinkages of 7-16% and 32 vol.% were obtained. The compressive strength and elastic modulus of the bioceramics are ≈0.5-1.0 and ≈20 MPa respectively.

  15. Sexual reproductive structures of Latest Proterozoic multicellular rhodophytes (red algae) from South China

    Institute of Scientific and Technical Information of China (English)

    张昀; 袁训来

    1996-01-01

    Carposporangium- and spermatangium-like reproductive structures associated with differentiated vegetative tissues have been observed in the multicellular rhodophyte fossils, which were well preserved in the 650-Ma-old phosphate rocks of Doushantuo Formation in Guizhou Province, South China. The fossils show details of cellular structures that are comparable to the female and male reproductive organs of some extant rhodophytes. The first fossil-histological evidence for sexuality of Precambrian non-vascular plants is provided.

  16. Role of spatial averaging in multicellular gradient sensing

    Science.gov (United States)

    Smith, Tyler; Fancher, Sean; Levchenko, Andre; Nemenman, Ilya; Mugler, Andrew

    2016-06-01

    Gradient sensing underlies important biological processes including morphogenesis, polarization, and cell migration. The precision of gradient sensing increases with the length of a detector (a cell or group of cells) in the gradient direction, since a longer detector spans a larger range of concentration values. Intuition from studies of concentration sensing suggests that precision should also increase with detector length in the direction transverse to the gradient, since then spatial averaging should reduce the noise. However, here we show that, unlike for concentration sensing, the precision of gradient sensing decreases with transverse length for the simplest gradient sensing model, local excitation-global inhibition. The reason is that gradient sensing ultimately relies on a subtraction of measured concentration values. While spatial averaging indeed reduces the noise in these measurements, which increases precision, it also reduces the covariance between the measurements, which results in the net decrease in precision. We demonstrate how a recently introduced gradient sensing mechanism, regional excitation-global inhibition (REGI), overcomes this effect and recovers the benefit of transverse averaging. Using a REGI-based model, we compute the optimal two- and three-dimensional detector shapes, and argue that they are consistent with the shapes of naturally occurring gradient-sensing cell populations.

  17. Transcriptome analysis in Cucumis sativus identifies genes involved in multicellular trichome development.

    Science.gov (United States)

    Zhao, Jun-Long; Pan, Jun-Song; Guan, Yuan; Nie, Jing-Tao; Yang, Jun-Jun; Qu, Mei-Ling; He, Huan-Le; Cai, Run

    2015-05-01

    The regulatory gene network of unicellular trichome development in Arabidopsis thaliana has been studied intensively, but that of multicellular remains unclear. In the present study, we characterized cucumber trichomes as representative multicellular and unbranched structures, but in a spontaneous mutant, mict (micro-trichome), all trichomes showed a micro-size and stunted morphologies. We revealed the transcriptome profile using Illumina HiSeq 2000 sequencing technology, and determined that a total of 1391 genes exhibited differential expression. We further validated the accuracy of the transcriptome data by RT-qPCR and found that 43 genes encoding critical transcription factors were likely involved in multicellular trichome development. These 43 candidate genes were subdivided into seven groups: homeodomain, MYB-domain, WRKY-domain, bHLH-domain, ethylene-responsive, zinc finger and other transcription factor genes. Our findings also serve as a powerful tool to further study the relevant molecular networks, and provide a new perspective for investigating this complex and species-specific developmental process.

  18. Genomic analysis of organismal complexity in the multicellular green alga Volvox carteri

    Energy Technology Data Exchange (ETDEWEB)

    Prochnik, Simon E.; Umen, James; Nedelcu, Aurora; Hallmann, Armin; Miller, Stephen M.; Nishii, Ichiro; Ferris, Patrick; Kuo, Alan; Mitros, Therese; Fritz-Laylin, Lillian K.; Hellsten, Uffe; Chapman, Jarrod; Simakov, Oleg; Rensing, Stefan A.; Terry, Astrid; Pangilinan, Jasmyn; Kapitonov, Vladimir; Jurka, Jerzy; Salamov, Asaf; Shapiro, Harris; Schmutz, Jeremy; Grimwood, Jane; Lindquist, Erika; Lucas, Susan; Grigoriev, Igor V.; Schmitt, Rudiger; Kirk, David; Rokhsar, Daniel S.

    2010-07-01

    Analysis of the Volvox carteri genome reveals that this green alga's increased organismal complexity and multicellularity are associated with modifications in protein families shared with its unicellular ancestor, and not with large-scale innovations in protein coding capacity. The multicellular green alga Volvox carteri and its morphologically diverse close relatives (the volvocine algae) are uniquely suited for investigating the evolution of multicellularity and development. We sequenced the 138 Mb genome of V. carteri and compared its {approx}14,500 predicted proteins to those of its unicellular relative, Chlamydomonas reinhardtii. Despite fundamental differences in organismal complexity and life history, the two species have similar protein-coding potentials, and few species-specific protein-coding gene predictions. Interestingly, volvocine algal-specific proteins are enriched in Volvox, including those associated with an expanded and highly compartmentalized extracellular matrix. Our analysis shows that increases in organismal complexity can be associated with modifications of lineage-specific proteins rather than large-scale invention of protein-coding capacity.

  19. Directed self-assembly of large scaffold-free multi-cellular honeycomb structures

    Energy Technology Data Exchange (ETDEWEB)

    Tejavibulya, Nalin; Youssef, Jacquelyn; Bao, Brian; Ferruccio, Toni-Marie; Morgan, Jeffrey R, E-mail: Jeffrey_Morgan@Brown.edu [Department of Molecular Pharmacology, Physiology and Biotechnology, Center for Biomedical Engineering, Brown University, G-B 393, Biomed Center, 171 Meeting St, Providence, RI 02912 (United States)

    2011-09-15

    A significant challenge to the field of biofabrication is the rapid construction of large three-dimensional (3D) living tissues and organs. Multi-cellular spheroids have been used as building blocks. In this paper, we create large multi-cellular honeycomb building blocks using directed self-assembly, whereby cell-to-cell adhesion, in the context of the shape and obstacles of a micro-mold, drives the formation of a 3D structure. Computer-aided design, rapid prototyping and replica molding were used to fabricate honeycomb-shaped micro-molds. Nonadhesive hydrogels cast from these micro-molds were equilibrated in the cell culture medium and seeded with two types of mammalian cells. The cells settled into the honeycomb recess were unable to attach to the nonadhesive hydrogel and so cell-to-cell adhesion drove the self-assembly of a large multi-cellular honeycomb within 24 h. Distinct morphological changes occurred to the honeycomb and its cells indicating the presence of significant cell-mediated tension. Unlike the spheroid, whose size is constrained by a critical diffusion distance needed to maintain cell viability, the overall size of the honeycomb is not limited. The rapid production of the honeycomb building unit, with its multiple rings of high-density cells and open lumen spaces, offers interesting new possibilities for biofabrication strategies.

  20. Quark Model and multiquark system

    CERN Document Server

    da Silva, Cristiane Oldoni

    2010-01-01

    The discovery of many particles, especially in the 50's, when the firsts accelerators appeared, caused the searching for a model that would describe in a simple form the whole of known particles. The Quark Model, based in the mathematical structures of group theory, provided in the beginning of the 60's a simplified description of hadronic matter already known, proposing that three particles, called quarks, would originate all the observed hadrons. This model was able to preview the existence of particles that were later detected, confirming its consistency. Extensions of the Quark Model were made in the beginning of the 70's, focusing in describing observed particles that were excited states of the fundamental particles and others that presented new quantum numbers (flavors). Recently, exotic states as tetraquarks and pentaquarks types, also called multiquarks systems, previewed by the model, were observed, what renewed the interest in the way as quarks are confined inside the hadrons. In this article we pre...

  1. GENERIC model for multiphase systems

    NARCIS (Netherlands)

    Sagis, L.M.C.

    2010-01-01

    GENERIC is a nonequilibrium thermodynamic formalism in which the dynamic behavior of a system is described by a single compact equation involving two types of brackets: a Poisson bracket and a dissipative bracket. This formalism has proved to be a very powerful instrument to model the dynamic behavi

  2. Cotangent Models for Integrable Systems

    Science.gov (United States)

    Kiesenhofer, Anna; Miranda, Eva

    2017-03-01

    We associate cotangent models to a neighbourhood of a Liouville torus in symplectic and Poisson manifolds focusing on b-Poisson/ b-symplectic manifolds. The semilocal equivalence with such models uses the corresponding action-angle theorems in these settings: the theorem of Liouville-Mineur-Arnold for symplectic manifolds and an action-angle theorem for regular Liouville tori in Poisson manifolds (Laurent- Gengoux et al., IntMath Res Notices IMRN 8: 1839-1869, 2011). Our models comprise regular Liouville tori of Poisson manifolds but also consider the Liouville tori on the singular locus of a b-Poisson manifold. For this latter class of Poisson structures we define a twisted cotangent model. The equivalence with this twisted cotangent model is given by an action-angle theorem recently proved by the authors and Scott (Math. Pures Appl. (9) 105(1):66-85, 2016). This viewpoint of cotangent models provides a new machinery to construct examples of integrable systems, which are especially valuable in the b-symplectic case where not many sources of examples are known. At the end of the paper we introduce non-degenerate singularities as lifted cotangent models on b-symplectic manifolds and discuss some generalizations of these models to general Poisson manifolds.

  3. INTEGRATED HYDROGEN STORAGE SYSTEM MODEL

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, B

    2007-11-16

    Hydrogen storage is recognized as a key technical hurdle that must be overcome for the realization of hydrogen powered vehicles. Metal hydrides and their doped variants have shown great promise as a storage material and significant advances have been made with this technology. In any practical storage system the rate of H2 uptake will be governed by all processes that affect the rate of mass transport through the bed and into the particles. These coupled processes include heat and mass transfer as well as chemical kinetics and equilibrium. However, with few exceptions, studies of metal hydrides have focused primarily on fundamental properties associated with hydrogen storage capacity and kinetics. A full understanding of the complex interplay of physical processes that occur during the charging and discharging of a practical storage system requires models that integrate the salient phenomena. For example, in the case of sodium alanate, the size of NaAlH4 crystals is on the order of 300nm and the size of polycrystalline particles may be approximately 10 times larger ({approx}3,000nm). For the bed volume to be as small as possible, it is necessary to densely pack the hydride particles. Even so, in packed beds composed of NaAlH{sub 4} particles alone, it has been observed that the void fraction is still approximately 50-60%. Because of the large void fraction and particle to particle thermal contact resistance, the thermal conductivity of the hydride is very low, on the order of 0.2 W/m-{sup o}C, Gross, Majzoub, Thomas and Sandrock [2002]. The chemical reaction for hydrogen loading is exothermic. Based on the data in Gross [2003], on the order of 10{sup 8}J of heat of is released for the uptake of 5 kg of H{sub 2}2 and complete conversion of NaH to NaAlH{sub 4}. Since the hydride reaction transitions from hydrogen loading to discharge at elevated temperatures, it is essential to control the temperature of the bed. However, the low thermal conductivity of the hydride

  4. Probabilistic models for feedback systems.

    Energy Technology Data Exchange (ETDEWEB)

    Grace, Matthew D.; Boggs, Paul T.

    2011-02-01

    In previous work, we developed a Bayesian-based methodology to analyze the reliability of hierarchical systems. The output of the procedure is a statistical distribution of the reliability, thus allowing many questions to be answered. The principal advantage of the approach is that along with an estimate of the reliability, we also can provide statements of confidence in the results. The model is quite general in that it allows general representations of all of the distributions involved, it incorporates prior knowledge into the models, it allows errors in the 'engineered' nodes of a system to be determined by the data, and leads to the ability to determine optimal testing strategies. In this report, we provide the preliminary steps necessary to extend this approach to systems with feedback. Feedback is an essential component of 'complexity' and provides interesting challenges in modeling the time-dependent action of a feedback loop. We provide a mechanism for doing this and analyze a simple case. We then consider some extensions to more interesting examples with local control affecting the entire system. Finally, a discussion of the status of the research is also included.

  5. Modeling Advance Life Support Systems

    Science.gov (United States)

    Pitts, Marvin; Sager, John; Loader, Coleen; Drysdale, Alan

    1996-01-01

    Activities this summer consisted of two projects that involved computer simulation of bioregenerative life support systems for space habitats. Students in the Space Life Science Training Program (SLSTP) used the simulation, space station, to learn about relationships between humans, fish, plants, and microorganisms in a closed environment. One student complete a six week project to modify the simulation by converting the microbes from anaerobic to aerobic, and then balancing the simulation's life support system. A detailed computer simulation of a closed lunar station using bioregenerative life support was attempted, but there was not enough known about system restraints and constants in plant growth, bioreactor design for space habitats and food preparation to develop an integrated model with any confidence. Instead of a completed detailed model with broad assumptions concerning the unknown system parameters, a framework for an integrated model was outlined and work begun on plant and bioreactor simulations. The NASA sponsors and the summer Fell were satisfied with the progress made during the 10 weeks, and we have planned future cooperative work.

  6. Minisuperspace models of discrete systems

    CERN Document Server

    Baytaş, Bekir

    2016-01-01

    A discrete quantum spin system is presented in which several modern methods of canonical quantum gravity can be tested with promising results. In particular, features of interacting dynamics are analyzed with an emphasis on homogeneous configurations and the dynamical building-up and stability of long-range correlations. Different types of homogeneous minisuperspace models are introduced for the system, including one based on condensate states, and shown to capture different aspects of the discrete system. They are evaluated with effective methods and by means of continuum limits, showing good agreement with operator calculations whenever the latter are available. As a possibly quite general result, it is concluded that an analysis of the building-up of long-range correlations in discrete systems requires non-perturbative solutions of the dynamical equations. Some questions related to stability can be analyzed perturbatively, but suggest that matter couplings may be relevant for this question in the context o...

  7. The female gametophyte: an emerging model for cell type-specific systems biology in plant development

    Directory of Open Access Journals (Sweden)

    Marc William Schmid

    2015-11-01

    Full Text Available Systems biology, a holistic approach describing a system emerging from the interactions of its molecular components, critically depends on accurate qualitative determination and quantitative measurements of these components. Development and improvement of large-scale profiling methods (omics now facilitates comprehensive measurements of many relevant molecules. For multicellular organisms, such as animals, fungi, algae, and plants, the complexity of the system is augmented by the presence of specialized cell types and organs, and a complex interplay within and between them. Cell type-specific analyses are therefore crucial for the understanding of developmental processes and environmental responses. This review first gives an overview of current methods used for large-scale profiling of specific cell types exemplified by recent advances in plant biology. The focus then lies on suitable model systems to study plant development and cell type specification. We introduce the female gametophyte of flowering plants as an ideal model to study fundamental developmental processes. Moreover, the female reproductive lineage is of importance for the emergence of evolutionary novelties such as an unequal parental contribution to the tissue nurturing the embryo or the clonal production of seeds by asexual reproduction (apomixis. Understanding these processes is not only interesting from a developmental or evolutionary perspective, but bears great potential for further crop improvement and the simplification of breeding efforts. We finally highlight novel methods, which are already available or which will likely soon facilitate large-scale profiling of the specific cell types of the female gametophyte in both model and non-model species. We conclude that it may take only few years until an evolutionary systems biology approach toward female gametogenesis may decipher some of its biologically most interesting and economically most valuable processes.

  8. Evaluation by quantitative image analysis of anticancer drug activity on multicellular spheroids grown in 3D matrices

    Science.gov (United States)

    Gomes, Aurélie; Russo, Adrien; Vidal, Guillaume; Demange, Elise; Pannetier, Pauline; Souguir, Zied; Lagarde, Jean-Michel; Ducommun, Bernard; Lobjois, Valérie

    2016-01-01

    Pharmacological evaluation of anticancer drugs using 3D in vitro models provides invaluable information for predicting in vivo activity. Artificial matrices are currently available that scale up and increase the power of such 3D models. The aim of the present study was to propose an efficient and robust imaging and analysis pipeline to assess with quantitative parameters the efficacy of a particular cytotoxic drug. HCT116 colorectal adenocarcinoma tumor cell multispheres were grown in a 3D physiological hyaluronic acid matrix. 3D microscopy was performed with structured illumination, whereas image processing and feature extraction were performed with custom analysis tools. This procedure makes it possible to automatically detect spheres in a large volume of matrix in 96-well plates. It was used to evaluate drug efficacy in HCT116 spheres treated with different concentrations of topotecan, a DNA topoisomerase inhibitor. Following automatic detection and quantification, changes in cluster size distribution with a topotecan concentration-dependent increase of small clusters according to drug cytotoxicity were observed. Quantitative image analysis is thus an effective means to evaluate and quantify the cytotoxic and cytostatic activities of anticancer drugs on 3D multicellular models grown in a physiological matrix. PMID:28105152

  9. The Control System Modeling Language

    CERN Document Server

    Zagar, K; Sekoranja, M; Tkacik, G; Vodovnik, A; Zagar, Klemen; Plesko, Mark; Sekoranja, Matej; Tkacik, Gasper; Vodovnik, Anze

    2001-01-01

    The well-known Unified Modeling Language (UML) describes software entities, such as interfaces, classes, operations and attributes, as well as relationships among them, e.g. inheritance, containment and dependency. The power of UML lies in Computer Aided Software Engineering (CASE) tools such as Rational Rose, which are also capable of generating software structures from visual object definitions and relations. UML also allows add-ons that define specific structures and patterns in order to steer and automate the design process. We have developed an add-on called Control System Modeling Language (CSML). It introduces entities and relationships that we know from control systems, such as "property" representing a single controllable point/channel, or an "event" specifying that a device is capable of notifying its clients through events. Entities can also possess CSML-specific characteristics, such as physical units and valid ranges for input parameters. CSML is independent of any specific language or technology...

  10. Contextual Modelling of Collaboration System

    Directory of Open Access Journals (Sweden)

    Wafaa DACHRY

    2012-03-01

    Full Text Available Faced with new environmental constraints, firms decide to collaborate in collective entities and adopt new patterns of behavior. So, this firms’ collaboration becomes an unavoidable approach. Indeed, our aim interest in our study is to propose a collaborative information system for supply chain. Our proposed platform ensures cooperation and information sharing between partners in real time. In fact, several questions have to be asked: What is the information nature may be shared between partners? What processes are implemented between actors? What functional services are supported by the platform? In order to answer these questions, we present, in this article, our methodological approach of modelling, called CMCS (Contextual Modelling of Collaborative System

  11. Stochastic Models of Polymer Systems

    Science.gov (United States)

    2016-01-01

    field limit of a dynamical model for polymer systems, Science China Mathematics , (11 2012): 0. doi: TOTAL: 1 Number of Non Peer-Reviewed Conference...4.0 (4.0 max scale): Number of graduating undergraduates funded by a DoD funded Center of Excellence grant for Education , Research and Engineering...undergraduates funded by your agreement who graduated during this period and will receive scholarships or fellowships for further studies in science

  12. Sialylation facilitates self-assembly of 3D multicellular prostaspheres by using cyclo-RGDfK(TPP peptide

    Directory of Open Access Journals (Sweden)

    Haq S

    2017-05-01

    Full Text Available Sabah Haq,1 Vanessa Samuel,1 Fiona Haxho,1 Roman Akasov,2,3 Maria Leko,4 Sergey V Burov,4 Elena Markvicheva,2 Myron R Szewczuk1 1Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada; 2Polymers for Biology Laboratory, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 3Sechenov First Moscow State Medical University, Institute for Regenerative Medicine, Moscow, 4Synthesis of Peptides and Polymer Microspheres Laboratory, Institute of Macromolecular Compounds, Russian Academy of Sciences, St Petersburg, Russia Background: Prostaspheres-based three dimensional (3D culture models have provided insight into prostate cancer (PCa biology, highlighting the importance of cell–cell interactions and the extracellular matrix (EMC in the tumor microenvironment. Although these 3D classical spheroid platforms provide a significant advance over 2D models mimicking in vivo tumors, the limitations involve no control of assembly and structure with only limited spatial or glandular organization. Here, matrix-free prostaspheres from human metastatic prostate carcinoma PC3 and DU145 cell lines and their respective gemcitabine resistant (GemR variants were generated by using cyclic Arg-Gly-Asp-D-Phe-Lys peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo-RGDfK(TPP.Materials and methods: Microscopic imaging, immunocytochemistry (ICC, flow cytometry, sialidase, and WST-1 cell viability assays were used to evaluate the formation of multicellular tumor spheroid (MCTS, cell survival, morphologic changes, and expression levels of α2,6 and α2,3 sialic acid (SA and E- and N-cadherin in DU145, PC3, and their GemR variants.Results: By using the cyclo-RGDfK(TPP peptide platform in a dose- and time-dependent manner, both DU145 and DU145GemR cells formed small MCTS. In contrast, PC3 and PC3GemR cells formed irregular multicellular aggregates at all concentrations of cyclo

  13. Molecular and functional assessment of multicellular cancer spheroids produced in double emulsions enabled by efficient airway resistance based selective surface treatment

    Science.gov (United States)

    Ma, Xiao; Leth Jepsen, Morten; Ivarsen, Anne Kathrine R.; Knudsen, Birgitta R.; Ho, Yi-Ping

    2017-09-01

    Multicellular spheroids have garnered significant attention as an in vitro three-dimensional cancer model which can mimick the in vivo microenvironmental features. While microfluidics generated double emulsions have become a potential method to generate spheroids, challenges remain on the tedious procedures. Enabled by a novel ‘airway resistance’ based selective surface treatment, this study presents an easy and facile generation of double emulsions for the initiation and cultivation of multicellular spheroids in a scaffold-free format. Combining with our previously developed DNA nanosensors, intestinal spheroids produced in the double emulsions have shown an elevated activities of an essential DNA modifying enzyme, the topoisomerase I. The observed molecular and functional characteristics of spheroids produced in double emulsions are similar to the counterparts produced by the commercially available ultra-low attachment plates. However, the double emulsions excel for their improved uniformity, and the consistency of the results obtained by subsequent analysis of the spheroids. The presented technique is expected to ease the burden of producing spheroids and to promote the spheroids model for cancer or stem cell study.

  14. Model reduction of parametrized systems

    CERN Document Server

    Ohlberger, Mario; Patera, Anthony; Rozza, Gianluigi; Urban, Karsten

    2017-01-01

    The special volume offers a global guide to new concepts and approaches concerning the following topics: reduced basis methods, proper orthogonal decomposition, proper generalized decomposition, approximation theory related to model reduction, learning theory and compressed sensing, stochastic and high-dimensional problems, system-theoretic methods, nonlinear model reduction, reduction of coupled problems/multiphysics, optimization and optimal control, state estimation and control, reduced order models and domain decomposition methods, Krylov-subspace and interpolatory methods, and applications to real industrial and complex problems. The book represents the state of the art in the development of reduced order methods. It contains contributions from internationally respected experts, guaranteeing a wide range of expertise and topics. Further, it reflects an important effor t, carried out over the last 12 years, to build a growing research community in this field. Though not a textbook, some of the chapters ca...

  15. Computational models of complex systems

    CERN Document Server

    Dabbaghian, Vahid

    2014-01-01

    Computational and mathematical models provide us with the opportunities to investigate the complexities of real world problems. They allow us to apply our best analytical methods to define problems in a clearly mathematical manner and exhaustively test our solutions before committing expensive resources. This is made possible by assuming parameter(s) in a bounded environment, allowing for controllable experimentation, not always possible in live scenarios. For example, simulation of computational models allows the testing of theories in a manner that is both fundamentally deductive and experimental in nature. The main ingredients for such research ideas come from multiple disciplines and the importance of interdisciplinary research is well recognized by the scientific community. This book provides a window to the novel endeavours of the research communities to present their works by highlighting the value of computational modelling as a research tool when investigating complex systems. We hope that the reader...

  16. Time-lapse 3-D measurements of a glucose biosensor in multicellular spheroids by light sheet fluorescence microscopy in commercial 96-well plates

    Science.gov (United States)

    Maioli, Vincent; Chennell, George; Sparks, Hugh; Lana, Tobia; Kumar, Sunil; Carling, David; Sardini, Alessandro; Dunsby, Chris

    2016-11-01

    Light sheet fluorescence microscopy has previously been demonstrated on a commercially available inverted fluorescence microscope frame using the method of oblique plane microscopy (OPM). In this paper, OPM is adapted to allow time-lapse 3-D imaging of 3-D biological cultures in commercially available glass-bottomed 96-well plates using a stage-scanning OPM approach (ssOPM). Time-lapse 3-D imaging of multicellular spheroids expressing a glucose Förster resonance energy transfer (FRET) biosensor is demonstrated in 16 fields of view with image acquisition at 10 minute intervals. As a proof-of-principle, the ssOPM system is also used to acquire a dose response curve with the concentration of glucose in the culture medium being varied across 42 wells of a 96-well plate with the whole acquisition taking 9 min. The 3-D image data enable the FRET ratio to be measured as a function of distance from the surface of the spheroid. Overall, the results demonstrate the capability of the OPM system to measure spatio-temporal changes in FRET ratio in 3-D in multicellular spheroids over time in a multi-well plate format.

