Sample records for cellular network performance

  1. Supporting performance and configuration management of GTE cellular networks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tan, Ming; Lafond, C.; Jakobson, G.

    GTE Laboratories, in cooperation with GTE Mobilnet, has developed and deployed PERFFEX (PERFormance Expert), an intelligent system for performance and configuration management of cellular networks. PERFEX assists cellular network performance and radio engineers in the analysis of large volumes of cellular network performance and configuration data. It helps them locate and determine the probable causes of performance problems, and provides intelligent suggestions about how to correct them. The system combines an expert cellular network performance tuning capability with a map-based graphical user interface, data visualization programs, and a set of special cellular engineering tools. PERFEX is in daily use atmore » more than 25 GTE Mobile Switching Centers. Since the first deployment of the system in late 1993, PERFEX has become a major GTE cellular network performance optimization tool.« less

  2. 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…

  3. A Study on Cognitive Radio Coexisting with Cellular Systems

    NASA Astrophysics Data System (ADS)

    Tandai, Tomoya; Horiguchi, Tomoya; Deguchi, Noritaka; Tomizawa, Takeshi; Tomioka, Tazuko

    Cognitive Radios (CRs) are expected to perform more significant role in the view of efficient utilization of the spectrum resources in the future wireless communication networks. In this paper, a cognitive radio coexisting with cellular systems is proposed. In the case that a cellular system adopts Frequency Division Duplex (FDD) as a multiplexing scheme, the proposed CR terminals communicate in local area on uplink channels of the cellular system with transmission powers that don't interfere with base stations of the cellular system. Alternatively, in the case that a cellular system adopts Time Division Duplex (TDD), the CR terminals communicate on uplink slots of the cellular system. However if mobile terminals in the cellular system are near the CR network, uplink signals from the mobile terminals may interfere with the CR communications. In order to avoid interference from the mobile terminals, the CR terminal performs carrier sense during a beginning part of uplink slot, and only when the level of detected signal is below a threshold, then the CR terminal transmits a signal during the remained period of the uplink slot. In this paper, both the single carrier CR network that uses one frequency channel of the cellular system and the multicarrier CR network that uses multiple frequency channels of the cellular system are considered. The probabilities of successful CR communications, the average throughputs of the CR communications according to the positions of the CR network, and the interference levels from cognitive radio network to base stations of the cellular system are evaluated in the computer simulation then the effectiveness of the proposed network is clarified.

  4. Balancing Uplink and Downlink under Asymmetric Traffic Environments Using Distributed Receive Antennas

    NASA Astrophysics Data System (ADS)

    Sohn, Illsoo; Lee, Byong Ok; Lee, Kwang Bok

    Recently, multimedia services are increasing with the widespread use of various wireless applications such as web browsers, real-time video, and interactive games, which results in traffic asymmetry between the uplink and downlink. Hence, time division duplex (TDD) systems which provide advantages in efficient bandwidth utilization under asymmetric traffic environments have become one of the most important issues in future mobile cellular systems. It is known that two types of intercell interference, referred to as crossed-slot interference, additionally arise in TDD systems; the performances of the uplink and downlink transmissions are degraded by BS-to-BS crossed-slot interference and MS-to-MS crossed-slot interference, respectively. The resulting performance unbalance between the uplink and downlink makes network deployment severely inefficient. Previous works have proposed intelligent time slot allocation algorithms to mitigate the crossed-slot interference problem. However, they require centralized control, which causes large signaling overhead in the network. In this paper, we propose to change the shape of the cellular structure itself. The conventional cellular structure is easily transformed into the proposed cellular structure with distributed receive antennas (DRAs). We set up statistical Markov chain traffic model and analyze the bit error performances of the conventional cellular structure and proposed cellular structure under asymmetric traffic environments. Numerical results show that the uplink and downlink performances of the proposed cellular structure become balanced with the proper number of DRAs and thus the proposed cellular structure is notably cost-effective in network deployment compared to the conventional cellular structure. As a result, extending the conventional cellular structure into the proposed cellular structure with DRAs is a remarkably cost-effective solution to support asymmetric traffic environments in future mobile cellular systems.

  5. Modeling and Analysis of Hybrid Cellular/WLAN Systems with Integrated Service-Based Vertical Handoff Schemes

    NASA Astrophysics Data System (ADS)

    Xia, Weiwei; Shen, Lianfeng

    We propose two vertical handoff schemes for cellular network and wireless local area network (WLAN) integration: integrated service-based handoff (ISH) and integrated service-based handoff with queue capabilities (ISHQ). Compared with existing handoff schemes in integrated cellular/WLAN networks, the proposed schemes consider a more comprehensive set of system characteristics such as different features of voice and data services, dynamic information about the admitted calls, user mobility and vertical handoffs in two directions. The code division multiple access (CDMA) cellular network and IEEE 802.11e WLAN are taken into account in the proposed schemes. We model the integrated networks by using multi-dimensional Markov chains and the major performance measures are derived for voice and data services. The important system parameters such as thresholds to prioritize handoff voice calls and queue sizes are optimized. Numerical results demonstrate that the proposed ISHQ scheme can maximize the utilization of overall bandwidth resources with the best quality of service (QoS) provisioning for voice and data services.

