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Sample records for outage-limited cellular network

  1. MSAT and cellular hybrid networking

    NASA Technical Reports Server (NTRS)

    Baranowsky, Patrick W., II

    1993-01-01

    Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

  2. Predicting and Analyzing Cellular Networks

    NASA Astrophysics Data System (ADS)

    Singh, Mona

    High-throughput experimental technologies, along with computational predictions, have resulted in large-scale biological networks for numerous organisms. Global analyses of biological networks provide new opportunities for revealing protein functions and pathways, and for uncovering cellular organization principles. In my talk, I will discuss a number of approaches we have developed over the years for the complementary problems of predicting interactions and analyzing interaction networks. First, I will describe a genomic approach for uncovering high-confidence regulatory interactions, and show how it can be effectively combined with a framework for predicting regulatory interactions for proteins with known structural domains but unknown binding specificity. Next, I will describe algorithms for analyzing protein interaction networks in order to uncover protein function and functional modules, and demonstrate the importance of considering the topological structure of interaction networks in order to make high quality predictions. Finally, I will present a framework for explicitly incorporating known attributes of individual proteins into the analysis of biological networks, and utilize it to discover recurring network patterns underlying a range of biological processes.

  3. Micromechanics of cellularized biopolymer networks

    PubMed Central

    Jones, Christopher A. R.; Cibula, Matthew; Feng, Jingchen; Krnacik, Emma A.; McIntyre, David H.; Levine, Herbert; Sun, Bo

    2015-01-01

    Collagen gels are widely used in experiments on cell mechanics because they mimic the extracellular matrix in physiological conditions. Collagen gels are often characterized by their bulk rheology; however, variations in the collagen fiber microstructure and cell adhesion forces cause the mechanical properties to be inhomogeneous at the cellular scale. We study the mechanics of type I collagen on the scale of tens to hundreds of microns by using holographic optical tweezers to apply pN forces to microparticles embedded in the collagen fiber network. We find that in response to optical forces, particle displacements are inhomogeneous, anisotropic, and asymmetric. Gels prepared at 21 °C and 37 °C show qualitative difference in their micromechanical characteristics. We also demonstrate that contracting cells remodel the micromechanics of their surrounding extracellular matrix in a strain- and distance-dependent manner. To further understand the micromechanics of cellularized extracellular matrix, we have constructed a computational model which reproduces the main experiment findings. PMID:26324923

  4. Aging cellular networks: chaperones as major participants.

    PubMed

    Soti, C; Csermely, P

    2007-01-01

    We increasingly rely on the network approach to understand the complexity of cellular functions. Chaperones (heat shock proteins) are key "networkers", which sequester and repair damaged proteins. In order to link the network approach and chaperones with the aging process, we first summarize the properties of aging networks suggesting a "weak link theory of aging". This theory suggests that age-related random damage primarily affects the overwhelming majority of the low affinity, transient interactions (weak links) in cellular networks leading to increased noise, destabilization and diversity. These processes may be further amplified by age-specific network remodelling and by the sequestration of weakly linked cellular proteins to protein aggregates of aging cells. Chaperones are weakly linked hubs (i.e., network elements with a large number of connections) and inter-modular bridge elements of protein-protein interaction, signalling and mitochondrial networks. As aging proceeds, the increased overload of damaged proteins is an especially important element contributing to cellular disintegration and destabilization. Additionally, chaperone overload may contribute to the increase of "noise" in aging cells, which leads to an increased stochastic resonance resulting in a deficient discrimination between signals and noise. Chaperone- and other multi-target therapies, which restore the missing weak links in aging cellular networks, may emerge as important anti-aging interventions. PMID:16814508

  5. Stability of Stochastic Neutral Cellular Neural Networks

    NASA Astrophysics Data System (ADS)

    Chen, Ling; Zhao, Hongyong

    In this paper, we study a class of stochastic neutral cellular neural networks. By constructing a suitable Lyapunov functional and employing the nonnegative semi-martingale convergence theorem we give some sufficient conditions ensuring the almost sure exponential stability of the networks. The results obtained are helpful to design stability of networks when stochastic noise is taken into consideration. Finally, two examples are provided to show the correctness of our analysis.

  6. Inferring cellular networks – a review

    PubMed Central

    Markowetz, Florian; Spang, Rainer

    2007-01-01

    In this review we give an overview of computational and statistical methods to reconstruct cellular networks. Although this area of research is vast and fast developing, we show that most currently used methods can be organized by a few key concepts. The first part of the review deals with conditional independence models including Gaussian graphical models and Bayesian networks. The second part discusses probabilistic and graph-based methods for data from experimental interventions and perturbations. PMID:17903286

  7. Heterogeneous Force Chains in Cellularized Biopolymer Network

    NASA Astrophysics Data System (ADS)

    Liang, Long; Jones, Christopher Allen Rucksack; Sun, Bo; Jiao, Yang

    Biopolymer Networks play an important role in coordinating and regulating collective cellular dynamics via a number of signaling pathways. Here, we investigate the mechanical response of a model biopolymer network due to the active contraction of embedded cells. Specifically, a graph (bond-node) model derived from confocal microscopy data is used to represent the network microstructure, and cell contraction is modeled by applying correlated displacements at specific nodes, representing the focal adhesion sites. A force-based stochastic relaxation method is employed to obtain force-balanced network under cell contraction. We find that the majority of the forces are carried by a small number of heterogeneous force chains emerged from the contracting cells. The force chains consist of fiber segments that either possess a high degree of alignment before cell contraction or are aligned due to the reorientation induced by cell contraction. Large fluctuations of the forces along different force chains are observed. Importantly, the decay of the forces along the force chains is significantly slower than the decay of radially averaged forces in the system, suggesting that the fibreous nature of biopolymer network structure could support long-range mechanical signaling between cells.

  8. Cellular automata modelling of biomolecular networks dynamics.

    PubMed

    Bonchev, D; Thomas, S; Apte, A; Kier, L B

    2010-01-01

    The modelling of biological systems dynamics is traditionally performed by ordinary differential equations (ODEs). When dealing with intracellular networks of genes, proteins and metabolites, however, this approach is hindered by network complexity and the lack of experimental kinetic parameters. This opened the field for other modelling techniques, such as cellular automata (CA) and agent-based modelling (ABM). This article reviews this emerging field of studies on network dynamics in molecular biology. The basics of the CA technique are discussed along with an extensive list of related software and websites. The application of CA to networks of biochemical reactions is exemplified in detail by the case studies of the mitogen-activated protein kinase (MAPK) signalling pathway, the FAS-ligand (FASL)-induced and Bcl-2-related apoptosis. The potential of the CA method to model basic pathways patterns, to identify ways to control pathway dynamics and to help in generating strategies to fight with cancer is demonstrated. The different line of CA applications presented includes the search for the best-performing network motifs, an analysis of importance for effective intracellular signalling and pathway cross-talk. PMID:20373215

  9. Optimal flux patterns in cellular metabolic networks

    SciTech Connect

    Almaas, E

    2007-01-20

    The availability of whole-cell level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy-tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations have relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reaction are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central-carbon metabolic pathways for the sample of random environments.

  10. Optimal flux patterns in cellular metabolic networks

    NASA Astrophysics Data System (ADS)

    Almaas, Eivind

    2007-06-01

    The availability of whole-cell-level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate the metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30 000 random cellular environments. The distribution of reaction fluxes is heavy tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations has relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reactions are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central carbon metabolic pathways for the sample of random environments.

  11. A Wireless Communications Laboratory on Cellular Network Planning

    ERIC Educational Resources Information Center

    Dawy, Z.; Husseini, A.; Yaacoub, E.; Al-Kanj, L.

    2010-01-01

    The field of radio network planning and optimization (RNPO) is central for wireless cellular network design, deployment, and enhancement. Wireless cellular operators invest huge sums of capital on deploying, launching, and maintaining their networks in order to ensure competitive performance and high user satisfaction. This work presents a lab…

  12. Optimizing Cellular Networks Enabled with Renewal Energy via Strategic Learning.

    PubMed

    Sohn, Insoo; Liu, Huaping; Ansari, Nirwan

    2015-01-01

    An important issue in the cellular industry is the rising energy cost and carbon footprint due to the rapid expansion of the cellular infrastructure. Greening cellular networks has thus attracted attention. Among the promising green cellular network techniques, the renewable energy-powered cellular network has drawn increasing attention as a critical element towards reducing carbon emissions due to massive energy consumption in the base stations deployed in cellular networks. Game theory is a branch of mathematics that is used to evaluate and optimize systems with multiple players with conflicting objectives and has been successfully used to solve various problems in cellular networks. In this paper, we model the green energy utilization and power consumption optimization problem of a green cellular network as a pilot power selection strategic game and propose a novel distributed algorithm based on a strategic learning method. The simulation results indicate that the proposed algorithm achieves correlated equilibrium of the pilot power selection game, resulting in optimum green energy utilization and power consumption reduction. PMID:26167934

  13. Optimizing Cellular Networks Enabled with Renewal Energy via Strategic Learning

    PubMed Central

    Sohn, Insoo; Liu, Huaping; Ansari, Nirwan

    2015-01-01

    An important issue in the cellular industry is the rising energy cost and carbon footprint due to the rapid expansion of the cellular infrastructure. Greening cellular networks has thus attracted attention. Among the promising green cellular network techniques, the renewable energy-powered cellular network has drawn increasing attention as a critical element towards reducing carbon emissions due to massive energy consumption in the base stations deployed in cellular networks. Game theory is a branch of mathematics that is used to evaluate and optimize systems with multiple players with conflicting objectives and has been successfully used to solve various problems in cellular networks. In this paper, we model the green energy utilization and power consumption optimization problem of a green cellular network as a pilot power selection strategic game and propose a novel distributed algorithm based on a strategic learning method. The simulation results indicate that the proposed algorithm achieves correlated equilibrium of the pilot power selection game, resulting in optimum green energy utilization and power consumption reduction. PMID:26167934

  14. Extracting insight from noisy cellular networks.

    PubMed

    Landry, Christian R; Levy, Emmanuel D; Abd Rabbo, Diala; Tarassov, Kirill; Michnick, Stephen W

    2013-11-21

    Network biologists attempt to extract meaningful relationships among genes or their products from very noisy data. We argue that what we categorize as noisy data may sometimes reflect noisy biology and therefore may shield a hidden meaning about how networks evolve and how matter is organized in the cell. We present practical solutions, based on existing evolutionary and biophysical concepts, through which our understanding of cell biology can be enormously enriched. PMID:24267884

  15. Energy efficiency analysis of relay-assisted cellular networks

    NASA Astrophysics Data System (ADS)

    Yu, Huan; Li, Yunzhou; Kountouris, Marios; Xu, Xibin; Wang, Jing

    2014-12-01

    To meet the demand for higher throughput, improved coverage and enhanced reliability, future wireless cellular networks face significant technical challenges. One promising solution is to place relay stations between transmitters and receivers in the cellular network. Meanwhile, as energy consumption reduction has been an important concern for the wireless industry, energy-efficient communications is of prime interest for future networks. In this paper, we study whether and how relays can improve the energy efficiency of cellular networks. Specifically, the energy efficiency of relay-assisted cellular networks is analyzed using tools of stochastic geometry. We first derive the coverage probability for the macro base station (MBS) to user (UE), the MBS to relay station (RS), and the RS to UE links, and then we model the power consumption at the MBS and RS. Based on the analytical model and expressions, the energy efficiency of relay-assisted cellular networks is then evaluated and is shown to be strictly quasi-concave on the transmit power for MBS to UE link or the RS to UE link. Numerical results show that the energy efficiency first improves while it hits a ceiling as the MBS density increases.

  16. A new small-world network created by Cellular Automata

    NASA Astrophysics Data System (ADS)

    Ruan, Yuhong; Li, Anwei

    2016-08-01

    In this paper, we generate small-world networks by the Cellular Automaton based on starting with one-dimensional regular networks. Besides the common properties of small-world networks with small average shortest path length and large clustering coefficient, the small-world networks generated in this way have other properties: (i) The edges which are cut in the regular network can be controlled that whether the edges are reconnected or not, and (ii) the number of the edges of the small-world network model equals the number of the edges of the original regular network. In other words, the average degree of the small-world network model equals to the average degree of the original regular network.

  17. Optimal Prediction by Cellular Signaling Networks

    NASA Astrophysics Data System (ADS)

    Becker, Nils B.; Mugler, Andrew; ten Wolde, Pieter Rein

    2015-12-01

    Living cells can enhance their fitness by anticipating environmental change. We study how accurately linear signaling networks in cells can predict future signals. We find that maximal predictive power results from a combination of input-noise suppression, linear extrapolation, and selective readout of correlated past signal values. Single-layer networks generate exponential response kernels, which suffice to predict Markovian signals optimally. Multilayer networks allow oscillatory kernels that can optimally predict non-Markovian signals. At low noise, these kernels exploit the signal derivative for extrapolation, while at high noise, they capitalize on signal values in the past that are strongly correlated with the future signal. We show how the common motifs of negative feedback and incoherent feed-forward can implement these optimal response functions. Simulations reveal that E. coli can reliably predict concentration changes for chemotaxis, and that the integration time of its response kernel arises from a trade-off between rapid response and noise suppression.

  18. Stochastic cellular automata model of neural networks.

    PubMed

    Goltsev, A V; de Abreu, F V; Dorogovtsev, S N; Mendes, J F F

    2010-06-01

    We propose a stochastic dynamical model of noisy neural networks with complex architectures and discuss activation of neural networks by a stimulus, pacemakers, and spontaneous activity. This model has a complex phase diagram with self-organized active neural states, hybrid phase transitions, and a rich array of behaviors. We show that if spontaneous activity (noise) reaches a threshold level then global neural oscillations emerge. Stochastic resonance is a precursor of this dynamical phase transition. These oscillations are an intrinsic property of even small groups of 50 neurons. PMID:20866454

  19. Personal communication in traditional cellular networks

    NASA Astrophysics Data System (ADS)

    Neuer, Ellwood I.

    1996-01-01

    The purpose of this paper is to describe the flow of calls through the mobile network as it applies to the operation of Basic and Enhanced Services. Included in the discussion is the overall network layout, the physical connections between the network entities, and the signaling protocols which allow the entities to be integrated. The specific functionality of the applications and services are not detailed as the specific implementation varies from vendor to vendor and from service provider to service provider. The Enhanced Services Platform is installed in a service providers network in order to offer mobile subscribers services and applications which would otherwise not be available. The service providers' objective is to increase revenue/subscriber, increase subscriber loyalty/decrease churn, and build competitive advantages through differentiation. The services provided on the Enhanced Services platform can be viewed as either Basic or Enhanced. For the purpose of this paper, Basic Services refers to Numeric Paging, Call Answering, and Voice Messaging while Enhanced Services refers to FAX Messaging, One Number Service, Voice Dialing and other Voice Recognition applications, Information Services including FAX on Demand, and Automated Call Routing.

  20. Increasing cellular coverage within integrated terrestrial/satellite mobile networks

    NASA Technical Reports Server (NTRS)

    Castro, Jonathan P.

    1995-01-01

    When applying the hierarchical cellular concept, the satellite acts as giant umbrella cell covering a region with some terrestrial cells. If a mobile terminal traversing the region arrives to the border-line or limits of a regular cellular ground service, network transition occurs and the satellite system continues the mobile coverage. To adequately assess the boundaries of service of a mobile satellite system an a cellular network within an integrated environment, this paper provides an optimized scheme to predict when a network transition may be necessary. Under the assumption of a classified propagation phenomenon and Lognormal shadowing, the study applies an analytical approach to estimate the location of a mobile terminal based on a reception of the signal strength emitted by a base station.

  1. Optimising base station location for UMTS cellular networks

    NASA Astrophysics Data System (ADS)

    Kalata, G.; Pozniak-Koszalka, I.; Koszalka, L.; Kasprzak, A.

    2014-12-01

    Rapid development of universal mobile telecommunication systems put demands on tools for assisting planning of cellular network infrastructure. The tools need to focus on critical issues in modern cellular networks and techniques used for previous generation system no longer serve useful. In this paper, an algorithm based on Branch & Bound approach is proposed for solving base station location problem, covering interference levels, traffic demands and power control mechanism. The efficiency of the algorithm is evaluated with respect to existing approaches for solving this problem - using the designed and implemented experimentation system.

  2. Millimeter-Wave Evolution for 5G Cellular Networks

    NASA Astrophysics Data System (ADS)

    Sakaguchi, Kei; Tran, Gia Khanh; Shimodaira, Hidekazu; Nanba, Shinobu; Sakurai, Toshiaki; Takinami, Koji; Siaud, Isabelle; Strinati, Emilio Calvanese; Capone, Antonio; Karls, Ingolf; Arefi, Reza; Haustein, Thomas

    Triggered by the explosion of mobile traffic, 5G (5th Generation) cellular network requires evolution to increase the system rate 1000 times higher than the current systems in 10 years. Motivated by this common problem, there are several studies to integrate mm-wave access into current cellular networks as multi-band heterogeneous networks to exploit the ultra-wideband aspect of the mm-wave band. The authors of this paper have proposed comprehensive architecture of cellular networks with mm-wave access, where mm-wave small cell basestations and a conventional macro basestation are connected to Centralized-RAN (C-RAN) to effectively operate the system by enabling power efficient seamless handover as well as centralized resource control including dynamic cell structuring to match the limited coverage of mm-wave access with high traffic user locations via user-plane/control-plane splitting. In this paper, to prove the effectiveness of the proposed 5G cellular networks with mm-wave access, system level simulation is conducted by introducing an expected future traffic model, a measurement based mm-wave propagation model, and a centralized cell association algorithm by exploiting the C-RAN architecture. The numerical results show the effectiveness of the proposed network to realize 1000 times higher system rate than the current network in 10 years which is not achieved by the small cells using commonly considered 3.5 GHz band. Furthermore, the paper also gives latest status of mm-wave devices and regulations to show the feasibility of using mm-wave in the 5G systems.

  3. Cellular neural networks for welding arc thermograms segmentation

    NASA Astrophysics Data System (ADS)

    Jamrozik, Wojciech

    2014-09-01

    Machine vision systems are used in many areas for monitoring of technological processes. Among this processes welding takes important place, where often infrared cameras are used. Besides reliable hardware, successful application of vision systems requires suitable software based on proper algorithms. One of most important group of image processing algorithms is connected to image segmentation. Obtainment of exact boundary of an object that changes shape in time, such as the welding arc, represented on a thermogram is not a trivial task. In the paper a segmentation method using supervised approach based on a cellular neural networks is presented. Simulated annealing and genetic algorithm were used for training of the network (template optimization). Comparison of proposed method to a well elaborated segmentation method based on region growing approach was made. Obtained results prove that the cellular neural network can be a valuable tool for infrared welding pool images segmentation.

  4. The role of actin networks in cellular mechanosensing

    NASA Astrophysics Data System (ADS)

    Azatov, Mikheil

    Physical processes play an important role in many biological phenomena, such as wound healing, organ development, and tumor metastasis. During these processes, cells constantly interact with and adapt to their environment by exerting forces to mechanically probe the features of their surroundings and generating appropriate biochemical responses. The mechanisms underlying how cells sense the physical properties of their environment are not well understood. In this thesis, I present my studies to investigate cellular responses to the stiffness and topography of the environment. In order to sense the physical properties of their environment, cells dynamically reorganize the structure of their actin cytoskeleton, a dynamic network of biopolymers, altering the shape and spatial distribution of protein assemblies. Several observations suggest that proteins that crosslink actin filaments may play an important role in cellular mechanosensitivity. Palladin is an actin-crosslinking protein that is found in the lamellar actin network, stress fibers and focal adhesions, cellular structures that are critical for mechanosensing of the physical environment. By virtue of its close interactions with these structures in the cell, palladin may play an important role in cell mechanics. However, the role of actin crosslinkers in general, and palladin in particular, in cellular force generation and mechanosensing is not well known. I have investigated the role of palladin in regulating the plasticity of the actin cytoskeleton and cellular force generation in response to alterations in substrate stiffness. I have shown that the expression levels of palladin modulate the forces exerted by cells and their ability to sense substrate stiffness. Perturbation experiments also suggest that palladin levels in cells altered myosin motor activity. These results suggest that the actin crosslinkers, such as palladin, and myosin motors coordinate for optimal cell function and to prevent aberrant

  5. Using Cellular Communication Networks To Detect Air Pollution.

    PubMed

    David, Noam; Gao, H Oliver

    2016-09-01

    Accurate real time monitoring of atmospheric conditions at ground level is vital for hazard warning, meteorological forecasting, and various environmental applications required for public health and safety. However, conventional monitoring facilities are costly and often insufficient, for example, since they are not representative of the larger space and are not deployed densely enough in the field. There have been numerous scientific works showing the ability of commercial microwave links that comprise the data transmission infrastructure in cellular communication networks to monitor hydrometeors as a potential complementary solution. However, despite the large volume of research carried out in this emerging field during the past decade, no study has shown the ability of the system to provide critical information regarding air quality. Here we reveal the potential for identifying atmospheric conditions prone to air pollution by detecting temperature inversions that trap pollutants at ground level. The technique is based on utilizing standard signal measurements from an existing cellular network during routine operation. PMID:27490182

  6. Analysing Dynamical Behavior of Cellular Networks via Stochastic Bifurcations

    PubMed Central

    Zakharova, Anna; Kurths, Jürgen; Vadivasova, Tatyana; Koseska, Aneta

    2011-01-01

    The dynamical structure of genetic networks determines the occurrence of various biological mechanisms, such as cellular differentiation. However, the question of how cellular diversity evolves in relation to the inherent stochasticity and intercellular communication remains still to be understood. Here, we define a concept of stochastic bifurcations suitable to investigate the dynamical structure of genetic networks, and show that under stochastic influence, the expression of given proteins of interest is defined via the probability distribution of the phase variable, representing one of the genes constituting the system. Moreover, we show that under changing stochastic conditions, the probabilities of expressing certain concentration values are different, leading to different functionality of the cells, and thus to differentiation of the cells in the various types. PMID:21647432

  7. Performance evaluation of cellular phone network based portable ECG device.

    PubMed

    Hong, Joo-Hyun; Cha, Eun-Jong; Lee, Tae-Soo

    2008-01-01

    In this study, cellular phone network based portable ECG device was developed and three experiments were performed to evaluate the accuracy, reliability and operability, applicability during daily life of the developed device. First, ECG signals were measured using the developed device and Biopac device (reference device) during sitting and marking time and compared to verify the accuracy of R-R intervals. Second, the reliable data transmission to remote server was verified on two types of simulated emergency event using patient simulator. Third, during daily life with five types of motion, accuracy of data transmission to remote server was verified on two types of event occurring. By acquiring and comparing subject's biomedical signal and motion signal, the accuracy, reliability and operability, applicability during daily life of the developed device were verified. Therefore, cellular phone network based portable ECG device can monitor patient with inobtrusive manner. PMID:19162767

  8. Cellular Automata with network incubation in information technology diffusion

    NASA Astrophysics Data System (ADS)

    Guseo, Renato; Guidolin, Mariangela

    2010-06-01

    Innovation diffusion of network goods determines direct network externalities that depress sales for long periods and delay full benefits. We model this effect through a multiplicative dynamic market potential driven by a latent individual threshold embedded in a special Cellular Automata representation. The corresponding mean field approximation of its aggregate version is a Riccati equation with a closed form solution. This allows the detection of a change-point time separating an incubation period from a subsequent take-off due to a collective threshold (critical mass). Weighted nonlinear least squares are the main inferential methodology. An application is analysed with reference to USA fax machine diffusion.

  9. Ion beam analysis based on cellular nonlinear networks

    NASA Astrophysics Data System (ADS)

    Senger, V.; Tetzlaff, R.; Reichau, H.; Ratzinger, U.

    2011-07-01

    The development of a non- destructive measurement method for ion beam parameters has been treated in various projects. Although results are promising, the high complexity of beam dynamics has made it impossible to implement a real time process control up to now. In this paper we will propose analysing methods based on the dynamics of Cellular Nonlinear Networks (CNN) that can be implemented on pixel parallel CNN based architectures and yield satisfying results even at low resolutions.

  10. Network Medicine: From Cellular Networks to the Human Diseasome

    NASA Astrophysics Data System (ADS)

    Barabasi, Albert-Laszlo

    2014-03-01

    Given the functional interdependencies between the molecular components in a human cell, a disease is rarely a consequence of an abnormality in a single gene, but reflects the perturbations of the complex intracellular network. The tools of network science offer a platform to explore systematically not only the molecular complexity of a particular disease, leading to the identification of disease modules and pathways, but also the molecular relationships between apparently distinct (patho)phenotypes. Advances in this direction not only enrich our understanding of complex systems, but are also essential to identify new disease genes, to uncover the biological significance of disease-associated mutations identified by genome-wide association studies and full genome sequencing, and to identify drug targets and biomarkers for complex diseases.

  11. Tensegrity II. How structural networks influence cellular information processing networks

    NASA Technical Reports Server (NTRS)

    Ingber, Donald E.

    2003-01-01

    The major challenge in biology today is biocomplexity: the need to explain how cell and tissue behaviors emerge from collective interactions within complex molecular networks. Part I of this two-part article, described a mechanical model of cell structure based on tensegrity architecture that explains how the mechanical behavior of the cell emerges from physical interactions among the different molecular filament systems that form the cytoskeleton. Recent work shows that the cytoskeleton also orients much of the cell's metabolic and signal transduction machinery and that mechanical distortion of cells and the cytoskeleton through cell surface integrin receptors can profoundly affect cell behavior. In particular, gradual variations in this single physical control parameter (cell shape distortion) can switch cells between distinct gene programs (e.g. growth, differentiation and apoptosis), and this process can be viewed as a biological phase transition. Part II of this article covers how combined use of tensegrity and solid-state mechanochemistry by cells may mediate mechanotransduction and facilitate integration of chemical and physical signals that are responsible for control of cell behavior. In addition, it examines how cell structural networks affect gene and protein signaling networks to produce characteristic phenotypes and cell fate transitions during tissue development.

  12. Hybrid Spectral Efficient Cellular Network Deployment to Reduce RF Pollution

    NASA Astrophysics Data System (ADS)

    Katiyar, Sumit; K. Jain, R.; K. Agrawal, N.

    2012-09-01

    As the mobile telecommunication systems are growing tremendously all over the world, the numbers of handheld and base stations are also rapidly growing and it became very popular to see these base stations distributed everywhere in the neighborhood and on roof tops which has caused a considerable amount of panic to the public in Palestine concerning wither the radiated electromagnetic fields from these base stations may cause any health effect or hazard. Recently UP High Court in India ordered for removal of BTS towers from residential area, it has created panic among cellular communication network designers too. Green cellular networks could be a solution for the above problem. This paper deals with green cellular networks with the help of multi-layer overlaid hierarchical structure (macro / micro / pico / femto cells). Macrocell for area coverage, micro for pedestrian and a slow moving traffic while pico for indoor use and femto for individual high capacity users. This could be the answer of the problem of energy conservation and enhancement of spectral density also.

  13. ATR inhibition rewires cellular signaling networks induced by replication stress.

    PubMed

    Wagner, Sebastian A; Oehler, Hannah; Voigt, Andrea; Dalic, Denis; Freiwald, Anja; Serve, Hubert; Beli, Petra

    2016-02-01

    The slowing down or stalling of replication forks is commonly known as replication stress and arises from multiple causes such as DNA lesions, nucleotide depletion, RNA-DNA hybrids, and oncogene activation. The ataxia telangiectasia and Rad3-related kinase (ATR) plays an essential role in the cellular response to replication stress and inhibition of ATR has emerged as therapeutic strategy for the treatment of cancers that exhibit high levels of replication stress. However, the cellular signaling induced by replication stress and the substrate spectrum of ATR has not been systematically investigated. In this study, we employed quantitative MS-based proteomics to define the cellular signaling after nucleotide depletion-induced replication stress and replication fork collapse following ATR inhibition. We demonstrate that replication stress results in increased phosphorylation of a subset of proteins, many of which are involved in RNA splicing and transcription and have previously not been associated with the cellular replication stress response. Furthermore, our data reveal the ATR-dependent phosphorylation following replication stress and discover novel putative ATR target sites on MCM6, TOPBP1, RAD51AP1, and PSMD4. We establish that ATR inhibition rewires cellular signaling networks induced by replication stress and leads to the activation of the ATM-driven double-strand break repair signaling. PMID:26572502

  14. Distinctive Behaviors of Druggable Proteins in Cellular Networks

    PubMed Central

    Workman, Paul; Al-Lazikani, Bissan

    2015-01-01

    The interaction environment of a protein in a cellular network is important in defining the role that the protein plays in the system as a whole, and thus its potential suitability as a drug target. Despite the importance of the network environment, it is neglected during target selection for drug discovery. Here, we present the first systematic, comprehensive computational analysis of topological, community and graphical network parameters of the human interactome and identify discriminatory network patterns that strongly distinguish drug targets from the interactome as a whole. Importantly, we identify striking differences in the network behavior of targets of cancer drugs versus targets from other therapeutic areas and explore how they may relate to successful drug combinations to overcome acquired resistance to cancer drugs. We develop, computationally validate and provide the first public domain predictive algorithm for identifying druggable neighborhoods based on network parameters. We also make available full predictions for 13,345 proteins to aid target selection for drug discovery. All target predictions are available through canSAR.icr.ac.uk. Underlying data and tools are available at https://cansar.icr.ac.uk/cansar/publications/druggable_network_neighbourhoods/. PMID:26699810

  15. Network Coordinated Opportunistic Beamforming in Downlink Cellular Networks

    NASA Astrophysics Data System (ADS)

    Shin, Won-Yong; Jung, Bang Chul

    We propose a network coordinated opportunistic beamforming (NC-OBF) protocol for downlink K-cell networks with M-antenna base stations (BSs). In the NC-OBF scheme, based on pseudo-randomly generated BF vectors, a user scheduling strategy is introduced, where each BS opportunistically selects a set of mobile stations (MSs) whose desired signals generate the minimum interference to the other MSs. Its performance is then analyzed in terms of degrees-of-freedom (DoFs). As our achievability result, it is shown that KM DoFs are achievable if the number N of MSs in a cell scales at least as SNRKM-1, where SNR denotes the received signal-to-noise ratio. Furthermore, by deriving the corresponding upper bound on the DoFs, it is shown that the NC-OBF scheme is DoF-optimal. Note that the proposed scheme does not require the global channel state information and dimension expansion, thereby resulting in easier implementation.

  16. Mechanics of composite actin networks: in vitro and cellular perspectives

    NASA Astrophysics Data System (ADS)

    Upadhyaya, Arpita

    2014-03-01

    Actin filaments and associated actin binding proteins play an essential role in governing the mechanical properties of eukaryotic cells. Even though cells have multiple actin binding proteins (ABPs) that exist simultaneously to maintain the structural and mechanical integrity of the cellular cytoskeleton, how these proteins work together to determine the properties of actin networks is not well understood. The ABP, palladin, is essential for the integrity of cell morphology and movement during development. Palladin coexists with alpha-actinin in stress fibers and focal adhesions and binds to both actin and alpha-actinin. To obtain insight into how mutually interacting actin crosslinking proteins modulate the properties of actin networks, we have characterized the micro-structure and mechanics of actin networks crosslinked with palladin and alpha-actinin. Our studies on composite networks of alpha-actinin/palladin/actin show that palladin and alpha-actinin synergistically determine network viscoelasticity. We have further examined the role of palladin in cellular force generation and mechanosensing. Traction force microscopy revealed that TAFs are sensitive to substrate stiffness as they generate larger forces on substrates of increased stiffness. Contrary to expectations, knocking down palladin increased the forces generated by cells, and also inhibited the ability to sense substrate stiffness for very stiff gels. This was accompanied by significant differences in the actin organization and adhesion dynamics of palladin knock down cells. Perturbation experiments also suggest altered myosin activity in palladin KD cells. Our results suggest that the actin crosslinkers such as palladin and myosin motors coordinate for optimal cell function and to prevent aberrant behavior as in cancer metastasis.

  17. Study and Simulation of Traffic Behavior in Cellular Network

    NASA Astrophysics Data System (ADS)

    Madhup, D. K.; Shrestha, C. L.; Sharma, R. K.

    2007-07-01

    Cellular radio systems accommodate a large number of users with a limited radio spectrum. The concept of trunking allows a large number of users to share the relatively small number of channels in a cell by providing access to each user, on demand, from a pool of available channels. Traffic engineering deals with provisioning of communication circuits in a given area for a number of subscribers with a required grade of service. Traffic in any cell depends upon the number of users, the average request rate and average call duration. Certain number of channels is required for the required GOS. To design an optimum capacity cellular system, traffic behavior on that system is important. The number of channel required can be estimated by using Erlang formula and Erlang table. Erlang table is not always useful to calculate the probability of blocking in various complex scenarios such as channel borrowing strategies. When the total number of channel available in a given cell are divided to serve partly for newly generated calls and partly for handover calls, and if they use dynamic channel assignment strategies like channel borrowing, then the probability of blocking can't be calculated from Erlang table. Simulation model of the behavior help us to determine the blocking and the channel utilization while using various channel assignment strategies. The title "Study and Simulation of Traffic Behavior in Cellular Network" entail the study of the blocking probability of traffic in cellular network for static channel assignment strategies and dynamic channel borrowing strategies through MATLAB programming language and graphic user interface (GUI). The result shows that the dynamic scheme can perform better than static maximizing the overall utilization of the circuits and minimizing the overall blocking.

  18. Cutting the Wires: Modularization of Cellular Networks for Experimental Design

    PubMed Central

    Lang, Moritz; Summers, Sean; Stelling, Jörg

    2014-01-01

    Understanding naturally evolved cellular networks requires the consecutive identification and revision of the interactions between relevant molecular species. In this process, initially often simplified and incomplete networks are extended by integrating new reactions or whole subnetworks to increase consistency between model predictions and new measurement data. However, increased consistency with experimental data alone is not sufficient to show the existence of biomolecular interactions, because the interplay of different potential extensions might lead to overall similar dynamics. Here, we present a graph-based modularization approach to facilitate the design of experiments targeted at independently validating the existence of several potential network extensions. Our method is based on selecting the outputs to measure during an experiment, such that each potential network extension becomes virtually insulated from all others during data analysis. Each output defines a module that only depends on one hypothetical network extension, and all other outputs act as virtual inputs to achieve insulation. Given appropriate experimental time-series measurements of the outputs, our modules can be analyzed, simulated, and compared to the experimental data separately. Our approach exemplifies the close relationship between structural systems identification and modularization, an interplay that promises development of related approaches in the future. PMID:24411264

  19. Country-wide rainfall maps from cellular communication networks

    PubMed Central

    Overeem, Aart; Leijnse, Hidde; Uijlenhoet, Remko

    2013-01-01

    Accurate and timely surface precipitation measurements are crucial for water resources management, agriculture, weather prediction, climate research, as well as ground validation of satellite-based precipitation estimates. However, the majority of the land surface of the earth lacks such data, and in many parts of the world the density of surface precipitation gauging networks is even rapidly declining. This development can potentially be counteracted by using received signal level data from the enormous number of microwave links used worldwide in commercial cellular communication networks. Along such links, radio signals propagate from a transmitting antenna at one base station to a receiving antenna at another base station. Rain-induced attenuation and, subsequently, path-averaged rainfall intensity can be retrieved from the signal’s attenuation between transmitter and receiver. Here, we show how one such a network can be used to retrieve the space–time dynamics of rainfall for an entire country (The Netherlands, ∼35,500 km2), based on an unprecedented number of links (∼2,400) and a rainfall retrieval algorithm that can be applied in real time. This demonstrates the potential of such networks for real-time rainfall monitoring, in particular in those parts of the world where networks of dedicated ground-based rainfall sensors are often virtually absent. PMID:23382210

  20. Country-wide rainfall maps from cellular communication networks.

    PubMed

    Overeem, Aart; Leijnse, Hidde; Uijlenhoet, Remko

    2013-02-19

    Accurate and timely surface precipitation measurements are crucial for water resources management, agriculture, weather prediction, climate research, as well as ground validation of satellite-based precipitation estimates. However, the majority of the land surface of the earth lacks such data, and in many parts of the world the density of surface precipitation gauging networks is even rapidly declining. This development can potentially be counteracted by using received signal level data from the enormous number of microwave links used worldwide in commercial cellular communication networks. Along such links, radio signals propagate from a transmitting antenna at one base station to a receiving antenna at another base station. Rain-induced attenuation and, subsequently, path-averaged rainfall intensity can be retrieved from the signal's attenuation between transmitter and receiver. Here, we show how one such a network can be used to retrieve the space-time dynamics of rainfall for an entire country (The Netherlands, ∼35,500 km(2)), based on an unprecedented number of links (∼2,400) and a rainfall retrieval algorithm that can be applied in real time. This demonstrates the potential of such networks for real-time rainfall monitoring, in particular in those parts of the world where networks of dedicated ground-based rainfall sensors are often virtually absent. PMID:23382210

  1. Application-Aware Dynamic Retransmission Control in Mobile Cellular Networks

    NASA Astrophysics Data System (ADS)

    Halima, Nadhir Ben; Kliazovich, Dzmitry; Granelli, Fabrizio

    This paper proposes an application-aware cross-layer approach between application/transport layers on the mobile terminal and link layer at the wireless base station to enable dynamic control on the strength of per-packet error protection for multimedia and data transfers. Specifically, in the context of cellular networks, the proposed scheme allows to control the desired level of Hybrid ARQ (HARQ) protection by using an in-band control feedback channel. Such protection is dynamically adapted on a per-packet basis and depends on the perceptual importance of different packets as well as on the reception history of the flow.

  2. Emulating fire propagation by using cellular nonlinear networks

    NASA Astrophysics Data System (ADS)

    Buscarino, A.; Fortuna, L.; Frasca, M.; Xibilia, M. G.

    2012-09-01

    In this paper a new approach based on Cellular Nonlinear Networks (CNNs) for modeling the diffusion of forest fires is presented. Based on a model relying on an hyperbolic reaction-diffusion equation, the proposed approach exploits the peculiarity of CNNs allowing the investigation of different types of forest fires, also considering specific morphological characteristics of the terrain and the presence of external perturbations like wind flows. Results show the emergence of particular phenomena really observed in wildfires, allowing to assess the validity of the approach.

  3. GPM ground validation via commercial cellular networks: an exploratory approach

    NASA Astrophysics Data System (ADS)

    Rios Gaona, Manuel Felipe; Overeem, Aart; Leijnse, Hidde; Brasjen, Noud; Uijlenhoet, Remko

    2016-04-01

    The suitability of commercial microwave link networks for ground validation of GPM (Global Precipitation Measurement) data is evaluated here. Two state-of-the-art rainfall products are compared over the land surface of the Netherlands for a period of 7 months, i.e., rainfall maps from commercial cellular communication networks and Integrated Multi-satellite Retrievals for GPM (IMERG). Commercial microwave link networks are nowadays the core component in telecommunications worldwide. Rainfall rates can be retrieved from measurements of attenuation between transmitting and receiving antennas. If adequately set up, these networks enable rainfall monitoring tens of meters above the ground at high spatiotemporal resolutions (temporal sampling of seconds to tens of minutes, and spatial sampling of hundreds of meters to tens of kilometers). The GPM mission is the successor of TRMM (Tropical Rainfall Measurement Mission). For two years now, IMERG offers rainfall estimates across the globe (180°W - 180°E and 60°N - 60°S) at spatiotemporal resolutions of 0.1° x 0.1° every 30 min. These two data sets are compared against a Dutch gauge-adjusted radar data set, considered to be the ground truth given its accuracy, spatiotemporal resolution and availability. The suitability of microwave link networks in satellite rainfall evaluation is of special interest, given the independent character of this technique, its high spatiotemporal resolutions and availability. These are valuable assets for water management and modeling of floods, landslides, and weather extremes; especially in places where rain gauge networks are scarce or poorly maintained, or where weather radar networks are too expensive to acquire and/or maintain.

  4. Sources of Uncertainty in Rainfall Maps from Cellular Communication Networks

    NASA Astrophysics Data System (ADS)

    Rios Gaona, Manuel Felipe; Overeem, Aart; Leijnse, Hidde; Uijlenhoet, Remko

    2015-04-01

    and quantify the sources of uncertainty in such rainfall maps, but also to test the actual and optimal performance of one commercial microwave network from one of the cellular providers in The Netherlands.

  5. Cellular telephone-based wide-area radiation detection network

    DOEpatents

    Craig, William W.; Labov, Simon E.

    2009-06-09

    A network of radiation detection instruments, each having a small solid state radiation sensor module integrated into a cellular phone for providing radiation detection data and analysis directly to a user. The sensor module includes a solid-state crystal bonded to an ASIC readout providing a low cost, low power, light weight compact instrument to detect and measure radiation energies in the local ambient radiation field. In particular, the photon energy, time of event, and location of the detection instrument at the time of detection is recorded for real time transmission to a central data collection/analysis system. The collected data from the entire network of radiation detection instruments are combined by intelligent correlation/analysis algorithms which map the background radiation and detect, identify and track radiation anomalies in the region.

  6. Assessing the weather monitoring capabilities of cellular microwave link networks

    NASA Astrophysics Data System (ADS)

    Fencl, Martin; Vrzba, Miroslav; Rieckermann, Jörg; Bareš, Vojtěch

    2016-04-01

    Using of microwave links for rainfall monitoring was suggested already by (Atlas and Ulbrich, 1977). However, this technique attracted broader attention of scientific community only in the recent decade, with the extensive growth of cellular microwave link (CML) networks, which form the backbone of today's cellular telecommunication infrastructure. Several studies have already shown that CMLs can be conveniently used as weather sensors and have potential to provide near-ground path-integrated observations of rainfall but also humidity or fog. However, although research is still focusing on algorithms to improve the weather sensing capabilities (Fencl et al., 2015), it is not clear how to convince cellular operators to provide the power levels of their network. One step in this direction is to show in which regions or municipalities the networks are sufficiently dense to provide/develop good services. In this contribution we suggest a standardized approach to evaluate CML networks in terms of rainfall observation and to identify suitable regions for CML rainfall monitoring. We estimate precision of single CML based on its sensitivity to rainfall, i.e. as a function of frequency, polarization and path length. Capability of a network to capture rainfall spatial patterns is estimated from the CML coverage and path lengths considering that single CML provides path-integrated rain rates. We also search for suitable predictors for regions where no network topologies are available. We test our approach on several European networks and discuss the results. Our results show that CMLs are very dense in urban areas (> 1 CML/km2), but less in rural areas (< 0.02 CML/km2). We found a strong correlation between a population and CML network density (e.g. R2 = 0.97 in Czech Republic), thus population could be a simple proxy to identify suitable regions for CML weather monitoring. To enable a simple and efficient assessment of the CML monitoring potential for any region worldwide

  7. Sigma-delta cellular neural network for 2D modulation.

    PubMed

    Aomori, Hisashi; Otake, Tsuyoshi; Takahashi, Nobuaki; Tanaka, Mamoru

    2008-01-01

    Although sigma-delta modulation is widely used for analog-to-digital (A/D) converters, sigma-delta concepts are only for 1D signals. Signal processing in the digital domain is extremely useful for 2D signals such as used in image processing, medical imaging, ultrasound imaging, and so on. The intricate task that provides true 2D sigma-delta modulation is feasible in the spatial domain sigma-delta modulation using the discrete-time cellular neural network (DT-CNN) with a C-template. In the proposed architecture, the A-template is used for a digital-to-analog converter (DAC), the C-template works as an integrator, and the nonlinear output function is used for the bilevel output. In addition, due to the cellular neural network (CNN) characteristics, each pixel of an image corresponds to a cell of a CNN, and each cell is connected spatially by the A-template. Therefore, the proposed system can be thought of as a very large-scale and super-parallel sigma-delta modulator. Moreover, the spatio-temporal dynamics is designed to obtain an optimal reconstruction signal. The experimental results show the excellent reconstruction performance and capabilities of the CNN as a sigma-delta modulator. PMID:18215502

  8. Mesoscale assembly of chemically modified graphene into complex cellular networks

    NASA Astrophysics Data System (ADS)

    Barg, Suelen; Perez, Felipe Macul; Ni, Na; Do Vale Pereira, Paula; Maher, Robert C.; Garcia-Tuñon, Esther; Eslava, Salvador; Agnoli, Stefano; Mattevi, Cecilia; Saiz, Eduardo

    2014-07-01

    The widespread technological introduction of graphene beyond electronics rests on our ability to assemble this two-dimensional building block into three-dimensional structures for practical devices. To achieve this goal we need fabrication approaches that are able to provide an accurate control of chemistry and architecture from nano to macroscopic levels. Here, we describe a versatile technique to build ultralight (density ≥1 mg cm-3) cellular networks based on the use of soft templates and the controlled segregation of chemically modified graphene to liquid interfaces. These novel structures can be tuned for excellent conductivity; versatile mechanical response (elastic-brittle to elastomeric, reversible deformation, high energy absorption) and organic absorption capabilities (above 600 g per gram of material). The approach can be used to uncover the basic principles that will guide the design of practical devices that by combining unique mechanical and functional performance will generate new technological opportunities.

  9. Mesoscale assembly of chemically modified graphene into complex cellular networks

    PubMed Central

    Barg, Suelen; Perez, Felipe Macul; Ni, Na; do Vale Pereira, Paula; Maher, Robert C.; Garcia-Tuñon, Esther; Eslava, Salvador; Agnoli, Stefano; Mattevi, Cecilia; Saiz, Eduardo

    2014-01-01

    The widespread technological introduction of graphene beyond electronics rests on our ability to assemble this two-dimensional building block into three-dimensional structures for practical devices. To achieve this goal we need fabrication approaches that are able to provide an accurate control of chemistry and architecture from nano to macroscopic levels. Here, we describe a versatile technique to build ultralight (density ≥1 mg cm−3) cellular networks based on the use of soft templates and the controlled segregation of chemically modified graphene to liquid interfaces. These novel structures can be tuned for excellent conductivity; versatile mechanical response (elastic-brittle to elastomeric, reversible deformation, high energy absorption) and organic absorption capabilities (above 600 g per gram of material). The approach can be used to uncover the basic principles that will guide the design of practical devices that by combining unique mechanical and functional performance will generate new technological opportunities. PMID:24999766

  10. A 'bioproduction breadboard': programming, assembling, and actuating cellular networks.

    PubMed

    Zargar, Amin; Payne, Gregory F; Bentley, William E

    2015-12-01

    With advances in synthetic biology and biofabrication, cellular networks can be functionalized and connected with unprecedented sophistication. We describe a platform for the creation of a 'bioproduction breadboard'. This would consist of physically isolated product-producing cell populations, product capture devices, and other unit operations that function as programmed in place, using unique, orthogonal inputs. For product synthesis, customized cell populations would be connected through standardized, generic inputs allowing 'plug and play' functionality and primary, user-mediated regulation. In addition, through autonomous pathway redirection and balancing, the cells themselves would provide secondary, self-directed regulation to optimize bioproduction. By leveraging specialization and division of labor, we envision diverse cell populations linked to create new pathway designs. PMID:26342587

  11. Automatic generation of multipath algorithms in the cellular nonlinear network

    NASA Astrophysics Data System (ADS)

    Preciado, Victor M.; Guinea, Domingo; Montufar-Chaveznava, Rodrigo

    2001-04-01

    The objective of this work is to generate a learning machine capable of find solutions for complex image processing task by Cellular Neural Network (CNN's). First a general machine for automatic analog algorithm design independent of the problem to solve is created, this is accomplished through an evolutionary strategy that is an extension of genetic programming. Second, this work introduces a suite of sub- mechanisms that increase the power of genetic programming and contribute to reduce the enormous space search for producing a plentiful search. Some concepts in this section are related with AI theory, in such a way that in this work we are in the intersection field of AI and Image Processing by CNN.

  12. Edge detection of noisy images based on cellular neural networks

    NASA Astrophysics Data System (ADS)

    Li, Huaqing; Liao, Xiaofeng; Li, Chuandong; Huang, Hongyu; Li, Chaojie

    2011-09-01

    This paper studies a technique employing both cellular neural networks (CNNs) and linear matrix inequality (LMI) for edge detection of noisy images. Our main work focuses on training templates of noise reduction and edge detection CNNs. Based on the Lyapunov stability theorem, we derive a criterion for global asymptotical stability of a unique equilibrium of the noise reduction CNN. Then we design an approach to train edge detection templates, and this approach can detect the edge precisely and efficiently, i.e., by only one iteration. Finally, we illustrate performance of the proposed methodology from the aspect of peak signal to noise ratio (PSNR) through computer simulations. Moreover, some comparisons are also given to prove that our method outperforms classical operators in gray image edge detection.

  13. Country-wide rainfall maps from cellular communication networks

    NASA Astrophysics Data System (ADS)

    Leijnse, Hidde; Overeem, Aart; Uijlenhoet, Remko

    2013-04-01

    Accurate rainfall observations with high spatial and temporal resolutions are needed for hydrological applications, agriculture, meteorology, and climate monitoring. However, the majority of the land surface of the earth lacks accurate rainfall information and the number of rain gauges is even severely declining in Europe, South-America, and Africa. This calls for alternative sources of rainfall information. Various studies have shown that microwave links from operational cellular telecommunication networks may be employed for rainfall monitoring. Such networks cover 20% of the land surface of the earth and have a high density, especially in urban areas. The basic principle of rainfall monitoring using microwave links is as follows. Rainfall attenuates the electromagnetic signals transmitted from one telephone tower to another. By measuring the received power at one end of a microwave link as a function of time, the path-integrated attenuation due to rainfall can be calculated. Previous studies have shown that average rainfall intensities over the length of a link can be derived from the path-integrated attenuation. Here we show how one cellular telecommunication network can be used to retrieve the space-time dynamics of rainfall for an entire country. A dataset from a commercial microwave link network over the Netherlands is analyzed, containing data from an unprecedented number of links (2400) covering the land surface of the Netherlands (35500 km2). This dataset consists of 24 days with substantial rainfall in June - September 2011. A rainfall retrieval algorithm is presented to derive rainfall intensities from the microwave link data, which have a temporal resolution of 15 min. Rainfall maps (1 km spatial resolution) are generated from these rainfall intensities using Kriging. This algorithm is suited for real-time application, and is calibrated on a subset (12 days) of the dataset. The other 12 days in the dataset are used to validate the algorithm. Both

  14. Simulating Quantitative Cellular Responses Using Asynchronous Threshold Boolean Network Ensembles

    PubMed Central

    2011-01-01

    Background With increasing knowledge about the potential mechanisms underlying cellular functions, it is becoming feasible to predict the response of biological systems to genetic and environmental perturbations. Due to the lack of homogeneity in living tissues it is difficult to estimate the physiological effect of chemicals, including potential toxicity. Here we investigate a biologically motivated model for estimating tissue level responses by aggregating the behavior of a cell population. We assume that the molecular state of individual cells is independently governed by discrete non-deterministic signaling mechanisms. This results in noisy but highly reproducible aggregate level responses that are consistent with experimental data. Results We developed an asynchronous threshold Boolean network simulation algorithm to model signal transduction in a single cell, and then used an ensemble of these models to estimate the aggregate response across a cell population. Using published data, we derived a putative crosstalk network involving growth factors and cytokines - i.e., Epidermal Growth Factor, Insulin, Insulin like Growth Factor Type 1, and Tumor Necrosis Factor α - to describe early signaling events in cell proliferation signal transduction. Reproducibility of the modeling technique across ensembles of Boolean networks representing cell populations is investigated. Furthermore, we compare our simulation results to experimental observations of hepatocytes reported in the literature. Conclusion A systematic analysis of the results following differential stimulation of this model by growth factors and cytokines suggests that: (a) using Boolean network ensembles with asynchronous updating provides biologically plausible noisy individual cellular responses with reproducible mean behavior for large cell populations, and (b) with sufficient data our model can estimate the response to different concentrations of extracellular ligands. Our results suggest that this

  15. Cellular computational networks--a scalable architecture for learning the dynamics of large networked systems.

    PubMed

    Luitel, Bipul; Venayagamoorthy, Ganesh Kumar

    2014-02-01

    Neural networks for implementing large networked systems such as smart electric power grids consist of multiple inputs and outputs. Many outputs lead to a greater number of parameters to be adapted. Each additional variable increases the dimensionality of the problem and hence learning becomes a challenge. Cellular computational networks (CCNs) are a class of sparsely connected dynamic recurrent networks (DRNs). By proper selection of a set of input elements for each output variable in a given application, a DRN can be modified into a CCN which significantly reduces the complexity of the neural network and allows use of simple training methods for independent learning in each cell thus making it scalable. This article demonstrates this concept of developing a CCN using dimensionality reduction in a DRN for scalability and better performance. The concept has been analytically explained and empirically verified through application. PMID:24300549

  16. Sources of uncertainty in rainfall maps from cellular communication networks

    NASA Astrophysics Data System (ADS)

    Rios Gaona, M. F.; Overeem, A.; Leijnse, H.; Uijlenhoet, R.

    2015-03-01

    ground truth). Thus, we were able to not only identify and quantify the sources of uncertainty in such rainfall maps, but also to test the actual and optimal performance of one commercial microwave network from one of the cellular providers in the Netherlands.

  17. Environmental Monitoring using Measurements from Cellular Network Infrastructure

    NASA Astrophysics Data System (ADS)

    David, N.; Gao, O. H.

    2015-12-01

    atmospheric phenomena using current and future planned frequencies of cellular network infrastructure will be introduced.

  18. Cellular and network mechanisms of genetically-determined absence seizures.

    PubMed

    Pinault, Didier; O'Brien, Terence J

    2005-01-01

    The absence epilepsies are characterized by recurrent episodes of loss of consciousness associated with generalized spike-and-wave discharges, with an abrupt onset and offset, in the thalamocortical system. In the absence of detailed neurophysiological studies in humans, many of the concepts regarding the pathophysiological basis of absence seizures are based on studies in animal models. Each of these models has its particular strengths and limitations, and the validity of findings from these models for the human condition cannot be assumed. Consequently, studies in different models have produced some conflicting findings and conclusions. A long-standing concept, based primarily from studies in vivo in cats and in vitro brain slices, is that these paroxysmal electrical events develop suddenly from sleep-related spindle oscillations. More specifically, it is proposed that the initial mechanisms that underlie absence-related spike-and-wave discharges are located in the thalamus, involving especially the thalamic reticular nucleus. By contrast, more recent studies in well-established, genetic models of absence epilepsy in rats demonstrate that spike-and-wave discharges originate in a cortical focus and develop from a wake-related natural corticothalamic sensorimotor rhythm. In this review we integrate recent findings showing that, in both the thalamus and the neocortex, genetically-determined, absence-related spike-and-wave discharges are the manifestation of hypersynchronized, cellular, rhythmic excitations and inhibitions that result from a combination of complex, intrinsic, synaptic mechanisms. Arguments are put forward supporting the hypothesis that layer VI corticothalamic neurons act as 'drivers' in the generation of spike-and-wave discharges in the somatosensory thalamocortical system that result in corticothalamic resonances particularly initially involving the thalamic reticular nucleus. However an important unresolved question is: what are the cellular and

  19. Radio Resource Allocation on Complex 4G Wireless Cellular Networks

    NASA Astrophysics Data System (ADS)

    Psannis, Kostas E.

    2015-09-01

    In this article we consider the heuristic algorithm which improves step by step wireless data delivery over LTE cellular networks by using the total transmit power with the constraint on users’ data rates, and the total throughput with the constraints on the total transmit power as well as users’ data rates, which are jointly integrated into a hybrid-layer design framework to perform radio resource allocation for multiple users, and to effectively decide the optimal system parameter such as modulation and coding scheme (MCS) in order to adapt to the varying channel quality. We propose new heuristic algorithm which balances the accessible data rate, the initial data rates of each user allocated by LTE scheduler, the priority indicator which signals delay- throughput- packet loss awareness of the user, and the buffer fullness by achieving maximization of radio resource allocation for multiple users. It is noted that the overall performance is improved with the increase in the number of users, due to multiuser diversity. Experimental results illustrate and validate the accuracy of the proposed methodology.

  20. Cellular nonlinear networks for strike-point localization at JET

    NASA Astrophysics Data System (ADS)

    Arena, P.; Fortuna, L.; Bruno, M.; Vagliasindi, G.; Murari, A.; Andrew, P.; Mazzitelli, G.

    2005-11-01

    At JET, the potential of fast image processing for real-time purposes is thoroughly investigated. Particular attention is devoted to smart sensors based on system on chip technology. The data of the infrared cameras were processed with a chip implementing a cellular nonlinear network (CNN) structure so as to support and complement the magnetic diagnostics in the real-time localization of the strike-point position in the divertor. The circuit consists of two layers of complementary metal-oxide semiconductor components, the first being the sensor and the second implementing the actual CNN. This innovative hardware has made it possible to determine the position of the maximum thermal load with a time resolution of the order of 30 ms. Good congruency has been found with the measurement from the thermocouples in the divertor, proving the potential of the infrared data in locating the region of the maximum thermal load. The results are also confirmed by JET magnetic codes, both those used for the equilibrium reconstructions and those devoted to the identification of the plasma boundary.

  1. Network signatures of cellular immortalization in human lymphoblastoid cell lines

    SciTech Connect

    Shim, Sung-Mi; Jung, So-Young; Nam, Hye-Young; Kim, Hye-Ryun; Lee, Mee-Hee; Kim, Jun-Woo; Han, Bok-Ghee; Jeon, Jae-Pil

    2013-11-15

    Highlights: •We identified network signatures of LCL immortalization from transcriptomic profiles. •More than 41% of DEGs are possibly regulated by miRNAs in LCLs. •MicroRNA target genes in LCLs are involved in apoptosis and immune-related functions. •This approach is useful to find functional miRNA targets in specific cell conditions. -- Abstract: Human lymphoblastoid cell line (LCL) has been used as an in vitro cell model in genetic and pharmacogenomic studies, as well as a good model for studying gene expression regulatory machinery using integrated genomic analyses. In this study, we aimed to identify biological networks of LCL immortalization from transcriptomic profiles of microRNAs and their target genes in LCLs. We first selected differentially expressed genes (DEGs) and microRNAs (DEmiRs) between early passage LCLs (eLCLs) and terminally differentiated late passage LCLs (tLCLs). The in silico and correlation analysis of these DEGs and DEmiRs revealed that 1098 DEG–DEmiR pairs were found to be positively (n = 591 pairs) or negatively (n = 507 pairs) correlated with each other. More than 41% of DEGs are possibly regulated by miRNAs in LCL immortalizations. The target DEGs of DEmiRs were enriched for cellular functions associated with apoptosis, immune response, cell death, JAK–STAT cascade and lymphocyte activation while non-miRNA target DEGs were over-represented for basic cell metabolisms. The target DEGs correlated negatively with miR-548a-3p and miR-219-5p were significantly associated with protein kinase cascade, and the lymphocyte proliferation and apoptosis, respectively. In addition, the miR-106a and miR-424 clusters located in the X chromosome were enriched in DEmiR–mRNA pairs for LCL immortalization. In this study, the integrated transcriptomic analysis of LCLs could identify functional networks of biologically active microRNAs and their target genes involved in LCL immortalization.

  2. When are two multi-layer cellular neural networks the same?

    PubMed

    Ban, Jung-Chao; Chang, Chih-Hung

    2016-07-01

    This paper aims to characterize whether a multi-layer cellular neural network is of deep architecture; namely, when can an n-layer cellular neural network be replaced by an m-layer cellular neural network for mnetwork is revealed. PMID:27085113

  3. Predict drug-protein interaction in cellular networking.

    PubMed

    Xiao, Xuan; Min, Jian-Liang; Wang, Pu; Chou, Kuo-Chen

    2013-01-01

    Involved with many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, GPCRs (G-protein-coupled receptors) are the most frequent targets for drug development: over 50% of all prescription drugs currently on the market are actually acting by targeting GPCRs directly or indirectly. Found in every living thing and nearly all cells, ion channels play crucial roles for many vital functions in life, such as heartbeat, sensory transduction, and central nervous system response. Their dysfunction may have significant impact to human health, and hence ion channels are deemed as "the next GPCRs". To develop GPCR-targeting or ion-channel-targeting drugs, the first important step is to identify the interactions between potential drug compounds with the two kinds of protein receptors in the cellular networking. In this minireview, we are to introduce two predictors. One is called iGPCR-Drug accessible at http://www.jci-bioinfo.cn/iGPCR-Drug/; the other called iCDI-PseFpt at http://www.jci-bioinfo.cn/iCDI-PseFpt. The former is for identifying the interactions of drug compounds with GPCRs; while the latter for that with ion channels. In both predictors, the drug compound was formulated by the two-dimensional molecular fingerprint, and the protein receptor by the pseudo amino acid composition generated with the grey model theory, while the operation engine was the fuzzy K-nearest neighbor algorithm. For the convenience of most experimental pharmaceutical and medical scientists, a step-bystep guide is provided on how to use each of the two web-servers to get the desired results without the need to follow the complicated mathematics involved originally for their establishment. PMID:23889048

  4. Design mobile satellite system architecture as an integral part of the cellular access digital network

    NASA Technical Reports Server (NTRS)

    Chien, E. S. K.; Marinho, J. A.; Russell, J. E., Sr.