  17. Identification and Modelling of Linear Dynamic Systems

    Directory of Open Access Journals (Sweden)

    Stanislav Kocur

    2006-01-01

    Full Text Available System identification and modelling are very important parts of system control theory. System control is only as good as good is created model of system. So this article deals with identification and modelling problems. There are simple classification and evolution of identification methods, and then the modelling problem is described. Rest of paper is devoted to two most known and used models of linear dynamic systems.

  18. Trichomes as models for studying plant cell differentiation.

    Science.gov (United States)

    Yang, Changxian; Ye, Zhibiao

    2013-06-01

    Trichomes, originating from epidermal cells, are present on nearly all terrestrial plants. They exist in diverse forms, are readily accessible, and serve as an excellent model system for analyzing the molecular mechanisms in plant cell differentiation, including cell fate choices, cell cycle control, and cell morphogenesis. In Arabidopsis, two regulatory models have been identified that function in parallel in trichome formation; the activator-inhibitor model and the activator-depletion model. Cotton fiber, a similar unicellular structure, is controlled by some functional homologues of Arabidopsis trichome-patterning genes. Multicellular trichomes, as in tobacco and tomato, may form through a distinct pathway from unicellular trichomes. Recent research has shown that cell cycle control participates in trichome formation. In this review, we summarize the molecular mechanisms involved in the formation of unicellular and multicellular trichomes, and discuss the integration of the cell cycle in its initiation and morphogenesis.

  19. ISSM: Ice Sheet System Model

    Science.gov (United States)

    Larour, Eric; Schiermeier, John E.; Seroussi, Helene; Morlinghem, Mathieu

    2013-01-01

    In order to have the capability to use satellite data from its own missions to inform future sea-level rise projections, JPL needed a full-fledged ice-sheet/iceshelf flow model, capable of modeling the mass balance of Antarctica and Greenland into the near future. ISSM was developed with such a goal in mind, as a massively parallelized, multi-purpose finite-element framework dedicated to ice-sheet modeling. ISSM features unstructured meshes (Tria in 2D, and Penta in 3D) along with corresponding finite elements for both types of meshes. Each finite element can carry out diagnostic, prognostic, transient, thermal 3D, surface, and bed slope simulations. Anisotropic meshing enables adaptation of meshes to a certain metric, and the 2D Shelfy-Stream, 3D Blatter/Pattyn, and 3D Full-Stokes formulations capture the bulk of the ice-flow physics. These elements can be coupled together, based on the Arlequin method, so that on a large scale model such as Antarctica, each type of finite element is used in the most efficient manner. For each finite element referenced above, ISSM implements an adjoint. This adjoint can be used to carry out model inversions of unknown model parameters, typically ice rheology and basal drag at the ice/bedrock interface, using a metric such as the observed InSAR surface velocity. This data assimilation capability is crucial to allow spinning up of ice flow models using available satellite data. ISSM relies on the PETSc library for its vectors, matrices, and solvers. This allows ISSM to run efficiently on any parallel platform, whether shared or distrib- ISSM: Ice Sheet System Model NASA's Jet Propulsion Laboratory, Pasadena, California uted. It can run on the largest clusters, and is fully scalable. This allows ISSM to tackle models the size of continents. ISSM is embedded into MATLAB and Python, both open scientific platforms. This improves its outreach within the science community. It is entirely written in C/C++, which gives it flexibility in its

  20. Integrated Modeling for Flood Hazard Mapping Using Watershed Modeling System

    National Research Council Canada - National Science Library

    Seyedeh S. Sadrolashrafi; Thamer A. Mohamed; Ahmad R.B. Mahmud; Majid K. Kholghi; Amir Samadi

    2008-01-01

    ...) with the Watershed Modeling System (WMS) for flood modeling is developed. It also interconnects the terrain models and the GIS software, with commercial standard hydrological and hydraulic models, including HEC-1, HEC-RAS, etc...

  1. Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Klausen, Mikkel; Aaes-Jorgensen, A.; Molin, Søren

    2003-01-01

    development, we have performed an investigation with time-lapse confocal laser scanning microscopy of biofilms formed by various combinations of colour-coded P. aeruginosa wild type and motility mutants. We show that mushroom-shaped multicellular structures in P. aeruginosa biofilms can form in a sequential...... process involving a non-motile bacterial subpopulation and a migrating bacterial subpopulation. The non-motile bacteria form the mushroom stalks by growth in certain foci of the biofilm. The migrating bacteria form the mushroom caps by climbing the stalks and aggregating on the tops in a process which...

  2. Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Klausen, Mikkel; Aaes-Jorgensen, A.; Molin, Søren;

    2003-01-01

    development, we have performed an investigation with time-lapse confocal laser scanning microscopy of biofilms formed by various combinations of colour-coded P. aeruginosa wild type and motility mutants. We show that mushroom-shaped multicellular structures in P. aeruginosa biofilms can form in a sequential...... process involving a non-motile bacterial subpopulation and a migrating bacterial subpopulation. The non-motile bacteria form the mushroom stalks by growth in certain foci of the biofilm. The migrating bacteria form the mushroom caps by climbing the stalks and aggregating on the tops in a process which...

  3. Network models in anatomical systems.

    Science.gov (United States)

    Esteve-Altava, Borja; Marugán-Lobón, Jesús; Botella, Héctor; Rasskin-Gutman, Diego

    2011-01-01

    Network theory has been extensively used to model the underlying structure of biological processes. From genetics to ecology, network thinking is changing our understanding of complex systems, specifically how their internal structure determines their overall behavior. Concepts such as hubs, scale-free or small-world networks, common in the complexity literature, are now used more and more in sociology, neurosciences, as well as other anthropological fields. Even though the use of network models is nowadays so widely applied, few attempts have been carried out to enrich our understanding in the classical morphological sciences such as in comparative anatomy or physical anthropology. The purpose of this article is to introduce the usage of network tools in morphology; specifically by building anatomical networks, dealing with the most common analyses and problems, and interpreting their outcome.

  4. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    Offshore reservoirs represent one of the major growth areas of the oil and gas industry, and environmental safety is one of the biggest challenges for the offshore exploration and production. The oil accidents in the Gulf of Mexico in 1979 and 2010 were two of the biggest disasters in history...... after an oil spill. Engineering thermodynamics could be applied in the state-of-the-art sonar products through advanced artificial technology, if the speed of sound, solubility and density of oil-seawater systems could be satisfactorily modelled. The addition of methanol or glycols into unprocessed well...

  5. Models for Gaze Tracking Systems

    Directory of Open Access Journals (Sweden)

    Villanueva Arantxa

    2007-01-01

    Full Text Available One of the most confusing aspects that one meets when introducing oneself into gaze tracking technology is the wide variety, in terms of hardware equipment, of available systems that provide solutions to the same matter, that is, determining the point the subject is looking at. The calibration process permits generally adjusting nonintrusive trackers based on quite different hardware and image features to the subject. The negative aspect of this simple procedure is that it permits the system to work properly but at the expense of a lack of control over the intrinsic behavior of the tracker. The objective of the presented article is to overcome this obstacle to explore more deeply the elements of a video-oculographic system, that is, eye, camera, lighting, and so forth, from a purely mathematical and geometrical point of view. The main contribution is to find out the minimum number of hardware elements and image features that are needed to determine the point the subject is looking at. A model has been constructed based on pupil contour and multiple lighting, and successfully tested with real subjects. On the other hand, theoretical aspects of video-oculographic systems have been thoroughly reviewed in order to build a theoretical basis for further studies.

  6. Models for Gaze Tracking Systems

    Directory of Open Access Journals (Sweden)

    Arantxa Villanueva

    2007-10-01

    Full Text Available One of the most confusing aspects that one meets when introducing oneself into gaze tracking technology is the wide variety, in terms of hardware equipment, of available systems that provide solutions to the same matter, that is, determining the point the subject is looking at. The calibration process permits generally adjusting nonintrusive trackers based on quite different hardware and image features to the subject. The negative aspect of this simple procedure is that it permits the system to work properly but at the expense of a lack of control over the intrinsic behavior of the tracker. The objective of the presented article is to overcome this obstacle to explore more deeply the elements of a video-oculographic system, that is, eye, camera, lighting, and so forth, from a purely mathematical and geometrical point of view. The main contribution is to find out the minimum number of hardware elements and image features that are needed to determine the point the subject is looking at. A model has been constructed based on pupil contour and multiple lighting, and successfully tested with real subjects. On the other hand, theoretical aspects of video-oculographic systems have been thoroughly reviewed in order to build a theoretical basis for further studies.

  7. From the complex system leadership perspective: DNA leadership

    Directory of Open Access Journals (Sweden)

    Hasan Basri Gündüz

    2011-01-01

    Full Text Available Traditional leadership models are based on the paradigm of bureaucratic top-down administration. These models were suitable for industrial societies and organizations. However, the complex and quickly changing structure of information societies and because market conditions become more and more challenging conditions require different and more flexible organizational structures and leadership approaches. Complexity leadership approach is one of the approaches that were put forward to meet these needs. This approach suggests a new paradigm for leadership, and leadership is defined as a complex interactive dynamic from which adaptive outcomes (learning, innovation, and adaptability emerge.  Multi-cellular higher organisms are complex systems like information societies. In this context, DNA that leads the processes in multi-cellular higher organisms may be taken as a metaphor for leadership. In this study, considering the functions and role of DNA in a cell, the concept of DNA leadership was discussed from the complex system leadership perspective.

  8. Area Logistics System Based on System Dynamics Model

    Institute of Scientific and Technical Information of China (English)

    GUI Shouping; ZHU Qiang; LU Lifang

    2005-01-01

    At present, there are few effective ways to analyze area logistics systems. This paper uses system dynamics to analyze the area logistics system and establishes a system dynamics model for the area logistics system based on the characteristics of the area logistics system and system dynamics. Numerical simulations with the system dynamic model were used to analyze a logistic system. Analysis of the Guangzhou economy shows that the model can reflect the actual state of the system objectively and can be used to make policy and harmonize environment.

  9. Enterprise Modelling supported by Manufacturing Systems Theory

    OpenAIRE

    MYKLEBUST, Odd

    2002-01-01

    There exist today a large number of enterprise models or enterprise modelling approaches. In a study of standards and project developed models there are two approaches: CIMOSA “The Open Systems Architecture for CIM” and GERAM, “Generalised Enterprise Reference Architecture”, which show a system orientation that can be further followed as interesting research topics for a system theory oriented approach for enterprise models. In the selection of system theories, manufacturing system theory...

  10. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

    2003-01-01

    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering o

  11. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

    2003-01-01

    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering

  12. Nonlinear System Identification and Behavioral Modeling

    CERN Document Server

    Huq, Kazi Mohammed Saidul; Kabir, A F M Sultanul

    2010-01-01

    The problem of determining a mathematical model for an unknown system by observing its input-output data pair is generally referred to as system identification. A behavioral model reproduces the required behavior of the original analyzed system, such as there is a one-to-one correspondence between the behavior of the original system and the simulated system. This paper presents nonlinear system identification and behavioral modeling using a work assignment.

  13. A View of Earth System Model Development

    Institute of Scientific and Technical Information of China (English)

    ZHOU Tianjun; YU Yongqiang; WANG Bin

    2009-01-01

    This paper gives a definition of earth system model and shows three development phases of it, including physical climate system model, earth climate system model, and earth system model, based on an inves-tigation of climate system models in the world. It provides an expatiation on the strategic significance of future development of earth system model, an introduction of some representative scientific research plans on development of earth system model home and abroad, and a review of its status and trends based on the models of the fourth assessment report (AR4) of the Intergovernmental Panel on Climate Change (IPCC).Some suggestions on future development of earth system model in China are given, which are expected to be helpful to advance the development.

  14. Inter-specific coral chimerism: Genetically distinct multicellular structures associated with tissue loss in Montipora capitata

    Science.gov (United States)

    Work, Thierry M.; Forsman, Zac H.; Szabo, Zoltan; Lewis, Teresa D.; Aeby, Greta S.; Toonen, Robert J.

    2011-01-01

    Montipora white syndrome (MWS) results in tissue-loss that is often lethal to Montipora capitata, a major reef building coral that is abundant and dominant in the Hawai'ian Archipelago. Within some MWS-affected colonies in Kane'ohe Bay, Oahu, Hawai'i, we saw unusual motile multicellular structures within gastrovascular canals (hereafter referred to as invasive gastrovascular multicellular structure-IGMS) that were associated with thinning and fragmentation of the basal body wall. IGMS were in significantly greater densities in coral fragments manifesting tissue-loss compared to paired normal fragments. Mesenterial filaments from these colonies yielded typical M. capitata mitochondrial haplotypes (CO1, CR), while IGMS from the same colony consistently yielded distinct haplotypes previously only found in a different Montipora species (Montipora flabellata). Protein profiles showed consistent differences between paired mesenterial filaments and IGMS from the same colonies as did seven microsatellite loci that also exhibited an excess of alleles per locus inconsistent with a single diploid organism. We hypothesize that IGMS are a parasitic cellular lineage resulting from the chimeric fusion between M. capitata and M. flabellata larvae followed by morphological reabsorption of M. flabellata and subsequent formation of cell-lineage parasites. We term this disease Montiporaiasis. Although intra-specific chimerism is common in colonial animals, this is the first suspected inter-specific example and the first associated with tissue loss.

  15. Inter-specific coral chimerism: genetically distinct multicellular structures associated with tissue loss in Montipora capitata.

    Directory of Open Access Journals (Sweden)

    Thierry M Work

    Full Text Available Montipora white syndrome (MWS results in tissue-loss that is often lethal to Montipora capitata, a major reef building coral that is abundant and dominant in the Hawai'ian Archipelago. Within some MWS-affected colonies in Kane'ohe Bay, Oahu, Hawai'i, we saw unusual motile multicellular structures within gastrovascular canals (hereafter referred to as invasive gastrovascular multicellular structure-IGMS that were associated with thinning and fragmentation of the basal body wall. IGMS were in significantly greater densities in coral fragments manifesting tissue-loss compared to paired normal fragments. Mesenterial filaments from these colonies yielded typical M. capitata mitochondrial haplotypes (CO1, CR, while IGMS from the same colony consistently yielded distinct haplotypes previously only found in a different Montipora species (Montipora flabellata. Protein profiles showed consistent differences between paired mesenterial filaments and IGMS from the same colonies as did seven microsatellite loci that also exhibited an excess of alleles per locus inconsistent with a single diploid organism. We hypothesize that IGMS are a parasitic cellular lineage resulting from the chimeric fusion between M. capitata and M. flabellata larvae followed by morphological reabsorption of M. flabellata and subsequent formation of cell-lineage parasites. We term this disease Montiporaiasis. Although intra-specific chimerism is common in colonial animals, this is the first suspected inter-specific example and the first associated with tissue loss.

  16. Indole affects the formation of multicellular aggregate structures in Pantoea agglomerans YS19.

    Science.gov (United States)

    Yu, Xuemei; Jiang, Jing; Liang, Chen; Zhang, Xiao; Wang, Jieru; Shen, Delong; Feng, Yongjun

    2016-01-01

    Pantoea agglomerans YS19 is an endophytic diazotrophic bacterium isolated from rice. As well as having the ability to form a biofilm, as do most bacteria, it is characterized by the formation of a unique multicellular aggregate structure called symplasmata. Indole is traditionally known as a metabolite of the amino acid tryptophan, which, however, has recently been shown to participate in various regulations of bacterial physiological processes, including stress resistance, quorum sensing and biofilm formation. Here, an indole signal was found to promote symplasmata formation, yet inhibit biofilm formation, indicating different regulatory pathways of indole in the construction of the two structures. However, symplasmata showed almost an equivalent stress-resistant capability, as compared with biofilms, for YS19 to confront acids, heavy metals (Cu(2+)), and UV treatments. Moreover, indole was tested to show a promoting effect on exopolysaccharides (EPS) production and an inhibition effect on the expression of an outer membrane protein OmpW. These results provide evidence for understanding the regulatory mechanisms of indole on such multicellular aggregates.

  17. Dissolved Gases and Ice Fracturing During the Freezing of a Multicellular Organism: Lessons from Tardigrades.

    Science.gov (United States)

    Kletetschka, Gunther; Hruba, Jolana

    2015-01-01

    Three issues are critical for successful cryopreservation of multicellular material: gases dissolved in liquid, thermal conductivity of the tissue, and localization of microstructures. Here we show that heat distribution is controlled by the gas amount dissolved in liquids and that when changing the liquid into solid, the dissolved gases either form bubbles due to the absence of space in the lattice of solids and/or are migrated toward the concentrated salt and sugar solution at the cost of amount of heat required to be removed to complete a solid-state transition. These factors affect the heat distribution in the organs to be cryopreserved. We show that the gas concentration issue controls fracturing of ice when freezing. There are volumetric changes not only when changing the liquid into solid (volume increases) but also reduction of the volume when reaching lower temperatures (volume decreases). We discuss these issues parallel with observations of the cryosurvivability of multicellular organisms, tardigrades, and discuss their analogy for cryopreservation of large organs.

  18. Inferring Growth Control Mechanisms in Growing Multi-cellular Spheroids of NSCLC Cells from Spatial-Temporal Image Data.

    Directory of Open Access Journals (Sweden)

    Nick Jagiella

    2016-02-01

    Full Text Available We develop a quantitative single cell-based mathematical model for multi-cellular tumor spheroids (MCTS of SK-MES-1 cells, a non-small cell lung cancer (NSCLC cell line, growing under various nutrient conditions: we confront the simulations performed with this model with data on the growth kinetics and spatial labeling patterns for cell proliferation, extracellular matrix (ECM, cell distribution and cell death. We start with a simple model capturing part of the experimental observations. We then show, by performing a sensitivity analysis at each development stage of the model that its complexity needs to be stepwise increased to account for further experimental growth conditions. We thus ultimately arrive at a model that mimics the MCTS growth under multiple conditions to a great extent. Interestingly, the final model, is a minimal model capable of explaining all data simultaneously in the sense, that the number of mechanisms it contains is sufficient to explain the data and missing out any of its mechanisms did not permit fit between all data and the model within physiological parameter ranges. Nevertheless, compared to earlier models it is quite complex i.e., it includes a wide range of mechanisms discussed in biological literature. In this model, the cells lacking oxygen switch from aerobe to anaerobe glycolysis and produce lactate. Too high concentrations of lactate or too low concentrations of ATP promote cell death. Only if the extracellular matrix density overcomes a certain threshold, cells are able to enter the cell cycle. Dying cells produce a diffusive growth inhibitor. Missing out the spatial information would not permit to infer the mechanisms at work. Our findings suggest that this iterative data integration together with intermediate model sensitivity analysis at each model development stage, provide a promising strategy to infer predictive yet minimal (in the above sense quantitative models of tumor growth, as prospectively of

  19. System identification application using Hammerstein model

    Indian Academy of Sciences (India)

    SABAN OZER; HASAN ZORLU; SELCUK METE

    2016-06-01

    Generally, memoryless polynomial nonlinear model for nonlinear part and finite impulse response (FIR) model or infinite impulse response model for linear part are preferred in Hammerstein models in literature. In this paper, system identification applications of Hammerstein model that is cascade of nonlinear second order volterra and linear FIR model are studied. Recursive least square algorithm is used to identify the proposed Hammerstein model parameters. Furthermore, the results are compared to identify the success of proposed Hammerstein model and different types of models

  20. Modeling of economic systems with Petri nets

    Directory of Open Access Journals (Sweden)

    Pavel Valeryevich Skorodumov

    2014-09-01

    Full Text Available Modeling is one of the most important tools to study complex systems. Components of both continuous and discrete nature are present in the behavior of contemporary economic systems. The article uses formalism of nested hybrid Petri nets as a tool to study complex economic systems. The author describes basic approaches of simulation modelling, concepts of classical Petri nets, modified means of nested hybrid Petri nets, benefits of their use for systems modeling. The article presents the concept of a universal system of simulation modeling. On the basis of considered approaches the article proposes to develop a universal system of simulation modeling on the basis of the modified machine Petri nets

  1. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  2. Neuman systems model in holland: an update.

    Science.gov (United States)

    Merks, André; Verberk, Frans; de Kuiper, Marlou; Lowry, Lois W

    2012-10-01

    The authors of this column, leading members of the International Neuman Systems Model Association, provide an update on the use of Neuman systems model in Holland and document the various changes in The Netherlands that have influenced the use of the model in that country. The model's link to systems theory and stress theory are discussed, as well as a shift to greater emphasis on patient self-management. The model is also linked to healthcare quality improvement and interprofessional collaboration in Holland.

  3. New model systems for experimental evolution.

    Science.gov (United States)

    Collins, Sinéad

    2013-07-01

    Microbial experimental evolution uses a few well-characterized model systems to answer fundamental questions about how evolution works. This special section highlights novel model systems for experimental evolution, with a focus on marine model systems that can be used to understand evolutionary responses to global change in the oceans.

  4. Performance modeling of automated manufacturing systems

    Science.gov (United States)

    Viswanadham, N.; Narahari, Y.

    A unified and systematic treatment is presented of modeling methodologies and analysis techniques for performance evaluation of automated manufacturing systems. The book is the first treatment of the mathematical modeling of manufacturing systems. Automated manufacturing systems are surveyed and three principal analytical modeling paradigms are discussed: Markov chains, queues and queueing networks, and Petri nets.

  5. Modeling human operator involvement in robotic systems

    NARCIS (Netherlands)

    Wewerinke, P.H.

    1991-01-01

    A modeling approach is presented to describe complex manned robotic systems. The robotic system is modeled as a (highly) nonlinear, possibly time-varying dynamic system including any time delays in terms of optimal estimation, control and decision theory. The role of the human operator(s) is modeled

  6. Visual computing model for immune system and medical system.

    Science.gov (United States)

    Gong, Tao; Cao, Xinxue; Xiong, Qin

    2015-01-01

    Natural immune system is an intelligent self-organizing and adaptive system, which has a variety of immune cells with different types of immune mechanisms. The mutual cooperation between the immune cells shows the intelligence of this immune system, and modeling this immune system has an important significance in medical science and engineering. In order to build a comprehensible model of this immune system for better understanding with the visualization method than the traditional mathematic model, a visual computing model of this immune system was proposed and also used to design a medical system with the immune system, in this paper. Some visual simulations of the immune system were made to test the visual effect. The experimental results of the simulations show that the visual modeling approach can provide a more effective way for analyzing this immune system than only the traditional mathematic equations.

  7. High-order sliding mode control of a DC motor drive via a switched controlled multi-cellular converter

    Science.gov (United States)

    Djemaï, M.; Busawon, K.; Benmansour, K.; Marouf, A.

    2011-11-01

    In this article, we present a high-order sliding mode controller of a DC motor drive connected to a multi-cellular converter. More specifically, we design a second-order (super-twisting) control algorithm for the speed regulation of a DC motor. For this, a switching control for the multi-cellular converter is derived in order to supply the correct reference value for the speed regulation. A practical implementation of the controller is realised using a laboratory set-up. The performance and the validity of the controller are shown experimentally.

  8. Externalizing Behaviour for Analysing System Models

    NARCIS (Netherlands)

    Ivanova, Marieta Georgieva; Probst, Christian W.; Hansen, René Rydhof; Kammüller, Florian

    Systems models have recently been introduced to model organisationsandevaluate their vulnerability to threats and especially insiderthreats. Especially for the latter these models are very suitable, since insiders can be assumed to have more knowledge about the attacked organisation than outside

  9. CONTROL SYSTEM IDENTIFICATION THROUGH MODEL MODULATION METHODS

    Science.gov (United States)

    identification has been achieved by using model modulation techniques to drive dynamic models into correspondence with operating control systems. The system ... identification then proceeded from examination of the model and the adaptive loop. The model modulation techniques applied to adaptive control

  10. Two sustainable energy system analysis models

    DEFF Research Database (Denmark)

    Lund, Henrik; Goran Krajacic, Neven Duic; da Graca Carvalho, Maria

    2005-01-01

    This paper presents a comparative study of two energy system analysis models both designed with the purpose of analysing electricity systems with a substantial share of fluctuating renewable energy.......This paper presents a comparative study of two energy system analysis models both designed with the purpose of analysing electricity systems with a substantial share of fluctuating renewable energy....