  6. Comparison of neural network applications for channel assignment in cellular TDMA networks and dynamically sectored PCS networks

    NASA Astrophysics Data System (ADS)

    Hortos, William S.

    1997-04-01

    The use of artificial neural networks (NNs) to address the channel assignment problem (CAP) for cellular time-division multiple access and code-division multiple access networks has previously been investigated by this author and many others. The investigations to date have been based on a hexagonal cell structure established by omnidirectional antennas at the base stations. No account was taken of the use of spatial isolation enabled by directional antennas to reduce interference between mobiles. Any reduction in interference translates into increased capacity and consequently alters the performance of the NNs. Previous studies have sought to improve the performance of Hopfield- Tank network algorithms and self-organizing feature map algorithms applied primarily to static channel assignment (SCA) for cellular networks that handle uniformly distributed, stationary traffic in each cell for a single type of service. The resulting algorithms minimize energy functions representing interference constraint and ad hoc conditions that promote convergence to optimal solutions. While the structures of the derived neural network algorithms (NNAs) offer the potential advantages of inherent parallelism and adaptability to changing system conditions, this potential has yet to be fulfilled the CAP for emerging mobile networks. The next-generation communication infrastructures must accommodate dynamic operating conditions. Macrocell topologies are being refined to microcells and picocells that can be dynamically sectored by adaptively controlled, directional antennas and programmable transceivers. These networks must support the time-varying demands for personal communication services (PCS) that simultaneously carry voice, data and video and, thus, require new dynamic channel assignment (DCA) algorithms. This paper examines the impact of dynamic cell sectoring and geometric conditioning on NNAs developed for SCA in omnicell networks with stationary traffic to improve the metrics of convergence rate and call blocking. Genetic algorithms (GAs) are also considered in PCS networks as a means to overcome the known weakness of Hopfield NNAs in determining global minima. The resulting GAs for DCA in PCS networks are compared to improved DCA algorithms based on Hopfield NNs for stationary cellular networks. Algorithm performance is compared on the basis of rate of convergence, blocking probability, analytic complexity, and parametric sensitivity to transient traffic demands and channel interference.

  7. Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information

    PubMed Central

    2009-01-01

    Background The identification of essential genes is important for the understanding of the minimal requirements for cellular life and for practical purposes, such as drug design. However, the experimental techniques for essential genes discovery are labor-intensive and time-consuming. Considering these experimental constraints, a computational approach capable of accurately predicting essential genes would be of great value. We therefore present here a machine learning-based computational approach relying on network topological features, cellular localization and biological process information for prediction of essential genes. Results We constructed a decision tree-based meta-classifier and trained it on datasets with individual and grouped attributes-network topological features, cellular compartments and biological processes-to generate various predictors of essential genes. We showed that the predictors with better performances are those generated by datasets with integrated attributes. Using the predictor with all attributes, i.e., network topological features, cellular compartments and biological processes, we obtained the best predictor of essential genes that was then used to classify yeast genes with unknown essentiality status. Finally, we generated decision trees by training the J48 algorithm on datasets with all network topological features, cellular localization and biological process information to discover cellular rules for essentiality. We found that the number of protein physical interactions, the nuclear localization of proteins and the number of regulating transcription factors are the most important factors determining gene essentiality. Conclusion We were able to demonstrate that network topological features, cellular localization and biological process information are reliable predictors of essential genes. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing essentiality. PMID:19758426

  8. 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...

  9. Network analysis of oyster transcriptome revealed a cascade of cellular responses during recovery after heat shock.

    PubMed

    Zhang, Lingling; Hou, Rui; Su, Hailin; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

    2012-01-01

    Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes.

  10. Intelligent call admission control for multi-class services in mobile cellular networks

    NASA Astrophysics Data System (ADS)

    Ma, Yufeng; Hu, Xiulin; Zhang, Yunyu

    2005-11-01

    Scarcity of the spectrum resource and mobility of users make quality of service (QoS) provision a critical issue in mobile cellular networks. This paper presents a fuzzy call admission control scheme to meet the requirement of the QoS. A performance measure is formed as a weighted linear function of new call and handoff call blocking probabilities of each service class. Simulation compares the proposed fuzzy scheme with complete sharing and guard channel policies. Simulation results show that fuzzy scheme has a better robust performance in terms of average blocking criterion.