    1988-01-01

    The Cellular Access Digital Network (CADN) is the access vehicle through which cellular technology is brought into the mainstream of the evolving integrated telecommunications network. Beyond the integrated end-to-end digital access and per call network services provisioning of the Integrated Services Digital Network (ISDN), the CADN engenders the added capability of mobility freedom via wireless access. One key element of the CADN network architecture is the standard user to network interface that is independent of RF transmission technology. Since the Mobile Satellite System (MSS) is envisioned to not only complement but also enhance the capabilities of the terrestrial cellular telecommunications network, compatibility and interoperability between terrestrial cellular and mobile satellite systems are vitally important to provide an integrated moving telecommunications network of the future. From a network standpoint, there exist very strong commonalities between the terrestrial cellular system and the mobile satellite system. Therefore, the MSS architecture should be designed as an integral part of the CADN. This paper describes the concept of the CADN, the functional architecture of the MSS, and the user-network interface signaling protocols.

  5. Analysis of Blocking Rate and Bandwidth Usage of Mobile IPTV Services in Wireless Cellular Networks

    PubMed Central

    Li, Mingfu

    2014-01-01

    Mobile IPTV services over wireless cellular networks become more and more popular, owing to the significant growth in access bandwidth of wireless cellular networks such as 3G/4G and WiMAX. However, the spectrum resources of wireless cellular networks is rare. How to enhance the spectral efficiency of mobile networks becomes an important issue. Unicast, broadcast, and multicast are the most important transport schemes for offering mobile IPTV services over wireless cellular networks. Therefore, bandwidth usages and blocking rates of unicast, broadcast, and multicast IPTV services were analyzed and compared in this paper. Simulations were also conducted to validate the analytical results. Numerical results demonstrate that the presented analysis is correct, and multicast scheme achieves the best bandwidth usage and blocking rate performance, relative to the other two schemes. PMID:25379521

  6. Analysis of blocking rate and bandwidth usage of mobile IPTV services in wireless cellular networks.

    PubMed

    Li, Mingfu

    2014-01-01

    Mobile IPTV services over wireless cellular networks become more and more popular, owing to the significant growth in access bandwidth of wireless cellular networks such as 3G/4G and WiMAX. However, the spectrum resources of wireless cellular networks is rare. How to enhance the spectral efficiency of mobile networks becomes an important issue. Unicast, broadcast, and multicast are the most important transport schemes for offering mobile IPTV services over wireless cellular networks. Therefore, bandwidth usages and blocking rates of unicast, broadcast, and multicast IPTV services were analyzed and compared in this paper. Simulations were also conducted to validate the analytical results. Numerical results demonstrate that the presented analysis is correct, and multicast scheme achieves the best bandwidth usage and blocking rate performance, relative to the other two schemes. PMID:25379521

  7. Traffic Driven Analysis of Cellular and WiFi Networks

    ERIC Educational Resources Information Center

    Paul, Utpal Kumar

    2012-01-01

    Since the days Internet traffic proliferated, measurement, monitoring and analysis of network traffic have been critical to not only the basic understanding of large networks, but also to seek improvements in resource management, traffic engineering and security. At the current times traffic in wireless local and wide area networks are facing…

  8. Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks.

    PubMed

    White, Forest M; Wolf-Yadlin, Alejandro

    2016-06-12

    Protein phosphorylation-mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks. PMID:27049636

  9. Methods for the Analysis of Protein Phosphorylation–Mediated Cellular Signaling Networks

    NASA Astrophysics Data System (ADS)

    White, Forest M.; Wolf-Yadlin, Alejandro

    2016-06-01

    Protein phosphorylation–mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks.

  10. Effects of cellular homeostatic intrinsic plasticity on dynamical and computational properties of biological recurrent neural networks.

    PubMed

    Naudé, Jérémie; Cessac, Bruno; Berry, Hugues; Delord, Bruno

    2013-09-18

    Homeostatic intrinsic plasticity (HIP) is a ubiquitous cellular mechanism regulating neuronal activity, cardinal for the proper functioning of nervous systems. In invertebrates, HIP is critical for orchestrating stereotyped activity patterns. The functional impact of HIP remains more obscure in vertebrate networks, where higher order cognitive processes rely on complex neural dynamics. The hypothesis has emerged that HIP might control the complexity of activity dynamics in recurrent networks, with important computational consequences. However, conflicting results about the causal relationships between cellular HIP, network dynamics, and computational performance have arisen from machine-learning studies. Here, we assess how cellular HIP effects translate into collective dynamics and computational properties in biological recurrent networks. We develop a realistic multiscale model including a generic HIP rule regulating the neuronal threshold with actual molecular signaling pathways kinetics, Dale's principle, sparse connectivity, synaptic balance, and Hebbian synaptic plasticity (SP). Dynamic mean-field analysis and simulations unravel that HIP sets a working point at which inputs are transduced by large derivative ranges of the transfer function. This cellular mechanism ensures increased network dynamics complexity, robust balance with SP at the edge of chaos, and improved input separability. Although critically dependent upon balanced excitatory and inhibitory drives, these effects display striking robustness to changes in network architecture, learning rates, and input features. Thus, the mechanism we unveil might represent a ubiquitous cellular basis for complex dynamics in neural networks. Understanding this robustness is an important challenge to unraveling principles underlying self-organization around criticality in biological recurrent neural networks. PMID:24048833

  11. Cues for cellular assembly of vascular elastin networks

    NASA Astrophysics Data System (ADS)

    Kothapalli, Chandrasekhar R.

    Elastin, a structural protein distributed in the extracellular matrix of vascular tissues is critical to the maintenance of vascular mechanics, besides regulation of cell-signaling pathways involved in injury response and morphogenesis. Thus, congenital absence or disease-mediated degradation of vascular elastin and its malformation within native vessels due to innately poor elastin synthesis by adult vascular cells compromise vascular homeostasis. Current elastin regenerative strategies using tissue engineering principles are limited by the progressive destabilization of tropoelastin mRNA expression in adult vascular cells and the unavailability of scaffolds that can provide cellular cues necessary to up-regulate elastin synthesis and regenerate faithful mimics of native elastin. Since our earlier studies demonstrated the elastogenic utility of hyaluronan (HA)-based cues, we have currently sought to identify a unique set of culture conditions based on HA fragments (0.756-2000 kDa), growth factors (TGF-beta1, IGF-1) and other biomolecules (Cu2+ ions, LOX), which will together enhance synthesis, crosslinking, maturation and fibrous elastin matrix formation by adult SMCs, under both healthy and inflammatory conditions. It was observed that TGF-beta1 (1 ng/mL) together with HA oligomers (0.2 microg/mL) synergistically suppressed SMC proliferation, enhanced tropoelastin (8-fold) and matrix elastin synthesis (5.5-fold), besides improving matrix yield (4.5-fold), possibly by increasing production and activity of lysyl oxidase (LOX). Though addition of IGF-1 alone did not offer any advantage, HA fragments (20-200 kDa) in the presence of IGF-1 stimulated tropoelastin and soluble elastin synthesis more than 2.2-fold, with HMW HA contributing for ˜5-fold increase in crosslinked matrix elastin synthesis. Similarly, 0.1 M of Cu2+ ions, alone or together with HA fragments stimulated synthesis of tropoelastin (4-fold) and crosslinked matrix elastin (4.5-fold), via increases in

  12. Participatory sensing as an enabler for self-organisation in future cellular networks

    NASA Astrophysics Data System (ADS)

    Imran, Muhammad Ali; Imran, Ali; Onireti, Oluwakayode

    2013-12-01

    In this short review paper we summarise the emerging challenges in the field of participatory sensing for the self-organisation of the next generation of wireless cellular networks. We identify the potential of participatory sensing in enabling the self-organisation, deployment optimisation and radio resource management of wireless cellular networks. We also highlight how this approach can meet the future goals for the next generation of cellular system in terms of infrastructure sharing, management of multiple radio access techniques, flexible usage of spectrum and efficient management of very small data cells.

  13. Performance evaluation of power control algorithms in wireless cellular networks

    NASA Astrophysics Data System (ADS)

    Temaneh-Nyah, C.; Iita, V.

    2014-10-01

    Power control in a mobile communication network intents to control the transmission power levels in such a way that the required quality of service (QoS) for the users is guaranteed with lowest possible transmission powers. Most of the studies of power control algorithms in the literature are based on some kind of simplified assumptions which leads to compromise in the validity of the results when applied in a real environment. In this paper, a CDMA network was simulated. The real environment was accounted for by defining the analysis area and the network base stations and mobile stations are defined by their geographical coordinates, the mobility of the mobile stations is accounted for. The simulation also allowed for a number of network parameters including the network traffic, and the wireless channel models to be modified. Finally, we present the simulation results of a convergence speed based comparative analysis of three uplink power control algorithms.

  14. Simulating Quantitative Cellular Responses Using Asynchronous Threshold Boolean Network Ensembles

    EPA Science Inventory

    With increasing knowledge about the potential mechanisms underlying cellular functions, it is becoming feasible to predict the response of biological systems to genetic and environmental perturbations. Due to the lack of homogeneity in living tissues it is difficult to estimate t...

  15. Tools and Models for Integrating Multiple Cellular Networks

    SciTech Connect

    Gerstein, Mark

    2015-11-06

    In this grant, we have systematically investigated the integrated networks, which are responsible for the coordination of activity between metabolic pathways in prokaryotes. We have developed several computational tools to analyze the topology of the integrated networks consisting of metabolic, regulatory, and physical interaction networks. The tools are all open-source, and they are available to download from Github, and can be incorporated in the Knowledgebase. Here, we summarize our work as follow. Understanding the topology of the integrated networks is the first step toward understanding its dynamics and evolution. For Aim 1 of this grant, we have developed a novel algorithm to determine and measure the hierarchical structure of transcriptional regulatory networks [1]. The hierarchy captures the direction of information flow in the network. The algorithm is generally applicable to regulatory networks in prokaryotes, yeast and higher organisms. Integrated datasets are extremely beneficial in understanding the biology of a system in a compact manner due to the conflation of multiple layers of information. Therefore for Aim 2 of this grant, we have developed several tools and carried out analysis for integrating system-wide genomic information. To make use of the structural data, we have developed DynaSIN for protein-protein interactions networks with various dynamical interfaces [2]. We then examined the association between network topology with phenotypic effects such as gene essentiality. In particular, we have organized E. coli and S. cerevisiae transcriptional regulatory networks into hierarchies. We then correlated gene phenotypic effects by tinkering with different layers to elucidate which layers were more tolerant to perturbations [3]. In the context of evolution, we also developed a workflow to guide the comparison between different types of biological networks across various species using the concept of rewiring [4], and Furthermore, we have developed

  16. C. elegans Metabolic Gene Regulatory Networks Govern the Cellular Economy

    PubMed Central

    Watson, Emma; Walhout, Albertha J.M.

    2014-01-01

    Diet greatly impacts metabolism in health and disease. In response to the presence or absence of specific nutrients, metabolic gene regulatory networks sense the metabolic state of the cell and regulate metabolic flux accordingly, for instance by the transcriptional control of metabolic enzymes. Here we discuss recent insights regarding metazoan metabolic regulatory networks using the nematode Caenorhabditis elegans as a model, including the modular organization of metabolic gene regulatory networks, the prominent impact of diet on the transcriptome and metabolome, specialized roles of nuclear hormone receptors in responding to dietary conditions, regulation of metabolic genes and metabolic regulators by microRNAs, and feedback between metabolic genes and their regulators. PMID:24731597

  17. Detection of silent cells, synchronization and modulatory activity in developing cellular networks.

    PubMed

    Hjorth, Johannes J J; Dawitz, Julia; Kroon, Tim; Pires, Johny; Dassen, Valerie J; Berkhout, Janna A; Emperador Melero, Javier; Nadadhur, Aish G; Alevra, Mihai; Toonen, Ruud F; Heine, Vivi M; Mansvelder, Huibert D; Meredith, Rhiannon M

    2016-04-01

    Developing networks in the immature nervous system and in cellular cultures are characterized by waves of synchronous activity in restricted clusters of cells. Synchronized activity in immature networks is proposed to regulate many different developmental processes, from neuron growth and cell migration, to the refinement of synapses, topographic maps, and the mature composition of ion channels. These emergent activity patterns are not present in all cells simultaneously within the network and more immature "silent" cells, potentially correlated with the presence of silent synapses, are prominent in different networks during early developmental periods. Many current network analyses for detection of synchronous cellular activity utilize activity-based pixel correlations to identify cellular-based regions of interest (ROIs) and coincident cell activity. However, using activity-based correlations, these methods first underestimate or ignore the inactive silent cells within the developing network and second, are difficult to apply within cell-dense regions commonly found in developing brain networks. In addition, previous methods may ignore ROIs within a network that shows transient activity patterns comprising both inactive and active periods. We developed analysis software to semi-automatically detect cells within developing neuronal networks that were imaged using calcium-sensitive reporter dyes. Using an iterative threshold, modulation of activity was tracked within individual cells across the network. The distribution pattern of both inactive and active, including synchronous cells, could be determined based on distance measures to neighboring cells and according to different anatomical layers. PMID:26097169

  18. Retrieval algorithm for rainfall mapping from microwave links in a cellular communication network

    NASA Astrophysics Data System (ADS)

    Overeem, Aart; Uijlenhoet, Remko; Leijnse, Hidde

    2016-04-01

    Microwave links in commercial cellular communication networks hold a promise for areal rainfall monitoring and could complement rainfall estimates from ground-based weather radars, rain gauges, and satellites. It has been shown that country-wide rainfall maps can be derived from the signal attenuations of microwave links in such a network. We present a rainfall retrieval algorithm, which is employed to obtain rainfall maps from microwave links in a cellular communication network. We compare these rainfall maps to gauge-adjusted radar rainfall maps. The microwave link data set, as well as the developed code, a package in the open source scripting language "R", are freely available at GitHub (https://github.com/overeem11/RAINLINK). The purpose of this presentation is to promote rainfall mapping utilizing microwave links from cellular communication networks as an alternative or complementary means for continental-scale rainfall monitoring.

  19. Quantifying Uncertainties in Rainfall Maps from Cellular Communication Networks

    NASA Astrophysics Data System (ADS)

    Uijlenhoet, R.; Rios Gaona, M. F.; Overeem, A.; Leijnse, H.

    2014-12-01

    The core idea behind rainfall retrievals from commercial microwave link networks is to measure the decrease in power due to attenuation of the electromagnetic signal by raindrops along the link path. Accurate rainfall measurements are of vital importance in hydrological applications, for instance, flash-flood early-warning systems, agriculture, and climate modeling. Hence, such an alternative technique fulfills the need for measurements with higher resolution in time and space, especially in places where standard rain gauge-networks are scarce or poorly maintained. Rainfall estimation via commercial microwave link networks, at country-wide scales, has recently been demonstrated. Despite their potential applicability in rainfall estimation at higher spatiotemporal resolutions, the uncertainties present in link-based rainfall maps are not yet fully comprehended. Now we attempt to quantify the inherent sources of uncertainty present in interpolated maps computed from commercial microwave link rainfall retrievals. In order to disentangle these sources of uncertainty we identified four main sources of error: 1) microwave link measurements, 2) availability of microwave link measurements, 3) spatial distribution of the network, and 4) interpolation methodology. We computed more than 1000 rainfall fields, for The Netherlands, from real and simulated microwave link data. These rainfall fields were compared to quality-controlled gauge-adjusted radar rainfall maps considered as ground-truth. Thus we were able to quantify the contribution of errors in microwave link measurements to the overall uncertainty. The actual performance of the commercial microwave link network is affected by the intermittent availability of the links, not only in time but also in space. We simulated a fully-operational network in time and space, and thus we quantified the role of the availability of microwave link measurements to the overall uncertainty. This research showed that the largest source of

  20. Resource Management in QoS-Aware Wireless Cellular Networks

    ERIC Educational Resources Information Center

    Zhang, Zhi

    2011-01-01

    Emerging broadband wireless networks that support high speed packet data with heterogeneous quality of service (QoS) requirements demand more flexible and efficient use of the scarce spectral resource. Opportunistic scheduling exploits the time-varying, location-dependent channel conditions to achieve multiuser diversity. In this work, we study…

  1. Reverse engineering cellular decisions for hybrid reconfigurable network modeling

    NASA Astrophysics Data System (ADS)

    Blair, Howard A.; Saranak, Jureepan; Foster, Kenneth W.

    2011-06-01

    Cells as microorganisms and within multicellular organisms make robust decisions. Knowing how these complex cells make decisions is essential to explain, predict or mimic their behavior. The discovery of multi-layer multiple feedback loops in the signaling pathways of these modular hybrid systems suggests their decision making is sophisticated. Hybrid systems coordinate and integrate signals of various kinds: discrete on/off signals, continuous sensory signals, and stochastic and continuous fluctuations to regulate chemical concentrations. Such signaling networks can form reconfigurable networks of attractors and repellors giving them an extra level of organization that has resilient decision making built in. Work on generic attractor and repellor networks and on the already identified feedback networks and dynamic reconfigurable regulatory topologies in biological cells suggests that biological systems probably exploit such dynamic capabilities. We present a simple behavior of the swimming unicellular alga Chlamydomonas that involves interdependent discrete and continuous signals in feedback loops. We show how to rigorously verify a hybrid dynamical model of a biological system with respect to a declarative description of a cell's behavior. The hybrid dynamical systems we use are based on a unification of discrete structures and continuous topologies developed in prior work on convergence spaces. They involve variables of discrete and continuous types, in the sense of type theory in mathematical logic. A unification such as afforded by convergence spaces is necessary if one wants to take account of the affect of the structural relationships within each type on the dynamics of the system.

  2. Application of Cellular Automata to Detection of Malicious Network Packets

    ERIC Educational Resources Information Center

    Brown, Robert L.

    2014-01-01

    A problem in computer security is identification of attack signatures in network packets. An attack signature is a pattern of bits that characterizes a particular attack. Because there are many kinds of attacks, there are potentially many attack signatures. Furthermore, attackers may seek to avoid detection by altering the attack mechanism so that…

  3. Frequency-dependent micromechanics of cellularized biopolymer networks

    NASA Astrophysics Data System (ADS)

    Jones, Chris; Kim, Jihan; McIntyre, David; Sun, Bo

    Mechanical interactions between cells and the extracellular matrix (ECM) influence many cellular behaviors such as growth, differentiation, and migration. These are dynamic processes in which the cells actively remodel the ECM. Reconstituted collagen gel is a common model ECM for studying cell-ECM interactions in vitro because collagen is the most abundant component of mammalian ECM and gives the ECM its material stiffness. We embed micron-sized particles in collagen and use holographic optical tweezers to apply forces to the particles in multiple directions and over a range of frequencies up to 10 Hz. We calculate the local compliance and show that it is dependent on both the direction and frequency of the applied force. Performing the same measurement on many particles allows us to characterize the spatial inhomogeneity of the mechanical properties and shows that the compliance decreases at higher frequencies. Performing these measurements on cell-populated collagen gels shows that cellular remodeling of the ECM changes the mechanical properties of the collagen and we investigate whether this change is dependent on the local strain and distance from nearby cells.

  4. Cellular network entropy as the energy potential in Waddington's differentiation landscape

    NASA Astrophysics Data System (ADS)

    Banerji, Christopher R. S.; Miranda-Saavedra, Diego; Severini, Simone; Widschwendter, Martin; Enver, Tariq; Zhou, Joseph X.; Teschendorff, Andrew E.

    2013-10-01

    Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape.

  5. Logical Modeling and Dynamical Analysis of Cellular Networks

    PubMed Central

    Abou-Jaoudé, Wassim; Traynard, Pauline; Monteiro, Pedro T.; Saez-Rodriguez, Julio; Helikar, Tomáš; Thieffry, Denis; Chaouiya, Claudine

    2016-01-01

    The logical (or logic) formalism is increasingly used to model regulatory and signaling networks. Complementing these applications, several groups contributed various methods and tools to support the definition and analysis of logical models. After an introduction to the logical modeling framework and to several of its variants, we review here a number of recent methodological advances to ease the analysis of large and intricate networks. In particular, we survey approaches to determine model attractors and their reachability properties, to assess the dynamical impact of variations of external signals, and to consistently reduce large models. To illustrate these developments, we further consider several published logical models for two important biological processes, namely the differentiation of T helper cells and the control of mammalian cell cycle. PMID:27303434

  6. Dynamical modeling and analysis of large cellular regulatory networks

    NASA Astrophysics Data System (ADS)

    Bérenguier, D.; Chaouiya, C.; Monteiro, P. T.; Naldi, A.; Remy, E.; Thieffry, D.; Tichit, L.

    2013-06-01

    The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.

  7. Cellular Metabolic Network Analysis: Discovering Important Reactions in Treponema pallidum

    PubMed Central

    Chen, Xueying; Zhao, Min; Qu, Hong

    2015-01-01

    T. pallidum, the syphilis-causing pathogen, performs very differently in metabolism compared with other bacterial pathogens. The desire for safe and effective vaccine of syphilis requests identification of important steps in T. pallidum's metabolism. Here, we apply Flux Balance Analysis to represent the reactions quantitatively. Thus, it is possible to cluster all reactions in T. pallidum. By calculating minimal cut sets and analyzing topological structure for the metabolic network of T. pallidum, critical reactions are identified. As a comparison, we also apply the analytical approaches to the metabolic network of H. pylori to find coregulated drug targets and unique drug targets for different microorganisms. Based on the clustering results, all reactions are further classified into various roles. Therefore, the general picture of their metabolic network is obtained and two types of reactions, both of which are involved in nucleic acid metabolism, are found to be essential for T. pallidum. It is also discovered that both hubs of reactions and the isolated reactions in purine and pyrimidine metabolisms play important roles in T. pallidum. These reactions could be potential drug targets for treating syphilis. PMID:26495292

  8. Cellular metabolic network analysis: discovering important reactions in Treponema pallidum.

    PubMed

    Chen, Xueying; Zhao, Min; Qu, Hong

    2015-01-01

    T. pallidum, the syphilis-causing pathogen, performs very differently in metabolism compared with other bacterial pathogens. The desire for safe and effective vaccine of syphilis requests identification of important steps in T. pallidum's metabolism. Here, we apply Flux Balance Analysis to represent the reactions quantitatively. Thus, it is possible to cluster all reactions in T. pallidum. By calculating minimal cut sets and analyzing topological structure for the metabolic network of T. pallidum, critical reactions are identified. As a comparison, we also apply the analytical approaches to the metabolic network of H. pylori to find coregulated drug targets and unique drug targets for different microorganisms. Based on the clustering results, all reactions are further classified into various roles. Therefore, the general picture of their metabolic network is obtained and two types of reactions, both of which are involved in nucleic acid metabolism, are found to be essential for T. pallidum. It is also discovered that both hubs of reactions and the isolated reactions in purine and pyrimidine metabolisms play important roles in T. pallidum. These reactions could be potential drug targets for treating syphilis. PMID:26495292

  9. Multiperiod cellular network design via price-influenced simulated annealing (PISA).

    PubMed

    Menon, Syam; Amiri, Ali

    2006-06-01

    Cellular telecommunications systems tend to be more flexible than traditional ones. As a result, traditional approaches to telecommunications network design are often inappropriate for the design of cellular networks, and approaches that explicitly incorporate the increased flexibility into the design process need to be developed. This paper presents one such multiperiod cellular network design problem and solves it via a hybrid heuristic that incorporates ideas from linear programming (LP) and simulated annealing (SA). Extensive computational results comparing the performance of the heuristic with the lower bound obtained from the LP relaxation are presented. These results indicate that this price-influenced simulated annealing (PISA) procedure is extremely efficient, consistently providing solutions with average gaps of 0.30% or less in fewer than 30 s. PMID:16761813

  10. Protease-associated cellular networks in malaria parasite Plasmodium falciparum

    PubMed Central

    2011-01-01

    Background Malaria continues to be one of the most severe global infectious diseases, responsible for 1-2 million deaths yearly. The rapid evolution and spread of drug resistance in parasites has led to an urgent need for the development of novel antimalarial targets. Proteases are a group of enzymes that play essential roles in parasite growth and invasion. The possibility of designing specific inhibitors for proteases makes them promising drug targets. Previously, combining a comparative genomics approach and a machine learning approach, we identified the complement of proteases (degradome) in the malaria parasite Plasmodium falciparum and its sibling species [1-3], providing a catalog of targets for functional characterization and rational inhibitor design. Network analysis represents another route to revealing the role of proteins in the biology of parasites and we use this approach here to expand our understanding of the systems involving the proteases of P. falciparum. Results We investigated the roles of proteases in the parasite life cycle by constructing a network using protein-protein association data from the STRING database [4], and analyzing these data, in conjunction with the data from protein-protein interaction assays using the yeast 2-hybrid (Y2H) system [5], blood stage microarray experiments [6-8], proteomics [9-12], literature text mining, and sequence homology analysis. Seventy-seven (77) out of 124 predicted proteases were associated with at least one other protein, constituting 2,431 protein-protein interactions (PPIs). These proteases appear to play diverse roles in metabolism, cell cycle regulation, invasion and infection. Their degrees of connectivity (i.e., connections to other proteins), range from one to 143. The largest protease-associated sub-network is the ubiquitin-proteasome system which is crucial for protein recycling and stress response. Proteases are also implicated in heat shock response, signal peptide processing, cell cycle

  11. [Construction and structural analysis of integrated cellular network of Corynebacterium glutamicum].

    PubMed

    Jiang, Jinguo; Song, Lifu; Zheng, Ping; Jia, Shiru; Sun, Jibin

    2012-05-01

    Corynebacterium glutamicum is one of the most important traditional industrial microorganisms and receiving more and more attention towards a novel cellular factory due to the recently rapid development in genomics and genetic operation toolboxes for Corynebacterium. However, compared to other model organisms such as Escherichia coli, there were few studies on its metabolic regulation, especially a genome-scale integrated cellular network model currently missing for Corynebacterium, which hindered the systematic study of Corynebacterium glutamicum and large-scale rational design and optimization for strains. Here, by gathering relevant information from a number of public databases, we successfully constructed an integrated cellular network, which was composed of 1384 reactions, 1276 metabolites, 88 transcriptional factors and 999 pairs of transcriptional regulatory relationships. The transcriptional regulatory sub-network could be arranged into five layers and the metabolic sub-network presented a clear bow-tie structure. We proposed a new method to extract complex metabolic and regulatory sub-network for product-orientated study taking lysine biosynthesis as an example. The metabolic and regulatory sub-network extracted by our method was more close to the real functional network than the simplex biochemical pathways. The results would be greatly helpful for understanding the high-yielding biomechanism for amino acids and the re-design of the industrial strains. PMID:22916496

  12. A malignant cellular network in gliomas: potential clinical implications.

    PubMed

    Osswald, Matthias; Solecki, Gergely; Wick, Wolfgang; Winkler, Frank

    2016-04-01

    The recent discovery of distinct, ultra-long, and highly functional membrane protrusions in gliomas, particularly in astrocytomas, extends our understanding of how these tumors progress in the brain and how they resist therapies. In this article, we will focus on ideas on how to target these membrane protrusions, for which we have suggested the term "tumor microtubes" (TMs), and the malignant multicellular network they form. First, we discuss TM-specific features and their differential biological functions known so far. Second, the connection between 1p/19q codeletion and the inability to form functional TMs via certain neurodevelopmental pathways is presented; this could provide an explanation for the distinct clinical features of oligodendrogliomas. Third, the role of TMs for primary and potentially also adaptive resistance to cytotoxic therapies is highlighted. Fourth, avenues for therapeutic approaches to inhibit TM formation and/or function are discussed, with a focus on disruption (or exploitation) of network functionality. Finally, we propose ideas on how to use TMs as a biomarker in glioma patients. An increasing understanding of TMs in clinical and preclinical settings will show us whether they really are a long-sought-after Achilles' heel of treatment-resistant gliomas. PMID:26995789

  13. Cellular Origins of Type IV Collagen Networks in Developing Glomeruli

    PubMed Central

    Abrahamson, Dale R.; Hudson, Billy G.; Stroganova, Larysa; Borza, Dorin-Bogdan; St. John, Patricia L.

    2009-01-01

    Laminin and type IV collagen composition of the glomerular basement membrane changes during glomerular development and maturation. Although it is known that both glomerular endothelial cells and podocytes produce different laminin isoforms at the appropriate stages of development, the cellular origins for the different type IV collagen heterotrimers that appear during development are unknown. Here, immunoelectron microscopy demonstrated that endothelial cells, mesangial cells, and podocytes of immature glomeruli synthesize collagen α1α2α1(IV). However, intracellular labeling revealed that podocytes, but not endothelial or mesangial cells, contain collagen α3α4α5(IV). To evaluate the origins of collagen IV further, we transplanted embryonic kidneys from Col4a3-null mutants (Alport mice) into kidneys of newborn, wildtype mice. Hybrid glomeruli within grafts containing numerous host-derived, wildtype endothelial cells never expressed collagen α3α4α5(IV). Finally, confocal microscopy of glomeruli from infant Alport mice that had been dually labeled with anti-collagen α5(IV) and the podocyte marker anti-GLEPP1 showed immunolabeling exclusively within podocytes. Together, these results indicate that collagen α3α4α5(IV) originates solely from podocytes; therefore, glomerular Alport disease is a genetic defect that manifests specifically within this cell type. PMID:19423686

  14. Cellular origins of type IV collagen networks in developing glomeruli.

    PubMed

    Abrahamson, Dale R; Hudson, Billy G; Stroganova, Larysa; Borza, Dorin-Bogdan; St John, Patricia L

    2009-07-01

    Laminin and type IV collagen composition of the glomerular basement membrane changes during glomerular development and maturation. Although it is known that both glomerular endothelial cells and podocytes produce different laminin isoforms at the appropriate stages of development, the cellular origins for the different type IV collagen heterotrimers that appear during development are unknown. Here, immunoelectron microscopy demonstrated that endothelial cells, mesangial cells, and podocytes of immature glomeruli synthesize collagen alpha 1 alpha 2 alpha1(IV). However, intracellular labeling revealed that podocytes, but not endothelial or mesangial cells, contain collagen alpha 3 alpha 4 alpha 5(IV). To evaluate the origins of collagen IV further, we transplanted embryonic kidneys from Col4a3-null mutants (Alport mice) into kidneys of newborn, wildtype mice. Hybrid glomeruli within grafts containing numerous host-derived, wildtype endothelial cells never expressed collagen alpha 3 alpha 4 alpha 5(IV). Finally, confocal microscopy of glomeruli from infant Alport mice that had been dually labeled with anti-collagen alpha 5(IV) and the podocyte marker anti-GLEPP1 showed immunolabeling exclusively within podocytes. Together, these results indicate that collagen alpha 3 alpha 4 alpha 5(IV) originates solely from podocytes; therefore, glomerular Alport disease is a genetic defect that manifests specifically within this cell type. PMID:19423686

  15. The role of topological features of intercellular communication networks by the synchronization of cellular oscillators

    NASA Astrophysics Data System (ADS)

    Markovič, R.; Gosak, M.; Marhl, M.

    2012-08-01

    Because of the complexity of processes that govern the regulatory mechanisms which control the cellular functions and dynamic behavior, mathematical models and numerical simulations are needed to fully grasp the mechanisms and functions of biological rhythms. In the last decade the theory of complex networks is frequently applied to address those issues. In the present paper we investigate theoretically the role of the intercellular communication network structure by synchronization of cellular oscillators. Motivated by the fact that in biological systems the interplay between the network structure and the dynamics taking place on it is closely interrelated, we develop a spatial network representation of an ensemble of cells in which we can tune the network organization between a scale-free network with dominating long-range connections and a homogeneous network with mostly adjacent neurons connected. Our results reveal that for noise-induced oscillations in excitable cells and for chaotic bursting oscillations the most synchronized response is obtained for the intermediate regime where long-as well as short-range connections constitute the intercellular network. On the other hand, for periodic oscillations it is found than the scale-free network topology ensures the greatest collective response. We argue that those findings are related to flexibility properties of individual cells.

  16. A Mathematical Model to study the Dynamics of Epithelial Cellular Networks

    PubMed Central

    Abate, Alessandro; Vincent, Stéphane; Dobbe, Roel; Silletti, Alberto; Master, Neal; Axelrod, Jeffrey D.; Tomlin, Claire J.

    2013-01-01

    Epithelia are sheets of connected cells that are essential across the animal kingdom. Experimental observations suggest that the dynamical behavior of many single-layered epithelial tissues has strong analogies with that of specific mechanical systems, namely large networks consisting of point masses connected through spring-damper elements and undergoing the influence of active and dissipating forces. Based on this analogy, this work develops a modeling framework to enable the study of the mechanical properties and of the dynamic behavior of large epithelial cellular networks. The model is built first by creating a network topology that is extracted from the actual cellular geometry as obtained from experiments, then by associating a mechanical structure and dynamics to the network via spring-damper elements. This scalable approach enables running simulations of large network dynamics: the derived modeling framework in particular is predisposed to be tailored to study general dynamics (for example, morphogenesis) of various classes of single-layered epithelial cellular networks. In this contribution we test the model on a case study of the dorsal epithelium of the Drosophila melanogaster embryo during early dorsal closure (and, less conspicuously, germband retraction). PMID:23221083

  17. Identification of driving network of cellular differentiation from single sample time course gene expression data

    NASA Astrophysics Data System (ADS)

    Chen, Ye; Wolanyk, Nathaniel; Ilker, Tunc; Gao, Shouguo; Wang, Xujing

    Methods developed based on bifurcation theory have demonstrated their potential in driving network identification for complex human diseases, including the work by Chen, et al. Recently bifurcation theory has been successfully applied to model cellular differentiation. However, there one often faces a technical challenge in driving network prediction: time course cellular differentiation study often only contains one sample at each time point, while driving network prediction typically require multiple samples at each time point to infer the variation and interaction structures of candidate genes for the driving network. In this study, we investigate several methods to identify both the critical time point and the driving network through examination of how each time point affects the autocorrelation and phase locking. We apply these methods to a high-throughput sequencing (RNA-Seq) dataset of 42 subsets of thymocytes and mature peripheral T cells at multiple time points during their differentiation (GSE48138 from GEO). We compare the predicted driving genes with known transcription regulators of cellular differentiation. We will discuss the advantages and limitations of our proposed methods, as well as potential further improvements of our methods.

  18. Retrieval algorithm for rainfall mapping from microwave links in a cellular communication network

    NASA Astrophysics Data System (ADS)

    Overeem, A.; Leijnse, H.; Uijlenhoet, R.

    2015-08-01

    Microwave links in commercial cellular communication networks hold a promise for areal rainfall monitoring and could complement rainfall estimates from ground-based weather radars, rain gauges, and satellites. It has been shown that country-wide rainfall maps can be derived from the signal attenuations of microwave links in such a network. Here we give a detailed description of the employed rainfall retrieval algorithm and provide the corresponding code. Moreover, the code (in the scripting language "R") is made available including a data set of commercial microwave links. The purpose of this paper is to promote rainfall monitoring utilizing microwave links from cellular communication networks as an alternative or complementary means for global, continental-scale rainfall monitoring.

  19. Retrieval algorithm for rainfall mapping from microwave links in a cellular communication network

    NASA Astrophysics Data System (ADS)

    Overeem, Aart; Leijnse, Hidde; Uijlenhoet, Remko

    2016-06-01

    Microwave links in commercial cellular communication networks hold a promise for areal rainfall monitoring and could complement rainfall estimates from ground-based weather radars, rain gauges, and satellites. It has been shown that country-wide (≈ 35 500 km2) 15 min rainfall maps can be derived from the signal attenuations of approximately 2400 microwave links in such a network. Here we give a detailed description of the employed rainfall retrieval algorithm. Moreover, the documented, modular, and user-friendly code (a package in the scripting language "R") is made available, including a 2-day data set of approximately 2600 commercial microwave links from the Netherlands. The purpose of this paper is to promote rainfall mapping utilising microwave links from cellular communication networks as an alternative or complementary means for continental-scale rainfall monitoring.

  20. A self-learning call admission control scheme for CDMA cellular networks.

    PubMed

    Liu, Derong; Zhang, Yi; Zhang, Huaguang

    2005-09-01

    In the present paper, a call admission control scheme that can learn from the network environment and user behavior is developed for code division multiple access (CDMA) cellular networks that handle both voice and data services. The idea is built upon a novel learning control architecture with only a single module instead of two or three modules in adaptive critic designs (ACDs). The use of adaptive critic approach for call admission control in wireless cellular networks is new. The call admission controller can perform learning in real-time as well as in offline environments and the controller improves its performance as it gains more experience. Another important contribution in the present work is the choice of utility function for the present self-learning control approach which makes the present learning process much more efficient than existing learning control methods. The performance of our algorithm will be shown through computer simulation and compared with existing algorithms. PMID:16252828

  1. The Electrophysiological MEMS Device with Micro Channel Array for Cellular Network Analysis

    NASA Astrophysics Data System (ADS)

    Tonomura, Wataru; Kurashima, Toshiaki; Takayama, Yuzo; Moriguchi, Hiroyuki; Jimbo, Yasuhiko; Konishi, Satoshi

    This paper describes a new type of MCA (Micro Channel Array) for simultaneous multipoint measurement of cellular network. Presented MCA employing the measurement principles of the patch-clamp technique is designed for advanced neural network analysis which has been studied by co-authors using 64ch MEA (Micro Electrode Arrays) system. First of all, sucking and clamping of cells through channels of developed MCA is expected to improve electrophysiological signal detections. Electrophysiological sensing electrodes integrated around individual channels of MCA by using MEMS (Micro Electro Mechanical System) technologies are electrically isolated for simultaneous multipoint measurement. In this study, we tested the developed MCA using the non-cultured rat's cerebral cortical slice and the hippocampal neurons. We could measure the spontaneous action potential of the slice simultaneously at multiple points and culture the neurons on developed MCA. Herein, we describe the experimental results together with the design and fabrication of the electrophysiological MEMS device with MCA for cellular network analysis.

  2. Cellular automata with object-oriented features for parallel molecular network modeling.

    PubMed

    Zhu, Hao; Wu, Yinghui; Huang, Sui; Sun, Yan; Dhar, Pawan

    2005-06-01

    Cellular automata are an important modeling paradigm for studying the dynamics of large, parallel systems composed of multiple, interacting components. However, to model biological systems, cellular automata need to be extended beyond the large-scale parallelism and intensive communication in order to capture two fundamental properties characteristic of complex biological systems: hierarchy and heterogeneity. This paper proposes extensions to a cellular automata language, Cellang, to meet this purpose. The extended language, with object-oriented features, can be used to describe the structure and activity of parallel molecular networks within cells. Capabilities of this new programming language include object structure to define molecular programs within a cell, floating-point data type and mathematical functions to perform quantitative computation, message passing capability to describe molecular interactions, as well as new operators, statements, and built-in functions. We discuss relevant programming issues of these features, including the object-oriented description of molecular interactions with molecule encapsulation, message passing, and the description of heterogeneity and anisotropy at the cell and molecule levels. By enabling the integration of modeling at the molecular level with system behavior at cell, tissue, organ, or even organism levels, the program will help improve our understanding of how complex and dynamic biological activities are generated and controlled by parallel functioning of molecular networks. Index Terms-Cellular automata, modeling, molecular network, object-oriented. PMID:16117022

  3. Interference Avoiding Radio Resource Allocation Scheme for Multi-hop OFDMA Cellular Networks with Random Topology

    NASA Astrophysics Data System (ADS)

    Lim, Sunggook; Lee, Jaiyong

    Relaying technology is the one of the solutions to expand the coverage and enhance the throughput of a cellular network with low cost, therefore numerous smart relay stations (RSs) which are able to schedule its own transmission frame and manage radio resources allocated by its serving base station (BS) will be deployed within the cellular network. while more RSs are deployed, the network topology is turning to the random topology. In the random topology, however, conventional frequency reuse schemes based on the uniformly distributed RSs are not adoptable because of the randomness for locations of RSs. Another problem is severe increase of interference during the transmission period for an access link because more transmitters including BSs and RSs are existed within a cell. We suggest the random-topology frequency reuse (RFR) scheme supporting the frequency reuse in the cellular multi-hop network with random topology to reduce intra-cell interference. The simulation results show RFR is reducing the overall intra-cell interference compared to the full allocation scheme whose reuse factor is one. The throughput and average signal to interference plus noise ratio (SINR) is still greater than the full allocation scheme although the spectral efficiency is lower than the compared scheme.

  4. Relating the sequential dynamics of excitatory neural networks to synaptic cellular automata.

    PubMed

    Nekorkin, V I; Dmitrichev, A S; Kasatkin, D V; Afraimovich, V S

    2011-12-01

    We have developed a new approach for the description of sequential dynamics of excitatory neural networks. Our approach is based on the dynamics of synapses possessing the short-term plasticity property. We suggest a model of such synapses in the form of a second-order system of nonlinear ODEs. In the framework of the model two types of responses are realized-the fast and the slow ones. Under some relations between their timescales a cellular automaton (CA) on the graph of connections is constructed. Such a CA has only a finite number of attractors and all of them are periodic orbits. The attractors of the CA determine the regimes of sequential dynamics of the original neural network, i.e., itineraries along the network and the times of successive firing of neurons in the form of bunches of spikes. We illustrate our approach on the example of a Morris-Lecar neural network. PMID:22225361

  5. Two programmed replicative lifespans of Saccharomyces cerevisiae formed by the endogenous molecular-cellular network.

    PubMed

    Hu, Jie; Zhu, Xiaomei; Wang, Xinan; Yuan, Ruoshi; Zheng, Wei; Xu, Minjuan; Ao, Ping

    2014-12-01

    Cellular replicative capacity is a therapeutic target for regenerative medicine as well as cancer treatment. The mechanism of replicative senescence and cell immortality is still unclear. We investigated the diauxic growth of Saccharomyces cerevisiae and demonstrate that the replicative capacity revealed by the yeast growth curve can be understood by using the dynamical property of the molecular-cellular network regulating S. cerevisiae. The endogenous network we proposed has a limit cycle when pheromone signaling is disabled, consistent with the exponential growth phase with an infinite replicative capacity. In the post-diauxic phase, the cooperative effect of the pheromone activated mitogen-activated protein kinase (MAPK) signaling pathway with the cell cycle leads to a fixed point attractor instead of the limit cycle. The cells stop dividing after several generations counting from the beginning of the post-diauxic growth. By tuning the MAPK pathway, S. cerevisiae therefore programs the number of offsprings it replicates. PMID:24447585

  6. A new cellular nonlinear network emulation on FPGA for EEG signal processing in epilepsy

    NASA Astrophysics Data System (ADS)

    Müller, Jens; Müller, Jan; Tetzlaff, Ronald

    2011-05-01

    For processing of EEG signals, we propose a new architecture for the hardware emulation of discrete-time Cellular Nonlinear Networks (DT-CNN). Our results show the importance of a high computational accuracy in EEG signal prediction that cannot be achieved with existing analogue VLSI circuits. The refined architecture of the processing elements and its resource schedule, the cellular network structure with local couplings, the FPGA-based embedded system containing the DT-CNN, and the data flow in the entire system will be discussed in detail. The proposed DT-CNN design has been implemented and tested on an Xilinx FPGA development platform. The embedded co-processor with a multi-threading kernel is utilised for control and pre-processing tasks and data exchange to the host via Ethernet. The performance of the implemented DT-CNN has been determined for a popular example and compared to that of a conventional computer.

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

    NASA Astrophysics Data System (ADS)

    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. Application of neural networks to channel assignment for cellular CDMA networks with multiple services and mobile base stations

    NASA Astrophysics Data System (ADS)

    Hortos, William S.

    1996-03-01

    The use of artificial neural networks to the channel assignment problem for cellular code- division multiple access (CDMA) telecommunications systems is considered. CDMA takes advantage of voice activity and spatial isolation because its capacity is only interference limited, unlike time-division multiple access (TDMA) and frequency-division multiple access (FDMA) where capacities are bandwidth limited. Any reduction in interference in CDMA translates linearly into increased capacity. FDMA and TDMA use a frequency reuse pattern as a method to increase capacity, while CDMA reuses the same frequency for all cells and gains a reuse efficiency by means of orthogonal codes. The latter method can improve system capacity by factors of four to six over digital TDMA or FDMA. Cellular carriers are planning to provide multiple communication services using CDMA in the next generation cellular system infrastructure. The approach of this study is the use of neural network methods for automatic and local network control, based on traffic behavior in specific cell cites and demand history. The goal is to address certain problems associated with the management of mobile and personal communication services in a cellular radio communications environment. In planning a cellular radio network, the operator assigns channels to the radio cells so that the probability of the processed carrier-to-interference ratio, CII, exceeding a predefined value is sufficiently low. The RF propagation, determined from the topography and infrastructure in the operating area, is used in conjunction with the densities of expected communications traffic to formulate interference constraints. These constraints state which radio cells may use the same code (channel) or adjacent channels at a time. The traffic loading and the number of service grades can also be used to calculate the number of required channels (codes) for each cell. The general assignment problem is the task of assigning the required number

  9. Cellular Neural Network Models of Growth and Immune of Effector Cells Response to Cancer

    NASA Astrophysics Data System (ADS)

    Su, Yongmei; Min, Lequan

    Four reaction-diffusion cellular neural network (R-D CNN) models are set up based on the differential equation models for the growths of effector cells and cancer cells, and the model of the immune response to cancer proposed by Allison et al. The CNN models have different reaction-diffusion coefficients and coupling parameters. The R-D CNN models may provide possible quantitative interpretations, and are good in agreement with the in vitro experiment data reported by Allison et al.

  10. Measuring information flow in cellular networks by the systems biology method through microarray data

    PubMed Central

    Chen, Bor-Sen; Li, Cheng-Wei

    2015-01-01

    In general, it is very difficult to measure the information flow in a cellular network directly. In this study, based on an information flow model and microarray data, we measured the information flow in cellular networks indirectly by using a systems biology method. First, we used a recursive least square parameter estimation algorithm to identify the system parameters of coupling signal transduction pathways and the cellular gene regulatory network (GRN). Then, based on the identified parameters and systems theory, we estimated the signal transductivities of the coupling signal transduction pathways from the extracellular signals to each downstream protein and the information transductivities of the GRN between transcription factors in response to environmental events. According to the proposed method, the information flow, which is characterized by signal transductivity in coupling signaling pathways and information transductivity in the GRN, can be estimated by microarray temporal data or microarray sample data. It can also be estimated by other high-throughput data such as next-generation sequencing or proteomic data. Finally, the information flows of the signal transduction pathways and the GRN in leukemia cancer cells and non-leukemia normal cells were also measured to analyze the systematic dysfunction in this cancer from microarray sample data. The results show that the signal transductivities of signal transduction pathways change substantially from normal cells to leukemia cancer cells. PMID:26082788

  11. A New Cellular Architecture for Information Retrieval from Sensor Networks through Embedded Service and Security Protocols.

    PubMed

    Shahzad, Aamir; Landry, René; Lee, Malrey; Xiong, Naixue; Lee, Jongho; Lee, Changhoon

    2016-01-01

    Substantial changes have occurred in the Information Technology (IT) sectors and with these changes, the demand for remote access to field sensor information has increased. This allows visualization, monitoring, and control through various electronic devices, such as laptops, tablets, i-Pads, PCs, and cellular phones. The smart phone is considered as a more reliable, faster and efficient device to access and monitor industrial systems and their corresponding information interfaces anywhere and anytime. This study describes the deployment of a protocol whereby industrial system information can be securely accessed by cellular phones via a Supervisory Control And Data Acquisition (SCADA) server. To achieve the study goals, proprietary protocol interconnectivity with non-proprietary protocols and the usage of interconnectivity services are considered in detail. They support the visualization of the SCADA system information, and the related operations through smart phones. The intelligent sensors are configured and designated to process real information via cellular phones by employing information exchange services between the proprietary protocol and non-proprietary protocols. SCADA cellular access raises the issue of security flaws. For these challenges, a cryptography-based security method is considered and deployed, and it could be considered as a part of a proprietary protocol. Subsequently, transmission flows from the smart phones through a cellular network. PMID:27314351

  12. A New Cellular Architecture for Information Retrieval from Sensor Networks through Embedded Service and Security Protocols

    PubMed Central

    Shahzad, Aamir; Landry, René; Lee, Malrey; Xiong, Naixue; Lee, Jongho; Lee, Changhoon

    2016-01-01

    Substantial changes have occurred in the Information Technology (IT) sectors and with these changes, the demand for remote access to field sensor information has increased. This allows visualization, monitoring, and control through various electronic devices, such as laptops, tablets, i-Pads, PCs, and cellular phones. The smart phone is considered as a more reliable, faster and efficient device to access and monitor industrial systems and their corresponding information interfaces anywhere and anytime. This study describes the deployment of a protocol whereby industrial system information can be securely accessed by cellular phones via a Supervisory Control And Data Acquisition (SCADA) server. To achieve the study goals, proprietary protocol interconnectivity with non-proprietary protocols and the usage of interconnectivity services are considered in detail. They support the visualization of the SCADA system information, and the related operations through smart phones. The intelligent sensors are configured and designated to process real information via cellular phones by employing information exchange services between the proprietary protocol and non-proprietary protocols. SCADA cellular access raises the issue of security flaws. For these challenges, a cryptography-based security method is considered and deployed, and it could be considered as a part of a proprietary protocol. Subsequently, transmission flows from the smart phones through a cellular network. PMID:27314351

  13. An Asynchronous Recurrent Network of Cellular Automaton-Based Neurons and Its Reproduction of Spiking Neural Network Activities.

    PubMed

    Matsubara, Takashi; Torikai, Hiroyuki

    2016-04-01

    Modeling and implementation approaches for the reproduction of input-output relationships in biological nervous tissues contribute to the development of engineering and clinical applications. However, because of high nonlinearity, the traditional modeling and implementation approaches encounter difficulties in terms of generalization ability (i.e., performance when reproducing an unknown data set) and computational resources (i.e., computation time and circuit elements). To overcome these difficulties, asynchronous cellular automaton-based neuron (ACAN) models, which are described as special kinds of cellular automata that can be implemented as small asynchronous sequential logic circuits have been proposed. This paper presents a novel type of such ACAN and a theoretical analysis of its excitability. This paper also presents a novel network of such neurons, which can mimic input-output relationships of biological and nonlinear ordinary differential equation model neural networks. Numerical analyses confirm that the presented network has a higher generalization ability than other major modeling and implementation approaches. In addition, Field-Programmable Gate Array-implementations confirm that the presented network requires lower computational resources. PMID:25974951

  14. Motion Adaptive Vertical Handoff in Cellular/WLAN Heterogeneous Wireless Network

    PubMed Central

    Ma, Lin; Xu, Yubin; Fu, Yunhai

    2014-01-01

    In heterogeneous wireless network, vertical handoff plays an important role for guaranteeing quality of service and overall performance of network. Conventional vertical handoff trigger schemes are mostly developed from horizontal handoff in homogeneous cellular network. Basically, they can be summarized as hysteresis-based and dwelling-timer-based algorithms, which are reliable on avoiding unnecessary handoff caused by the terminals dwelling at the edge of WLAN coverage. However, the coverage of WLAN is much smaller compared with cellular network, while the motion types of terminals can be various in a typical outdoor scenario. As a result, traditional algorithms are less effective in avoiding unnecessary handoff triggered by vehicle-borne terminals with various speeds. Besides that, hysteresis and dwelling-timer thresholds usually need to be modified to satisfy different channel environments. For solving this problem, a vertical handoff algorithm based on Q-learning is proposed in this paper. Q-learning can provide the decider with self-adaptive ability for handling the terminals' handoff requests with different motion types and channel conditions. Meanwhile, Neural Fuzzy Inference System (NFIS) is embedded to retain a continuous perception of the state space. Simulation results verify that the proposed algorithm can achieve lower unnecessary handoff probability compared with the other two conventional algorithms. PMID:24741347

  15. Motion adaptive vertical handoff in cellular/WLAN heterogeneous wireless network.

    PubMed

    Li, Limin; Ma, Lin; Xu, Yubin; Fu, Yunhai

    2014-01-01

    In heterogeneous wireless network, vertical handoff plays an important role for guaranteeing quality of service and overall performance of network. Conventional vertical handoff trigger schemes are mostly developed from horizontal handoff in homogeneous cellular network. Basically, they can be summarized as hysteresis-based and dwelling-timer-based algorithms, which are reliable on avoiding unnecessary handoff caused by the terminals dwelling at the edge of WLAN coverage. However, the coverage of WLAN is much smaller compared with cellular network, while the motion types of terminals can be various in a typical outdoor scenario. As a result, traditional algorithms are less effective in avoiding unnecessary handoff triggered by vehicle-borne terminals with various speeds. Besides that, hysteresis and dwelling-timer thresholds usually need to be modified to satisfy different channel environments. For solving this problem, a vertical handoff algorithm based on Q-learning is proposed in this paper. Q-learning can provide the decider with self-adaptive ability for handling the terminals' handoff requests with different motion types and channel conditions. Meanwhile, Neural Fuzzy Inference System (NFIS) is embedded to retain a continuous perception of the state space. Simulation results verify that the proposed algorithm can achieve lower unnecessary handoff probability compared with the other two conventional algorithms. PMID:24741347

  16. Phase transitions in pancreatic islet cellular networks and implications for type-1 diabetes

    NASA Astrophysics Data System (ADS)

    Stamper, I. J.; Jackson, Elais; Wang, Xujing

    2014-01-01

    In many aspects the onset of a chronic disease resembles a phase transition in a complex dynamic system: Quantitative changes accumulate largely unnoticed until a critical threshold is reached, which causes abrupt qualitative changes of the system. In this study we examine a special case, the onset of type-1 diabetes (T1D), a disease that results from loss of the insulin-producing pancreatic islet β cells. Within each islet, the β cells are electrically coupled to each other via gap-junctional channels. This intercellular coupling enables the β cells to synchronize their insulin release, thereby generating the multiscale temporal rhythms in blood insulin that are critical to maintaining blood glucose homeostasis. Using percolation theory we show how normal islet function is intrinsically linked to network connectivity. In particular, the critical amount of β-cell death at which the islet cellular network loses site percolation is consistent with laboratory and clinical observations of the threshold loss of β cells that causes islet functional failure. In addition, numerical simulations confirm that the islet cellular network needs to be percolated for β cells to synchronize. Furthermore, the interplay between site percolation and bond strength predicts the existence of a transient phase of islet functional recovery after onset of T1D and introduction of treatment, potentially explaining the honeymoon phenomenon. Based on these results, we hypothesize that the onset of T1D may be the result of a phase transition of the islet β-cell network.

  17. A computable cellular stress network model for non-diseased pulmonary and cardiovascular tissue

    PubMed Central

    2011-01-01

    Background Humans and other organisms are equipped with a set of responses that can prevent damage from exposure to a multitude of endogenous and environmental stressors. If these stress responses are overwhelmed, this can result in pathogenesis of diseases, which is reflected by an increased development of, e.g., pulmonary and cardiac diseases in humans exposed to chronic levels of environmental stress, including inhaled cigarette smoke (CS). Systems biology data sets (e.g., transcriptomics, phosphoproteomics, metabolomics) could enable comprehensive investigation of the biological impact of these stressors. However, detailed mechanistic networks are needed to determine which specific pathways are activated in response to different stressors and to drive the qualitative and eventually quantitative assessment of these data. A current limiting step in this process is the availability of detailed mechanistic networks that can be used as an analytical substrate. Results We have built a detailed network model that captures the biology underlying the physiological cellular response to endogenous and exogenous stressors in non-diseased mammalian pulmonary and cardiovascular cells. The contents of the network model reflect several diverse areas of signaling, including oxidative stress, hypoxia, shear stress, endoplasmic reticulum stress, and xenobiotic stress, that are elicited in response to common pulmonary and cardiovascular stressors. We then tested the ability of the network model to identify the mechanisms that are activated in response to CS, a broad inducer of cellular stress. Using transcriptomic data from the lungs of mice exposed to CS, the network model identified a robust increase in the oxidative stress response, largely mediated by the anti-oxidant NRF2 pathways, consistent with previous reports on the impact of CS exposure in the mammalian lung. Conclusions The results presented here describe the construction of a cellular stress network model and its

  18. Increasing the coverage area through relay node deployment in long term evolution advanced cellular networks

    NASA Astrophysics Data System (ADS)

    Aldhaibani, Jaafar A.; Ahmad, R. B.; Yahya, A.; Azeez, Suzan A.

    2015-05-01

    Wireless multi-hop relay networks have become very important technologies in mobile communications. These networks ensure high throughput and coverage extension with a low cost. The poor capacity at cell edges is not enough to meet with growing demand of high capacity and throughput irrespective of user's placement in the cellular network. In this paper we propose optimal placement of relay node that provides maximum achievable rate at users and enhances the throughput and coverage at cell edge region. The proposed scheme is based on the outage probability at users and taken on account the interference between nodes. Numerical analyses along with simulation results indicated there are an improvement in capacity for users at the cell edge is 40% increment from all cell capacity.

  19. Optimal design of sewer networks using cellular automata-based hybrid methods: Discrete and continuous approaches

    NASA Astrophysics Data System (ADS)

    Afshar, M. H.; Rohani, M.

    2012-01-01

    In this article, cellular automata based hybrid methods are proposed for the optimal design of sewer networks and their performance is compared with some of the common heuristic search methods. The problem of optimal design of sewer networks is first decomposed into two sub-optimization problems which are solved iteratively in a two stage manner. In the first stage, the pipe diameters of the network are assumed fixed and the nodal cover depths of the network are determined by solving a nonlinear sub-optimization problem. A cellular automata (CA) method is used for the solution of the optimization problem with the network nodes considered as the cells and their cover depths as the cell states. In the second stage, the nodal cover depths calculated from the first stage are fixed and the pipe diameters are calculated by solving a second nonlinear sub-optimization problem. Once again a CA method is used to solve the optimization problem of the second stage with the pipes considered as the CA cells and their corresponding diameters as the cell states. Two different updating rules are derived and used for the CA of the second stage depending on the treatment of the pipe diameters. In the continuous approach, the pipe diameters are considered as continuous variables and the corresponding updating rule is derived mathematically from the original objective function of the problem. In the discrete approach, however, an adhoc updating rule is derived and used taking into account the discrete nature of the pipe diameters. The proposed methods are used to optimally solve two sewer network problems and the results are presented and compared with those obtained by other methods. The results show that the proposed CA based hybrid methods are more efficient and effective than the most powerful search methods considered in this work.

  20. Cellular neural network-based hybrid approach toward automatic image registration

    NASA Astrophysics Data System (ADS)

    Arun, Pattathal VijayaKumar; Katiyar, Sunil Kumar

    2013-01-01

    Image registration is a key component of various image processing operations that involve the analysis of different image data sets. Automatic image registration domains have witnessed the application of many intelligent methodologies over the past decade; however, inability to properly model object shape as well as contextual information has limited the attainable accuracy. A framework for accurate feature shape modeling and adaptive resampling using advanced techniques such as vector machines, cellular neural network (CNN), scale invariant feature transform (SIFT), coreset, and cellular automata is proposed. CNN has been found to be effective in improving feature matching as well as resampling stages of registration and complexity of the approach has been considerably reduced using coreset optimization. The salient features of this work are cellular neural network approach-based SIFT feature point optimization, adaptive resampling, and intelligent object modelling. Developed methodology has been compared with contemporary methods using different statistical measures. Investigations over various satellite images revealed that considerable success was achieved with the approach. This system has dynamically used spectral and spatial information for representing contextual knowledge using CNN-prolog approach. This methodology is also illustrated to be effective in providing intelligent interpretation and adaptive resampling.