  11. Tumorigenic fragments of APC cause dominant defects in directional cell migration in multiple model systems

    Directory of Open Access Journals (Sweden)

    Scott A. Nelson

    2012-11-01

    Nonsense mutations that result in the expression of truncated, N-terminal, fragments of the adenomatous polyposis coli (APC tumour suppressor protein are found in most sporadic and some hereditary colorectal cancers. These mutations can cause tumorigenesis by eliminating β-catenin-binding sites from APC, which leads to upregulation of β-catenin and thereby results in the induction of oncogenes such as MYC. Here we show that, in three distinct experimental model systems, expression of an N-terminal fragment of APC (N-APC results in loss of directionality, but not speed, of cell motility independently of changes in β-catenin regulation. We developed a system to culture and fluorescently label live pieces of gut tissue to record high-resolution three-dimensional time-lapse movies of cells in situ. This revealed an unexpected complexity of normal gut cell migration, a key process in gut epithelial maintenance, with cells moving with spatial and temporal discontinuity. Quantitative comparison of gut tissue from wild-type mice and APC heterozygotes (APCMin/+; multiple intestinal neoplasia model demonstrated that cells in precancerous epithelia lack directional preference when moving along the crypt-villus axis. This effect was reproduced in diverse experimental systems: in developing chicken embryos, mesoderm cells expressing N-APC failed to migrate normally; in amoeboid Dictyostelium, which lack endogenous APC, expressing an N-APC fragment maintained cell motility, but the cells failed to perform directional chemotaxis; and multicellular Dictyostelium slug aggregates similarly failed to perform phototaxis. We propose that N-terminal fragments of APC represent a gain-of-function mutation that causes cells within tissue to fail to migrate directionally in response to relevant guidance cues. Consistent with this idea, crypts in histologically normal tissues of APCMin/+ intestines are overpopulated with cells, suggesting that a lack of migration might cause cell

  12. Graphical Model Debugger Framework for Embedded Systems

    DEFF Research Database (Denmark)

    Zeng, Kebin; Guo, Yu; Angelov, Christo K.

    2010-01-01

    Model Driven Software Development has offered a faster way to design and implement embedded real-time software by moving the design to a model level, and by transforming models to code. However, the testing of embedded systems has remained at the code level. This paper presents a Graphical Model...... Debugger Framework, providing an auxiliary avenue of analysis of system models at runtime by executing generated code and updating models synchronously, which allows embedded developers to focus on the model level. With the model debugger, embedded developers can graphically test their design model...

  13. Particle Tracking Model (PTM) with Coastal Modeling System (CMS)

    Science.gov (United States)

    2014-10-31

    System ( CMS ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER...www.erdc.usace.army.mil/Missions/WaterResources/CIRP.aspx Coastal Inlets Research Program Particle Tracking Model (PTM) with Coastal Modeling System ( CMS ) The...System ( CMS ), which provides coupled wave and current forcing for PTM simulations. CMS -PTM is implemented in the Surface-water Modeling System, a

  14. Analysis hierarchical model for discrete event systems

    Science.gov (United States)

    Ciortea, E. M.

    2015-11-01

    The This paper presents the hierarchical model based on discrete event network for robotic systems. Based on the hierarchical approach, Petri network is analysed as a network of the highest conceptual level and the lowest level of local control. For modelling and control of complex robotic systems using extended Petri nets. Such a system is structured, controlled and analysed in this paper by using Visual Object Net ++ package that is relatively simple and easy to use, and the results are shown as representations easy to interpret. The hierarchical structure of the robotic system is implemented on computers analysed using specialized programs. Implementation of hierarchical model discrete event systems, as a real-time operating system on a computer network connected via a serial bus is possible, where each computer is dedicated to local and Petri model of a subsystem global robotic system. Since Petri models are simplified to apply general computers, analysis, modelling, complex manufacturing systems control can be achieved using Petri nets. Discrete event systems is a pragmatic tool for modelling industrial systems. For system modelling using Petri nets because we have our system where discrete event. To highlight the auxiliary time Petri model using transport stream divided into hierarchical levels and sections are analysed successively. Proposed robotic system simulation using timed Petri, offers the opportunity to view the robotic time. Application of goods or robotic and transmission times obtained by measuring spot is obtained graphics showing the average time for transport activity, using the parameters sets of finished products. individually.

  15. Extensions in model-based system analysis

    OpenAIRE

    Graham, Matthew R.

    2007-01-01

    Model-based system analysis techniques provide a means for determining desired system performance prior to actual implementation. In addition to specifying desired performance, model-based analysis techniques require mathematical descriptions that characterize relevant behavior of the system. The developments of this dissertation give ex. tended formulations for control- relevant model estimation as well as model-based analysis conditions for performance requirements specified as frequency do...

  16. Inductive modelling of an entrepreneurial system

    OpenAIRE

    Yearworth, M

    2010-01-01

    We describe the development of a novel approach to generating theory about the behaviour of an entrepreneurial or start-up system. The new technology business creation system in and around the cities of Bath and Bristol in the UK was analysed using an inductive modelling approach that hybridises grounded theory with system dynamics, a technique we have called grounded systems modelling. Three models that represent the stages of development of an idea through to successful exploitation have be...

  17. Control model for reconfigurable assembly systems

    Institute of Scientific and Technical Information of China (English)

    Yu Jianfeng; Yin Yuehong; Chen Zhaoneng

    2005-01-01

    This paper proposes knowledge based object-oriented timed colored Petri net, a modeling method for reconfigurable assembly systems. Combining knowledge and object-oriented method into timed colored Petri net, a comprehensive and powerful representation model for control of RAS is obtained. With object-oriented method the whole system can be decomposed into concrete objects explicitly, and their relationships are constructed according to the system assembly requirements. Finally, a simple assembly system modeled by the KTCOPN is presented.

  18. Lineage Specification of Ovarian Theca Cells Requires Multi-Cellular Interactions via Oocyte and Granulosa Cells

    Science.gov (United States)

    Liu, Chang; Peng, Jia; Matzuk, Martin M.; Yao, Humphrey H-C

    2015-01-01

    Organogenesis of the ovary is a highly orchestrated process involving multiple lineage determinations of ovarian surface epithelium, granulosa cells, and theca cells. While the sources of ovarian surface epithelium and granulosa cells are known, the origin(s) of theca progenitor cells have not been definitively identified. Here we show that theca cells derive from two sources: Wt1+ cells indigenous to the ovary and Gli1+ mesenchymal cells migrated from the mesonephros. These progenitors acquire theca lineage marker Gli1 in response to paracrine signals Desert hedgehog (Dhh) and Indian hedgehog (Ihh) from granulosa cells. Ovaries lacking Dhh/Ihh exhibit theca layer loss, blunted steroid production, arrested folliculogenesis, and failure to form corpora lutea. Production of Dhh/Ihh in granulosa cells requires Growth differentiation factor 9 (GDF9) from the oocyte. Our studies provide the first genetic evidence for the origins of theca cells and reveal a multicellular interaction critical for the formation of a functional theca. PMID:25917826

  19. Rapid Engineering of Three-Dimensional, Multicellular Tissues With Polymeric Scaffolds

    Science.gov (United States)

    Gonda, Steve R.; Jordan, Jacqueline; Fraga, Denise N.

    2007-01-01

    A process has been developed for the rapid tissue engineering of multicellular-tissue-equivalent assemblies by the controlled enzymatic degradation of polymeric beads in a low-fluid-shear bioreactor. In this process, the porous polymeric beads serve as temporary scaffolds to support the assemblies of cells in a tissuelike 3D configuration during the critical initial growth phases of attachment of anchorage-dependent cells, aggregation of the cells, and formation of a 3D extracellular matrix. Once the cells are assembled into a 3D array and enmeshed in a structural supportive 3D extracellular matrix (ECM), the polymeric scaffolds can be degraded in the low-fluid-shear environment of the NASA-designed bioreactor. The natural 3D tissuelike assembly, devoid of any artificial support structure, is maintained in the low-shear bioreactor environment by the newly formed natural cellular/ECM. The elimination of the artificial scaffold allows normal tissue structure and function.

  20. Modelling Immune System: Principles, Models,Analysis and Perspectives

    Institute of Scientific and Technical Information of China (English)

    Xiang-hua Li; Zheng-xuan Wang; Tian-yang Lu; Xiang-jiu Che

    2009-01-01

    The biological immune system is a complex adaptive system. There are lots of benefits for building the model of the immune system. For biological researchers, they can test some hypotheses about the infection process or simulate the responses of some drugs. For computer researchers, they can build distributed, robust and fault tolerant networks inspired by the functions of the immune system. This paper provides a comprehensive survey of the literatures on modelling the immune system. From the methodology perspective, the paper compares and analyzes the existing approaches and models, and also demonstrates the focusing research effort on the future immune models in the next few years.

  1. Comparison of Photovoltaic Models in the System Advisor Model: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Blair, N. J.; Dobos, A. P.; Gilman, P.

    2013-08-01

    The System Advisor Model (SAM) is free software developed by the National Renewable Energy Laboratory (NREL) for predicting the performance of renewable energy systems and analyzing the financial feasibility of residential, commercial, and utility-scale grid-connected projects. SAM offers several options for predicting the performance of photovoltaic (PV) systems. The model requires that the analyst choose from three PV system models, and depending on that choice, possibly choose from three module and two inverter component models. To obtain meaningful results from SAM, the analyst must be aware of the differences between the model options and their applicability to different modeling scenarios. This paper presents an overview the different PV model options and presents a comparison of results for a 200-kW system using different model options.

  2. Graphical Model Debugger Framework for Embedded Systems

    DEFF Research Database (Denmark)

    Zeng, Kebin

    2010-01-01

    Debugger Framework, providing an auxiliary avenue of analysis of system models at runtime by executing generated code and updating models synchronously, which allows embedded developers to focus on the model level. With the model debugger, embedded developers can graphically test their design model......Model Driven Software Development has offered a faster way to design and implement embedded real-time software by moving the design to a model level, and by transforming models to code. However, the testing of embedded systems has remained at the code level. This paper presents a Graphical Model...... and check the running status of the system, which offers a debugging capability on a higher level of abstraction. The framework intends to contribute a tool to the Eclipse society, especially suitable for model-driven development of embedded systems....

  3. Generation of Multicellular Tumor Spheroids with Microwell-Based Agarose Scaffolds for Drug Testing.

    Directory of Open Access Journals (Sweden)

    Xue Gong

    Full Text Available Three dimensional multicellular aggregate, also referred to as cell spheroid or microtissue, is an indispensable tool for in vitro evaluating antitumor activity and drug efficacy. Compared with classical cellular monolayer, multicellular tumor spheroid (MCTS offers a more rational platform to predict in vivo drug efficacy and toxicity. Nevertheless, traditional processing methods such as plastic dish culture with nonadhesive surfaces are regularly time-consuming, laborious and difficult to provide uniform-sized spheroids, thus causing poor reproducibility of experimental data and impeding high-throughput drug screening. In order to provide a robust and effective platform for in vitro drug evaluation, we present an agarose scaffold prepared with the template containing uniform-sized micro-wells in commercially available cell culture plates. The agarose scaffold allows for good adjustment of MCTS size and large-scale production of MCTS. Transparent agarose scaffold also allows for monitoring of spheroid formation under an optical microscopy. The formation of MCTS from MCF-7 cells was prepared using different-size-well templates and systematically investigated in terms of spheroid growth curve, circularity, and cell viability. The doxorubicin cytotoxicity against MCF-7 spheroid and MCF-7 monolayer cells was compared. The drug penetration behavior, cell cycle distribution, cell apoptosis, and gene expression were also evaluated in MCF-7 spheroid. The findings of this study indicate that, compared with cellular monolayer, MCTS provides a valuable platform for the assessment of therapeutic candidates in an in vivo-mimic microenvironment, and thus has great potential for use in drug discovery and tumor biology research.

  4. Modeling and Identification of Multirate Systems

    Institute of Scientific and Technical Information of China (English)

    Feng DING; Tongwen CHEN

    2005-01-01

    Multirate systems are abundant in industry; for example, many soft-sensor design problems are related to modeling, parameter identification, or state estimation involving multirate systems. The study of multirate systems goes back to the early 1950's, and has become an active research area in systems and control. This paper briefly surveys the history of development in the area of multirate systems, and introduces some basic concepts and latest results on multirate systems, including a polynomial transformation technique and the lifting technique as tools for handling multirate systems, lifted state space models, parameter identification of dual-rate systems, how to determine fast single-rate models from dual-rate models and directly from dual-rate data, and a hierarchical identification method for general multirate systems. Finally, some further research topics for multirate systems are given.

  5. On Problems of Multicomponent System Maintenance Modelling

    Institute of Scientific and Technical Information of China (English)

    Tomasz Nowakowski; Sylwia Werbinka

    2009-01-01

    We present an overview of some recent developments in the area of mathematical modeling of maintenance decisions for multi-unit systems. The emphasis is on three main groups of multicomponent maintenance optimization models: the block replacement models, group maintenance models, and opportunistic maintenance models. Moreover, an example of a two-unit system maintenance process is provided in order to compare various maintenance policies.

  6. Traffic Modeling in WCDMA System Level Simulations

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Traffic modeling is a crucial element in WCDMA system level simulations. A clear understanding of the nature of traffic in the WCDMA system and subsequent selection of an appropriate random traffic model are critical to the success of the modeling enterprise. The resultant performances will evidently be of a function that our design has been well adapted to the traffic, channel and user mobility models, and these models are also accurate. In this article, our attention will be focused on modeling voice and WWW data traffic with the SBBP model and Victor model respectively.

  7. Towards Modelling of Hybrid Systems

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2006-01-01

    The article is an attempt to use methods of category theory and topology for analysis of hybrid systems. We use the notion of a directed topological space; it is a topological space together with a set of privileged paths. Dynamical systems are examples of directed topological spaces. A hybrid...... system consists of a number of dynamical systems that are glued together according to information encoded in the discrete part of the system. We develop a definition of a hybrid system as a functor from the category generated by a transition system to the category of directed topological spaces. Its...... directed homotopy colimit (geometric realization) is a single directed topological space. The behavior of hybrid systems can be then understood in terms of the behavior of dynamical systems through the directed homotopy colimit....

  8. Service systems concepts, modeling, and programming

    CERN Document Server

    Cardoso, Jorge; Poels, Geert

    2014-01-01

    This SpringerBrief explores the internal workings of service systems. The authors propose a lightweight semantic model for an effective representation to capture the essence of service systems. Key topics include modeling frameworks, service descriptions and linked data, creating service instances, tool support, and applications in enterprises.Previous books on service system modeling and various streams of scientific developments used an external perspective to describe how systems can be integrated. This brief introduces the concept of white-box service system modeling as an approach to mo

  9. Hydrological modelling in forested systems

    Science.gov (United States)

    This chapter provides a brief overview of forest hydrology modelling approaches for answering important global research and management questions. Many hundreds of hydrological models have been applied globally across multiple decades to represent and predict forest hydrological p...

  10. Modeling, Control and Coordination of Helicopter Systems

    CERN Document Server

    Ren, Beibei; Chen, Chang; Fua, Cheng-Heng; Lee, Tong Heng

    2012-01-01

    Modeling, Control and Coordination of Helicopter Systems provides a comprehensive treatment of helicopter systems, ranging from related nonlinear flight dynamic modeling and stability analysis to advanced control design for single helicopter systems, and also covers issues related to the coordination and formation control of multiple helicopter systems to achieve high performance tasks. Ensuring stability in helicopter flight is a challenging problem for nonlinear control design and development. This book is a valuable reference on modeling, control and coordination of helicopter systems,providing readers with practical solutions for the problems that still plague helicopter system design and implementation. Readers will gain a complete picture of helicopters at the systems level, as well as a better understanding of the technical intricacies involved. This book also: Presents a complete picture of modeling, control and coordination for helicopter systems Provides a modeling platform for a general class of ro...

  11. Electronic Education System Model-2

    Science.gov (United States)

    Güllü, Fatih; Kuusik, Rein; Laanpere, Mart

    2015-01-01

    In this study we presented new EES Model-2 extended from EES model for more productive implementation in e-learning process design and modelling in higher education. The most updates were related to uppermost instructional layer. We updated learning processes object of the layer for adaptation of educational process for young and old people,…

  12. Network and adaptive system of systems modeling and analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, Craig R.; Campbell, James E. Dr. (.; .); Anderson, Dennis James; Eddy, John P.

    2007-05-01

    This report documents the results of an LDRD program entitled ''Network and Adaptive System of Systems Modeling and Analysis'' that was conducted during FY 2005 and FY 2006. The purpose of this study was to determine and implement ways to incorporate network communications modeling into existing System of Systems (SoS) modeling capabilities. Current SoS modeling, particularly for the Future Combat Systems (FCS) program, is conducted under the assumption that communication between the various systems is always possible and occurs instantaneously. A more realistic representation of these communications allows for better, more accurate simulation results. The current approach to meeting this objective has been to use existing capabilities to model network hardware reliability and adding capabilities to use that information to model the impact on the sustainment supply chain and operational availability.

  13. On Verification Modelling of Embedded Systems

    NARCIS (Netherlands)

    Brinksma, Ed; Mader, Angelika

    2004-01-01

    Computer-aided verification of embedded systems hinges on the availability of good verification models of the systems at hand. Such models must be much simpler than full design models or specifications to be of practical value, because of the unavoidable combinatorial complexities in the verificatio

  14. Applying Modeling Tools to Ground System Procedures

    Science.gov (United States)

    Di Pasquale, Peter

    2012-01-01

    As part of a long-term effort to revitalize the Ground Systems (GS) Engineering Section practices, Systems Modeling Language (SysML) and Business Process Model and Notation (BPMN) have been used to model existing GS products and the procedures GS engineers use to produce them.

  15. System Level Modelling and Performance Estimation of Embedded Systems

    DEFF Research Database (Denmark)

    Tranberg-Hansen, Anders Sejer

    is simulation based and allows performance estimation to be carried out throughout all design phases ranging from early functional to cycle accurate and bit true descriptions of the system, modelling both hardware and software components in a unied way. Design space exploration and performance estimation...... an efficient system level design methodology, a modelling framework for performance estimation and design space exploration at the system level is required. This thesis presents a novel component based modelling framework for system level modelling and performance estimation of embedded systems. The framework...... is performed by having the framework produce detailed quantitative information about the system model under investigation. The project is part of the national Danish research project, Danish Network of Embedded Systems (DaNES), which is funded by the Danish National Advanced Technology Foundation. The project...

  16. EXPOSURE ANALYSIS MODELING SYSTEM (EXAMS): USER MANUAL AND SYSTEM DOCUMENTATION

    Science.gov (United States)

    The Exposure Analysis Modeling System, first published in 1982 (EPA-600/3-82-023), provides interactive computer software for formulating aquatic ecosystem models and rapidly evaluating the fate, transport, and exposure concentrations of synthetic organic chemicals - pesticides, ...

  17. Asynchronous adaptive time step in quantitative cellular automata modeling

    Directory of Open Access Journals (Sweden)

    Sun Yan

    2004-06-01

    Full Text Available Abstract Background The behaviors of cells in metazoans are context dependent, thus large-scale multi-cellular modeling is often necessary, for which cellular automata are natural candidates. Two related issues are involved in cellular automata based multi-cellular modeling: how to introduce differential equation based quantitative computing to precisely describe cellular activity, and upon it, how to solve the heavy time consumption issue in simulation. Results Based on a modified, language based cellular automata system we extended that allows ordinary differential equations in models, we introduce a method implementing asynchronous adaptive time step in simulation that can considerably improve efficiency yet without a significant sacrifice of accuracy. An average speedup rate of 4–5 is achieved in the given example. Conclusions Strategies for reducing time consumption in simulation are indispensable for large-scale, quantitative multi-cellular models, because even a small 100 × 100 × 100 tissue slab contains one million cells. Distributed and adaptive time step is a practical solution in cellular automata environment.

  18. Pǎun's systems as models of economic systems

    Institute of Scientific and Technical Information of China (English)

    Waldemar Korczynski

    2007-01-01

    In the paper a concept for modeling the economic systems by the formalism of Pǎun's systems is proposed. The main idea is to represent economic systems as homomorphic images of Petri nets corresponding to the (super) cells of Pǎun's systems.

  19. Modeling Control Situations in Power System Operations

    DEFF Research Database (Denmark)

    Saleem, Arshad; Lind, Morten; Singh, Sri Niwas

    2010-01-01

    Increased interconnection and loading of the power system along with deregulation has brought new challenges for electric power system operation, control and automation. Traditional power system models used in intelligent operation and control are highly dependent on the task purpose. Thus, a model...... for intelligent operation and control must represent system features, so that information from measurements can be related to possible system states and to control actions. These general modeling requirements are well understood, but it is, in general, difficult to translate them into a model because of the lack...... of explicit principles for model construction. This paper presents a work on using explicit means-ends model based reasoning about complex control situations which results in maintaining consistent perspectives and selecting appropriate control action for goal driven agents. An example of power system...

  20. Modeling Control Situations in Power System Operations

    DEFF Research Database (Denmark)

    Saleem, Arshad; Lind, Morten; Singh, Sri Niwas

    2010-01-01

    Increased interconnection and loading of the power system along with deregulation has brought new challenges for electric power system operation, control and automation. Traditional power system models used in intelligent operation and control are highly dependent on the task purpose. Thus, a model...... for intelligent operation and control must represent system features, so that information from measurements can be related to possible system states and to control actions. These general modeling requirements are well understood, but it is, in general, difficult to translate them into a model because of the lack...... of explicit principles for model construction. This paper presents a work on using explicit means-ends model based reasoning about complex control situations which results in maintaining consistent perspectives and selecting appropriate control action for goal driven agents. An example of power system...

  1. Assessment of pancreatic carcinoma cell chemosensitivity using a three-dimensional culture system

    Institute of Scientific and Technical Information of China (English)

    LIAO Quan; HU Ya; ZHAO Yu-pei; ZHOU Tao; ZHANG Qiang

    2010-01-01

    Background Monolayer cell culture models are the traditional culture models used for in vitro research of pancreatic carcinoma chemosensitivity. However, these models neglect the interactions between tumor cells and the impact of the tumor microenvironment. Such tumor cell monolayers poorly mimic the solid tumor microenvironment. The present study aimed to investigate the chemosensitivity characteristics of pancreatic cancer cells in a three-dimensional culture system by analyzing the differences in drug sensitivity between a scattered cell culture model and a multicellular spheroid culture model.Methods Three pancreatic cancer cell lines (SW1990, ASPC-1 and PCT-3) were cultured in three-dimensional collagen gels as well as in traditional two-dimensional monolayers. The chemosensitivities of the pancreatic carcinoma cells to 5-fluorouracil (5-FU), gemcitabine, and oxaliplatin in vitro were detected by both the Cell Counting Kit-8 test and the collagen gel droplet-embedded culture drug-sensitivity test.Results In the two-dimensional culture model, differences in the chemosensitivities of the cloned pancreatic carcinoma cells and scattered cells existed for some concentrations of 5-FU, gemcitabine and oxaliplatin. In the three-dimensional culture model, there were significant differences in the chemosensitivities of the pancreatic cancer cells between the scattered cells and multicellular spheroids (P <0.05).Conclusion Pancreatic carcinoma cells exhibit multicellular resistance in three-dimensional cultures.

  2. Modeling noisy resonant system response

    Science.gov (United States)

    Weber, Patrick Thomas; Walrath, David Edwin

    2017-02-01

    In this paper, a theory-based model replicating empirical acoustic resonant signals is presented and studied to understand sources of noise present in acoustic signals. Statistical properties of empirical signals are quantified and a noise amplitude parameter, which models frequency and amplitude-based noise, is created, defined, and presented. This theory-driven model isolates each phenomenon and allows for parameters to be independently studied. Using seven independent degrees of freedom, this model will accurately reproduce qualitative and quantitative properties measured from laboratory data. Results are presented and demonstrate success in replicating qualitative and quantitative properties of experimental data.

  3. Generic Model Host System Design

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Chungming; /SLAC; Wu, Juhao; /SLAC; Qiang, Ji; /LBL, Berkeley; Shen, Guobao; /Brookhaven

    2012-06-22

    There are many simulation codes for accelerator modelling; each one has some strength but not all. A platform which can host multiple modelling tools would be ideal for various purposes. The model platform along with infrastructure support can be used not only for online applications but also for offline purposes. Collaboration is formed for the effort of providing such a platform. In order to achieve such a platform, a set of common physics data structure has to be set. Application Programming Interface (API) for physics applications should also be defined within a model data provider. A preliminary platform design and prototype is discussed.

  4. Four MATLAB-Simulink models ofphotovoltaic system

    Directory of Open Access Journals (Sweden)

    Jawad Radhi Mahmood, Nasir Hussein Selman

    2016-01-01

    Full Text Available This paper presents four different MATLAB models to simulate the output I-V and P-V characteristics of photovoltaic (PV cells or systems. All of the models are implemented with Matlab-Simulink. Detailed modeling procedure for one-diode equivalent circuit model with all equations and numerical values is presented. The parameters required for the modeling have been taken from manufacturer's datasheet for 240W SOLIMPEKS solar panel. I-V and P-V characteristics of a typical 1.92 kW PV system have been simulated using the proposed models. The simulation took into account the sunlight insolation and temperature effect. Results of the models are validated with I-V and P-V curves provided by the manufacturer(s. The proposed models are very useful for those interested in working in the field of solar systems because they emulate and analyze the characteristics of all the solar systems easily.