  11. Condition monitoring of 3G cellular networks through competitive neural models.

    PubMed

    Barreto, Guilherme A; Mota, João C M; Souza, Luis G M; Frota, Rewbenio A; Aguayo, Leonardo

    2005-09-01

    We develop an unsupervised approach to condition monitoring of cellular networks using competitive neural algorithms. Training is carried out with state vectors representing the normal functioning of a simulated CDMA2000 network. Once training is completed, global and local normality profiles (NPs) are built from the distribution of quantization errors of the training state vectors and their components, respectively. The global NP is used to evaluate the overall condition of the cellular system. If abnormal behavior is detected, local NPs are used in a component-wise fashion to find abnormal state variables. Anomaly detection tests are performed via percentile-based confidence intervals computed over the global and local NPs. We compared the performance of four competitive algorithms [winner-take-all (WTA), frequency-sensitive competitive learning (FSCL), self-organizing map (SOM), and neural-gas algorithm (NGA)] and the results suggest that the joint use of global and local NPs is more efficient and more robust than current single-threshold methods.

  12. Selfish cellular networks and the evolution of complex organisms.

    PubMed

    Kourilsky, Philippe

    2012-03-01

    Human gametogenesis takes years and involves many cellular divisions, particularly in males. Consequently, gametogenesis provides the opportunity to acquire multiple de novo mutations. A significant portion of these is likely to impact the cellular networks linking genes, proteins, RNA and metabolites, which constitute the functional units of cells. A wealth of literature shows that these individual cellular networks are complex, robust and evolvable. To some extent, they are able to monitor their own performance, and display sufficient autonomy to be termed "selfish". Their robustness is linked to quality control mechanisms which are embedded in and act upon the individual networks, thereby providing a basis for selection during gametogenesis. These selective processes are equally likely to affect cellular functions that are not gamete-specific, and the evolution of the most complex organisms, including man, is therefore likely to occur via two pathways: essential housekeeping functions would be regulated and evolve during gametogenesis within the parents before being transmitted to their progeny, while classical selection would operate on other traits of the organisms that shape their fitness with respect to the environment. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  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.

  14. Investigating cellular network heterogeneity and modularity in cancer: a network entropy and unbalanced motif approach.

    PubMed

    Cheng, Feixiong; Liu, Chuang; Shen, Bairong; Zhao, Zhongming

    2016-08-26

    Cancer is increasingly recognized as a cellular system phenomenon that is attributed to the accumulation of genetic or epigenetic alterations leading to the perturbation of the molecular network architecture. Elucidation of network properties that can characterize tumor initiation and progression, or pinpoint the molecular targets related to the drug sensitivity or resistance, is therefore of critical importance for providing systems-level insights into tumorigenesis and clinical outcome in the molecularly targeted cancer therapy. In this study, we developed a network-based framework to quantitatively examine cellular network heterogeneity and modularity in cancer. Specifically, we constructed gene co-expressed protein interaction networks derived from large-scale RNA-Seq data across 8 cancer types generated in The Cancer Genome Atlas (TCGA) project. We performed gene network entropy and balanced versus unbalanced motif analysis to investigate cellular network heterogeneity and modularity in tumor versus normal tissues, different stages of progression, and drug resistant versus sensitive cancer cell lines. We found that tumorigenesis could be characterized by a significant increase of gene network entropy in all of the 8 cancer types. The ratio of the balanced motifs in normal tissues is higher than that of tumors, while the ratio of unbalanced motifs in tumors is higher than that of normal tissues in all of the 8 cancer types. Furthermore, we showed that network entropy could be used to characterize tumor progression and anticancer drug responses. For example, we found that kinase inhibitor resistant cancer cell lines had higher entropy compared to that of sensitive cell lines using the integrative analysis of microarray gene expression and drug pharmacological data collected from the Genomics of Drug Sensitivity in Cancer database. In addition, we provided potential network-level evidence that smoking might increase cancer cellular network heterogeneity and further contribute to tyrosine kinase inhibitor (e.g., gefitinib) resistance. In summary, we demonstrated that network properties such as network entropy and unbalanced motifs associated with tumor initiation, progression, and anticancer drug responses, suggesting new potential network-based prognostic and predictive measure in cancer.

  15. Evolutionary Conservation and Emerging Functional Diversity of the Cytosolic Hsp70:J Protein Chaperone Network of Arabidopsis thaliana.