  1. A multimedia session-aware QoS provisioning scheme for cellular networks

    NASA Astrophysics Data System (ADS)

    Rizvi, Mona E.; Olariu, Stephan

    2005-03-01

    Multimedia applications often involve a set of cooperating streams that together form a multimedia session. We propose a novel local QoS provisioning scheme for cellular networks that is aware of the relationships between the streams that compose a session. As a rule, existing schemes either allow composite streams to compete with one another for resources or else provide QoS to the session as an atomic entity, leaving to the application the task of managing QoS for the individual streams. Our new MUltimedia SessIon-aware Cellular (MUSIC) QoS provisioning scheme manages the QoS of the individual streams in a session, and with the knowledge of their relationships, it prevents competition between the streams. Further, by allowing an application-specified prioritization between streams in a session, MUSIC scheme features a significant improvement in performance over session-unaware schemes.

  2. Segmentation algorithm via Cellular Neural/Nonlinear Network: implementation on Bio-inspired hardware platform

    NASA Astrophysics Data System (ADS)

    Karabiber, Fethullah; Vecchio, Pietro; Grassi, Giuseppe

    2011-12-01

    The Bio-inspired (Bi-i) Cellular Vision System is a computing platform consisting of sensing, array sensing-processing, and digital signal processing. The platform is based on the Cellular Neural/Nonlinear Network (CNN) paradigm. This article presents the implementation of a novel CNN-based segmentation algorithm onto the Bi-i system. Each part of the algorithm, along with the corresponding implementation on the hardware platform, is carefully described through the article. The experimental results, carried out for Foreman and Car-phone video sequences, highlight the feasibility of the approach, which provides a frame rate of about 26 frames/s. Comparisons with existing CNN-based methods show that the conceived approach is more accurate, thus representing a good trade-off between real-time requirements and accuracy.

  3. Cellular Signaling Networks Function as Generalized Wiener-Kolmogorov Filters to Suppress Noise

    NASA Astrophysics Data System (ADS)

    Hinczewski, Michael; Thirumalai, D.

    2014-10-01

    Cellular signaling involves the transmission of environmental information through cascades of stochastic biochemical reactions, inevitably introducing noise that compromises signal fidelity. Each stage of the cascade often takes the form of a kinase-phosphatase push-pull network, a basic unit of signaling pathways whose malfunction is linked with a host of cancers. We show that this ubiquitous enzymatic network motif effectively behaves as a Wiener-Kolmogorov optimal noise filter. Using concepts from umbral calculus, we generalize the linear Wiener-Kolmogorov theory, originally introduced in the context of communication and control engineering, to take nonlinear signal transduction and discrete molecule populations into account. This allows us to derive rigorous constraints for efficient noise reduction in this biochemical system. Our mathematical formalism yields bounds on filter performance in cases important to cellular function—such as ultrasensitive response to stimuli. We highlight features of the system relevant for optimizing filter efficiency, encoded in a single, measurable, dimensionless parameter. Our theory, which describes noise control in a large class of signal transduction networks, is also useful both for the design of synthetic biochemical signaling pathways and the manipulation of pathways through experimental probes such as oscillatory input.

  4. Cellular network formation of hydrophobic alkanethiol capped gold nanoparticles on mica surface mediated by water islands.

    PubMed

    John, Neena S; Raina, Gargi; Sharma, Ashutosh; Kulkarni, Giridhar U

    2010-09-01

    Dendritic and cellular networks of nanoparticles are known to form commonly either by random diffusion-limited aggregation or by solvent evaporation dynamics. Using alkanethiol capped gold nanoparticles deposited on mica imaged under ambient and controlled water vapor conditions by atomic force microscope and in situ scanning electron microscope, respectively, we show a third mechanism in action. The cellular network consisting of open and closed polygons is formed by the nucleation and lateral growth of adsorbed water islands, the contact lines of which push the randomly distributed hydrophobic nanoparticles along the growth directions, eventually leading to the polygonal structure formation as the boundaries of the growing islands meet. Such nanoparticle displacement has been possible due to the weakly adhering nature of the hydrophilic substrate, mica. These results demonstrate an important but hitherto neglected effect of adsorbed water in the structure formation on hydrophilic substrates and provide a facile tool for the fabrication of nanoparticle networks without specific particle or substrate modifications and without a tight control on particle deposition conditions during the solvent evaporation. PMID:20831330

  5. Alzheimer's as a Systems-Level Disease Involving the Interplay of Multiple Cellular Networks.

    PubMed

    Castrillo, Juan I; Oliver, Stephen G

    2016-01-01

    Alzheimer's disease (AD), and many neurodegenerative disorders, are multifactorial in nature. They involve a combination of genomic, epigenomic, interactomic and environmental factors. Progress is being made, and these complex diseases are beginning to be understood as having their origin in altered states of biological networks at the cellular level. In the case of AD, genomic susceptibility and mechanisms leading to (or accompanying) the impairment of the central Amyloid Precursor Protein (APP) processing and tau networks are widely accepted as major contributors to the diseased state. The derangement of these networks may result in both the gain and loss of functions, increased generation of toxic species (e.g., toxic soluble oligomers and aggregates) and imbalances, whose effects can propagate to supra-cellular levels. Although well sustained by empirical data and widely accepted, this global perspective often overlooks the essential roles played by the main counteracting homeostatic networks (e.g., protein quality control/proteostasis, unfolded protein response, protein folding chaperone networks, disaggregases, ER-associated degradation/ubiquitin proteasome system, endolysosomal network, autophagy, and other stress-protective and clearance networks), whose relevance to AD is just beginning to be fully realized. In this chapter, an integrative perspective is presented. Alzheimer's disease is characterized to be a result of: (a) intrinsic genomic/epigenomic susceptibility and, (b) a continued dynamic interplay between the deranged networks and the central homeostatic networks of nerve cells. This interplay of networks will underlie both the onset and rate of progression of the disease in each individual. Integrative Systems Biology approaches are required to effect its elucidation. Comprehensive Systems Biology experiments at different 'omics levels in simple model organisms, engineered to recapitulate the basic features of AD may illuminate the onset and

  6. Robust tracking by cellular automata and neural networks with nonlocal weights

    NASA Astrophysics Data System (ADS)

    Ososkov, Gennadii A.

    1995-04-01

    A modified rotor model of the Hopfield neural networks (HNN) is proposed for finding tracks in multiwire proportional chambers. That requires us to apply both raw data prefiltering by cellular automaton and HNN weights furnishing by a special robust multiplier. Then this model is developed to be applicable for a more general type of data and detectors. As an example, data processing of ionospheric measurements are considered. For handling tracks detected by high pressure drift chambers with their up-down ambiguity a modification of deformable templates method is proposed. A new concept of controlled HNN is proposed for solving the so-called track-match problem.

  7. Functional recognition imaging using artificial neural networks: applications to rapid cellular identification via broadband electromechanical response

    NASA Astrophysics Data System (ADS)

    Nikiforov, M. P.; Reukov, V. V.; Thompson, G. L.; Vertegel, A. A.; Guo, S.; Kalinin, S. V.; Jesse, S.

    2009-10-01

    Functional recognition imaging in scanning probe microscopy (SPM) using artificial neural network identification is demonstrated. This approach utilizes statistical analysis of complex SPM responses at a single spatial location to identify the target behavior, which is reminiscent of associative thinking in the human brain, obviating the need for analytical models. We demonstrate, as an example of recognition imaging, rapid identification of cellular organisms using the difference in electromechanical activity over a broad frequency range. Single-pixel identification of model Micrococcus lysodeikticus and Pseudomonas fluorescens bacteria is achieved, demonstrating the viability of the method.

  8. Existence and stability of traveling wave solutions for multilayer cellular neural networks

    NASA Astrophysics Data System (ADS)

    Hsu, Cheng-Hsiung; Lin, Jian-Jhong; Yang, Tzi-Sheng

    2015-08-01

    The purpose of this article is to investigate the existence and stability of traveling wave solutions for one-dimensional multilayer cellular neural networks. We first establish the existence of traveling wave solutions using the truncated technique. Then we study the asymptotic behaviors of solutions for the Cauchy problem of the neural model. Applying two kinds of comparison principles and the weighed energy method, we show that all solutions of the Cauchy problem converge exponentially to the traveling wave solutions provided that the initial data belong to a suitable weighted space.

  9. A new design for reconfigurable XOR function based on cellular neural networks

    NASA Astrophysics Data System (ADS)

    Liu, Yanyi; Liu, Wenbo

    2014-10-01

    We have described a new method to construct the reconfigurable XOR logic circuit by using the modification of the standard uncoupled cellular neural network (CNN) cells. The modification of the cell is easier to implement in engineering applications. The scheme proposed in this paper, using the modification of standard uncoupled CNN cells, allows less hardware consumption in comparison to the utilisation of chaos computing system or harnessing piecewise-linear systems. The template parameters of the modified cell have been discussed, and the physical circuit implementing the reconfigurable two-input and three-input XOR function has also been presented.

  10. Anisotropic optical flow algorithm based on self-adaptive cellular neural network

    NASA Astrophysics Data System (ADS)

    Zhang, Congxuan; Chen, Zhen; Li, Ming; Sun, Kaiqiong

    2013-01-01

    An anisotropic optical flow estimation method based on self-adaptive cellular neural networks (CNN) is proposed. First, a novel optical flow energy function which contains a robust data term and an anisotropic smoothing term is projected. Next, the CNN model which has the self-adaptive feedback operator and threshold is presented according to the Euler-Lagrange partial differential equations of the proposed optical flow energy function. Finally, the elaborate evaluation experiments indicate the significant effects of the various proposed strategies for optical flow estimation, and the comparison results with the other methods show that the proposed algorithm has better performance in computing accuracy and efficiency.

  11. Evolving Transport Networks With Cellular Automata Models Inspired by Slime Mould.

    PubMed

    Tsompanas, Michail-Antisthenis I; Sirakoulis, Georgios Ch; Adamatzky, Andrew I

    2015-09-01

    Man-made transport networks and their design are closely related to the shortest path problem and considered amongst the most debated problems of computational intelligence. Apart from using conventional or bio-inspired computer algorithms, many researchers tried to solve this kind of problem using biological computing substrates, gas-discharge solvers, prototypes of a mobile droplet, and hot ice computers. In this aspect, another example of biological computer is the plasmodium of acellular slime mould Physarum polycephalum (P. polycephalum), which is a large single cell visible by an unaided eye and has been proven as a reliable living substrate for implementing biological computing devices for computational geometry, graph-theoretical problems, and optimization and imitation of transport networks. Although P. polycephalum is easy to experiment with, computing devices built with the living slime mould are extremely slow; it takes slime mould days to execute a computation. Consequently, mapping key computing mechanisms of the slime mould onto silicon would allow us to produce efficient bio-inspired computing devices to tackle with hard to solve computational intelligence problems like the aforementioned. Toward this direction, a cellular automaton (CA)-based, Physarum-inspired, network designing model is proposed. This novel CA-based model is inspired by the propagating strategy, the formation of tubular networks, and the computing abilities of the plasmodium of P. polycephalum. The results delivered by the CA model demonstrate a good match with several previously published results of experimental laboratory studies on imitation of man-made transport networks with P. polycephalum. Consequently, the proposed CA model can be used as a virtual, easy-to-access, and biomimicking laboratory emulator that will economize large time periods needed for biological experiments while producing networks almost identical to the tubular networks of the real-slime mould. PMID

  12. Cellular telephone-based radiation sensor and wide-area detection network

    DOEpatents

    Craig, William W.; Labov, Simon E.

    2006-12-12

    A network of radiation detection instruments, each having a small solid state radiation sensor module integrated into a cellular phone for providing radiation detection data and analysis directly to a user. The sensor module includes a solid-state crystal bonded to an ASIC readout providing a low cost, low power, light weight compact instrument to detect and measure radiation energies in the local ambient radiation field. In particular, the photon energy, time of event, and location of the detection instrument at the time of detection is recorded for real time transmission to a central data collection/analysis system. The collected data from the entire network of radiation detection instruments are combined by intelligent correlation/analysis algorithms which map the background radiation and detect, identify and track radiation anomalies in the region.

  13. Multilayer cellular neural network and fuzzy C-mean classifiers: comparison and performance analysis

    NASA Astrophysics Data System (ADS)

    Trujillo San-Martin, Maite; Hlebarov, Vejen; Sadki, Mustapha

    2004-11-01

    Neural Networks and Fuzzy systems are considered two of the most important artificial intelligent algorithms which provide classification capabilities obtained through different learning schemas which capture knowledge and process it according to particular rule-based algorithms. These methods are especially suited to exploit the tolerance for uncertainty and vagueness in cognitive reasoning. By applying these methods with some relevant knowledge-based rules extracted using different data analysis tools, it is possible to obtain a robust classification performance for a wide range of applications. This paper will focus on non-destructive testing quality control systems, in particular, the study of metallic structures classification according to the corrosion time using a novel cellular neural network architecture, which will be explained in detail. Additionally, we will compare these results with the ones obtained using the Fuzzy C-means clustering algorithm and analyse both classifiers according to its classification capabilities.

  14. Evaluating a Novel Cellular Automata-Based Distributed Power Management Approach for Mobile Wireless Sensor Networks

    NASA Astrophysics Data System (ADS)

    Adabi, Sepideh; Adabi, Sahar; Rezaee, Ali

    According to the traditional definition of Wireless Sensor Networks (WSNs), static sensors have limited the feasibility of WSNs in some kind of approaches, so the mobility was introduced in WSN. Mobile nodes in a WSN come equipped with battery and from the point of deployment, this battery reserve becomes a valuable resource since it cannot be replenished. Hence, maximizing the network lifetime by minimizing the energy is an important challenge in Mobile WSN. Energy conservation can be accomplished by different approaches. In this paper, we presented an energy conservation solution based on Cellular Automata. The main objective of this solution is based on dynamically adjusting the transmission range and switching between operational states of the sensor nodes.

  15. Using prior knowledge from cellular pathways and molecular networks for diagnostic specimen classification

    PubMed Central

    2016-01-01

    For many complex diseases, an earlier and more reliable diagnosis is considered a key prerequisite for developing more effective therapies to prevent or delay disease progression. Classical statistical learning approaches for specimen classification using omics data, however, often cannot provide diagnostic models with sufficient accuracy and robustness for heterogeneous diseases like cancers or neurodegenerative disorders. In recent years, new approaches for building multivariate biomarker models on omics data have been proposed, which exploit prior biological knowledge from molecular networks and cellular pathways to address these limitations. This survey provides an overview of these recent developments and compares pathway- and network-based specimen classification approaches in terms of their utility for improving model robustness, accuracy and biological interpretability. Different routes to translate omics-based multifactorial biomarker models into clinical diagnostic tests are discussed, and a previous study is presented as example. PMID:26141830

  16. Effect of crystals and fibrous network polymer additives on cellular morphology of microcellular foams

    NASA Astrophysics Data System (ADS)

    Miyamoto, Ryoma; Utano, Tatsumi; Yasuhara, Shunya; Ishihara, Shota; Ohshima, Masahiro

    2015-05-01

    In this study, the core-back foam injection molding was used for preparing microcelluar polypropylene (PP) foam with either a 1,3:2,4 bis-O-(4-methylbenzylidene)-D-sorbitol gelling agent (Gel-all MD) or a fibros network polymer additive (Metablen 3000). Both agent and addiive could effectively control the celluar morphology in foams but somehow different ways. In course of cooling the polymer with Gel-all MD in the mold caity, the agent enhanced the crystal nucleation and resulted in the large number of small crystals. The crystals acted as effective bubble nucleation agent in foaming process. Thus, the agent reduced the cell size and increased the cell density, drastically. Furthermore, the small crystals provided an inhomogenuity to the expanding cell wall and produced the high open cell content with nano-scale fibril structure. Gell-all as well as Metablene 3000 formed a gel-like fibrous network in melt. The network increased the elongational viscosity and tended to prevent the cell wall from breaking up. The foaming temperature window was widened by the presence of the network. Especially, the temperature window where the macro-fibrous structure was formed was expanded to the higher temperature. The effects of crystal nucleating agent and PTFE on crystals' size and number, viscoelsticity, rheological propreties of PP and cellular morphology were compared and thorougly investigated.

  17. ComPPI: a cellular compartment-specific database for protein–protein interaction network analysis

    PubMed Central

    Veres, Daniel V.; Gyurkó, Dávid M.; Thaler, Benedek; Szalay, Kristóf Z.; Fazekas, Dávid; Korcsmáros, Tamás; Csermely, Peter

    2015-01-01

    Here we present ComPPI, a cellular compartment-specific database of proteins and their interactions enabling an extensive, compartmentalized protein–protein interaction network analysis (URL: http://ComPPI.LinkGroup.hu). ComPPI enables the user to filter biologically unlikely interactions, where the two interacting proteins have no common subcellular localizations and to predict novel properties, such as compartment-specific biological functions. ComPPI is an integrated database covering four species (S. cerevisiae, C. elegans, D. melanogaster and H. sapiens). The compilation of nine protein–protein interaction and eight subcellular localization data sets had four curation steps including a manually built, comprehensive hierarchical structure of >1600 subcellular localizations. ComPPI provides confidence scores for protein subcellular localizations and protein–protein interactions. ComPPI has user-friendly search options for individual proteins giving their subcellular localization, their interactions and the likelihood of their interactions considering the subcellular localization of their interacting partners. Download options of search results, whole-proteomes, organelle-specific interactomes and subcellular localization data are available on its website. Due to its novel features, ComPPI is useful for the analysis of experimental results in biochemistry and molecular biology, as well as for proteome-wide studies in bioinformatics and network science helping cellular biology, medicine and drug design. PMID:25348397

  18. Uniqueness and stability of traveling waves for cellular neural networks with multiple delays

    NASA Astrophysics Data System (ADS)

    Yu, Zhi-Xian; Mei, Ming

    2016-01-01

    In this paper, we investigate the properties of traveling waves to a class of lattice differential equations for cellular neural networks with multiple delays. Following the previous study [38] on the existence of the traveling waves, here we focus on the uniqueness and the stability of these traveling waves. First of all, by establishing the a priori asymptotic behavior of traveling waves and applying Ikehara's theorem, we prove the uniqueness (up to translation) of traveling waves ϕ (n - ct) with c ≤c* for the cellular neural networks with multiple delays, where c* < 0 is the critical wave speed. Then, by the weighted energy method together with the squeezing technique, we further show the global stability of all non-critical traveling waves for this model, that is, for all monotone waves with the speed c

  19. Network, cellular, and molecular mechanisms underlying long-term memory formation.

    PubMed

    Carasatorre, Mariana; Ramírez-Amaya, Víctor

    2013-01-01

    The neural network stores information through activity-dependent synaptic plasticity that occurs in populations of neurons. Persistent forms of synaptic plasticity may account for long-term memory storage, and the most salient forms are the changes in the structure of synapses. The theory proposes that encoding should use a sparse code and evidence suggests that this can be achieved through offline reactivation or by sparse initial recruitment of the network units. This idea implies that in some cases the neurons that underwent structural synaptic plasticity might be a subpopulation of those originally recruited; However, it is not yet clear whether all the neurons recruited during acquisition are the ones that underwent persistent forms of synaptic plasticity and responsible for memory retrieval. To determine which neural units underlie long-term memory storage, we need to characterize which are the persistent forms of synaptic plasticity occurring in these neural ensembles and the best hints so far are the molecular signals underlying structural modifications of the synapses. Structural synaptic plasticity can be achieved by the activity of various signal transduction pathways, including the NMDA-CaMKII and ACh-MAPK. These pathways converge with the Rho family of GTPases and the consequent ERK 1/2 activation, which regulates multiple cellular functions such as protein translation, protein trafficking, and gene transcription. The most detailed explanation may come from models that allow us to determine the contribution of each piece of this fascinating puzzle that is the neuron and the neural network. PMID:22976275

  20. A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.

    PubMed

    Taipale, Mikko; Tucker, George; Peng, Jian; Krykbaeva, Irina; Lin, Zhen-Yuan; Larsen, Brett; Choi, Hyungwon; Berger, Bonnie; Gingras, Anne-Claude; Lindquist, Susan

    2014-07-17

    Chaperones are abundant cellular proteins that promote the folding and function of their substrate proteins (clients). In vivo, chaperones also associate with a large and diverse set of cofactors (cochaperones) that regulate their specificity and function. However, how these cochaperones regulate protein folding and whether they have chaperone-independent biological functions is largely unknown. We combined mass spectrometry and quantitative high-throughput LUMIER assays to systematically characterize the chaperone-cochaperone-client interaction network in human cells. We uncover hundreds of chaperone clients, delineate their participation in specific cochaperone complexes, and establish a surprisingly distinct network of protein-protein interactions for cochaperones. As a salient example of the power of such analysis, we establish that NUDC family cochaperones specifically associate with structurally related but evolutionarily distinct β-propeller folds. We provide a framework for deciphering the proteostasis network and its regulation in development and disease and expand the use of chaperones as sensors for drug-target engagement. PMID:25036637

  1. Proof-of-Concept of a Millimeter-Wave Integrated Heterogeneous Network for 5G Cellular.

    PubMed

    Okasaka, Shozo; Weiler, Richard J; Keusgen, Wilhelm; Pudeyev, Andrey; Maltsev, Alexander; Karls, Ingolf; Sakaguchi, Kei

    2016-01-01

    The fifth-generation mobile networks (5G) will not only enhance mobile broadband services, but also enable connectivity for a massive number of Internet-of-Things devices, such as wireless sensors, meters or actuators. Thus, 5G is expected to achieve a 1000-fold or more increase in capacity over 4G. The use of the millimeter-wave (mmWave) spectrum is a key enabler to allowing 5G to achieve such enhancement in capacity. To fully utilize the mmWave spectrum, 5G is expected to adopt a heterogeneous network (HetNet) architecture, wherein mmWave small cells are overlaid onto a conventional macro-cellular network. In the mmWave-integrated HetNet, splitting of the control plane (CP) and user plane (UP) will allow continuous connectivity and increase the capacity of the mmWave small cells. mmWave communication can be used not only for access linking, but also for wireless backhaul linking, which will facilitate the installation of mmWave small cells. In this study, a proof-of-concept (PoC) was conducted to demonstrate the practicality of a prototype mmWave-integrated HetNet, using mmWave technologies for both backhaul and access. PMID:27571074

  2. Firing patterns in a random network cellular automata model of the brain

    NASA Astrophysics Data System (ADS)

    Acedo, L.; Lamprianidou, E.; Moraño, J.-A.; Villanueva-Oller, J.; Villanueva, R.-J.

    2015-10-01

    One of the main challenges in the simulation of even reduced areas of the brain is the presence of a large number of neurons and a large number of connections among them. Even from a theoretical point of view, the behaviour of dynamical models of complex networks with high connectivity is unknown, precisely because the cost of computation is still unaffordable and it will likely be in the near future. In this paper we discuss the simulation of a cellular automata network model of the brain including up to one million sites with a maximum average of three hundred connections per neuron. This level of connectivity was achieved thanks to a distributed computing environment based on the BOINC (Berkeley Open Infrastructure for Network Computing) platform. Moreover, in this work we consider the interplay among excitatory neurons (which induce the excitation of their neighbours) and inhibitory neurons (which prevent resting neurons from firing and induce firing neurons to pass to the refractory state). Our objective is to classify the normal (noisy but asymptotically constant patterns) and the abnormal (high oscillations with spindle-like behaviour) patterns of activity in the model brain and their stability and parameter ranges in order to determine the role of excitatory and inhibitory compensatory effects in healthy and diseased individuals.

  3. Viral Replication Protein Inhibits Cellular Cofilin Actin Depolymerization Factor to Regulate the Actin Network and Promote Viral Replicase Assembly

    PubMed Central

    Kovalev, Nikolay; de Castro Martín, Isabel Fernández; Barajas, Daniel; Risco, Cristina; Nagy, Peter D.

    2016-01-01

    RNA viruses exploit host cells by co-opting host factors and lipids and escaping host antiviral responses. Previous genome-wide screens with Tomato bushy stunt virus (TBSV) in the model host yeast have identified 18 cellular genes that are part of the actin network. In this paper, we show that the p33 viral replication factor interacts with the cellular cofilin (Cof1p), which is an actin depolymerization factor. Using temperature-sensitive (ts) Cof1p or actin (Act1p) mutants at a semi-permissive temperature, we find an increased level of TBSV RNA accumulation in yeast cells and elevated in vitro activity of the tombusvirus replicase. We show that the large p33 containing replication organelle-like structures are located in the close vicinity of actin patches in yeast cells or around actin cable hubs in infected plant cells. Therefore, the actin filaments could be involved in VRC assembly and the formation of large viral replication compartments containing many individual VRCs. Moreover, we show that the actin network affects the recruitment of viral and cellular components, including oxysterol binding proteins and VAP proteins to form membrane contact sites for efficient transfer of sterols to the sites of replication. Altogether, the emerging picture is that TBSV, via direct interaction between the p33 replication protein and Cof1p, controls cofilin activities to obstruct the dynamic actin network that leads to efficient subversion of cellular factors for pro-viral functions. In summary, the discovery that TBSV interacts with cellular cofilin and blocks the severing of existing filaments and the formation of new actin filaments in infected cells opens a new window to unravel the way by which viruses could subvert/co-opt cellular proteins and lipids. By regulating the functions of cofilin and the actin network, which are central nodes in cellular pathways, viruses could gain supremacy in subversion of cellular factors for pro-viral functions. PMID:26863541

  4. Smart-Pixel Array Processors Based on Optimal Cellular Neural Networks for Space Sensor Applications

    NASA Technical Reports Server (NTRS)

    Fang, Wai-Chi; Sheu, Bing J.; Venus, Holger; Sandau, Rainer

    1997-01-01

    A smart-pixel cellular neural network (CNN) with hardware annealing capability, digitally programmable synaptic weights, and multisensor parallel interface has been under development for advanced space sensor applications. The smart-pixel CNN architecture is a programmable multi-dimensional array of optoelectronic neurons which are locally connected with their local neurons and associated active-pixel sensors. Integration of the neuroprocessor in each processor node of a scalable multiprocessor system offers orders-of-magnitude computing performance enhancements for on-board real-time intelligent multisensor processing and control tasks of advanced small satellites. The smart-pixel CNN operation theory, architecture, design and implementation, and system applications are investigated in detail. The VLSI (Very Large Scale Integration) implementation feasibility was illustrated by a prototype smart-pixel 5x5 neuroprocessor array chip of active dimensions 1380 micron x 746 micron in a 2-micron CMOS technology.

  5. Multiscale Systems Analysis of Root Growth and Development: Modeling Beyond the Network and Cellular Scales

    PubMed Central

    Band, Leah R.; Fozard, John A.; Godin, Christophe; Jensen, Oliver E.; Pridmore, Tony; Bennett, Malcolm J.; King, John R.

    2012-01-01

    Over recent decades, we have gained detailed knowledge of many processes involved in root growth and development. However, with this knowledge come increasing complexity and an increasing need for mechanistic modeling to understand how those individual processes interact. One major challenge is in relating genotypes to phenotypes, requiring us to move beyond the network and cellular scales, to use multiscale modeling to predict emergent dynamics at the tissue and organ levels. In this review, we highlight recent developments in multiscale modeling, illustrating how these are generating new mechanistic insights into the regulation of root growth and development. We consider how these models are motivating new biological data analysis and explore directions for future research. This modeling progress will be crucial as we move from a qualitative to an increasingly quantitative understanding of root biology, generating predictive tools that accelerate the development of improved crop varieties. PMID:23110897

  6. Modeling of trophospheric ozone concentrations using genetically trained multi-level cellular neural networks

    NASA Astrophysics Data System (ADS)

    Ozcan, H. Kurtulus; Bilgili, Erdem; Sahin, Ulku; Ucan, O. Nuri; Bayat, Cuma

    2007-09-01

    Tropospheric ozone concentrations, which are an important air pollutant, are modeled by the use of an artificial intelligence structure. Data obtained from air pollution measurement stations in the city of Istanbul are utilized in constituting the model. A supervised algorithm for the evaluation of ozone concentration using a genetically trained multi-level cellular neural network (ML-CNN) is introduced, developed, and applied to real data. A genetic algorithm is used in the optimization of CNN templates. The model results and the actual measurement results are compared and statistically evaluated. It is observed that seasonal changes in ozone concentrations are reflected effectively by the concentrations estimated by the multilevel-CNN model structure, with a correlation value of 0.57 ascertained between actual and model results. It is shown that the multilevel-CNN modeling technique is as satisfactory as other modeling techniques in associating the data in a complex medium in air pollution applications.

  7. Convergence and attractivity of memristor-based cellular neural networks with time delays.

    PubMed

    Qin, Sitian; Wang, Jun; Xue, Xiaoping

    2015-03-01

    This paper presents theoretical results on the convergence and attractivity of memristor-based cellular neural networks (MCNNs) with time delays. Based on a realistic memristor model, an MCNN is modeled using a differential inclusion. The essential boundedness of its global solutions is proven. The state of MCNNs is further proven to be convergent to a critical-point set located in saturated region of the activation function, when the initial state locates in a saturated region. It is shown that the state convergence time period is finite and can be quantitatively estimated using given parameters. Furthermore, the positive invariance and attractivity of state in non-saturated regions are also proven. The simulation results of several numerical examples are provided to substantiate the results. PMID:25562569

  8. Parallelism on the Intel 860 Hypercube:. Ising Magnets, Hydrodynamical Cellular Automata and Neural Networks

    NASA Astrophysics Data System (ADS)

    Kohring, G. A.; Stauffer, D.

    Geometric parallelization was tested on the Intel Hypercube with 32 MIMD processors of 1860 type, each with 16 Mbytes of distributed memory. We applied it to Ising models in two and three dimensions as well as to neural networks and two-dimensional hydrodynamic cellular automata. For system sizes suited to this machine, up to 60960*60960 and 1410*1410*1408 Ising spins, we found nearly hundred percent parallel efficiency in spite of the needed inter-processor communications. For small systems, the observed deviations from full efficiency were compared with the scaling concepts of Heermann and Burkitt and of Jakobs and Gerling. For Ising models, we determined the Glauber kinetic exponent z≃2.18 in two dimensions and confirmed the stretched exponential relaxation of the magnetization towards the spontaneous magnetization below Tc. For three dimensions we found z≃2.09 and simple exponential relaxation.

  9. Global Detection of Live Virtual Machine Migration Based on Cellular Neural Networks

    PubMed Central

    Xie, Kang; Yang, Yixian; Zhang, Ling; Jing, Maohua; Xin, Yang; Li, Zhongxian

    2014-01-01

    In order to meet the demands of operation monitoring of large scale, autoscaling, and heterogeneous virtual resources in the existing cloud computing, a new method of live virtual machine (VM) migration detection algorithm based on the cellular neural networks (CNNs), is presented. Through analyzing the detection process, the parameter relationship of CNN is mapped as an optimization problem, in which improved particle swarm optimization algorithm based on bubble sort is used to solve the problem. Experimental results demonstrate that the proposed method can display the VM migration processing intuitively. Compared with the best fit heuristic algorithm, this approach reduces the processing time, and emerging evidence has indicated that this new approach is affordable to parallelism and analog very large scale integration (VLSI) implementation allowing the VM migration detection to be performed better. PMID:24959631

  10. Global detection of live virtual machine migration based on cellular neural networks.

    PubMed

    Xie, Kang; Yang, Yixian; Zhang, Ling; Jing, Maohua; Xin, Yang; Li, Zhongxian

    2014-01-01

    In order to meet the demands of operation monitoring of large scale, autoscaling, and heterogeneous virtual resources in the existing cloud computing, a new method of live virtual machine (VM) migration detection algorithm based on the cellular neural networks (CNNs), is presented. Through analyzing the detection process, the parameter relationship of CNN is mapped as an optimization problem, in which improved particle swarm optimization algorithm based on bubble sort is used to solve the problem. Experimental results demonstrate that the proposed method can display the VM migration processing intuitively. Compared with the best fit heuristic algorithm, this approach reduces the processing time, and emerging evidence has indicated that this new approach is affordable to parallelism and analog very large scale integration (VLSI) implementation allowing the VM migration detection to be performed better. PMID:24959631

  11. A novel method to assess human population exposure induced by a wireless cellular network.

    PubMed

    Varsier, Nadège; Plets, David; Corre, Yoann; Vermeeren, Günter; Joseph, Wout; Aerts, Sam; Martens, Luc; Wiart, Joe

    2015-09-01

    This paper presents a new metric to evaluate electromagnetic exposure induced by wireless cellular networks. This metric takes into account the exposure induced by base station antennas as well as exposure induced by wireless devices to evaluate average global exposure of the population in a specific geographical area. The paper first explains the concept and gives the formulation of the Exposure Index (EI). Then, the EI computation is illustrated through simple phone call scenarios (indoor office, in train) and a complete macro urban data long-term evolution scenario showing how, based on simulations, radio-planning predictions, realistic population statistics, user traffic data, and specific absorption rate calculations can be combined to assess the index. Bioelectromagnetics. 36:451-463, 2015. © 2015 Wiley Periodicals, Inc. PMID:26113174

  12. Co-evolutionary networks of genes and cellular processes across fungal species

    PubMed Central

    Tuller, Tamir; Kupiec, Martin; Ruppin, Eytan

    2009-01-01

    Background The introduction of measures such as evolutionary rate and propensity for gene loss have significantly advanced our knowledge of the evolutionary history and selection forces acting upon individual genes and cellular processes. Results We present two new measures, the 'relative evolutionary rate pattern' (rERP), which records the relative evolutionary rates of conserved genes across the different branches of a species' phylogenetic tree, and the 'copy number pattern' (CNP), which quantifies the rate of gene loss of less conserved genes. Together, these measures yield a high-resolution study of the co-evolution of genes in 9 fungal species, spanning 3,540 sets of orthologs. We find that the evolutionary tempo of conserved genes varies in different evolutionary periods. The co-evolution of genes' Gene Ontology categories exhibits a significant correlation with their functional distance in the Gene Ontology hierarchy, but not with their location on chromosomes, showing that cellular functions are a more important driving force in gene co-evolution than their chromosomal proximity. Two fundamental patterns of co-evolution of conserved genes, cooperative and reciprocal, are identified; only genes co-evolving cooperatively functionally back each other up. The co-evolution of conserved and less conserved genes exhibits both commonalities and differences; DNA metabolism is positively correlated with nuclear traffic, transcription processes and vacuolar biology in both analyses. Conclusions Overall, this study charts the first global network view of gene co-evolution in fungi. The future application of the approach presented here to other phylogenetic trees holds much promise in characterizing the forces that shape cellular co-evolution. PMID:19416514

  13. BioJazz: in silico evolution of cellular networks with unbounded complexity using rule-based modeling

    PubMed Central

    Feng, Song; Ollivier, Julien F.; Swain, Peter S.; Soyer, Orkun S.

    2015-01-01

    Systems biologists aim to decipher the structure and dynamics of signaling and regulatory networks underpinning cellular responses; synthetic biologists can use this insight to alter existing networks or engineer de novo ones. Both tasks will benefit from an understanding of which structural and dynamic features of networks can emerge from evolutionary processes, through which intermediary steps these arise, and whether they embody general design principles. As natural evolution at the level of network dynamics is difficult to study, in silico evolution of network models can provide important insights. However, current tools used for in silico evolution of network dynamics are limited to ad hoc computer simulations and models. Here we introduce BioJazz, an extendable, user-friendly tool for simulating the evolution of dynamic biochemical networks. Unlike previous tools for in silico evolution, BioJazz allows for the evolution of cellular networks with unbounded complexity by combining rule-based modeling with an encoding of networks that is akin to a genome. We show that BioJazz can be used to implement biologically realistic selective pressures and allows exploration of the space of network architectures and dynamics that implement prescribed physiological functions. BioJazz is provided as an open-source tool to facilitate its further development and use. Source code and user manuals are available at: http://oss-lab.github.io/biojazz and http://osslab.lifesci.warwick.ac.uk/BioJazz.aspx. PMID:26101250

  14. Intragranular cellular segregation network structure strengthening 316L stainless steel prepared by selective laser melting

    NASA Astrophysics Data System (ADS)

    Zhong, Yuan; Liu, Leifeng; Wikman, Stefan; Cui, Daqing; Shen, Zhijian

    2016-03-01

    A feasibility study was performed to fabricate ITER In-Vessel components by Selective Laser Melting (SLM) supported by Fusion for Energy (F4E). Almost fully dense 316L stainless steel (SS316L) components were prepared from gas-atomized powder and with optimized SLM processing parameters. Tensile tests and Charpy-V tests were carried out at 22 °C and 250 °C and the results showed that SLM SS316L fulfill the RCC-MR code. Microstructure characterization reveals the presence of hierarchical macro-, micro- and nano-structures in as-built samples that were very different from SS316L microstructures prepared by other established methods. The formation of a characteristic intragranular cellular segregation network microstructure appears to contribute to the increase of yield strength without losing ductility. Silicon oxide nano-inclusions were formed during the SLM process that generated a micro-hardness fluctuation in the building direction. The combined influence of a cellular microstructure and the nano-inclusions constraints the size of ductile dimples to nano-scale. The crack propagation is hindered by a pinning effect that improves the defect-tolerance of the SLM SS316L. This work proves that it was possible to manufacture SS316L with properties suitable for ITER First Wall panels. Further studies on irradiation properties of SLM SS316L and manufacturing of larger real-size components are needed.

  15. Computerized detection of pulmonary nodules using cellular neural networks in CT images

    NASA Astrophysics Data System (ADS)

    Zhang, Xiangwei; McLennan, Geoffrey; Hoffman, Eric A.; Sonka, Milan

    2004-05-01

    The purpose of this study is to develop a computer-aided diagnosis (CAD) system to detect small-sized (from 2mm to 10mm) non-pleural pulmonary nodules in high resolution helical CT scans. A new 3D automated scheme using cellular neural networks is presented. Different from most previous methods, this scheme employed the local shape property to perform voxel classification. The shape index feature successfully captured the local shape difference between nodules and non-nodules, especially vessels. A 3D discrete-time cellular neural network (DTCNN) was constructed to give a reliable voxel classification by collecting information in a neighborhood. To tailor it for lung nodule detection, this DTCNN was trained using genetic algorithms (GAs) to derive the shape index variation pattern of nodules. 19 clinical thoracic CT cases involving a total of 4838 sectional images were used in this work, with 2 scans forming the training set, and the remaining 17 cases being the testing set. The evaluation was composed of two stages. During the first stage, a pulmonologist and our CAD system independently detected nodules in the testing set. Then, the suspected nodule areas located by the computer were reviewed by the pulmonologist to confirm nodules missed by the human in the first review. There were 32 true nodules detected by the computer but missed by the pulmonologist in the first review, in which 30 non-juxtapleural nodules were found. Considering the nodules detected by the pulmonologist during the first and second reviews as the truth, 52 of 62 non-pleural nodules were detected by the CAD system (sensitivity being 83.9%), with the number of false positives being 3.47 per case.

  16. Cellular Nonlinear Networks for the emergence of perceptual states: application to robot navigation control.

    PubMed

    Arena, Paolo; De Fiore, Sebastiano; Patané, Luca

    2009-01-01

    In this paper a new general purpose perceptual control architecture, based on nonlinear neural lattices, is presented and applied to solve robot navigation tasks. Insects show the ability to react to certain stimuli with simple reflexes, using direct sensory-motor pathways, which can be considered as basic behaviors, inherited and pre-wired. Relevant brain centres, known as Mushroom Bodies (MB) and Central Complex (CX) were recently identified in insects: though their functional details are not yet fully understood, it is known that they provide secondary pathways allowing the emergence of cognitive behaviors. These are gained through the coordination of the basic abilities to satisfy the insect's needs. Taking inspiration from this evidence, our architecture modulates, through a reinforcement learning, a set of competitive and concurrent basic behaviors in order to accomplish the task assigned through a reward function. The core of the architecture is constituted by the so-called Representation layer, used to create a concise picture of the current environment situation, fusing together different stimuli for the emergence of perceptual states. These perceptual states are steady state solutions of lattices of Reaction-Diffusion Cellular Nonlinear Networks (RD-CNN), designed to show Turing patterns. The exploitation of the dynamics of the multiple equilibria of the network is emphasized through the adaptive shaping of the basins of attraction for each emerged pattern. New experimental campaigns on standard robotic platforms are reported to demonstrate the potentiality and the effectiveness of the approach. PMID:19596552

  17. Energy-Efficient Crowdsensing of Human Mobility and Signal Levels in Cellular Networks

    PubMed Central

    Foremski, Paweł; Gorawski, Michał; Grochla, Krzysztof; Polys, Konrad

    2015-01-01

    The paper presents a practical application of the crowdsensing idea to measure human mobility and signal coverage in cellular networks. Currently, virtually everyone is carrying a mobile phone, which may be used as a sensor to gather research data by measuring, e.g., human mobility and radio signal levels. However, many users are unwilling to participate in crowdsensing experiments. This work begins with the analysis of the barriers for engaging people in crowdsensing. A survey showed that people who agree to participate in crowdsensing expect a minimum impact on their battery lifetime and phone usage habits. To address these requirements, this paper proposes an application for measuring the location and signal strength data based on energy-efficient GPS tracking, which allows one to perform the measurements of human mobility and radio signal levels with minimum energy utilization and without any engagement of the user. The method described combines measurements from the accelerometer with effective management of the GPS to monitor the user mobility with the decrease in battery lifetime by approximately 20%. To show the applicability of the proposed platform, the sample results of signal level distribution and coverage maps gathered for an LTE network and representing human mobility are shown. PMID:26340633

  18. Measurement and interpolation uncertainties in rainfall maps from cellular communication networks

    NASA Astrophysics Data System (ADS)

    Rios Gaona, M. F.; Overeem, A.; Leijnse, H.; Uijlenhoet, R.

    2015-08-01

    compared against quality-controlled gauge-adjusted radar rainfall fields (assumed to be the ground truth). Thus, we were able to not only identify and quantify the sources of uncertainty in such rainfall maps, but also test the actual and optimal performance of one commercial microwave network from one of the cellular providers in the Netherlands. Errors in microwave link measurements were found to be the source that contributes most to the overall uncertainty.

  19. Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

    PubMed Central

    Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

    2015-01-01

    Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases. PMID:26608097

  20. Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

    NASA Astrophysics Data System (ADS)

    Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

    2015-11-01

    Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

  1. Noise-robust realization of Turing-complete cellular automata by using neural networks with pattern representation

    NASA Astrophysics Data System (ADS)

    Oku, Makito; Aihara, Kazuyuki

    2010-11-01

    A modularly-structured neural network model is considered. Each module, which we call a ‘cell’, consists of two parts: a Hopfield neural network model and a multilayered perceptron. An array of such cells is used to simulate the Rule 110 cellular automaton with high accuracy even when all the units of neural networks are replaced by stochastic binary ones. We also find that noise not only degrades but also facilitates computation if the outputs of multilayered perceptrons are below the threshold required to update the states of the cells, which is a stochastic resonance in computation.

  2. Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

    SciTech Connect

    Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo

    2014-02-07

    Highlights: • Astrocytes exhibit characteristic changes in [Ca{sup 2+}]{sub i} under OGD. • Astrocytic [Ca{sup 2+}]{sub i} increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca{sup 2+}]{sub i}) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca{sup 2+}]{sub i} oscillations followed by larger and sustained [Ca{sup 2+}]{sub i} increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca{sup 2+}]{sub i} increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca{sup 2+}]{sub i} increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca{sup 2+}]{sub i} increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage

  3. Numerically evaluated functional equivalence between chaotic dynamics in neural networks and cellular automata under totalistic rules.

    PubMed

    Takada, Ryu; Munetaka, Daigo; Kobayashi, Shoji; Suemitsu, Yoshikazu; Nara, Shigetoshi

    2007-09-01

    Chaotic dynamics in a recurrent neural network model and in two-dimensional cellular automata, where both have finite but large degrees of freedom, are investigated from the viewpoint of harnessing chaos and are applied to motion control to indicate that both have potential capabilities for complex function control by simple rule(s). An important point is that chaotic dynamics generated in these two systems give us autonomous complex pattern dynamics itinerating through intermediate state points between embedded patterns (attractors) in high-dimensional state space. An application of these chaotic dynamics to complex controlling is proposed based on an idea that with the use of simple adaptive switching between a weakly chaotic regime and a strongly chaotic regime, complex problems can be solved. As an actual example, a two-dimensional maze, where it should be noted that the spatial structure of the maze is one of typical ill-posed problems, is solved with the use of chaos in both systems. Our computer simulations show that the success rate over 300 trials is much better, at least, than that of a random number generator. Our functional simulations indicate that both systems are almost equivalent from the viewpoint of functional aspects based on our idea, harnessing of chaos. PMID:19003512

  4. Synchronization schemes for coupled identical Yang-Yang type fuzzy cellular neural networks

    NASA Astrophysics Data System (ADS)

    Xia, Yonghui; Yang, Zijiang; Han, Maoan

    2009-09-01

    This paper proposes an adaptive procedure to the problem of synchronization for a class of coupled identical Yang-Yang type fuzzy cellular neural networks (YYFCNN) with time-varying delays. Based on the simple adaptive controller, a set of sufficient conditions are developed to guarantee the synchronization of the coupled YYFCNN with time-varying delays. The results are much different from previous ones. It is proved that two coupled identical YYFCNN with time-varying delays can achieve synchronization by enhancing the coupled strength dynamically. In addition, this kind of controller is simple to be implemented and it is fairly robust against the effect of weak noise in the given time series. The approaches are based on using the invariance principle of functional differential equations, constructing a general Lyapunov-Krasovskii functional and employing a linear matrix inequality (LMI). An illustrative example and its simulations show the feasibility of our results. Finally, an application is given to show how to apply the presented synchronization scheme of YYFCNN to secure communication.

  5. Data fusion and classification using a hybrid intrinsic cellular inference network

    NASA Astrophysics Data System (ADS)

    Woodley, Robert; Walenz, Brett; Seiffertt, John; Robinette, Paul; Wunsch, Donald

    2010-04-01

    Hybrid Intrinsic Cellular Inference Network (HICIN) is designed for battlespace decision support applications. We developed an automatic method of generating hypotheses for an entity-attribute classifier. The capability and effectiveness of a domain specific ontology was used to generate automatic categories for data classification. Heterogeneous data is clustered using an Adaptive Resonance Theory (ART) inference engine on a sample (unclassified) data set. The data set is the Lahman baseball database. The actual data is immaterial to the architecture, however, parallels in the data can be easily drawn (i.e., "Team" maps to organization, "Runs scored/allowed" to Measure of organization performance (positive/negative), "Payroll" to organization resources, etc.). Results show that HICIN classifiers create known inferences from the heterogonous data. These inferences are not explicitly stated in the ontological description of the domain and are strictly data driven. HICIN uses data uncertainty handling to reduce errors in the classification. The uncertainty handling is based on subjective logic. The belief mass allows evidence from multiple sources to be mathematically combined to increase or discount an assertion. In military operations the ability to reduce uncertainty will be vital in the data fusion operation.

  6. Memristor-based cellular nonlinear/neural network: design, analysis, and applications.

    PubMed

    Duan, Shukai; Hu, Xiaofang; Dong, Zhekang; Wang, Lidan; Mazumder, Pinaki

    2015-06-01

    Cellular nonlinear/neural network (CNN) has been recognized as a powerful massively parallel architecture capable of solving complex engineering problems by performing trillions of analog operations per second. The memristor was theoretically predicted in the late seventies, but it garnered nascent research interest due to the recent much-acclaimed discovery of nanocrossbar memories by engineers at the Hewlett-Packard Laboratory. The memristor is expected to be co-integrated with nanoscale CMOS technology to revolutionize conventional von Neumann as well as neuromorphic computing. In this paper, a compact CNN model based on memristors is presented along with its performance analysis and applications. In the new CNN design, the memristor bridge circuit acts as the synaptic circuit element and substitutes the complex multiplication circuit used in traditional CNN architectures. In addition, the negative differential resistance and nonlinear current-voltage characteristics of the memristor have been leveraged to replace the linear resistor in conventional CNNs. The proposed CNN design has several merits, for example, high density, nonvolatility, and programmability of synaptic weights. The proposed memristor-based CNN design operations for implementing several image processing functions are illustrated through simulation and contrasted with conventional CNNs. Monte-Carlo simulation has been used to demonstrate the behavior of the proposed CNN due to the variations in memristor synaptic weights. PMID:25069124

  7. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modelling.

    PubMed

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2015-01-15

    Following partial hepatectomy, the liver initiates a regenerative programme involving hepatocyte priming and replication driven by the coordinated actions of cytokine and growth factors. We investigated the mechanisms underlying adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn(-/-) mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn(-/-) mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to interleukin-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver. PMID:25630259

  8. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modelling

    PubMed Central

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2015-01-01

    Following partial hepatectomy, the liver initiates a regenerative programme involving hepatocyte priming and replication driven by the coordinated actions of cytokine and growth factors. We investigated the mechanisms underlying adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn–/– mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn–/– mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to interleukin-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver. PMID:25630259

  9. The potential of cellular network infrastructures for sudden rainfall monitoring in dry climate regions

    NASA Astrophysics Data System (ADS)

    David, N.; Alpert, P.; Messer, H.

    2013-09-01

    Monitoring of precipitation and in particular sudden rain, in rural dry climate regions, is a subject of great significance in several weather related processes such as soil erosion, flash flooding, triggering epidemics and more. The rainfall monitoring facilities in these regions and as a result precipitation data are, however, commonly, severely lacking. As was recently shown, cellular networks infrastructures supply high resolution precipitation measurements at ground level while often being situated in dry areas, covering large parts of these climatic zones. The potential found in these systems to provide early monitoring and essential precipitation information, directly from arid regions, based on standard measurements of commercial microwave links, is exemplified here over the Negev and the Southern Judean desert, South Israel. We present the results of two different rainfall events occurred in these regions. It is shown that the microwave system measured precipitation between at least 50 min (in case 1) and at least 1 h and 40 min (in case 2) before each of the sparse rain gauges. During each case, the radar system, located relatively far from the arid sites, provided measurements from heights of at least 1500 m and 2000 m above surface, respectively. A third case study demonstrates a relative advantage of microwave links to measure precipitation intensity with respect to the radar system, over an area of complex topography located in northeastern Israel, which is relatively far (~ 150 km) from the radar.

  10. On-chip training for cellular neural networks using iterative annealing

    NASA Astrophysics Data System (ADS)

    Feiden, Dirk; Tetzlaff, Ronald

    2003-04-01

    Cellular Neural Network-Universal Machines (CNN-UM) are analog devices, which are excellently suited for image processing. A big challenge thereby is the determination of CNN templates for special image processing tasks. In many cases appropriate templates can only be found by a parameter optimization. The determination of templates for complex applications in the area of CNN is usually performed by using a CNN software simulator. Unfortunately, in many cases the determined templates cannot be used in hardware realizations of CNN caused by realization effects. In order to find robust templates, which are not only working on CNN simulators, but also on hardware implementations, we present in this contribution a new kind of on-chip-multi-template-training. Furthermore, as a possible application, we will also present a CNN-based solution of the problem of Pattern Matching, which is a processing step in many areas of image processing, like e.g. in Motion Estimation, Image- and Video-Compression.

  11. Residual Separation of Magnetic Fields Using a Cellular Neural Network Approach

    NASA Astrophysics Data System (ADS)

    Albora, A. M.; Özmen, A.; Uçan, O. N.

    - In this paper, a Cellular Neural Network (CNN) has been applied to a magnetic regional/residual anomaly separation problem. CNN is an analog parallel computing paradigm defined in space and characterized by the locality of connections between processing neurons. The behavior of the CNN is defined by the template matrices A, B and the template vector I. We have optimized weight coefficients of these templates using Recurrent Perceptron Learning Algorithm (RPLA). The advantages of CNN as a real-time stochastic method are that it introduces little distortion to the shape of the original image and that it is not effected significantly by factors such as the overlap of power spectra of residual fields. The proposed method is tested using synthetic examples and the average depth of the buried objects has been estimated by power spectrum analysis. Next the CNN approach is applied to magnetic data over the Golalan chromite mine in Elazig which lies East of Turkey. This area is among the largest and richest chromite masses of the world. We compared the performance of CNN to classical derivative approaches.

  12. A universal concept based on cellular neural networks for ultrafast and flexible solving of differential equations.

    PubMed

    Chedjou, Jean Chamberlain; Kyamakya, Kyandoghere

    2015-04-01

    This paper develops and validates a comprehensive and universally applicable computational concept for solving nonlinear differential equations (NDEs) through a neurocomputing concept based on cellular neural networks (CNNs). High-precision, stability, convergence, and lowest-possible memory requirements are ensured by the CNN processor architecture. A significant challenge solved in this paper is that all these cited computing features are ensured in all system-states (regular or chaotic ones) and in all bifurcation conditions that may be experienced by NDEs.One particular quintessence of this paper is to develop and demonstrate a solver concept that shows and ensures that CNN processors (realized either in hardware or in software) are universal solvers of NDE models. The solving logic or algorithm of given NDEs (possible examples are: Duffing, Mathieu, Van der Pol, Jerk, Chua, Rössler, Lorenz, Burgers, and the transport equations) through a CNN processor system is provided by a set of templates that are computed by our comprehensive templates calculation technique that we call nonlinear adaptive optimization. This paper is therefore a significant contribution and represents a cutting-edge real-time computational engineering approach, especially while considering the various scientific and engineering applications of this ultrafast, energy-and-memory-efficient, and high-precise NDE solver concept. For illustration purposes, three NDE models are demonstratively solved, and related CNN templates are derived and used: the periodically excited Duffing equation, the Mathieu equation, and the transport equation. PMID:25794380

  13. Spatio-temporal analysis of brain electrical activity in epilepsy based on cellular nonlinear networks

    NASA Astrophysics Data System (ADS)

    Gollas, Frank; Tetzlaff, Ronald

    2009-05-01

    Epilepsy is the most common chronic disorder of the nervous system. Generally, epileptic seizures appear without foregoing sign or warning. The problem of detecting a possible pre-seizure state in epilepsy from EEG signals has been addressed by many authors over the past decades. Different approaches of time series analysis of brain electrical activity already are providing valuable insights into the underlying complex dynamics. But the main goal the identification of an impending epileptic seizure with a sufficient specificity and reliability, has not been achieved up to now. An algorithm for a reliable, automated prediction of epileptic seizures would enable the realization of implantable seizure warning devices, which could provide valuable information to the patient and time/event specific drug delivery or possibly a direct electrical nerve stimulation. Cellular Nonlinear Networks (CNN) are promising candidates for future seizure warning devices. CNN are characterized by local couplings of comparatively simple dynamical systems. With this property these networks are well suited to be realized as highly parallel, analog computer chips. Today available CNN hardware realizations exhibit a processing speed in the range of TeraOps combined with low power consumption. In this contribution new algorithms based on the spatio-temporal dynamics of CNN are considered in order to analyze intracranial EEG signals and thus taking into account mutual dependencies between neighboring regions of the brain. In an identification procedure Reaction-Diffusion CNN (RD-CNN) are determined for short segments of brain electrical activity, by means of a supervised parameter optimization. RD-CNN are deduced from Reaction-Diffusion Systems, which usually are applied to investigate complex phenomena like nonlinear wave propagation or pattern formation. The Local Activity Theory provides a necessary condition for emergent behavior in RD-CNN. In comparison linear spatio

  14. Design and simulation of cellular nonlinear networks using single-electron tunneling transistor technology

    NASA Astrophysics Data System (ADS)

    Gerousis, Costa P.

    It is currently predicted that semiconductor device scaling will end at the 22-nm device feature size (7 nm physical channel length) according to the International Technology Roadmap for Semiconductors. The main challenge is then to develop innovative technologies that will extend the scaling beyond roadmap projection. Any new technology must be well matched with complementary metal oxide semiconductor (CMOS) technology and scaleable beyond CMOS scaling projections and must provide low-power high-speed signal processing. Nanotechnology will become an appealing option for developing devices for integrated circuits with dimensions and performances well beyond roadmap predictions. Such devices, based on the controllable transfer of charge between dots or 'islands', can take advantage of the quantum mechanical effects, such as tunneling and energy quantization, which would normally occur at the nanometer scale. An outstanding challenge is in arranging such nanodevices in new architectures that can be integrated on a single chip. In particular, locally interconnected architectures are believed to be necessary to alleviate the problems associated with increasing interconnect length and complexity in ultra-dense circuits. The goal of this work is to investigate the use of nanoelectronic structures in cellular non-linear network (CNN) architectures for potential application in future high-density and low-power CMOS-nanodevice hybrid circuits. The operation of the single-electron tunneling (SET) transistor is first reviewed, followed by a discussion of simple CNN linear architectures using a SET inverter topology as the basis for the non-linear transfer characteristics for individual cells to be used in analog processing arrays for image-processing applications. The basic SET CNN cell acts as a summing node that is capacitively coupled to the inputs and outputs of nearest neighbor cells. Monte Carlo simulation results are used to show CNN-like behavior in attempting to

  15. Implementation of a cellular neural network-based segmentation algorithm on the bio-inspired vision system

    NASA Astrophysics Data System (ADS)

    Karabiber, Fethullah; Grassi, Giuseppe; Vecchio, Pietro; Arik, Sabri; Yalcin, M. Erhan

    2011-01-01

    Based on the cellular neural network (CNN) paradigm, the bio-inspired (bi-i) cellular vision system is a computing platform consisting of state-of-the-art sensing, cellular sensing-processing and digital signal processing. This paper presents the implementation of a novel CNN-based segmentation algorithm onto the bi-i system. The experimental results, carried out for different benchmark video sequences, highlight the feasibility of the approach, which provides a frame rate of about 26 frame/sec. Comparisons with existing CNN-based methods show that, even though these methods are from two to six times faster than the proposed one, the conceived approach is more accurate and, consequently, represents a satisfying trade-off between real-time requirements and accuracy.

  16. Impedance matching network for high frequency ultrasonic transducer for cellular applications.

    PubMed

    Kim, Min Gon; Yoon, Sangpil; Kim, Hyung Ham; Shung, K Kirk

    2016-02-01

    An approach for the design of an impedance matching network (IMN) for high frequency ultrasonic transducers with large apertures based on impedance analysis for cellular applications is presented in this paper. The main objectives were to maximize energy transmission from the excitation source to the ultrasonic transducers for cell manipulation and to achieve low input parameters for the safe operation of an ultrasonic transducer because the piezoelectric material in high frequency ultrasonic transducers is prone to breakage due to its being extremely thin. Two ultrasonic transducers, which were made of lithium niobate single crystal with the thickness of 15 μm, having apertures of 4.3 mm (fnumber=1.23) and 2.6mm (fnumber=0.75) were tested. L-type IMN was selected for high sensitivity and compact design of the ultrasonic transducers. The target center frequency was chosen as the frequency where the electrical admittance (|Y|) and phase angle (θz) from impedance analysis was maximal and zero, respectively. The reference center frequency and reference echo magnitude were selected as the center frequency and echo magnitude, measured by pulse-echo testing, of the ultrasonic transducer without IMN. Initial component values and topology of IMN were determined using the Smith chart, and pulse-echo testing was analyzed to verify the performance of the ultrasonic transducers with and without IMN. After several iterations between changing component values and topology of IMN, and pulse-echo measurement of the ultrasonic transducer with IMN, optimized component values and topology of IMN were chosen when the measured center frequency from pulse-echo testing was comparable to the target frequency, and the measured echo magnitude was at least 30% larger than the reference echo magnitude. Performance of an ultrasonic transducer with and without IMN was tested by observing a tangible dent on the surface of a plastic petridish and single cell response after an acoustic pulse was

  17. Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction

    PubMed Central

    Lapidus, Saul; Han, Bo; Wang, Jin

    2008-01-01

    We develop a probabilistic method for analyzing global features of a cellular network under intrinsic statistical fluctuations, which is important when there are finite numbers of molecules. By making a self-consistent mean field approximation of splitting the variables in order to reduce the large number of degrees of freedom, which is reasonable for a not very strongly interacting network, we discovered that the underlying energy landscape of the mitogen-activated protein kinases (MAPKs) signal transduction network (with experimentally measured or inferred parameters such as chemical reaction rate coefficients in the network) is funneled toward a global minimum characterized by the nonequilibrium steady-state fixed point of the system at the end of the signal transduction process. For this system, we also show that the energy landscape is robust against intrinsic fluctuations and random perturbation to the inherent chemical reaction rates. The ratio of the slope versus the roughness of the energy landscape becomes a quantitative measure of robustness and stability of the network. Furthermore, we quantify the dissipation cost of this nonequilibrium system through entropy production, caused by the nonequilibrium flux in the system. We found that a lower dissipation cost corresponds to a more robust network. This least dissipation property might provide a design principle for robust and functional networks. Finally, we find the possibility of bistable and oscillatory-like solutions, which are important for cell fate decisions, upon perturbations. The method described here can be used in a variety of biological networks. PMID:18420822

  18. Geometric phase transition in the cellular network of the pancreatic islets may underlie the onset of type 1diabetes

    NASA Astrophysics Data System (ADS)

    Wang, Xujing

    Living systems are characterized by complexity in structure and emergent dynamic orders. In many aspects the onset of a chronic disease resembles phase transition in a dynamic system: quantitative changes accumulate largely unnoticed until a critical threshold is reached, which causes abrupt qualitative changes of the system. In this study we investigate this idea in a real example, the insulin-producing pancreatic islet β-cells and the onset of type 1 diabetes. Within each islet, the β-cells are electrically coupled to each other, and function as a network with synchronized actions. Using percolation theory we show how normal islet function is intrinsically linked to network connectivity, and the critical point where the islet cellular network loses site percolation, is consistent with laboratory and clinical observations of the threshold β-cell loss that causes islet functional failure. Numerical simulations confirm that the islet cellular network needs to be percolated for β-cells to synchronize. Furthermore, the interplay between site percolation and bond strength predicts the existence of a transient phase of islet functional recovery after disease onset and introduction of treatment, potentially explaining a long time mystery in the clinical study of type 1 diabetes: the honeymoon phenomenon. Based on these results, we hypothesized that the onset of T1D may be the result of a phase transition of the islet β-cell network. We further discuss the potential applications in identifying disease-driving factors, and the critical parameters that are predictive of disease onset.