  5. CTL Model Update for System Modifications

    CERN Document Server

    Ding, Yulin; Zhang, Yan; Zhang, Y; 10.1613/jair.2420

    2011-01-01

    Model checking is a promising technology, which has been applied for verification of many hardware and software systems. In this paper, we introduce the concept of model update towards the development of an automatic system modification tool that extends model checking functions. We define primitive update operations on the models of Computation Tree Logic (CTL) and formalize the principle of minimal change for CTL model update. These primitive update operations, together with the underlying minimal change principle, serve as the foundation for CTL model update. Essential semantic and computational characterizations are provided for our CTL model update approach. We then describe a formal algorithm that implements this approach. We also illustrate two case studies of CTL model updates for the well-known microwave oven example and the Andrew File System 1, from which we further propose a method to optimize the update results in complex system modifications.

  6. Computational Models for Nonlinear Aeroelastic Systems Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Clear Science Corp. and Duke University propose to develop and demonstrate new and efficient computational methods of modeling nonlinear aeroelastic systems. The...

  7. Model Updating Nonlinear System Identification Toolbox Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ZONA Technology (ZONA) proposes to develop an enhanced model updating nonlinear system identification (MUNSID) methodology that utilizes flight data with...

  8. Modeling and analysis of biomass production systems

    Energy Technology Data Exchange (ETDEWEB)

    Mishoe, J.W.; Lorber, M.N.; Peart, R.M.; Fluck, R.C.; Jones, J.W.

    1984-01-01

    BIOMET is an interactive simulation model that is used to analyze specific biomass and methane production systems. The system model is composed of crop growth models, harvesting, transportation, conversion and economic submodels. By use of menus the users can configure the structure and set selected parameters of the system to analyze the effects of variables within the component models. For example, simulations of a water hyacinth system resulted in yields of 63, 48 and 37 mg/ha/year for different harvest schedules. For napier grass, unit methane costs were $3.04, $2.86 and $2.98 for various yields of biomass. 10 references.

  9. Error Propagation in a System Model

    Science.gov (United States)

    Schloegel, Kirk (Inventor); Bhatt, Devesh (Inventor); Oglesby, David V. (Inventor); Madl, Gabor (Inventor)

    2015-01-01

    Embodiments of the present subject matter can enable the analysis of signal value errors for system models. In an example, signal value errors can be propagated through the functional blocks of a system model to analyze possible effects as the signal value errors impact incident functional blocks. This propagation of the errors can be applicable to many models of computation including avionics models, synchronous data flow, and Kahn process networks.

  10. Hydrological modeling in forested systems

    Science.gov (United States)

    H.E. Golden; G.R. Evenson; S. Tian; Devendra Amatya; Ge Sun

    2015-01-01

    Characterizing and quantifying interactions among components of the forest hydrological cycle is complex and usually requires a combination of field monitoring and modelling approaches (Weiler and McDonnell, 2004; National Research Council, 2008). Models are important tools for testing hypotheses, understanding hydrological processes and synthesizing experimental data...

  11. Stochastic Modelling of Energy Systems

    DEFF Research Database (Denmark)

    Andersen, Klaus Kaae

    2001-01-01

    equations are expressed in terms of stochastic differential equations. From a theoretical viewpoint the techniques for experimental design, parameter estimation and model validation are considered. From the practical viewpoint emphasis is put on how this methods can be used to construct models adequate...

  12. Stochastic Modelling of Hydrologic Systems

    DEFF Research Database (Denmark)

    Jonsdottir, Harpa

    2007-01-01

    In this PhD project several stochastic modelling methods are studied and applied on various subjects in hydrology. The research was prepared at Informatics and Mathematical Modelling at the Technical University of Denmark. The thesis is divided into two parts. The first part contains an introduct......In this PhD project several stochastic modelling methods are studied and applied on various subjects in hydrology. The research was prepared at Informatics and Mathematical Modelling at the Technical University of Denmark. The thesis is divided into two parts. The first part contains...... an introduction and an overview of the papers published. Then an introduction to basic concepts in hydrology along with a description of hydrological data is given. Finally an introduction to stochastic modelling is given. The second part contains the research papers. In the research papers the stochastic methods...

  13. Hypervirial Models of Stellar Systems

    CERN Document Server

    Evans, N W

    2005-01-01

    A family of cusped potential-density pairs is introduced for modelling galaxies and dark haloes. The density profile is cusped like 1/r^(2-p) at small radii. The distribution function takes the simple form L^(p-2) E^([3p+1]/2) (where E is the binding energy and L is the angular momentum). The models all possess the remarkable property that the virial theorem holds locally, from which they earn their name as the hypervirial family. Famously, this property was first discovered by Eddington to hold for the Plummer model in 1916. In fact, the seductive properties of the Plummer model extend to the whole hypervirial family, including the members possessing the cosmologically important cusps with density behaving like 1/r or 1/r^1.5 or 1/r^1.33. The intrinsic and projected properties of the family of models are discussed in some detail.

  14. Semantic models for adaptive interactive systems

    CERN Document Server

    Hussein, Tim; Lukosch, Stephan; Ziegler, Jürgen; Calvary, Gaëlle

    2013-01-01

    Providing insights into methodologies for designing adaptive systems based on semantic data, and introducing semantic models that can be used for building interactive systems, this book showcases many of the applications made possible by the use of semantic models.Ontologies may enhance the functional coverage of an interactive system as well as its visualization and interaction capabilities in various ways. Semantic models can also contribute to bridging gaps; for example, between user models, context-aware interfaces, and model-driven UI generation. There is considerable potential for using

  15. Model reduction of linear conservative mechanical systems

    NARCIS (Netherlands)

    Schaft, van der A.J.; Oeloff, J.E.

    1990-01-01

    An approach for model reduction of linear conservative or weakly damped mechanical systems is proposed. It is based on the balancing of an associated gradient system. It uses the joint knowledge of the system matrix and the input and output matrices of the Hamiltonian system. The key idea is to asso

  16. Modeling complex work systems - method meets reality

    OpenAIRE

    Veer, van der, C.G.; Hoeve, Machteld; Lenting, Bert F.

    1996-01-01

    Modeling an existing task situation is often a first phase in the (re)design of information systems. For complex systems design, this model should consider both the people and the organization involved, the work, and situational aspects. Groupware Task Analysis (GTA) as part of a method for the design of complex systems, has been applied in a situation of redesign of a Dutch public administration system. The most feasible method to collect information in this case was ethnography, the resulti...

  17. From single cell mechanics and intercellular forces to collective aggregate dynamics Individual cell-based modeling of cell cultures for tissue engineering

    OpenAIRE

    Smeets, Bart

    2016-01-01

    The mechanisms that biological cells exploit to organize themselves into multicellular aggregates and tissue-like structures are based on fundamental physical principles. Yet, the natural emergence of complexity in biological systems, while of great importance for many applications in biology and medicine, is still poorly understood. For this, mathematical models can be of great help by identifying key components and mechanisms that govern a system, and based on these, predict the inception o...

  18. Computational Genetic Regulatory Networks Evolvable, Self-organizing Systems

    CERN Document Server

    Knabe, Johannes F

    2013-01-01

    Genetic Regulatory Networks (GRNs) in biological organisms are primary engines for cells to enact their engagements with environments, via incessant, continually active coupling. In differentiated multicellular organisms, tremendous complexity has arisen in the course of evolution of life on earth. Engineering and science have so far achieved no working system that can compare with this complexity, depth and scope of organization. Abstracting the dynamics of genetic regulatory control to a computational framework in which artificial GRNs in artificial simulated cells differentiate while connected in a changing topology, it is possible to apply Darwinian evolution in silico to study the capacity of such developmental/differentiated GRNs to evolve. In this volume an evolutionary GRN paradigm is investigated for its evolvability and robustness in models of biological clocks, in simple differentiated multicellularity, and in evolving artificial developing 'organisms' which grow and express an ontogeny starting fr...

  19. Modeling of power electronic systems with EMTP

    Science.gov (United States)

    Tam, Kwa-Sur; Dravid, Narayan V.

    1989-01-01

    In view of the potential impact of power electronics on power systems, there is need for a computer modeling/analysis tool to perform simulation studies on power systems with power electronic components as well as to educate engineering students about such systems. The modeling of the major power electronic components of the NASA Space Station Freedom Electric Power System is described along with ElectroMagnetic Transients Program (EMTP) and it is demonstrated that EMTP can serve as a very useful tool for teaching, design, analysis, and research in the area of power systems with power electronic components. EMTP modeling of power electronic circuits is described and simulation results are presented.

  20. Models of the venous system

    DEFF Research Database (Denmark)

    Mehlsen, J

    2000-01-01

    of the venous system require at least three elements: a resistor, a capacitor and an inductor, with the latter being of more importance in the venous than in the arterial system. Non-linearities must be considered in pressure/flow relations in the small venules, during venous collapse, or low flow conditions...

  1. Learning Markov models for stationary system behaviors

    DEFF Research Database (Denmark)

    Chen, Yingke; Mao, Hua; Jaeger, Manfred

    2012-01-01

    Establishing an accurate model for formal verification of an existing hardware or software system is often a manual process that is both time consuming and resource demanding. In order to ease the model construction phase, methods have recently been proposed for automatically learning accurate...... system models from data in the form of observations of the target system. Common for these approaches is that they assume the data to consist of multiple independent observation sequences. However, for certain types of systems, in particular many running embedded systems, one would only have access...... the learned model. Experiments demonstrate that system properties (formulated as stationary probabilities of LTL formulas) can be reliably identified using the learned model....

  2. Integrating systems biology models and biomedical ontologies

    Directory of Open Access Journals (Sweden)

    de Bono Bernard

    2011-08-01

    Full Text Available Abstract Background Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology. Results We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models. Conclusions We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms.

  3. Integrating systems biology models and biomedical ontologies

    Science.gov (United States)

    2011-01-01

    Background Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology. Results We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models. Conclusions We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms. PMID:21835028

  4. Very Large System Dynamics Models - Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    Jacob J. Jacobson; Leonard Malczynski

    2008-10-01

    This paper provides lessons learned from developing several large system dynamics (SD) models. System dynamics modeling practice emphasize the need to keep models small so that they are manageable and understandable. This practice is generally reasonable and prudent; however, there are times that large SD models are necessary. This paper outlines two large SD projects that were done at two Department of Energy National Laboratories, the Idaho National Laboratory and Sandia National Laboratories. This paper summarizes the models and then discusses some of the valuable lessons learned during these two modeling efforts.

  5. Precipitation-runoff modeling system; user's manual

    Science.gov (United States)

    Leavesley, G.H.; Lichty, R.W.; Troutman, B.M.; Saindon, L.G.

    1983-01-01

    The concepts, structure, theoretical development, and data requirements of the precipitation-runoff modeling system (PRMS) are described. The precipitation-runoff modeling system is a modular-design, deterministic, distributed-parameter modeling system developed to evaluate the impacts of various combinations of precipitation, climate, and land use on streamflow, sediment yields, and general basin hydrology. Basin response to normal and extreme rainfall and snowmelt can be simulated to evaluate changes in water balance relationships, flow regimes, flood peaks and volumes, soil-water relationships, sediment yields, and groundwater recharge. Parameter-optimization and sensitivity analysis capabilites are provided to fit selected model parameters and evaluate their individual and joint effects on model output. The modular design provides a flexible framework for continued model system enhancement and hydrologic modeling research and development. (Author 's abstract)

  6. Network model of security system

    Directory of Open Access Journals (Sweden)

    Adamczyk Piotr

    2016-01-01

    Full Text Available The article presents the concept of building a network security model and its application in the process of risk analysis. It indicates the possibility of a new definition of the role of the network models in the safety analysis. Special attention was paid to the development of the use of an algorithm describing the process of identifying the assets, vulnerability and threats in a given context. The aim of the article is to present how this algorithm reduced the complexity of the problem by eliminating from the base model these components that have no links with others component and as a result and it was possible to build a real network model corresponding to reality.

  7. Evaluation Model of System Survivability

    Institute of Scientific and Technical Information of China (English)

    LIU Yuling; PAN Shiying; TIAN Junfeng

    2006-01-01

    This paper puts forward a survivability evaluation model, SQEM(Survivability Quantitative Evaluation Model), based on lucubrating the main method existed. Then it defines the measurement factors and parses the survivability mathematically, introduces state change probability and the idea of setting the weights of survivability factors dynamically into the evaluating process of SQEM, which improved the accuracy of evaluation. An example is presented to illustrate the way SQEM works, which demonstrated the validity and feasibility of the method.

  8. Brief history of agricultural systems modeling.

    Science.gov (United States)

    Jones, James W; Antle, John M; Basso, Bruno; Boote, Kenneth J; Conant, Richard T; Foster, Ian; Godfray, H Charles J; Herrero, Mario; Howitt, Richard E; Janssen, Sander; Keating, Brian A; Munoz-Carpena, Rafael; Porter, Cheryl H; Rosenzweig, Cynthia; Wheeler, Tim R

    2017-07-01

    Agricultural systems science generates knowledge that allows researchers to consider complex problems or take informed agricultural decisions. The rich history of this science exemplifies the diversity of systems and scales over which they operate and have been studied. Modeling, an essential tool in agricultural systems science, has been accomplished by scientists from a wide range of disciplines, who have contributed concepts and tools over more than six decades. As agricultural scientists now consider the "next generation" models, data, and knowledge products needed to meet the increasingly complex systems problems faced by society, it is important to take stock of this history and its lessons to ensure that we avoid re-invention and strive to consider all dimensions of associated challenges. To this end, we summarize here the history of agricultural systems modeling and identify lessons learned that can help guide the design and development of next generation of agricultural system tools and methods. A number of past events combined with overall technological progress in other fields have strongly contributed to the evolution of agricultural system modeling, including development of process-based bio-physical models of crops and livestock, statistical models based on historical observations, and economic optimization and simulation models at household and regional to global scales. Characteristics of agricultural systems models have varied widely depending on the systems involved, their scales, and the wide range of purposes that motivated their development and use by researchers in different disciplines. Recent trends in broader collaboration across institutions, across disciplines, and between the public and private sectors suggest that the stage is set for the major advances in agricultural systems science that are needed for the next generation of models, databases, knowledge products and decision support systems. The lessons from history should be

  9. Information modeling system for blast furnace control

    Science.gov (United States)

    Spirin, N. A.; Gileva, L. Y.; Lavrov, V. V.

    2016-09-01

    Modern Iron & Steel Works as a rule are equipped with powerful distributed control systems (DCS) and databases. Implementation of DSC system solves the problem of storage, control, protection, entry, editing and retrieving of information as well as generation of required reporting data. The most advanced and promising approach is to use decision support information technologies based on a complex of mathematical models. The model decision support system for control of blast furnace smelting is designed and operated. The basis of the model system is a complex of mathematical models created using the principle of natural mathematical modeling. This principle provides for construction of mathematical models of two levels. The first level model is a basic state model which makes it possible to assess the vector of system parameters using field data and blast furnace operation results. It is also used to calculate the adjustment (adaptation) coefficients of the predictive block of the system. The second-level model is a predictive model designed to assess the design parameters of the blast furnace process when there are changes in melting conditions relative to its current state. Tasks for which software is developed are described. Characteristics of the main subsystems of the blast furnace process as an object of modeling and control - thermal state of the furnace, blast, gas dynamic and slag conditions of blast furnace smelting - are presented.

  10. MODELING AND ANALYSIS OF REGIONAL BOUNDARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    YAN Guangle; WANG Huanchen

    2001-01-01

    In this paper, the problems of modeling and analyzing the system with change able boundary are researched. First, a kind of expanding system is set up, in which the changeable boundary is dealt with as a regional boundary. Then some relative models are developed to describe the regional boundary system. Next, the transition or the driftage of bifurcation points in the system is discussed. A fascinating case is studied in which two or more than two classes of chaotic attractive points coexist together or exist alternatively in the same system. Lastly, an effective new method of chaos avoidance for the system is put forward.

  11. Formal heterogeneous system modeling with SystemC

    DEFF Research Database (Denmark)

    Niaki, Seyed Hosein Attarzadeh; Jakobsen, Mikkel Koefoed; Sulonen, Tero;

    2012-01-01

    Electronic System Level (ESL) design of embedded systems proposes raising the abstraction level of the design entry to cope with the increasing complexity of such systems. To exploit the benefits of ESL, design languages should allow specification of models which are a) heterogeneous, to describe...... different aspects of systems; b) formally defined, for application of analysis and synthesis methods; c) executable, to enable early detection of specification; and d) parallel, to exploit the multi- and many-core platforms for simulation and implementation. We present a modeling library on top of System......C, targeting heterogeneous embedded system design, based on four models of computation. The library has a formal basis where all elements are well defined and lead in construction of analyzable models. The semantics of communication and computation are implemented by the library, which allows the designer...

  12. Grey Box Modelling of Hydrological Systems

    DEFF Research Database (Denmark)

    Thordarson, Fannar Ørn

    The main topic of the thesis is grey box modelling of hydrologic systems, as well as formulation and assessment of their embedded uncertainties. Grey box model is a combination of a white box model, a physically-based model that is traditionally formulated using deterministic ordinary differential...... the lack of fit in state space formulation, and further support decisions for a model expansion. By using stochastic differential equations to formulate the dynamics of the hydrological system, either the complexity of the model can be increased by including the necessary hydrological processes...... in the model, or formulation of process noise can be considered so that it meets the physical limits of the hydrological system and give an adequate description of the embedded uncertainty in model structure. The thesis consists of two parts: a summary report and a part which contains six scientific papers...

  13. A Model-Based Systems Engineering Methodology for Employing Architecture In System Analysis: Developing Simulation Models Using Systems Modeling Language Products to Link Architecture and Analysis

    Science.gov (United States)

    2016-06-01

    ENGINEERING METHODOLOGY FOR EMPLOYING ARCHITECTURE IN SYSTEM ANALYSIS: DEVELOPING SIMULATION MODELS USING SYSTEMS MODELING LANGUAGE PRODUCTS TO LINK... ENGINEERING METHODOLOGY FOR EMPLOYING ARCHITECTURE IN SYSTEM ANALYSIS: DEVELOPING SIMULATION MODELS USING SYSTEMS MODELING LANGUAGE PRODUCTS TO LINK...to model-based systems engineering (MBSE) by formally defining an MBSE methodology for employing architecture in system analysis (MEASA) that presents

  14. System Advisor Model: Flat Plate Photovoltaic Performance Modeling Validation Report

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, J.; Whitmore, J.; Kaffine, L.; Blair, N.; Dobos, A. P.

    2013-12-01

    The System Advisor Model (SAM) is a free software tool that performs detailed analysis of both system performance and system financing for a variety of renewable energy technologies. This report provides detailed validation of the SAM flat plate photovoltaic performance model by comparing SAM-modeled PV system generation data to actual measured production data for nine PV systems ranging from 75 kW to greater than 25 MW in size. The results show strong agreement between SAM predictions and field data, with annualized prediction error below 3% for all fixed tilt cases and below 8% for all one axis tracked cases. The analysis concludes that snow cover and system outages are the primary sources of disagreement, and other deviations resulting from seasonal biases in the irradiation models and one axis tracking issues are discussed in detail.

  15. Modeling Cytoskeletal Active Matter Systems

    Science.gov (United States)

    Blackwell, Robert

    Active networks of filamentous proteins and crosslinking motor proteins play a critical role in many important cellular processes. One of the most important microtubule-motor protein assemblies is the mitotic spindle, a self-organized active liquid-crystalline structure that forms during cell division and that ultimately separates chromosomes into two daughter cells. Although the spindle has been intensively studied for decades, the physical principles that govern its self-organization and function remain mysterious. To evolve a better understanding of spindle formation, structure, and dynamics, I investigate course-grained models of active liquid-crystalline networks composed of microtubules, modeled as hard spherocylinders, in diffusive equilibrium with a reservoir of active crosslinks, modeled as hookean springs that can adsorb to microtubules and and translocate at finite velocity along the microtubule axis. This model is investigated using a combination of brownian dynamics and kinetic monte carlo simulation. I have further refined this model to simulate spindle formation and kinetochore capture in the fission yeast S. pombe. I then make predictions for experimentally realizable perturbations in motor protein presence and function in S. pombe.

  16. A molecular timescale of eukaryote evolution and the rise of complex multicellular life

    Science.gov (United States)

    Hedges, S. Blair; Blair, Jaime E.; Venturi, Maria L.; Shoe, Jason L.

    2004-01-01

    BACKGROUND: The pattern and timing of the rise in complex multicellular life during Earth's history has not been established. Great disparity persists between the pattern suggested by the fossil record and that estimated by molecular clocks, especially for plants, animals, fungi, and the deepest branches of the eukaryote tree. Here, we used all available protein sequence data and molecular clock methods to place constraints on the increase in complexity through time. RESULTS: Our phylogenetic analyses revealed that (i) animals are more closely related to fungi than to plants, (ii) red algae are closer to plants than to animals or fungi, (iii) choanoflagellates are closer to animals than to fungi or plants, (iv) diplomonads, euglenozoans, and alveolates each are basal to plants+animals+fungi, and (v) diplomonads are basal to other eukaryotes (including alveolates and euglenozoans). Divergence times were estimated from global and local clock methods using 20-188 proteins per node, with data treated separately (multigene) and concatenated (supergene). Different time estimation methods yielded similar results (within 5%): vertebrate-arthropod (964 million years ago, Ma), Cnidaria-Bilateria (1,298 Ma), Porifera-Eumetozoa (1,351 Ma), Pyrenomycetes-Plectomycetes (551 Ma), Candida-Saccharomyces (723 Ma), Hemiascomycetes-filamentous Ascomycota (982 Ma), Basidiomycota-Ascomycota (968 Ma), Mucorales-Basidiomycota (947 Ma), Fungi-Animalia (1,513 Ma), mosses-vascular plants (707 Ma), Chlorophyta-Tracheophyta (968 Ma), Rhodophyta-Chlorophyta+Embryophyta (1,428 Ma), Plantae-Animalia (1,609 Ma), Alveolata-plants+animals+fungi (1,973 Ma), Euglenozoa-plants+animals+fungi (1,961 Ma), and Giardia-plants+animals+fungi (2,309 Ma). By extrapolation, mitochondria arose approximately 2300-1800 Ma and plastids arose 1600-1500 Ma. Estimates of the maximum number of cell types of common ancestors, combined with divergence times, showed an increase from two cell types at 2500 Ma to

  17. A molecular timescale of eukaryote evolution and the rise of complex multicellular life

    Directory of Open Access Journals (Sweden)

    Venturi Maria L

    2004-01-01

    Full Text Available Abstract Background The pattern and timing of the rise in complex multicellular life during Earth's history has not been established. Great disparity persists between the pattern suggested by the fossil record and that estimated by molecular clocks, especially for plants, animals, fungi, and the deepest branches of the eukaryote tree. Here, we used all available protein sequence data and molecular clock methods to place constraints on the increase in complexity through time. Results Our phylogenetic analyses revealed that (i animals are more closely related to fungi than to plants, (ii red algae are closer to plants than to animals or fungi, (iii choanoflagellates are closer to animals than to fungi or plants, (iv diplomonads, euglenozoans, and alveolates each are basal to plants+animals+fungi, and (v diplomonads are basal to other eukaryotes (including alveolates and euglenozoans. Divergence times were estimated from global and local clock methods using 20–188 proteins per node, with data treated separately (multigene and concatenated (supergene. Different time estimation methods yielded similar results (within 5%: vertebrate-arthropod (964 million years ago, Ma, Cnidaria-Bilateria (1,298 Ma, Porifera-Eumetozoa (1,351 Ma, Pyrenomycetes-Plectomycetes (551 Ma, Candida-Saccharomyces (723 Ma, Hemiascomycetes-filamentous Ascomycota (982 Ma, Basidiomycota-Ascomycota (968 Ma, Mucorales-Basidiomycota (947 Ma, Fungi-Animalia (1,513 Ma, mosses-vascular plants (707 Ma, Chlorophyta-Tracheophyta (968 Ma, Rhodophyta-Chlorophyta+Embryophyta (1,428 Ma, Plantae-Animalia (1,609 Ma, Alveolata-plants+animals+fungi (1,973 Ma, Euglenozoa-plants+animals+fungi (1,961 Ma, and Giardia-plants+animals+fungi (2,309 Ma. By extrapolation, mitochondria arose approximately 2300-1800 Ma and plastids arose 1600-1500 Ma. Estimates of the maximum number of cell types of common ancestors, combined with divergence times, showed an increase from two cell types at 2500 Ma to ~10

  18. A molecular timescale of eukaryote evolution and the rise of complex multicellular life

    Science.gov (United States)

    Hedges, S. Blair; Blair, Jaime E.; Venturi, Maria L.; Shoe, Jason L.