    PubMed

    Verma, Amit K; Diwan, Danish; Raut, Sandeep; Dobriyal, Neha; Brown, Rebecca E; Gowda, Vinita; Hines, Justin K; Sahi, Chandan

    2017-06-07

    Heat shock proteins of 70 kDa (Hsp70s) partner with structurally diverse Hsp40s (J proteins), generating distinct chaperone networks in various cellular compartments that perform myriad housekeeping and stress-associated functions in all organisms. Plants, being sessile, need to constantly maintain their cellular proteostasis in response to external environmental cues. In these situations, the Hsp70:J protein machines may play an important role in fine-tuning cellular protein quality control. Although ubiquitous, the functional specificity and complexity of the plant Hsp70:J protein network has not been studied. Here, we analyzed the J protein network in the cytosol of Arabidopsis thaliana and, using yeast genetics, show that the functional specificities of most plant J proteins in fundamental chaperone functions are conserved across long evolutionary timescales. Detailed phylogenetic and functional analysis revealed that increased number, regulatory differences, and neofunctionalization in J proteins together contribute to the emerging functional diversity and complexity in the Hsp70:J protein network in higher plants. Based on the data presented, we propose that higher plants have orchestrated their "chaperome," especially their J protein complement, according to their specialized cellular and physiological stipulations. Copyright © 2017 Verma et al.

  16. 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.

  17. 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.

  18. UMA/GAN network architecture analysis

    NASA Astrophysics Data System (ADS)

    Yang, Liang; Li, Wensheng; Deng, Chunjian; Lv, Yi

    2009-07-01

    This paper is to critically analyze the architecture of UMA which is one of Fix Mobile Convergence (FMC) solutions, and also included by the third generation partnership project(3GPP). In UMA/GAN network architecture, UMA Network Controller (UNC) is the key equipment which connects with cellular core network and mobile station (MS). UMA network could be easily integrated into the existing cellular networks without influencing mobile core network, and could provides high-quality mobile services with preferentially priced indoor voice and data usage. This helps to improve subscriber's experience. On the other hand, UMA/GAN architecture helps to integrate other radio technique into cellular network which includes WiFi, Bluetooth, and WiMax and so on. This offers the traditional mobile operators an opportunity to integrate WiMax technique into cellular network. In the end of this article, we also give an analysis of potential influence on the cellular core networks ,which is pulled by UMA network.

  19. Interference Alignment With Partial CSI Feedback in MIMO Cellular Networks

    NASA Astrophysics Data System (ADS)

    Rao, Xiongbin; Lau, Vincent K. N.

    2014-04-01

    Interference alignment (IA) is a linear precoding strategy that can achieve optimal capacity scaling at high SNR in interference networks. However, most existing IA designs require full channel state information (CSI) at the transmitters, which would lead to significant CSI signaling overhead. There are two techniques, namely CSI quantization and CSI feedback filtering, to reduce the CSI feedback overhead. In this paper, we consider IA processing with CSI feedback filtering in MIMO cellular networks. We introduce a novel metric, namely the feedback dimension, to quantify the first order CSI feedback cost associated with the CSI feedback filtering. The CSI feedback filtering poses several important challenges in IA processing. First, there is a hidden partial CSI knowledge constraint in IA precoder design which cannot be handled using conventional IA design methodology. Furthermore, existing results on the feasibility conditions of IA cannot be applied due to the partial CSI knowledge. Finally, it is very challenging to find out how much CSI feedback is actually needed to support IA processing. We shall address the above challenges and propose a new IA feasibility condition under partial CSIT knowledge in MIMO cellular networks. Based on this, we consider the CSI feedback profile design subject to the degrees of freedom requirements, and we derive closed-form trade-off results between the CSI feedback cost and IA performance in MIMO cellular networks.

  20. (abstract) Experimental Results From Internetworking Data Applications Over Various Wireless Networks Using a Single Flexible Error Control Protocol

    NASA Technical Reports Server (NTRS)

    Kanai, T.; Kramer, M.; McAuley, A. J.; Nowack, S.; Pinck, D. S.; Ramirez, G.; Stewart, I.; Tohme, H.; Tong, L.

    1995-01-01

    This paper describes results from several wireless field trials in New Jersey, California, and Colorado, conducted jointly by researchers at Bellcore, JPL, and US West over the course of 1993 and 1994. During these trials, applications communicated over multiple wireless networks including satellite, low power PCS, high power cellular, packet data, and the wireline Public Switched Telecommunications Network (PSTN). Key goals included 1) designing data applications and an API suited to mobile users, 2) investigating internetworking issues, 3) characterizing wireless networks under various field conditions, and 4) comparing the performance of different protocol mechanisms over the diverse networks and applications. We describe experimental results for different protocol mechanisms and parameters, such as acknowledgment schemes and packet sizes. We show the need for powerful error control mechanisms such as selective acknowledgements and combining data from multiple transmissions. We highlight the possibility of a common protocol for all wireless networks, from micro-cellular PCS to satellite networks.

  1. 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.

  2. Landauer in the Age of Synthetic Biology: Energy Consumption and Information Processing in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Mehta, Pankaj; Lang, Alex H.; Schwab, David J.

    2016-03-01

    A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellular circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular circuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using "post-translational" synthetic biology that exploits reversible protein modification.

  3. Comparison of home and away-from-home physical activity using accelerometers and cellular network-based tracking devices.