  19. An asynchronous communication system based on the hyperchaotic system of 6th-order cellular neural network

    NASA Astrophysics Data System (ADS)

    Wang, Xingyuan; Xu, Bing; Luo, Chao

    2012-11-01

    This paper proposes a novel asynchronous communication scheme. Based on this scheme, a model using the hyperchaotic system of 6th-order Cellular Neural Network (CNN) is designed. This scheme enhances the security of asynchronous communication compared to the conventional ones. It is noteworthy that the proposed communication scheme does not depend on synchronization, and almost all chaotic systems can be involved in this scheme. Numerical simulations show the effectiveness of this scheme.

  20. Mechanical models of the cellular cytoskeletal network for the analysis of intracellular mechanical properties and force distributions: a review.

    PubMed

    Chen, Ting-Jung; Wu, Chia-Ching; Su, Fong-Chin

    2012-12-01

    The cytoskeleton, which is the major mechanical component of cells, supports the cell body and regulates the cellular motility to assist the cell in performing its biological functions. Several cytoskeletal network models have been proposed to investigate the mechanical properties of cells. This review paper summarizes these models with a focus on the prestressed cable network, the semi-flexible chain network, the open-cell foam, the tensegrity, and the granular models. The components, material parameters, types of connection joints, tension conditions, and the advantages and disadvantages of each model are evaluated from a structural and biological point of view. The underlying mechanisms that are associated with the morphological changes of spreading cells are expected to be simulated using a cytoskeletal model; however, it is still paid less attention most likely due to the lack of a suitable cytoskeletal model that can accurately model the spreading process. In this review article, the established cytoskeletal models are hoped to provide useful information for the development of future cytoskeletal models with different degrees of cell attachment for the study of the mechanical mechanisms underlying the cellular behaviors in response to external stimulations. PMID:23062682

  1. Position and Velocity Tracking in Cellular Networks Using the Kalman Filter

    SciTech Connect

    Olama, Mohammed M; Djouadi, Seddik M; Kuruganti, Phani Teja

    2009-01-01

    Access to the right information anytime, anywhere is becoming the new driving force for the information technology revolution. The 'right' information's relevance is based on the user's profile and his/her current geographical position and/or time. Location Based Service (LBS) is an innovative technology that provides information or makes information available based on the geographical location of the mobile user. Analysts predict that LBSs will lead to new applications, generating billions of US dollars worldwide (Leite, 2001; Searle, 2001). The need for an efficient and accurate mobile station (MS) positioning system is growing day by day. The ability to pinpoint the location of an individual has an obvious and vital value in the context of emergency services (Chan, 2003; Olama et al., 2008). Pinpointing the location of people and other valuable assets also opens the door to a new world of previously unimagined information services and m-commerce probabilities. For example, availability of services like 'Where is the nearest ATM?', 'Check traffic conditions on the highway on my route', 'Find a parking lot nearby', as well as answers to 'Where is my advisor?', and 'Where is my car?' will be an everyday rule in our lives (Charalambous & Panayiotou, 2004). A technology independent LBS architecture can be considered as comprised by three main parts (Girodon, 2002): A user requesting information, a mobile network operator and its partners, and several content providers (e.g. data, maps). The subscriber requests a personalized service dependant on his geographic location. The system will ask the Location Services Manager (which is in charge of handling requests, i.e., send/receive to the Location Calculator and the Content Providers) to pinpoint the location of the mobile. The Location Services Manager (LSM), using the Location Calculator, will ask the Content Provider (CP) to supply qualified information according to the mobile's geographical position. The LSM will

  2. Comparative analysis of Salmonella susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defense network.

    PubMed

    Condell, Orla; Power, Karen A; Händler, Kristian; Finn, Sarah; Sheridan, Aine; Sergeant, Kjell; Renaut, Jenny; Burgess, Catherine M; Hinton, Jay C D; Nally, Jarlath E; Fanning, Séamus

    2014-01-01

    Chlorhexidine is one of the most widely used biocides in health and agricultural settings as well as in the modern food industry. It is a cationic biocide of the biguanide class. Details of its mechanism of action are largely unknown. The frequent use of chlorhexidine has been questioned recently, amidst concerns that an overuse of this compound may select for bacteria displaying an altered susceptibility to antimicrobials, including clinically important anti-bacterial agents. We generated a Salmonella enterica serovar Typhimurium isolate (ST24(CHX)) that exhibited a high-level tolerant phenotype to chlorhexidine, following several rounds of in vitro selection, using sub-lethal concentrations of the biocide. This mutant showed altered suceptibility to a panel of clinically important antimicrobial compounds. Here we describe a genomic, transcriptomic, proteomic, and phenotypic analysis of the chlorhexidine tolerant S. Typhimurium compared with its isogenic sensitive progenitor. Results from this study describe a chlorhexidine defense network that functions in both the reference chlorhexidine sensitive isolate and the tolerant mutant. The defense network involved multiple cell targets including those associated with the synthesis and modification of the cell wall, the SOS response, virulence, and a shift in cellular metabolism toward anoxic pathways, some of which were regulated by CreB and Fur. In addition, results indicated that chlorhexidine tolerance was associated with more extensive modifications of the same cellular processes involved in this proposed network, as well as a divergent defense response involving the up-regulation of additional targets such as the flagellar apparatus and an altered cellular phosphate metabolism. These data show that sub-lethal concentrations of chlorhexidine induce distinct changes in exposed Salmonella, and our findings provide insights into the mechanisms of action and tolerance to this biocidal agent. PMID:25136333

  3. Comparative analysis of Salmonella susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defense network

    PubMed Central

    Condell, Orla; Power, Karen A.; Händler, Kristian; Finn, Sarah; Sheridan, Aine; Sergeant, Kjell; Renaut, Jenny; Burgess, Catherine M.; Hinton, Jay C. D.; Nally, Jarlath E.; Fanning, Séamus

    2014-01-01

    Chlorhexidine is one of the most widely used biocides in health and agricultural settings as well as in the modern food industry. It is a cationic biocide of the biguanide class. Details of its mechanism of action are largely unknown. The frequent use of chlorhexidine has been questioned recently, amidst concerns that an overuse of this compound may select for bacteria displaying an altered susceptibility to antimicrobials, including clinically important anti-bacterial agents. We generated a Salmonella enterica serovar Typhimurium isolate (ST24CHX) that exhibited a high-level tolerant phenotype to chlorhexidine, following several rounds of in vitro selection, using sub-lethal concentrations of the biocide. This mutant showed altered suceptibility to a panel of clinically important antimicrobial compounds. Here we describe a genomic, transcriptomic, proteomic, and phenotypic analysis of the chlorhexidine tolerant S. Typhimurium compared with its isogenic sensitive progenitor. Results from this study describe a chlorhexidine defense network that functions in both the reference chlorhexidine sensitive isolate and the tolerant mutant. The defense network involved multiple cell targets including those associated with the synthesis and modification of the cell wall, the SOS response, virulence, and a shift in cellular metabolism toward anoxic pathways, some of which were regulated by CreB and Fur. In addition, results indicated that chlorhexidine tolerance was associated with more extensive modifications of the same cellular processes involved in this proposed network, as well as a divergent defense response involving the up-regulation of additional targets such as the flagellar apparatus and an altered cellular phosphate metabolism. These data show that sub-lethal concentrations of chlorhexidine induce distinct changes in exposed Salmonella, and our findings provide insights into the mechanisms of action and tolerance to this biocidal agent. PMID:25136333

  4. Delay-dependent exponential passivity of uncertain cellular neural networks with discrete and distributed time-varying delays.

    PubMed

    Du, Yuanhua; Zhong, Shouming; Xu, Jia; Zhou, Nan

    2015-05-01

    This paper is concerned with the delay-dependent exponential passivity analysis issue for uncertain cellular neural networks with discrete and distributed time-varying delays. By decomposing the delay interval into multiple equidistant subintervals and multiple nonuniform subintervals, a suitable augmented Lyapunov-Krasovskii functionals are constructed on these intervals. A set of novel sufficient conditions are obtained to guarantee the exponential passivity analysis issue for the considered system. Finally, two numerical examples are provided to demonstrate the effectiveness of the proposed results. PMID:25702046

  5. Exact quantification of cellular robustness in genome-scale metabolic networks

    PubMed Central

    Gerstl, Matthias P.; Klamt, Steffen; Jungreuthmayer, Christian; Zanghellini, Jürgen

    2016-01-01

    Motivation: Robustness, the ability of biological networks to uphold their functionality in spite of perturbations, is a key characteristic of all living systems. Although several theoretical approaches have been developed to formalize robustness, it still eludes an exact quantification. Here, we present a rigorous and quantitative approach for the structural robustness of metabolic networks by measuring their ability to tolerate random reaction (or gene) knockouts. Results: In analogy to reliability theory, based on an explicit consideration of all possible knockout sets, we exactly quantify the probability of failure for a given network function (e.g. growth). This measure can be computed if the network’s minimal cut sets (MSCs) are known. We show that even in genome-scale metabolic networks the probability of (network) failure can be reliably estimated from MSCs with lowest cardinalities. We demonstrate the applicability of our theory by analyzing the structural robustness of multiple Enterobacteriaceae and Blattibacteriaceae and show a dramatically low structural robustness for the latter. We find that structural robustness develops from the ability to proliferate in multiple growth environments consistent with experimentally found knowledge. Conclusion: The probability of (network) failure provides thus a reliable and easily computable measure of structural robustness and redundancy in (genome-scale) metabolic networks. Availability and implementation: Source code is available under the GNU General Public License at https://github.com/mpgerstl/networkRobustnessToolbox. Contact: juergen.zanghellini@boku.ac.at Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26543173

  6. The Speckle Noise Reduction and the Boundary Enhancement on Medical Ultrasound Images using the Cellular Neural Networks

    NASA Astrophysics Data System (ADS)

    Park, Hyunkyung; Miyazaki, Ryota; Nishimura, Toshihiro; Tamaki, Yasuhiro

    The purpose is to remove the speckle noise and to emphasize the boundary of a tumor by filtering based on the intensity difference in the medical ultrasound images. The proposed method is evaluated using numerical phantom simulating ultrasound B-mode images, and the effect is confirmed by applying to medical ultrasound images. Therefore, some important features such as tissue boundaries and small tumors may be overlooked. A CNN (cellular neural networks) for the speckle reduction and the edge enhancement are proposed in this paper. A CNN which is a kind of recurrent neural network can deal with images by the weight of neurons called a cell. It could be obtained more detail images recognition compared with the previous studies. A determination template parameters of the CNN for ultrasound image processing is discussed. The experimental results show effectiveness of applying the proposed method to boundary enhancement and the speckle reduction of medical ultrasound image.

  7. Multi-Hop Link Capacity of Multi-Route Multi-Hop MRC Diversity for a Virtual Cellular Network

    NASA Astrophysics Data System (ADS)

    Daou, Imane; Kudoh, Eisuke; Adachi, Fumiyuki

    In virtual cellular network (VCN), proposed for high-speed mobile communications, the signal transmitted from a mobile terminal is received by some wireless ports distributed in each virtual cell and relayed to the central port that acts as a gateway to the core network. In this paper, we apply the multi-route MHMRC diversity in order to decrease the transmit power and increase the multi-hop link capacity. The transmit power, the interference power and the link capacity are evaluated for DS-CDMA multi-hop VCN by computer simulation. The multi-route MHMRC diversity can be applied to not only DS-CDMA but also other access schemes (i. e. MC-CDMA, OFDM, etc.).

  8. Mitigating Handoff Call Dropping in Wireless Cellular Networks: A Call Admission Control Technique

    NASA Astrophysics Data System (ADS)

    Ekpenyong, Moses Effiong; Udoh, Victoria Idia; Bassey, Udoma James

    2016-06-01

    Handoff management has been an important but challenging issue in the field of wireless communication. It seeks to maintain seamless connectivity of mobile users changing their points of attachment from one base station to another. This paper derives a call admission control model and establishes an optimal step-size coefficient (k) that regulates the admission probability of handoff calls. An operational CDMA network carrier was investigated through the analysis of empirical data collected over a period of 1 month, to verify the performance of the network. Our findings revealed that approximately 23 % of calls in the existing system were lost, while 40 % of the calls (on the average) were successfully admitted. A simulation of the proposed model was then carried out under ideal network conditions to study the relationship between the various network parameters and validate our claim. Simulation results showed that increasing the step-size coefficient degrades the network performance. Even at optimum step-size (k), the network could still be compromised in the presence of severe network crises, but our model was able to recover from these problems and still functions normally.

  9. Beta Cell Formation in vivo Through Cellular Networking, Integration and Processing (CNIP) in Wild Type Adult Mice.

    PubMed

    Doiron, Bruno; Hu, Wenchao; DeFronzo, Ralph A

    2016-01-01

    Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50% of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-stem (somatic) cells into pancreatic beta cells. The Cellular Networking, Integration and Processing (CNIP) approach targets cellular mechanisms involved in pancreatic function in the organ's adult state and utilizes a synergistic mechanism that integrates three important levels of cellular regulation to induce beta cell formation: (i) glucose metabolism, (ii) membrane receptor function, and (iii) gene transcription. The aim of the present study was to induce pancreatic beta cell formation in vivo in adult animals without stem cells and without dedifferentiating cells to recapitulate the embryonic pathway as previously published (1-3). Our results employing CNIP demonstrate that: (i) insulin secreting cells can be generated in adult pancreatic tissue in vivo and circumvent the problem of generating endocrine (glucagon and somatostatin) cells that exert deleterious effects on glucose homeostasis, and (ii) longterm normalization of glucose tolerance and insulin secretion can be achieved in a wild type diabetic mouse model. The CNIP cocktail has the potential to be used as a preventative or therapeutic treatment or cure for both type 1 and type 2 diabetes. PMID:26696016

  10. A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

    PubMed

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

    Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle. PMID:27087101

  11. The dynamic and geometric phase transition in the cellular network of pancreatic islet

    NASA Astrophysics Data System (ADS)

    Wang, Xujing

    2013-03-01

    The pancreatic islet is a micro-organ that contains several thousands of endocrine cells, majority of which being the insulin releasing β - cells . - cellsareexcitablecells , andarecoupledtoeachother through gap junctional channels. Here, using percolation theory, we investigate the role of network structure in determining the dynamics of the β-cell network. We show that the β-cell synchronization depends on network connectivity. More specifically, as the site occupancy is reducing, initially the β-cell synchronization is barely affected, until it reaches around a critical value, where the synchronization exhibit a sudden rapid decline, followed by an slow exponential tail. This critical value coincides with the critical site open probability for percolation transition. The dependence over bond strength is similar, exhibiting critical-behavior like dependence around a certain value of bond strength. These results suggest that the β-cell network undergoes a dynamic phase transition when the network is percolated. We further apply the findings to study diabetes. During the development of diabetes, the β - cellnetworkconnectivitydecreases . Siteoccupancyreducesfromthe reducing β-cell mass, and the bond strength is increasingly impaired from β-cell stress and chronic hyperglycemia. We demonstrate that the network dynamics around the percolation transition explain the disease dynamics around onset, including a long time mystery in diabetes, the honeymoon phenomenon.

  12. A modified size-dependent core-shell model and its application in the wave propagation of square cellular networks

    NASA Astrophysics Data System (ADS)

    Xu, Xiao-Jian; Wang, Ya-Chuan; Wang, Bo; Zhang, Kai

    2016-06-01

    We propose a modified core-shell model to depict the size-dependent elastic properties of materials with several different cross-sections. By using the Young-Laplace equation, a modified Euler-Bernoulli equation, which has taken a power-law relation between the bulk and surface moduli into account, is derived. A finite element method of the modified Euler-Bernoulli equation is formulated, and assembled to investigate the dispersion relations of the infinite two-dimensional periodic square cellular networks. The effectiveness of the proposed core-shell model is verified by comparing with results of the experiments and the molecular dynamics simulations available in the literature. Numerical results show that surface effects play an important role on the cellular networks with small diameters, large aspect ratios and high wave frequencies. Meanwhile, the analytical expressions for the size-dependent elastic modulus may be useful for the study of the size-dependent elasticity of materials and structures at small length scales.

  13. Robust synchronization analysis in nonlinear stochastic cellular networks with time-varying delays, intracellular perturbations and intercellular noise.

    PubMed

    Chen, Po-Wei; Chen, Bor-Sen

    2011-08-01

    Naturally, a cellular network consisted of a large amount of interacting cells is complex. These cells have to be synchronized in order to emerge their phenomena for some biological purposes. However, the inherently stochastic intra and intercellular interactions are noisy and delayed from biochemical processes. In this study, a robust synchronization scheme is proposed for a nonlinear stochastic time-delay coupled cellular network (TdCCN) in spite of the time-varying process delay and intracellular parameter perturbations. Furthermore, a nonlinear stochastic noise filtering ability is also investigated for this synchronized TdCCN against stochastic intercellular and environmental disturbances. Since it is very difficult to solve a robust synchronization problem with the Hamilton-Jacobi inequality (HJI) matrix, a linear matrix inequality (LMI) is employed to solve this problem via the help of a global linearization method. Through this robust synchronization analysis, we can gain a more systemic insight into not only the robust synchronizability but also the noise filtering ability of TdCCN under time-varying process delays, intracellular perturbations and intercellular disturbances. The measures of robustness and noise filtering ability of a synchronized TdCCN have potential application to the designs of neuron transmitters, on-time mass production of biochemical molecules, and synthetic biology. Finally, a benchmark of robust synchronization design in Escherichia coli repressilators is given to confirm the effectiveness of the proposed methods. PMID:21624379

  14. Coverage Extension and Balancing the Transmitted Power of the Moving Relay Node at LTE-A Cellular Network

    PubMed Central

    Aldhaibani, Jaafar A.; Yahya, Abid; Ahmad, R. Badlishah

    2014-01-01

    The poor capacity at cell boundaries is not enough to meet the growing demand and stringent design which required high capacity and throughput irrespective of user's location in the cellular network. In this paper, we propose new schemes for an optimum fixed relay node (RN) placement in LTE-A cellular network to enhance throughput and coverage extension at cell edge region. The proposed approach mitigates interferences between all nodes and ensures optimum utilization with the optimization of transmitted power. Moreover, we proposed a new algorithm to balance the transmitted power of moving relay node (MR) over cell size and providing required SNR and throughput at the users inside vehicle along with reducing the transmitted power consumption by MR. The numerical analysis along with the simulation results indicates that an improvement in capacity for users is 40% increment at downlink transmission from cell capacity. Furthermore, the results revealed that there is saving nearly 75% from transmitted power in MR after using proposed balancing algorithm. ATDI simulator was used to verify the numerical results, which deals with real digital cartographic and standard formats for terrain. PMID:24672378

  15. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network.

    PubMed

    Couto, Narciso; Wood, Jennifer; Barber, Jill

    2016-06-01

    In this review article we examine the role of glutathione reductase in the regulation, modulation and maintenance of cellular redox homoeostasis. Glutathione reductase is responsible for maintaining the supply of reduced glutathione; one of the most abundant reducing thiols in the majority of cells. In its reduced form, glutathione plays key roles in the cellular control of reactive oxygen species. Reactive oxygen species act as intracellular and extracellular signalling molecules and complex cross talk between levels of reactive oxygen species, levels of oxidised and reduced glutathione and other thiols, and antioxidant enzymes such as glutathione reductase determine the most suitable conditions for redox control within a cell or for activation of programmed cell death. Additionally, we discuss the translation and expression of glutathione reductase in a number of organisms including yeast and humans. In yeast and human cells, a single gene expresses more than one form of glutathione reductase, destined for residence in the cytoplasm or for translocation to different organelles; in plants, however, two genes encoding this protein have been described. In general, insects and kinetoplastids (a group of protozoa, including Plasmodia and Trypanosoma) do not express glutathione reductase or glutathione biosynthetic enzymes. Instead, they express either the thioredoxin system or the trypanothione system. The thioredoxin system is also present in organisms that have the glutathione system and there may be overlapping functions with cross-talk between the two systems. Finally we evaluate therapeutic targets to overcome oxidative stress associated cellular disorders. PMID:26923386

  16. Analysis of the local organization and dynamics of cellular actin networks

    PubMed Central

    Luo, Weiwei; Yu, Cheng-han; Lieu, Zi Zhao; Allard, Jun; Mogilner, Alex; Sheetz, Michael P.

    2013-01-01

    A ctin filaments, with the aid of multiple accessory proteins, self-assemble into a variety of network patterns. We studied the organization and dynamics of the actin network in nonadhesive regions of cells bridging fibronectin-coated adhesive strips. The network was formed by actin nodes associated with and linked by myosin II and containing the formin disheveled-associated activator of morphogenesis 1 (DAAM1) and the cross-linker filamin A (FlnA). After Latrunculin A (LatA) addition, actin nodes appeared to be more prominent and demonstrated drift-diffusion motion. Superresolution microscopy revealed that, in untreated cells, DAAM1 formed patches with a similar spatial arrangement to the actin nodes. Node movement (diffusion coefficient and velocity) in LatA-treated cells was dependent on the level and activity of myosin IIA, DAAM1, and FlnA. Based on our results, we developed a computational model of the dynamic formin-filamin-actin asters that can self-organize into a contractile actomyosin network. We suggest that such networks are critical for connecting distant parts of the cell to maintain the mechanical coherence of the cytoplasm. PMID:24081490

  17. Analysis of the local organization and dynamics of cellular actin networks.

    PubMed

    Luo, Weiwei; Yu, Cheng-han; Lieu, Zi Zhao; Allard, Jun; Mogilner, Alex; Sheetz, Michael P; Bershadsky, Alexander D

    2013-09-30

    Actin filaments, with the aid of multiple accessory proteins, self-assemble into a variety of network patterns. We studied the organization and dynamics of the actin network in nonadhesive regions of cells bridging fibronectin-coated adhesive strips. The network was formed by actin nodes associated with and linked by myosin II and containing the formin disheveled-associated activator of morphogenesis 1 (DAAM1) and the cross-linker filamin A (FlnA). After Latrunculin A (LatA) addition, actin nodes appeared to be more prominent and demonstrated drift-diffusion motion. Superresolution microscopy revealed that, in untreated cells, DAAM1 formed patches with a similar spatial arrangement to the actin nodes. Node movement (diffusion coefficient and velocity) in LatA-treated cells was dependent on the level and activity of myosin IIA, DAAM1, and FlnA. Based on our results, we developed a computational model of the dynamic formin-filamin-actin asters that can self-organize into a contractile actomyosin network. We suggest that such networks are critical for connecting distant parts of the cell to maintain the mechanical coherence of the cytoplasm. PMID:24081490

  18. Rainfall measurements from cellular networks microwave links : an alternative ground reference for satellite validation and hydrology in Africa .

    NASA Astrophysics Data System (ADS)

    Gosset, Marielle; cazenave, frederic; Zougmore, françois; Doumounia, Ali; kacou, Modeste

    2015-04-01

    In many part of the Tropics the ground based gauge networks are sparse, often degrading and accessing this data for monitoring rainfall or for validating satellite products is sometime difficult. Here, an alternative rainfall measuring technique is proposed and tested in West Africa. It is based on using commercial microwave links from cellular telephone networks to detect and quantify rainfall. Rainfall monitoring based on commercial terrestrial microwave links has been tested for the first time in Burkina Faso, in Sahel. The rainfall regime is characterized by intense rainfall intensities brought by mesoscale Convective systems (MCS), generated by deep organized convection. The region is subjected to drought as well as dramatic floods associated with the intense rainfall provided by a few MCSs. The hydrometeorological risk is increasing and need to be monitored. In collaboration with the national cellular phone operator, Telecel Faso, the attenuation on 29 km long microwave links operating at 7 GHz was monitored at 1s time rate for the monsoon season 2012. The time series of attenuation is transformed into rain rates and compared with rain gauge data. The method is successful in quantifying rainfall: 95% of the rainy days are detected. The correlation with the daily raingauge series is 0.8 and the season bias is 5%. The correlation at the 5 min time step within each event is also high. We will present the quantitative results, discuss the uncertainties and compare the time series and the 2D maps with those derived from a polarimetric radar. The results demonstrate the potential interest of exploiting national and regional wireless telecommunication networks to provide rainfall maps for various applications : urban hydrology, agro-hydrological risk monitoring, satellite validation and development of combined rainfall products. We will also present the outcome of the first international Rain Cell Africa workshop held in Ouagadougou early 2015.

  19. From Cellular Attractor Selection to Adaptive Signal Control for Traffic Networks.

    PubMed

    Tian, Daxin; Zhou, Jianshan; Sheng, Zhengguo; Wang, Yunpeng; Ma, Jianming

    2016-01-01

    The management of varying traffic flows essentially depends on signal controls at intersections. However, design an optimal control that considers the dynamic nature of a traffic network and coordinates all intersections simultaneously in a centralized manner is computationally challenging. Inspired by the stable gene expressions of Escherichia coli in response to environmental changes, we explore the robustness and adaptability performance of signalized intersections by incorporating a biological mechanism in their control policies, specifically, the evolution of each intersection is induced by the dynamics governing an adaptive attractor selection in cells. We employ a mathematical model to capture such biological attractor selection and derive a generic, adaptive and distributed control algorithm which is capable of dynamically adapting signal operations for the entire dynamical traffic network. We show that the proposed scheme based on attractor selection can not only promote the balance of traffic loads on each link of the network but also allows the global network to accommodate dynamical traffic demands. Our work demonstrates the potential of bio-inspired intelligence emerging from cells and provides a deep understanding of adaptive attractor selection-based control formation that is useful to support the designs of adaptive optimization and control in other domains. PMID:26972968

  20. From Cellular Attractor Selection to Adaptive Signal Control for Traffic Networks

    PubMed Central

    Tian, Daxin; Zhou, Jianshan; Sheng, Zhengguo; Wang, Yunpeng; Ma, Jianming

    2016-01-01

    The management of varying traffic flows essentially depends on signal controls at intersections. However, design an optimal control that considers the dynamic nature of a traffic network and coordinates all intersections simultaneously in a centralized manner is computationally challenging. Inspired by the stable gene expressions of Escherichia coli in response to environmental changes, we explore the robustness and adaptability performance of signalized intersections by incorporating a biological mechanism in their control policies, specifically, the evolution of each intersection is induced by the dynamics governing an adaptive attractor selection in cells. We employ a mathematical model to capture such biological attractor selection and derive a generic, adaptive and distributed control algorithm which is capable of dynamically adapting signal operations for the entire dynamical traffic network. We show that the proposed scheme based on attractor selection can not only promote the balance of traffic loads on each link of the network but also allows the global network to accommodate dynamical traffic demands. Our work demonstrates the potential of bio-inspired intelligence emerging from cells and provides a deep understanding of adaptive attractor selection-based control formation that is useful to support the designs of adaptive optimization and control in other domains. PMID:26972968

  1. From Cellular Attractor Selection to Adaptive Signal Control for Traffic Networks

    NASA Astrophysics Data System (ADS)

    Tian, Daxin; Zhou, Jianshan; Sheng, Zhengguo; Wang, Yunpeng; Ma, Jianming

    2016-03-01

    The management of varying traffic flows essentially depends on signal controls at intersections. However, design an optimal control that considers the dynamic nature of a traffic network and coordinates all intersections simultaneously in a centralized manner is computationally challenging. Inspired by the stable gene expressions of Escherichia coli in response to environmental changes, we explore the robustness and adaptability performance of signalized intersections by incorporating a biological mechanism in their control policies, specifically, the evolution of each intersection is induced by the dynamics governing an adaptive attractor selection in cells. We employ a mathematical model to capture such biological attractor selection and derive a generic, adaptive and distributed control algorithm which is capable of dynamically adapting signal operations for the entire dynamical traffic network. We show that the proposed scheme based on attractor selection can not only promote the balance of traffic loads on each link of the network but also allows the global network to accommodate dynamical traffic demands. Our work demonstrates the potential of bio-inspired intelligence emerging from cells and provides a deep understanding of adaptive attractor selection-based control formation that is useful to support the designs of adaptive optimization and control in other domains.

  2. Actin-binding proteins: the long road to understanding the dynamic landscape of cellular actin networks.

    PubMed

    Lappalainen, Pekka

    2016-08-15

    The actin cytoskeleton supports a vast number of cellular processes in nonmuscle cells. It is well established that the organization and dynamics of the actin cytoskeleton are controlled by a large array of actin-binding proteins. However, it was only 40 years ago that the first nonmuscle actin-binding protein, filamin, was identified and characterized. Filamin was shown to bind and cross-link actin filaments into higher-order structures and contribute to phagocytosis in macrophages. Subsequently many other nonmuscle actin-binding proteins were identified and characterized. These proteins regulate almost all steps of the actin filament assembly and disassembly cycles, as well as the arrangement of actin filaments into diverse three-dimensional structures. Although the individual biochemical activities of most actin-regulatory proteins are relatively well understood, knowledge of how these proteins function together in a common cytoplasm to control actin dynamics and architecture is only beginning to emerge. Furthermore, understanding how signaling pathways and mechanical cues control the activities of various actin-binding proteins in different cellular, developmental, and pathological processes will keep researchers busy for decades. PMID:27528696

  3. Biological pattern generation: the cellular and computational logic of networks in motion.

    PubMed

    Grillner, Sten

    2006-12-01

    In 1900, Ramón y Cajal advanced the neuron doctrine, defining the neuron as the fundamental signaling unit of the nervous system. Over a century later, neurobiologists address the circuit doctrine: the logic of the core units of neuronal circuitry that control animal behavior. These are circuits that can be called into action for perceptual, conceptual, and motor tasks, and we now need to understand whether there are coherent and overriding principles that govern the design and function of these modules. The discovery of central motor programs has provided crucial insight into the logic of one prototypic set of neural circuits: those that generate motor patterns. In this review, I discuss the mode of operation of these pattern generator networks and consider the neural mechanisms through which they are selected and activated. In addition, I will outline the utility of computational models in analysis of the dynamic actions of these motor networks. PMID:17145498

  4. Mobility-Aware Caching and Computation Offloading in 5G Ultra-Dense Cellular Networks.

    PubMed

    Chen, Min; Hao, Yixue; Qiu, Meikang; Song, Jeungeun; Wu, Di; Humar, Iztok

    2016-01-01

    Recent trends show that Internet traffic is increasingly dominated by content, which is accompanied by the exponential growth of traffic. To cope with this phenomena, network caching is introduced to utilize the storage capacity of diverse network devices. In this paper, we first summarize four basic caching placement strategies, i.e., local caching, Device-to-Device (D2D) caching, Small cell Base Station (SBS) caching and Macrocell Base Station (MBS) caching. However, studies show that so far, much of the research has ignored the impact of user mobility. Therefore, taking the effect of the user mobility into consideration, we proposes a joint mobility-aware caching and SBS density placement scheme (MS caching). In addition, differences and relationships between caching and computation offloading are discussed. We present a design of a hybrid computation offloading and support it with experimental results, which demonstrate improved performance in terms of energy cost. Finally, we discuss the design of an incentive mechanism by considering network dynamics, differentiated user's quality of experience (QoE) and the heterogeneity of mobile terminals in terms of caching and computing capabilities. PMID:27347975

  5. Mobility-Aware Caching and Computation Offloading in 5G Ultra-Dense Cellular Networks

    PubMed Central

    Chen, Min; Hao, Yixue; Qiu, Meikang; Song, Jeungeun; Wu, Di; Humar, Iztok

    2016-01-01

    Recent trends show that Internet traffic is increasingly dominated by content, which is accompanied by the exponential growth of traffic. To cope with this phenomena, network caching is introduced to utilize the storage capacity of diverse network devices. In this paper, we first summarize four basic caching placement strategies, i.e., local caching, Device-to-Device (D2D) caching, Small cell Base Station (SBS) caching and Macrocell Base Station (MBS) caching. However, studies show that so far, much of the research has ignored the impact of user mobility. Therefore, taking the effect of the user mobility into consideration, we proposes a joint mobility-aware caching and SBS density placement scheme (MS caching). In addition, differences and relationships between caching and computation offloading are discussed. We present a design of a hybrid computation offloading and support it with experimental results, which demonstrate improved performance in terms of energy cost. Finally, we discuss the design of an incentive mechanism by considering network dynamics, differentiated user’s quality of experience (QoE) and the heterogeneity of mobile terminals in terms of caching and computing capabilities. PMID:27347975

  6. Cellular location and major terminal networks of the orexinergic system in the brain of two megachiropterans.

    PubMed

    Dell, Leigh-Anne; Kruger, Jean-Leigh; Pettigrew, John D; Manger, Paul R

    2013-11-01

    The present study describes the distribution of orexin-A immunoreactive neurons and their terminal networks in the brains of two species of megachiropterans. In general the organization of the orexinergic system in the mammalian brain is conserved across species, but as one of two groups of mammals that fly and have a high metabolic rate, it was of interest to determine whether there were any specific differences in the organization of this system in the megachiropterans. Orexinergic neurons were limited in distribution to the hypothalamus, and formed three distinct clusters, or nuclei, a main cluster with a perifornical location, a zona incerta cluster in the dorsolateral hypothalamus and an optic tract cluster in the ventrolateral hypothalamus. The nuclear parcellation of the orexinergic system in the megachiropterans is similar to that seen in many mammals, but differs from the microchiropterans where the optic tract cluster is absent. The terminal networks of the orexinergic neurons in the megachiropterans was similar to that seen in a range of mammalian species, with significant terminal networks being found in the hypothalamus, cholinergic pedunculopontine and laterodorsal tegemental nuclei, the noradrenergic locus coeruleus complex, all serotonergic nuclei, the paraventricular nuclei of the epithalamus and adjacent to the habenular nuclei. While the megachiropteran orexinergic system is typically mammalian in form, it does differ from that reported for microchiropterans, and thus provides an additional neural character arguing for independent evolution of these two chiropteran suborders. PMID:24041616

  7. Cellular and circuit models of increased resting-state network gamma activity in schizophrenia.

    PubMed

    White, R S; Siegel, S J

    2016-05-01

    Schizophrenia (SCZ) is a disorder characterized by positive symptoms (hallucinations, delusions), negative symptoms (blunted affect, alogia, reduced sociability, and anhedonia), as well as persistent cognitive deficits (memory, concentration, and learning). While the biology underlying subjective experiences is difficult to study, abnormalities in electroencephalographic (EEG) measures offer a means to dissect potential circuit and cellular changes in brain function. EEG is indispensable for studying cerebral information processing due to the introduction of techniques for the decomposition of event-related activity into its frequency components. Specifically, brain activity in the gamma frequency range (30-80Hz) is thought to underlie cognitive function and may be used as an endophenotype to aid in diagnosis and treatment of SCZ. In this review we address evidence indicating that there is increased resting-state gamma power in SCZ. We address how modeling this aspect of the illness in animals may help treatment development as well as providing insights into the etiology of SCZ. PMID:26577758

  8. From molecular interaction to acute promyelocytic leukemia: Calculating leukemogenesis and remission from endogenous molecular-cellular network.

    PubMed

    Yuan, Ruoshi; Zhu, Xiaomei; Radich, Jerald P; Ao, Ping

    2016-01-01

    Acute promyelocytic leukemia (APL) remains the best example of a malignancy that can be cured clinically by differentiation therapy. We demonstrate that APL may emerge from a dynamical endogenous molecular-cellular network obtained from normal, non-cancerous molecular interactions such as signal transduction and translational regulation under physiological conditions. This unifying framework, which reproduces APL, normal progenitor, and differentiated granulocytic phenotypes as different robust states from the network dynamics, has the advantage to study transition between these states, i.e. critical drivers for leukemogenesis and targets for differentiation. The simulation results quantitatively reproduce microarray profiles of NB4 and HL60 cell lines in response to treatment and normal neutrophil differentiation, and lead to new findings such as biomarkers for APL and additional molecular targets for arsenic trioxide therapy. The modeling shows APL and normal states mutually suppress each other, both in "wiring" and in dynamical cooperation. Leukemogenesis and recovery under treatment may be a consequence of spontaneous or induced transitions between robust states, through "passes" or "dragging" by drug effects. Our approach rationalizes leukemic complexity and constructs a platform towards extending differentiation therapy by performing "dry" molecular biology experiments. PMID:27098097

  9. From molecular interaction to acute promyelocytic leukemia: Calculating leukemogenesis and remission from endogenous molecular-cellular network

    PubMed Central

    Yuan, Ruoshi; Zhu, Xiaomei; Radich, Jerald P.; Ao, Ping

    2016-01-01

    Acute promyelocytic leukemia (APL) remains the best example of a malignancy that can be cured clinically by differentiation therapy. We demonstrate that APL may emerge from a dynamical endogenous molecular-cellular network obtained from normal, non-cancerous molecular interactions such as signal transduction and translational regulation under physiological conditions. This unifying framework, which reproduces APL, normal progenitor, and differentiated granulocytic phenotypes as different robust states from the network dynamics, has the advantage to study transition between these states, i.e. critical drivers for leukemogenesis and targets for differentiation. The simulation results quantitatively reproduce microarray profiles of NB4 and HL60 cell lines in response to treatment and normal neutrophil differentiation, and lead to new findings such as biomarkers for APL and additional molecular targets for arsenic trioxide therapy. The modeling shows APL and normal states mutually suppress each other, both in “wiring” and in dynamical cooperation. Leukemogenesis and recovery under treatment may be a consequence of spontaneous or induced transitions between robust states, through “passes” or “dragging” by drug effects. Our approach rationalizes leukemic complexity and constructs a platform towards extending differentiation therapy by performing “dry” molecular biology experiments. PMID:27098097

  10. TRPV1 mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and network-formation

    PubMed Central

    Hofmann, Nicole A.; Barth, Sonja; Waldeck-Weiermair, Markus; Klec, Christiane; Strunk, Dirk; Malli, Roland; Graier, Wolfgang F.

    2014-01-01

    ABSTRACT Anandamide (N-arachidonyl ethanolamide, AEA) is an endogenous cannabinoid that is involved in various pathological conditions, including cardiovascular diseases and tumor-angiogenesis. Herein, we tested the involvement of classical cannabinoid receptors (CBRs) and the Ca2+-channel transient receptor potential vanilloid 1 (TRPV1) on cellular AEA uptake and its effect on endothelial cell proliferation and network-formation. Uptake of the fluorescence-labeled anandamide (SKM4-45-1) was monitored in human endothelial colony-forming cells (ECFCs) and a human endothelial-vein cell line (EA.hy926). Involvement of the receptors during AEA translocation was determined by selective pharmacological inhibition (AM251, SR144528, CID16020046, SB366791) and molecular interference by TRPV1-selective siRNA-mediated knock-down and TRPV1 overexpression. We show that exclusively TRPV1 contributes essentially to AEA transport into endothelial cells in a Ca2+-independent manner. This TRPV1 function is a prerequisite for AEA-induced endothelial cell proliferation and network-formation. Our findings point to a so far unknown moonlighting function of TRPV1 as Ca2+-independent contributor/regulator of AEA uptake. We propose TRPV1 as representing a promising target for development of pharmacological therapies against AEA-triggered endothelial cell functions, including their stimulatory effect on tumor-angiogenesis. PMID:25395667

  11. The p53 network: Cellular and systemic DNA damage responses in aging and cancer

    PubMed Central

    Reinhardt, H. Christian; Schumacher, Björn

    2014-01-01

    Genome instability contributes to cancer development and accelerates age-related pathologies as evidenced by a variety of congenital cancer susceptibility and progeroid syndromes that are caused by defects in genome maintenance mechanisms. DNA damage response pathways that are mediated through the tumor suppressor p53 play an important role in the cell intrinsic responses to genome instability, including a transient cell cycle arrest, senescence and apoptosis. Both senescence and apoptosis are powerful tumor suppressive pathways preventing the uncontrolled proliferation of transformed cells. However, both pathways can potentially deplete stem and progenitor cell pools, thus promoting tissue degeneration and organ failure, which are both hallmarks of aging. p53 signaling is also involved in mediating non-cell autonomous interactions with the innate immune system and in the systemic adjustments during the aging process. The network of p53 target genes thus functions as an important regulator of cancer prevention and the physiology of aging. PMID:22265392

  12. Evolving gene regulation networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system

    PubMed Central

    Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L.

    2014-01-01

    Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs, their localized patterning into remarkably different cell types aggregated into variably sized parts of the central nervous system begin to emerge. Insights at the cellular and molecular level begin to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early and not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system. PMID:25416504

  13. Structurally Dynamic Cellular Networks as Models for Planck Scale Physics and the Quantum Vacuum

    NASA Astrophysics Data System (ADS)

    Requardt, Manfred

    Starting from the working hypothesis that both physics and the corresponding mathematics have to be described by means of discrete concepts on the Planck scale, one of the many problems one has to face in this enterprise is to find the discrete protoforms of the building blocks of our ordinary continuum physics and mathematics. We regard these continuum concepts and continuum space-time (S-T) in particular as being emergent, coarse-grained and derived relative to an underlying erratic and disordered microscopic substratum which is expected to play by quite different rules. A central role in our analysis is played by a geometric renormalization group which creates (among other things) a kind of sparse translocal network of correlations in classical continuous space-time and underlies in our view such mysterious phenomena as holography and the black hole entropy-area law. The same point of view holds for quantum theory which we also regard as a low-energy, coarse-grained continuum theory, being emergent from something more fundamental.

  14. A Dynamic Programming Approach for Base Station Sleeping in Cellular Networks

    NASA Astrophysics Data System (ADS)

    Gong, Jie; Zhou, Sheng; Niu, Zhisheng

    The energy consumption of the information and communication technology (ICT) industry, which has become a serious problem, is mostly due to the network infrastructure rather than the mobile terminals. In this paper, we focus on reducing the energy consumption of base stations (BSs) by adjusting their working modes (active or sleep). Specifically, the objective is to minimize the energy consumption while satisfying quality of service (QoS, e.g., blocking probability) requirement and, at the same time, avoiding frequent mode switching to reduce signaling and delay overhead. The problem is modeled as a dynamic programming (DP) problem, which is NP-hard in general. Based on cooperation among neighboring BSs, a low-complexity algorithm is proposed to reduce the size of state space as well as that of action space. Simulations demonstrate that, with the proposed algorithm, the active BS pattern well meets the time variation and the non-uniform spatial distribution of system traffic. Moreover, the tradeoff between the energy saving from BS sleeping and the cost of switching is well balanced by the proposed scheme.

  15. Ultra-Porous Nanoparticle Networks: A Biomimetic Coating Morphology for Enhanced Cellular Response and Infiltration

    PubMed Central

    Nasiri, Noushin; Ceramidas, Anthony; Mukherjee, Shayanti; Panneerselvan, Anitha; Nisbet, David R.; Tricoli, Antonio

    2016-01-01

    Orthopedic treatments are amongst the most common cause of surgery and are responsible for a large share of global healthcare expenditures. Engineering materials that can hasten bone integration will improve the quality of life of millions of patients per year and reduce associated medical costs. Here, we present a novel hierarchical biomimetic coating that mimics the inorganic constituent of mammalian bones with the aim of improving osseointegration of metallic implants. We exploit the thermally-driven self-organization of metastable core-shell nanoparticles during their aerosol self-assembly to rapidly fabricate robust, ultra-porous nanoparticle networks (UNN) of crystalline hydroxyapatite (HAp). Comparative analysis of the response of osteoblast cells to the ultra-porous nanostructured HAp surfaces and to the spin coated HAp surfaces revealed superior osseointegrative properties of the UNN coatings with significant cell and filopodia infiltration. This flexible synthesis approach for the engineering of UNN HAp coatings on titanium implants provides a platform technology to study the bone-implant interface for improved osseointegration and osteoconduction. PMID:27076035

  16. Incorporation of aggrecan in interpenetrating network hydrogels to improve cellular performance for cartilage tissue engineering.

    PubMed

    Ingavle, Ganesh C; Frei, Anthony W; Gehrke, Stevin H; Detamore, Michael S

    2013-06-01

    Interpenetrating network (IPN) hydrogels were recently introduced to the cartilage tissue engineering literature, with the approach of encapsulating cells in thermally gelling agarose that is then soaked in a poly(ethylene glycol) diacrylate (PEGDA) solution, which is then photopolymerized. These IPNs possess significantly enhanced mechanical performance desirable for cartilage regeneration, potentially allowing patients to return to weight-bearing activities quickly after surgical implantation. In an effort to improve cell viability and performance, inspiration was drawn from previous studies that have elicited positive chondrogenic responses to aggrecan, the proteoglycan largely responsible for the compressive stiffness of cartilage. Aggrecan was incorporated into the IPNs in conservative concentrations (40 μg/mL), and its effect was contrasted with the incorporation of chondroitin sulfate (CS), the primary glycosaminoglycan associated with aggrecan. Aggrecan was incorporated by physical entrapment within agarose and methacrylated CS was incorporated by copolymerization with PEGDA. The IPNs incorporating aggrecan or CS exhibited over 50% viability with encapsulated chondrocytes after 6 weeks. Both aggrecan and CS improved cell viability by 15.6% and 20%, respectively, relative to pure IPNs at 6 weeks culture time. In summary, we have introduced the novel approach of including a raw material from cartilage, namely aggrecan, to serve as a bioactive signal to cells encapsulated in IPN hydrogels for cartilage tissue engineering, which led to improved performance of encapsulated chondrocytes. PMID:23379843

  17. Ultra-Porous Nanoparticle Networks: A Biomimetic Coating Morphology for Enhanced Cellular Response and Infiltration.

    PubMed

    Nasiri, Noushin; Ceramidas, Anthony; Mukherjee, Shayanti; Panneerselvan, Anitha; Nisbet, David R; Tricoli, Antonio

    2016-01-01

    Orthopedic treatments are amongst the most common cause of surgery and are responsible for a large share of global healthcare expenditures. Engineering materials that can hasten bone integration will improve the quality of life of millions of patients per year and reduce associated medical costs. Here, we present a novel hierarchical biomimetic coating that mimics the inorganic constituent of mammalian bones with the aim of improving osseointegration of metallic implants. We exploit the thermally-driven self-organization of metastable core-shell nanoparticles during their aerosol self-assembly to rapidly fabricate robust, ultra-porous nanoparticle networks (UNN) of crystalline hydroxyapatite (HAp). Comparative analysis of the response of osteoblast cells to the ultra-porous nanostructured HAp surfaces and to the spin coated HAp surfaces revealed superior osseointegrative properties of the UNN coatings with significant cell and filopodia infiltration. This flexible synthesis approach for the engineering of UNN HAp coatings on titanium implants provides a platform technology to study the bone-implant interface for improved osseointegration and osteoconduction. PMID:27076035

  18. Evidence for progressive reduction and loss of telocytes in the dermal cellular network of systemic sclerosis.

    PubMed

    Manetti, Mirko; Guiducci, Serena; Ruffo, Martina; Rosa, Irene; Faussone-Pellegrini, Maria Simonetta; Matucci-Cerinic, Marco; Ibba-Manneschi, Lidia

    2013-04-01

    Telocytes, a peculiar type of stromal cells, have been recently identified in a variety of tissues and organs, including human skin. Systemic sclerosis (SSc, scleroderma) is a complex connective tissue disease characterized by fibrosis of the skin and internal organs. We presently investigated telocyte distribution and features in the skin of SSc patients compared with normal skin. By an integrated immunohistochemical and transmission electron microscopy approach, we confirmed that telocytes were present in human dermis, where they were mainly recognizable by their typical ultrastructural features and were immunophenotypically characterized by CD34 expression. Our findings also showed that dermal telocytes were immunophenotypically negative for CD31/PECAM-1 (endothelial cells), α-SMA (myofibroblasts, pericytes, vascular smooth muscle cells), CD11c (dendritic cells, macrophages), CD90/Thy-1 (fibroblasts) and c-kit/CD117 (mast cells). In normal skin, telocytes were organized to form three-dimensional networks distributed among collagen bundles and elastic fibres, and surrounded microvessels, nerves and skin adnexa (hair follicles, sebaceous and sweat glands). Telocytes displayed severe ultrastructural damages (swollen mitochondria, cytoplasmic vacuolization, lipofuscinic bodies) suggestive of ischaemia-induced cell degeneration and were progressively lost from the clinically affected skin of SSc patients. Telocyte damage and loss evolved differently according to SSc subsets and stages, being more rapid and severe in diffuse SSc. Briefly, in human skin telocytes are a distinct stromal cell population. In SSc skin, the progressive loss of telocytes might (i) contribute to the altered three-dimensional organization of the extracellular matrix, (ii) reduce the control of fibroblast, myofibroblast and mast cell activity, and (iii) impair skin regeneration and/or repair. PMID:23444845

  19. Mapping the Hsp90 Genetic Network Reveals Ergosterol Biosynthesis and Phosphatidylinositol-4-Kinase Signaling as Core Circuitry Governing Cellular Stress

    PubMed Central

    O’Meara, Teresa R.; Valaei, Seyedeh Fereshteh; Diezmann, Stephanie; Cowen, Leah E.

    2016-01-01

    Candida albicans is a leading human fungal pathogen that causes life-threatening systemic infections. A key regulator of C. albicans stress response, drug resistance, morphogenesis, and virulence is the molecular chaperone Hsp90. Targeting Hsp90 provides a powerful strategy to treat fungal infections, however, the therapeutic utility of current inhibitors is compromised by toxicity due to inhibition of host Hsp90. To identify components of the Hsp90-dependent circuitry governing virulence and drug resistance that are sufficiently divergent for selective targeting in the pathogen, we pioneered chemical genomic profiling of the Hsp90 genetic network in C. albicans. Here, we screen mutant collections covering ~10% of the genome for hypersensitivity to Hsp90 inhibition in multiple environmental conditions. We identify 158 HSP90 chemical genetic interactors, most of which are important for growth only in specific environments. We discovered that the sterol C-22 desaturase gene ERG5 and the phosphatidylinositol-4-kinase (PI4K) gene STT4 are HSP90 genetic interactors under multiple conditions, suggesting a function upstream of Hsp90. By systematic analysis of the ergosterol biosynthetic cascade, we demonstrate that defects in ergosterol biosynthesis induce cellular stress that overwhelms Hsp90’s functional capacity. By analysis of the phosphatidylinositol pathway, we demonstrate that there is a genetic interaction between the PI4K Stt4 and Hsp90. We also establish that Stt4 is required for normal actin polarization through regulation of Wal1, and suggest a model in which defects in actin remodeling induces stress that creates a cellular demand for Hsp90 that exceeds its functional capacity. Consistent with this model, actin inhibitors are synergistic with Hsp90 inhibitors. We highlight new connections between Hsp90 and virulence traits, demonstrating that Erg5 and Stt4 enable activation of macrophage pyroptosis. This work uncovers novel circuitry regulating Hsp90

  20. Mapping the Hsp90 Genetic Network Reveals Ergosterol Biosynthesis and Phosphatidylinositol-4-Kinase Signaling as Core Circuitry Governing Cellular Stress.

    PubMed

    O'Meara, Teresa R; Veri, Amanda O; Polvi, Elizabeth J; Li, Xinliu; Valaei, Seyedeh Fereshteh; Diezmann, Stephanie; Cowen, Leah E

    2016-06-01

    Candida albicans is a leading human fungal pathogen that causes life-threatening systemic infections. A key regulator of C. albicans stress response, drug resistance, morphogenesis, and virulence is the molecular chaperone Hsp90. Targeting Hsp90 provides a powerful strategy to treat fungal infections, however, the therapeutic utility of current inhibitors is compromised by toxicity due to inhibition of host Hsp90. To identify components of the Hsp90-dependent circuitry governing virulence and drug resistance that are sufficiently divergent for selective targeting in the pathogen, we pioneered chemical genomic profiling of the Hsp90 genetic network in C. albicans. Here, we screen mutant collections covering ~10% of the genome for hypersensitivity to Hsp90 inhibition in multiple environmental conditions. We identify 158 HSP90 chemical genetic interactors, most of which are important for growth only in specific environments. We discovered that the sterol C-22 desaturase gene ERG5 and the phosphatidylinositol-4-kinase (PI4K) gene STT4 are HSP90 genetic interactors under multiple conditions, suggesting a function upstream of Hsp90. By systematic analysis of the ergosterol biosynthetic cascade, we demonstrate that defects in ergosterol biosynthesis induce cellular stress that overwhelms Hsp90's functional capacity. By analysis of the phosphatidylinositol pathway, we demonstrate that there is a genetic interaction between the PI4K Stt4 and Hsp90. We also establish that Stt4 is required for normal actin polarization through regulation of Wal1, and suggest a model in which defects in actin remodeling induces stress that creates a cellular demand for Hsp90 that exceeds its functional capacity. Consistent with this model, actin inhibitors are synergistic with Hsp90 inhibitors. We highlight new connections between Hsp90 and virulence traits, demonstrating that Erg5 and Stt4 enable activation of macrophage pyroptosis. This work uncovers novel circuitry regulating Hsp90

  1. A cellular nonlinear network: real-time technology for the analysis of microfluidic phenomena in blood vessels

    NASA Astrophysics Data System (ADS)

    Sapuppo, F.; Bucolo, M.; Intaglietta, M.; Fortuna, L.; Arena, P.

    2006-02-01

    A new approach to the observation and analysis of dynamic structural and functional parameters in the microcirculation is described. The new non-invasive optical system is based on cellular nonlinear networks (CNNs), highly integrated analogue processor arrays whose processing elements, the cells, interact directly within a finite local neighbourhood. CNNs, thanks to their parallel processing feature and spatially distributed structure, are widely used to solve high-speed image processing and recognition problems and in the description and modelling of biological dynamics through the solution of time continuous partial differential equations (PDEs). They are therefore considered extremely suitable for spatial-temporal dynamic characterization of fluidic phenomena at micrometric to nanometric scales, such as blood flow in microvessels and its interaction with the cells of the vessel wall. A CNN universal machine (CNN-UM) structure was used to implement, via simulation and hardware (ACE16k), the algorithms to determine the functional capillarity density (FCD) and red blood cell velocity (RBCV) in capillaries obtained by intravital microscopy during in vivo experiments on hamsters. The system exploits the moving particles to distinguish the functional capillaries from the stationary background. This information is used to reconstruct a map and to calculate the velocity of the moving objects.

  2. A 181 GOPS AKAZE Accelerator Employing Discrete-Time Cellular Neural Networks for Real-Time Feature Extraction

    PubMed Central

    Jiang, Guangli; Liu, Leibo; Zhu, Wenping; Yin, Shouyi; Wei, Shaojun

    2015-01-01

    This paper proposes a real-time feature extraction VLSI architecture for high-resolution images based on the accelerated KAZE algorithm. Firstly, a new system architecture is proposed. It increases the system throughput, provides flexibility in image resolution, and offers trade-offs between speed and scaling robustness. The architecture consists of a two-dimensional pipeline array that fully utilizes computational similarities in octaves. Secondly, a substructure (block-serial discrete-time cellular neural network) that can realize a nonlinear filter is proposed. This structure decreases the memory demand through the removal of data dependency. Thirdly, a hardware-friendly descriptor is introduced in order to overcome the hardware design bottleneck through the polar sample pattern; a simplified method to realize rotation invariance is also presented. Finally, the proposed architecture is designed in TSMC 65 nm CMOS technology. The experimental results show a performance of 127 fps in full HD resolution at 200 MHz frequency. The peak performance reaches 181 GOPS and the throughput is double the speed of other state-of-the-art architectures. PMID:26404305

  3. Decoding genome-wide GadEWX-transcriptional regulatory networks reveals multifaceted cellular responses to acid stress in Escherichia coli.

    PubMed

    Seo, Sang Woo; Kim, Donghyuk; O'Brien, Edward J; Szubin, Richard; Palsson, Bernhard O

    2015-01-01

    The regulators GadE, GadW and GadX (which we refer to as GadEWX) play a critical role in the transcriptional regulation of the glutamate-dependent acid resistance (GDAR) system in Escherichia coli K-12 MG1655. However, the genome-wide regulatory role of GadEWX is still unknown. Here we comprehensively reconstruct the genome-wide GadEWX transcriptional regulatory network and RpoS involvement in E. coli K-12 MG1655 under acidic stress. Integrative data analysis reveals that GadEWX regulons consist of 45 genes in 31 transcription units and 28 of these genes were associated with RpoS-binding sites. We demonstrate that GadEWX directly and coherently regulate several proton-generating/consuming enzymes with pairs of negative-feedback loops for pH homeostasis. In addition, GadEWX regulate genes with assorted functions, including molecular chaperones, acid resistance, stress response and other regulatory activities. These results show how GadEWX simultaneously coordinate many cellular processes to produce the overall response of E. coli to acid stress. PMID:26258987

  4. Decoding genome-wide GadEWX-transcriptional regulatory networks reveals multifaceted cellular responses to acid stress in Escherichia coli

    PubMed Central

    Seo, Sang Woo; Kim, Donghyuk; O'Brien, Edward J.; Szubin, Richard; Palsson, Bernhard O.

    2015-01-01

    The regulators GadE, GadW and GadX (which we refer to as GadEWX) play a critical role in the transcriptional regulation of the glutamate-dependent acid resistance (GDAR) system in Escherichia coli K-12 MG1655. However, the genome-wide regulatory role of GadEWX is still unknown. Here we comprehensively reconstruct the genome-wide GadEWX transcriptional regulatory network and RpoS involvement in E. coli K-12 MG1655 under acidic stress. Integrative data analysis reveals that GadEWX regulons consist of 45 genes in 31 transcription units and 28 of these genes were associated with RpoS-binding sites. We demonstrate that GadEWX directly and coherently regulate several proton-generating/consuming enzymes with pairs of negative-feedback loops for pH homeostasis. In addition, GadEWX regulate genes with assorted functions, including molecular chaperones, acid resistance, stress response and other regulatory activities. These results show how GadEWX simultaneously coordinate many cellular processes to produce the overall response of E. coli to acid stress. PMID:26258987

  5. A 181 GOPS AKAZE Accelerator Employing Discrete-Time Cellular Neural Networks for Real-Time Feature Extraction.

    PubMed

    Jiang, Guangli; Liu, Leibo; Zhu, Wenping; Yin, Shouyi; Wei, Shaojun

    2015-01-01

    This paper proposes a real-time feature extraction VLSI architecture for high-resolution images based on the accelerated KAZE algorithm. Firstly, a new system architecture is proposed. It increases the system throughput, provides flexibility in image resolution, and offers trade-offs between speed and scaling robustness. The architecture consists of a two-dimensional pipeline array that fully utilizes computational similarities in octaves. Secondly, a substructure (block-serial discrete-time cellular neural network) that can realize a nonlinear filter is proposed. This structure decreases the memory demand through the removal of data dependency. Thirdly, a hardware-friendly descriptor is introduced in order to overcome the hardware design bottleneck through the polar sample pattern; a simplified method to realize rotation invariance is also presented. Finally, the proposed architecture is designed in TSMC 65 nm CMOS technology. The experimental results show a performance of 127 fps in full HD resolution at 200 MHz frequency. The peak performance reaches 181 GOPS and the throughput is double the speed of other state-of-the-art architectures. PMID:26404305

  6. Proteomic, cellular, and network analyses reveal new DUSP3 interactions with nucleolar proteins in HeLa cells.

    PubMed

    Panico, Karine; Forti, Fabio Luis

    2013-12-01

    DUSP3 (or Vaccinia virus phosphatase VH1-related; VHR) is a small dual-specificity phosphatase known to dephosphorylate c-Jun N-terminal kinases and extracellular signal-regulated kinases. In human cervical cancer cells, DUSP3 is overexpressed, localizes preferentially to the nucleus, and plays a key role in cellular proliferation and senescence triggering. Other DUSP3 functions are still unknown, as illustrated by recent and unpublished results from our group showing that this enzyme mediates DNA damage response or repair processes. In this study, we sought to identify new interactions between DUSP3 and proteins directly or indirectly involved in or correlated with its biological roles in HeLa cells exposed to gamma or UV radiation. By using GST-DUSP as bait, we pulled down interacting proteins and identified them by LC-MS/MS. Of the 46 proteins obtained, six hits were extensively validated by immune techniques; the proteins Nucleophosmin, HnRNP C1/C2, and Nucleolin were the most promising targets found to directly interact with DUSP3. We then analyzed the DUSP3 interactomes using physical protein-protein interaction networks using our hits as the seed list. The validated hits as well as unvalidated hits fluctuated on the DUSP3 interactomes of HeLa cells, independent of the time post radiation, which confirmed our proteomic and experimental data and clearly showed the proximity of DUSP3 to proteins involved in processes intimately related to DNA repair and senescence, such as Ku70 and Tert, via interactions with nucleolar proteins, which were identified in this study, that regulate DNA/RNA structure and functions. PMID:24245651

  7. Modeling land use and land cover changes in a vulnerable coastal region using artificial neural networks and cellular automata.