    2004-01-01

    BACKGROUND: The pattern and timing of the rise in complex multicellular life during Earth's history has not been established. Great disparity persists between the pattern suggested by the fossil record and that estimated by molecular clocks, especially for plants, animals, fungi, and the deepest branches of the eukaryote tree. Here, we used all available protein sequence data and molecular clock methods to place constraints on the increase in complexity through time. RESULTS: Our phylogenetic analyses revealed that (i) animals are more closely related to fungi than to plants, (ii) red algae are closer to plants than to animals or fungi, (iii) choanoflagellates are closer to animals than to fungi or plants, (iv) diplomonads, euglenozoans, and alveolates each are basal to plants+animals+fungi, and (v) diplomonads are basal to other eukaryotes (including alveolates and euglenozoans). Divergence times were estimated from global and local clock methods using 20-188 proteins per node, with data treated separately (multigene) and concatenated (supergene). Different time estimation methods yielded similar results (within 5%): vertebrate-arthropod (964 million years ago, Ma), Cnidaria-Bilateria (1,298 Ma), Porifera-Eumetozoa (1,351 Ma), Pyrenomycetes-Plectomycetes (551 Ma), Candida-Saccharomyces (723 Ma), Hemiascomycetes-filamentous Ascomycota (982 Ma), Basidiomycota-Ascomycota (968 Ma), Mucorales-Basidiomycota (947 Ma), Fungi-Animalia (1,513 Ma), mosses-vascular plants (707 Ma), Chlorophyta-Tracheophyta (968 Ma), Rhodophyta-Chlorophyta+Embryophyta (1,428 Ma), Plantae-Animalia (1,609 Ma), Alveolata-plants+animals+fungi (1,973 Ma), Euglenozoa-plants+animals+fungi (1,961 Ma), and Giardia-plants+animals+fungi (2,309 Ma). By extrapolation, mitochondria arose approximately 2300-1800 Ma and plastids arose 1600-1500 Ma. Estimates of the maximum number of cell types of common ancestors, combined with divergence times, showed an increase from two cell types at 2500 Ma to

  19. Systemic change increases model projection uncertainty

    NARCIS (Netherlands)

    Verstegen, Judith; Karssenberg, Derek; van der Hilst, Floortje; Faaij, André

    2014-01-01

    Most spatio-temporal models are based on the assumption that the relationship between system state change and its explanatory processes is stationary. This means that model structure and parameterization are usually kept constant over time, ignoring potential systemic changes in this relationship re

  20. Dynamic modeling of the INAPRO aquaponic system

    NARCIS (Netherlands)

    Karimanzira, Divas; Keesman, Karel J.; Kloas, Werner; Baganz, Daniela; Rauschenbach, Thomas

    2016-01-01

    The use of modeling techniques to analyze aquaponics systems is demonstrated with an example of dynamic modeling for the production of Nile tilapia (Oreochromis niloticus) and tomatoes (Solanum lycopersicon) using the innovative double recirculating aquaponic system ASTAF-PRO. For the management and

  1. Modeling complex work systems - method meets reality

    NARCIS (Netherlands)

    van der Veer, Gerrit C.; Hoeve, Machteld; Lenting, Bert

    1996-01-01

    Modeling an existing task situation is often a first phase in the (re)design of information systems. For complex systems design, this model should consider both the people and the organization involved, the work, and situational aspects. Groupware Task Analysis (GTA) as part of a method for the

  2. Modeling complex work systems - method meets reality

    NARCIS (Netherlands)

    Veer, van der Gerrit C.; Hoeve, Machteld; Lenting, Bert F.

    1996-01-01

    Modeling an existing task situation is often a first phase in the (re)design of information systems. For complex systems design, this model should consider both the people and the organization involved, the work, and situational aspects. Groupware Task Analysis (GTA) as part of a method for the desi

  3. System dynamics modelling of situation awareness

    CSIR Research Space (South Africa)

    Oosthuizen, R

    2015-11-01

    Full Text Available . The feedback loops and delays in the Command and Control system also contribute to the complex dynamic behavior. This paper will build on existing situation awareness models to develop a System Dynamics model to support a qualitative investigation through...

  4. Statistical Model Checking for Stochastic Hybrid Systems

    DEFF Research Database (Denmark)

    David, Alexandre; Du, Dehui; Larsen, Kim Guldstrand

    2012-01-01

    This paper presents novel extensions and applications of the UPPAAL-SMC model checker. The extensions allow for statistical model checking of stochastic hybrid systems. We show how our race-based stochastic semantics extends to networks of hybrid systems, and indicate the integration technique ap...

  5. Models of the venous system

    DEFF Research Database (Denmark)

    Mehlsen, J

    2000-01-01

    Cardiac output is largely controlled by venous return, the driving force of which is the energy remaining at the postcapillary venous site. This force is influenced by forces acting close to the right atrium, and internally or externally upon the veins along their course. Analogue models....... The venous capacitance is also non-linear, but may be considered linear under certain conditions. The models have to include time varying pressure sources created by respiration and skeletal muscles, and if the description includes the upright position, the partly unidirectional flow through the venous...

  6. Systematic modelling and simulation of refrigeration systems

    DEFF Research Database (Denmark)

    Rasmussen, Bjarne D.; Jakobsen, Arne

    1998-01-01

    The task of developing a simulation model of a refrigeration system can be very difficult and time consuming. In order for this process to be effective, a systematic method for developing the system model is required. This method should aim at guiding the developer to clarify the purpose of the s......The task of developing a simulation model of a refrigeration system can be very difficult and time consuming. In order for this process to be effective, a systematic method for developing the system model is required. This method should aim at guiding the developer to clarify the purpose...... of the simulation, to select appropriate component models and to set up the equations in a well-arranged way. In this paper the outline of such a method is proposed and examples showing the use of this method for simulation of refrigeration systems are given....

  7. Heating, ventilation and air conditioning system modelling

    Energy Technology Data Exchange (ETDEWEB)

    Whalley, R.; Abdul-Ameer, A. [British University in Dubai (United Arab Emirates)

    2011-03-15

    Heating, ventilation and air conditioning modelling methods, for large scale, spatially dispersed systems are considered. Existing techniques are discussed and proposals for the application of novel analysis approaches are outlined. The use of distributed-lumped parameter procedures enabling the incorporation of the relatively concentrated and significantly dispersed, system element characteristics, is advocated. A dynamic model for a heating, ventilation and air conditioning system comprising inlet and exhaust fans, with air recirculation, heating/cooling and filtration units is presented. Pressure, airflow and temperature predictions within the system are computed following input, disturbance changes and purging operations. The generalised modelling advancements adopted and the applicability of the model for heating, ventilation and air conditioning system simulation, re-configuration and diagnostics is emphasised. The employment of the model for automatic, multivariable controller design purposes is commented upon. (author)

  8. Model Driven Development of Data Sensitive Systems

    DEFF Research Database (Denmark)

    Olsen, Petur

    2014-01-01

    Model-driven development strives to use formal artifacts during the development process. Formal artifacts enables automatic analyses of some aspects of the system under development. This serves to increase the understanding of the (intended) behavior of the system as well as increasing error...... detection and pushing error detection to earlier stages of development. The complexity of modeling and the size of systems which can be analyzed is severely limited when introducing data variables. The state space grows exponentially in the number of variable and the domain size of the variables...... to the values of variables. This theses strives to improve model-driven development of such data-sensitive systems. This is done by addressing three research questions. In the first we combine state-based modeling and abstract interpretation, in order to ease modeling of data-sensitive systems, while allowing...

  9. Modeling and analysis of stochastic systems

    CERN Document Server

    Kulkarni, Vidyadhar G

    2011-01-01

    Based on the author's more than 25 years of teaching experience, Modeling and Analysis of Stochastic Systems, Second Edition covers the most important classes of stochastic processes used in the modeling of diverse systems, from supply chains and inventory systems to genetics and biological systems. For each class of stochastic process, the text includes its definition, characterization, applications, transient and limiting behavior, first passage times, and cost/reward models. Along with reorganizing the material, this edition revises and adds new exercises and examples. New to the second edi

  10. System Convergence in Transport Modelling

    DEFF Research Database (Denmark)

    Rich, Jeppe; Nielsen, Otto Anker; Cantarella, Guilio E.

    2010-01-01

    -of-successive-averages (MSA) have been proposed. Convergence of the MSA under fairly weak regularity conditions was shown in Robbins and Monro (1951). The iteration between demand and assignment ? the external equilibrium ? are in many models either decoupled or follow a very simple iteration pattern. However, as demand...

  11. Models of the venous system

    DEFF Research Database (Denmark)

    Mehlsen, J

    2000-01-01

    . The venous capacitance is also non-linear, but may be considered linear under certain conditions. The models have to include time varying pressure sources created by respiration and skeletal muscles, and if the description includes the upright position, the partly unidirectional flow through the venous...

  12. Systems Engineering Model for ART Energy Conversion

    Energy Technology Data Exchange (ETDEWEB)

    Mendez Cruz, Carmen Margarita [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rochau, Gary E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wilson, Mollye C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-02-01

    The near-term objective of the EC team is to establish an operating, commercially scalable Recompression Closed Brayton Cycle (RCBC) to be constructed for the NE - STEP demonstration system (demo) with the lowest risk possible. A systems engineering approach is recommended to ensure adequate requirements gathering, documentation, and mode ling that supports technology development relevant to advanced reactors while supporting crosscut interests in potential applications. A holistic systems engineering model was designed for the ART Energy Conversion program by leveraging Concurrent Engineering, Balance Model, Simplified V Model, and Project Management principles. The resulting model supports the identification and validation of lifecycle Brayton systems requirements, and allows designers to detail system-specific components relevant to the current stage in the lifecycle, while maintaining a holistic view of all system elements.

  13. Comparison of three replication strategies in complex multicellular organisms: Asexual replication, sexual replication with identical gametes, and sexual replication with distinct sperm and egg gametes

    Science.gov (United States)

    Tannenbaum, Emmanuel

    2008-01-01

    This paper studies the mutation-selection balance in three simplified replication models. The first model considers a population of organisms replicating via the production of asexual spores. The second model considers a sexually replicating population that produces identical gametes. The third model considers a sexually replicating population that produces distinct sperm and egg gametes. All models assume diploid organisms whose genomes consist of two chromosomes, each of which is taken to be functional if equal to some master sequence, and defective otherwise. In the asexual population, the asexual diploid spores develop directly into adult organisms. In the sexual populations, the haploid gametes enter a haploid pool, where they may fuse with other haploids. The resulting immature diploid organisms then proceed to develop into mature organisms. Based on an analysis of all three models, we find that, as organism size increases, a sexually replicating population can only outcompete an asexually replicating population if the adult organisms produce distinct sperm and egg gametes. A sexual replication strategy that is based on the production of large numbers of sperm cells to fertilize a small number of eggs is found to be necessary in order to maintain a sufficiently low cost for sex for the strategy to be selected for over a purely asexual strategy. We discuss the usefulness of this model in understanding the evolution and maintenance of sexual replication as the preferred replication strategy in complex, multicellular organisms.

  14. Building multivariate systems biology models

    NARCIS (Netherlands)

    Kirwan, G.M.; Johansson, E.; Kleemann, R.; Verheij, E.R.; Wheelock, A.M.; Goto, S.; Trygg, J.; Wheelock, C.E.

    2012-01-01

    Systems biology methods using large-scale "omics" data sets face unique challenges: integrating and analyzing near limitless data space, while recognizing and removing systematic variation or noise. Herein we propose a complementary multivariate analysis workflow to both integrate "omics" data from

  15. Models of complex attitude systems

    DEFF Research Database (Denmark)

    Sørensen, Bjarne Taulo

    production, food and the environment, technological progress, animal welfare, local employment and the local economy. In addition, the survey included a conjoint task by which participants’ evaluations of the importance of production system attributes were measured. The data were analysed by means of causal...

  16. Adsorption Rate Models for Multicomponent Adsorption Systems

    Institute of Scientific and Technical Information of China (English)

    姚春才

    2004-01-01

    Three adsorption rate models are derived for multicomponent adsorption systems under either pore diffusion or surface diffusion control. The linear driving force (LDF) model is obtained by assuming a parabolic intraparticle concentration profile. Models I and Ⅱ are obtained from the parabolic concentration layer approximation. Examples are presented to demonstrate the usage and accuracy of these models. It is shown that Model I is suitable for batch adsorption calculations and Model Ⅱ provides a good approximation in fixed-bed adsorption processes while the LDF model should not be used in batch adsorption and may be considered acceptable in fixed-bed adsorption where the parameter Ti is relatively large.

  17. Modeling approach suitable for energy system

    Energy Technology Data Exchange (ETDEWEB)

    Goetschel, D. V.

    1979-01-01

    Recently increased attention has been placed on optimization problems related to the determination and analysis of operating strategies for energy systems. Presented in this paper is a nonlinear model that can be used in the formulation of certain energy-conversion systems-modeling problems. The model lends itself nicely to solution approaches based on nonlinear-programming algorithms and, in particular, to those methods falling into the class of variable metric algorithms for nonlinearly constrained optimization.

  18. Development and application of earth system models

    OpenAIRE

    Prinn, Ronald G.

    2012-01-01

    The global environment is a complex and dynamic system. Earth system modeling is needed to help understand changes in interacting subsystems, elucidate the influence of human activities, and explore possible future changes. Integrated assessment of environment and human development is arguably the most difficult and most important “systems” problem faced. To illustrate this approach, we present results from the integrated global system model (IGSM), which consists of coupled submodels address...

  19. Statistical Model Checking for Stochastic Hybrid Systems

    DEFF Research Database (Denmark)

    David, Alexandre; Du, Dehui; Larsen, Kim Guldstrand

    2012-01-01

    This paper presents novel extensions and applications of the UPPAAL-SMC model checker. The extensions allow for statistical model checking of stochastic hybrid systems. We show how our race-based stochastic semantics extends to networks of hybrid systems, and indicate the integration technique...... applied for implementing this semantics in the UPPAAL-SMC simulation engine. We report on two applications of the resulting tool-set coming from systems biology and energy aware buildings....

  20. A model for international border management systems.

    Energy Technology Data Exchange (ETDEWEB)

    Duggan, Ruth Ann

    2008-09-01

    To effectively manage the security or control of its borders, a country must understand its border management activities as a system. Using its systems engineering and security foundations as a Department of Energy National Security Laboratory, Sandia National Laboratories has developed such an approach to modeling and analyzing border management systems. This paper describes the basic model and its elements developed under Laboratory Directed Research and Development project 08-684.

  1. A Conceptual Data Model of Datum Systems

    Science.gov (United States)

    McCaleb, Michael R.

    1999-01-01

    A new conceptual data model that addresses the geometric dimensioning and tolerancing concepts of datum systems, datums, datum features, datum targets, and the relationships among these concepts, is presented. Additionally, a portion of a related data model, Part 47 of STEP (ISO 10303-47), is reviewed and a comparison is made between it and the new conceptual data model.

  2. Modelling of Generic Slung Load System

    DEFF Research Database (Denmark)

    Bisgaard, Morten; Bendtsen, Jan Dimon; La Cour-Harbo, Anders

    2006-01-01

    This paper presents the result of modelling and verification of a generic slung load system using a small-scale helicopter. The model is intended for use in simulation, pilot training, estimation, and control. The model is derived using a redundant coordinate formulation based on Gauss Principle ...

  3. Human performance modeling for system of systems analytics.

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Kevin R.; Lawton, Craig R.; Basilico, Justin Derrick; Longsine, Dennis E. (INTERA, Inc., Austin, TX); Forsythe, James Chris; Gauthier, John Henry; Le, Hai D.

    2008-10-01

    A Laboratory-Directed Research and Development project was initiated in 2005 to investigate Human Performance Modeling in a System of Systems analytic environment. SAND2006-6569 and SAND2006-7911 document interim results from this effort; this report documents the final results. The problem is difficult because of the number of humans involved in a System of Systems environment and the generally poorly defined nature of the tasks that each human must perform. A two-pronged strategy was followed: one prong was to develop human models using a probability-based method similar to that first developed for relatively well-understood probability based performance modeling; another prong was to investigate more state-of-art human cognition models. The probability-based modeling resulted in a comprehensive addition of human-modeling capability to the existing SoSAT computer program. The cognitive modeling resulted in an increased understanding of what is necessary to incorporate cognition-based models to a System of Systems analytic environment.

  4. Complex system modelling for veterinary epidemiology.

    Science.gov (United States)

    Lanzas, Cristina; Chen, Shi

    2015-02-01

    The use of mathematical models has a long tradition in infectious disease epidemiology. The nonlinear dynamics and complexity of pathogen transmission pose challenges in understanding its key determinants, in identifying critical points, and designing effective mitigation strategies. Mathematical modelling provides tools to explicitly represent the variability, interconnectedness, and complexity of systems, and has contributed to numerous insights and theoretical advances in disease transmission, as well as to changes in public policy, health practice, and management. In recent years, our modelling toolbox has considerably expanded due to the advancements in computing power and the need to model novel data generated by technologies such as proximity loggers and global positioning systems. In this review, we discuss the principles, advantages, and challenges associated with the most recent modelling approaches used in systems science, the interdisciplinary study of complex systems, including agent-based, network and compartmental modelling. Agent-based modelling is a powerful simulation technique that considers the individual behaviours of system components by defining a set of rules that govern how individuals ("agents") within given populations interact with one another and the environment. Agent-based models have become a recent popular choice in epidemiology to model hierarchical systems and address complex spatio-temporal dynamics because of their ability to integrate multiple scales and datasets.

  5. Engineered three-dimensional multicellular culture model to recapitulate morphogenetic fusion using human cells

    Science.gov (United States)

    Tissue fusion during early mammalian development requires crosstalk between multiple cell types. For example, paracrine signaling between palatal epithelial cells and palatal mesenchyme mediates the fusion of opposing palatal shelves during embryonic development. Fusion events in...

  6. Using Interaction Scenarios to Model Information Systems

    DEFF Research Database (Denmark)

    Bækgaard, Lars; Bøgh Andersen, Peter

    The purpose of this paper is to define and discuss a set of interaction primitives that can be used to model the dynamics of socio-technical activity systems, including information systems, in a way that emphasizes structural aspects of the interaction that occurs in such systems. The primitives...

  7. Port-based modeling of mechatronic systems

    NARCIS (Netherlands)

    Breedveld, Peter C.

    2004-01-01

    Many engineering activities, including mechatronic design, require that a multidomain or ‘multi-physics’ system and its control system be designed as an integrated system. This contribution discusses the background and tools for a port-based approach to integrated modeling and simulation of physical

  8. Lattice models of ionic systems

    Science.gov (United States)

    Kobelev, Vladimir; Kolomeisky, Anatoly B.; Fisher, Michael E.

    2002-05-01

    A theoretical analysis of Coulomb systems on lattices in general dimensions is presented. The thermodynamics is developed using Debye-Hückel theory with ion-pairing and dipole-ion solvation, specific calculations being performed for three-dimensional lattices. As for continuum electrolytes, low-density results for simple cubic (sc), body-centered cubic (bcc), and face-centered cubic (fcc) lattices indicate the existence of gas-liquid phase separation. The predicted critical densities have values comparable to those of continuum ionic systems, while the critical temperatures are 60%-70% higher. However, when the possibility of sublattice ordering as well as Debye screening is taken into account systematically, order-disorder transitions and a tricritical point are found on sc and bcc lattices, and gas-liquid coexistence is suppressed. Our results agree with recent Monte Carlo simulations of lattice electrolytes.

  9. Heteroexpression and characterization of a monomeric isocitrate dehydrogenase from the multicellular prokaryote Streptomyces avermitilis MA-4680.

    Science.gov (United States)

    Wang, Ao; Cao, Zheng-Yu; Wang, Peng; Liu, Ai-Min; Pan, Wei; Wang, Jie; Zhu, Guo-Ping

    2011-08-01

    A monomeric NADP-dependent isocitrate dehydrogenase from the multicellular prokaryote Streptomyces avermitilis MA-4680 (SaIDH) was heteroexpressed in Escherichia coli, and the His-tagged enzyme was further purified to homogeneity. The molecular weight of SaIDH was about 80 kDa which is typical for monomeric isocitrate dehydrogenases. Structure-based sequence alignment reveals that the deduced amino acid sequence of SaIDH shows high sequence identity with known momomeric isocitrate dehydrogenase, and the coenzyme, substrate and metal ion binding sites are completely conserved. The optimal pH and temperature of SaIDH were found to be pH 9.4 and 45°C, respectively. Heat-inactivation studies showed that heating for 20 min at 50°C caused a 50% loss in enzymatic activity. In addition, SaIDH was absolutely specific for NADP+ as electron acceptor. Apparent Km values were 4.98 μM for NADP+ and 6,620 μM for NAD+, respectively, using Mn2+ as divalent cation. The enzyme performed a 33,000-fold greater specificity (kcat/Km) for NADP+ than NAD+. Moreover, SaIDH activity was entirely dependent on the presence of Mn2+ or Mg2+, but was strongly inhibited by Ca2+ and Zn2+. Taken together, our findings implicate the recombinant SaIDH is a divalent cation-dependent monomeric isocitrate dehydrogenase which presents a remarkably high cofactor preference for NADP+.

  10. Aragonite crystallization in primary cell cultures of multicellular isolates from a hard coral, Pocillopora damicornis.

    Science.gov (United States)

    Domart-Coulon, I J; Elbert, D C; Scully, E P; Calimlim, P S; Ostrander, G K

    2001-10-09

    The foundation of marine coral reef ecosystems is calcium carbonate accumulated primarily by the action of hard corals (Coelenterata: Anthozoa: Scleractinia). Colonial hard coral polyps cover the surface of the reef and deposit calcium carbonate as the aragonite polymorph, stabilized into a continuous calcareous skeleton. Scleractinian coral skeleton composition and architecture are well documented; however, the cellular mechanisms of calcification are poorly understood. There is little information on the nature of the coral cell types involved or their cooperation in biocalcification. We report aragonite crystallization in primary cell cultures of a hard coral, Pocillopora damicornis. Cells of apical coral colony fragments were isolated by spontaneous in vitro dissociation. Single dissociated cell types were separated by density in a discontinuous Percoll gradient. Primary cell cultures displayed a transient increase in alkaline phosphatase (ALP) activity, to the level observed in intact corals. In adherent multicellular isolate cultures, enzyme activation was followed by precipitation of aragonite. Modification of the ionic formulation of the medium prolonged maintenance of isolates, delayed ALP activation, and delayed aragonite precipitation. These results demonstrate that in vitro crystallization of aragonite in coral cell cultures is possible, and provides an innovative approach to investigate reef-building coral calcification at the cellular level.

  11. A microfluidic platform for chemoresistive testing of multicellular pleural cancer spheroids.

    Science.gov (United States)

    Ruppen, Janine; Cortes-Dericks, Lourdes; Marconi, Emanuele; Karoubi, Golnaz; Schmid, Ralph A; Peng, Renwang; Marti, Thomas M; Guenat, Olivier T

    2014-03-21

    This study reports on a microfluidic platform on which single multicellular spheroids from malignant pleural mesothelioma (MPM), an aggressive tumor with poor prognosis, can be loaded, trapped and tested for chemotherapeutic drug response. A new method to detect the spheroid viability cultured on the microfluidic chip as a function of the drug concentration is presented. This approach is based on the evaluation of the caspase activity in the supernatant sampled from the chip and tested using a microplate reader. This simple and time-saving method does only require a minimum amount of manipulations and was established for very low numbers of cells. This feature is particularly important in view of personalised medicine applications for which the number of cells obtained from the patients is low. MPM spheroids were continuously perfused for 48 hours with cisplatin, one of the standard chemotherapeutic drugs used to treat MPM. The 50% growth inhibitory concentration of cisplatin in perfused MPM spheroids was found to be twice as high as in spheroids cultured under static conditions. This chemoresistance increase might be due to the continuous support of nutrients and oxygen to the perfused spheroids.