    PubMed

    Ramulu, Pradeep Y; Chan, Emilie S; Loyd, Tara L; Ferrucci, Luigi; Friedman, David S

    2012-08-01

    Measuring physical at home and away from home is essential for assessing health and well-being, and could help design interventions to increase physical activity. Here, we describe how physical activity at home and away from home can be quantified by combining information from cellular network-based tracking devices and accelerometers. Thirty-five working adults wore a cellular network-based tracking device and an accelerometer for 6 consecutive days and logged their travel away from home. Performance of the tracking device was determined using the travel log for reference. Tracking device and accelerometer data were merged to compare physical activity at home and away from home. The tracking device detected 98.6% of all away-from-home excursions, accurately measured time away from home and demonstrated few prolonged signal drop-out periods. Most physical activity took place away from home on weekdays, but not on weekends. Subjects were more physically active per unit of time while away from home, particularly on weekends. Cellular network-based tracking devices represent an alternative to global positioning systems for tracking location, and provide information easily integrated with accelerometers to determine where physical activity takes place. Promoting greater time spent away from home may increase physical activity.

  4. Base Station Placement Algorithm for Large-Scale LTE Heterogeneous Networks.

    PubMed

    Lee, Seungseob; Lee, SuKyoung; Kim, Kyungsoo; Kim, Yoon Hyuk

    2015-01-01

    Data traffic demands in cellular networks today are increasing at an exponential rate, giving rise to the development of heterogeneous networks (HetNets), in which small cells complement traditional macro cells by extending coverage to indoor areas. However, the deployment of small cells as parts of HetNets creates a key challenge for operators' careful network planning. In particular, massive and unplanned deployment of base stations can cause high interference, resulting in highly degrading network performance. Although different mathematical modeling and optimization methods have been used to approach various problems related to this issue, most traditional network planning models are ill-equipped to deal with HetNet-specific characteristics due to their focus on classical cellular network designs. Furthermore, increased wireless data demands have driven mobile operators to roll out large-scale networks of small long term evolution (LTE) cells. Therefore, in this paper, we aim to derive an optimum network planning algorithm for large-scale LTE HetNets. Recently, attempts have been made to apply evolutionary algorithms (EAs) to the field of radio network planning, since they are characterized as global optimization methods. Yet, EA performance often deteriorates rapidly with the growth of search space dimensionality. To overcome this limitation when designing optimum network deployments for large-scale LTE HetNets, we attempt to decompose the problem and tackle its subcomponents individually. Particularly noting that some HetNet cells have strong correlations due to inter-cell interference, we propose a correlation grouping approach in which cells are grouped together according to their mutual interference. Both the simulation and analytical results indicate that the proposed solution outperforms the random-grouping based EA as well as an EA that detects interacting variables by monitoring the changes in the objective function algorithm in terms of system throughput performance.

  5. Assessment of General Public Exposure to LTE signals compared to other Cellular Networks Present in Thessaloniki, Greece.

    PubMed

    Gkonis, Fotios; Boursianis, Achilles; Samaras, Theodoros

    2017-07-01

    To assess general public exposure to electromagnetic fields from Long Term Evolution (LTE) base stations, measurements at 10 sites in Thessaloniki, Greece were performed. Results are compared with other mobile cellular networks currently in use. All exposure values satisfy the guidelines for general public exposure of the International Commission on Non-Ionizing Radiation Protection (ICNIRP), as well as the reference levels by the Greek legislation at all sites. LTE electric field measurements were recorded up to 0.645 V/m. By applying the ICNIRP guidelines, the exposure ratio for all LTE signals is between 2.9 × 10-5 and 2.8 × 10-2. From the measurements results it is concluded that the average and maximum power density contribution of LTE downlink signals to the overall cellular networks signals are 7.8% and 36.7%, respectively. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. ChainMail based neural dynamics modeling of soft tissue deformation for surgical simulation.

    PubMed

    Zhang, Jinao; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

    2017-07-20

    Realistic and real-time modeling and simulation of soft tissue deformation is a fundamental research issue in the field of surgical simulation. In this paper, a novel cellular neural network approach is presented for modeling and simulation of soft tissue deformation by combining neural dynamics of cellular neural network with ChainMail mechanism. The proposed method formulates the problem of elastic deformation into cellular neural network activities to avoid the complex computation of elasticity. The local position adjustments of ChainMail are incorporated into the cellular neural network as the local connectivity of cells, through which the dynamic behaviors of soft tissue deformation are transformed into the neural dynamics of cellular neural network. Experiments demonstrate that the proposed neural network approach is capable of modeling the soft tissues' nonlinear deformation and typical mechanical behaviors. The proposed method not only improves ChainMail's linear deformation with the nonlinear characteristics of neural dynamics but also enables the cellular neural network to follow the principle of continuum mechanics to simulate soft tissue deformation.