    PubMed

    Qiang, Yi; Lam, Nina S N

    2015-03-01

    As one of the most vulnerable coasts in the continental USA, the Lower Mississippi River Basin (LMRB) region has endured numerous hazards over the past decades. The sustainability of this region has drawn great attention from the international, national, and local communities, wanting to understand how the region as a system develops under intense interplay between the natural and human factors. A major problem in this deltaic region is significant land loss over the years due to a combination of natural and human factors. The main scientific and management questions are what factors contribute to the land use land cover (LULC) changes in this region, can we model the changes, and how would the LULC look like in the future given the current factors? This study analyzed the LULC changes of the region between 1996 and 2006 by utilizing an artificial neural network (ANN) to derive the LULC change rules from 15 human and natural variables. The rules were then used to simulate future scenarios in a cellular automation model. A stochastic element was added in the model to represent factors that were not included in the current model. The analysis was conducted for two sub-regions in the study area for comparison. The results show that the derived ANN models could simulate the LULC changes with a high degree of accuracy (above 92 % on average). A total loss of 263 km(2) in wetlands from 2006 to 2016 was projected, whereas the trend of forest loss will cease. These scenarios provide useful information to decision makers for better planning and management of the region. PMID:25647797

  8. Stackelberg Game Based Power Allocation for Physical Layer Security of Device-to-device Communication Underlaying Cellular Networks

    NASA Astrophysics Data System (ADS)

    Qu, Junyue; Cai, Yueming; Wu, Dan; Chen, Hualiang

    2014-05-01

    The problem of power allocation for device-to-device (D2D) underlay communication to improve physical layer security is addressed. Specifically, to improve the secure communication of the cellular users, we introduce a Stackelberg game for allocating the power of the D2D link under a total power constraint and a rate constraint at the D2D pair. In the introduced Stackelberg game the D2D pair works as a seller and the cellular UEs work as buyers. Firstly, because the interference signals from D2D pair are unknown to both the legitimate receiver and the illegitimate eavesdropper, it is possible that a cellular UE decline to participate in the introduced Stackelberg game. So the condition under which a legitimate user will participate in the introduced Stackelberg game is discussed. Then, based on the Stackelberg game, we propose a semi-distributed power allocation algorithm, which is proved to conclude after finite-time iterations. In the end, some simulations are presented to verify the performance improvement in the physical layer security of cellular UEs using the proposed power allocation algorithm. We can determine that with the proposed algorithm, while the D2D pair's communication demand is met, the physical layer security of cellular UEs can be improved.

  9. Cellular resilience.

    PubMed

    Smirnova, Lena; Harris, Georgina; Leist, Marcel; Hartung, Thomas

    2015-01-01

    Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after the hit or end in programmed cell death, the ensuing stress responses promote a new homeostasis under stress. The processes of reverting "back to normal" and reversal of apoptosis ("anastasis") have been studied little at the cellular level. Cell types show astonishingly similar vulnerability to most toxicants, except for those that require a very specific target, metabolism or mechanism present only in specific cell types. The majority of chemicals triggers "general cytotoxicity" in any cell at similar concentrations. We hypothesize that cells differ less in their vulnerability to a given toxicant than in their resilience (coping with the "hit"). In many cases, cells do not return to the naive state after a toxic insult. The phenomena of "pre-conditioning", "tolerance" and "hormesis" describe this for low-dose exposures to toxicants that render the cell more resistant to subsequent hits. The defense and resilience programs include epigenetic changes that leave a "memory/scar" - an alteration as a consequence of the stress the cell has experienced. These memories might have long-term consequences, both positive (resistance) and negative, that contribute to chronic and delayed manifestations of hazard and, ultimately, disease. This article calls for more systematic analyses of how cells cope with toxic perturbations in the long-term after stressor withdrawal. A technical prerequisite for these are stable (organotypic) cultures and a characterization of stress response molecular networks. PMID:26536287

  10. Multiscale modeling of cellular epigenetic states: stochasticity in molecular networks, chromatin folding in cell nuclei, and tissue pattern formation of cells

    PubMed Central

    Liang, Jie; Cao, Youfang; Gürsoy, Gamze; Naveed, Hammad; Terebus, Anna; Zhao, Jieling

    2016-01-01

    Genome sequences provide the overall genetic blueprint of cells, but cells possessing the same genome can exhibit diverse phenotypes. There is a multitude of mechanisms controlling cellular epigenetic states and that dictate the behavior of cells. Among these, networks of interacting molecules, often under stochastic control, depending on the specific wirings of molecular components and the physiological conditions, can have a different landscape of cellular states. In addition, chromosome folding in three-dimensional space provides another important control mechanism for selective activation and repression of gene expression. Fully differentiated cells with different properties grow, divide, and interact through mechanical forces and communicate through signal transduction, resulting in the formation of complex tissue patterns. Developing quantitative models to study these multi-scale phenomena and to identify opportunities for improving human health requires development of theoretical models, algorithms, and computational tools. Here we review recent progress made in these important directions. PMID:27480462

  11. Global Exponential Stability of Almost Periodic Solution for Neutral-Type Cohen-Grossberg Shunting Inhibitory Cellular Neural Networks with Distributed Delays and Impulses

    PubMed Central

    Xu, Lijun; Jiang, Qi; Gu, Guodong

    2016-01-01

    A kind of neutral-type Cohen-Grossberg shunting inhibitory cellular neural networks with distributed delays and impulses is considered. Firstly, by using the theory of impulsive differential equations and the contracting mapping principle, the existence and uniqueness of the almost periodic solution for the above system are obtained. Secondly, by constructing a suitable Lyapunov functional, the global exponential stability of the unique almost periodic solution is also investigated. The work in this paper improves and extends some results in recent years. As an application, an example and numerical simulations are presented to demonstrate the feasibility and effectiveness of the main results. PMID:27190502

  12. New Markov-Shannon Entropy models to assess connectivity quality in complex networks: from molecular to cellular pathway, Parasite-Host, Neural, Industry, and Legal-Social networks.

    PubMed

    Riera-Fernández, Pablo; Munteanu, Cristian R; Escobar, Manuel; Prado-Prado, Francisco; Martín-Romalde, Raquel; Pereira, David; Villalba, Karen; Duardo-Sánchez, Aliuska; González-Díaz, Humberto

    2012-01-21

    Graph and Complex Network theory is expanding its application to different levels of matter organization such as molecular, biological, technological, and social networks. A network is a set of items, usually called nodes, with connections between them, which are called links or edges. There are many different experimental and/or theoretical methods to assign node-node links depending on the type of network we want to construct. Unfortunately, the use of a method for experimental reevaluation of the entire network is very expensive in terms of time and resources; thus the development of cheaper theoretical methods is of major importance. In addition, different methods to link nodes in the same type of network are not totally accurate in such a way that they do not always coincide. In this sense, the development of computational methods useful to evaluate connectivity quality in complex networks (a posteriori of network assemble) is a goal of major interest. In this work, we report for the first time a new method to calculate numerical quality scores S(L(ij)) for network links L(ij) (connectivity) based on the Markov-Shannon Entropy indices of order k-th (θ(k)) for network nodes. The algorithm may be summarized as follows: (i) first, the θ(k)(j) values are calculated for all j-th nodes in a complex network already constructed; (ii) A Linear Discriminant Analysis (LDA) is used to seek a linear equation that discriminates connected or linked (L(ij)=1) pairs of nodes experimentally confirmed from non-linked ones (L(ij)=0); (iii) the new model is validated with external series of pairs of nodes; (iv) the equation obtained is used to re-evaluate the connectivity quality of the network, connecting/disconnecting nodes based on the quality scores calculated with the new connectivity function. This method was used to study different types of large networks. The linear models obtained produced the following results in terms of overall accuracy for network reconstruction

  13. Interaction between cellular voltage-sensitive conductance and network parameters in a model of neocortex can generate epileptiform bursting.

    SciTech Connect

    van Drongelen, W.; Lee, H. C.; Koch, H.; Elsen, F.; Carroll, M. S.; Hereld, M.; Stevens, R. L.; Mathematics and Computer Science; Univ. of Chicago

    2004-01-01

    We examined the effects of both intrinsic neuronal membrane properties and network parameters on oscillatory activity in a model of neocortex. A scalable network model with six different cell types was built with the pGENESIS neural simulator. The neocortical network consisted of two types of pyramidal cells and four types of inhibitory interneurons. All cell types contained both fast sodium and delayed rectifier potassium channels for generation of action potentials. A subset of the pyramidal neurons contained an additional slow inactivating (persistent) sodium current (NaP). The neurons with the NaP current showed spontaneous bursting activity in the absence of external stimulation. The model also included a routine to calculate a simulated electroencephalogram (EEG) trace from the population activity. This revealed emergent network behavior which ranged from desynchronized activity to different types of seizure-like bursting patterns. At settings with weaker excitatory network effects, the propensity to generate seizure-like behavior increased. Strong excitatory network connectivity destroyed oscillatory behavior, whereas weak connectivity enhanced the relative importance of the spontaneously bursting cells. Our findings are in contradiction with the general opinion that strong excitatory synaptic and/or insufficient inhibition effects are associated with seizure initiation, but are in agreement with previously reported behavior in neocortex.

  14. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway by a genome wide siRNA screen

    PubMed Central

    Hitomi, Junichi; Christofferson, Dana E.; Ng, Aylwin; Yao, Jianhua; Degterev, Alexei; Xavier, Ramnik J.; Yuan, Junying

    2009-01-01

    Stimulation of death receptors by agonists such as FasL and TNFα activates apoptotic cell death in apoptotic competent conditions or a type of necrotic cell death dependent on RIP1 kinase, termed necroptosis, in apoptotic deficient conditions. In a genome-wide siRNA screen for regulators of necroptosis, we identify a set of 432 genes that regulate necroptosis, a subset of 32 genes that act downstream and/or as regulators of RIP1 kinase, 32 genes required for death receptor mediated apoptosis, and 7 genes involved in both necroptosis and apoptosis. We show that the expression of subsets of the 432 genes are enriched in the immune and nervous systems, and cellular sensitivity to necroptosis is regulated by an extensive signaling network mediating innate immunity. Interestingly, Bmf, a BH3-only Bcl-2 family member, is required for death receptor-induced necroptosis. Our study defines a cellular signaling network that regulates necroptosis and the molecular bifurcation that controls apoptosis and necroptosis. PMID:19109899

  15. Equine Infectious Anemia Virus Gag Assembly and Export Are Directed by Matrix Protein through trans-Golgi Networks and Cellular Vesicles

    PubMed Central

    Zhang, Zeli; Ma, Jian; Zhang, Xiang; Su, Chao; Yao, Qiu-Cheng

    2015-01-01

    ABSTRACT Gag intracellular assembly and export are very important processes for lentiviruses replication. Previous studies have demonstrated that equine infectious anemia virus (EIAV) matrix (MA) possesses distinct phosphoinositide affinity compared with HIV-1 MA and that phosphoinositide-mediated targeting to peripheral and internal membranes is a critical factor in EIAV assembly and release. In this study, we compared the cellular assembly sites of EIAV and HIV-1. We observed that the assembly of EIAV particles occurred on interior cellular membranes, while HIV-1 was targeted to the plasma membrane (PM) for assembly. Then, we determined that W7 and K9 in the EIAV MA N terminus were essential for Gag assembly and release but did not affect the cellular distribution of Gag. The replacement of EIAV MA with HIV-1 MA directed chimeric Gag to the PM but severely impaired Gag release. MA structural analysis indicated that the EIAV and HIV-1 MAs had similar spatial structures but that helix 1 of the EIAV MA was closer to loop 2. Further investigation indicated that EIAV Gag accumulated in the trans-Golgi network (TGN) but not the early and late endosomes. The 9 N-terminal amino acids of EIAV MA harbored the signal that directed Gag to the TGN membrane system. Additionally, we demonstrated that EIAV particles were transported to the extracellular space by the cellular vesicle system. This type of EIAV export was not associated with multivesicular bodies or microtubule depolymerization but could be inhibited by the actin-depolymerizing drug cytochalasin D, suggesting that dynamic actin depolymerization may be associated with EIAV production. IMPORTANCE In previous studies, EIAV Gag was reported to localize to both the cell interior and the plasma membrane. Here, we demonstrate that EIAV likely uses the TGN as the assembly site in contrast to HIV-1, which is targeted to the PM for assembly. These distinct assembly features are determined by the MA domain. We also identified

  16. System-Level Insights into the Cellular Interactome of a Non-Model Organism: Inferring, Modelling and Analysing Functional Gene Network of Soybean (Glycine max)

    PubMed Central

    Xu, Yungang; Guo, Maozu; Zou, Quan; Liu, Xiaoyan; Wang, Chunyu; Liu, Yang

    2014-01-01

    Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN), a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max), due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs), in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional interactome at the genome

  17. Why Are Cortical GABA Neurons Relevant to Internal Focus in Depression? A cross-level model linking cellular, biochemical, and neural network findings

    PubMed Central

    2014-01-01

    Major Depression is a complex and severe psychiatric disorder whose symptomatology encompasses a critical shift in awareness, specifically in the balance from external to internal mental focus. This is reflected by unspecific somatic symptoms and the predominance of the own cognitions manifested in increased self-focus and rumination. We posit here that sufficient empirical data has accumulated to build a coherent biological model that links these psychological concepts and symptom dimensions to observed biochemical, cellular, regional and neural network deficits. Specifically, deficits in inhibitory gamma amino butyric acid (GABA) regulating excitatory cell input/output and local cell circuit processing of information in key brain regions may underlie the shift that is observed in depressed subjects in resting state activities between the perigenual anterior cingulate cortex (PACC) and the dorsolateral prefrontal cortex (DLPFC). This regional dysbalance translates at the network level in a dysbalance between default-mode and executive networks, which psychopathologically surfaces as a shift in focus from external to internal mental content and associated symptoms (See overview in Figure 1). We focus here on primary evidence at each of those levels and on putative mechanistic links between those levels. Apart from its implications for neuropsychiatric disorders, our model provides for the first time a set of hypotheses for cross-level mechanisms of how internal and external mental contents may be constituted and balanced in healthy subjects, and thus also contributes to the neuroscientific debate on the neural correlates of consciousness. PMID:25048001

  18. Perturbation of cellular proteostasis networks identifies pathways that modulate precursor and intermediate but not mature levels of frataxin

    PubMed Central

    Nabhan, Joseph F.; Gooch, Renea L.; Piatnitski Chekler, Eugene L.; Pierce, Betsy; Bulawa, Christine E.

    2015-01-01

    Friedreich’s Ataxia is a genetic disease caused by expansion of an intronic trinucleotide repeat in the frataxin (FXN) gene yielding diminished FXN expression and consequently disease. Since increasing FXN protein levels is desirable to ameliorate pathology, we explored the role of major cellular proteostasis pathways and mitochondrial proteases in FXN processing and turnover. We targeted p97/VCP, the ubiquitin proteasome pathway (UPP), and autophagy with chemical inhibitors in cell lines and patient-derived cells. p97 inhibition by DBeQ increased precursor FXN levels, while UPP and autophagic flux modulators had variable effects predominantly on intermediate FXN. Our data suggest that these pathways cannot be modulated to influence mature functional FXN levels. We also targeted known mitochondrial proteases by RNA interference and discovered a novel protease PITRM1 that regulates intermediate FXN levels. Treatment with the aforementioned chemical and genetic modulators did not have a differential effect in patient cells containing lower amounts of FXN. Interestingly, a number of treatments caused a change in total amount of FXN protein, without an effect on mature FXN. Our results imply that regulation of FXN protein levels is complex and that total amounts can be modulated chemically and genetically without altering the absolute amount of mature FXN protein. PMID:26671574

  19. C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4.

    PubMed

    Huggins, Christopher J; Mayekar, Manasi K; Martin, Nancy; Saylor, Karen L; Gonit, Mesfin; Jailwala, Parthav; Kasoji, Manjula; Haines, Diana C; Quiñones, Octavio A; Johnson, Peter F

    2016-03-01

    The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBPγ:ATF4 heterodimers, but not C/EBPβ:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBPγ and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBPβ and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg(-/-) mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg(-/-) mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBPγ-deficient newborns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant, N-acetyl-cysteine. Cebpg(-/-) mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBPγ as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells. PMID:26667036

  20. Cellular Protein WDR11 Interacts with Specific Herpes Simplex Virus Proteins at the trans-Golgi Network To Promote Virus Replication

    PubMed Central

    Taylor, Kathryne E.

    2015-01-01

    ABSTRACT It has recently been proposed that the herpes simplex virus (HSV) protein ICP0 has cytoplasmic roles in blocking antiviral signaling and in promoting viral replication in addition to its well-known proteasome-dependent functions in the nucleus. However, the mechanisms through which it produces these effects remain unclear. While investigating this further, we identified a novel cytoplasmic interaction between ICP0 and the poorly characterized cellular protein WDR11. During an HSV infection, WDR11 undergoes a dramatic change in localization at late times in the viral replication cycle, moving from defined perinuclear structures to a dispersed cytoplasmic distribution. While this relocation was not observed during infection with viruses other than HSV-1 and correlated with efficient HSV-1 replication, the redistribution was found to occur independently of ICP0 expression, instead requiring viral late gene expression. We demonstrate for the first time that WDR11 is localized to the trans-Golgi network (TGN), where it interacts specifically with some, but not all, HSV virion components, in addition to ICP0. Knockdown of WDR11 in cultured human cells resulted in a modest but consistent decrease in yields of both wild-type and ICP0-null viruses, in the supernatant and cell-associated fractions, without affecting viral gene expression. Although further study is required, we propose that WDR11 participates in viral assembly and/or secondary envelopment. IMPORTANCE While the TGN has been proposed to be the major site of HSV-1 secondary envelopment, this process is incompletely understood, and in particular, the role of cellular TGN components in this pathway is unknown. Additionally, little is known about the cellular functions of WDR11, although the disruption of this protein has been implicated in multiple human diseases. Therefore, our finding that WDR11 is a TGN-resident protein that interacts with specific viral proteins to enhance viral yields improves both

  1. Hybrid alginate-polyester bimodal network hydrogel for tissue engineering--Influence of structured water on long-term cellular growth.

    PubMed

    Finosh, G T; Jayabalan, M; Vandana, S; Raghu, K G

    2015-11-01

    The development of biodegradable scaffolds (which promote cell-binding, proliferation, long-term cell viability and required biomechanical stability) for cardiac tissue engineering is a challenge. In this study, biosynthetic amphiphilic hybrid hydrogels were prepared using a graft comacromer of natural polysaccharide alginate and synthetic polyester polypropylene fumarate (PPF). Monomodal network hydrogel (HPAS-NO) and bimodal network hydrogel (HPAS-AA) were prepared. Between the two hydrogels, HPAS-AA hydrogel excels over the HPAS-NO hydrogel. HPAS-AA hydrogel is mechanically more stable in the culture medium and undergoes gradual degradation in vitro in PBS (phosphate buffered saline). HPAS-AA contains nano-porous structure and acquires structured water (non-freezing-bound water) (53.457%) along with free water (11.773%). It absorbs more plasma proteins and prevents platelet adsorption and hemolysis when contacted with blood. HPAS-AA hydrogel is cytocompatible and promote 3D cell growth (≈ 70%) of L929 fibroblast even after 18 days and H9C2 cardiomyoblasts. The enhanced and long-term cellular growth of HPAS-AA hydrogel is attributed to the cell responsive features of structured water. HPAS-AA hydrogel can be a better candidate for cardiac tissue engineering applications. PMID:25843368

  2. Irregular Cellular Learning Automata.

    PubMed

    Esnaashari, Mehdi; Meybodi, Mohammad Reza

    2015-08-01

    Cellular learning automaton (CLA) is a recently introduced model that combines cellular automaton (CA) and learning automaton (LA). The basic idea of CLA is to use LA to adjust the state transition probability of stochastic CA. This model has been used to solve problems in areas such as channel assignment in cellular networks, call admission control, image processing, and very large scale integration placement. In this paper, an extension of CLA called irregular CLA (ICLA) is introduced. This extension is obtained by removing the structure regularity assumption in CLA. Irregularity in the structure of ICLA is needed in some applications, such as computer networks, web mining, and grid computing. The concept of expediency has been introduced for ICLA and then, conditions under which an ICLA becomes expedient are analytically found. PMID:25291810

  3. Review of quantitative phase-digital holographic microscopy: promising novel imaging technique to resolve neuronal network activity and identify cellular biomarkers of psychiatric disorders

    PubMed Central

    Marquet, Pierre; Depeursinge, Christian; Magistretti, Pierre J.

    2014-01-01

    Abstract. Quantitative phase microscopy (QPM) has recently emerged as a new powerful quantitative imaging technique well suited to noninvasively explore a transparent specimen with a nanometric axial sensitivity. In this review, we expose the recent developments of quantitative phase-digital holographic microscopy (QP-DHM). Quantitative phase-digital holographic microscopy (QP-DHM) represents an important and efficient quantitative phase method to explore cell structure and dynamics. In a second part, the most relevant QPM applications in the field of cell biology are summarized. A particular emphasis is placed on the original biological information, which can be derived from the quantitative phase signal. In a third part, recent applications obtained, with QP-DHM in the field of cellular neuroscience, namely the possibility to optically resolve neuronal network activity and spine dynamics, are presented. Furthermore, potential applications of QPM related to psychiatry through the identification of new and original cell biomarkers that, when combined with a range of other biomarkers, could significantly contribute to the determination of high risk developmental trajectories for psychiatric disorders, are discussed. PMID:26157976

  4. Image processing with cellular nonlinear networks implemented on field-programmable gate arrays for real-time applications in nuclear fusion

    SciTech Connect

    Palazzo, S.; Vagliasindi, G.; Arena, P.; Murari, A.; Mazon, D.; De Maack, A.; Collaboration: JET-EFDA Contributors

    2010-08-15

    In the past years cameras have become increasingly common tools in scientific applications. They are now quite systematically used in magnetic confinement fusion, to the point that infrared imaging is starting to be used systematically for real-time machine protection in major devices. However, in order to guarantee that the control system can always react rapidly in case of critical situations, the time required for the processing of the images must be as predictable as possible. The approach described in this paper combines the new computational paradigm of cellular nonlinear networks (CNNs) with field-programmable gate arrays and has been tested in an application for the detection of hot spots on the plasma facing components in JET. The developed system is able to perform real-time hot spot recognition, by processing the image stream captured by JET wide angle infrared camera, with the guarantee that computational time is constant and deterministic. The statistical results obtained from a quite extensive set of examples show that this solution approximates very well an ad hoc serial software algorithm, with no false or missed alarms and an almost perfect overlapping of alarm intervals. The computational time can be reduced to a millisecond time scale for 8 bit 496x560-sized images. Moreover, in our implementation, the computational time, besides being deterministic, is practically independent of the number of iterations performed by the CNN - unlike software CNN implementations.

  5. Cellular Homeostasis and Aging.

    PubMed

    Hartl, F Ulrich

    2016-06-01

    Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans. PMID:27050288

  6. Preliminary Analysis of the efficacy of Artificial neural Network (ANN) and Cellular Automaton (CA) based Land Use Models in Urban Land-Use Planning

    NASA Astrophysics Data System (ADS)

    Harun, R.

    2013-05-01

    This research provides an opportunity of collaboration between urban planners and modellers by providing a clear theoretical foundations on the two most widely used urban land use models, and assessing the effectiveness of applying the models in urban planning context. Understanding urban land cover change is an essential element for sustainable urban development as it affects ecological functioning in urban ecosystem. Rapid urbanization due to growing inclination of people to settle in urban areas has increased the complexities in predicting that at what shape and size cities will grow. The dynamic changes in the spatial pattern of urban landscapes has exposed the policy makers and environmental scientists to great challenge. But geographic science has grown in symmetry to the advancements in computer science. Models and tools are developed to support urban planning by analyzing the causes and consequences of land use changes and project the future. Of all the different types of land use models available in recent days, it has been found by researchers that the most frequently used models are Cellular Automaton (CA) and Artificial Neural Networks (ANN) models. But studies have demonstrated that the existing land use models have not been able to meet the needs of planners and policy makers. There are two primary causes identified behind this prologue. First, there is inadequate understanding of the fundamental theories and application of the models in urban planning context i.e., there is a gap in communication between modellers and urban planners. Second, the existing models exclude many key drivers in the process of simplification of the complex urban system that guide urban spatial pattern. Thus the models end up being effective in assessing the impacts of certain land use policies, but cannot contribute in new policy formulation. This paper is an attempt to increase the knowledge base of planners on the most frequently used land use model and also assess the

  7. Networks.

    ERIC Educational Resources Information Center

    Maughan, George R.; Petitto, Karen R.; McLaughlin, Don

    2001-01-01

    Describes the connectivity features and options of modern campus communication and information system networks, including signal transmission (wire-based and wireless), signal switching, convergence of networks, and network assessment variables, to enable campus leaders to make sound future-oriented decisions. (EV)

  8. Investigating the specific core genetic-and-epigenetic networks of cellular mechanisms involved in human aging in peripheral blood mononuclear cells

    PubMed Central

    Li, Cheng-Wei; Wang, Wen-Hsin; Chen, Bor-Sen

    2016-01-01

    Aging is an inevitable part of life for humans, and slowing down the aging process has become a main focus of human endeavor. Here, we applied a systems biology approach to construct protein-protein interaction networks, gene regulatory networks, and epigenetic networks, i.e. genetic and epigenetic networks (GENs), of elderly individuals and young controls. We then compared these GENs to extract aging mechanisms using microarray data in peripheral blood mononuclear cells, microRNA (miRNA) data, and database mining. The core GENs of elderly individuals and young controls were obtained by applying principal network projection to GENs based on Principal Component Analysis. By comparing the core networks, we identified that to overcome the accumulated mutation of genes in the aging process the transcription factor JUN can be activated by stress signals, including the MAPK signaling, T-cell receptor signaling, and neurotrophin signaling pathways through DNA methylation of BTG3, G0S2, and AP2B1 and the regulations of mir-223 let-7d, and mir-130a. We also address the aging mechanisms in old men and women. Furthermore, we proposed that drugs designed to target these DNA methylated genes or miRNAs may delay aging. A multiple drug combination comprising phenylalanine, cholesterol, and palbociclib was finally designed for delaying the aging process. PMID:26895224

  9. Networking.

    ERIC Educational Resources Information Center

    Duvall, Betty

    Networking is an information giving and receiving system, a support system, and a means whereby women can get ahead in careers--either in new jobs or in current positions. Networking information can create many opportunities: women can talk about how other women handle situations and tasks, and previously established contacts can be used in…

  10. Integrative omics reveals MYCN as a global suppressor of cellular signalling and enables network-based therapeutic target discovery in neuroblastoma.

    PubMed

    Duffy, David J; Krstic, Aleksandar; Halasz, Melinda; Schwarzl, Thomas; Fey, Dirk; Iljin, Kristiina; Mehta, Jai Prakash; Killick, Kate; Whilde, Jenny; Turriziani, Benedetta; Haapa-Paananen, Saija; Fey, Vidal; Fischer, Matthias; Westermann, Frank; Henrich, Kai-Oliver; Bannert, Steffen; Higgins, Desmond G; Kolch, Walter

    2015-12-22

    Despite intensive study, many mysteries remain about the MYCN oncogene's functions. Here we focus on MYCN's role in neuroblastoma, the most common extracranial childhood cancer. MYCN gene amplification occurs in 20% of cases, but other recurrent somatic mutations are rare. This scarcity of tractable targets has hampered efforts to develop new therapeutic options. We employed a multi-level omics approach to examine MYCN functioning and identify novel therapeutic targets for this largely un-druggable oncogene. We used systems medicine based computational network reconstruction and analysis to integrate a range of omic techniques: sequencing-based transcriptomics, genome-wide chromatin immunoprecipitation, siRNA screening and interaction proteomics, revealing that MYCN controls highly connected networks, with MYCN primarily supressing the activity of network components. MYCN's oncogenic functions are likely independent of its classical heterodimerisation partner, MAX. In particular, MYCN controls its own protein interaction network by transcriptionally regulating its binding partners.Our network-based approach identified vulnerable therapeutically targetable nodes that function as critical regulators or effectors of MYCN in neuroblastoma. These were validated by siRNA knockdown screens, functional studies and patient data. We identified β-estradiol and MAPK/ERK as having functional cross-talk with MYCN and being novel targetable vulnerabilities of MYCN-amplified neuroblastoma. These results reveal surprising differences between the functioning of endogenous, overexpressed and amplified MYCN, and rationalise how different MYCN dosages can orchestrate cell fate decisions and cancerous outcomes. Importantly, this work describes a systems-level approach to systematically uncovering network based vulnerabilities and therapeutic targets for multifactorial diseases by integrating disparate omic data types. PMID:26673823

  11. Integrative omics reveals MYCN as a global suppressor of cellular signalling and enables network-based therapeutic target discovery in neuroblastoma

    PubMed Central

    Fey, Dirk; Iljin, Kristiina; Mehta, Jai Prakash; Killick, Kate; Whilde, Jenny; Turriziani, Benedetta; Haapa-Paananen, Saija; Fey, Vidal; Fischer, Matthias; Westermann, Frank; Henrich, Kai-Oliver; Bannert, Steffen; Higgins, Desmond G.; Kolch, Walter

    2015-01-01

    Despite intensive study, many mysteries remain about the MYCN oncogene's functions. Here we focus on MYCN's role in neuroblastoma, the most common extracranial childhood cancer. MYCN gene amplification occurs in 20% of cases, but other recurrent somatic mutations are rare. This scarcity of tractable targets has hampered efforts to develop new therapeutic options. We employed a multi-level omics approach to examine MYCN functioning and identify novel therapeutic targets for this largely un-druggable oncogene. We used systems medicine based computational network reconstruction and analysis to integrate a range of omic techniques: sequencing-based transcriptomics, genome-wide chromatin immunoprecipitation, siRNA screening and interaction proteomics, revealing that MYCN controls highly connected networks, with MYCN primarily supressing the activity of network components. MYCN's oncogenic functions are likely independent of its classical heterodimerisation partner, MAX. In particular, MYCN controls its own protein interaction network by transcriptionally regulating its binding partners. Our network-based approach identified vulnerable therapeutically targetable nodes that function as critical regulators or effectors of MYCN in neuroblastoma. These were validated by siRNA knockdown screens, functional studies and patient data. We identified β-estradiol and MAPK/ERK as having functional cross-talk with MYCN and being novel targetable vulnerabilities of MYCN-amplified neuroblastoma. These results reveal surprising differences between the functioning of endogenous, overexpressed and amplified MYCN, and rationalise how different MYCN dosages can orchestrate cell fate decisions and cancerous outcomes. Importantly, this work describes a systems-level approach to systematically uncovering network based vulnerabilities and therapeutic targets for multifactorial diseases by integrating disparate omic data types. PMID:26673823

  12. Adaptive stochastic cellular automata: Applications

    NASA Astrophysics Data System (ADS)

    Qian, S.; Lee, Y. C.; Jones, R. D.; Barnes, C. W.; Flake, G. W.; O'Rourke, M. K.; Lee, K.; Chen, H. H.; Sun, G. Z.; Zhang, Y. Q.; Chen, D.; Giles, C. L.

    1990-09-01

    The stochastic learning cellular automata model has been applied to the problem of controlling unstable systems. Two example unstable systems studied are controlled by an adaptive stochastic cellular automata algorithm with an adaptive critic. The reinforcement learning algorithm and the architecture of the stochastic CA controller are presented. Learning to balance a single pole is discussed in detail. Balancing an inverted double pendulum highlights the power of the stochastic CA approach. The stochastic CA model is compared to conventional adaptive control and artificial neural network approaches.

  13. Engineering Cellular Metabolism.

    PubMed

    Nielsen, Jens; Keasling, Jay D

    2016-03-10

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation. PMID:26967285

  14. Integration of mobile satellite and cellular systems

    NASA Technical Reports Server (NTRS)

    Drucker, Elliott H.; Estabrook, Polly; Pinck, Deborah; Ekroot, Laura

    1993-01-01

    By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established. Users equipped for both cellular and satellite service can take advantage of a number of features made possible by such integration, including seamless handoff and universal roaming. To provide maximum benefit at lowest posible cost, the means by which these systems are integrated must be carefully considered. Mobile satellite hub stations must be configured to efficiently interface with cellular Mobile Telephone Switching Offices (MTSO's), and cost effective mobile units that provide both cellular and satellite capability must be developed.

  15. Docking studies and network analyses reveal capacity of compounds from Kandelia rheedii to strengthen cellular immunity by interacting with host proteins during tuberculosis infection

    PubMed Central

    Zaman, Aubhishek

    2012-01-01

    Kandelia rheedii (locally known as Guria or Rasunia), widely found and used in Indian subcontinent, is a well-known herbal cure to tuberculosis. However, neither the mechanism nor the active components of the plant extract responsible for mediating this action has yet been confirmed. Here in this study, molecular interactions of three compounds (emodin, fusaric acid and skyrin) from the plant extract with the host protein targets (casein kinase (CSNK), estrogen receptor (ERBB), dopamine β-hydroxylase (DBH) and glucagon receptor (Gcgr)) has been found. These protein targets are known to be responsible for strengthening cellular immunity against Mycobacteria tuberculosis. The specific interactions of these three compounds with the respective protein targets have been discussed here. The insights from study should further help us designing molecular medicines against tuberculosis. PMID:23275699

  16. Cellular mechanics and motility

    NASA Astrophysics Data System (ADS)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    cross-linked or branched networks. It is a highly dynamical system in which filaments are able to elongate or slide one on the other with the contribution of very active cellular proteins like molecular motors. The versatile properties of this cytoskeleton ensure the diversity of mechanical behaviors to explain cell rigidity as well as cell motility.

  17. Analysis of train movement dynamics under various temporal-spatial constraints in fixed-block railway network using extended cellular automaton model

    NASA Astrophysics Data System (ADS)

    Zhou, Yonghua; Zhang, Zhenlin; Liu, Deng

    2014-03-01

    In the fixed-block railway traffic, the trains adjust their speeds in view of their preceding allowable spaces caused by their respective front adjacent trains or specified by scheduling commands. The railway lines have the line-type speed limits within some block sections and the point-type ones at the terminals of block sections. Those speed limits originate from line conditions, scheduling commands and indications of signal equipment. This paper attempts to in detail reveal the train movement mechanism synthetically considering those temporal-spatial constraints. The proposed train movement model defines four kinds of target points and utilizes them to successively engender the instantaneous target points with their corresponding target speeds. It adopts the rule-based description mechanism in cellular automata (CA) but with continuous spaces to replicate restrictive, autonomous and synergistic behaviors of and among trains. The selections of accelerations and decelerations are based upon the data models of practical acceleration and deceleration processes; thereupon, the model is data-driven. The analysis of train movement dynamics through case studies demonstrates that the extended CA model can reproduce the train movement mechanism of grading speed control to satisfy the aforementioned temporal-spatial constraints. The model is applicable to represent the as-is or should-be states of train movements when adjustable parameters are properly configured.

  18. Robustness of networks of networks with degree-degree correlation

    NASA Astrophysics Data System (ADS)

    Min, Byungjoon; Canals, Santiago; Makse, Hernan

    Many real-world complex systems ranging from critical infrastructure and transportation networks to living systems including brain and cellular networks are not formed by an isolated network but by a network of networks. Randomly coupled networks with interdependency between different networks may easily result in abrupt collapse. Here, we seek a possible explanation of stable functioning in natural networks of networks including functional brain networks. Specifically, we analyze the robustness of networks of networks focused on one-to-many interconnections between different networks and degree-degree correlation. Implication of the network robustness on functional brain networks of rats is also discussed.

  19. Female sex steroids and glia cells: Impact on multiple sclerosis lesion formation and fine tuning of the local neurodegenerative cellular network.

    PubMed

    Kipp, Markus; Hochstrasser, Tanja; Schmitz, Christoph; Beyer, Cordian

    2016-08-01

    Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease that shows a female-to-male gender prevalence and alleviation of disease activity during late stage pregnancy. In MS-related animal models, sex steroids ameliorate symptoms and protect from demyelination and neuronal damage. Underlying mechanisms of these protective avenues are continuously discovered, in part by using novel transgenic animal models. In this review article, we highlight the regulation of glia cell function by female sex steroids. We specifically focus on the relevance of glia cells for immune cell recruitment into the central nervous system and show how estrogen and progesterone can modulate these cell-cell communication pathways. Since MS is considered to have a strong neurodegenerative component, principal neuroprotective mechanisms, exerted by sex-steroids will be discussed as well. Activation of steroid receptors might not just act as immunosuppressant but at the same time harmonize brain-intrinsic networks to dampen neurodegeneration and, thus, disease progression in MS. PMID:26698019

  20. Cellular Stress Responses and Monitored Cellular Activities.

    PubMed

    Sawa, Teiji; Naito, Yoshifumi; Kato, Hideya; Amaya, Fumimasa

    2016-08-01

    To survive, organisms require mechanisms that enable them to sense changes in the outside environment, introduce necessary responses, and resist unfavorable distortion. Consequently, through evolutionary adaptation, cells have become equipped with the apparatus required to monitor their fundamental intracellular processes and the mechanisms needed to try to offset malfunction without receiving any direct signals from the outside environment. It has been shown recently that eukaryotic cells are equipped with a special mechanism that monitors their fundamental cellular functions and that some pathogenic proteobacteria can override this monitoring mechanism to cause harm. The monitored cellular activities involved in the stressed intracellular response have been researched extensively in Caenorhabditis elegans, where discovery of an association between key mitochondrial activities and innate immune responses was named "cellular associated detoxification and defenses (cSADD)." This cellular surveillance pathway (cSADD) oversees core cellular activities such as mitochondrial respiration and protein transport into mitochondria, detects xenobiotics and invading pathogens, and activates the endocrine pathways controlling behavior, detoxification, and immunity. The cSADD pathway is probably associated with cellular responses to stress in human inflammatory diseases. In the critical care field, the pathogenesis of lethal inflammatory syndromes (e.g., respiratory distress syndromes and sepsis) involves the disturbance of mitochondrial respiration leading to cell death. Up-to-date knowledge about monitored cellular activities and cSADD, especially focusing on mitochondrial involvement, can probably help fill a knowledge gap regarding the pathogenesis of lethal inflammatory syndromes in the critical care field. PMID:26954943

  1. Cellular Phone Towers

    MedlinePlus

    ... the call. How are people exposed to the energy from cellular phone towers? As people use cell ... where people can be exposed to them. The energy from a cellular phone tower antenna, like that ...

  2. Identification of a Protein Network Interacting with TdRF1, a Wheat RING Ubiquitin Ligase with a Protective Role against Cellular Dehydration1[C][W

    PubMed Central

    Guerra, Davide; Mastrangelo, Anna Maria; Lopez-Torrejon, Gema; Marzin, Stephan; Schweizer, Patrick; Stanca, Antonio Michele; del Pozo, Juan Carlos; Cattivelli, Luigi; Mazzucotelli, Elisabetta

    2012-01-01

    Plants exploit ubiquitination to modulate the proteome with the final aim to ensure environmental adaptation and developmental plasticity. Ubiquitination targets are specifically driven to degradation through the action of E3 ubiquitin ligases. Genetic analyses have indicated wide functions of ubiquitination in plant life; nevertheless, despite the large number of predicted E3s, only a few of them have been characterized so far, and only a few ubiquitination targets are known. In this work, we characterized durum wheat (Triticum durum) RING Finger1 (TdRF1) as a durum wheat nuclear ubiquitin ligase. Moreover, its barley (Hordeum vulgare) homolog was shown to protect cells from dehydration stress. A protein network interacting with TdRF1 has been defined. The transcription factor WHEAT BEL1-TYPE HOMEODOMAIN1 (WBLH1) was degraded in a TdRF1-dependent manner through the 26S proteasome in vivo, the mitogen-activated protein kinase TdWNK5 [for Triticum durum WITH NO LYSINE (K)5] was able to phosphorylate TdRF1 in vitro, and the RING-finger protein WHEAT VIVIPAROUS-INTERACTING PROTEIN2 (WVIP2) was shown to have a strong E3 ligase activity. The genes coding for the TdRF1 interactors were all responsive to cold and/or dehydration stress, and a negative regulative function in dehydration tolerance was observed for the barley homolog of WVIP2. A role in the control of plant development was previously known, or predictable based on homology, for wheat BEL1-type homeodomain1(WBLH1). Thus, TdRF1 E3 ligase might act regulating the response to abiotic stress and remodeling plant development in response to environmental constraints. PMID:22167118

  3. Wrinkling in Cellular Structured Composites

    NASA Astrophysics Data System (ADS)

    Kaynia, Narges; Li, Yaning; Boyce, Mary C.

    2013-03-01

    Many structured composites found in nature possess undulating and wrinkled interfacial layers that regulate mechanical, chemical, acoustic, adhesive, thermal, electrical and optical functions of the material. This research focused on the formation of wrinkling patterns in cellular structured composites and the effect of the wrinkling pattern on the overall structural response. The cellular composites consisted of stiffer interfacial layers constructing a network submerged in a soft matrix. Analytical and finite element models were developed to capture various aspects of the wrinkling mechanism. The characteristics of the undulation patterns and the instability modes were investigated as functions of model geometry and material composition. Mechanical experiments were designed to further explore the modeling results. The cellular composite samples were fabricated by using different types of elastomers and by varying the geometry and the material properties. The experimental and numerical results were consistent with the analytical predictions. The results in this research improve understanding of the mechanisms governing the undulation pattern formation in cellular composites and can be used to enable on-demand tunability of different functions to provide, among others, active control of wave propagation, mechanical stiffness and deformation, and material swelling and growth.

  4. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-01-01

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young's modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  5. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-12-31

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young`s modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  6. Passive Noise Filtering by Cellular Compartmentalization.

    PubMed

    Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

    2016-03-10

    Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity. PMID:26967282

  7. Thermodynamics of cellular statistical inference

    NASA Astrophysics Data System (ADS)

    Lang, Alex; Fisher, Charles; Mehta, Pankaj

    2014-03-01

    Successful organisms must be capable of accurately sensing the surrounding environment in order to locate nutrients and evade toxins or predators. However, single cell organisms face a multitude of limitations on their accuracy of sensing. Berg and Purcell first examined the canonical example of statistical limitations to cellular learning of a diffusing chemical and established a fundamental limit to statistical accuracy. Recent work has shown that the Berg and Purcell learning limit can be exceeded using Maximum Likelihood Estimation. Here, we recast the cellular sensing problem as a statistical inference problem and discuss the relationship between the efficiency of an estimator and its thermodynamic properties. We explicitly model a single non-equilibrium receptor and examine the constraints on statistical inference imposed by noisy biochemical networks. Our work shows that cells must balance sample number, specificity, and energy consumption when performing statistical inference. These tradeoffs place significant constraints on the practical implementation of statistical estimators in a cell.

  8. Peroxisome Metabolism and Cellular Aging

    PubMed Central

    Titorenko, Vladimir I.; Terlecky, Stanley R.

    2010-01-01

    The essential role of peroxisomes in fatty acid oxidation, anaplerotic metabolism, and hydrogen peroxide turnover is well established. Recent findings suggest these and other related biochemical processes governed by the organelle may also play a critical role in regulating cellular aging. The goal of this review is to summarize and integrate into a model, the evidence that peroxisome metabolism actually helps define the replicative and chronological age of a eukaryotic cell. In this model, peroxisomal reactive oxygen species (ROS) are seen as altering organelle biogenesis and function, and eliciting changes in the dynamic communication networks that exist between peroxisomes and other cellular compartments. At low levels, peroxisomal ROS activate an anti-aging program in the cell; at concentrations beyond a specific threshold, a pro-aging course is triggered. PMID:21083858

  9. Fundamental Limits to Cellular Sensing

    NASA Astrophysics Data System (ADS)

    ten Wolde, Pieter Rein; Becker, Nils B.; Ouldridge, Thomas E.; Mugler, Andrew

    2016-03-01

    In recent years experiments have demonstrated that living cells can measure low chemical concentrations with high precision, and much progress has been made in understanding what sets the fundamental limit to the precision of chemical sensing. Chemical concentration measurements start with the binding of ligand molecules to receptor proteins, which is an inherently noisy process, especially at low concentrations. The signaling networks that transmit the information on the ligand concentration from the receptors into the cell have to filter this receptor input noise as much as possible. These networks, however, are also intrinsically stochastic in nature, which means that they will also add noise to the transmitted signal. In this review, we will first discuss how the diffusive transport and binding of ligand to the receptor sets the receptor correlation time, which is the timescale over which fluctuations in the state of the receptor, arising from the stochastic receptor-ligand binding, decay. We then describe how downstream signaling pathways integrate these receptor-state fluctuations, and how the number of receptors, the receptor correlation time, and the effective integration time set by the downstream network, together impose a fundamental limit on the precision of sensing. We then discuss how cells can remove the receptor input noise while simultaneously suppressing the intrinsic noise in the signaling network. We describe why this mechanism of time integration requires three classes (groups) of resources—receptors and their integration time, readout molecules, energy—and how each resource class sets a fundamental sensing limit. We also briefly discuss the scheme of maximum-likelihood estimation, the role of receptor cooperativity, and how cellular copy protocols differ from canonical copy protocols typically considered in the computational literature, explaining why cellular sensing systems can never reach the Landauer limit on the optimal trade

  10. Modelling cellular behaviour

    NASA Astrophysics Data System (ADS)

    Endy, Drew; Brent, Roger

    2001-01-01

    Representations of cellular processes that can be used to compute their future behaviour would be of general scientific and practical value. But past attempts to construct such representations have been disappointing. This is now changing. Increases in biological understanding combined with advances in computational methods and in computer power make it possible to foresee construction of useful and predictive simulations of cellular processes.

  11. Cellular Reflectarray Antenna

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  12. CELLULAR MAGNESIUM HOMEOSTASIS

    PubMed Central

    Romani, Andrea M.P.

    2011-01-01

    Magnesium, the second most abundant cellular cation after potassium, is essential to regulate numerous cellular functions and enzymes, including ion channels, metabolic cycles, and signaling pathways, as attested by more than 1000 entries in the literature. Despite significant recent progress, however, our understanding of how cells regulate Mg2+ homeostasis and transport still remains incomplete. For example, the occurrence of major fluxes of Mg2+ in either direction across the plasma membrane of mammalian cells following metabolic or hormonal stimuli has been extensively documented. Yet, the mechanisms ultimately responsible for magnesium extrusion across the cell membrane have not been cloned. Even less is known about the regulation in cellular organelles. The present review is aimed at providing the reader with a comprehensive and up-to-date understanding of the mechanisms enacted by eukaryotic cells to regulate cellular Mg2+ homeostasis and how these mechanisms are altered under specific pathological conditions. PMID:21640700

  13. Architected Cellular Materials

    NASA Astrophysics Data System (ADS)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  14. Approaches to Biosimulation of Cellular Processes

    PubMed Central

    Westerhoff, H. V.

    2006-01-01

    Modelling and simulation are at the heart of the rapidly developing field of systems biology. This paper reviews various types of models, simulation methods, and theoretical approaches that are presently being used in the quantitative description of cellular processes. We first describe how molecular interaction networks can be represented by means of stoichiometric, topological and kinetic models. We briefly discuss the formulation of kinetic models using mesoscopic (stochastic) or macroscopic (continuous) approaches, and we go on to describe how detailed models of molecular interaction networks (silicon cells) can be constructed on the basis of experimentally determined kinetic parameters for cellular processes. We show how theory can help in analyzing models by applying control analysis to a recently published silicon cell model. Finally, we review some of the theoretical approaches available to analyse kinetic models and experimental data, respectively. PMID:19669467

  15. Genetic Dominance & Cellular Processes

    ERIC Educational Resources Information Center

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  16. Teaching cellular engineering.

    PubMed

    Hammer, Daniel A; Waugh, Richard E

    2006-02-01

    Cellular engineering is one of the fastest growing subdisciplines in the field of Biomedical Engineering. It involves the application of engineering analysis to understand and control cellular behavior, with the ultimate objective of developing novel therapeutic or diagnostic approaches for the clinic or harnessing cellular function for commercial applications. Well-educated students in this area need strong foundational knowledge in engineering science, chemistry, and cell and molecular biology. In undergraduate curricula, the challenge is to include essential engineering skills plus appropriate levels of training in chemistry and biology while satisfying accreditation-mandated breadth in engineering training. At the graduate level, educators must accommodate students with diverse backgrounds and provide them with both a state-of-the-art understanding of the life sciences and the most advanced engineering skills. Engineering curricular content should include mechanics and materials, physical chemistry, transport phenomena, and control theory. Training from faculty with appointments and research programs in the life sciences is generally recommended, and additional life science content should also be integrated within the engineering curriculum. A capstone course in cellular engineering that includes opportunities for students to have hands-on experiences with state-of-the-art laboratory techniques is highly recommended. PMID:16450196

  17. Auxin and Cellular Elongation.

    PubMed

    Velasquez, Silvia Melina; Barbez, Elke; Kleine-Vehn, Jürgen; Estevez, José M

    2016-03-01

    Auxin is a crucial growth regulator in plants. However, a comprehensive understanding of how auxin induces cell expansion is perplexing, because auxin acts in a concentration- and cell type-dependent manner. Consequently, it is desirable to focus on certain cell types to exemplify the underlying growth mechanisms. On the other hand, plant tissues display supracellular growth (beyond the level of single cells); hence, other cell types might compromise the growth of a certain tissue. Tip-growing cells do not display neighbor-induced growth constraints and, therefore, are a valuable source of information for growth-controlling mechanisms. Here, we focus on auxin-induced cellular elongation in root hairs, exposing a mechanistic view of plant growth regulation. We highlight a complex interplay between auxin metabolism and transport, steering root hair development in response to internal and external triggers. Auxin signaling modules and downstream cascades of transcription factors define a developmental program that appears rate limiting for cellular growth. With this knowledge in mind, the root hair cell is a very suitable model system in which to dissect cellular effectors required for cellular expansion. PMID:26787325

  18. The New Cellular Immunology

    ERIC Educational Resources Information Center

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  19. Statistical properties of cellular automata in the context of learning and recognition: Part 1, Introduction

    SciTech Connect

    Gutowitz, H.A.

    1988-11-17

    In this lecture the map from a cellular automaton to a sequence of analytical approximations called the local structure theory is described. Connections are drawn between cellular automata and neural network models. It is suggested that the process by which a cellular automaton holds particular probability measures invariant is an appropriate model for biological memory. 20 figs.

  20. Fabrication of cellular materials

    NASA Astrophysics Data System (ADS)

    Prud'homme, Robert K.; Aksay, Ilhan A.; Garg, Rajeev

    1996-02-01

    Nature uses cellular materials in applications requiring strength while, simultaneously, minimizing raw materials requirements. Minimizing raw materials is efficient both in terms of the energy expended by the organism to synthesize the structure and in terms of the strength- to-weight ratio of the structure. Wood is the most obvious example of cellular bio-materials, and it is the focus of other presentations in this symposium. The lightweight bone structure of birds is another excellent example where weight is a key criterion. The anchoring foot of the common muscle [Mytilus edulis] whereby it attaches itself to objects is a further example of a biological system that uses a foam to fill space and yet conserve on raw materials. In the case of the muscle the foam is water filled and the foot structure distributes stress over a larger area so that the strength of the byssal thread from which it is suspended is matched to the strength of interfacial attachment of the foot to a substrate. In these examples the synthesis and fabrication of the cellular material is directed by intercellular, genetically coded, biochemical reactions. The resulting cell sizes are microns in scale. Cellular materials at the next larger scale are created by organisms at the next higher level of integration. For example an African tree frog lays her eggs in a gas/fluid foam sack she builds on a branch overhanging a pond. The outside of the foam sack hardens in the sun and prevents water evaporation. The foam structure minimizes the amount of fluid that needs to be incorporated into the sack and minimizes its weight. However, as far as the developing eggs are concerned, they are in an aqueous medium, i.e. the continuous fluid phase of the foam. After precisely six days the eggs hatch, and the solidified outer wall re-liquefies and dumps the emerging tadpoles into the pond below. The bee honeycomb is an example of a cellular material with exquisite periodicity at millimeter length scales. The

  1. Integration of cellular signals in chattering environments.

    PubMed

    Rué, P; Domedel-Puig, N; Garcia-Ojalvo, J; Pons, A J

    2012-09-01

    Cells are constantly exposed to fluctuating environmental conditions. External signals are sensed, processed and integrated by cellular signal transduction networks, which translate input signals into specific cellular responses by means of biochemical reactions. These networks have a complex nature, and we are still far from having a complete characterization of the process through which they integrate information, specially given the noisy environment in which that information is embedded. Guided by the many instances of constructive influences of noise that have been reported in the physical sciences in the last decades, here we explore how multiple signals are integrated in an eukaryotic cell in the presence of background noise, or chatter. To that end, we use a Boolean model of a typical human signal transduction network. Despite its complexity, we find that the network is able to display simple patterns of signal integration. Furthermore, our computational analysis shows that these integration patterns depend on the levels of fluctuating background activity carried by other cell inputs. Taken together, our results indicate that signal integration is sensitive to environmental fluctuations, and that this background noise effectively determines the information integration capabilities of the cell. PMID:22584015

  2. Cellular growth in biofilms

    SciTech Connect

    Wood, B.D.; Whitaker, S.

    1999-09-20

    In this paper the authors develop a macroscopic evolutionary equation for the growth of the cellular phase starting from a microscopic description of mass transport and a simple structured model for product formation. The methods of continuum mechanics and volume averaging are used to develop the macroscopic representation by carefully considering the fluxes of chemical species that pertain to cell growth. The concept of structured models is extended to include the transport of reacting chemical species at the microscopic scale. The resulting macroscopic growth model is similar in form to previously published models for the transport of a single substrate and electron donor and for the production of cellular mass and exopolymer. The method of volume averaging indicated under what conditions the developed growth model is valid and provides an explicit connection between the relevant microscopic model parameters and their corresponding macroscopic counterparts.

  3. Cellular dysfunction in sepsis.

    PubMed

    Singer, Mervyn

    2008-12-01

    Cellular dysfunction is a commonplace sequelum of sepsis and other systemic inflammatory conditions. Impaired energy production (related to mitochondrial inhibition, damage, and reduced protein turnover) appears to be a core mechanism underlying the development of organ dysfunction. The reduction in energy availability appears to trigger a metabolic shutdown that impairs normal functioning of the cell. This may well represent an adaptive mechanism analogous to hibernation that prevents a massive degree of cell death and thus enables eventual recovery in survivors. PMID:18954700

  4. Radiolabeled cellular blood elements

    SciTech Connect

    Thakur, M.L.; Ezikowitz, M.D.; Hardeman, M.R.

    1985-01-01

    This book contains papers delivered by guest lectures and participants at the Advanced Study Institute's colloquium on Radiolabeled Cellular Blood Elements at Maratea, Italy on August 29, to September 9, 1982. The book includes chapters on basic cell physiology and critical reviews of data and experience in the preparation and use of radiolabeled cells, as well as reports on very recent developments, from a faculty that included experts on cell physiology in health and disease and on the technology of in vivo labeling.

  5. Predictability in cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

    2014-01-01

    Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case. PMID:25271778

  6. Probabilistic cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

    2014-09-01

    Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata. PMID:24999557

  7. Quantum cellular automata

    NASA Astrophysics Data System (ADS)

    Porod, Wolfgang; Lent, Craig S.; Bernstein, Gary H.

    1994-06-01

    The Notre Dame group has developed a new paradigm for ultra-dense and ultra-fast information processing in nanoelectronic systems. These Quantum Cellular Automata (QCA's) are the first concrete proposal for a technology based on arrays of coupled quantum dots. The basic building block of these cellular arrays is the Notre Dame Logic Cell, as it has been called in the literature. The phenomenon of Coulomb exclusion, which is a synergistic interplay of quantum confinement and Coulomb interaction, leads to a bistable behavior of each cell which makes possible their use in large-scale cellular arrays. The physical interaction between neighboring cells has been exploited to implement logic functions. New functionality may be achieved in this fashion, and the Notre Dame group invented a versatile majority logic gate. In a series of papers, the feasibility of QCA wires, wire crossing, inverters, and Boolean logic gates was demonstrated. A major finding is that all logic functions may be integrated in a hierarchial fashion which allows the design of complicated QCA structures. The most complicated system which was simulated to date is a one-bit full adder consisting of some 200 cells. In addition to exploring these new concepts, efforts are under way to physically realize such structures both in semiconductor and metal systems. Extensive modeling work of semiconductor quantum dot structures has helped identify optimum design parameters for QCA experimental implementations.

  8. Inter-Cellular Forces Orchestrate Contact Inhibition of Locomotion

    PubMed Central

    Davis, John R.; Luchici, Andrei; Mosis, Fuad; Thackery, James; Salazar, Jesus A.; Mao, Yanlan; Dunn, Graham A.; Betz, Timo; Miodownik, Mark; Stramer, Brian M.

    2015-01-01

    Summary Contact inhibition of locomotion (CIL) is a multifaceted process that causes many cell types to repel each other upon collision. During development, this seemingly uncoordinated reaction is a critical driver of cellular dispersion within embryonic tissues. Here, we show that Drosophila hemocytes require a precisely orchestrated CIL response for their developmental dispersal. Hemocyte collision and subsequent repulsion involves a stereotyped sequence of kinematic stages that are modulated by global changes in cytoskeletal dynamics. Tracking actin retrograde flow within hemocytes in vivo reveals synchronous reorganization of colliding actin networks through engagement of an inter-cellular adhesion. This inter-cellular actin-clutch leads to a subsequent build-up in lamellar tension, triggering the development of a transient stress fiber, which orchestrates cellular repulsion. Our findings reveal that the physical coupling of the flowing actin networks during CIL acts as a mechanotransducer, allowing cells to haptically sense each other and coordinate their behaviors. PMID:25799385

  9. A synthetic biology approach to understanding cellular information processing

    PubMed Central

    Riccione, Katherine A; Smith, Robert P; Lee, Anna J; You, Lingchong

    2012-01-01

    The survival of cells and organisms requires proper responses to environmental signals. These responses are governed by cellular networks, which serve to process diverse environmental cues. Biological networks often contain recurring network topologies called ‘motifs’. It has been recognized that the study of such motifs allows one to predict the response of a biological network, and thus cellular behavior. However, studying a single motif in complete isolation of all other network motifs in a natural setting is difficult. Synthetic biology has emerged as a powerful approach to understanding the dynamic properties of network motifs. In addition to testing existing theoretical predictions, construction and analysis of synthetic gene circuits has led to the discovery of novel motif dynamics such as how the combination of simple motifs can lead to autonomous dynamics or how noise in transcription and translation can affect the dynamics of a motif. Here, we review developments in synthetic biology as they pertain to increasing our understanding of cellular information processing. We highlight several types of dynamic behaviors that diverse motifs can generate, including the control of input/output responses, the generation of autonomous spatial and temporal dynamics, as well as the influence of noise in motif dynamics and cellular behavior. PMID:23411668

  10. Capacity Limit, Link Scheduling and Power Control in Wireless Networks

    ERIC Educational Resources Information Center

    Zhou, Shan

    2013-01-01

    The rapid advancement of wireless technology has instigated the broad deployment of wireless networks. Different types of networks have been developed, including wireless sensor networks, mobile ad hoc networks, wireless local area networks, and cellular networks. These networks have different structures and applications, and require different…

  11. Formin’ cellular structures

    PubMed Central

    Bogdan, Sven; Schultz, Jörg; Grosshans, Jörg

    2014-01-01

    Members of the Diaphanous (Dia) protein family are key regulators of fundamental actin driven cellular processes, which are conserved from yeast to humans. Researchers have uncovered diverse physiological roles in cell morphology, cell motility, cell polarity, and cell division, which are involved in shaping cells into tissues and organs. The identification of numerous binding partners led to substantial progress in our understanding of the differential functions of Dia proteins. Genetic approaches and new microscopy techniques allow important new insights into their localization, activity, and molecular principles of regulation. PMID:24719676

  12. Control of cellular automata

    NASA Astrophysics Data System (ADS)

    Bagnoli, Franco; Rechtman, Raúl; El Yacoubi, Samira

    2012-12-01

    We study the problem of master-slave synchronization and control of totalistic cellular automata. The synchronization mechanism is that of setting a fraction of sites of the slave system equal to those of the master one (pinching synchronization). The synchronization observable is the distance between the two configurations. We present three control strategies that exploit local information (the number of nonzero first-order Boolean derivatives) in order to choose the sites to be synchronized. When no local information is used, we speak of simple pinching synchronization. We find the critical properties of control and discuss the best control strategy compared with simple synchronization.