  12. Characterization of Hydrogen Metabolism in the Multicellular Green Alga Volvox carteri.

    Directory of Open Access Journals (Sweden)

    Adam J Cornish

    Full Text Available Hydrogen gas functions as a key component in the metabolism of a wide variety of microorganisms, often acting as either a fermentative end-product or an energy source. The number of organisms reported to utilize hydrogen continues to grow, contributing to and expanding our knowledge of biological hydrogen processes. Here we demonstrate that Volvox carteri f. nagariensis, a multicellular green alga with differentiated cells, evolves H2 both when supplied with an abiotic electron donor and under physiological conditions. The genome of Volvox carteri contains two genes encoding putative [FeFe]-hydrogenases (HYDA1 and HYDA2, and the transcripts for these genes accumulate under anaerobic conditions. The HYDA1 and HYDA2 gene products were cloned, expressed, and purified, and both are functional [FeFe]-hydrogenases. Additionally, within the genome the HYDA1 and HYDA2 genes cluster with two putative genes which encode hydrogenase maturation proteins. This gene cluster resembles operon-like structures found within bacterial genomes and may provide further insight into evolutionary relationships between bacterial and algal [FeFe]-hydrogenase genes.

  13. Visualizing spatiotemporal dynamics of multicellular cell-cycle progressions with fucci technology.

    Science.gov (United States)

    Sakaue-Sawano, Asako; Miyawaki, Atsushi

    2014-05-01

    The visualization of cell-cycle behavior of individual cells within complex tissues presents an irresistible challenge to biologists studying multicellular structures. However, the transition from G1 to S in the cell cycle is difficult to monitor despite the fact that the process involves the critical decision to initiate a new round of DNA replication. Here, we use ubiquitination oscillators that control cell-cycle transitions to develop genetically encoded fluorescent probes for cell-cycle progression. Fucci (fluorescent ubiquitination-based cell-cycle indicator) probes exploit the regulation of cell-cycle-dependent ubiquitination to effectively label individual nuclei in G1 phase red, and those in S/G2/M phases green. Cultured cells and transgenic mice constitutively expressing the probes have been generated, such that every cell nucleus shows either red or green fluorescence. This protocol details two experiments that use biological samples expressing Fucci probes. One experiment involves time-lapse imaging of cells stably expressing a Fucci derivative (Fucci2), which allows for the exploration of the spatiotemporal patterns of cell-cycle dynamics during structural and behavioral changes of cultured cells. The other experiment involves large-field, high-resolution imaging of fixed sections of Fucci transgenic mouse embryos, which provides maps that illustrate cell proliferation versus differentiation in various developing organs.

  14. Nonmagnetotactic multicellular prokaryotes from low-saline, nonmarine aquatic environments and their unusual negative phototactic behavior.

    Science.gov (United States)

    Lefèvre, Christopher T; Abreu, Fernanda; Lins, Ulysses; Bazylinski, Dennis A

    2010-05-01

    Magnetotactic multicellular prokaryotes (MMPs) are unique magnetotactic bacteria of the Deltaproteobacteria class and the first found to biomineralize the magnetic mineral greigite (Fe(3)S(4)). Thus far they have been reported only from marine habitats. We questioned whether MMPs exist in low-saline, nonmarine environments. MMPs were observed in samples from shallow springs in the Great Boiling Springs geothermal field and Pyramid Lake, both located in northwestern Nevada. The temperature at all sites was ambient, and salinities ranged from 5 to 11 ppt. These MMPs were not magnetotactic and did not contain magnetosomes (called nMMPs here). nMMPs ranged from 7 to 11 microm in diameter, were composed of about 40 to 60 Gram-negative cells, and were motile by numerous flagella that covered each cell on one side, characteristics similar to those of MMPs. 16S rRNA gene sequences of nMMPs show that they form a separate phylogenetic branch within the MMP group in the Deltaproteobacteria class, probably representing a single species. nMMPs exhibited a negative phototactic behavior to white light and to wavelengths of low in the sample. Our results show that the unique morphology of the MMP is not restricted to marine and magnetotactic prokaryotes. Discovery of nonmagnetotactic forms of the MMP might support the hypothesis that acquisition of the magnetosome genes involves horizontal gene transfer. To our knowledge, this is the first report of phototaxis in bacteria of the Deltaproteobacteria class.

  15. Cellular and functional specificity among ferritin-like proteins in the multicellular cyanobacterium Nostoc punctiforme.

    Science.gov (United States)

    Ekman, Martin; Sandh, Gustaf; Nenninger, Anja; Oliveira, Paulo; Stensjö, Karin

    2014-03-01

    Ferritin-like proteins constitute a remarkably heterogeneous protein family, including ferritins, bacterioferritins and Dps proteins. The genome of the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme encodes five ferritin-like proteins. In the present paper, we report a multidimensional characterization of these proteins. Our phylogenetic and bioinformatics analyses suggest both structural and physiological differences among the ferritin-like proteins. The expression of these five genes responded differently to hydrogen peroxide treatment, with a significantly higher rise in transcript level for Npun_F3730 as compared with the other four genes. A specific role for Npun_F3730 in the cells tolerance against hydrogen peroxide was also supported by the inactivation of Npun_F3730, Npun_R5701 and Npun_R6212; among these, only the ΔNpun_F3730 strain showed an increased sensitivity to hydrogen peroxide compared with wild type. Analysis of promoter-GFP reporter fusions of the ferritin-like genes indicated that Npun_F3730 and Npun_R5701 were expressed in all cell types of a diazotrophic culture, while Npun_F6212 was expressed specifically in heterocysts. Our study provides the first comprehensive analysis combining functional differentiation and cellular specificity within this important group of proteins in a multicellular cyanobacterium. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

  16. Occurrence and regulation of the multicellular morphotype in Salmonella serovars important in human disease.

    Science.gov (United States)

    Römling, Ute; Bokranz, Werner; Rabsch, Wolfgang; Zogaj, Xhavit; Nimtz, Manfred; Tschäpe, Helmut

    2003-08-01

    Multicellular behavior in Salmonella Typhimurium ATCC14028 called the rdar morphotype is characterized by the expression of the extracellular matrix components cellulose and curli fimbriae. Over 90% of S. Typhimurium and S. Enteritidis strains from human disease, food and animals expressed the rdar morphotype at 28 degrees C. Regulation of the rdar morphotype occurred via the response regulator ompR, which activated transcription of csgD required for production of cellulose and curli fimbriae. Serovar-specific regulation of csgD required rpoS in S. Typhimurium, but was partially independent of rpoS in S. Enteritidis. Rarely, strain-specific temperature-deregulated expression of the rdar morphotype was observed. The host-restricted serovars S. Typhimurium var. Copenhagen phage type DT2 and DT99, Salmonella Typhi and Salmonella Choleraesuis did not express the rdar morphotype, while in Salmonella Gallinarum cellulose expression at 37 degrees C was seen in some strains. Therefore, the expression pattern of the rdar morphotype is serovar specific and correlates with a disease phenotype breaching the intestinal epithelial cell lining.

  17. The number of cell types, information content, and the evolution of complex multicellularity

    Directory of Open Access Journals (Sweden)

    Karl J. Niklas

    2014-12-01

    Full Text Available The number of different cell types (NCT characterizing an organism is often used to quantify organismic complexity. This method results in the tautology that more complex organisms have a larger number of different kinds of cells, and that organisms with more different kinds of cells are more complex. This circular reasoning can be avoided (and simultaneously tested when NCT is plotted against different measures of organismic information content (e.g., genome or proteome size. This approach is illustrated by plotting the NCT of representative diatoms, green and brown algae, land plants, invertebrates, and vertebrates against data for genome size (number of base-pairs, proteome size (number of amino acids, and proteome functional versatility (number of intrinsically disordered protein domains or residues. Statistical analyses of these data indicate that increases in NCT fail to keep pace with increases in genome size, but exceed a one-to-one scaling relationship with increasing proteome size and with increasing numbers of intrinsically disordered protein residues. We interpret these trends to indicate that comparatively small increases in proteome (and not genome size are associated with disproportionate increases in NCT, and that proteins with intrinsically disordered domains enhance cell type diversity and thus contribute to the evolution of complex multicellularity.

  18. Salinity dependence of the distribution of multicellular magnetotactic prokaryotes in a hypersaline lagoon.

    Science.gov (United States)

    Martins, Juliana L; Silveira, Thaís S; Silva, Karen T; Lins, Ulysses

    2009-09-01

    Candidatus Magnetoglobus multicellularis is an unusual magnetotactic multicellular microorganism composed of a highly organized assemblage of gram-negative bacterial cells. In this work, the salinity dependence of Ca. M. multicellularis and its abundance in the hypersaline Araruama Lagoon, Brazil were studied. Viability experiments showed that Ca. M. multicellularis died in salinities upper than 55 per thousand and lower than 40 per thousand. Low salinities were also observed to modify the cellular assemblage. In microcosms prepared with different salinities, the microorganism grew better at intermediate salinities whereas in high or low salinities, the size of the population did not increase over time. The concentrations of Ca. M. multicellularis in the lagoon were related to salinity; sites with lower and higher salinities than the lagoon average contained less Ca. M. multicellularis. These results demonstrate the influence of salinity on the survival and distribution of Ca. M. multicellularis in the environment. In sediments, the abundance of Ca. M. multicellularis ranged from 0 to 103 microorganisms/ml, which represented 0.001% of the counts of total bacteria. The ability of Ca. M. multicellularis to accumulate iron and sulfur in high numbers of magnetosomes (up to 905 per microorganism) suggests that its impact on the sequestration of these elements (0.1% for biogenic bacterial iron) is not proportional to its abundance in the lagoon.

  19. Occurrence and microscopic analyses of multicellular magnetotactic prokaryotes from coastal sediments in the Yellow Sea

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ke; PAN Hongmiao; ZHANG Shengda; YUE Haidong; XIAO Tian; WU Longfei

    2011-01-01

    Multicellular magnetotactic prokaryotes (MMPs) are a group of aggregates composed of 7-45 gram-negative cells synthesizing intracellular magnetic crystals. Although they are thought to be globally distributed, MMPs have been observed only in marine environments in America and Europe. Most MMPs share a rosette-like morphology and biomineralize iron sulfide crystals. In the present study, abundant MMPs were observed, with a density of 26 ind./cm3, in the sediments of a coastal lagoon, Lake Yuehu, in the Yellow Sea. Optical microscopy showed that all of them were rosette shaped with a diameter of 5.5±0.8 μm. Transmission electron microscopy revealed that these MMPs were composed of 10-16 ovoid cells and flagellated peritrichously. High-resolution transmission electron microscopy and energy dispersive X-ray analysis indicated that they biomineralized bullet-shaped magnetite crystals in highly organized parallel chains within which the magnetosomes were oriented in the same direction. This is the first report of MMPs from Asia and demonstrates the ubiquitous distribution of MMPs.

  20. Tissues development in stems of Aristolochia clematitis L. in the point of view of multicellular complexes formation

    Directory of Open Access Journals (Sweden)

    Zofia Puławska

    2014-01-01

    Full Text Available After cytokinesis the cells do not separate but remain within the wall of the mother cell. After a series of divisions a multicellular complex arises. In the stems of Aristolochia clematitis procambium is closer related to protoxylem than to protophloem, and metaphloem is closer related to metaxylem than to protophloem. Since protophloem has a closer common origin with fibre primordia than with the remaining tissues, it cannot be decided unequivocally what is the origin of the fibres or when procambium differentiates. The common origin of the primary vascular tissues is visible in the pattern of the multicellular complexes, whereas the common origin of the secondary vascular tissue developing in the underground several-year-old parts of the stem can be traced in the arrangement of the single radial tiers. Some characteristics of symplastic growth are discussed.

  1. Quantitative Models and Analysis for Reactive Systems

    DEFF Research Database (Denmark)

    Thrane, Claus

    phones and websites. Acknowledging that now more than ever, systems come in contact with the physical world, we need to revise the way we construct models and verification algorithms, to take into account the behavior of systems in the presence of approximate, or quantitative information, provided...... by the environment in which they are embedded. This thesis studies the semantics and properties of a model-based framework for re- active systems, in which models and specifications are assumed to contain quantifiable information, such as references to time or energy. Our goal is to develop a theory of approximation......, by studying how small changes to our models affect the verification results. A key source of motivation for this work can be found in The Embedded Systems Design Challenge [HS06] posed by Thomas A. Henzinger and Joseph Sifakis. It contains a call for advances in the state-of-the-art of systems verification...

  2. Simulation Model of Brushless Excitation System

    Directory of Open Access Journals (Sweden)

    Ahmed N.A.  Alla

    2007-01-01

    Full Text Available Excitation system is key element in the dynamic performance of electric power systems, accurate excitation models are of great importance in simulating and investigating the power system transient phenomena. Parameter identification of the Brushless excitation system was presented. First a block diagram for the EXS parameter was proposed based on the documents and maps in the power station. To identify the parameters of this model, a test procedure to obtain step response, was presented. Using the Genetic Algorithm with the Matlab-software it was possible to identify all the necessary parameters of the model. Using the same measured input signals the response from the standard model showed nearly the same behavior as the excitation system.

  3. Mechatronic Systems Design Methods, Models, Concepts

    CERN Document Server

    Janschek, Klaus

    2012-01-01

    In this textbook, fundamental methods for model-based design of mechatronic systems are presented in a systematic, comprehensive form. The method framework presented here comprises domain-neutral methods for modeling and performance analysis: multi-domain modeling (energy/port/signal-based), simulation (ODE/DAE/hybrid systems), robust control methods, stochastic dynamic analysis, and quantitative evaluation of designs using system budgets. The model framework is composed of analytical dynamic models for important physical and technical domains of realization of mechatronic functions, such as multibody dynamics, digital information processing and electromechanical transducers. Building on the modeling concept of a technology-independent generic mechatronic transducer, concrete formulations for electrostatic, piezoelectric, electromagnetic, and electrodynamic transducers are presented. More than 50 fully worked out design examples clearly illustrate these methods and concepts and enable independent study of th...

  4. Improvements in continuum modeling for biomolecular systems

    CERN Document Server

    Qiao, Yu

    2015-01-01

    Modeling of biomolecular systems plays an essential role in understanding biological processes, such as ionic flow across channels, protein modification or interaction, and cell signaling. The continuum model described by the Poisson-Boltzmann (PB)/Poisson-Nernst-Planck (PNP) equations has made great contributions towards simulation of these processes. However, the model has shortcomings in its commonly used form and cannot capture (or cannot accurately capture) some important physical properties of biological systems. Considerable efforts have been made to improve the continuum model to account for discrete particle interactions and to make progress in numerical methods to provide accurate and efficient simulation. This review will summarize recent main improvements in continuum modeling for biomolecular systems, with focus on the size-modified models, the coupling of the classical density functional theory and PNP equations, the coupling of polar and nonpolar interactions, and numerical progress.

  5. Structural system identification: Structural dynamics model validation

    Energy Technology Data Exchange (ETDEWEB)

    Red-Horse, J.R.

    1997-04-01

    Structural system identification is concerned with the development of systematic procedures and tools for developing predictive analytical models based on a physical structure`s dynamic response characteristics. It is a multidisciplinary process that involves the ability (1) to define high fidelity physics-based analysis models, (2) to acquire accurate test-derived information for physical specimens using diagnostic experiments, (3) to validate the numerical simulation model by reconciling differences that inevitably exist between the analysis model and the experimental data, and (4) to quantify uncertainties in the final system models and subsequent numerical simulations. The goal of this project was to develop structural system identification techniques and software suitable for both research and production applications in code and model validation.

  6. FSM Model of a Simple Photovoltaic System

    Directory of Open Access Journals (Sweden)

    Martina Latkova

    2015-01-01

    Full Text Available The paper describes a simulation model of a simple photovoltaic system intended as a tool for testing the use of finite state machines for simulations representing a long-term operation of renewable energy sources. The mathematical model of the photovoltaic system is described first. Then it is used to build a finite state machine model that calculates a power output of the photovoltaic system for changing values of a solar irradiance and a temperature. Data measured on a real photovoltaic installation are used to verify model’s accuracy through its comparison with a previously created and verified Matlab model. The finite state machine model presented in this paper was created using Ptolemy II software.

  7. Simulation-based Manufacturing System Modeling

    Institute of Scientific and Technical Information of China (English)

    卫东; 金烨; 范秀敏; 严隽琪

    2003-01-01

    In recent years, computer simulation appears to be very advantageous technique for researching the resource-constrained manufacturing system. This paper presents an object-oriented simulation modeling method, which combines the merits of traditional methods such as IDEF0 and Petri Net. In this paper, a four-layer-one-angel hierarchical modeling framework based on OOP is defined. And the modeling description of these layers is expounded, such as: hybrid production control modeling and human resource dispatch modeling. To validate the modeling method, a case study of an auto-product line in a motor manufacturing company has been carried out.

  8. Modelling of Generic Slung Load System

    DEFF Research Database (Denmark)

    Bisgaard, Morten; Bendtsen, Jan Dimon; La Cour-Harbo, Anders

    2006-01-01

    of Least Constraint using the Udwadia-Kalaba equation and can be used to model all body to body slung load suspension types. The model gives an intuitive and easy-to-use way of modelling and simulating di erent slung load suspension types and it includes detection and response of wire slacking......This paper presents the result of modelling and verification of a generic slung load system using a small-scale helicopter. The model is intended for use in simulation, pilot training, estimation, and control. The model is derived using a redundant coordinate formulation based on Gauss Principle...

  9. HVDC System Characteristics and Simulation Models

    Energy Technology Data Exchange (ETDEWEB)

    Moon, S.I.; Han, B.M.; Jang, G.S. [Electric Enginnering and Science Research Institute, Seoul (Korea)

    2001-07-01

    This report deals with the AC-DC power system simulation method by PSS/E and EUROSTAG for the development of a strategy for the reliable operation of the Cheju-Haenam interconnected system. The simulation using both programs is performed to analyze HVDC simulation models. In addition, the control characteristics of the Cheju-Haenam HVDC system as well as Cheju AC system characteristics are described in this work. (author). 104 figs., 8 tabs.

  10. AlgiMatrix™ based 3D cell culture system as an in-vitro tumor model for anticancer studies.

    Directory of Open Access Journals (Sweden)

    Chandraiah Godugu

    Full Text Available BACKGROUND: Three-dimensional (3D in-vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in-vivo conditions. Taking the advantages of 3D culture, we have developed the in-vitro tumor model for anticancer drug screening. METHODS: Cancer cells grown in 6 and 96 well AlgiMatrix™ scaffolds resulted in the formation of multicellular spheroids in the size range of 100-300 µm. Spheroids were grown in two weeks in cultures without compromising the growth characteristics. Different marketed anticancer drugs were screened by incubating them for 24 h at 7, 9 and 11 days in 3D cultures and cytotoxicity was measured by AlamarBlue® assay. Effectiveness of anticancer drug treatments were measured based on spheroid number and size distribution. Evaluation of apoptotic and anti-apoptotic markers was done by immunohistochemistry and RT-PCR. The 3D results were compared with the conventional 2D monolayer cultures. Cellular uptake studies for drug (Doxorubicin and nanoparticle (NLC were done using spheroids. RESULTS: IC(50 values for anticancer drugs were significantly higher in AlgiMatrix™ systems compared to 2D culture models. The cleaved caspase-3 expression was significantly decreased (2.09 and 2.47 folds respectively for 5-Fluorouracil and Camptothecin in H460 spheroid cultures compared to 2D culture system. The cytotoxicity, spheroid size distribution, immunohistochemistry, RT-PCR and nanoparticle penetration data suggested that in vitro tumor models show higher resistance to anticancer drugs and supporting the fact that 3D culture is a better model for the cytotoxic evaluation of anticancer drugs in vitro. CONCLUSION: The results from our studies are useful to develop a high throughput in vitro tumor model to study the effect of various anticancer agents and various molecular pathways affected by the anticancer drugs and formulations.

  11. Modeling the Dynamics of an Information System

    Directory of Open Access Journals (Sweden)

    Jacek Unold

    2003-11-01

    Full Text Available The article concentrates on the nature of a social subsystem of an information system. It analyzes the nature of information processes of collectivity within an IS and introduces a model of IS dynamics. The model is based on the assumption that a social subsystem of an information system works as a nonlinear dynamic system. The model of IS dynamics is verified on the indexes of the stock market. It arises from the basic assumption of the technical analysis of the markets, that is, the index chart reflects the play of demand and supply, which in turn represents the crowd sentiment on the market.

  12. Systematic modelling and simulation of refrigeration systems

    DEFF Research Database (Denmark)

    Rasmussen, Bjarne D.; Jakobsen, Arne

    1998-01-01

    The task of developing a simulation model of a refrigeration system can be very difficult and time consuming. In order for this process to be effective, a systematic method for developing the system model is required. This method should aim at guiding the developer to clarify the purpose...... of the simulation, to select appropriate component models and to set up the equations in a well-arranged way. In this paper the outline of such a method is proposed and examples showing the use of this method for simulation of refrigeration systems are given....

  13. MODEL DRIVEN DEVELOPMENT OF ONLINE BANKING SYSTEMS

    Directory of Open Access Journals (Sweden)

    Bresfelean Vasile Paul

    2011-07-01

    Full Text Available In case of online applications the cycle of software development varies from the routine. The online environment, the variety of users, the treatability of the mass of information created by them, the reusability and the accessibility from different devices are all factors of these systems complexity. The use of model drive approach brings several advantages that ease up the development process. Working prototypes that simplify client relationship and serve as the base of model tests can be easily made from models describing the system. These systems make possible for the banks clients to make their desired actions from anywhere. The user has the possibility of accessing information or making transactions.

  14. Development and Integration of Control System Models

    Science.gov (United States)

    Kim, Young K.

    1998-01-01

    The computer simulation tool, TREETOPS, has been upgraded and used at NASA/MSFC to model various complicated mechanical systems and to perform their dynamics and control analysis with pointing control systems. A TREETOPS model of Advanced X-ray Astrophysics Facility - Imaging (AXAF-1) dynamics and control system was developed to evaluate the AXAF-I pointing performance for Normal Pointing Mode. An optical model of Shooting Star Experiment (SSE) was also developed and its optical performance analysis was done using the MACOS software.

  15. Models for the study of whole systems.

    Science.gov (United States)

    Bell, Iris R; Koithan, Mary

    2006-12-01

    This article summarizes a network and complex systems science model for research on whole systems of complementary and alternative medicine (CAM) such as homeopathy and traditional Chinese medicine. The holistic concepts of networks and nonlinear dynamical complex systems are well matched to the global and interactive perspectives of whole systems of CAM, whereas the reductionistic science model is well matched to the isolated local organ, cell, and molecular mechanistic perspectives of pharmaceutically based biomedicine. Whole systems of CAM are not drugs with specific actions. The diagnostic and therapeutic approaches of whole systems of CAM produce effects that involve global and patterned shifts across multiple subsystems of the person as a whole. For homeopathy, several characteristics of complex systems, including the probabilistic nature of attractor patterns, variable sensitivity of complex systems to initial conditions, and emergent behaviors in the evolution of a system in its full environmental context over time, could help account for the mixed basic science and controlled clinical trial research findings, in contrast with the consistently positive outcomes of observational studies in the literature. Application of theories and methods from complex systems and network science can open a new era of advances in understanding factors that lead to good versus poor individual global outcome patterns and to rational triage of patients to one type of care over another. The growing reliance on complex systems thinking and systems biology for cancer research affords a unique opportunity to bridge between the CAM and conventional medical worlds with some common language and conceptual models.

  16. Multi-cellular natural killer (NK) cell clusters enhance NK cell activation through localizing IL-2 within the cluster

    Science.gov (United States)

    Kim, Miju; Kim, Tae-Jin; Kim, Hye Mi; Doh, Junsang; Lee, Kyung-Mi

    2017-01-01

    Multi-cellular cluster formation of natural killer (NK) cells occurs during in vivo priming and potentiates their activation to IL-2. However, the precise mechanism underlying this synergy within NK cell clusters remains unclear. We employed lymphocyte-laden microwell technologies to modulate contact-mediated multi-cellular interactions among activating NK cells and to quantitatively assess the molecular events occurring in multi-cellular clusters of NK cells. NK cells in social microwells, which allow cell-to-cell contact, exhibited significantly higher levels of IL-2 receptor (IL-2R) signaling compared with those in lonesome microwells, which prevent intercellular contact. Further, CD25, an IL-2R α chain, and lytic granules of NK cells in social microwells were polarized toward MTOC. Live cell imaging of lytic granules revealed their dynamic and prolonged polarization toward neighboring NK cells without degranulation. These results suggest that IL-2 bound on CD25 of one NK cells triggered IL-2 signaling of neighboring NK cells. These results were further corroborated by findings that CD25-KO NK cells exhibited lower proliferation than WT NK cells, and when mixed with WT NK cells, underwent significantly higher level of proliferation. These data highlights the existence of IL-2 trans-presentation between NK cells in the local microenvironment where the availability of IL-2 is limited.