  7. Integrated cellular network of transcription regulations and protein-protein interactions

    PubMed Central

    2010-01-01

    Background With the accumulation of increasing omics data, a key goal of systems biology is to construct networks at different cellular levels to investigate cellular machinery of the cell. However, there is currently no satisfactory method to construct an integrated cellular network that combines the gene regulatory network and the signaling regulatory pathway. Results In this study, we integrated different kinds of omics data and developed a systematic method to construct the integrated cellular network based on coupling dynamic models and statistical assessments. The proposed method was applied to S. cerevisiae stress responses, elucidating the stress response mechanism of the yeast. From the resulting integrated cellular network under hyperosmotic stress, the highly connected hubs which are functionally relevant to the stress response were identified. Beyond hyperosmotic stress, the integrated network under heat shock and oxidative stress were also constructed and the crosstalks of these networks were analyzed, specifying the significance of some transcription factors to serve as the decision-making devices at the center of the bow-tie structure and the crucial role for rapid adaptation scheme to respond to stress. In addition, the predictive power of the proposed method was also demonstrated. Conclusions We successfully construct the integrated cellular network which is validated by literature evidences. The integration of transcription regulations and protein-protein interactions gives more insight into the actual biological network and is more predictive than those without integration. The method is shown to be powerful and flexible and can be used under different conditions and for different species. The coupling dynamic models of the whole integrated cellular network are very useful for theoretical analyses and for further experiments in the fields of network biology and synthetic biology. PMID:20211003

  8. Integrated cellular network of transcription regulations and protein-protein interactions.

    PubMed

    Wang, Yu-Chao; Chen, Bor-Sen

    2010-03-08

    With the accumulation of increasing omics data, a key goal of systems biology is to construct networks at different cellular levels to investigate cellular machinery of the cell. However, there is currently no satisfactory method to construct an integrated cellular network that combines the gene regulatory network and the signaling regulatory pathway. In this study, we integrated different kinds of omics data and developed a systematic method to construct the integrated cellular network based on coupling dynamic models and statistical assessments. The proposed method was applied to S. cerevisiae stress responses, elucidating the stress response mechanism of the yeast. From the resulting integrated cellular network under hyperosmotic stress, the highly connected hubs which are functionally relevant to the stress response were identified. Beyond hyperosmotic stress, the integrated network under heat shock and oxidative stress were also constructed and the crosstalks of these networks were analyzed, specifying the significance of some transcription factors to serve as the decision-making devices at the center of the bow-tie structure and the crucial role for rapid adaptation scheme to respond to stress. In addition, the predictive power of the proposed method was also demonstrated. We successfully construct the integrated cellular network which is validated by literature evidences. The integration of transcription regulations and protein-protein interactions gives more insight into the actual biological network and is more predictive than those without integration. The method is shown to be powerful and flexible and can be used under different conditions and for different species. The coupling dynamic models of the whole integrated cellular network are very useful for theoretical analyses and for further experiments in the fields of network biology and synthetic biology.

  9. Analysis of Soldier Radio Waveform Performance in Operational Test

    DTIC Science & Technology

    2015-05-01

    different frequencies based on carrier, uplink/downlink, and generation. In general, 2G and 3G cellular phones operate at 850 MHz uplink, and 1,900 MHz...spectrum management that may not be operationally feasible. These issues are not unique to SRW, but rather have plagued the mobile ad-hoc network... mobile ad-hoc network (MANET), enabling communication through a self-configuring, infrastructure-less network of mobile nodes. In the SS domain, these

  10. 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.

  11. Systematic network assessment of the carcinogenic activities of cadmium

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Peizhan; Duan, Xiaohua; Li, Mian

    Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscapemore » software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human. - Highlights: • A cadmium-influenced network with 850 nodes and 8770 edges was established. • The cadmium-rewired gene network was scale-free and highly connected. • Nine modules were identified, and 60 key signaling pathways related to cadmium-induced carcinogenesis were found. • Key mediators in the network were validated in multiple cellular models.« less

  12. Impact of network structure on the capacity of wireless multihop ad hoc communication

    NASA Astrophysics Data System (ADS)

    Krause, Wolfram; Glauche, Ingmar; Sollacher, Rudolf; Greiner, Martin

    2004-07-01

    As a representative of a complex technological system, the so-called wireless multihop ad hoc communication networks are discussed. They represent an infrastructure-less generalization of todays wireless cellular phone networks. Lacking a central control authority, the ad hoc nodes have to coordinate themselves such that the overall network performs in an optimal way. A performance indicator is the end-to-end throughput capacity. Various models, generating differing ad hoc network structure via differing transmission power assignments, are constructed and characterized. They serve as input for a generic data traffic simulation as well as some semi-analytic estimations. The latter reveal that due to the most-critical-node effect the end-to-end throughput capacity sensitively depends on the underlying network structure, resulting in differing scaling laws with respect to network size.