  13. Efficiency of cellular information processing

    NASA Astrophysics Data System (ADS)

    Barato, Andre C.; Hartich, David; Seifert, Udo

    2014-10-01

    We show that a rate of conditional Shannon entropy reduction, characterizing the learning of an internal process about an external process, is bounded by the thermodynamic entropy production. This approach allows for the definition of an informational efficiency that can be used to study cellular information processing. We analyze three models of increasing complexity inspired by the Escherichia coli sensory network, where the external process is an external ligand concentration jumping between two values. We start with a simple model for which ATP must be consumed so that a protein inside the cell can learn about the external concentration. With a second model for a single receptor we show that the rate at which the receptor learns about the external environment can be nonzero even without any dissipation inside the cell since chemical work done by the external process compensates for this learning rate. The third model is more complete, also containing adaptation. For this model we show inter alia that a bacterium in an environment that changes at a very slow time-scale is quite inefficient, dissipating much more than it learns. Using the concept of a coarse-grained learning rate, we show for the model with adaptation that while the activity learns about the external signal the option of changing the methylation level increases the concentration range for which the learning rate is substantial.

  14. GENE EXPRESSION NETWORKS

    EPA Science Inventory

    "Gene expression network" is the term used to describe the interplay, simple or complex, between two or more gene products in performing a specific cellular function. Although the delineation of such networks is complicated by the existence of multiple and subtle types of intera...

  15. Cellular Contraction and Polarization Drive Collective Cellular Motion.

    PubMed

    Notbohm, Jacob; Banerjee, Shiladitya; Utuje, Kazage J C; Gweon, Bomi; Jang, Hwanseok; Park, Yongdoo; Shin, Jennifer; Butler, James P; Fredberg, Jeffrey J; Marchetti, M Cristina

    2016-06-21

    Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity. PMID:27332131

  16. Integrated cellular systems

    NASA Astrophysics Data System (ADS)

    Harper, Jason C.

    The generation of new three-dimensional (3D) matrices that enable integration of biomolecular components and whole cells into device architectures, without adversely altering their morphology or activity, continues to be an expanding and challenging field of research. This research is driven by the promise that encapsulated biomolecules and cells can significantly impact areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, photonics, smart prosthetics, advanced physiological sensors, portable medical diagnostic devices, and tissue/organ replacement. This work focuses on the development of a fundamental understanding of the biochemical and nanomaterial mechanisms that govern the cell directed assembly and integration process. It was shown that this integration process relies on the ability of cells to actively develop a pH gradient in response to evaporation induced osmotic stress, which catalyzes silica condensation within a thin 3D volume surrounding the cells, creating a functional bio/nano interface. The mechanism responsible for introducing functional foreign membrane-bound proteins via proteoliposome addition to the silica-lipid-cell matrix was also determined. Utilizing this new understanding, 3D cellular immobilization capabilities were extended using sol-gel matrices endowed with glycerol, trehalose, and media components. The effects of these additives, and the metabolic phase of encapsulated S. cerivisiase cells, on long-term viability and the rate of inducible gene expression was studied. This enabled the entrapment of cells within a novel microfluidic platform capable of simultaneous colorimetric, fluorescent, and electrochemical detection of a single analyte, significantly improving confidence in the biosensor output. As a complementary approach, multiphoton protein lithography was utilized to engineer 3D protein matrices in which to

  17. Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment for Cellular Physiology

    PubMed Central

    Byrne, Michael J.; Waxham, M. Neal; Kubota, Yoshihisa

    2010-01-01

    In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into account volume exclusion and molecular crowding that may impact signaling cascades in small sub-cellular compartments such as dendritic spines. With the CDS, we can simulate simple enzyme reactions; aggregation, channel transport, as well as highly complicated chemical reaction networks of both freely diffusing and membrane bound multi-protein complexes. Components of the CDS are generally defined such that the simulator can be applied to a wide range of environments in terms of scale and level of detail. Through an initialization GUI, a simple simulation environment can be created and populated within minutes yet is powerful enough to design complex 3D cellular architecture. The initialization tool allows visual confirmation of the environment construction prior to execution by the simulator. This paper describes the CDS algorithm, design implementation, and provides an overview of the types of features available and the utility of those features are highlighted in demonstrations. PMID:20361275

  18. The Cellular Building Blocks of Breathing

    PubMed Central

    Ramirez, J.M.; Doi, A.; Garcia, A.J.; Elsen, F.P.; Koch, H.; Wei, A.D.

    2013-01-01

    Respiratory brainstem neurons fulfill critical roles in controlling breathing: they generate the activity patterns for breathing and contribute to various sensory responses including changes in O2 and CO2. These complex sensorimotor tasks depend on the dynamic interplay between numerous cellular building blocks that consist of voltage-, calcium-, and ATP-dependent ionic conductances, various ionotropic and metabotropic synaptic mechanisms, as well as neuromodulators acting on G-protein coupled receptors and second messenger systems. As described in this review, the sensorimotor responses of the respiratory network emerge through the state-dependent integration of all these building blocks. There is no known respiratory function that involves only a small number of intrinsic, synaptic, or modulatory properties. Because of the complex integration of numerous intrinsic, synaptic, and modulatory mechanisms, the respiratory network is capable of continuously adapting to changes in the external and internal environment, which makes breathing one of the most integrated behaviors. Not surprisingly, inspiration is critical not only in the control of ventilation, but also in the context of “inspiring behaviors” such as arousal of the mind and even creativity. Far-reaching implications apply also to the underlying network mechanisms, as lessons learned from the respiratory network apply to network functions in general. PMID:23720262

  19. Cellular Morphogenesis In Silico

    PubMed Central

    Shinbrot, Troy; Chun, Young; Caicedo-Carvajal, Carlos; Foty, Ramsey

    2009-01-01

    Abstract We describe a model that simulates spherical cells of different types that can migrate and interact either attractively or repulsively. We find that both expected morphologies and previously unreported patterns spontaneously self-assemble. Among the newly discovered patterns are a segmented state of alternating discs, and a “shish-kebab” state, in which one cell type forms a ring around a second type. We show that these unique states result from cellular attraction that increases with distance (e.g., as membranes stretch viscoelastically), and would not be seen in traditional, e.g., molecular, potentials that diminish with distance. Most of the states found computationally have been observed in vitro, and it remains to be established what role these self-assembled states may play in in vivo morphogenesis. PMID:19686642

  20. Rapid Cellular Identification by Dynamic Electromechanical Response

    SciTech Connect

    Nikiforov, Maxim; Jesse, Stephen; Kalinin, Sergei V; Reukov, Vladimir V; Vertegel, Alexey; Thompson, Gary L

    2009-01-01

    Coupling between electrical and mechanical phenomena is ubiquitous in living systems. Here, we demonstrate rapid identification of cellular organisms using difference in electromechanical activity in a broad frequency range. Principal component analysis of the dynamic electromechanical response spectra bundled with neural network based recognition provides a robust identification algorithm based on their electromechanical signature, and allows unambiguous differentiation of model Micrococcus Lysodeikticus and Pseudomonas Fluorescens system. This methodology provides a universal pathway for biological identification obviating the need for well-defined analytical models of Scanning Probe Microscopy response.

  1. Cellular telephone-based radiation detection instrument

    DOEpatents

    Craig, William W.; Labov, Simon E.

    2011-06-14

    A network of radiation detection instruments, each having a small solid state radiation sensor module integrated into a cellular phone for providing radiation detection data and analysis directly to a user. The sensor module includes a solid-state crystal bonded to an ASIC readout providing a low cost, low power, light weight compact instrument to detect and measure radiation energies in the local ambient radiation field. In particular, the photon energy, time of event, and location of the detection instrument at the time of detection is recorded for real time transmission to a central data collection/analysis system. The collected data from the entire network of radiation detection instruments are combined by intelligent correlation/analysis algorithms which map the background radiation and detect, identify and track radiation anomalies in the region.

  2. Cellular energy metabolism

    SciTech Connect

    Glaser, M.

    1991-06-01

    Studies have been carried out on adenylate kinase which is an important enzyme in determining the concentrations of the adenine nucleotides. An efficient method has been developed to clone mutant adenylate kinase genes in E. coli. Site-specific mutagenesis of the wild type gene also has been used to obtain forms of adenylate kinase with altered amino acids. The wild type and mutant forms of adenylate kinase have been overexpressed and large quantities were readily isolated. The kinetic and fluorescence properties of the different forms of adenylate kinase were characterized. This has led to a new model for the location of the AMP and ATP bindings sites on the enzyme and a proposal for the mechanism of substrate inhibition. Crystals of the wild type enzyme were obtained that diffract to at least 2.3 {angstrom} resolution. Experiments were also initiated to determine the function of adenylate kinase in vivo. In one set of experiments, E. coli strains with mutations in adenylate kinase showed large changes in cellular nucleotides after reaching the stationary phase in a low phosphate medium. This was caused by selective proteolytic degradation of the mutant adenylate kinase caused by phosphate starvation.

  3. Molecular and Cellular Biophysics

    NASA Astrophysics Data System (ADS)

    Jackson, Meyer B.

    2006-01-01

    Molecular and Cellular Biophysics provides advanced undergraduate and graduate students with a foundation in the basic concepts of biophysics. Students who have taken physical chemistry and calculus courses will find this book an accessible and valuable aid in learning how these concepts can be used in biological research. The text provides a rigorous treatment of the fundamental theories in biophysics and illustrates their application with examples. Conformational transitions of proteins are studied first using thermodynamics, and subsequently with kinetics. Allosteric theory is developed as the synthesis of conformational transitions and association reactions. Basic ideas of thermodynamics and kinetics are applied to topics such as protein folding, enzyme catalysis and ion channel permeation. These concepts are then used as the building blocks in a treatment of membrane excitability. Through these examples, students will gain an understanding of the general importance and broad applicability of biophysical principles to biological problems. Offers a unique synthesis of concepts across a wide range of biophysical topics Provides a rigorous theoretical treatment, alongside applications in biological systems Author has been teaching biophysics for nearly 25 years

  4. Electrosurgery with cellular precision.

    PubMed

    Palanker, Daniel V; Vankov, Alexander; Huie, Philip

    2008-02-01

    Electrosurgery, one of the most-often used surgical tools, is a robust but somewhat crude technology that has changed surprisingly little since its invention almost a century ago. Continuous radiofrequency is still used for tissue cutting, with thermal damage extending to hundreds of micrometers. In contrast, lasers developed 70 years later, have been constantly perfected, and the laser-tissue interactions explored in great detail, which has allowed tissue ablation with cellular precision in many laser applications. We discuss mechanisms of tissue damage by electric field, and demonstrate that electrosurgery with properly optimized waveforms and microelectrodes can rival many advanced lasers. Pulsed electric waveforms with burst durations ranging from 10 to 100 micros applied via insulated planar electrodes with 12 microm wide exposed edges produced plasma-mediated dissection of tissues with the collateral damage zone ranging from 2 to 10 microm. Length of the electrodes can vary from micrometers to centimeters and all types of soft tissues-from membranes to cartilage and skin could be dissected in liquid medium and in a dry field. This technology may allow for major improvements in outcomes of the current surgical procedures and development of much more refined surgical techniques. PMID:18270030

  5. Active Cellular Nematics

    NASA Astrophysics Data System (ADS)

    Duclos, Guillaume; Erlenkaemper, Christoph; Garcia, Simon; Yevick, Hannah; Joanny, Jean-François; Silberzan, Pascal; Biology inspired physics at mesoscales Team; Physical approach of biological problems Team

    We study the emergence of a nematic order in a two-dimensional tissue of apolar elongated fibroblast cells. Initially, these cells are very motile and the monolayer is characterized by giant density fluctuations, a signature of far-from-equilibrium systems. As the cell density increases because of proliferation, the cells align with each other forming large perfectly oriented domains while the cellular movements slow down and eventually freeze. Therefore topological defects characteristic of nematic phases remain trapped at long times, preventing the development of infinite domains. By analogy with classical non-active nematics, we have investigated the role of boundaries and we have shown that cells confined in stripes of width smaller than typically 500 µm are perfectly aligned in the stripe direction. Experiments performed in cross-shaped patterns show that both the number of cells and the degree of alignment impact the final orientation. Reference: Duclos G., Garcia S., Yevick H.G. and Silberzan P., ''Perfect nematic order in confined monolayers of spindle-shaped cells'', Soft Matter, 10, 14, 2014

  6. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  7. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  8. Elements of the cellular metabolic structure

    PubMed Central

    De la Fuente, Ildefonso M.

    2015-01-01

    A large number of studies have demonstrated the existence of metabolic covalent modifications in different molecular structures, which are able to store biochemical information that is not encoded by DNA. Some of these covalent mark patterns can be transmitted across generations (epigenetic changes). Recently, the emergence of Hopfield-like attractor dynamics has been observed in self-organized enzymatic networks, which have the capacity to store functional catalytic patterns that can be correctly recovered by specific input stimuli. Hopfield-like metabolic dynamics are stable and can be maintained as a long-term biochemical memory. In addition, specific molecular information can be transferred from the functional dynamics of the metabolic networks to the enzymatic activity involved in covalent post-translational modulation, so that determined functional memory can be embedded in multiple stable molecular marks. The metabolic dynamics governed by Hopfield-type attractors (functional processes), as well as the enzymatic covalent modifications of specific molecules (structural dynamic processes) seem to represent the two stages of the dynamical memory of cellular metabolism (metabolic memory). Epigenetic processes appear to be the structural manifestation of this cellular metabolic memory. Here, a new framework for molecular information storage in the cell is presented, which is characterized by two functionally and molecularly interrelated systems: a dynamic, flexible and adaptive system (metabolic memory) and an essentially conservative system (genetic memory). The molecular information of both systems seems to coordinate the physiological development of the whole cell. PMID:25988183

  9. Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

    PubMed

    Olson, D K; Fröhlich, F; Farese, R V; Walther, T C

    2016-08-01

    Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26747648

  10. Material and mechanical factors: new strategy in cellular neurogenesis

    PubMed Central

    Stoll, Hillary; Kwon, Il Keun; Lim, Jung Yul

    2014-01-01

    Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharmacological factors on the cellular neurogenesis. On the other hand, it is now recognized that the other extracellular factors, including material and mechanical cues, also have a strong potential to induce cellular neurogenesis. This article will review recent data on the material (chemical patterning, micro/nano-topography, carbon nanotube, graphene) and mechanical (static cue from substrate stiffness, dynamic cue from stretch and flow shear) stimulations of cellular neurogenesis. These approaches may provide new neural regenerative medicine protocols. Scaffolding material templates capable of triggering cellular neurogenesis can be explored in the presence of neurogenesis-stimulatory mechanical environments, and also with conventional soluble factors, to enhance axonal growth and neural network formation in neural tissue engineering. PMID:25422642

  11. Leucocyte cellular adhesion molecules.

    PubMed

    Yong, K; Khwaja, A

    1990-12-01

    Leucocytes express adhesion promoting receptors which mediate cell-cell and cell-matrix interactions. These adhesive interactions are crucial to the regulation of haemopoiesis and thymocyte maturation, the direction and control of leucocyte traffic and migration through tissues, and in the development of immune and non-immune inflammatory responses. Several families of adhesion receptors have been identified (Table). The leucocyte integrin family comprises 3 alpha beta heterodimeric membrane glycoproteins which share a common beta subunit, designated CD18. The alpha subunits of each of the 3 members, lymphocyte function associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and p150,95 are designated CD11a, b and c respectively. These adhesion molecules play a critical part in the immune and inflammatory responses of leucocytes. The leucocyte integrin family is, in turn, part of the integrin superfamily, members of which are evolutionally, structurally and functionally related. Another Integrin subfamily found on leucocytes is the VLA group, so-called because the 'very late activation antigens' VLA-1 and VLA-2 were originally found to appear late in T-cell activation. Members of this family function mainly as extracellular matrix adhesion receptors and are found both on haemopoietic and non-haemopoietic cells. They play a part in diverse cellular functions including tissue organisation, lymphocyte recirculation and T-cell immune responses. A third integrin subfamily, the cytoadhesins, are receptors on platelets and endothelial cells which bind extracellular matrix proteins. A second family of adhesion receptors is the immunoglobulin superfamily, members of which include CD2, LFA-3 and ICAM-1, which participate in T-cell adhesive interactions, and the antigen-specific receptors of T and B cells, CD4, CD8 and the MHC Class I and II molecules. A recently recognised family of adhesion receptors is the selectins, characterised by a common lectin domain. Leucocyte

  12. Mobile Virtual Private Networking

    NASA Astrophysics Data System (ADS)

    Pulkkis, Göran; Grahn, Kaj; Mårtens, Mathias; Mattsson, Jonny

    Mobile Virtual Private Networking (VPN) solutions based on the Internet Security Protocol (IPSec), Transport Layer Security/Secure Socket Layer (SSL/TLS), Secure Shell (SSH), 3G/GPRS cellular networks, Mobile IP, and the presently experimental Host Identity Protocol (HIP) are described, compared and evaluated. Mobile VPN solutions based on HIP are recommended for future networking because of superior processing efficiency and network capacity demand features. Mobile VPN implementation issues associated with the IP protocol versions IPv4 and IPv6 are also evaluated. Mobile VPN implementation experiences are presented and discussed.

  13. Origin of cells and network information

    PubMed Central

    Tanabe, Shihori

    2015-01-01

    All cells are derived from one cell, and the origin of different cell types is a subject of curiosity. Cells construct life through appropriately timed networks at each stage of development. Communication among cells and intracellular signaling are essential for cell differentiation and for life processes. Cellular molecular networks establish cell diversity and life. The investigation of the regulation of each gene in the genome within the cellular network is therefore of interest. Stem cells produce various cells that are suitable for specific purposes. The dynamics of the information in the cellular network changes as the status of cells is altered. The components of each cell are subject to investigation. PMID:25914760

  14. Cellular compartmentalization of secondary metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors sh...

  15. Cellular therapy for haematological malignancies.

    PubMed

    Roddie, P H; Turner, M L

    2002-11-01

    The aim of this review was to summarize the recent progress made in the field of cellular therapeutics in haematological malignancy. The review also examined the role that the National Transfusion Services might play in the manufacture of new cellular therapeutic agents, given both their expertise in the safe provision of blood products and their possession of accredited cell manipulation facilities. Cellular therapy is entering an era in which novel cellular products will find increasing clinical use, particularly in the areas of haematopoietic stem cell transplantation and immunotherapy. The production of novel cell-based therapies, both in Europe and North America, is now under strict regulatory control and therefore collaboration with the National Transfusion Services in the manufacture of these agents may well be beneficial if the production standards demanded by the regulatory authorities are to be fulfilled. PMID:12437515

  16. Mathematical Modeling of Cellular Metabolism.

    PubMed

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    2016-01-01

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research. PMID:27557541

  17. Biomimetic superelastic graphene-based cellular monoliths.

    PubMed

    Qiu, Ling; Liu, Jeffery Z; Chang, Shery L Y; Wu, Yanzhe; Li, Dan

    2012-01-01

    Many applications proposed for graphene require multiple sheets be assembled into a monolithic structure. The ability to maintain structural integrity upon large deformation is essential to ensure a macroscopic material which functions reliably. However, it has remained a great challenge to achieve high elasticity in three-dimensional graphene networks. Here we report that the marriage of graphene chemistry with ice physics can lead to the formation of ultralight and superelastic graphene-based cellular monoliths. Mimicking the hierarchical structure of natural cork, the resulting materials can sustain their structural integrity under a load of >50,000 times their own weight and can rapidly recover from >80% compression. The unique biomimetic hierarchical structure also provides this new class of elastomers with exceptionally high energy absorption capability and good electrical conductivity. The successful synthesis of such fascinating materials paves the way to explore the application of graphene in a self-supporting, structurally adaptive and 3D macroscopic form. PMID:23212370

  18. Analytical Solution of Traffic Cellular Automata Model

    NASA Astrophysics Data System (ADS)

    Lo, Shih-Ching; Hsu, Chia-Hung

    2009-08-01

    Complex traffic system seems to be simulated successfully by cellular automaton (CA) models. Various models are developed to understand single-lane traffic, multilane traffic, lane-changing behavior and network traffic situations. However, the result of CA simulation can only be obtained after massive microscopic computation. Although, the mean field theory (MFT) has been studied to be the approximation of CA model, the MFT can only applied to the simple CA rules or small value of parameters. In this study, we simulate traffic flow by the NaSch model under different combination of parameters, which are maximal speed, dawdling probability and density. After that, the position of critical density, the slope of free-flow and congested regime are observed and modeled due to the simulated data. Finally, the coefficients of the model will be calibrated by the simulated data and the analytical solution of traffic CA is obtained.

  19. Traffic jam dynamics in stochastic cellular automata

    SciTech Connect

    Nagel, K. |; Schreckenberg, M.

    1995-09-01

    Simple models for particles hopping on a grid (cellular automata) are used to simulate (single lane) traffic flow. Despite their simplicity, these models are astonishingly realistic in reproducing start-stop-waves and realistic fundamental diagrams. One can use these models to investigate traffic phenomena near maximum flow. A so-called phase transition at average maximum flow is visible in the life-times of jams. The resulting dynamic picture is consistent with recent fluid-dynamical results by Kuehne/Kerner/Konhaeuser, and with Treiterer`s hysteresis description. This places CA models between car-following models and fluid-dynamical models for traffic flow. CA models are tested in projects in Los Alamos (USA) and in NRW (Germany) for large scale microsimulations of network traffic.

  20. Prenatal Alcohol Exposure and Cellular Differentiation

    PubMed Central

    Veazey, Kylee J.; Muller, Daria; Golding, Michael C.

    2013-01-01

    Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell–cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell’s identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes—the Polycomb and Trithorax proteins—are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder. PMID:24313167

  1. Cellular Decision-Making and Biological Noise: From Microbes to Mammals

    PubMed Central

    Balázsi, Gábor; van Oudenaarden, Alexander; Collins, James J.

    2011-01-01

    Cellular decision-making is the process wherein cells assume different, functionally important and heritable fates without an associated genetic or environmental difference. Such stochastic cell-fate decisions generate non-genetic cellular diversity, which may be critical for metazoan development as well as optimized microbial resource utilization and survival in a fluctuating, frequently stressful environment. Here we review several examples of cellular decision-making from viruses, bacteria, yeast, lower metazoans and mammals, highlighting the role of regulatory network structure and molecular noise. We propose that cellular decision-making is one of at least three key processes underlying development at various scales of biological organization. PMID:21414483

  2. Overview of molecular, cellular, and genetic neurotoxicology.

    PubMed

    Wallace, David R

    2005-05-01

    It has become increasingly evident that the field of neurotoxicology is not only rapidly growing but also rapidly evolving, especially over the last 20 years. As the number of drugs and environmental and bacterial/viral agents with potential neurotoxic properties has grown, the need for additional testing has increased. Only recently has the technology advanced to a level that neurotoxicologic studies can be performed without operating in a "black box." Examination of the effects of agents that are suspected of being toxic can occur on the molecular (protein-protein), cellular (biomarkers, neuronal function), and genetic (polymorphisms) level. Together, these areas help to elucidate the potential toxic profiles of unknown (and in some cases, known) agents. The area of proteomics is one of the fastest growing areas in science and particularly applicable to neurotoxicology. Lubec et al, provide a review of the potential and limitations of proteomics. Proteomics focuses on a more comprehensive view of cellular proteins and provides considerably more information about the effects of toxins on the CNS. Proteomics can be classified into three different focuses: post-translational modification, protein-expression profiling, and protein-network mapping. Together, these methods represent a more complete and powerful image of protein modifications following potential toxin exposure. Cellular neurotoxicology involves many cellular processes including alterations in cellular energy homeostasis, ion homeostasis, intracellular signaling function, and neurotransmitter release, uptake, and storage. The greatest hurdle in cellular neurotoxicology has been the discovery of appropriate biomarkers that are reliable, reproducible, and easy to obtain. There are biomarkers of exposure effect, and susceptibility. Finding the appropriate biomarker for a particular toxin is a daunting task. The appropriate biomarker for a particular toxin is a daunting task. The advantage to biomarker

  3. Continuum representations of cellular solids

    SciTech Connect

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  4. Parameter-less approaches for interpreting dynamic cellular response

    PubMed Central

    2014-01-01

    Cellular response such as cell signaling is an integral part of information processing in biology. Upon receptor stimulation, numerous intracellular molecules are invoked to trigger the transcription of genes for specific biological purposes, such as growth, differentiation, apoptosis or immune response. How complex are such specialized and sophisticated machinery? Computational modeling is an important tool for investigating dynamic cellular behaviors. Here, I focus on certain types of key signaling pathways that can be interpreted well using simple physical rules based on Boolean logic and linear superposition of response terms. From the examples shown, it is conceivable that for small-scale network modeling, reaction topology, rather than parameter values, is crucial for understanding population-wide cellular behaviors. For large-scale response, non-parametric statistical approaches have proven valuable for revealing emergent properties. PMID:25183996

  5. In Vivo Cellular Reprogramming: The Next Generation.

    PubMed

    Srivastava, Deepak; DeWitt, Natalie

    2016-09-01

    Cellular reprogramming technology has created new opportunities in understanding human disease, drug discovery, and regenerative medicine. While a combinatorial code was initially found to reprogram somatic cells to pluripotency, a "second generation" of cellular reprogramming involves lineage-restricted transcription factors and microRNAs that directly reprogram one somatic cell to another. This technology was enabled by gene networks active during development, which induce global shifts in the epigenetic landscape driving cell fate decisions. A major utility of direct reprogramming is the potential of harnessing resident support cells within damaged organs to regenerate lost tissue by converting them into the desired cell type in situ. Here, we review the progress in direct cellular reprogramming, with a focus on the paradigm of in vivo reprogramming for regenerative medicine, while pointing to hurdles that must be overcome to translate this technology into future therapeutics. PMID:27610565

  6. Aging, Cellular Senescence, and Cancer

    PubMed Central

    Campisi, Judith

    2014-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyper-plastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  7. Aging, cellular senescence, and cancer.

    PubMed

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  8. Fracture mechanics of cellular glass

    NASA Technical Reports Server (NTRS)

    Zwissler, J. G.; Adams, M. A.

    1981-01-01

    The fracture mechanics of cellular glasses (for the structural substrate of mirrored glass for solr concentrator reflecting panels) are discussed. Commercial and developmental cellular glasses were tested and analyzed using standard testing techniques and models developed from linear fracture mechanics. Two models describing the fracture behavior of these materials were developed. Slow crack growth behavior in cellular glass was found to be more complex than that encountered in dense glasses or ceramics. The crack velocity was found to be strongly dependent upon water vapor transport to the tip of the moving crack. The existence of a static fatigue limit was not conclusively established, however, it is speculated that slow crack growth behavior in Region 1 may be slower, by orders of magnitude, than that found in dense glasses.

  9. Cellular-based preemption system

    NASA Technical Reports Server (NTRS)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  10. GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits.

    PubMed

    Tremblay, Robin; Lee, Soohyun; Rudy, Bernardo

    2016-07-20

    Cortical networks are composed of glutamatergic excitatory projection neurons and local GABAergic inhibitory interneurons that gate signal flow and sculpt network dynamics. Although they represent a minority of the total neocortical neuronal population, GABAergic interneurons are highly heterogeneous, forming functional classes based on their morphological, electrophysiological, and molecular features, as well as connectivity and in vivo patterns of activity. Here we review our current understanding of neocortical interneuron diversity and the properties that distinguish cell types. We then discuss how the involvement of multiple cell types, each with a specific set of cellular properties, plays a crucial role in diversifying and increasing the computational power of a relatively small number of simple circuit motifs forming cortical networks. We illustrate how recent advances in the field have shed light onto the mechanisms by which GABAergic inhibition contributes to network operations. PMID:27477017

  11. Methods for Determining the Cellular Functions of Vimentin Intermediate Filaments.

    PubMed

    Ridge, Karen M; Shumaker, Dale; Robert, Amélie; Hookway, Caroline; Gelfand, Vladimir I; Janmey, Paul A; Lowery, Jason; Guo, Ming; Weitz, David A; Kuczmarski, Edward; Goldman, Robert D

    2016-01-01

    The type III intermediate filament protein vimentin was once thought to function mainly as a static structural protein in the cytoskeleton of cells of mesenchymal origin. Now, however, vimentin is known to form a dynamic, flexible network that plays an important role in a number of signaling pathways. Here, we describe various methods that have been developed to investigate the cellular functions of the vimentin protein and intermediate filament network, including chemical disruption, photoactivation and photoconversion, biolayer interferometry, soluble bead binding assay, three-dimensional substrate experiments, collagen gel contraction, optical-tweezer active microrheology, and force spectrum microscopy. Using these techniques, the contributions of vimentin to essential cellular processes can be probed in ever further detail. PMID:26795478

  12. Methods for Determining the Cellular Functions of Vimentin Intermediate Filaments

    PubMed Central

    Ridge, Karen M.; Shumaker, Dale; Robert, Amélie; Hookway, Caroline; Gelfand, Vladimir I.; Janmey, Paul A.; Lowery, Jason; Guo, Ming; Weitz, David A.; Kuczmarski, Edward; Goldman, Robert D.

    2016-01-01

    The type III intermediate filament protein vimentin was once thought to function mainly as a static structural protein in the cytoskeleton of cells of mesenchymal origin. Now, however, vimentin is known to form a dynamic, flexible network that plays an important role in a number of signaling pathways. Here, we describe various methods that have been developed to investigate the cellular functions of the vimentin protein and intermediate filament network, including chemical disruption, photoactivation and photoconversion, biolayer interferometry, soluble bead binding assay, three-dimensional substrate experiments, collagen gel contraction, optical-tweezer active microrheology, and force spectrum microscopy. Using these techniques, the contributions of vimentin to essential cellular processes can be probed in ever further detail. PMID:26795478

  13. Synthetic biology in cellular immunotherapy

    PubMed Central

    Chakravarti, Deboki; Wong, Wilson W.

    2015-01-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. PMID:26088008

  14. Global properties of cellular automata

    SciTech Connect

    Jen, E.

    1986-04-01

    Cellular automata are discrete mathematical systems that generate diverse, often complicated, behavior using simple deterministic rules. Analysis of the local structure of these rules makes possible a description of the global properties of the associated automata. A class of cellular automata that generate infinitely many aperoidic temporal sequences is defined,a s is the set of rules for which inverses exist. Necessary and sufficient conditions are derived characterizing the classes of ''nearest-neighbor'' rules for which arbitrary finite initial conditions (i) evolve to a homogeneous state; (ii) generate at least one constant temporal sequence.

  15. Cellular automaton for chimera states

    NASA Astrophysics Data System (ADS)

    García-Morales, Vladimir

    2016-04-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the system spontaneously splitting into stable domains separated by static boundaries, some synchronously oscillating and the others incoherent. When the coupling range is local, nontrivial coherent structures with different periodicities are formed.

  16. Cellular senescence in aging primates.

    PubMed

    Herbig, Utz; Ferreira, Mark; Condel, Laura; Carey, Dee; Sedivy, John M

    2006-03-01

    The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status. PMID:16456035

  17. Cellular basis of Alzheimer's disease.

    PubMed

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-12-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD. PMID:21369424

  18. An Evolutionary Hybrid Cellular Automaton Model of Solid Tumour Growth

    PubMed Central

    Gerlee, P.; Anderson, A.R.A.

    2007-01-01

    We propose a cellular automaton model of solid tumour growth, in which each cell is equipped with a micro-environment response network. This network is modelled using a feed-forward artificial neural network, that takes environmental variables as an input and from these determines the cellular behaviour as the output. The response of the network is determined by connection weights and thresholds in the network, which are subject to mutations when the cells divide. As both available space and nutrients are limited resources for the tumour this gives rise to clonal evolution where only the fittest cells survive. Using this approach we have investigated the impact of the tissue oxygen concentration on the growth and evolutionary dynamics of the tumour. The results show that the oxygen concentration affects the selection pressure, cell population diversity and morphology of the tumour. A low oxygen concentration in the tissue gives rise to a tumour with a fingered morphology that contains aggressive phenotypes with a small apoptotic potential, while a high oxygen concentration in the tissue gives rise to a tumour with a round morphology containing less evolved phenotypes. The tissue oxygen concentration thus affects the tumour at both the morphological level and on the phenotype level. PMID:17374383

  19. Quantitative Analysis of Cellular Metabolic Dissipative, Self-Organized Structures

    PubMed Central

    de la Fuente, Ildefonso Martínez

    2010-01-01

    One of the most important goals of the postgenomic era is understanding the metabolic dynamic processes and the functional structures generated by them. Extensive studies during the last three decades have shown that the dissipative self-organization of the functional enzymatic associations, the catalytic reactions produced during the metabolite channeling, the microcompartmentalization of these metabolic processes and the emergence of dissipative networks are the fundamental elements of the dynamical organization of cell metabolism. Here we present an overview of how mathematical models can be used to address the properties of dissipative metabolic structures at different organizational levels, both for individual enzymatic associations and for enzymatic networks. Recent analyses performed with dissipative metabolic networks have shown that unicellular organisms display a singular global enzymatic structure common to all living cellular organisms, which seems to be an intrinsic property of the functional metabolism as a whole. Mathematical models firmly based on experiments and their corresponding computational approaches are needed to fully grasp the molecular mechanisms of metabolic dynamical processes. They are necessary to enable the quantitative and qualitative analysis of the cellular catalytic reactions and also to help comprehend the conditions under which the structural dynamical phenomena and biological rhythms arise. Understanding the molecular mechanisms responsible for the metabolic dissipative structures is crucial for unraveling the dynamics of cellular life. PMID:20957111

  20. Cellular Automata and the Humanities.

    ERIC Educational Resources Information Center

    Gallo, Ernest

    1994-01-01

    The use of cellular automata to analyze several pre-Socratic hypotheses about the evolution of the physical world is discussed. These hypotheses combine characteristics of both rigorous and metaphoric language. Since the computer demands explicit instructions for each step in the evolution of the automaton, such models can reveal conceptual…

  1. Gene regulatory networks and the underlying biology of developmental toxicity

    EPA Science Inventory

    Embryonic cells are specified by large-scale networks of functionally linked regulatory genes. Knowledge of the relevant gene regulatory networks is essential for understanding phenotypic heterogeneity that emerges from disruption of molecular functions, cellular processes or sig...

  2. Optofluidic Detection for Cellular Phenotyping

    PubMed Central

    Tung, Yi-Chung; Huang, Nien-Tsu; Oh, Bo-Ram; Patra, Bishnubrata; Pan, Chi-Chun; Qiu, Teng; Paul, K. Chu; Zhang, Wenjun; Kurabayashi, Katsuo

    2012-01-01

    Quantitative analysis of the output of processes and molecular interactions within a single cell is highly critical to the advancement of accurate disease screening and personalized medicine. Optical detection is one of the most broadly adapted measurement methods in biological and clinical assays and serves cellular phenotyping. Recently, microfluidics has obtained increasing attention due to several advantages, such as small sample and reagent volumes, very high throughput, and accurate flow control in the spatial and temporal domains. Optofluidics, which is the attempt to integrate optics with microfluidic, shows great promise to enable on-chip phenotypic measurements with high precision, sensitivity, specificity, and simplicity. This paper reviews the most recent developments of optofluidic technologies for cellular phenotyping optical detection. PMID:22854915

  3. Hox Targets and Cellular Functions

    PubMed Central

    Sánchez-Herrero, Ernesto

    2013-01-01

    Hox genes are a group of genes that specify structures along the anteroposterior axis in bilaterians. Although in many cases they do so by modifying a homologous structure with a different (or no) Hox input, there are also examples of Hox genes constructing new organs with no homology in other regions of the body. Hox genes determine structures though the regulation of targets implementing cellular functions and by coordinating cell behavior. The genetic organization to construct or modify a certain organ involves both a genetic cascade through intermediate transcription factors and a direct regulation of targets carrying out cellular functions. In this review I discuss new data from genome-wide techniques, as well as previous genetic and developmental information, to describe some examples of Hox regulation of different cell functions. I also discuss the organization of genetic cascades leading to the development of new organs, mainly using Drosophila melanogaster as the model to analyze Hox function. PMID:24490109

  4. Cellular solidification of transparent monotectics

    NASA Technical Reports Server (NTRS)

    Kaulker, W. F.

    1986-01-01

    Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

  5. Cellular tagging as a neural network mechanism for behavioural tagging

    PubMed Central

    Nomoto, Masanori; Ohkawa, Noriaki; Nishizono, Hirofumi; Yokose, Jun; Suzuki, Akinobu; Matsuo, Mina; Tsujimura, Shuhei; Takahashi, Yukari; Nagase, Masashi; Watabe, Ayako M.; Kato, Fusao; Inokuchi, Kaoru

    2016-01-01

    Behavioural tagging is the transformation of a short-term memory, induced by a weak experience, into a long-term memory (LTM) due to the temporal association with a novel experience. The mechanism by which neuronal ensembles, each carrying a memory engram of one of the experiences, interact to achieve behavioural tagging is unknown. Here we show that retrieval of a LTM formed by behavioural tagging of a weak experience depends on the degree of overlap with the neuronal ensemble corresponding to a novel experience. The numbers of neurons activated by weak training in a novel object recognition (NOR) task and by a novel context exploration (NCE) task, denoted as overlapping neurons, increases in the hippocampal CA1 when behavioural tagging is successfully achieved. Optical silencing of an NCE-related ensemble suppresses NOR–LTM retrieval. Thus, a population of cells recruited by NOR is tagged and then preferentially incorporated into the memory trace for NCE to achieve behavioural tagging. PMID:27477539

  6. Method for analyzing signaling networks in complex cellular systems.

    PubMed

    Plavec, Ivan; Sirenko, Oksana; Privat, Sylvie; Wang, Yuker; Dajee, Maya; Melrose, Jennifer; Nakao, Brian; Hytopoulos, Evangelos; Berg, Ellen L; Butcher, Eugene C

    2004-02-01

    Now that the human genome has been sequenced, the challenge of assigning function to human genes has become acute. Existing approaches using microarrays or proteomics frequently generate very large volumes of data not directly related to biological function, making interpretation difficult. Here, we describe a technique for integrative systems biology in which: (i) primary cells are cultured under biologically meaningful conditions; (ii) a limited number of biologically meaningful readouts are measured; and (iii) the results obtained under several different conditions are combined for analysis. Studies of human endothelial cells overexpressing different signaling molecules under multiple inflammatory conditions show that this system can capture a remarkable range of functions by a relatively small number of simple measurements. In particular, measurement of seven different protein levels by ELISA under four different conditions is capable of reconstructing pathway associations of 25 different proteins representing four known signaling pathways, implicating additional participants in the NF-kappaBorRAS/mitogen-activated protein kinase pathways and defining additional interactions between these pathways. PMID:14745015

  7. Method for analyzing signaling networks in complex cellular systems

    PubMed Central

    Plavec, Ivan; Sirenko, Oksana; Privat, Sylvie; Wang, Yuker; Dajee, Maya; Melrose, Jennifer; Nakao, Brian; Hytopoulos, Evangelos; Berg, Ellen L.; Butcher, Eugene C.

    2004-01-01

    Now that the human genome has been sequenced, the challenge of assigning function to human genes has become acute. Existing approaches using microarrays or proteomics frequently generate very large volumes of data not directly related to biological function, making interpretation difficult. Here, we describe a technique for integrative systems biology in which: (i) primary cells are cultured under biologically meaningful conditions; (ii) a limited number of biologically meaningful readouts are measured; and (iii) the results obtained under several different conditions are combined for analysis. Studies of human endothelial cells overexpressing different signaling molecules under multiple inflammatory conditions show that this system can capture a remarkable range of functions by a relatively small number of simple measurements. In particular, measurement of seven different protein levels by ELISA under four different conditions is capable of reconstructing pathway associations of 25 different proteins representing four known signaling pathways, implicating additional participants in the NF-κBorRAS/mitogen-activated protein kinase pathways and defining additional interactions between these pathways. PMID:14745015

  8. Cellular networks controlling Th2 polarization in allergy and immunity.

    PubMed

    Kool, Mirjam; Hammad, Hamida; Lambrecht, Bart N

    2012-01-01

    In contrast to the development of Th1 (type 1 T helper cells), Th17 and Treg (regulatory T cells), little is known of the mechanisms governing Th2 development, which is important for immunity to helminths and for us to understand the pathogenesis of allergy. A picture is emerging in which mucosal epithelial cells instruct dendritic cells to promote Th2 responses in the absence of IL-12 (interleukin 12) production and provide instruction through thymic stromal lymphopoieitin (TSLP) or granulocyte-macrophage colony stimulating factor (GM-CSF). At the same time, allergens, helminths and chemical adjuvants elicit the response of innate immune cells like basophils, which provide more polarizing cytokines and IL-4 and reinforce Th2 immunity. This unique communication between cells will only be fully appreciated if we study Th2 immunity in vivo and in a tissue-specific context, and can only be fully understood if we compare several models of Th2 immune response induction. PMID:22403589

  9. Xtoys: Cellular automata on xwindows

    SciTech Connect

    Creutz, M.

    1995-08-15

    Xtoys is a collection of xwindow programs for demonstrating simulations of various statistical models. Included are xising, for the two dimensional Ising model, xpotts, for the q-state Potts model, xautomalab, for a fairly general class of totalistic cellular automata, xsand, for the Bak-Tang-Wiesenfield model of self organized criticality, and xfires, a simple forest fire simulation. The programs should compile on any machine supporting xwindows.

  10. Competitive potential of cellular mobile telecommunications

    SciTech Connect

    Ware, H.

    1983-02-03

    The Federal Communications Commission (FCC) has recently issued rules for the commercial operation of a telecommunications technology not previously in commercial use: the cellular mobile radio. The author has carefully considered the potential for competition between cellular systems and for competition between cellular radio and alternative communications technologies under the regulatory scheme which has been adopted by the FCC. He finds that competition between cellular and wire-line services can be viable if cellular cost and demand data are carefully tracked to avoid market congestion and if cellular or other techniques are not allowed to undercut selected local exchange rates.

  11. Cellular automata simulation of traffic including cars and bicycles

    NASA Astrophysics Data System (ADS)

    Vasic, Jelena; Ruskin, Heather J.

    2012-04-01

    As 'greening' of all aspects of human activity becomes mainstream, transportation science is also increasingly focused around sustainability. Modal co-existence between motorised and non-motorised traffic on urban networks is, in this context, of particular interest for traffic flow modelling. The main modelling problems here are posed by the heterogeneity of vehicles, including size and dynamics, and by the complex interactions at intersections. Herein we address these with a novel technique, based on one-dimensional cellular automata components, for modelling network infrastructure and its occupancy by vehicles. We use this modelling approach, together with a corresponding vehicle behaviour model, to simulate combined car and bicycle traffic for two elemental scenarios-examples of components that would be used in the building of an arbitrary network. Results of simulations performed on these scenarios, (i) a stretch of road and (ii) an intersection causing conflict between cars and bicycles sharing a lane, are presented and analysed.

  12. Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities.

    PubMed

    Chen, Sisi; Bremer, Andrew W; Scheideler, Olivia J; Na, Yun Suk; Todhunter, Michael E; Hsiao, Sonny; Bomdica, Prithvi R; Maharbiz, Michel M; Gartner, Zev J; Schaffer, David V

    2016-01-01

    Recreating heterotypic cell-cell interactions in vitro is key to dissecting the role of cellular communication during a variety of biological processes. This is especially relevant for stem cell niches, where neighbouring cells provide instructive inputs that govern cell fate decisions. To investigate the logic and dynamics of cell-cell signalling networks, we prepared heterotypic cell-cell interaction arrays using DNA-programmed adhesion. Our platform specifies the number and initial position of up to four distinct cell types within each array and offers tunable control over cell-contact time during long-term culture. Here, we use the platform to study the dynamics of single adult neural stem cell fate decisions in response to competing juxtacrine signals. Our results suggest a potential signalling hierarchy between Delta-like 1 and ephrin-B2 ligands, as neural stem cells adopt the Delta-like 1 phenotype of stem cell maintenance on simultaneous presentation of both signals. PMID:26754526

  13. Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities

    PubMed Central

    Chen, Sisi; Bremer, Andrew W.; Scheideler, Olivia J.; Na, Yun Suk; Todhunter, Michael E.; Hsiao, Sonny; Bomdica, Prithvi R.; Maharbiz, Michel M.; Gartner, Zev J.; Schaffer, David V.

    2016-01-01

    Recreating heterotypic cell–cell interactions in vitro is key to dissecting the role of cellular communication during a variety of biological processes. This is especially relevant for stem cell niches, where neighbouring cells provide instructive inputs that govern cell fate decisions. To investigate the logic and dynamics of cell–cell signalling networks, we prepared heterotypic cell–cell interaction arrays using DNA-programmed adhesion. Our platform specifies the number and initial position of up to four distinct cell types within each array and offers tunable control over cell-contact time during long-term culture. Here, we use the platform to study the dynamics of single adult neural stem cell fate decisions in response to competing juxtacrine signals. Our results suggest a potential signalling hierarchy between Delta-like 1 and ephrin-B2 ligands, as neural stem cells adopt the Delta-like 1 phenotype of stem cell maintenance on simultaneous presentation of both signals. PMID:26754526

  14. Cellular proliferation, cellular viability, and biocompatibility of HA-ZnO composites.

    PubMed

    Saha, Naresh; Dubey, Ashutosh K; Basu, Bikramjit

    2012-01-01

    One of the important issues in the development of hydroxyapatite (HA)-based biomaterials is the prosthetic infection, which limits wider use of monolithic HA despite superior cellular response. Recently, we reported that ZnO addition to HA can induce bactericidal property. It is therefore important to assess how ZnO addition influences the cytotoxicity property and cell adhesion/proliferation on HA-ZnO composite surfaces in vitro. In the above perspective, the objective of this study is to investigate the cell type and material composition dependent cellular proliferation and viability of pressureless sintered HA-ZnO composites. The combination of cell viability data as well as morphological observations of cultured human osteoblast-like SaOS2 cells and mouse fibroblast L929 cells suggests that HA-ZnO composites containing 10 Wt % or lower ZnO exhibit the ability to support cell adhesion and proliferation. Both SaOS2 and L929 cells exhibit extensive multidirectional network of actin cytoskeleton and cell flattening on the lower ZnO containing (≤10 Wt %) HA-ZnO composites. The in vitro results illustrate how variation in ZnO content can influence significantly the cell vitality, as evaluated using MTT biochemical assay. Also, the critical statistical analysis reveals that ZnO addition needs to be carefully tailored to ensure good in vitro cytocompatibility. The underlying reasons for difference in biological properties are analyzed. It is suggested that surface wettability as well as dissolution of ZnO, both contribute to the observed differences in cellular viability and proliferation. PMID:22102555

  15. The Social Side of Information Networking.

    ERIC Educational Resources Information Center

    Katz, James E.

    1997-01-01

    Explores the social issues, including manners, security, crime (fraud), and social control associated with information networking, with emphasis on the Internet. Also addresses the influence of cellular phones, the Internet and other information technologies on society. (GR)

  16. Cellular mechanotransduction: putting all the pieces together again.

    PubMed

    Ingber, Donald E

    2006-05-01

    Analysis of cellular mechanotransduction, the mechanism by which cells convert mechanical signals into biochemical responses, has focused on identification of critical mechanosensitive molecules and cellular components. Stretch-activated ion channels, caveolae, integrins, cadherins, growth factor receptors, myosin motors, cytoskeletal filaments, nuclei, extracellular matrix, and numerous other structures and signaling molecules have all been shown to contribute to the mechanotransduction response. However, little is known about how these different molecules function within the structural context of living cells, tissues, and organs to produce the orchestrated cellular behaviors required for mechanosensation, embryogenesis, and physiological control. Recent work from a wide range of fields reveals that organ, tissue, and cell anatomy are as important for mechanotransduction as individual mechanosensitive proteins and that our bodies use structural hierarchies (systems within systems) composed of interconnected networks that span from the macroscale to the nanoscale in order to focus stresses on specific mechanotransducer molecules. The presence of isometric tension (prestress) at all levels of these multiscale networks ensures that various molecular scale mechanochemical transduction mechanisms proceed simultaneously and produce a concerted response. Future research in this area will therefore require analysis, understanding, and modeling of tensionally integrated (tensegrity) systems of mechanochemical control. PMID:16675838

  17. Network Medicine: A Network-based Approach to Human Diseases

    NASA Astrophysics Data System (ADS)

    Ghiassian, Susan Dina

    With the availability of large-scale data, it is now possible to systematically study the underlying interaction maps of many complex systems in multiple disciplines. Statistical physics has a long and successful history in modeling and characterizing systems with a large number of interacting individuals. Indeed, numerous approaches that were first developed in the context of statistical physics, such as the notion of random walks and diffusion processes, have been applied successfully to study and characterize complex systems in the context of network science. Based on these tools, network science has made important contributions to our understanding of many real-world, self-organizing systems, for example in computer science, sociology and economics. Biological systems are no exception. Indeed, recent studies reflect the necessity of applying statistical and network-based approaches in order to understand complex biological systems, such as cells. In these approaches, a cell is viewed as a complex network consisting of interactions among cellular components, such as genes and proteins. Given the cellular network as a platform, machinery, functionality and failure of a cell can be studied with network-based approaches, a field known as systems biology. Here, we apply network-based approaches to explore human diseases and their associated genes within the cellular network. This dissertation is divided in three parts: (i) A systematic analysis of the connectivity patterns among disease proteins within the cellular network. The quantification of these patterns inspires the design of an algorithm which predicts a disease-specific subnetwork containing yet unknown disease associated proteins. (ii) We apply the introduced algorithm to explore the common underlying mechanism of many complex diseases. We detect a subnetwork from which inflammatory processes initiate and result in many autoimmune diseases. (iii) The last chapter of this dissertation describes the

  18. Feed-forward regulation ensures stability and rapid reversibility of a cellular state

    PubMed Central

    Doncic, Andreas; Skotheim, Jan M.

    2013-01-01

    Cellular transitions are important for all life. Such transitions, including cell fate decisions, often employ positive feedback regulation to establish and stabilize new cellular states. However, positive feedback is unlikely to underlie stable cell cycle arrest in yeast exposed to mating pheromone because the signaling pathway is linear, rather than bistable, over a broad range of extracellular pheromone concentration. We show that the stability of the pheromone arrested state results from coherent feed-forward regulation of the cell cycle inhibitor Far1. This network motif is effectively isolated from the more complex regulatory network in which it is embedded. Fast regulation of Far1 by phosphorylation allows rapid cell cycle arrest and reentry, whereas slow Far1 synthesis reinforces arrest. We thus expect coherent feed-forward regulation to be frequently implemented at reversible cellular transitions because this network motif can achieve the ostensibly conflicting aims of arrest stability and rapid reversibility without loss of signaling information. PMID:23685071

  19. Cellular immune responses to HIV

    NASA Astrophysics Data System (ADS)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  20. Quantum cellular automata without particles

    NASA Astrophysics Data System (ADS)

    Meyer, David A.; Shakeel, Asif

    2016-01-01

    Quantum cellular automata (QCA) constitute space and time homogeneous discrete models for quantum field theories (QFTs). Although QFTs are defined without reference to particles, computations are done in terms of Feynman diagrams, which are explicitly interpreted in terms of interacting particles. Similarly, the easiest QCA to construct are quantum lattice gas automata (QLGA). A natural question then is, which QCA are not QLGA? Here we construct a nontrivial example of such a QCA; it provides a simple model in 1 +1 dimensions with no particle interpretation at the scale where the QCA dynamics are homogeneous.

  1. Universal map for cellular automata

    NASA Astrophysics Data System (ADS)

    García-Morales, V.

    2012-08-01

    A universal map is derived for all deterministic 1D cellular automata (CAs) containing no freely adjustable parameters and valid for any alphabet size and any neighborhood range (including non-symmetrical neighborhoods). The map can be extended to an arbitrary number of dimensions and topologies and to arbitrary order in time. Specific CA maps for the famous Conway's Game of Life and Wolfram's 256 elementary CAs are given. An induction method for CAs, based in the universal map, allows mathematical expressions for the orbits of a wide variety of elementary CAs to be systematically derived.

  2. Therapeutic cloning and cellular reprogramming.

    PubMed

    Rodriguez, Ramon M; Ross, Pablo J; Cibelli, Jose B

    2012-01-01

    Embryonic stem cells are capable of differentiating into any cell-type present in an adult organism, and constitute a renewable source of tissue for regenerative therapies. The transplant of allogenic stem cells is challenging due to the risk of immune rejection. Nevertheless, somatic cell reprogramming techniques allow the generation of isogenic embryonic stem cells, genetically identical to the patient. In this chapter we will discuss the cellular reprogramming techniques in the context of regenerative therapy and the biological and technical barriers that they will need to overcome before clinical use. PMID:22457116

  3. Symmetry analysis of cellular automata

    NASA Astrophysics Data System (ADS)

    García-Morales, V.

    2013-01-01

    By means of B-calculus [V. García-Morales, Phys. Lett. A 376 (2012) 2645] a universal map for deterministic cellular automata (CAs) has been derived. The latter is shown here to be invariant upon certain transformations (global complementation, reflection and shift). When constructing CA rules in terms of rules of lower range a new symmetry, “invariance under construction” is uncovered. Modular arithmetic is also reformulated within B-calculus and a new symmetry of certain totalistic CA rules, which calculate the Pascal simplices modulo an integer number p, is then also uncovered.

  4. Primitive control of cellular metabolism

    NASA Technical Reports Server (NTRS)

    Mitz, M. A.

    1974-01-01

    It is pointed out that control substances must have existed from the earliest times in the evolution of life and that the same control mechanisms must exist today. The investigation reported is concerned with the concept that carbon dioxide is a primitive regulator of cell function. The effects of carbon dioxide on cellular materials are examined, taking into account questions of solubilization, dissociation, changes of charge, stabilization, structural changes, wettability, the exclusion of other gases, the activation of compounds, changes in plasticity, and changes in membrane permeability.

  5. The Cellular Basis of Aging

    PubMed Central

    Scoggin, Charles H.

    1981-01-01

    Normal cells have only a finite life span before they die. The process known as aging may occur as a result of continued damage to the cell or as a result of expression of predetermined information within the genetic structure of the cell. Both processes lead to progressive cellular dysfunction which is evidenced by the organs of the body as aging. By understanding how individual cells age we will gain insight into how the body as a whole ages. The impact of such knowledge on science and society is a matter of both conjecture and concern. PMID:7336718

  6. Mitochondrial Variability as a Source of Extrinsic Cellular Noise

    PubMed Central

    Johnston, Iain G.; Gaal, Bernadett; Neves, Ricardo Pires das; Enver, Tariq; Iborra, Francisco J.; Jones, Nick S.

    2012-01-01

    We present a study investigating the role of mitochondrial variability in generating noise in eukaryotic cells. Noise in cellular physiology plays an important role in many fundamental cellular processes, including transcription, translation, stem cell differentiation and response to medication, but the specific random influences that affect these processes have yet to be clearly elucidated. Here we present a mechanism by which variability in mitochondrial volume and functionality, along with cell cycle dynamics, is linked to variability in transcription rate and hence has a profound effect on downstream cellular processes. Our model mechanism is supported by an appreciable volume of recent experimental evidence, and we present the results of several new experiments with which our model is also consistent. We find that noise due to mitochondrial variability can sometimes dominate over other extrinsic noise sources (such as cell cycle asynchronicity) and can significantly affect large-scale observable properties such as cell cycle length and gene expression levels. We also explore two recent regulatory network-based models for stem cell differentiation, and find that extrinsic noise in transcription rate causes appreciable variability in the behaviour of these model systems. These results suggest that mitochondrial and transcriptional variability may be an important mechanism influencing a large variety of cellular processes and properties. PMID:22412363

  7. Return of the Quantum Cellular Automata: Episode VI

    NASA Astrophysics Data System (ADS)

    Carr, Lincoln D.; Hillberry, Logan E.; Rall, Patrick; Halpern, Nicole Yunger; Bao, Ning; Montangero, Simone

    2016-05-01

    There are now over 150 quantum simulators or analog quantum computers worldwide. Although exploring quantum phase transitions, many-body localization, and the generalized Gibbs ensemble are exciting and worthwhile endeavors, there are totally untapped directions we have not yet pursued. One of these is quantum cellular automata. In the past a principal goal of quantum cellular automata was to reproduce continuum single particle quantum physics such as the Schrodinger or Dirac equation from simple rule sets. Now that we begin to really understand entanglement and many-body quantum physics at a deeper level, quantum cellular automata present new possibilities. We explore several time evolution schemes on simple spin chains leading to high degrees of quantum complexity and nontrivial quantum dynamics. We explain how the 256 known classical elementary cellular automata reduce to just a few exciting quantum cases. Our analysis tools include mutual information based complex networks as well as more familiar quantifiers like sound speed and diffusion rate. Funded by NSF and AFOSR.

  8. Protein accounting in the cellular economy

    PubMed Central

    Vázquez-Laslop, Nora; Mankin, Alexander S.