  17. Use of an operational model evaluation system for model intercomparison

    Energy Technology Data Exchange (ETDEWEB)

    Foster, K. T., LLNL

    1998-03-01

    The Atmospheric Release Advisory Capability (ARAC) is a centralized emergency response system used to assess the impact from atmospheric releases of hazardous materials. As part of an on- going development program, new three-dimensional diagnostic windfield and Lagrangian particle dispersion models will soon replace ARAC`s current operational windfield and dispersion codes. A prototype model performance evaluation system has been implemented to facilitate the study of the capabilities and performance of early development versions of these new models relative to ARAC`s current operational codes. This system provides tools for both objective statistical analysis using common performance measures and for more subjective visualization of the temporal and spatial relationships of model results relative to field measurements. Supporting this system is a database of processed field experiment data (source terms and meteorological and tracer measurements) from over 100 individual tracer releases.

  18. Evaluation of SystemC Modelling of Reconfigurable Embedded Systems

    CERN Document Server

    Rissa, Tero; Luk, Wayne

    2011-01-01

    This paper evaluates the use of pin and cycle accurate SystemC models for embedded system design exploration and early software development. The target system is MicroBlaze VanillaNet Platform running MicroBlaze uClinux operating system. The paper compares Register Transfer Level (RTL) Hardware Description Language (HDL) simulation speed to the simulation speed of several different SystemC models. It is shown that simulation speed of pin and cycle accurate models can go up to 150 kHz, compared to 100 Hz range of HDL simulation. Furthermore, utilising techniques that temporarily compromise cycle accuracy, effective simulation speed of up to 500 kHz can be obtained.

  19. Modeling of Generic Slung Load System

    DEFF Research Database (Denmark)

    Bisgaard, Morten; Bendtsen, Jan Dimon; la Cour-Harbo, Anders

    2009-01-01

    This paper presents the result of the modelling and verification of a generic slung load system using a small-scale helicopter. The model is intended for use in simulation, pilot training, estimation, and control. The model is derived using a redundant coordinate formulation based on Gauss......' Principle of Least Constraint using the Udwadia-Kalaba equation and can be used to model all body to body slung load suspension types. The model provides intuitive and easy-to-use means of modelling and simulating different slung load suspension types. It includes detection of, and response to, wire...... slackening and tightening as well as aerodynamic coupling between the helicopter and the load. Furthermore, it is shown how the model can be easily used for multi-lift systems either with multiple helicopters or multiple loads. A numerical stabilisation algorithm is introduced and finally the use...

  20. Systems Evaluation Methods, Models, and Applications

    CERN Document Server

    Liu, Siefeng; Xie, Naiming; Yuan, Chaoqing

    2011-01-01

    A book in the Systems Evaluation, Prediction, and Decision-Making Series, Systems Evaluation: Methods, Models, and Applications covers the evolutionary course of systems evaluation methods, clearly and concisely. Outlining a wide range of methods and models, it begins by examining the method of qualitative assessment. Next, it describes the process and methods for building an index system of evaluation and considers the compared evaluation and the logical framework approach, analytic hierarchy process (AHP), and the data envelopment analysis (DEA) relative efficiency evaluation method. Unique

  1. Analytical performance modeling for computer systems

    CERN Document Server

    Tay, Y C

    2013-01-01

    This book is an introduction to analytical performance modeling for computer systems, i.e., writing equations to describe their performance behavior. It is accessible to readers who have taken college-level courses in calculus and probability, networking and operating systems. This is not a training manual for becoming an expert performance analyst. Rather, the objective is to help the reader construct simple models for analyzing and understanding the systems that they are interested in.Describing a complicated system abstractly with mathematical equations requires a careful choice of assumpti

  2. Modeling the variation trends of glacier systems

    Directory of Open Access Journals (Sweden)

    Z. Xie

    2013-01-01

    Full Text Available The basic principles and methods for a functional glacier systems model are introduced and applied for glaciers of Northwest China. When running the model we assume that a glacier system is under steady state conditions in the initial year. The median size of a glacier system is used as representative for the system. The curve of glacier area distribution against elevation is used to compute the increase in equilibrium line altitude (ELA, and the annual glacier ablation is calculated using a global formula a = 1.33(9.66 + ts².⁸⁵ [4, p. 96]. The net mass balance near the ELA under steady state conditions represents the net mass balance of the whole glacier system, and the time required for glacier runoff to return to the initial year level is calculated according to the law of glacier runoff variation, and used to calculate the variation of glacier area. The variation of glacier runoff is modeled according to ablation at the ELA, and the variation of glacier volume is modeled according to the absolute value of the mass balance. The observed changes in surveyed glaciers in China over recent decades were broadly consistent with predictions of the glacier system model. The model therefore offers a reliable method for the prediction of changes in glacier systems in response to changing climate.

  3. Photovoltaic System Modeling. Uncertainty and Sensitivity Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Clifford W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Martin, Curtis E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-08-01

    We report an uncertainty and sensitivity analysis for modeling AC energy from ph otovoltaic systems . Output from a PV system is predicted by a sequence of models. We quantify u ncertainty i n the output of each model using empirical distribution s of each model's residuals. We propagate uncertainty through the sequence of models by sampli ng these distributions to obtain a n empirical distribution of a PV system's output. We consider models that: (1) translate measured global horizontal, direct and global diffuse irradiance to plane - of - array irradiance; (2) estimate effective irradiance; (3) predict cell temperature; (4) estimate DC voltage, current and power ; (5) reduce DC power for losses due to inefficient maximum power point tracking or mismatch among modules; and (6) convert DC to AC power . O ur analysis consider s a notional PV system com prising an array of FirstSolar FS - 387 modules and a 250 kW AC inverter ; we use measured irradiance and weather at Albuquerque, NM. We found the uncertainty in PV syste m output to be relatively small, on the order of 1% for daily energy. We found that unce rtainty in the models for POA irradiance and effective irradiance to be the dominant contributors to uncertainty in predicted daily energy. Our analysis indicates that efforts to reduce the uncertainty in PV system output predictions may yield the greatest improvements by focusing on the POA and effective irradiance models.

  4. Caenorhabditis elegans as a model system for studying non-cell-autonomous mechanisms in protein-misfolding diseases

    Directory of Open Access Journals (Sweden)

    Carmen I. Nussbaum-Krammer

    2014-01-01

    Full Text Available Caenorhabditis elegans has a number of distinct advantages that are useful for understanding the basis for cellular and organismal dysfunction underlying age-associated diseases of protein misfolding. Although protein aggregation, a key feature of human neurodegenerative diseases, has been typically explored in vivo at the single-cell level using cells in culture, there is now increasing evidence that proteotoxicity has a non-cell-autonomous component and is communicated between cells and tissues in a multicellular organism. These discoveries have opened up new avenues for the use of C. elegans as an ideal animal model system to study non-cell-autonomous proteotoxicity, prion-like propagation of aggregation-prone proteins, and the organismal regulation of stress responses and proteostasis. This Review focuses on recent evidence that C. elegans has mechanisms to transmit certain classes of toxic proteins between tissues and a complex stress response that integrates and coordinates signals from single cells and tissues across the organism. These findings emphasize the potential of C. elegans to provide insights into non-cell-autonomous proteotoxic mechanisms underlying age-related protein-misfolding diseases.

  5. System approaches to study root hairs as a single cell plant model: current status and future perspectives

    Directory of Open Access Journals (Sweden)

    Md Shakhawat eHossain

    2015-05-01

    Full Text Available Our current understanding of plant functional genomics derives primarily from measurements of gene, protein and/or metabolite levels averaged over the whole plant or multicellular tissues. These approaches risk diluting the response of specific cells that might respond strongly to the treatment but whose signal is diluted by the larger proportion of non-responding cells. For example, if a gene is expressed at a low level, does this mean that it is indeed lowly expressed or is it highly expressed, but only in a few cells? In order to avoid these issues, we adopted the soybean root hair cell, derived from a single, differentiated root epidermal cell, as a single-cell model for functional genomics. Root hair cells are intrinsically interesting since they are major conduits for root water and nutrient uptake and are also the preferred site of infection by nitrogen-fixing rhizobium bacteria. Although a variety of other approaches have been used to study single plant cells or single cell types, the root hair system is perhaps unique in allowing application of the full repertoire of functional genomic and biochemical approaches. In this mini review, we summarize our published work and place this within the broader context of root biology, with a significant focus on understanding the initial events in the soybean-rhizobium interaction.

  6. Climate Model Diagnostic Analyzer Web Service System

    Science.gov (United States)

    Lee, S.; Pan, L.; Zhai, C.; Tang, B.; Kubar, T. L.; Li, J.; Zhang, J.; Wang, W.

    2015-12-01

    Both the National Research Council Decadal Survey and the latest Intergovernmental Panel on Climate Change Assessment Report stressed the need for the comprehensive and innovative evaluation of climate models with the synergistic use of global satellite observations in order to improve our weather and climate simulation and prediction capabilities. The abundance of satellite observations for fundamental climate parameters and the availability of coordinated model outputs from CMIP5 for the same parameters offer a great opportunity to understand and diagnose model biases in climate models. In addition, the Obs4MIPs efforts have created several key global observational datasets that are readily usable for model evaluations. However, a model diagnostic evaluation process requires physics-based multi-variable comparisons that typically involve large-volume and heterogeneous datasets, making them both computationally- and data-intensive. In response, we have developed a novel methodology to diagnose model biases in contemporary climate models and implementing the methodology as a web-service based, cloud-enabled, provenance-supported climate-model evaluation system. The evaluation system is named Climate Model Diagnostic Analyzer (CMDA), which is the product of the research and technology development investments of several current and past NASA ROSES programs. The current technologies and infrastructure of CMDA are designed and selected to address several technical challenges that the Earth science modeling and model analysis community faces in evaluating and diagnosing climate models. In particular, we have three key technology components: (1) diagnostic analysis methodology; (2) web-service based, cloud-enabled technology; (3) provenance-supported technology. The diagnostic analysis methodology includes random forest feature importance ranking, conditional probability distribution function, conditional sampling, and time-lagged correlation map. We have implemented the

  7. CTBT integrated verification system evaluation model supplement

    Energy Technology Data Exchange (ETDEWEB)

    EDENBURN,MICHAEL W.; BUNTING,MARCUS; PAYNE JR.,ARTHUR C.; TROST,LAWRENCE C.

    2000-03-02

    Sandia National Laboratories has developed a computer based model called IVSEM (Integrated Verification System Evaluation Model) to estimate the performance of a nuclear detonation monitoring system. The IVSEM project was initiated in June 1994, by Sandia's Monitoring Systems and Technology Center and has been funded by the U.S. Department of Energy's Office of Nonproliferation and National Security (DOE/NN). IVSEM is a simple, ''top-level,'' modeling tool which estimates the performance of a Comprehensive Nuclear Test Ban Treaty (CTBT) monitoring system and can help explore the impact of various sensor system concepts and technology advancements on CTBT monitoring. One of IVSEM's unique features is that it integrates results from the various CTBT sensor technologies (seismic, in sound, radionuclide, and hydroacoustic) and allows the user to investigate synergy among the technologies. Specifically, IVSEM estimates the detection effectiveness (probability of detection), location accuracy, and identification capability of the integrated system and of each technology subsystem individually. The model attempts to accurately estimate the monitoring system's performance at medium interfaces (air-land, air-water) and for some evasive testing methods such as seismic decoupling. The original IVSEM report, CTBT Integrated Verification System Evaluation Model, SAND97-25 18, described version 1.2 of IVSEM. This report describes the changes made to IVSEM version 1.2 and the addition of identification capability estimates that have been incorporated into IVSEM version 2.0.

  8. CTBT integrated verification system evaluation model supplement

    Energy Technology Data Exchange (ETDEWEB)

    EDENBURN,MICHAEL W.; BUNTING,MARCUS; PAYNE JR.,ARTHUR C.; TROST,LAWRENCE C.

    2000-03-02

    Sandia National Laboratories has developed a computer based model called IVSEM (Integrated Verification System Evaluation Model) to estimate the performance of a nuclear detonation monitoring system. The IVSEM project was initiated in June 1994, by Sandia's Monitoring Systems and Technology Center and has been funded by the U.S. Department of Energy's Office of Nonproliferation and National Security (DOE/NN). IVSEM is a simple, ''top-level,'' modeling tool which estimates the performance of a Comprehensive Nuclear Test Ban Treaty (CTBT) monitoring system and can help explore the impact of various sensor system concepts and technology advancements on CTBT monitoring. One of IVSEM's unique features is that it integrates results from the various CTBT sensor technologies (seismic, in sound, radionuclide, and hydroacoustic) and allows the user to investigate synergy among the technologies. Specifically, IVSEM estimates the detection effectiveness (probability of detection), location accuracy, and identification capability of the integrated system and of each technology subsystem individually. The model attempts to accurately estimate the monitoring system's performance at medium interfaces (air-land, air-water) and for some evasive testing methods such as seismic decoupling. The original IVSEM report, CTBT Integrated Verification System Evaluation Model, SAND97-25 18, described version 1.2 of IVSEM. This report describes the changes made to IVSEM version 1.2 and the addition of identification capability estimates that have been incorporated into IVSEM version 2.0.

  9. Model Updating Nonlinear System Identification Toolbox Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ZONA Technology proposes to develop an enhanced model updating nonlinear system identification (MUNSID) methodology by adopting the flight data with state-of-the-art...

  10. Model and method for optimizing heterogeneous systems

    Science.gov (United States)

    Antamoshkin, O. A.; Antamoshkina, O. A.; Zelenkov, P. V.; Kovalev, I. V.

    2016-11-01

    Methodology of distributed computing performance boost by reduction of delays number is proposed. Concept of n-dimentional requirements triangle is introduced. Dynamic mathematical model of resource use in distributed computing systems is described.

  11. Modelling the evolution of human trail systems

    Science.gov (United States)

    Helbing, Dirk; Keltsch, Joachim; Molnár, Péter

    1997-07-01

    Many human social phenomena, such as cooperation, the growth of settlements, traffic dynamics and pedestrian movement, appear to be accessible to mathematical descriptions that invoke self-organization. Here we develop a model of pedestrian motion to explore the evolution of trails in urban green spaces such as parks. Our aim is to address such questions as what the topological structures of these trail systems are, and whether optimal path systems can be predicted for urban planning. We use an `active walker' model that takes into account pedestrian motion and orientation and the concomitant feedbacks with the surrounding environment. Such models have previously been applied to the study of complex structure formation in physical, chemical and biological systems. We find that our model is able to reproduce many of the observed large-scale spatial features of trail systems.

  12. Power system coherency and model reduction

    CERN Document Server

    Chow, Joe H

    2014-01-01

    This book provides a comprehensive treatment for understanding interarea modes in large power systems and obtaining reduced-order models using the coherency concept and selective modal analysis method.

  13. Propulsion System Models for Rotorcraft Conceptual Design

    Science.gov (United States)

    Johnson, Wayne

    2014-01-01

    The conceptual design code NDARC (NASA Design and Analysis of Rotorcraft) was initially implemented to model conventional rotorcraft propulsion systems, consisting of turboshaft engines burning jet fuel, connected to one or more rotors through a mechanical transmission. The NDARC propulsion system representation has been extended to cover additional propulsion concepts, including electric motors and generators, rotor reaction drive, turbojet and turbofan engines, fuel cells and solar cells, batteries, and fuel (energy) used without weight change. The paper describes these propulsion system components, the architecture of their implementation in NDARC, and the form of the models for performance and weight. Requirements are defined for improved performance and weight models of the new propulsion system components. With these new propulsion models, NDARC can be used to develop environmentally-friendly rotorcraft designs.

  14. Spinal Cord Injury Model System Information Network

    Science.gov (United States)

    ... Go New to Website Managing Bowel Function After Spinal Cord Injury Resilience, Depression and Bouncing Back after SCI Getting ... the UAB-SCIMS Contact the UAB-SCIMS UAB Spinal Cord Injury Model System Newly Injured Health Daily Living Consumer ...

  15. Systemic Therapy: A New Brief Intervention Model.

    Science.gov (United States)

    Searight, H. Russell; Openlander, Patrick

    1984-01-01

    Describes a newly developing mode of problem-oriented brief therapy. The systemic therapy model emphasizes the interactional context of clients' problems and represents an efficient intervention paradigm. (Author/JAC)

  16. Computational Models for Nonlinear Aeroelastic Systems Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Clear Science Corp. and Duke University propose to develop and demonstrate a new and efficient computational method of modeling nonlinear aeroelastic systems. The...

  17. Regional Ocean Modeling System (ROMS): Samoa

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Regional Ocean Modeling System (ROMS) 7-day, 3-hourly forecast for the region surrounding the islands of Samoa at approximately 3-km resolution. While considerable...

  18. Regional Ocean Modeling System (ROMS): CNMI

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Regional Ocean Modeling System (ROMS) 7-day, 3-hourly forecast for the region surrounding the Commonwealth of the Northern Mariana Islands (CNMI) at approximately...

  19. Forecasting Models in the State Education System

    Directory of Open Access Journals (Sweden)

    Gintautas DZEMYDA

    2003-04-01

    Full Text Available This paper presents model-based assessment and forecasting of the Lithuanian education system in the period of 2001-2010. In order to obtain satisfactory forecasting results, constructing of models used for these aims should be grounded on some interactive data mining. Data mining of data stored in the system of the Lithuanian teacher's database and of data from other sources representing the state of education system and the demographic changes in Lithuania was used. The models cover the estimation of data quality in the databases, the analysis of flow of teachers and pupils, the clustering of schools, the model of dynamics of pedagogical staff and pupils, and the quality analysis of teachers. The main results of forecasting and integrated analysis of the Lithuanian teachers' database with other data reflecting the state of the education system and demographic changes in Lithuania are presented.

  20. System Identification, Environmental Modelling, and Control System Design

    CERN Document Server

    Garnier, Hugues

    2012-01-01

    System Identification, Environmetric Modelling, and Control Systems Design is dedicated to Professor Peter Young on the occasion of his seventieth birthday. Professor Young has been a pioneer in systems and control, and over the past 45 years he has influenced many developments in this field. This volume is comprised of a collection of contributions by leading experts in system identification, time-series analysis, environmetric modelling and control system design – modern research in topics that reflect important areas of interest in Professor Young’s research career. Recent theoretical developments in and relevant applications of these areas are explored treating the various subjects broadly and in depth. The authoritative and up-to-date research presented here will be of interest to academic researcher in control and disciplines related to environmental research, particularly those to with water systems. The tutorial style in which many of the contributions are composed also makes the book suitable as ...

  1. Heuristic approaches to models and modeling in systems biology

    NARCIS (Netherlands)

    MacLeod, Miles

    2016-01-01

    Prediction and control sufficient for reliable medical and other interventions are prominent aims of modeling in systems biology. The short-term attainment of these goals has played a strong role in projecting the importance and value of the field. In this paper I identify the standard models must m

  2. Model of the Human Sleep Wake System

    CERN Document Server

    Rogers, Lisa

    2012-01-01

    A model and analysis of the human sleep/wake system is presented. The model is derived using the known neuronal groups, and their various projections, involved with sleep and wake. Inherent in the derivation is the existence of a slow time scale associated with homeostatic regulation, and a faster time scale associated with the dynamics within the sleep phase. A significant feature of the model is that it does not contain a periodic forcing term, common in other models, reflecting the fact that sleep/wake is not dependent upon a diurnal stimulus. Once derived, the model is analyzed using a linearized stability analysis. We then use experimental data from normal sleep-wake systems and orexin knockout systems to verify the physiological validity of the equations.

  3. Modelling of Signal - Level Crossing System

    Directory of Open Access Journals (Sweden)

    Daniel Novak

    2006-01-01

    Full Text Available The author presents an object-oriented model of a railway level-crossing system created for the purpose of functional requirements specification. Unified Modelling Language (UML, version 1.4, which enables specification, visualisation, construction and documentation of software system artefacts, was used. The main attention was paid to analysis and design phases. The former phase resulted in creation of use case diagrams and sequential diagrams, the latter in creation of class/object diagrams and statechart diagrams.

  4. A Prison/Parole System Simulation Model,

    Science.gov (United States)

    parole system on future prison and parole populations. A simulation model is presented, viewing a prison / parole system as a feedback process for...ciminal offenders . Transitions among the states in which an offender might be located, imprisoned, paroled , and discharged, are assumed to be in...accordance with a discrete time semi-Markov process. Projected prison and parole populations for sample data and applications of the model are discussed. (Author)

  5. Constructing a systems psychodynamic wellness model

    OpenAIRE

    Sanchen Henning; Frans Cilliers

    2012-01-01

    Orientation: The researchers constructed a Systems Psychodynamic Wellness Model (SPWM) by merging theory and concepts from systems psychodynamics and positive psychology. They then refined the model for application in organisations during a Listening Post (LP) that comprised experienced subject experts.Research purpose: The purpose of the research was to construct and refine the SPWM in order to understand psychological wellness at the individual, group and organisational levels.Motivation fo...

  6. New Directions in Modeling the Lighting Systems

    Directory of Open Access Journals (Sweden)

    P. Fiala

    2004-12-01

    Full Text Available This paper presents information about new directions in the modelingof lighting systems, and an overview of methods for the modeling oflighting systems. The new R-FEM method is described, which is acombination of the Radiosity method and the Finite Elements Method. Thepaper contains modeling results and their verification by experimentalmeasurements and by the Matlab simulation for this R-FEM method.

  7. Quantitative Models and Analysis for Reactive Systems

    DEFF Research Database (Denmark)

    Thrane, Claus

    phones and websites. Acknowledging that now more than ever, systems come in contact with the physical world, we need to revise the way we construct models and verification algorithms, to take into account the behavior of systems in the presence of approximate, or quantitative information, provided......, allowing verification procedures to quantify judgements, on how suitable a model is for a given specification — hence mitigating the usual harsh distinction between satisfactory and non-satisfactory system designs. This information, among other things, allows us to evaluate the robustness of our framework......, by studying how small changes to our models affect the verification results. A key source of motivation for this work can be found in The Embedded Systems Design Challenge [HS06] posed by Thomas A. Henzinger and Joseph Sifakis. It contains a call for advances in the state-of-the-art of systems verification...

  8. Hybrid Energy System Modeling in Modelica

    Energy Technology Data Exchange (ETDEWEB)

    William R. Binder; Christiaan J. J. Paredis; Humberto E. Garcia

    2014-03-01

    In this paper, a Hybrid Energy System (HES) configuration is modeled in Modelica. Hybrid Energy Systems (HES) have as their defining characteristic the use of one or more energy inputs, combined with the potential for multiple energy outputs. Compared to traditional energy systems, HES provide additional operational flexibility so that high variability in both energy production and consumption levels can be absorbed more effectively. This is particularly important when including renewable energy sources, whose output levels are inherently variable, determined by nature. The specific HES configuration modeled in this paper include two energy inputs: a nuclear plant, and a series of wind turbines. In addition, the system produces two energy outputs: electricity and synthetic fuel. The models are verified through simulations of the individual components, and the system as a whole. The simulations are performed for a range of component sizes, operating conditions, and control schemes.

  9. Model Reduction of Fuzzy Logic Systems

    Directory of Open Access Journals (Sweden)

    Zhandong Yu

    2014-01-01

    Full Text Available This paper deals with the problem of ℒ2-ℒ∞ model reduction for continuous-time nonlinear uncertain systems. The approach of the construction of a reduced-order model is presented for high-order nonlinear uncertain systems described by the T-S fuzzy systems, which not only approximates the original high-order system well with an ℒ2-ℒ∞ error performance level γ but also translates it into a linear lower-dimensional system. Then, the model approximation is converted into a convex optimization problem by using a linearization procedure. Finally, a numerical example is presented to show the effectiveness of the proposed method.

  10. Economic model of pipeline transportation systems

    Energy Technology Data Exchange (ETDEWEB)

    Banks, W. F.

    1977-07-29

    The objective of the work reported here was to develop a model which could be used to assess the economic effects of energy-conservative technological innovations upon the pipeline industry. The model is a dynamic simulator which accepts inputs of two classes: the physical description (design parameters, fluid properties, and financial structures) of the system to be studied, and the postulated market (throughput and price) projection. The model consists of time-independent submodels: the fluidics model which simulates the physical behavior of the system, and the financial model which operates upon the output of the fluidics model to calculate the economics outputs. Any of a number of existing fluidics models can be used in addition to that developed as a part of this study. The financial model, known as the Systems, Science and Software (S/sup 3/) Financial Projection Model, contains user options whereby pipeline-peculiar characteristics can be removed and/or modified, so that the model can be applied to virtually any kind of business enterprise. The several dozen outputs are of two classes: the energetics and the economics. The energetics outputs of primary interest are the energy intensity, also called unit energy consumption, and the total energy consumed. The primary economics outputs are the long-run average cost, profit, cash flow, and return on investment.

  11. A multilingual programming model for coupled systems.

    Energy Technology Data Exchange (ETDEWEB)

    Ong, E. T.; Larson, J. W.; Norris, B.; Tobis, M.; Steder, M.; Jacob, R. L.; Mathematics and Computer Science; Univ. of Wisconsin; Univ. of Chicago; The Australian National Univ.