  13. 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.

  14. 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

  15. A dynamically reconfigurable logic cell: from artificial neural networks to quantum-dot cellular automata

    NASA Astrophysics Data System (ADS)

    Naqvi, Syed Rameez; Akram, Tallha; Iqbal, Saba; Haider, Sajjad Ali; Kamran, Muhammad; Muhammad, Nazeer

    2018-02-01

    Considering the lack of optimization support for Quantum-dot Cellular Automata, we propose a dynamically reconfigurable logic cell capable of implementing various logic operations by means of artificial neural networks. The cell can be reconfigured to any 2-input combinational logic gate by altering the strength of connections, called weights and biases. We demonstrate how these cells may appositely be organized to perform multi-bit arithmetic and logic operations. The proposed work is important in that it gives a standard implementation of an 8-bit arithmetic and logic unit for quantum-dot cellular automata with minimal area and latency overhead. We also compare the proposed design with a few existing arithmetic and logic units, and show that it is more area efficient than any equivalent available in literature. Furthermore, the design is adaptable to 16, 32, and 64 bit architectures.

  16. A computational approach to identify cellular heterogeneity and tissue-specific gene regulatory networks.

    PubMed

    Jambusaria, Ankit; Klomp, Jeff; Hong, Zhigang; Rafii, Shahin; Dai, Yang; Malik, Asrar B; Rehman, Jalees

    2018-06-07

    The heterogeneity of cells across tissue types represents a major challenge for studying biological mechanisms as well as for therapeutic targeting of distinct tissues. Computational prediction of tissue-specific gene regulatory networks may provide important insights into the mechanisms underlying the cellular heterogeneity of cells in distinct organs and tissues. Using three pathway analysis techniques, gene set enrichment analysis (GSEA), parametric analysis of gene set enrichment (PGSEA), alongside our novel model (HeteroPath), which assesses heterogeneously upregulated and downregulated genes within the context of pathways, we generated distinct tissue-specific gene regulatory networks. We analyzed gene expression data derived from freshly isolated heart, brain, and lung endothelial cells and populations of neurons in the hippocampus, cingulate cortex, and amygdala. In both datasets, we found that HeteroPath segregated the distinct cellular populations by identifying regulatory pathways that were not identified by GSEA or PGSEA. Using simulated datasets, HeteroPath demonstrated robustness that was comparable to what was seen using existing gene set enrichment methods. Furthermore, we generated tissue-specific gene regulatory networks involved in vascular heterogeneity and neuronal heterogeneity by performing motif enrichment of the heterogeneous genes identified by HeteroPath and linking the enriched motifs to regulatory transcription factors in the ENCODE database. HeteroPath assesses contextual bidirectional gene expression within pathways and thus allows for transcriptomic assessment of cellular heterogeneity. Unraveling tissue-specific heterogeneity of gene expression can lead to a better understanding of the molecular underpinnings of tissue-specific phenotypes.

  17. Exploration of cellular reaction systems.

    PubMed

    Kirkilionis, Markus

    2010-01-01

    We discuss and review different ways to map cellular components and their temporal interaction with other such components to different non-spatially explicit mathematical models. The essential choices made in the literature are between discrete and continuous state spaces, between rule and event-based state updates and between deterministic and stochastic series of such updates. The temporal modelling of cellular regulatory networks (dynamic network theory) is compared with static network approaches in two first introductory sections on general network modelling. We concentrate next on deterministic rate-based dynamic regulatory networks and their derivation. In the derivation, we include methods from multiscale analysis and also look at structured large particles, here called macromolecular machines. It is clear that mass-action systems and their derivatives, i.e. networks based on enzyme kinetics, play the most dominant role in the literature. The tools to analyse cellular reaction networks are without doubt most complete for mass-action systems. We devote a long section at the end of the review to make a comprehensive review of related tools and mathematical methods. The emphasis is to show how cellular reaction networks can be analysed with the help of different associated graphs and the dissection into modules, i.e. sub-networks.

  18. Breast MR segmentation and lesion detection with cellular neural networks and 3D template matching.

    PubMed

    Ertaş, Gökhan; Gülçür, H Ozcan; Osman, Onur; Uçan, Osman N; Tunaci, Mehtap; Dursun, Memduh

    2008-01-01

    A novel fully automated system is introduced to facilitate lesion detection in dynamic contrast-enhanced, magnetic resonance mammography (DCE-MRM). The system extracts breast regions from pre-contrast images using a cellular neural network, generates normalized maximum intensity-time ratio (nMITR) maps and performs 3D template matching with three layers of 12x12 cells to detect lesions. A breast is considered to be properly segmented when relative overlap >0.85 and misclassification rate <0.10. Sensitivity, false-positive rate per slice and per lesion are used to assess detection performance. The system was tested with a dataset of 2064 breast MR images (344slicesx6 acquisitions over time) from 19 women containing 39 marked lesions. Ninety-seven percent of the breasts were segmented properly and all the lesions were detected correctly (detection sensitivity=100%), however, there were some false-positive detections (31%/lesion, 10%/slice).