    2014-01-01

    Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. (2014) gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the needs. PMID:24766801

  9. Protein accounting in the cellular economy.

    PubMed

    Vázquez-Laslop, Nora; Mankin, Alexander S

    2014-04-24

    Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the functional needs. PMID:24766801

  10. Modeling the topological organization of cellular processes.

    PubMed

    Giavitto, Jean-Louis; Michel, Olivier

    2003-07-01

    The cell as a dynamical system presents the characteristics of having a dynamical structure. That is, the exact phase space of the system cannot be fixed before the evolution and integrative cell models must state the evolution of the structure jointly with the evolution of the cell state. This kind of dynamical systems is very challenging to model and simulate. New programming concepts must be developed to ease their modeling and simulation. In this context, the goal of the MGS project is to develop an experimental programming language dedicated to the simulation of this kind of systems. MGS proposes a unified view on several computational mechanisms (CHAM, Lindenmayer systems, Paun systems, cellular automata) enabling the specification of spatially localized computations on heterogeneous entities. The evolution of a dynamical structure is handled through the concept of transformation which relies on the topological organization of the system components. An example based on the modeling of spatially distributed biochemical networks is used to illustrate how these notions can be used to model the spatial and temporal organization of intracellular processes. PMID:12915272

  11. Cellular pathways controlling integron cassette site folding.

    PubMed

    Loot, Céline; Bikard, David; Rachlin, Anna; Mazel, Didier

    2010-08-01

    By mobilizing small DNA units, integrons have a major function in the dissemination of antibiotic resistance among bacteria. The acquisition of gene cassettes occurs by recombination between the attI and attC sites catalysed by the IntI1 integron integrase. These recombination reactions use an unconventional mechanism involving a folded single-stranded attC site. We show that cellular bacterial processes delivering ssDNA, such as conjugation and replication, favour proper folding of the attC site. By developing a very sensitive in vivo assay, we also provide evidence that attC sites can recombine as cruciform structures by extrusion from double-stranded DNA. Moreover, we show an influence of DNA superhelicity on attC site extrusion in vitro and in vivo. We show that the proper folding of the attC site depends on both the propensity to form non-recombinogenic structures and the length of their variable terminal structures. These results draw the network of cell processes that regulate integron recombination. PMID:20628355

  12. Cellular functions of programmed cell death 5.

    PubMed

    Li, Ge; Ma, Dalong; Chen, Yingyu

    2016-04-01

    Programmed cell death 5 (PDCD5) was originally identified as an apoptosis-accelerating protein that is widely expressed and has been well conserved during the process of evolution. PDCD5 has complex biological functions, including programmed cell death and immune regulation. It can accelerate apoptosis in different type of cells in response to different stimuli. During this process, PDCD5 rapidly translocates from the cytoplasm to the nucleus. PDCD5 regulates the activities of TIP60, HDAC3, MDM2 and TP53 transcription factors. These proteins form part of a signaling network that is disrupted in most, if not all, cancer cells. Recent evidence suggests that PDCD5 participates in immune regulation by promoting regulatory T cell function via the PDCD5-TIP60-FOXP3 pathway. The stability and expression of PDCD5 are finely regulated by other molecules, such as NF-κB p65, OTUD5, YAF2 and DNAJB1. PDCD5 is phosphorylated by CK2 at Ser119, which is required for nuclear translocation in response to genotoxic stress. In this review, we describe what is known about PDCD5 and its cellular functions. PMID:26775586

  13. Myosin VI: cellular functions and motor properties.

    PubMed Central

    Roberts, Rhys; Lister, Ida; Schmitz, Stephan; Walker, Matthew; Veigel, Claudia; Trinick, John; Buss, Folma; Kendrick-Jones, John

    2004-01-01

    Myosin VI has been localized in membrane ruffles at the leading edge of cells, at the trans-Golgi network compartment of the Golgi complex and in clathrin-coated pits or vesicles, indicating that it functions in a wide variety of intracellular processes. Myosin VI moves along actin filaments towards their minus end, which is the opposite direction to all of the other myosins so far studied (to our knowledge), and is therefore thought to have unique properties and functions. To investigate the cellular roles of myosin VI, we identified various myosin VI binding partners and are currently characterizing their interactions within the cell. As an alternative approach, we have expressed and purified full-length myosin VI and studied its in vitro properties. Previous studies assumed that myosin VI was a dimer, but our biochemical, biophysical and electron microscopic studies reveal that myosin VI can exist as a stable monomer. We observed, using an optical tweezers force transducer, that monomeric myosin VI is a non-processive motor which, despite a relatively short lever arm, generates a large working stroke of 18 nm. Whether monomer and/or dimer forms of myosin VI exist in cells and their possible functions will be discussed. PMID:15647169

  14. Cellular and molecular mechanisms in liver fibrogenesis.

    PubMed

    Novo, Erica; Cannito, Stefania; Paternostro, Claudia; Bocca, Claudia; Miglietta, Antonella; Parola, Maurizio

    2014-04-15

    Liver fibrogenesis is a dynamic and highly integrated molecular, tissue and cellular process, potentially reversible, that drives the progression of chronic liver diseases (CLD) towards liver cirrhosis and hepatic failure. Hepatic myofibroblasts (MFs), the pro-fibrogenic effector cells, originate mainly from activation of hepatic stellate cells and portal fibroblasts being characterized by a proliferative and survival attitude. MFs also contract in response to vasoactive agents, sustain angiogenesis and recruit and modulate activity of cells of innate or adaptive immunity. Chronic activation of wound healing and oxidative stress as well as derangement of epithelial-mesenchymal interactions are "major" pro-fibrogenic mechanisms, whatever the etiology. However, literature has outlined a complex network of pro-fibrogenic factors and mediators proposed to modulate CLD progression, with some of them being at present highly debated in the field, including the role of epithelial to mesenchymal transition and Hedgehog signaling pathways. Hypoxia and angiogenesis as well as inflammasomes are recently emerged as ubiquitous pro-inflammatory and pro-fibrogenic determinants whereas adipokines are mostly involved in CLD related to metabolic disturbances (metabolic syndrome and/or obesity and type 2 diabetes). Finally, autophagy as well as natural killer and natural killer-T cells have been recently proposed to significantly affect fibrogenic CLD progression. PMID:24631571

  15. Cellular senescence and protein degradation

    PubMed Central

    Deschênes-Simard, Xavier; Lessard, Frédéric; Gaumont-Leclerc, Marie-France; Bardeesy, Nabeel; Ferbeyre, Gerardo

    2014-01-01

    Autophagy and the ubiquitin–proteasome pathway (UPP) are the major protein degradation systems in eukaryotic cells. Whereas the former mediate a bulk nonspecific degradation, the UPP allows a rapid degradation of specific proteins. Both systems have been shown to play a role in tumorigenesis, and the interest in developing therapeutic agents inhibiting protein degradation is steadily growing. However, emerging data point to a critical role for autophagy in cellular senescence, an established tumor suppressor mechanism. Recently, a selective protein degradation process mediated by the UPP was also shown to contribute to the senescence phenotype. This process is tightly regulated by E3 ubiquitin ligases, deubiquitinases, and several post-translational modifications of target proteins. Illustrating the complexity of UPP, more than 600 human genes have been shown to encode E3 ubiquitin ligases, a number which exceeds that of the protein kinases. Nevertheless, our knowledge of proteasome-dependent protein degradation as a regulated process in cellular contexts such as cancer and senescence remains very limited. Here we discuss the implications of protein degradation in senescence and attempt to relate this function to the protein degradation pattern observed in cancer cells. PMID:24866342

  16. Collective specification of cellular development.

    PubMed

    Sachs, Tsvi

    2003-09-01

    Studies of chimeras and in vivo development demonstrate that cell lineages are often quite variable, apparently in response to chance perturbations. This points to an apparent contradiction: although individual cells are the units of genetic information and differentiation, not all cellular events need be precise for the development of functional organisms. The social organization of ants can serve as a metaphor that helps understand the mechanisms that underlie such development. Ants suggest that continued cellular interactions and environmental conditions could specify the proportion and general location of specialized units. Leaf venation is used as a concrete example of this general principle. A signal produced continuously by all cells specifies a requirement for vein differentiation. The cells that respond by differentiation then transport the signal away from the leaf; this removal acting as a feedback indicating that the requirement is being met. Because transport increases during vein differentiation, early initiation occurs in excess and vein 'competition' for the signal assures an acceptable outcome. Such specification would be robust since it does not depend on events in any single cell, and chance events, rather than being corrected or reversed, may be built upon in reaching an expected, collective phenotype. The absence of detailed information preceding development distinguishes this hypothesis from the common alternatives of a program or blueprint. Collective specification would have important implications for developmental plasticity and evolution. PMID:12938179

  17. Cellular uptake of metallated cobalamins.

    PubMed

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry; Gammelgaard, Bente; Furger, Evelyne; Alberto, Roger

    2016-03-16

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives including [Cbl-OH2](+), [{Co}-CN-{cis-PtCl(NH3)2}](+), [{Re}-{Co}-CN-{cis-PtCl(NH3)2}](+), and [{Co}-CN-{trans-Pt(Cyt)(NH3)2}](2+) (Cyt = cytarabin) was high compared to neutral B12, which implied the existence of an additional internalization pathway for charged B12 vitamin analogs. The affinities of the charged B12 derivatives to the B12 transporters HC, IF and TC were similar to that of native vitamin B12. PMID:26739575

  18. Cellular Therapy for Heart Failure.

    PubMed

    Psaltis, Peter J; Schwarz, Nisha; Toledo-Flores, Deborah; Nicholls, Stephen J

    2016-01-01

    The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management. PMID:27280304

  19. CELLULAR PATHOGENESIS OF DIABETIC GASTROENTEROPATHY

    PubMed Central

    Ördög, Tamás; Hayashi, Yujiro; Gibbons, Simon J.

    2010-01-01

    SUMMARY Gastroenteropathy manifesting in upper gastrointestinal symptoms, delayed gastric emptying, constipation, diarrhea and fecal incontinence occurs frequently in patients with diabetes mellitus and represents a significant health care burden. Current treatments are largely symptomatic and ineffective. Better understanding of the cellular and molecular pathogenesis of these disorders is required for the development of more effective therapies. Recent advances in our understanding of the inherent, high-level complexities of the control systems that execute and regulate gastrointestinal motility, together with the utilization of new experimental models and sophisticated physiological, morphological and molecular techniques have lead to the realization that diabetic gastroenteropathies cannot be ascribed to any singular defect or dysfunction. In fact, these disorders are multifactorial and involve a spectrum of metabolic and dystrophic changes that can potentially affect all key components of motor control including the systemic autonomic and enteric nervous systems, interstitial cells of Cajal and smooth muscle cells. Candidate pathomechanisms are also varied and include imbalance between pro- and anti-oxidative factors, altered trophic stimuli to mature cells and their progenitors, and, possibly, autoimmune factors. The goal of this paper is to review the cellular changes underlying diabetic gastroenteropathies and their potential causes, with particular focus on functional interactions between various cell types. It is proposed that diabetic gastroenteropathies should be considered a form of gastrointestinal neuromuscular dystrophy rather than a “functional” disorder. Future research should identify ways to block cytotoxic factors, support the regeneration of damaged cells and translate the experimental findings into new treatment modalities. PMID:19829287

  20. Cellular Biology of Prion Diseases

    PubMed Central

    Harris, David A.

    1999-01-01

    Prion diseases are fatal neurodegenerative disorders of humans and animals that are important because of their impact on public health and because they exemplify a novel mechanism of infectivity and biological information transfer. These diseases are caused by conformational conversion of a normal host glycoprotein (PrPC) into an infectious isoform (PrPSc) that is devoid of nucleic acid. This review focuses on the current understanding of prion diseases at the cell biological level. The characteristics of the diseases are introduced, and a brief history and description of the prion hypothesis are given. Information is then presented about the structure, expression, biosynthesis, and possible function of PrPC, as well as its posttranslational processing, cellular localization, and trafficking. The latest findings concerning PrPSc are then discussed, including cell culture systems used to generate this pathogenic isoform, the subcellular distribution of the protein, its membrane attachment, proteolytic processing, and its kinetics and sites of synthesis. Information is also provided on molecular models of the PrPC→PrPSc conversion reaction and the possible role of cellular chaperones. The review concludes with suggestions of several important avenues for future investigation. PMID:10398674

  1. Physical modeling of traffic with stochastic cellular automata

    SciTech Connect

    Schreckenberg, M.; Nagel, K. |

    1995-09-01

    A new type of probabilistic cellular automaton for the physical description of single and multilane traffic is presented. In this model space, time and the velocity of the cars are represented by integer numbers (as usual in cellular automata) with local update rules for the velocity. The model is very efficient for both numerical simulations and analytical investigations. The numerical results from extensive simulations reproduce very well data taken from real traffic (e.g. fundamental diagrams). Several analytical results for the model are presented as well as new approximation schemes for stationary traffic. In addition the relation to continuum hydrodynamic theory (Lighthill-Whitham) and the follow-the-leader models is discussed. The model is part of an interdisciplinary research program in Northrhine-Westfalia (``NRW Forschungsverbund Verkehrssimulation``) for the construction of a large scale microsimulation model for network traffic, supported by the government of NRW.

  2. Controlled cellular energy conversion in brown adipose tissue thermogenesis

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.; Plant, R. E.

    1978-01-01

    Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

  3. Cellular Phone Face Recognition System Based on Optical Phase Correlation

    NASA Astrophysics Data System (ADS)

    Watanabe, Eriko; Ishikawa, Sayuri; Ohta, Maiko; Kodate, Kashiko

    We propose a high security facial recognition system using a cellular phone on the mobile network. This system is composed of a face recognition engine based on optical phase correlation which uses phase information with emphasis on a Fourier domain, a control sever and the cellular phone with a compact camera for taking pictures, as a portable terminal. Compared with various correlation methods, our face recognition engine revealed the most accurate EER of less than 1%. By using the JAVA interface on this system, we implemented the stable system taking pictures, providing functions to prevent spoofing while transferring images. This recognition system was tested on 300 women students and the results proved this system effective.

  4. Complement-Mediated Regulation of Metabolism and Basic Cellular Processes.

    PubMed

    Hess, Christoph; Kemper, Claudia

    2016-08-16

    Complement is well appreciated as a critical arm of innate immunity. It is required for the removal of invading pathogens and works by directly destroying them through the activation of innate and adaptive immune cells. However, complement activation and function is not confined to the extracellular space but also occurs within cells. Recent work indicates that complement activation regulates key metabolic pathways and thus can impact fundamental cellular processes, such as survival, proliferation, and autophagy. Newly identified functions of complement include a key role in shaping metabolic reprogramming, which underlies T cell effector differentiation, and a role as a nexus for interactions with other effector systems, in particular the inflammasome and Notch transcription-factor networks. This review focuses on the contributions of complement to basic processes of the cell, in particular the integration of complement with cellular metabolism and the potential implications in infection and other disease settings. PMID:27533012

  5. Optical Tools to Investigate Cellular Activity in the Intestinal Wall

    PubMed Central

    Boesmans, Werend; Hao, Marlene M; Berghe, Pieter Vanden

    2015-01-01

    Live imaging has become an essential tool to investigate the coordinated activity and output of cellular networks. Within the last decade, 2 Nobel prizes have been awarded to recognize innovations in the field of imaging: one for the discovery, use, and optimization of the green fluorescent protein (2008) and the second for the development of super-resolved fluorescence microscopy (2014). New advances in both optogenetics and microscopy now enable researchers to record and manipulate activity from specific populations of cells with better contrast and resolution, at higher speeds, and deeper into live tissues. In this review, we will discuss some of the recent developments in microscope technology and in the synthesis of fluorescent probes, both synthetic and genetically encoded. We focus on how live imaging of cellular physiology has progressed our understanding of the control of gastrointestinal motility, and we discuss the hurdles to overcome in order to apply the novel tools in the field of neurogastroenterology and motility. PMID:26130630

  6. Regulation of cellular actin architecture by S100A10.

    PubMed

    Jung, M Juliane; Murzik, Ulrike; Wehder, Liane; Hemmerich, Peter; Melle, Christian

    2010-04-15

    Actin structures are involved in several biological processes and the disruption of actin polymerisation induces impaired motility of eukaryotic cells. Different factors are involved in regulation and maintenance of the cytoskeletal actin architecture. Here we show that S100A10 participates in the particular organisation of actin filaments. Down-regulation of S100A10 by specific siRNA triggered a disorganisation of filamentous actin structures without a reduction of the total cellular actin concentration. In contrast, the formation of cytoskeleton structures containing tubulin was unhindered in S100A10 depleted cells. Interestingly, the cellular distribution of annexin A2, an interaction partner of S100A10, was unaffected in S100A10 depleted cells. Cells lacking S100A10 showed an impaired migration activity and were unable to close a scratched wound. Our data provide first insights of S100A10 function as a regulator of the filamentous actin network. PMID:20100475

  7. Integrating Cellular Metabolism into a Multiscale Whole-Body Model

    PubMed Central

    Krauss, Markus; Schaller, Stephan; Borchers, Steffen; Findeisen, Rolf; Lippert, Jörg; Kuepfer, Lars

    2012-01-01

    Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development. PMID:23133351

  8. Neuronal network analyses: premises, promises and uncertainties

    PubMed Central

    Parker, David

    2010-01-01

    Neuronal networks assemble the cellular components needed for sensory, motor and cognitive functions. Any rational intervention in the nervous system will thus require an understanding of network function. Obtaining this understanding is widely considered to be one of the major tasks facing neuroscience today. Network analyses have been performed for some years in relatively simple systems. In addition to the direct insights these systems have provided, they also illustrate some of the difficulties of understanding network function. Nevertheless, in more complex systems (including human), claims are made that the cellular bases of behaviour are, or will shortly be, understood. While the discussion is necessarily limited, this issue will examine these claims and highlight some traditional and novel aspects of network analyses and their difficulties. This introduction discusses the criteria that need to be satisfied for network understanding, and how they relate to traditional and novel approaches being applied to addressing network function. PMID:20603354

  9. Active Contraction of Microtubule Networks

    NASA Astrophysics Data System (ADS)

    Foster, Peter; Fürthauer, Sebastian; Shelley, Michael; Needleman, Daniel

    Many cellular processes are driven by cytoskeletal assemblies. It remains unclear how cytoskeletal filaments and motor proteins organize into cellular scale structures and how molecular properties of cytoskeletal components affect the large scale behaviors of these systems. Here we investigate the self-organization of stabilized microtubules in Xenopus oocyte extracts and find that they can form macroscopic networks that spontaneously contract. We propose that these contractions are driven by the clustering of microtubule minus ends by dynein. Based on this idea, we construct an active fluid theory of network contractions which predicts a dependence of the timescale of contraction on initial network geometry, a development of density inhomogeneities during contraction, a constant final network density, and a strong influence of dynein inhibition on the rate of contraction, all in quantitative agreement with experiments. These results demonstrate that the motor-driven clustering of filament ends is a generic mechanism leading to contraction.

  10. Active contraction of microtubule networks.

    PubMed

    Foster, Peter J; Fürthauer, Sebastian; Shelley, Michael J; Needleman, Daniel J

    2015-01-01

    Many cellular processes are driven by cytoskeletal assemblies. It remains unclear how cytoskeletal filaments and motor proteins organize into cellular scale structures and how molecular properties of cytoskeletal components affect the large-scale behaviors of these systems. Here, we investigate the self-organization of stabilized microtubules in Xenopus oocyte extracts and find that they can form macroscopic networks that spontaneously contract. We propose that these contractions are driven by the clustering of microtubule minus ends by dynein. Based on this idea, we construct an active fluid theory of network contractions, which predicts a dependence of the timescale of contraction on initial network geometry, a development of density inhomogeneities during contraction, a constant final network density, and a strong influence of dynein inhibition on the rate of contraction, all in quantitative agreement with experiments. These results demonstrate that the motor-driven clustering of filament ends is a generic mechanism leading to contraction. PMID:26701905

  11. Cellular Host Responses to Gliomas

    PubMed Central

    Barish, Michael E.; Garcia, Elizabeth; Metz, Marianne Z.; Myers, Sarah M.; Gutova, Margarita; Frank, Richard T.; Miletic, Hrvoje; Kendall, Stephen E.; Glackin, Carlotta A.; Bjerkvig, Rolf; Aboody, Karen S.

    2012-01-01

    Background Glioblastoma multiforme (GBM) is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. Methodology/Principal Findings Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a ‘network’ with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a ‘pair-wise’ manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a) low-generation tumors (first in vivo passage in rats) were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b) high-generation xenografts (fifth passage) had pronounced cellularity, were angiogenic with ‘glomerulus-like’ microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. Conclusions/Significance Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  12. Cellular Foundations of Mammary Tubulogenesis

    PubMed Central

    Huebner, Robert J.; Ewald, Andrew J.

    2014-01-01

    The mammary gland is composed of a highly branched network of epithelial tubes, embedded within a complex stroma. The mammary epithelium originates during embryonic development from an epidermal placode. However, the majority of ductal elongation and bifurcation occurs postnatally, in response to steroid hormone and growth factor receptor signaling. The process of pubertal branching morphogenesis involves both elongation of the primary ducts across the length of the fat pad and a wave of secondary branching that elaborates the ductal network. Recent studies have revealed that mammary epithelial morphogenesis is accomplished by transitions between simple and stratified organization. During active morphogenesis, the epithelium is stratified, highly proliferative, has few intercellular junctions, and exhibits incomplete apico-basal polarity. In this review, we discuss recent advances in our understanding of the relationship between epithelial architecture, epithelial polarity, and ductal elongation. PMID:24747369

  13. Cellular reprogramming through mitogen-activated protein kinases

    PubMed Central

    Lee, Justin; Eschen-Lippold, Lennart; Lassowskat, Ines; Böttcher, Christoph; Scheel, Dierk

    2015-01-01

    Mitogen-activated protein kinase (MAPK) cascades are conserved eukaryote signaling modules where MAPKs, as the final kinases in the cascade, phosphorylate protein substrates to regulate cellular processes. While some progress in the identification of MAPK substrates has been made in plants, the knowledge on the spectrum of substrates and their mechanistic action is still fragmentary. In this focused review, we discuss the biological implications of the data in our original paper (Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana; Frontiers in Plant Science 5: 554) in the context of related research. In our work, we mimicked in vivo activation of two stress-activated MAPKs, MPK3 and MPK6, through transgenic manipulation of Arabidopsis thaliana and used phosphoproteomics analysis to identify potential novel MAPK substrates. Here, we plotted the identified putative MAPK substrates (and downstream phosphoproteins) as a global protein clustering network. Based on a highly stringent selection confidence level, the core networks highlighted a MAPK-induced cellular reprogramming at multiple levels of gene and protein expression—including transcriptional, post-transcriptional, translational, post-translational (such as protein modification, folding, and degradation) steps, and also protein re-compartmentalization. Additionally, the increase in putative substrates/phosphoproteins of energy metabolism and various secondary metabolite biosynthesis pathways coincides with the observed accumulation of defense antimicrobial substances as detected by metabolome analysis. Furthermore, detection of protein networks in phospholipid or redox elements suggests activation of downstream signaling events. Taken in context with other studies, MAPKs are key regulators that reprogram cellular events to orchestrate defense signaling in eukaryotes. PMID:26579181

  14. Thermomechanical characterisation of cellular rubber

    NASA Astrophysics Data System (ADS)

    Seibert, H.; Scheffer, T.; Diebels, S.

    2016-01-01

    This contribution discusses an experimental possibility to characterise a cellular rubber in terms of the influence of multiaxiality, rate dependency under environmental temperature and its behaviour under hydrostatic pressure. In this context, a mixed open and closed cell rubber based on an ethylene propylene diene monomer is investigated exemplarily. The present article intends to give a general idea of the characterisation method and the considerable effects of this special type of material. The main focus lies on the experimental procedure and the used testing devices in combination with the analysis methods such as true three-dimensional digital image correlation. The structural compressibility is taken into account by an approach for a material model using the Theory of Porous Media with additional temperature dependence.

  15. [Cellular pathology of neurodegenerative disorders].

    PubMed

    Wakabayashi, Koichi

    2013-01-01

    Common cellular and molecular mechanisms including protein aggregation and inclusion body formation are involved in many neurodegenerative diseases. α-Synuclein is a major component of Lewy bodies in Parkinson's disease (PD) as well as in glial cytoplasmic inclusions in multiple system atrophy (MSA). Tau is a principal component of neurofibrillary and glial tangles in tauopathies. Recently, TDP-43 was identified as a component of ubiquitinated inclusions in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. PD is traditionally considered a movement disorder with hallmark lesions in the brainstem pigmented nuclei. However, pathological changes occur in widespread regions of the central and peripheral nervous systems in this disease. Furthermore, primary glial involvement ("gliodegeneration") can be observed in PD and MSA as well as in tauopathy. The present article reviews abnormal protein accumulation and inclusion body formation inside and outside the central nervous system. PMID:23965852

  16. Regulation of cellular chromatin state

    PubMed Central

    Mishra, Rakesh K; Dhawan, Jyotsna

    2010-01-01

    The identity and functionality of eukaryotic cells is defined not just by their genomic sequence which remains constant between cell types, but by their gene expression profiles governed by epigenetic mechanisms. Epigenetic controls maintain and change the chromatin state throughout development, as exemplified by the setting up of cellular memory for the regulation and maintenance of homeotic genes in proliferating progenitors during embryonic development. Higher order chromatin structure in reversibly arrested adult stem cells also involves epigenetic regulation and in this review we highlight common trends governing chromatin states, focusing on quiescence and differentiation during myogenesis. Together, these diverse developmental modules reveal the dynamic nature of chromatin regulation providing fresh insights into the role of epigenetic mechanisms in potentiating development and differentiation. PMID:20592864

  17. Cellular ageing mechanisms in osteoarthritis.

    PubMed

    Sacitharan, P K; Vincent, T L

    2016-08-01

    Age is the strongest independent risk factor for the development of osteoarthritis (OA) and for many years this was assumed to be due to repetitive microtrauma of the joint surface over time, the so-called 'wear and tear' arthritis. As our understanding of OA pathogenesis has become more refined, it has changed our appreciation of the role of ageing on disease. Cartilage breakdown in disease is not a passive process but one involving induction and activation of specific matrix-degrading enzymes; chondrocytes are exquisitely sensitive to changes in the mechanical, inflammatory and metabolic environment of the joint; cartilage is continuously adapting to these changes by altering its matrix. Ageing influences all of these processes. In this review, we will discuss how ageing affects tissue structure, joint use and the cellular metabolism. We describe what is known about pathways implicated in ageing in other model systems and discuss the potential value of targeting these pathways in OA. PMID:27215642

  18. Pressure-actuated cellular structures.

    PubMed

    Pagitz, M; Lamacchia, E; Hol, J M A M

    2012-03-01

    Shape changing structures will play an important role in future engineering designs since rigid structures are usually only optimal for a small range of service conditions. Hence, a concept for reliable and energy-efficient morphing structures that possess a large strength to self-weight ratio would be widely applicable. We propose a novel concept for morphing structures that is inspired by the nastic movement of plants. The idea is to connect prismatic cells with tailored pentagonal and/or hexagonal cross sections such that the resulting cellular structure morphs into given target shapes for certain cell pressures. An efficient algorithm for computing equilibrium shapes as well as cross-sectional geometries is presented. The potential of this novel concept is demonstrated by several examples that range from a flagellum like propulsion device to a morphing aircraft wing. PMID:22278936

  19. Force generation by cellular motors.

    PubMed

    Wanka, Friedrich; Van Zoelen, Everardus J J

    2003-01-01

    Cell motility processes in non-muscle cells depend on the activity of motor proteins that bind to either microtubules or actin filaments. From presently available data it must be concluded that the driving force is generated by transient interaction of the respective motors with microtubules or actin filaments which then activates the binding and hydrolysis of ATP. This reaction results in an abrupt discharge of the motor molecule, the direction of which is determined by the spatial orientation of its binding to the helical and polar vehicle. The latter is thereby propelled in its length direction and simultaneously undergoes an axial rotation, while the expelled motor exerts an oppositely directed current in the surrounding fluid, comparable to jet propulsion. Force production, propulsion velocities and energy requirements known from in vitro studies comply with those derived from the theory. The theory opens new ways for the understanding of cellular activities such as particle transport, mitosis and morphodynamics. PMID:14668925

  20. Cellular compartmentalization of secondary metabolism

    PubMed Central

    Kistler, H. Corby; Broz, Karen

    2015-01-01

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported. PMID:25709603

  1. Cellular tolerance to pulsed heating

    NASA Astrophysics Data System (ADS)

    Simanovski, Dimitrii; Sarkar, M.; Irani, A.; O'Connell-Rodwell, C.; Contag, C.; Schwettman, H. Alan; Palanker, D.

    2005-04-01

    Many laser therapies involve significant heating of tissue with pulses varying from picoseconds to minutes in duration. In some of the applications heating is a primary goal, while in others it is an undesirable side effect. In both cases, if a hyperthermia is involved, the knowledge about the threshold temperature leading to irreversible cellular damage is critically important. We study the dependence of the threshold temperature on duration of the heat exposure in the range of 0.3 ms to 5 seconds. Thin layer of cells cultured in a Petri dish was exposed to a pulsed CO2 laser radiation. Laser beam was focused onto sample providing Gaussian intensity distribution in the focal plane with a beam diameter (2w) 2-10 mm. Surface temperature in the central part of the focal spot (1mm in diameter) was measured by thermal infrared (IR) emission from the sample, recorded with a fast IR detector. For pulses shorter than 1 s the temperature profile across the focal spot was found to closely correspond to the radial distribution of the laser beam intensity, thus allowing for accurate determination of temperature at any given distance from the center of the spot. Immediate cellular damage was assessed using vital staining with the live/dead fluorescent assay. Threshold temperatures were found to vary from 65 °C at 5 s of heating to 160 °C at pulses of 0.3 ms in duration. The shorter end of this range was limited by vaporization, which occurs during the laser pulse and results in mechanical damage to cells. Dependence of the maximal temperature on pulse duration could be approximated by Arrhenius law with activation energy being about 1 eV.

  2. A cellular control architecture for compliant artificial muscles.

    PubMed

    Odhner, Lael U; Ueda, Jun; Asada, H Harry

    2006-01-01

    Dividing an artificial muscle material into a network of small cells could provide performance benefits and eliminate unwanted behaviors such as hysteresis. This paper presents a scheme for the position control or compliance control of an artificial muscle having this kind of cellular structure. Each cell contracts or relaxes probabilistically in response to a global feedback control loop, which measures only the aggregate force and displacement of the muscle. The stochastic nature of the cells produces smooth, reliable global behavior in the artificial muscle. By choosing a control law such that the expected response of the artificial muscle is equal to the desired response, good tracking control is achieved. PMID:17946978

  3. Cellular factors modulating the mechanism of tau protein aggregation.

    PubMed

    Fontaine, Sarah N; Sabbagh, Jonathan J; Baker, Jeremy; Martinez-Licha, Carlos R; Darling, April; Dickey, Chad A

    2015-05-01

    Pathological accumulation of the microtubule-associated protein tau, in the form of neurofibrillary tangles, is a major hallmark of Alzheimer's disease, the most prevalent neurodegenerative condition worldwide. In addition to Alzheimer's disease, a number of neurodegenerative diseases, called tauopathies, are characterized by the accumulation of aggregated tau in a variety of brain regions. While tau normally plays an important role in stabilizing the microtubule network of the cytoskeleton, its dissociation from microtubules and eventual aggregation into pathological deposits is an area of intense focus for therapeutic development. Here we discuss the known cellular factors that affect tau aggregation, from post-translational modifications to molecular chaperones. PMID:25666877

  4. Cellular factors modulating the mechanism of tau protein aggregation

    PubMed Central

    Fontaine, Sarah N.; Sabbagh, Jonathan J.; Baker, Jeremy; Martinez-Licha, Carlos R.; Darling, April

    2015-01-01

    Pathological accumulation of the microtubule-associated protein tau, in the form of neurofibrillary tangles, is a major hallmark of Alzheimer’s disease, the most prevalent neurodegenerative condition worldwide. In addition to Alzheimer’s disease, a number of neurodegenerative diseases, called tauopathies, are characterized by the accumulation of aggregated tau in a variety of brain regions. While tau normally plays an important role in stabilizing the microtubule network of the cytoskeleton, its dissociation from microtubules and eventual aggregation into pathological deposits is an area of intense focus for therapeutic development. Here we discuss the known cellular factors that affect tau aggregation, from post-translational modifications to molecular chaperones. PMID:25666877

  5. Control of fluxes in metabolic networks.

    PubMed

    Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

    2016-07-01

    Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. PMID:27197218

  6. A Cellular System for Spatial Signal Decoding in Chemical Gradients.

    PubMed

    Hegemann, Björn; Unger, Michael; Lee, Sung Sik; Stoffel-Studer, Ingrid; van den Heuvel, Jasmin; Pelet, Serge; Koeppl, Heinz; Peter, Matthias

    2015-11-23

    Directional cell growth requires that cells read and interpret shallow chemical gradients, but how the gradient directional information is identified remains elusive. We use single-cell analysis and mathematical modeling to define the cellular gradient decoding network in yeast. Our results demonstrate that the spatial information of the gradient signal is read locally within the polarity site complex using double-positive feedback between the GTPase Cdc42 and trafficking of the receptor Ste2. Spatial decoding critically depends on low Cdc42 activity, which is maintained by the MAPK Fus3 through sequestration of the Cdc42 activator Cdc24. Deregulated Cdc42 or Ste2 trafficking prevents gradient decoding and leads to mis-oriented growth. Our work discovers how a conserved set of components assembles a network integrating signal intensity and directionality to decode the spatial information contained in chemical gradients. PMID:26585298

  7. The challenges of cellular compartmentalization in plant metabolic engineering.

    PubMed

    Heinig, Uwe; Gutensohn, Michael; Dudareva, Natalia; Aharoni, Asaph

    2013-04-01

    The complex metabolic networks in plants are highly compartmentalized and biochemical steps of a single pathway can take place in multiple subcellular locations. Our knowledge regarding reactions and precursor compounds in the various cellular compartments has increased in recent years due to innovations in tracking the spatial distribution of proteins and metabolites. Nevertheless, to date only few studies have integrated subcellular localization criteria in metabolic engineering attempts. Here, we highlight the crucial factors for subcellular-localization-based strategies in plant metabolic engineering including substrate availability, enzyme targeting, the role of transporters, and multigene transfer approaches. The availability of compartmentalized metabolic network models for plants in the near future will greatly advance the integration of localization constraints in metabolic engineering experiments and aid in predicting their outcomes. PMID:23246154

  8. Cellular phones: are they detrimental?

    PubMed

    Salama, Osama E; Abou El Naga, Randa M

    2004-01-01

    The issue of possible health effects of cellular phones is very much alive in the public's mind where the rapid increase in the number of the users of cell phones in the last decade has increased the exposure of people to the electromagnetic fields (EMFs). Health consequences of long term use of mobile phones are not known in detail but available data indicates the development of non specific annoying symptoms on acute exposure to mobile phone radiations. In an attempt to determine the prevalence of such cell phones associated health manifestations and the factors affecting their occurrence, a cross sectional study was conducted in five randomly selected faculties of Alexandria University. Where, 300 individuals including teaching staff, students and literate employee were equally allocated and randomly selected among the five faculties. Data about mobile phone's users and their medical history, their pattern of mobile usage and the possible deleterious health manifestations associated with cellular phone use was collected. The results revealed 68% prevalence of mobile phone usage, nearly three quarters of them (72.5%) were complainers of the health manifestations. They suffered from headache (43%), earache (38.3%), sense of fatigue (31.6%), sleep disturbance (29.5%), concentration difficulty (28.5%) and face burning sensation (19.2%). Both univariate and multivariate analysis were consistent in their findings. Symptomatic users were found to have significantly higher frequency of calls/day, longer call duration and longer total duration of mobile phone usage/day than non symptomatic users. For headache both call duration and frequency of calls/day were the significant predicting factors for its occurrence (chi2 = 18.208, p = 0.0001). For earache, in addition to call duration, the longer period of owning the mobile phone were significant predictors (chi2 = 16.996, p = 0.0002). Sense of fatigue was significantly affected by both call duration and age of the user

  9. Survey of cellular radiosensitivity parameters.

    PubMed

    Katz, R; Zachariah, R; Cucinotta, F A; Zhang, C

    1994-12-01

    A model of the formation of particle tracks in emulsion has been extended through the use of biological target theory to formulate a theory of the response of biological cells and molecules of biological importance to irradiation with energetic heavy ions. For this purpose the response to gamma rays is represented by the single-hit, multitarget model with parameters m and D0, while additional parameters kappa (or a0) and sigma 0 are required to represent the size of internal cellular targets and the effective cross-sectional area of the cell nucleus, respectively, for heavy-ion bombardments. For one-or-more-hit detectors, only the first three of these parameters are required and m = 1. For cells m is typically 2 or more. The model is developed from the concept that response to secondary electrons follows the same functional form for gamma rays and for the gamma rays surrounding an ion's path. Originally applied to dry enzymes and viruses in 1967, the model of the one-hit detector has been extended to emulsions, to other physical and chemical detectors, to single- and double-strand breaks in DNA in EO buffer and to three E. coli strains. The two-hit response has been observed for "track core" effects in radiation chemistry, for supralinearity in thermoluminescent dosimeters and for desensitized nuclear emulsions, where hit numbers up to 6 have been observed. In its extension to biological cells, additional concepts are required relating to the character of the track, namely the grain-count and track-width regimes, and to the ability of multitarget systems to acquire damage from intertrack delta rays (called gamma kill) as well as from intratrack delta rays (called ion kill). The model has been applied to some 40 sets of radiobiological data obtained from gamma, track-segment heavy-ion and neutron irradiations. Here we elaborate on the meaning of these concepts, tabulate the cellular parameters, and display their systematic behavior and the relationships among them

  10. Cellular phosphatases facilitate combinatorial processing of receptor-activated signals

    PubMed Central

    Kumar, Dhiraj; Dua, Raina; Srikanth, Ravichandran; Jayaswal, Shilpi; Siddiqui, Zaved; Rao, Kanury VS

    2008-01-01

    Background Although reciprocal regulation of protein phosphorylation represents a key aspect of signal transduction, a larger perspective on how these various interactions integrate to contribute towards signal processing is presently unclear. For example, a key unanswered question is that of how phosphatase-mediated regulation of phosphorylation at the individual nodes of the signaling network translates into modulation of the net signal output and, thereby, the cellular phenotypic response. Results To address the above question we, in the present study, examined the dynamics of signaling from the B cell antigen receptor (BCR) under conditions where individual cellular phosphatases were selectively depleted by siRNA. Results from such experiments revealed a highly enmeshed structure for the signaling network where each signaling node was linked to multiple phosphatases on the one hand, and each phosphatase to several nodes on the other. This resulted in a configuration where individual signaling intermediates could be influenced by a spectrum of regulatory phosphatases, but with the composition of the spectrum differing from one intermediate to another. Consequently, each node differentially experienced perturbations in phosphatase activity, yielding a unique fingerprint of nodal signals characteristic to that perturbation. This heterogeneity in nodal experiences, to a given perturbation, led to combinatorial manipulation of the corresponding signaling axes for the downstream transcription factors. Conclusion Our cumulative results reveal that it is the tight integration of phosphatases into the signaling network that provides the plasticity by which perturbation-specific information can be transmitted in the form of a multivariate output to the downstream transcription factor network. This output in turn specifies a context-defined response, when translated into the resulting gene expression profile. PMID:18798986

  11. Autophagy in the cellular energetic balance.

    PubMed

    Singh, Rajat; Cuervo, Ana Maria

    2011-05-01

    Autophagy mediates the degradation of cellular components in lysosomes, assuring removal of altered or dysfunctional proteins and organelles. Autophagy is not only activated in response to cellular damage; in fact, one of its strongest and better-characterized stimuli is starvation. Activation of autophagy when nutrients are scarce allows cells to reutilize their own constituents for energy. Besides protein breakdown, autophagy also contributes to the mobilization of diverse cellular energy stores. This recently discovered interplay between autophagy and lipid and carbohydrate metabolism reveals the existence of a dynamic feedback between autophagy and cellular energy balance. PMID:21531332

  12. Review of cellular mechanotransduction on micropost substrates.

    PubMed

    Geng, Yuxu; Wang, Zhanjiang

    2016-03-01

    As physical entities, living cells can sense and respond to various stimulations within and outside the body through cellular mechanotransduction. Any deviation in cellular mechanotransduction will not only undermine the orchestrated regulation of mechanical responses, but also lead to the breakdown of their physiological function. Therefore, a quantitative study of cellular mechanotransduction needs to be conducted both in experiments and in computational simulations to investigate the underlying mechanisms of cellular mechanotransduction. In this review, we present an overview of the current knowledge and significant progress in cellular mechanotransduction via micropost substrates. In the aspect of experimental studies, we summarize significant experimental progress and place an emphasis on the coupled relationship among cellular spreading, focal adhesion and contractility as well as the influence of substrate properties on force-involved cellular behaviors. In the other aspect of computational investigations, we outline a coupled framework including the biochemically motivated stress fiber model and thermodynamically motivated adhesion model and present their predicted biomechanical responses and then compare predicted simulation results with experimental observations to further explore the mechanisms of cellular mechanotransduction. At last, we discuss the future perspectives both in experimental technologies and in computational models, as well as facing challenges in the area of cellular mechanotransduction. PMID:26245253

  13. [Photodynamic modulation of cellular functions].

    PubMed

    Li, Yuan; Jiang, Hong-Ning; Cui, Zong-Jie

    2016-08-25

    Photodynamic action, due to the rather limited lifetime (1 μs) and effective reactive distance of singlet oxygen (< 10 nm), could subcellular-specifically regulate different cellular functions. Photodynamic action could activate permanently cholecystokinin (CCK) 1 receptors, and sensitize or desensitize other G protein-coupled receptors. The emergence in recent years of genetically- encoded protein photosensitisers has enabled more precisely-targeted photodynamic modulation of subcellular organelles and functional proteins. Protein photosensitisers (such as KillerRed, miniSOG or SOPP) expressed on the plasma membrane, mitochondria, lysosomes or endoplasmic reticulum can modulate photodynamically subcellular functions and fine-tune protein activity by targeted photooxidation. With the newly emerged active illumination technique, simultaneous photodynamic action localized at multiple sites is now possible, and the contribution of subcellular regions to the whole cell or individual cells to a cell cluster could be quantitated. Photodynamic action with protein photosensitiser will be a powerful tool for nano-manipulation in cell physiology research. PMID:27546513

  14. Illuminating cellular physiology: recent developments.

    PubMed

    Brovko, Lubov Y; Griffiths, Mansel W

    2007-01-01

    Bioluminescent methods are gaining more and more attention among scientists due to their sensitivity, selectivity and simplicity; coupled with the fact that the bioluminescence can be monitored both in vitro and in vivo. Since the discovery of bioluminescence in the 19th century, enzymes involved in the bioluminescent process have been isolated and cloned. The bioluminescent reactions in several different organisms have also been fully characterized and used as reporters in a wide variety of biochemical assays. From the 1990s it became clear that bioluminescence can be detected and quantified directly from inside a living cell. This gave rise to numerous possibilities for the in vivo monitoring of intracellular processes non-invasively using bioluminescent molecules as reporters. This review describes recent developments in the area of bioluminescent imaging for cell biology. Newly developed imaging methods allow transcriptional/translational regulation, signal transduction, protein-protein interaction, oncogenic transformation, cell and protein trafficking, and target drug action to be monitored in vivo in real-time with high temporal and spatial resolution; thus providing researchers with priceless information on cellular functions. Advantages and limitations of these novel bioluminescent methods are discussed and possible future developments identified. PMID:17725230

  15. Ethical Decision Making, Therapeutic Boundaries, and Communicating Using Online Technology and Cellular Phones

    ERIC Educational Resources Information Center

    Yonan, Jesay; Bardick, Angela D.; Willment, Jo-Anne H.

    2011-01-01

    Cellular telephones and social networking sites pose new challenges to the maintenance of therapeutic boundaries. One such difficulty is the possible development of dual relationships between clients and counselling professionals as a result of communicating by these means. Most regulatory bodies advise professional counsellors and psychologists…

  16. Tuning of the electro-mechanical behavior of the cellular carbon nanotube structures with nanoparticle dispersions

    SciTech Connect

    Gowda, Prarthana; Misra, Abha; Ramamurty, Upadrasta

    2014-03-10

    The mechanical and electrical characteristics of cellular network of the carbon nanotubes (CNT) impregnated with metallic and nonmetallic nanoparticles were examined simultaneously by employing the nanoindentation technique. Experimental results show that the nanoparticle dispersion not only enhances the mechanical strength of the cellular CNT by two orders of magnitude but also imparts variable nonlinear electrical characteristics; the latter depends on the contact resistance between nanoparticles and CNT, which is shown to depend on the applied load while indentation. Impregnation with silver nanoparticles enhances the electrical conductance, the dispersion with copper oxide and zinc oxide nanoparticles reduces the conductance of CNT network. In all cases, a power law behavior with suppression in the differential conductivity at zero bias was noted, indicating electron tunneling through the channels formed at the CNT-nanoparticle interfaces. These results open avenues for designing cellular CNT foams with desired electro-mechanical properties and coupling.

  17. Evolving Synaptic Plasticity with an Evolutionary Cellular Development Model

    PubMed Central

    Yerushalmi, Uri; Teicher, Mina

    2008-01-01

    Since synaptic plasticity is regarded as a potential mechanism for memory formation and learning, there is growing interest in the study of its underlying mechanisms. Recently several evolutionary models of cellular development have been presented, but none have been shown to be able to evolve a range of biological synaptic plasticity regimes. In this paper we present a biologically plausible evolutionary cellular development model and test its ability to evolve different biological synaptic plasticity regimes. The core of the model is a genomic and proteomic regulation network which controls cells and their neurites in a 2D environment. The model has previously been shown to successfully evolve behaving organisms, enable gene related phenomena, and produce biological neural mechanisms such as temporal representations. Several experiments are described in which the model evolves different synaptic plasticity regimes using a direct fitness function. Other experiments examine the ability of the model to evolve simple plasticity regimes in a task -based fitness function environment. These results suggest that such evolutionary cellular development models have the potential to be used as a research tool for investigating the evolutionary aspects of synaptic plasticity and at the same time can serve as the basis for novel artificial computational systems. PMID:19002249

  18. Toward a systems-level view of dynamic phosphorylation networks

    PubMed Central

    Newman, Robert H.; Zhang, Jin; Zhu, Heng

    2014-01-01

    To better understand how cells sense and respond to their environment, it is important to understand the organization and regulation of the phosphorylation networks that underlie most cellular signal transduction pathways. These networks, which are composed of protein kinases, protein phosphatases and their respective cellular targets, are highly dynamic. Importantly, to achieve signaling specificity, phosphorylation networks must be regulated at several levels, including at the level of protein expression, substrate recognition, and spatiotemporal modulation of enzymatic activity. Here, we briefly summarize some of the traditional methods used to study the phosphorylation status of cellular proteins before focusing our attention on several recent technological advances, such as protein microarrays, quantitative mass spectrometry, and genetically-targetable fluorescent biosensors, that are offering new insights into the organization and regulation of cellular phosphorylation networks. Together, these approaches promise to lead to a systems-level view of dynamic phosphorylation networks. PMID:25177341

  19. Slowdown of growth controls cellular differentiation.

    PubMed

    Narula, Jatin; Kuchina, Anna; Zhang, Fang; Fujita, Masaya; Süel, Gürol M; Igoshin, Oleg A

    2016-01-01

    How can changes in growth rate affect the regulatory networks behavior and the outcomes of cellular differentiation? We address this question by focusing on starvation response in sporulating Bacillus subtilis We show that the activity of sporulation master regulator Spo0A increases with decreasing cellular growth rate. Using a mathematical model of the phosphorelay-the network controlling Spo0A-we predict that this increase in Spo0A activity can be explained by the phosphorelay protein accumulation and lengthening of the period between chromosomal replication events caused by growth slowdown. As a result, only cells growing slower than a certain rate reach threshold Spo0A activity necessary for sporulation. This growth threshold model accurately predicts cell fates and explains the distribution of sporulation deferral times. We confirm our predictions experimentally and show that the concentration rather than activity of phosphorelay proteins is affected by the growth slowdown. We conclude that sensing the growth rates enables cells to indirectly detect starvation without the need for evaluating specific stress signals. PMID:27216630

  20. Compartmentalization of the Edinburgh Human Metabolic Network

    PubMed Central

    2010-01-01

    Background Direct in vivo investigation of human metabolism is complicated by the distinct metabolic functions of various sub-cellular organelles. Diverse micro-environments in different organelles may lead to distinct functions of the same protein and the use of different enzymes for the same metabolic reaction. To better understand the complexity in the human metabolism, a compartmentalized human metabolic network with integrated sub-cellular location information is required. Results We extended the previously reconstructed Edinburgh Human Metabolic Network (EHMN) [Ma, et al. Molecular Systems Biology, 3:135, 2007] by integrating the sub-cellular location information for the reactions, adding transport reactions and refining the protein-reaction relationships based on the location information. Firstly, protein location information was obtained from Gene Ontology and complemented by a Swiss-Prot location keywords search. Then all the reactions in EHMN were assigned to a location based on the protein-reaction relationships to get a preliminary compartmentalized network. We investigated the localized sub-networks in each pathway to identify gaps and isolated reactions by connectivity analysis and refined the location information based on information from literature. As a result, location information for hundreds of reactions was revised and hundreds of incorrect protein-reaction relationships were corrected. Over 1400 transport reactions were added to link the location specific metabolic network. To validate the network, we have done pathway analysis to examine the capability of the network to synthesize or degrade certain key metabolites. Compared with a previously published human metabolic network (Human Recon 1), our network contains over 1000 more reactions assigned to clear cellular compartments. Conclusions By combining protein location information, network connectivity analysis and manual literature search, we have reconstructed a more complete

  1. The Road Less Traveled: HIV's Use of Alternative Routes through Cellular Pathways

    PubMed Central

    Marx, Ailie

    2015-01-01

    Pathogens such as HIV-1, with their minimalist genomes, must navigate cellular networks and rely on hijacking and manipulating the host machinery for successful replication. Limited overlap of host factors identified as vital for pathogen replication may be explained by considering that pathogens target, rather than specific cellular factors, crucial cellular pathways by targeting different, functionally equivalent, protein-protein interactions within that pathway. The ability to utilize alternative routes through cellular pathways may be essential for pathogen survival when restricted and provide flexibility depending on the viral replication stage and the environment in the infected host. In this minireview, we evaluate evidence supporting this notion, discuss specific HIV-1 examples, and consider the molecular mechanisms which allow pathogens to flexibly exploit different routes. PMID:25762730

  2. The Road Less Traveled: HIV's Use of Alternative Routes through Cellular Pathways.

    PubMed

    Marx, Ailie; Alian, Akram

    2015-05-01

    Pathogens such as HIV-1, with their minimalist genomes, must navigate cellular networks and rely on hijacking and manipulating the host machinery for successful replication. Limited overlap of host factors identified as vital for pathogen replication may be explained by considering that pathogens target, rather than specific cellular factors, crucial cellular pathways by targeting different, functionally equivalent, protein-protein interactions within that pathway. The ability to utilize alternative routes through cellular pathways may be essential for pathogen survival when restricted and provide flexibility depending on the viral replication stage and the environment in the infected host. In this minireview, we evaluate evidence supporting this notion, discuss specific HIV-1 examples, and consider the molecular mechanisms which allow pathogens to flexibly exploit different routes. PMID:25762730

  3. [Cell signaling pathways interaction in cellular proliferation: Potential target for therapeutic interventionism].

    PubMed

    Valdespino-Gómez, Víctor Manuel; Valdespino-Castillo, Patricia Margarita; Valdespino-Castillo, Víctor Edmundo

    2015-01-01

    Nowadays, cellular physiology is best understood by analysing their interacting molecular components. Proteins are the major components of the cells. Different proteins are organised in the form of functional clusters, pathways or networks. These molecules are ordered in clusters of receptor molecules of extracellular signals, transducers, sensors and biological response effectors. The identification of these intracellular signaling pathways in different cellular types has required a long journey of experimental work. More than 300 intracellular signaling pathways have been identified in human cells. They participate in cell homeostasis processes for structural and functional maintenance. Some of them participate simultaneously or in a nearly-consecutive progression to generate a cellular phenotypic change. In this review, an analysis is performed on the main intracellular signaling pathways that take part in the cellular proliferation process, and the potential use of some components of these pathways as target for therapeutic interventionism are also underlined. PMID:25986976

  4. Integrated segmentation of cellular structures

    NASA Astrophysics Data System (ADS)

    Ajemba, Peter; Al-Kofahi, Yousef; Scott, Richard; Donovan, Michael; Fernandez, Gerardo

    2011-03-01

    Automatic segmentation of cellular structures is an essential step in image cytology and histology. Despite substantial progress, better automation and improvements in accuracy and adaptability to novel applications are needed. In applications utilizing multi-channel immuno-fluorescence images, challenges include misclassification of epithelial and stromal nuclei, irregular nuclei and cytoplasm boundaries, and over and under-segmentation of clustered nuclei. Variations in image acquisition conditions and artifacts from nuclei and cytoplasm images often confound existing algorithms in practice. In this paper, we present a robust and accurate algorithm for jointly segmenting cell nuclei and cytoplasm using a combination of ideas to reduce the aforementioned problems. First, an adaptive process that includes top-hat filtering, Eigenvalues-of-Hessian blob detection and distance transforms is used to estimate the inverse illumination field and correct for intensity non-uniformity in the nuclei channel. Next, a minimum-error-thresholding based binarization process and seed-detection combining Laplacian-of-Gaussian filtering constrained by a distance-map-based scale selection is used to identify candidate seeds for nuclei segmentation. The initial segmentation using a local maximum clustering algorithm is refined using a minimum-error-thresholding technique. Final refinements include an artifact removal process specifically targeted at lumens and other problematic structures and a systemic decision process to reclassify nuclei objects near the cytoplasm boundary as epithelial or stromal. Segmentation results were evaluated using 48 realistic phantom images with known ground-truth. The overall segmentation accuracy exceeds 94%. The algorithm was further tested on 981 images of actual prostate cancer tissue. The artifact removal process worked in 90% of cases. The algorithm has now been deployed in a high-volume histology analysis application.

  5. Cellular toxicity of nicotinamide metabolites.

    PubMed

    Rutkowski, Bolesław; Rutkowski, Przemysław; Słomińska, Ewa; Smolenski, Ryszard T; Swierczyński, Julian

    2012-01-01

    There are almost 100 different substances called uremic toxins. Nicotinamide derivatives are known as new family of uremic toxins. These uremic compounds play a role in an increased oxidative stress and disturbances in cellular repair processes by inhibiting poly (ADP-ribose) polymerase activity. New members of this family were discovered and described. Their toxic properties were a subject of recent studies. This study evaluated the concentration of 4-pyridone-3-carboxamid-1-β-ribonucleoside-triphosphate (4PYTP) and 4-pyridone-3-carboxamid-1-β-ribonucleoside-monophosphate (4PYMP) in erythrocytes of patients with chronic renal failure. Serum and red blood cells were collected from chronic renal failure patients on conservative treatment, those treated with hemodialysis, and at different times from those who underwent kidney transplantation. Healthy volunteers served as a control group. Nicotinamide metabolites were determined using liquid chromatography with mass spectrometry based on originally discovered and described method. Three novel compounds were described: 4-pyridone-3-carboxamid-1-β-ribonucleoside (4PYR), 4PYMP, and 4PYTP. 4PYR concentration was elevated in the serum, whereas 4PYMP and 4PYTP concentrations were augmented in erythrocytes of dialysis patients. Interestingly, concentrations of these compounds were less elevated during the treatment with erythropoietin-stimulating agents (ESAs). After successful kidney transplantation, concentrations of 4PYR and 4PYMP normalized according to the graft function, whereas that of 4PYTP was still elevated. During the incubation of erythrocytes in the presence of 4PYR, concentration of 4PYMP rose very rapidly while that of 4PYTP increased slowly. Therefore, we hypothesized that 4PYR, as a toxic compound, was actively absorbed by erythrocytes and metabolized to the 4PYMP and 4PYTP, which may interfere with function and life span of these cells. PMID:22200423

  6. Electrodynamic eigenmodes in cellular morphology.

    PubMed

    Cifra, M

    2012-09-01

    Eigenmodes of the spherical and ellipsoidal dielectric electromagnetic resonator have been analysed. The sizes and shape of the resonators have been chosen to represent the shape of the interphase and dividing animal cell. Electromagnetic modes that have shape exactly suitable for positioning of the sufficiently large organelles in cell (centrosome, nucleus) have been identified. We analysed direction and magnitude of dielectrophoretic force exerted on large organelles by electric field of the modes. We found that the TM(1m1) mode in spherical resonator acts by centripetal force which drags the large organelles which have higher permittivity than the cytosol to the center of the cell. TM-kind of mode in the ellipsoidal resonator acts by force on large polarizable organelles in a direction that corresponds to the movement of the centrosomes (also nucleus) observed during the cell division, i.e. to the foci of the ellipsoidal cell. Minimal required force (10(-16) N), gradient of squared electric field and corresponding energy (10(-16) J) of the mode have been calculated to have biological significance within the periods on the order of time required for cell division. Minimal required energy of the mode, in order to have biological significance, can be lower in the case of resonance of organelle with the field of the cellular resonator mode. In case of sufficient energy in the biologically relevant mode, electromagnetic field of the mode will act as a positioning or steering mechanism for centrosome and nucleus in the cell, thus contribute to the spatial and dynamical self-organization in biological systems. PMID:22750075

  7. Cellular Manufacturing Internet Performance Support System

    SciTech Connect

    Bohley, M.C.; Schwartz, M.E.

    1998-03-04

    The objective of this project was to develop an Internet-based electronic performance support system (EPSS) for cellular manufacturing providing hardware/software specifications, process descriptions, estimated cost savings, manufacturing simulations, training information, and service resources for government and industry users of Cincinnati Milacron machine tools and products. AlliedSignal Federal Manufacturing and Technologies (ASFM and T) used expertise in the areas of Internet design and multimedia creation to develop a performance support system (PSS) for the Internet with assistance from CM's subject matter experts from engineering, manufacturing, and technical support. Reference information was both created and re-purposed from other existing formats, then made available on the Internet. On-line references on cellular manufacturing operations include: definitions of cells and cellular manufacturing; illustrations on how cellular manufacturing improves part throughput, resource utilization, part quality, and manufacturing flexibility; illustrations on how cellular manufacturing reduces labor and overhead costs; identification of critical factors driving decisions toward cellular manufacturing; a method for identifying process improvement areas using cellular manufacturing; a method for customizing the size of cells for a specific site; a simulation for making a part using cellular manufacturing technology; and a glossary of terms and concepts.

  8. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Metropolitan Areas and the Gulf of Mexico Service Area (water area of the Gulf of Mexico, border is the coastline), defined by the Office of Management and Budget, as modified by the FCC. (b) RSAs. Rural Service... used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  9. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Metropolitan Areas and the Gulf of Mexico Service Area (water area of the Gulf of Mexico, border is the coastline), defined by the Office of Management and Budget, as modified by the FCC. (b) RSAs. Rural Service... used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  10. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Metropolitan Areas and the Gulf of Mexico Service Area (water area of the Gulf of Mexico, border is the coastline), defined by the Office of Management and Budget, as modified by the FCC. (b) RSAs. Rural Service... used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  11. From Cnn Dynamics to Cellular Wave Computers

    NASA Astrophysics Data System (ADS)

    Roska, Tamas

    2013-01-01

    Embedded in a historical overview, the development of the Cellular Wave Computing paradigm is presented, starting from the standard CNN dynamics. The theoretical aspects, the physical implementation, the innovation process, as well as the biological relevance are discussed in details. Finally, the latest developments, the physical versus virtual cellular machines, as well as some open questions are presented.

  12. Small-world networks

    NASA Astrophysics Data System (ADS)

    Strogatz, Steven

    Everyone is familiar with the small-world phenomenon: soon after meeting a stranger, we are often suprised to discover that we have a mutual friend, or that we are somehow linked by a short chain of friends. In this talk, I'll present evidence that the small-world phenomenon is more than a curiosity of social networks — it is actually a general property of large, sparse networks whose topology is neither completely regular nor completely random. To check this idea, Duncan Watts and I have analyzed three networks of scientific interest: the neural network of the nematode worm C. elegans, the electrical power grid of the western United States, and the collaboration graph of actors in feature films. All three are small worlds, in the sense that the average number of "handshakes" separating any two members is extremely small (close to the theoretical lower limit set by a random graph). Yet at the same time, all three networks exhibit much more local clustering than a random net, demonstrating that they are not random. I'll also discuss a class of model networks that interpolate between regular lattices and random graphs. Previous theoretical research on complex systems in a wide range of disciplines has focused almost exclusively on networks that are either regular or random. Real networks often lie somewhere in between. Our mathematical model shows that networks in this middle ground tend to exhibit the small-world phenomenon, thanks to the presence of a few long-range edges that link parts of the graph that would otherwise be far apart. Furthermore, we find that when various dynamical systems are coupled in a small-world fashion, they exhibit much greater propagation speed, computational power, and synchronizability than their locally connected, regular counterparts. We explore the implications of these results for simple models of disease spreading, global computation in cellular automata, and collective locking of biological oscillators.

  13. Examining tissue differentiation stability through large scale, multi-cellular pathway modeling.

    SciTech Connect

    May, Elebeoba Eni; Schiek, Richard Louis

    2005-03-01

    Using a multi-cellular, pathway model approach, we investigate the Drosophila sp. segmental differentiation network's stability as a function of initial conditions. While this network's functionality has been investigated in the absence of noise, this is the first work to specifically investigate how natural systems respond to random errors or noise. Our findings agree with earlier results that the overall network is robust in the absence of noise. However, when one includes random initial perturbations in intracellular protein WG levels, the robustness of the system decreases dramatically. The effect of noise on the system is not linear, and appears to level out at high noise levels.