    2008-01-01

    Multiphysics and multiscale simulation systems share a common software requirement-infrastructure to implement data exchanges between their constituent parts-often called the coupling problem. On distributed-memory parallel platforms, the coupling problem is complicated by the need to describe, transfer, and transform distributed data, known as the parallel coupling problem. Parallel coupling is emerging as a new grand challenge in computational science as scientists attempt to build multiscale and multiphysics systems on parallel platforms. An additional coupling problem in these systems is language interoperability between their constituent codes. We have created a multilingual parallel coupling programming model based on a successful open-source parallel coupling library, the Model Coupling Toolkit (MCT). This programming model's capabilities reach beyond MCT's native Fortran implementation to include bindings for the C++ and Python programming languages. We describe the method used to generate the interlanguage bindings. This approach enables an object-based programming model for implementing parallel couplings in non-Fortran coupled systems and in systems with language heterogeneity. We describe the C++ and Python versions of the MCT programming model and provide short examples. We report preliminary performance results for the MCT interpolation benchmark. We describe a major Python application that uses the MCT Python bindings, a Python implementation of the control and coupling infrastructure for the community climate system model. We conclude with a discussion of the significance of this work to productivity computing in multidisciplinary computational science.

  12. The Guided System Development Framework: Modeling and Verifying Communication Systems

    DEFF Research Database (Denmark)

    Carvalho Quaresma, Jose Nuno; Probst, Christian W.; Nielson, Flemming

    2014-01-01

    In a world that increasingly relies on the Internet to function, application developers rely on the implementations of protocols to guarantee the security of data transferred. Whether a chosen protocol gives the required guarantees, and whether the implementation does the same, is usually unclear....... The Guided System Development framework contributes to more secure communication systems by aiding the development of such systems. The framework features a simple modelling language, step-wise refinement from models to implementation, interfaces to security verification tools, and code generation from...

  13. Human performance modeling for system of systems analytics :soldier fatigue.

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, Craig R.; Campbell, James E.; Miller, Dwight Peter

    2005-10-01

    The military has identified Human Performance Modeling (HPM) as a significant requirement and challenge of future systems modeling and analysis initiatives as can be seen in the Department of Defense's (DoD) Defense Modeling and Simulation Office's (DMSO) Master Plan (DoD 5000.59-P 1995). To this goal, the military is currently spending millions of dollars on programs devoted to HPM in various military contexts. Examples include the Human Performance Modeling Integration (HPMI) program within the Air Force Research Laboratory, which focuses on integrating HPMs with constructive models of systems (e.g. cockpit simulations) and the Navy's Human Performance Center (HPC) established in September 2003. Nearly all of these initiatives focus on the interface between humans and a single system. This is insufficient in the era of highly complex network centric SoS. This report presents research and development in the area of HPM in a system-of-systems (SoS). Specifically, this report addresses modeling soldier fatigue and the potential impacts soldier fatigue can have on SoS performance.

  14. On modeling and controlling intelligent systems

    Energy Technology Data Exchange (ETDEWEB)

    Dress, W.B.

    1993-11-01

    The aim of this paper is to show how certain diverse and advanced techniques of information processing and system theory might be integrated into a model of an intelligent, complex entity capable of materially enhancing an advanced information management system. To this end, we first examine the notion of intelligence and ask whether a semblance thereof can arise in a system consisting of ensembles of finite-state automata. Our goal is to find a functional model of intelligence in an information-management setting that can be used as a tool. The purpose of this tool is to allow us to create systems of increasing complexity and utility, eventually reaching the goal of an intelligent information management system that provides and anticipates needed data and information. We base our attempt on the ideas of general system theory where the four topics of system identification, modeling, optimization, and control provide the theoretical framework for constructing a complex system that will be capable of interacting with complex systems in the real world. These four key topics are discussed within the purview of cellular automata, neural networks, and evolutionary programming. This is a report of ongoing work, and not yet a success story of a synthetic intelligent system.

  15. On modeling and controlling intelligent systems

    Energy Technology Data Exchange (ETDEWEB)

    Dress, W.B.

    1993-11-01

    The aim of this paper is to show how certain diverse and advanced techniques of information processing and system theory might be integrated into a model of an intelligent, complex entity capable of materially enhancing an advanced information management system. To this end, we first examine the notion of intelligence and ask whether a semblance thereof can arise in a system consisting of ensembles of finite-state automata. Our goal is to find a functional model of intelligence in an information-management setting that can be used as a tool. The purpose of this tool is to allow us to create systems of increasing complexity and utility, eventually reaching the goal of an intelligent information management system that provides and anticipates needed data and information. We base our attempt on the ideas of general system theory where the four topics of system identification, modeling, optimization, and control provide the theoretical framework for constructing a complex system that will be capable of interacting with complex systems in the real world. These four key topics are discussed within the purview of cellular automata, neural networks, and evolutionary programming. This is a report of ongoing work, and not yet a success story of a synthetic intelligent system.

  16. Behavioral Reference Model for Pervasive Healthcare Systems.

    Science.gov (United States)

    Tahmasbi, Arezoo; Adabi, Sahar; Rezaee, Ali

    2016-12-01

    The emergence of mobile healthcare systems is an important outcome of application of pervasive computing concepts for medical care purposes. These systems provide the facilities and infrastructure required for automatic and ubiquitous sharing of medical information. Healthcare systems have a dynamic structure and configuration, therefore having an architecture is essential for future development of these systems. The need for increased response rate, problem limited storage, accelerated processing and etc. the tendency toward creating a new generation of healthcare system architecture highlight the need for further focus on cloud-based solutions for transfer data and data processing challenges. Integrity and reliability of healthcare systems are of critical importance, as even the slightest error may put the patients' lives in danger; therefore acquiring a behavioral model for these systems and developing the tools required to model their behaviors are of significant importance. The high-level designs may contain some flaws, therefor the system must be fully examined for different scenarios and conditions. This paper presents a software architecture for development of healthcare systems based on pervasive computing concepts, and then models the behavior of described system. A set of solutions are then proposed to improve the design's qualitative characteristics including, availability, interoperability and performance.

  17. XML Model of Planning System in Foundry

    Directory of Open Access Journals (Sweden)

    A. Stawowy

    2007-07-01

    Full Text Available Contemporary enterprises (including those manufacturing iron castings have at their disposal advanced computer resources for the management of production processes. The disadvantage of these solutions is an incoherent language for writing production planning and scheduling problems. The lack of the standard for data exchange and model description makes the work on designing, development and implementation difficult. Various dialects of XML language, among others for production planning purposes, which may change this situation have been developed for the last several years. The paper describes a PSLX language, which can be viewed first of all as an ontology and communication protocol inside and outside of the Advanced Planning and Scheduling (APS system, as well as an XML standard for production planning and scheduling. This language has been then used to develop a model of planning system in a foundry. The model consists of customer’s order model, resources model and scheduling model.

  18. Externalizing Behaviour for Analysing System Models

    DEFF Research Database (Denmark)

    Ivanova, Marieta Georgieva; Probst, Christian W.; Hansen, René Rydhof

    2013-01-01

    attackers. Therefore, many attacks are considerably easier to be performed for insiders than for outsiders. However, current models do not support explicit specification of different behaviours. Instead, behaviour is deeply embedded in the analyses supported by the models, meaning that it is a complex......, if not impossible task to change behaviours. Especially when considering social engineering or the human factor in general, the ability to use different kinds of behaviours is essential. In this work we present an approach to make the behaviour a separate component in system models, and explore how to integrate......System models have recently been introduced to model organisations and evaluate their vulnerability to threats and especially insider threats. Especially for the latter these models are very suitable, since insiders can be assumed to have more knowledge about the attacked organisation than outside...

  19. Reusing knowledge in embedded system modelling

    NARCIS (Netherlands)

    Marincic, J.; Mader, Angelika H.; Wieringa, Roelf J.; Lucas, Yan

    2013-01-01

    Model-based design is a promising technique to improve the quality of software and the efficiency of the software development process. We are investigating how to efficiently model embedded software and its environment to verify the requirements for the system controlled by the software. The softwar

  20. Complex Systems and Human Performance Modeling

    Science.gov (United States)

    2013-12-01

    constitute a cognitive architecture or decomposing the work flows and resource constraints that characterize human-system interactions, the modeler...also explored the generation of so-called “ fractal ” series from simple task network models where task times are the calculated by way of a moving

  1. Immune System Model Calibration by Genetic Algorithm

    NARCIS (Netherlands)

    Presbitero, A.; Krzhizhanovskaya, V.; Mancini, E.; Brands, R.; Sloot, P.

    2016-01-01

    We aim to develop a mathematical model of the human immune system for advanced individualized healthcare where medication plan is fine-tuned to fit a patient's conditions through monitored biochemical processes. One of the challenges is calibrating model parameters to satisfy existing experimental

  2. Test-driven modeling of embedded systems

    DEFF Research Database (Denmark)

    Munck, Allan; Madsen, Jan

    2015-01-01

    To benefit maximally from model-based systems engineering (MBSE) trustworthy high quality models are required. From the software disciplines it is known that test-driven development (TDD) can significantly increase the quality of the products. Using a test-driven approach with MBSE may have a sim...

  3. A system dynamics model for communications networks

    Science.gov (United States)

    Awcock, A. J.; King, T. E. G.

    1985-09-01

    An abstract model of a communications network in system dynamics terminology is developed as implementation of this model by a FORTRAN program package developed at RSRE is discussed. The result of this work is a high-level simulation package in which the performance of adaptive routing algorithms and other network controls may be assessed for a network of arbitrary topology.

  4. System level modelling with open source tools

    DEFF Research Database (Denmark)

    Jakobsen, Mikkel Koefoed; Madsen, Jan; Niaki, Seyed Hosein Attarzadeh;

    , called ForSyDe. ForSyDe is available under the open Source approach, which allows small and medium enterprises (SME) to get easy access to advanced modeling capabilities and tools. We give an introduction to the design methodology through the system level modeling of a simple industrial use case, and we...

  5. Heterogeneous Cadherin Expression and Multicellular Aggregate Dynamics in Ovarian Cancer Dissemination

    Directory of Open Access Journals (Sweden)

    Yuliya Klymenko

    2017-07-01

    Full Text Available Epithelial ovarian carcinoma spreads via shedding of cells and multicellular aggregates (MCAs from the primary tumor into peritoneal cavity, with subsequent intraperitoneal tumor cell:mesothelial cell adhesion as a key early event in metastatic seeding. Evaluation of human tumor extracts and tissues confirms that well-differentiated ovarian tumors express abundant E-cadherin (Ecad, whereas advanced lesions exhibit upregulated N-cadherin (Ncad. Two expression patterns are observed: “mixed cadherin,” in which distinct cells within the same tumor express either E- or Ncad, and “hybrid cadherin,” wherein single tumor cell(s simultaneously expresses both cadherins. We demonstrate striking cadherin-dependent differences in cell-cell interactions, MCA formation, and aggregate ultrastructure. Mesenchymal-type Ncad+ cells formed stable, highly cohesive solid spheroids, whereas Ecad+ epithelial-type cells generated loosely adhesive cell clusters covered by uniform microvilli. Generation of “mixed cadherin” MCAs using fluorescently tagged cell populations revealed preferential sorting into cadherin-dependent clusters, whereas mixing of cell lines with common cadherin profiles generated homogeneous aggregates. Recapitulation of the “hybrid cadherin” Ecad+/Ncad+ phenotype, via insertion of the CDH2 gene into Ecad+ cells, resulted in the ability to form heterogeneous clusters with Ncad+ cells, significantly enhanced adhesion to organotypic mesomimetic cultures and peritoneal explants, and increased both migration and matrix invasion. Alternatively, insertion of CDH1 gene into Ncad+ cells greatly reduced cell-to-collagen, cell-to-mesothelium, and cell-to-peritoneum adhesion. Acquisition of the hybrid cadherin phenotype resulted in altered MCA surface morphology with increased surface projections and increased cell proliferation. Overall, these findings support the hypothesis that MCA cadherin composition impacts intraperitoneal cell and MCA

  6. A central regulator of morphological differentiation in the multicellular bacterium Streptomyces coelicolor.

    Science.gov (United States)

    Nguyen, Kien T; Willey, Joanne M; Nguyen, Liem D; Nguyen, Lieu T; Viollier, Patrick H; Thompson, Charles J

    2002-12-01

    In the multicellular bacterium Streptomyces coelicolor, functions of developmental (bald) genes are required for the biosynthesis of SapB, a hydrophobic peptidic morphogen that facilitates aerial hyphae formation. Here, we show that aerial hyphal growth and SapB biosynthesis could be activated independently from the normal developmental cascade by providing unprogrammed expression of functionally interactive genes within the ram cluster. ramC, ramS and ramR were essential for normal growth of aerial hyphae, and ramR, a response regulator gene, was a key activator of development. The ramR gene restored growth of aerial hyphae and SapB formation in all bald strains tested (albeit only weakly in the bldC mutant), many of which are characterized by physiological defects. Disruption of the ramR gene abolished SapB biosynthesis and severely delayed growth of aerial hyphae. Transcription of ramR was developmentally controlled, and RamR function in vivo depended on its putative phosphorylation site (D53). We identified and mapped RamR targets immediately upstream of the region encoding ramC and ramS, a putative operon. Overexpression of ramR in the wild-type strain increased SapB levels and caused a distinctive wrinkled surface topology. Based on these results, we propose that phenotypes of bald mutations reflect an early stage in the Streptomyces developmental programme similar to the spo0 mutations in the unicellular bacterium Bacillus subtilis, and that RamR has analogies to Spo0A, the Bacillus response regulator that integrates physiological signals before triggering endospore formation.

  7. Probabilistic modeling of solar power systems

    Science.gov (United States)

    Safie, Fayssal M.

    1989-01-01

    The author presents a probabilistic approach based on Markov chain theory to model stand-alone photovoltaic power systems and predict their long-term service performance. The major advantage of this approach is that it allows designers and developers of these systems to analyze the system performance as well as the battery subsystem performance in the long run and determine the system design requirements that meet a specified service performance level. The methodology presented is illustrated by using data for a radio repeater system for the Boston, Massachusetts, location.

  8. Cost and Performance Model for Photovoltaic Systems

    Science.gov (United States)

    Borden, C. S.; Smith, J. H.; Davisson, M. C.; Reiter, L. J.

    1986-01-01

    Lifetime cost and performance (LCP) model assists in assessment of design options for photovoltaic systems. LCP is simulation of performance, cost, and revenue streams associated with photovoltaic power systems connected to electric-utility grid. LCP provides user with substantial flexibility in specifying technical and economic environment of application.

  9. Economic Models and Algorithms for Distributed Systems

    CERN Document Server

    Neumann, Dirk; Altmann, Jorn; Rana, Omer F

    2009-01-01

    Distributed computing models for sharing resources such as Grids, Peer-to-Peer systems, or voluntary computing are becoming increasingly popular. This book intends to discover fresh avenues of research and amendments to existing technologies, aiming at the successful deployment of commercial distributed systems

  10. Eclectic Model in the Malaysian Education System

    Science.gov (United States)

    Othman, Nooraini; Mohamad, Khairul Azmi; Ilmuwan, Yayasan

    2011-01-01

    The present work aims at analysing the adoption of eclectic model in the Malaysian education system. The analysis is specifically looked from the angle of Islam and the Muslims. Malaysia has a long history of education system developments, from pre to post independence of the country. From what was initially traditional, modernity later came to…

  11. CTBT Integrated Verification System Evaluation Model

    Energy Technology Data Exchange (ETDEWEB)

    Edenburn, M.W.; Bunting, M.L.; Payne, A.C. Jr.

    1997-10-01

    Sandia National Laboratories has developed a computer based model called IVSEM (Integrated Verification System Evaluation Model) to estimate the performance of a nuclear detonation monitoring system. The IVSEM project was initiated in June 1994, by Sandia`s Monitoring Systems and Technology Center and has been funded by the US Department of Energy`s Office of Nonproliferation and National Security (DOE/NN). IVSEM is a simple, top-level, modeling tool which estimates the performance of a Comprehensive Nuclear Test Ban Treaty (CTBT) monitoring system and can help explore the impact of various sensor system concepts and technology advancements on CTBT monitoring. One of IVSEM`s unique features is that it integrates results from the various CTBT sensor technologies (seismic, infrasound, radionuclide, and hydroacoustic) and allows the user to investigate synergy among the technologies. Specifically, IVSEM estimates the detection effectiveness (probability of detection) and location accuracy of the integrated system and of each technology subsystem individually. The model attempts to accurately estimate the monitoring system`s performance at medium interfaces (air-land, air-water) and for some evasive testing methods such as seismic decoupling. This report describes version 1.2 of IVSEM.

  12. Fem Modelling of Lumbar Vertebra System

    Directory of Open Access Journals (Sweden)

    Rimantas Kačianauskas

    2014-02-01

    Full Text Available The article presents modeling of human lumbar vertebra and it‘sdeformation analysis using finite elements method. The problemof tissue degradation is raised. Using the computer aided modelingwith SolidWorks software the models of lumbar vertebra(L1 and vertebra system L1-L4 were created. The article containssocial and medical problem analysis, description of modelingmethods and the results of deformation test for one vertebramodel and for model of 4 vertebras (L1-L4.

  13. Power electronics system modeling and simulation

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Jih-Sheng

    1994-12-31

    This paper introduces control system design based softwares, SIMNON and MATLAB/SIMULINK, for power electronics system simulation. A complete power electronics system typically consists of a rectifier bridge along with its smoothing capacitor, an inverter, and a motor. The system components, featuring discrete or continuous, linear or nonlinear, are modeled in mathematical equations. Inverter control methods,such as pulse-width-modulation and hysteresis current control, are expressed in either computer algorithms or digital circuits. After describing component models and control methods, computer programs are then developed for complete systems simulation. Simulation results are mainly used for studying system performances, such as input and output current harmonics, torque ripples, and speed responses. Key computer programs and simulation results are demonstrated for educational purposes.

  14. Modelling and control of dynamic systems using gaussian process models

    CERN Document Server

    Kocijan, Juš

    2016-01-01

    This monograph opens up new horizons for engineers and researchers in academia and in industry dealing with or interested in new developments in the field of system identification and control. It emphasizes guidelines for working solutions and practical advice for their implementation rather than the theoretical background of Gaussian process (GP) models. The book demonstrates the potential of this recent development in probabilistic machine-learning methods and gives the reader an intuitive understanding of the topic. The current state of the art is treated along with possible future directions for research. Systems control design relies on mathematical models and these may be developed from measurement data. This process of system identification, when based on GP models, can play an integral part of control design in data-based control and its description as such is an essential aspect of the text. The background of GP regression is introduced first with system identification and incorporation of prior know...

  15. Chain modeling for life cycle systems engineering

    Energy Technology Data Exchange (ETDEWEB)

    Rivera, J.J. [Sandia National Lab., Albuquerque, NM (United States); Shapiro, V. [Univ. of Wisconsin, Madison, WI (United States). Spatial Automation Lab.

    1997-12-01

    Throughout Sandia`s history, products have been represented by drawings. Solid modeling systems have recently replaced drawings as the preferred means for representing product geometry. These systems are used for product visualization, engineering analysis and manufacturing planning. Unfortunately, solid modeling technology is inadequate for life cycle systems engineering, which requires maintenance of technical history, efficient management of geometric and non-geometric data, and explicit representation of engineering and manufacturing characteristics. Such information is not part of the mathematical foundation of solid modeling. The current state-of-the-art in life cycle engineering is comprised of painstakingly created special purpose tools, which often are incompatible. New research on {open_quotes}chain modeling{close_quotes} provides a method of chaining the functionality of a part to the geometric representation. Chain modeling extends classical solid modeling to include physical, manufacturing, and procedural information required for life cycle engineering. In addition, chain modeling promises to provide the missing theoretical basis for Sandia`s parent/child product realization paradigm. In chain modeling, artifacts and systems are characterized in terms of their combinatorial properties: cell complexes, chains, and their operators. This approach is firmly rooted in algebraic topology and is a natural extension of current technology. The potential benefits of this approach include explicit hierarchical and combinatorial representation of physics, geometry, functionality, test, and legacy data in a common computational framework that supports a rational decision process and partial design automation. Chain modeling will have a significant impact on design preservation, system identification, parameterization, system reliability, and design simplification.

  16. World energy projection system: Model documentation

    Energy Technology Data Exchange (ETDEWEB)

    1992-06-01

    The World Energy Project System (WEPS) is an accounting framework that incorporates projects from independently documented models and assumptions about the future energy intensity of economic activity (ratios of total energy consumption divided by gross domestic product) and about the rate of incremental energy requirements met by hydropower, geothermal, coal, and natural gas to produce projections of world energy consumption published annually by the Energy Information Administration (EIA) in the International Energy Outlook (IEO) (Figure 1). Two independently documented models presented in Figure 1, the Oil Market Simulation (OMS) model and the World Integrated Nuclear Evaluation System (WINES) provide projections of oil and nuclear power consumption published in the IEO. Output from a third independently documented model, and the International Coal Trade Model (ICTM), is not published in the IEO but is used in WEPS as a supply check on projections of world coal consumption produced by WEPS and published in the IEO. A WEPS model of natural gas production documented in this report provides the same type of implicit supply check on the WEPS projections of world natural gas consumption published in the IEO. Two additional models are included in Figure 1, the OPEC Capacity model and the Non-OPEC Oil Production model. These WEPS models provide inputs to the OMS model and are documented in this report.

  17. Systemic change increases model projection uncertainty

    Science.gov (United States)

    Verstegen, Judith; Karssenberg, Derek; van der Hilst, Floor; Faaij, André

    2014-05-01

    Most spatio-temporal models are based on the assumption that the relationship between system state change and its explanatory processes is stationary. This means that model structure and parameterization are usually kept constant over time, ignoring potential systemic changes in this relationship resulting from e.g., climatic or societal changes, thereby overlooking a source of uncertainty. We define systemic change as a change in the system indicated by a system state change that cannot be simulated using a constant model structure. We have developed a method to detect systemic change, using a Bayesian data assimilation technique, the particle filter. The particle filter was used to update the prior knowledge about the model structure. In contrast to the traditional particle filter approach (e.g., Verstegen et al., 2014), we apply the filter separately for each point in time for which observations are available, obtaining the optimal model structure for each of the time periods in between. This allows us to create a time series of the evolution of the model structure. The Runs test (Wald and Wolfowitz, 1940), a stationarity test, is used to check whether variation in this time series can be attributed to randomness or not. If not, this indicates systemic change. The uncertainty that the systemic change adds to the existing model projection uncertainty can be determined by comparing model outcomes of a model with a stationary model structure and a model with a model structure changing according to the variation found in the time series. To test the systemic change detection methodology, we apply it to a land use change cellular automaton (CA) (Verstegen et al., 2012) and use observations of real land use from all years from 2004 to 2012 and associated uncertainty as observational data in the particle filter. A systemic change was detected for the period 2006 to 2008. In this period the influence on the location of sugar cane expansion of the driver sugar cane in

  18. Information systems validation using formal models

    Directory of Open Access Journals (Sweden)

    Azadeh Sarram

    2014-03-01

    Full Text Available During the past few years, there has been growing interest to use unified modeling language (UML to consider the functional requirements. However, lacking a tool to detect the accuracy and the logic of diagrams in this language makes a formal model indispensable. In this study, conversion of primary UML model of a system to a colored Petri net has been accomplished in order to examine the precision of the model. For this purpose, first the definition of priority and implementation tags for UML activity diagram are provided; then it is turned into colored Petri net. Second, the proposed model provides translated tags in terms of net transitions and some monitoring are used to control the system characteristics. Finally, an executable model of UML activity diagram is provided so that the designer could simulate the model by using the simulation results to detect and to refine the problems of the model. In addition, by checking the results, we find out the proposed method enhances authenticity and accuracy of early models and the ratio of system validation increases compared with previous methods.

  19. Security Communication Model of Wireless Trade System

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wen-kai; ZHANG Si-yu

    2005-01-01

    This paper proposes a C/S system model for K Java and PDA named Net-Wireless. It is a discussion and proposal on information security and solutions for K-Java handsets and PDAs in wireless network. It also explains the scheme which between client security module and server security module. Also, We have developed a Security Server and a K-Java encryption module for e-commerce system and other trade systems.

  20. Expert System Model for Educational Personnel Selection

    Directory of Open Access Journals (Sweden)

    Héctor A. Tabares-Ospina

    2013-06-01

    Full Text Available The staff selection is a difficult task due to the subjectivity that the evaluation means. This process can be complemented using a system to support decision. This paper presents the implementation of an expert system to systematize the selection process of professors. The management of software development is divided into 4 parts: requirements, design, implementation and commissioning. The proposed system models a specific knowledge through relationships between variables evidence and objective.