  14. Global Self-Organization of the Cellular Metabolic Structure

    PubMed Central

    De La Fuente, Ildefonso M.; Martínez, Luis; Pérez-Samartín, Alberto L.; Ormaetxea, Leire; Amezaga, Cristian; Vera-López, Antonio

    2008-01-01

    Background Over many years, it has been assumed that enzymes work either in an isolated way, or organized in small catalytic groups. Several studies performed using “metabolic networks models” are helping to understand the degree of functional complexity that characterizes enzymatic dynamic systems. In a previous work, we used “dissipative metabolic networks” (DMNs) to show that enzymes can present a self-organized global functional structure, in which several sets of enzymes are always in an active state, whereas the rest of molecular catalytic sets exhibit dynamics of on-off changing states. We suggested that this kind of global metabolic dynamics might be a genuine and universal functional configuration of the cellular metabolic structure, common to all living cells. Later, a different group has shown experimentally that this kind of functional structure does, indeed, exist in several microorganisms. Methodology/Principal Findings Here we have analyzed around 2.500.000 different DMNs in order to investigate the underlying mechanism of this dynamic global configuration. The numerical analyses that we have performed show that this global configuration is an emergent property inherent to the cellular metabolic dynamics. Concretely, we have found that the existence of a high number of enzymatic subsystems belonging to the DMNs is the fundamental element for the spontaneous emergence of a functional reactive structure characterized by a metabolic core formed by several sets of enzymes always in an active state. Conclusions/Significance This self-organized dynamic structure seems to be an intrinsic characteristic of metabolism, common to all living cellular organisms. To better understand cellular functionality, it will be crucial to structurally characterize these enzymatic self-organized global structures. PMID:18769681

  15. Simulations of Living Cell Origins Using a Cellular Automata Model

    NASA Astrophysics Data System (ADS)

    Ishida, Takeshi

    2014-04-01

    Understanding the generalized mechanisms of cell self-assembly is fundamental for applications in various fields, such as mass producing molecular machines in nanotechnology. Thus, the details of real cellular reaction networks and the necessary conditions for self-organized cells must be elucidated. We constructed a 2-dimensional cellular automata model to investigate the emergence of biological cell formation, which incorporated a looped membrane and a membrane-bound information system (akin to a genetic code and gene expression system). In particular, with an artificial reaction system coupled with a thermal system, the simultaneous formation of a looped membrane and an inner reaction process resulted in a more stable structure. These double structures inspired the primitive biological cell formation process from chemical evolution stage. With a model to simulate cellular self-organization in a 2-dimensional cellular automata model, 3 phenomena could be realized: (1) an inner reaction system developed as an information carrier precursor (akin to DNA); (2) a cell border emerged (akin to a cell membrane); and (3) these cell structures could divide into 2. This double-structured cell was considered to be a primary biological cell. The outer loop evolved toward a lipid bilayer membrane, and inner polymeric particles evolved toward precursor information carriers (evolved toward DNA). This model did not completely clarify all the necessary and sufficient conditions for biological cell self-organization. Further, our virtual cells remained unstable and fragile. However, the "garbage bag model" of Dyson proposed that the first living cells were deficient; thus, it would be reasonable that the earliest cells were more unstable and fragile than the simplest current unicellular organisms.

  16. Robustness of metabolic networks

    NASA Astrophysics Data System (ADS)

    Jeong, Hawoong

    2009-03-01

    We investigated the robustness of cellular metabolism by simulating the system-level computational models, and also performed the corresponding experiments to validate our predictions. We address the cellular robustness from the ``metabolite''-framework by using the novel concept of ``flux-sum,'' which is the sum of all incoming or outgoing fluxes (they are the same under the pseudo-steady state assumption). By estimating the changes of the flux-sum under various genetic and environmental perturbations, we were able to clearly decipher the metabolic robustness; the flux-sum around an essential metabolite does not change much under various perturbations. We also identified the list of the metabolites essential to cell survival, and then ``acclimator'' metabolites that can control the cell growth were discovered. Furthermore, this concept of ``metabolite essentiality'' should be useful in developing new metabolic engineering strategies for improved production of various bioproducts and designing new drugs that can fight against multi-antibiotic resistant superbacteria by knocking-down the enzyme activities around an essential metabolite. Finally, we combined a regulatory network with the metabolic network to investigate its effect on dynamic properties of cellular metabolism.

  17. Leaf development: a cellular perspective

    PubMed Central

    Kalve, Shweta; De Vos, Dirk; Beemster, Gerrit T. S.

    2014-01-01

    Through its photosynthetic capacity the leaf provides the basis for growth of the whole plant. In order to improve crops for higher productivity and resistance for future climate scenarios, it is important to obtain a mechanistic understanding of leaf growth and development and the effect of genetic and environmental factors on the process. Cells are both the basic building blocks of the leaf and the regulatory units that integrate genetic and environmental information into the developmental program. Therefore, to fundamentally understand leaf development, one needs to be able to reconstruct the developmental pathway of individual cells (and their progeny) from the stem cell niche to their final position in the mature leaf. To build the basis for such understanding, we review current knowledge on the spatial and temporal regulation mechanisms operating on cells, contributing to the formation of a leaf. We focus on the molecular networks that control exit from stem cell fate, leaf initiation, polarity, cytoplasmic growth, cell division, endoreduplication, transition between division and expansion, expansion and differentiation and their regulation by intercellular signaling molecules, including plant hormones, sugars, peptides, proteins, and microRNAs. We discuss to what extent the knowledge available in the literature is suitable to be applied in systems biology approaches to model the process of leaf growth, in order to better understand and predict leaf growth starting with the model species Arabidopsis thaliana. PMID:25132838

  18. Geometric morphology of cellular solids

    SciTech Connect

    Schlei, B. R.; Prasad, L.; Skourikhine, A. N.

    2001-01-01

    We demonstrate how to derive morphological information from micrographs, i.e., grey-level images, of polymeric foams. The segmentation of the images is performed by applying a pulse-coupled neural network. This processing generates blobs of the foams walls/struts and voids, respectively. The contours of the blobs and their corresponding points form the input to a constrained Delaunay tessellation, which provides an unstructured grid of the material under consideration. The subsequently applied Chordal Axis Transform captures the intrinsic shape characteristics, and facilitates the identification and localization of key morphological features. While stochastic features of the polymeric foams struts/walls such as areas, aspect ratios, etc., already can be computed at this stage, the foams voids require further geometric processing. The voids are separated into single foam cells. This shape manipulation leads to a refinement of the initial blob contours, which then requires the repeated application of the constrained Delaunay tessellation and Chordal Axis Transform, respectively. Using minimum enclosing rectangles for each foam cell, finally the stochastic features of the foam voids are computed.

  19. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence

    PubMed Central

    2016-01-01

    The cellular senescence definition comes to the fact of cells irreversible proliferation disability. Besides the cell cycle arrest, senescent cells go through some morphological, biochemical, and functional changes which are the signs of cellular senescence. The senescent cells (including replicative senescence and stress-induced premature senescence) of all the tissues look alike. They are metabolically active and possess the set of characteristics in vitro and in vivo, which are known as biomarkers of aging and cellular senescence. Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data. PMID:26805432

  20. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence.

    PubMed

    Bernadotte, Alexandra; Mikhelson, Victor M; Spivak, Irina M

    2016-01-01

    The cellular senescence definition comes to the fact of cells irreversible proliferation disability. Besides the cell cycle arrest, senescent cells go through some morphological, biochemical, and functional changes which are the signs of cellular senescence. The senescent cells (including replicative senescence and stress-induced premature senescence) of all the tissues look alike. They are metabolically active and possess the set of characteristics in vitro and in vivo, which are known as biomarkers of aging and cellular senescence. Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data. PMID:26805432

  1. Statistical Mechanics of Surjective Cellular Automata

    NASA Astrophysics Data System (ADS)

    Kari, Jarkko; Taati, Siamak

    2015-09-01

    Reversible cellular automata are seen as microscopic physical models, and their states of macroscopic equilibrium are described using invariant probability measures. We establish a connection between the invariance of Gibbs measures and the conservation of additive quantities in surjective cellular automata. Namely, we show that the simplex of shift-invariant Gibbs measures associated to a Hamiltonian is invariant under a surjective cellular automaton if and only if the cellular automaton conserves the Hamiltonian. A special case is the (well-known) invariance of the uniform Bernoulli measure under surjective cellular automata, which corresponds to the conservation of the trivial Hamiltonian. As an application, we obtain results indicating the lack of (non-trivial) Gibbs or Markov invariant measures for "sufficiently chaotic" cellular automata. We discuss the relevance of the randomization property of algebraic cellular automata to the problem of approach to macroscopic equilibrium, and pose several open questions. As an aside, a shift-invariant pre-image of a Gibbs measure under a pre-injective factor map between shifts of finite type turns out to be always a Gibbs measure. We provide a sufficient condition under which the image of a Gibbs measure under a pre-injective factor map is not a Gibbs measure. We point out a potential application of pre-injective factor maps as a tool in the study of phase transitions in statistical mechanical models.

  2. Cellular telephones and non-Hodgkin lymphoma.

    PubMed

    Linet, Martha S; Taggart, Theresa; Severson, Richard K; Cerhan, James R; Cozen, Wendy; Hartge, Patricia; Colt, Joanne

    2006-11-15

    Dramatic increase in hand-held cellular telephone use since the 1980s and excess risk of lymphoproliferative malignancies associated with radio-frequency radiation (RFR) exposures in epidemiological and experimental studies motivated assessment of cellular telephones within a comprehensive US case-control investigation of non-Hodgkin lymphoma (NHL). A questionnaire ascertained cellular telephone use in 551 NHL cases and 462 frequency-matched population controls. Compared to persons who had never used cellular telephones, risks were not increased among individuals whose lifetime use was fewer than 10 (odds ratio (OR) = 0.9, 95% confidence intervals (CI): 0.6, 1.3), 10-100 (OR = 1.0, 95 % CI: 0.7, 1.5) or more than 100 times (e.g., regular users, OR = 0.9, 95% CI: 0.6, 1.4). Among regular users compared to those who had never used hand-held cellular telephones, risks of NHL were not significantly associated with minutes per week, duration, cumulative lifetime or year of first use, although NHL was non-significantly higher in men who used cellular telephones for more than 8 years. Little evidence linked use of cellular telephones with total, diffuse large B-cell lymphoma or follicular NHL. These findings must be interpreted in the context of less than 5% of the population reporting duration of use of 6 or more years or lifetime cumulative use of 200 or more hours. PMID:16894556

  3. Cellular automata modeling of weld solidification structure

    SciTech Connect

    Dress, W.B.; Zacharia, T.; Radhakrishnan, B.

    1993-12-31

    The authors explore the use of cellular automata in modeling arc-welding processes. A brief discussion of cellular automata and their previous use in micro-scale solidification simulations is presented. Macro-scale thermal calculations for arc-welding at a thin plate are shown to give good quantitative and qualitative results. Combining the two calculations in a single cellular array provides a realistic simulation of grain growth in a welding process. Results of simulating solidification in a moving melt pool in a poly-crystalline alloy sheet are presented.

  4. Nanomechanics of magnetically driven cellular endocytosis

    NASA Astrophysics Data System (ADS)

    Zablotskii, V.; Lunov, O.; Dejneka, A.; Jastrabík, L.; Polyakova, T.; Syrovets, T.; Simmet, Th.

    2011-10-01

    Being essential for many pharmacodynamic and pharmacokinetic processes and playing a crucial role in regulating substrate detachment that enables cellular locomotion, endocytotic mechanisms in many aspects still remain a mystery and therefore can hardly be controlled. Here, we report on experimental and modeling studies of the magnetically assisted endocytosis of functionalized superparamagnetic iron oxide nanoparticles by prostate cancer cells (PC-3) and characterize the time and force scales of the cellular uptake machinery. The results indicate how the cellular uptake rate could be controlled by applied magnetic field, membrane elasticity, and nanoparticle magnetic moment.

  5. Cellular solidification in a monotectic system

    NASA Technical Reports Server (NTRS)

    Kaukler, W. F.; Curreri, P. A.

    1987-01-01

    Succinonitrile-glycerol, SN-G, transparent organic monotectic alloy is studied with particular attention to cellular growth. The phase diagram is determined, near the monotectic composition, with greater accuracy than previous studies. A solidification interface stability diagram is determined for planar growth. The planar-to-cellular transition is compared to predictions from the Burton, Primm, Schlichter theory. A new technique to determine the solute segregation by Fourier transform infrared spectroscopy is developed. Proposed models that involve the cellular interface for alignment of monotectic second-phase spheres or rods are compared with observations.

  6. Cellular and molecular mechanisms in kidney fibrosis

    PubMed Central

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution. PMID:24892703

  7. IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

    SciTech Connect

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  8. A positive feedback at the cellular level promotes robustness and modulation at the circuit level.

    PubMed

    Dethier, Julie; Drion, Guillaume; Franci, Alessio; Sepulchre, Rodolphe

    2015-10-01

    This article highlights the role of a positive feedback gating mechanism at the cellular level in the robustness and modulation properties of rhythmic activities at the circuit level. The results are presented in the context of half-center oscillators, which are simple rhythmic circuits composed of two reciprocally connected inhibitory neuronal populations. Specifically, we focus on rhythms that rely on a particular excitability property, the postinhibitory rebound, an intrinsic cellular property that elicits transient membrane depolarization when released from hyperpolarization. Two distinct ionic currents can evoke this transient depolarization: a hyperpolarization-activated cation current and a low-threshold T-type calcium current. The presence of a slow activation is specific to the T-type calcium current and provides a slow positive feedback at the cellular level that is absent in the cation current. We show that this slow positive feedback is required to endow the network rhythm with physiological modulation and robustness properties. This study thereby identifies an essential cellular property to be retained at the network level in modeling network robustness and modulation. PMID:26311181

  9. Network Cosmology

    PubMed Central

    Krioukov, Dmitri; Kitsak, Maksim; Sinkovits, Robert S.; Rideout, David; Meyer, David; Boguñá, Marián

    2012-01-01

    Prediction and control of the dynamics of complex networks is a central problem in network science. Structural and dynamical similarities of different real networks suggest that some universal laws might accurately describe the dynamics of these networks, albeit the nature and common origin of such laws remain elusive. Here we show that the causal network representing the large-scale structure of spacetime in our accelerating universe is a power-law graph with strong clustering, similar to many complex networks such as the Internet, social, or biological networks. We prove that this structural similarity is a consequence of the asymptotic equivalence between the large-scale growth dynamics of complex networks and causal networks. This equivalence suggests that unexpectedly similar laws govern the dynamics of complex networks and spacetime in the universe, with implications to network science and cosmology. PMID:23162688

  10. Broadband network selection issues

    NASA Astrophysics Data System (ADS)

    Leimer, Michael E.

    1996-01-01

    vary as well. Cellular quality will not be tolerated by the home or business consumer. The network choices are not simple or obvious. Careful consideration of the cost and performance trades along with cable or telephone company strategic plans is required to ensure selecting the best network.

  11. Cellular and System Biology of Memory: Timing, Molecules, and Beyond.

    PubMed

    Korte, Martin; Schmitz, Dietmar

    2016-04-01

    The storage of information in the mammalian nervous systems is dependent on a delicate balance between change and stability of neuronal networks. The induction and maintenance of processes that lead to changes in synaptic strength to a multistep process which can lead to long-lasting changes, which starts and ends with a highly choreographed and perfectly timed dance of molecules in different cell types of the central nervous system. This is accompanied by synchronization of specific networks, resulting in the generation of characteristic "macroscopic" rhythmic electrical fields, whose characteristic frequencies correspond to certain activity and information-processing states of the brain. Molecular events and macroscopic fields influence each other reciprocally. We review here cellular processes of synaptic plasticity, particularly functional and structural changes, and focus on timing events that are important for the initial memory acquisition, as well as mechanisms of short- and long-term memory storage. Then, we cover the importance of epigenetic events on the long-time range. Furthermore, we consider how brain rhythms at the network level participate in processes of information storage and by what means they participating in it. Finally, we examine memory consolidation at the system level during processes of sleep. PMID:26960344

  12. MILLIMETER-WAVE EMISSIVITY OF CELLULAR SYSTEMS

    EPA Science Inventory

    A general analysis has been presented of the millimeter-wave and farinfrared spectroscopic properties of in vivo cellular systems, and of the boson radiative equilibrium with steady-state nonequilibrium molecular systems. The frequency threshhold of spectroscopic properties assoc...

  13. The Roles of Cellular Nanomechanics in Cancer

    PubMed Central

    Yallapu, Murali M.; Katti, Kalpana S.; Katti, Dinesh R.; Mishra, Sanjay R.; Khan, Sheema; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    The biomechanical properties of cells and tissues may be instrumental in increasing our understanding of cellular behavior and cellular manifestations of diseases such as cancer. Nanomechanical properties can offer clinical translation of therapies beyond what are currently employed. Nanomechanical properties, often measured by nanoindentation methods using atomic force microscopy, may identify morphological variations, cellular binding forces, and surface adhesion behaviors that efficiently differentiate normal cells and cancer cells. The aim of this review is to examine current research involving the general use of atomic force microscopy/nanoindentation in measuring cellular nanomechanics; various factors and instrumental conditions that influence the nanomechanical properties of cells; and implementation of nanoindentation methods to distinguish cancer cells from normal cells or tissues. Applying these fundamental nanomechanical properties to current discoveries in clinical treatment may result in greater efficiency in diagnosis, treatment, and prevention of cancer, which ultimately can change the lives of patients. PMID:25137233

  14. Modeling of fatigue for cellular materials

    SciTech Connect

    Huang, J.S.; Lin, J.Y.

    1998-12-31

    Dimensional arguments are used to analyze the fatigue of cellular materials. A modeling describing the fatigue of foams with or without macrocrack is derived and compared to the existing experimental data of cementitious foams and phenolic foams; agreement is good.

  15. Measurement Techniques for Cellular Biomechanics In Vitro

    PubMed Central

    Addae-Mensah, Kweku A; Wikswo, John P

    2014-01-01

    Living cells and tissues experience mechanical forces in their physiological environments that are known to affect many cellular processes. Also of importance are the mechanical properties of cells, as well as the microforces generated by cellular processes themselves in their microenvironments. The difficulty associated with studying these phenomena in vivo has led to alternatives such as using in vitro models. The need for experimental techniques for investigating cellular biomechanics and mechanobiology in vitro has fueled an evolution in the technology used in these studies. Particularly noteworthy are some of the new biomicroelectromechanical systems (BioMEMs) devices and techniques that have been introduced to the field. We describe some of the cellular micromechanical techniques and methods that have been developed for in vitro studies, and provide summaries of the ranges of measured values of various biomechanical quantities. We also briefly address some of our experiences in using these methods and include modifications we have introduced in order to improve them. PMID:18445766

  16. The role of sirtuins in cellular homeostasis.

    PubMed

    Kupis, Wioleta; Pałyga, Jan; Tomal, Ewa; Niewiadomska, Ewa

    2016-09-01

    Sirtuins are evolutionarily conserved nicotinamide adenine dinucleotide (NAD(+))-dependent lysine deacylases or ADP-ribosyltransferases. These cellular enzymes are metabolic sensors sensitive to NAD(+) levels that maintain physiological homeostasis in the animal and plant cells. PMID:27154583

  17. Cellular automata to describe seismicity: A review

    NASA Astrophysics Data System (ADS)

    Jiménez, Abigail

    2013-12-01

    Cellular Automata have been used in the literature to describe seismicity. We first historically introduce Cellular Automata and provide some important definitions. Then we proceed to review the most important models, most of them being variations of the spring-block model proposed by Burridge and Knopoff, and describe the most important results obtained from them. We discuss the relation with criticality and also describe some models that try to reproduce real data.

  18. Cellular reprogramming and hepatocellular carcinoma development.

    PubMed

    Zheng, Yun-Wen; Nie, Yun-Zhong; Taniguchi, Hideki

    2013-12-21

    Hepatocellular carcinoma (HCC) is one of the most common cancers, and is also the leading cause of death worldwide. Studies have shown that cellular reprogramming contributes to chemotherapy and/or radiotherapy resistance and the recurrence of cancers. In this article, we summarize and discuss the latest findings in the area of cellular reprogramming in HCC. The aberrant expression of transcription factors OCT4, KLF4, SOX2, c-MYC, NANOG, and LIN28 have been also observed, and the expression of these transcription factors is associated with unfavorable clinical outcomes in HCC. Studies indicate that cellular reprogramming may play a critical role in the occurrence and recurrence of HCC. Recent reports have shown that DNA methylation, miRNAs, tumor microenvironment, and signaling pathways can induce the expression of stemness transcription factors, which leads to cellular reprogramming in HCC. Furthermore, studies indicate that therapies based on cellular reprogramming could revolutionize HCC treatment. Finally, a novel therapeutic concept is discussed: reprogramming control therapy. A potential reprogramming control therapy method could be developed based on the reprogramming demonstrated in HCC studies and applied at two opposing levels: differentiation and reprogramming. Our increasing understanding and control of cellular programming should facilitate the exploitation of this novel therapeutic concept and its application in clinical HCC treatment, which may represent a promising strategy in the future that is not restricted to liver cancer. PMID:24379607

  19. Recent Advances in Cellular Glycomic Analyses

    PubMed Central

    Furukawa, Jun-ichi; Fujitani, Naoki; Shinohara, Yasuro

    2013-01-01

    A large variety of glycans is intricately located on the cell surface, and the overall profile (the glycome, given the entire repertoire of glycoconjugate-associated sugars in cells and tissues) is believed to be crucial for the diverse roles of glycans, which are mediated by specific interactions that control cell-cell adhesion, immune response, microbial pathogenesis and other cellular events. The glycomic profile also reflects cellular alterations, such as development, differentiation and cancerous change. A glycoconjugate-based approach would therefore be expected to streamline discovery of novel cellular biomarkers. Development of such an approach has proven challenging, due to the technical difficulties associated with the analysis of various types of cellular glycomes; however, recent progress in the development of analytical methodologies and strategies has begun to clarify the cellular glycomics of various classes of glycoconjugates. This review focuses on recent advances in the technical aspects of cellular glycomic analyses of major classes of glycoconjugates, including N- and O-linked glycans, derived from glycoproteins, proteoglycans and glycosphingolipids. Articles that unveil the glycomics of various biologically important cells, including embryonic and somatic stem cells, induced pluripotent stem (iPS) cells and cancer cells, are discussed. PMID:24970165

  20. Network Solutions.

    ERIC Educational Resources Information Center

    Vietzke, Robert; And Others

    1996-01-01

    This special section explains the latest developments in networking technologies, profiles school districts benefiting from successful implementations, and reviews new products for building networks. Highlights include ATM (asynchronous transfer mode), cable modems, networking switches, Internet screening software, file servers, network management…

  1. IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway.

    PubMed

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

    2012-08-24

    Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated β-galactosidase (SA-β-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, γH2AX, the increased levels of p53 and p21 proteins, and activated SA-β-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-β-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. PMID:22877754

  2. Networking standards

    NASA Technical Reports Server (NTRS)

    Davies, Mark

    1991-01-01

    The enterprise network is currently a multivendor environment consisting of many defacto and proprietary standards. During the 1990s, these networks will evolve towards networks which are based on international standards in both Local Area Network (LAN) and Wide Area Network (WAN) space. Also, you can expect to see the higher level functions and applications begin the same transition. Additional information is given in viewgraph form.

  3. Semantic Networks and Social Networks

    ERIC Educational Resources Information Center

    Downes, Stephen

    2005-01-01

    Purpose: To illustrate the need for social network metadata within semantic metadata. Design/methodology/approach: Surveys properties of social networks and the semantic web, suggests that social network analysis applies to semantic content, argues that semantic content is more searchable if social network metadata is merged with semantic web…

  4. Cellular Growth Arrest and Persistence from Enzyme Saturation

    PubMed Central

    Ray, J. Christian J.; Wickersheim, Michelle L.; Jalihal, Ameya P.; Adeshina, Yusuf O.; Cooper, Tim F.; Balázsi, Gábor

    2016-01-01

    Metabolic efficiency depends on the balance between supply and demand of metabolites, which is sensitive to environmental and physiological fluctuations, or noise, causing shortages or surpluses in the metabolic pipeline. How cells can reliably optimize biomass production in the presence of metabolic fluctuations is a fundamental question that has not been fully answered. Here we use mathematical models to predict that enzyme saturation creates distinct regimes of cellular growth, including a phase of growth arrest resulting from toxicity of the metabolic process. Noise can drive entry of single cells into growth arrest while a fast-growing majority sustains the population. We confirmed these predictions by measuring the growth dynamics of Escherichia coli utilizing lactose as a sole carbon source. The predicted heterogeneous growth emerged at high lactose concentrations, and was associated with cell death and production of antibiotic-tolerant persister cells. These results suggest how metabolic networks may balance costs and benefits, with important implications for drug tolerance. PMID:27010473

  5. Cellular Dewetting: Opening of Macroapertures in Endothelial Cells

    NASA Astrophysics Data System (ADS)

    Gonzalez-Rodriguez, David; Maddugoda, Madhavi P.; Stefani, Caroline; Janel, Sebastien; Lafont, Frank; Cuvelier, Damien; Lemichez, Emmanuel; Brochard-Wyart, Françoise

    2012-05-01

    Pathogenic bacteria can cross from blood vessels to host tissues by opening transendothelial cell macroapertures (TEMs). To induce TEM opening, bacteria intoxicate endothelial cells with proteins that disrupt the contractile cytoskeletal network. Cell membrane tension is no longer resisted by contractile fibers, leading to the opening of TEMs. Here we model the opening of TEMs as a new form of dewetting. While liquid dewetting is irreversible, we show that cellular dewetting is transient. Our model predicts the minimum radius for hole nucleation, the maximum TEM size, and the dynamics of TEM opening, in good agreement with experimental data. The physical model is then coupled with biological experimental data to reveal that the protein missing in metastasis (MIM) controls the line tension at the rim of the TEM and opposes its opening.

  6. Motor Schema-Based Cellular Automaton Model for Pedestrian Dynamics

    NASA Astrophysics Data System (ADS)

    Weng, Wenguo; Hasemi, Yuji; Fan, Weicheng

    A new cellular automaton model for pedestrian dynamics based on motor schema is presented. Each pedestrian is treated as an intelligent mobile robot, and motor schemas including move-to-goal, avoid-away and avoid-around drive pedestrians to interact with their environment. We investigate the phenomenon of many pedestrians with different move velocities escaping from a room. The results show that the pedestrian with high velocity have predominance in competitive evacuation, if we only consider repulsion from or avoiding around other pedestrians, and interaction with each other leads to disordered evacuation, i.e., decreased evacuation efficiency. Extensions of the model using learning algorithms for controlling pedestrians, i.e., reinforcement learning, neural network and genetic algorithms, etc. are noted.

  7. Cellular automaton modeling of mesospheric optical emissions: Sprites

    SciTech Connect

    Hayakawa, M.; Iudin, D. I.; Mareev, E. A.; Trakhtengerts, V. Y.

    2007-04-15

    This paper presents a new attempt to model two-dimensional mesospheric optical emissions named sprites with the use of a cellular automaton network. A large-scale model of sprites based on the phenomenological percolation-like probabilistic approach is developed to model streamer discharges in sprites. It is shown that a sprite is a self-affine structure rather than a simple fractal one, and that this self-affine structure is tightly connected with directed percolation phenomena. The system is found to evolve in the vicinity of the percolation threshold, which results in a wide variety of sprite characteristics even under similar initial conditions. The approach developed allows us to estimate a maximum size of the discharge pattern to be formed.

  8. Cellular MYCro Economics: Balancing MYC Function with MYC Expression

    PubMed Central

    Levens, David

    2013-01-01

    The expression levels of the MYC oncoprotein have long been recognized to be associated with the outputs of major cellular processes including proliferation, cell growth, apoptosis, differentiation, and metabolism. Therefore, to understand how MYC operates, it is important to define quantitatively the relationship between MYC input and expression output for its targets as well as the higher-order relationships between the expression levels of subnetwork components and the flow of information and materials through those networks. Two different views of MYC are considered, first as a molecular microeconomic manager orchestrating specific positive and negative responses at individual promoters in collaboration with other transcription and chromatin components, and second, as a macroeconomic czar imposing an overarching rule onto all active genes. In either case, c-myc promoter output requires multiple inputs and exploits diverse mechanisms to tune expression to the appropriate levels relative to the thresholds of expression that separate health and disease. PMID:24186489

  9. Cellular origin and ultrastructure of membranes induced during poliovirus infection.

    PubMed Central

    Schlegel, A; Giddings, T H; Ladinsky, M S; Kirkegaard, K

    1996-01-01

    Poliovirus RNA replicative complexes are associated with cytoplasmic membranous structures that accumulate during viral infection. These membranes were immunoisolated by using a monoclonal antibody against the viral nonstructural protein 2C. Biochemical analysis of the isolated membranes revealed that several organelles of the host cell (lysosomes, trans-Golgi stack and trans-Golgi network, and endoplasmic reticulum) contributed to the virus-induced membranous structures. Electron microscopy of infected cells preserved by high-pressure freezing revealed that the virus-induced membranes contain double lipid bilayers that surround apparently cytosolic material. Immunolabeling experiments showed that poliovirus proteins 2C and 3D were localized to the same membranes as the cellular markers tested. The morphological and biochemical data are consistent with the hypothesis that autophagy or a similar host process is involved in the formation of the poliovirus-induced membranes. PMID:8794292

  10. PIFs: pivotal components in a cellular signaling hub

    PubMed Central

    Leivar, Pablo; Quail, Peter H.

    2010-01-01

    A small subset of basic helix–loop–helix transcription factors called PIFs [phytochrome (phy)-interacting factors] act to repress seed germination, promote seedling skotomorphogenesis and promote shade-avoidance through regulated expression of over a thousand genes. Light-activated phy molecules directly reverse these activities by inducing rapid degradation of the PIF proteins. Here, we review recent advances in dissecting this signaling pathway and examine emerging evidence that indicates that other pathways also converge to regulate PIF activity, including the gibberellin pathway, the circadian clock and high temperature. The PIFs thus have broader roles than previously appreciated, functioning as a cellular signaling hub that integrates multiple signals to orchestrate regulation of the transcriptional network that drives multiple facets of downstream morphogenesis. The relative contributions of the individual PIFs to this spectrum of regulatory functions ranges from quantitatively redundant to qualitatively distinct. PMID:20833098

  11. Cellular Automata Generalized To An Inferential System

    NASA Astrophysics Data System (ADS)

    Blower, David J.

    2007-11-01

    Stephen Wolfram popularized elementary one-dimensional cellular automata in his book, A New Kind of Science. Among many remarkable things, he proved that one of these cellular automata was a Universal Turing Machine. Such cellular automata can be interpreted in a different way by viewing them within the context of the formal manipulation rules from probability theory. Bayes's Theorem is the most famous of such formal rules. As a prelude, we recapitulate Jaynes's presentation of how probability theory generalizes classical logic using modus ponens as the canonical example. We emphasize the important conceptual standing of Boolean Algebra for the formal rules of probability manipulation and give an alternative demonstration augmenting and complementing Jaynes's derivation. We show the complementary roles played in arguments of this kind by Bayes's Theorem and joint probability tables. A good explanation for all of this is afforded by the expansion of any particular logic function via the disjunctive normal form (DNF). The DNF expansion is a useful heuristic emphasized in this exposition because such expansions point out where relevant 0s should be placed in the joint probability tables for logic functions involving any number of variables. It then becomes a straightforward exercise to rely on Boolean Algebra, Bayes's Theorem, and joint probability tables in extrapolating to Wolfram's cellular automata. Cellular automata are seen as purely deductive systems, just like classical logic, which probability theory is then able to generalize. Thus, any uncertainties which we might like to introduce into the discussion about cellular automata are handled with ease via the familiar inferential path. Most importantly, the difficult problem of predicting what cellular automata will do in the far future is treated like any inferential prediction problem.

  12. Multiplexed imaging of intracellular protein networks.

    PubMed

    Grecco, Hernán E; Imtiaz, Sarah; Zamir, Eli

    2016-08-01

    Cellular functions emerge from the collective action of a large number of different proteins. Understanding how these protein networks operate requires monitoring their components in intact cells. Due to intercellular and intracellular molecular variability, it is important to monitor simultaneously multiple components at high spatiotemporal resolution. However, inherent trade-offs narrow the boundaries of achievable multiplexed imaging. Pushing these boundaries is essential for a better understanding of cellular processes. Here the motivations, challenges and approaches for multiplexed imaging of intracellular protein networks are discussed. © 2016 International Society for Advancement of Cytometry. PMID:27183498

  13. Approximating the stabilization of cellular metabolism by compartmentalization.

    PubMed

    Fürtauer, Lisa; Nägele, Thomas

    2016-06-01

    Biochemical regulation in compartmentalized metabolic networks is highly complex and non-intuitive. This is particularly true for cells of higher plants showing one of the most compartmentalized cellular structures across all kingdoms of life. The interpretation and testable hypothesis generation from experimental data on such complex systems is a challenging step in biological research and biotechnological applications. While it is known that subcellular compartments provide defined reaction spaces within a cell allowing for the tight coordination of complex biochemical reaction sequences, its role in the coordination of metabolic signals during metabolic reprogramming due to environmental fluctuations is less clear. In the present study, we numerically analysed the effects of environmental fluctuations in a subcellular metabolic network with regard to the stability of an experimentally observed steady state in the genetic model plant Arabidopsis thaliana. Applying a method for kinetic parameter normalization, several millions of probable enzyme kinetic parameter constellations were simulated and evaluated with regard to the stability information of the metabolic homeostasis. Information about the stability of the metabolic steady state was derived from real parts of eigenvalues of Jacobian matrices. Our results provide evidence for a differential stabilizing contribution of different subcellular compartments. We could identify stabilizing and destabilizing network components which we could classify according to their subcellular localization. The findings prove that a highly dynamic interplay between intracellular compartments is preliminary for an efficient stabilization of a metabolic homeostasis after environmental perturbation. Further, our results provide evidence that feedback-inhibition originating from the cytosol and plastid seem to stabilize the sucrose homeostasis more efficiently than vacuolar control. In summary, our results indicate stabilizing and

  14. A Programmable Cellular-Automata Polarized Dirac Vacuum

    NASA Astrophysics Data System (ADS)

    Osoroma, Drahcir S.

    2013-09-01

    We explore properties of a `Least Cosmological Unit' (LCU) as an inherent spacetime raster tiling or tessellating the unique backcloth of Holographic Anthropic Multiverse (HAM) cosmology as an array of programmable cellular automata. The HAM vacuum is a scale-invariant HD extension of a covariant polarized Dirac vacuum with `bumps' and `holes' typically described by extended electromagnetic theory corresponding to an Einstein energy-dependent spacetime metric admitting a periodic photon mass. The new cosmology incorporates a unique form of M-Theoretic Calabi-Yau-Poincaré Dodecadedral-AdS5-DS5space (PDS) with mirror symmetry best described by an HD extension of Cramer's Transactional Interpretation when integrated also with an HD extension of the de Broglie-Bohm-Vigier causal interpretation of quantum theory. We incorporate a unique form of large-scale additional dimensionality (LSXD) bearing some similarity to that conceived by Randall and Sundrum; and extend the fundamental basis of our model to the Unified Field, UF. A Sagnac Effect rf-pulsed incursive resonance hierarchy is utilized to manipulate and ballistically program the geometric-topological properties of this putative LSXD space-spacetime network. The model is empirically testable; and it is proposed that a variety of new technologies will arise from ballistic programming of tessellated LCU vacuum cellular automata.

  15. Identification of cellular senescence-specific genes by comparative transcriptomics

    PubMed Central

    Nagano, Taiki; Nakano, Masayuki; Nakashima, Akio; Onishi, Kengo; Yamao, Shunsuke; Enari, Masato; Kikkawa, Ushio; Kamada, Shinji

    2016-01-01

    Cellular senescence is defined as permanent cell cycle arrest induced by various stresses. Although the p53 transcriptional activity is essential for senescence induction, the downstream genes that are crucial for senescence remain unsolved. Here, by using a developed experimental system in which cellular senescence or apoptosis is induced preferentially by altering concentration of etoposide, a DNA-damaging drug, we compared gene expression profiles of senescent and apoptotic cells by microarray analysis. Subtraction of the expression profile of apoptotic cells identified 20 genes upregulated specifically in senescent cells. Furthermore, 6 out of 20 genes showed p53-dependent upregulation by comparing gene expression between p53-proficient and -deficient cells. These 6 genes were also upregulated during replicative senescence of normal human diploid fibroblasts, suggesting that upregulation of these genes is a general phenomenon in senescence. Among these genes, 2 genes (PRODH and DAO) were found to be directly regulated by p53, and ectopic expression of 4 genes (PRODH, DAO, EPN3, and GPR172B) affected senescence phenotypes induced by etoposide treatment. Collectively, our results identified several proteins as novel downstream effectors of p53-mediated senescence and provided new clues for further research on the complex signalling networks underlying the induction and maintenance of senescence. PMID:27545311

  16. Antioxidant responses and cellular adjustments to oxidative stress

    PubMed Central

    Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

    2015-01-01

    Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases. PMID:26233704

  17. Microtubules and Their Role in Cellular Stress in Cancer

    PubMed Central

    Parker, Amelia L.; Kavallaris, Maria; McCarroll, Joshua A.

    2014-01-01

    Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers, and are involved in cell movement, intracellular trafficking, and mitosis. In the context of cancer, the tubulin family of proteins is recognized as the target of the tubulin-binding chemotherapeutics, which suppress the dynamics of the mitotic spindle to cause mitotic arrest and cell death. Importantly, changes in microtubule stability and the expression of different tubulin isotypes as well as altered post-translational modifications have been reported for a range of cancers. These changes have been correlated with poor prognosis and chemotherapy resistance in solid and hematological cancers. However, the mechanisms underlying these observations have remained poorly understood. Emerging evidence suggests that tubulins and microtubule-associated proteins may play a role in a range of cellular stress responses, thus conferring survival advantage to cancer cells. This review will focus on the importance of the microtubule–protein network in regulating critical cellular processes in response to stress. Understanding the role of microtubules in this context may offer novel therapeutic approaches for the treatment of cancer. PMID:24995158

  18. Identification of cellular senescence-specific genes by comparative transcriptomics.

    PubMed

    Nagano, Taiki; Nakano, Masayuki; Nakashima, Akio; Onishi, Kengo; Yamao, Shunsuke; Enari, Masato; Kikkawa, Ushio; Kamada, Shinji

    2016-01-01

    Cellular senescence is defined as permanent cell cycle arrest induced by various stresses. Although the p53 transcriptional activity is essential for senescence induction, the downstream genes that are crucial for senescence remain unsolved. Here, by using a developed experimental system in which cellular senescence or apoptosis is induced preferentially by altering concentration of etoposide, a DNA-damaging drug, we compared gene expression profiles of senescent and apoptotic cells by microarray analysis. Subtraction of the expression profile of apoptotic cells identified 20 genes upregulated specifically in senescent cells. Furthermore, 6 out of 20 genes showed p53-dependent upregulation by comparing gene expression between p53-proficient and -deficient cells. These 6 genes were also upregulated during replicative senescence of normal human diploid fibroblasts, suggesting that upregulation of these genes is a general phenomenon in senescence. Among these genes, 2 genes (PRODH and DAO) were found to be directly regulated by p53, and ectopic expression of 4 genes (PRODH, DAO, EPN3, and GPR172B) affected senescence phenotypes induced by etoposide treatment. Collectively, our results identified several proteins as novel downstream effectors of p53-mediated senescence and provided new clues for further research on the complex signalling networks underlying the induction and maintenance of senescence. PMID:27545311

  19. Model of cellular mechanotransduction via actin stress fibers.

    PubMed

    Gouget, Cecile L M; Hwang, Yongyun; Barakat, Abdul I

    2016-04-01

    Mechanical stresses due to blood flow regulate vascular endothelial cell structure and function and play a key role in arterial physiology and pathology. In particular, the development of atherosclerosis has been shown to correlate with regions of disturbed blood flow where endothelial cells are round and have a randomly organized cytoskeleton. Thus, deciphering the relation between the mechanical environment, cell structure, and cell function is a key step toward understanding the early development of atherosclerosis. Recent experiments have demonstrated very rapid ([Formula: see text]100 ms) and long-distance ([Formula: see text]10 [Formula: see text]m) cellular mechanotransduction in which prestressed actin stress fibers play a critical role. Here, we develop a model of mechanical signal transmission within a cell by describing strains in a network of prestressed viscoelastic stress fibers following the application of a force to the cell surface. We find force transmission dynamics that are consistent with experimental results. We also show that the extent of stress fiber alignment and the direction of the applied force relative to this alignment are key determinants of the efficiency of mechanical signal transmission. These results are consistent with the link observed experimentally between cytoskeletal organization, mechanical stress, and cellular responsiveness to stress. Based on these results, we suggest that mechanical strain of actin stress fibers under force constitutes a key link in the mechanotransduction chain. PMID:26081725

  20. Daily magnesium fluxes regulate cellular timekeeping and energy balance.

    PubMed

    Feeney, Kevin A; Hansen, Louise L; Putker, Marrit; Olivares-Yañez, Consuelo; Day, Jason; Eades, Lorna J; Larrondo, Luis F; Hoyle, Nathaniel P; O'Neill, John S; van Ooijen, Gerben

    2016-04-21

    Circadian clocks are fundamental to the biology of most eukaryotes, coordinating behaviour and physiology to resonate with the environmental cycle of day and night through complex networks of clock-controlled genes. A fundamental knowledge gap exists, however, between circadian gene expression cycles and the biochemical mechanisms that ultimately facilitate circadian regulation of cell biology. Here we report circadian rhythms in the intracellular concentration of magnesium ions, [Mg(2+)]i, which act as a cell-autonomous timekeeping component to determine key clock properties both in a human cell line and in a unicellular alga that diverged from each other more than 1 billion years ago. Given the essential role of Mg(2+) as a cofactor for ATP, a functional consequence of [Mg(2+)]i oscillations is dynamic regulation of cellular energy expenditure over the daily cycle. Mechanistically, we find that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression. The global regulation of nucleotide triphosphate turnover by intracellular Mg(2+) availability has potential to impact upon many of the cell's more than 600 MgATP-dependent enzymes and every cellular system where MgNTP hydrolysis becomes rate limiting. Indeed, we find that circadian control of translation by mTOR is regulated through [Mg(2+)]i oscillations. It will now be important to identify which additional biological processes are subject to this form of regulation in tissues of multicellular organisms such as plants and humans, in the context of health and disease. PMID:27074515

  1. Cellular phenotype database: a repository for systems microscopy data

    PubMed Central

    Kirsanova, Catherine; Brazma, Alvis; Rustici, Gabriella; Sarkans, Ugis

    2015-01-01

    Motivation: The Cellular Phenotype Database (CPD) is a repository for data derived from high-throughput systems microscopy studies. The aims of this resource are: (i) to provide easy access to cellular phenotype and molecular localization data for the broader research community; (ii) to facilitate integration of independent phenotypic studies by means of data aggregation techniques, including use of an ontology and (iii) to facilitate development of analytical methods in this field. Results: In this article we present CPD, its data structure and user interface, propose a minimal set of information describing RNA interference experiments, and suggest a generic schema for management and aggregation of outputs from phenotypic or molecular localization experiments. The database has a flexible structure for management of data from heterogeneous sources of systems microscopy experimental outputs generated by a variety of protocols and technologies and can be queried by gene, reagent, gene attribute, study keywords, phenotype or ontology terms. Availability and implementation: CPD is developed as part of the Systems Microscopy Network of Excellence and is accessible at http://www.ebi.ac.uk/fg/sym. Contact: jes@ebi.ac.uk or ugis@ebi.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25861964

  2. Decisions on the fly in cellular sensory systems

    PubMed Central

    Siggia, Eric D.; Vergassola, Massimo

    2013-01-01

    Cells send and receive signals through pathways that have been defined in great detail biochemically, and it is often presumed that the signals convey only level information. Cell signaling in the presence of noise is extensively studied but only rarely is the speed required to make a decision considered. However, in the immune system, rapidly developing embryos, and cellular response to stress, fast and accurate actions are required. Statistical theory under the rubric of “exploit–explore” quantifies trade-offs between decision speed and accuracy and supplies rigorous performance bounds and algorithms that realize them. We show that common protein phosphorylation networks can implement optimal decision theory algorithms and speculate that the ubiquitous chemical modifications to receptors during signaling actually perform analog computations. We quantify performance trade-offs when the cellular system has incomplete knowledge of the data model. For the problem of sensing the time when the composition of a ligand mixture changes, we find a nonanalytic dependence on relative concentrations and specify the number of parameters needed for near-optimal performance and how to adjust them. The algorithms specify the minimal computation that has to take place on a single receptor before the information is pooled across the cell. PMID:24019464

  3. Quantifying cellular interaction dynamics in 3-D fluorescence microscopy data

    PubMed Central

    Klauschen, Frederick; Ishii, Masaru; Qi, Hai; Bajénoff, Marc; Egen, Jackson G.; Germain, Ronald N.; Meier-Schellersheim, Martin

    2012-01-01

    The wealth of information available from advanced fluorescence imaging techniques used to analyze biological processes with high spatial and temporal resolution calls for high-throughput image analysis methods. Here, we describe a fully automated approach to analyzing cellular interaction behavior in 3-D fluorescence microscopy images. As example application we present the analysis of drug-induced and S1P1-knock-out-related changes in bone-osteoclast interactions. Moreover, we apply our approach to images showing the spatial association of dendritic cells with the fibroblastic reticular cell network within lymph nodes and to microscopy data about T-B lymphocyte synapse formation. Such analyses that yield important information about the molecular mechanisms determining cellular interaction behavior would be very difficult to perform with approaches that rely on manual/semi-automated analyses. This protocol integrates adaptive threshold segmentation, object detection, adaptive color channel merging and neighborhood analysis and permits rapid, standardized, quantitative analysis and comparison of the relevant features in large data sets. PMID:19696749

  4. Network representations of immune system complexity

    PubMed Central

    Subramanian, Naeha; Torabi-Parizi, Parizad; Gottschalk, Rachel A.; Germain, Ronald N.; Dutta, Bhaskar

    2015-01-01

    The mammalian immune system is a dynamic multi-scale system composed of a hierarchically organized set of molecular, cellular and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single cell responses to increasingly complex networks of in vivo cellular interaction, positioning and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather non-linear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multi-scale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating ‘omics’ and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks. PMID:25625853

  5. Network representations of immune system complexity.

    PubMed

    Subramanian, Naeha; Torabi-Parizi, Parizad; Gottschalk, Rachel A; Germain, Ronald N; Dutta, Bhaskar

    2015-01-01

    The mammalian immune system is a dynamic multiscale system composed of a hierarchically organized set of molecular, cellular, and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single-cell responses to increasingly complex networks of in vivo cellular interaction, positioning, and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather nonlinear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multiscale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels, while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating 'omics' and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular- and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks. PMID:25625853

  6. A Biologically Inspired Network Design Model

    PubMed Central

    Zhang, Xiaoge; Adamatzky, Andrew; Chan, Felix T.S.; Deng, Yong; Yang, Hai; Yang, Xin-She; Tsompanas, Michail-Antisthenis I.; Sirakoulis, Georgios Ch.; Mahadevan, Sankaran

    2015-01-01

    A network design problem is to select a subset of links in a transport network that satisfy passengers or cargo transportation demands while minimizing the overall costs of the transportation. We propose a mathematical model of the foraging behaviour of slime mould P. polycephalum to solve the network design problem and construct optimal transport networks. In our algorithm, a traffic flow between any two cities is estimated using a gravity model. The flow is imitated by the model of the slime mould. The algorithm model converges to a steady state, which represents a solution of the problem. We validate our approach on examples of major transport networks in Mexico and China. By comparing networks developed in our approach with the man-made highways, networks developed by the slime mould, and a cellular automata model inspired by slime mould, we demonstrate the flexibility and efficiency of our approach. PMID:26041508

  7. Dynamic network analysis of protein interactions

    NASA Astrophysics Data System (ADS)

    Almaas, Eivind; Deri, Joya

    2007-03-01

    Network approaches have recently become a popular tool to study complex systems such as cellular metabolism and protein interactions. A substantial number of analyses of the protein interaction network (PIN) of the yeast Saccharomyces cerevisiae have considered this network as a static entity, not taking the network's dynamic nature into account. Here, we examine the time-variation of gene regulation superimposed on the PIN by defining mRNA expression profiles throughout the cell cycle as node weights. To characterize these network dynamics, we have both developed a set of novel network measures as well as studied previously published measures for weighted networks. We expect that our approach will provide a deeper understanding of protein regulation during the cell cycle.

  8. Analytically solvable processes on networks.

    PubMed

    Smilkov, Daniel; Kocarev, Ljupco

    2011-07-01

    We introduce a broad class of analytically solvable processes on networks. In the special case, they reduce to random walk and consensus process, the two most basic processes on networks. Our class differs from previous models of interactions (such as the stochastic Ising model, cellular automata, infinite particle systems, and the voter model) in several ways, the two most important being (i) the model is analytically solvable even when the dynamical equation for each node may be different and the network may have an arbitrary finite graph and influence structure and (ii) when local dynamics is described by the same evolution equation, the model is decomposable, with the equilibrium behavior of the system expressed as an explicit function of network topology and node dynamics. PMID:21867254

  9. Bioinformatic characterization of plant networks

    SciTech Connect

    McDermott, Jason E.; Samudrala, Ram

    2008-06-30

    Cells and organisms are governed by networks of interactions, genetic, physical and metabolic. Large-scale experimental studies of interactions between components of biological systems have been performed for a variety of eukaryotic organisms. However, there is a dearth of such data for plants. Computational methods for prediction of relationships between proteins, primarily based on comparative genomics, provide a useful systems-level view of cellular functioning and can be used to extend information about other eukaryotes to plants. We have predicted networks for Arabidopsis thaliana, Oryza sativa indica and japonica and several plant pathogens using the Bioverse (http://bioverse.compbio.washington.edu) and show that they are similar to experimentally-derived interaction networks. Predicted interaction networks for plants can be used to provide novel functional annotations and predictions about plant phenotypes and aid in rational engineering of biosynthesis pathways.

  10. Cellular ubiquitin pool dynamics and homeostasis

    PubMed Central

    Ryu, Kwon-Yul

    2014-01-01

    Ubiquitin (Ub) is a versatile signaling molecule that plays important roles in a variety of cellular processes. Cellular Ub pools, which are composed of free Ub and Ub conjugates, are in dynamic equilibrium inside cells. In particular, increasing evidence suggests that Ub homeostasis, or the maintenance of free Ub above certain threshold levels, is important for cellular function and survival under normal or stress conditions. Accurate determination of various Ub species, including levels of free Ub and specific Ub chain linkages, have become possible in biological specimens as a result of the introduction of the proteomic approach using mass spectrometry. This technology has facilitated research on dynamic properties of cellular Ub pools and has provided tools for in-depth investigation of Ub homeostasis. In this review, we have also discussed the consequences of the disruption of Ub pool dynamics and homeostasis via deletion of polyubiquitin genes or mutations of deubiquitinating enzymes. The common consequence was a reduced availability of free Ub and a significant impact on the function and viability of cells. These observations further indicate that the levels of free Ub are important determinants for cellular protection. [BMB Reports 2014; 47(9): 475-482] PMID:24924398

  11. Stochastic dynamics of macromolecular-assembly networks.

    NASA Astrophysics Data System (ADS)

    Saiz, Leonor; Vilar, Jose

    2006-03-01

    The formation and regulation of macromolecular complexes provides the backbone of most cellular processes, including gene regulation and signal transduction. The inherent complexity of assembling macromolecular structures makes current computational methods strongly limited for understanding how the physical interactions between cellular components give rise to systemic properties of cells. Here we present a stochastic approach to study the dynamics of networks formed by macromolecular complexes in terms of the molecular interactions of their components [1]. Exploiting key thermodynamic concepts, this approach makes it possible to both estimate reaction rates and incorporate the resulting assembly dynamics into the stochastic kinetics of cellular networks. As prototype systems, we consider the lac operon and phage λ induction switches, which rely on the formation of DNA loops by proteins [2] and on the integration of these protein-DNA complexes into intracellular networks. This cross-scale approach offers an effective starting point to move forward from network diagrams, such as those of protein-protein and DNA-protein interaction networks, to the actual dynamics of cellular processes. [1] L. Saiz and J.M.G. Vilar, submitted (2005). [2] J.M.G. Vilar and L. Saiz, Current Opinion in Genetics & Development, 15, 136-144 (2005).

  12. Cellular-automata method for phase unwrapping

    SciTech Connect

    Ghiglia, D.C.; Mastin, G.A.; Romero, L.A.

    1987-01-01

    Research into two-dimensional phase unwrapping has uncovered interesting and troublesome inconsistencies that cause path-dependent results. Cellular automata, which are simple, discrete mathematical systems, offered promise of computation in nondirectional, parallel manner. A cellular automaton was discovered that can unwrap consistent phase data in n dimensions in a path-independent manner and can automatically accommodate noise-induced (pointlike) inconsistencies and arbitrary boundary conditions (region partitioning). For data with regional (nonpointlike) inconsistencies, no phase-unwrapping algorithm will converge, including the cellular-automata approach. However, the automata method permits more simple visualization of the regional inconsistencies. Examples of its behavior on one- and two-dimensional data are presented.

  13. Infrared image enhancement using Cellular Automata

    NASA Astrophysics Data System (ADS)

    Qi, Wei; Han, Jing; Zhang, Yi; Bai, Lian-fa

    2016-05-01

    Image enhancement is a crucial technique for infrared images. The clear image details are important for improving the quality of infrared images in computer vision. In this paper, we propose a new enhancement method based on two priors via Cellular Automata. First, we directly learn the gradient distribution prior from the images via Cellular Automata. Second, considering the importance of image details, we propose a new gradient distribution error to encode the structure information via Cellular Automata. Finally, an iterative method is applied to remap the original image based on two priors, further improving the quality of enhanced image. Our method is simple in implementation, easy to understand, extensible to accommodate other vision tasks, and produces more accurate results. Experiments show that the proposed method performs better than other methods using qualitative and quantitative measures.

  14. Crack Propagation in Bamboo's Hierarchical Cellular Structure

    PubMed Central

    Habibi, Meisam K.; Lu, Yang

    2014-01-01

    Bamboo, as a natural hierarchical cellular material, exhibits remarkable mechanical properties including excellent flexibility and fracture toughness. As far as bamboo as a functionally graded bio-composite is concerned, the interactions of different constituents (bamboo fibers; parenchyma cells; and vessels.) alongside their corresponding interfacial areas with a developed crack should be of high significance. Here, by using multi-scale mechanical characterizations coupled with advanced environmental electron microscopy (ESEM), we unambiguously show that fibers' interfacial areas along with parenchyma cells' boundaries were preferred routes for crack growth in both radial and longitudinal directions. Irrespective of the honeycomb structure of fibers along with cellular configuration of parenchyma ground, the hollow vessels within bamboo culm affected the crack propagation too, by crack deflection or crack-tip energy dissipation. It is expected that the tortuous crack propagation mode exhibited in the present study could be applicable to other cellular natural materials as well. PMID:24998298

  15. Pelvic Retroperitoneal Cellular Leiomyoma: A Case Report.

    PubMed

    Tantitamit, Tanitra; Hamontri, Suttha; Rangsiratanakul, Likit; Suksamarnwong, Maysita

    2015-10-01

    Leiomyomas are common benign gynecological tumors and usually arise in the uterus. The retroperitoneal cellular leiomyoma, one of the unusual manifestations, is a rare tumor. Diagnosis and treatment are challenges. We report a case of 65-year-old women presented with an asymptomatic mass beneath the right posterior vaginal mucosa. CT imaging revealed heterogeneous mass 6 cm in the pelvic cavity abutted lower segment of uterus, cervix, and vagina. The provisional diagnosis was subserosal cervical leiomyoma. She underwent exploratory laparotomy. Intra-operative, a normal size uterus was found separately from retroperitoneal pelvic mass at the level of internal os. Histological report confirmed cellular leiomyoma later Total hysterectomy, bilateral salpingoophorectomy and completely excision of tumor were achieved with good outcome. Our patient represents the rare case of retroperitoneal cellular leiomyoma, which is hardly identified from internal examination and preoperative imaging. Surgical removal is essential for pathological diagnosis and treatment. PMID:26817226

  16. Cellular automatons applied to gas dynamic problems

    NASA Astrophysics Data System (ADS)

    Long, Lyle N.; Coopersmith, Robert M.; McLachlan, B. G.

    1987-06-01

    This paper compares the results of a relatively new computational fluid dynamics method, cellular automatons, with experimental data and analytical results. This technique has been shown to qualitatively predict fluidlike behavior; however, there have been few published comparisons with experiment or other theories. Comparisons are made for a one-dimensional supersonic piston problem, Stokes first problem, and the flow past a normal flat plate. These comparisons are used to assess the ability of the method to accurately model fluid dynamic behavior and to point out its limitations. Reasonable results were obtained for all three test cases, but the fundamental limitations of cellular automatons are numerous. It may be misleading, at this time, to say that cellular automatons are a computationally efficient technique. Other methods, based on continuum or kinetic theory, would also be very efficient if as little of the physics were included.

  17. Cellular automatons applied to gas dynamic problems

    NASA Technical Reports Server (NTRS)

    Long, Lyle N.; Coopersmith, Robert M.; Mclachlan, B. G.

    1987-01-01

    This paper compares the results of a relatively new computational fluid dynamics method, cellular automatons, with experimental data and analytical results. This technique has been shown to qualitatively predict fluidlike behavior; however, there have been few published comparisons with experiment or other theories. Comparisons are made for a one-dimensional supersonic piston problem, Stokes first problem, and the flow past a normal flat plate. These comparisons are used to assess the ability of the method to accurately model fluid dynamic behavior and to point out its limitations. Reasonable results were obtained for all three test cases, but the fundamental limitations of cellular automatons are numerous. It may be misleading, at this time, to say that cellular automatons are a computationally efficient technique. Other methods, based on continuum or kinetic theory, would also be very efficient if as little of the physics were included.

  18. Parametric study of double cellular detonation structure

    NASA Astrophysics Data System (ADS)

    Khasainov, B.; Virot, F.; Presles, H.-N.; Desbordes, D.

    2013-05-01

    A parametric numerical study is performed of a detonation cellular structure in a model gaseous explosive mixture whose decomposition occurs in two successive exothermic reaction steps with markedly different characteristic times. Kinetic and energetic parameters of both reactions are varied in a wide range in the case of one-dimensional steady and two-dimensional (2D) quasi-steady self-supported detonations. The range of governing parameters of both exothermic steps is defined where a "marked" double cellular structure exists. It is shown that the two-level cellular structure is completely governed by the kinetic parameters and the local overdrive ratio of the detonation front propagating inside large cells. Furthermore, since it is quite cumbersome to use detailed chemical kinetics in unsteady 2D case, the proposed work should help to identify the mixtures and the domain of their equivalence ratio where double detonation structure could be observed.

  19. Understanding cellular architecture in cancer cells

    NASA Astrophysics Data System (ADS)

    Bianco, Simone; Tang, Chao

    2011-03-01

    Understanding the development of cancer is an important goal for today's science. The morphology of cellular organelles, such as the nucleus, the nucleoli and the mitochondria, which is referred to as cellular architecture or cytoarchitecture, is an important indicator of the state of the cell. In particular, there are striking difference between the cellular architecture of a healthy cell versus a cancer cell. In this work we present a dynamical model for the evolution of organelles morphology in cancer cells. Using a dynamical systems approach, we describe the evolution of a cell on its way to cancer as a trajectory in a multidimensional morphology state. The results provided by this work may increase our insight on the mechanism of tumorigenesis and help build new therapeutic strategies.

  20. Cellular complexity captured in durable silica biocomposites

    PubMed Central

    Kaehr, Bryan; Townson, Jason L.; Kalinich, Robin M.; Awad, Yasmine H.; Swartzentruber, B. S.; Dunphy, Darren R.; Brinker, C. Jeffrey

    2012-01-01

    Tissue-derived cultured cells exhibit a remarkable range of morphological features in vitro, depending on phenotypic expression and environmental interactions. Translation of these cellular architectures into inorganic materials would provide routes to generate hierarchical nanomaterials with stabilized structures and functions. Here, we describe the fabrication of cell/silica composites (CSCs) and their conversion to silica replicas using mammalian cells as scaffolds to direct complex structure formation. Under mildly acidic solution conditions, silica deposition is restricted to the molecularly crowded cellular template. Inter- and intracellular heterogeneity from the nano- to macroscale is captured and dimensionally preserved in CSCs following drying and subjection to extreme temperatures allowing, for instance, size and shape preserving pyrolysis of cellular architectures to form conductive carbon replicas. The structural and behavioral malleability of the starting material (cultured cells) provides opportunities to develop robust and economical biocomposites with programmed structures and functions. PMID:23045634