  19. Identification of Modules in Protein-Protein Interaction Networks

    NASA Astrophysics Data System (ADS)

    Erten, Sinan; Koyutürk, Mehmet

    In biological systems, most processes are carried out through orchestration of multiple interacting molecules. These interactions are often abstracted using network models. A key feature of cellular networks is their modularity, which contributes significantly to the robustness, as well as adaptability of biological systems. Therefore, modularization of cellular networks is likely to be useful in obtaining insights into the working principles of cellular systems, as well as building tractable models of cellular organization and dynamics. A common, high-throughput source of data on molecular interactions is in the form of physical interactions between proteins, which are organized into protein-protein interaction (PPI) networks. This chapter provides an overview on identification and analysis of functional modules in PPI networks, which has been an active area of research in the last decade.

  20. Contrast research of CDMA and GSM network optimization

    NASA Astrophysics Data System (ADS)

    Wu, Yanwen; Liu, Zehong; Zhou, Guangyue

    2004-03-01

    With the development of mobile telecommunication network, users of CDMA advanced their request of network service quality. While the operators also change their network management object from signal coverage to performance improvement. In that case, reasonably layout & optimization of mobile telecommunication network, reasonably configuration of network resource, improvement of the service quality, and increase the enterprise's core competition ability, all those have been concerned by the operator companies. This paper firstly looked into the flow of CDMA network optimization. Then it dissertated to some keystones in the CDMA network optimization, like PN code assignment, calculation of soft handover, etc. As GSM is also the similar cellular mobile telecommunication system like CDMA, so this paper also made a contrast research of CDMA and GSM network optimization in details, including the similarity and the different. In conclusion, network optimization is a long time job; it will run through the whole process of network construct. By the adjustment of network hardware (like BTS equipments, RF systems, etc.) and network software (like parameter optimized, configuration optimized, capacity optimized, etc.), network optimization work can improve the performance and service quality of the network.

  1. A novel method for identifying disease associated protein complexes based on functional similarity protein complex networks.

    PubMed

    Le, Duc-Hau

    2015-01-01

    Protein complexes formed by non-covalent interaction among proteins play important roles in cellular functions. Computational and purification methods have been used to identify many protein complexes and their cellular functions. However, their roles in terms of causing disease have not been well discovered yet. There exist only a few studies for the identification of disease-associated protein complexes. However, they mostly utilize complicated heterogeneous networks which are constructed based on an out-of-date database of phenotype similarity network collected from literature. In addition, they only apply for diseases for which tissue-specific data exist. In this study, we propose a method to identify novel disease-protein complex associations. First, we introduce a framework to construct functional similarity protein complex networks where two protein complexes are functionally connected by either shared protein elements, shared annotating GO terms or based on protein interactions between elements in each protein complex. Second, we propose a simple but effective neighborhood-based algorithm, which yields a local similarity measure, to rank disease candidate protein complexes. Comparing the predictive performance of our proposed algorithm with that of two state-of-the-art network propagation algorithms including one we used in our previous study, we found that it performed statistically significantly better than that of these two algorithms for all the constructed functional similarity protein complex networks. In addition, it ran about 32 times faster than these two algorithms. Moreover, our proposed method always achieved high performance in terms of AUC values irrespective of the ways to construct the functional similarity protein complex networks and the used algorithms. The performance of our method was also higher than that reported in some existing methods which were based on complicated heterogeneous networks. Finally, we also tested our method with prostate cancer and selected the top 100 highly ranked candidate protein complexes. Interestingly, 69 of them were evidenced since at least one of their protein elements are known to be associated with prostate cancer. Our proposed method, including the framework to construct functional similarity protein complex networks and the neighborhood-based algorithm on these networks, could be used for identification of novel disease-protein complex associations.

  2. Primary Respiratory Chain Disease Causes Tissue-Specific Dysregulation of the Global Transcriptome and Nutrient-Sensing Signaling Network

    PubMed Central

    Zhang, Zhe; Tsukikawa, Mai; Peng, Min; Polyak, Erzsebet; Nakamaru-Ogiso, Eiko; Ostrovsky, Julian; McCormack, Shana; Place, Emily; Clarke, Colleen; Reiner, Gail; McCormick, Elizabeth; Rappaport, Eric; Haas, Richard; Baur, Joseph A.; Falk, Marni J.

    2013-01-01

    Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. Mechanism(s) by which RC dysfunction causes global cellular sequelae are poorly understood. To identify a common cellular response to RC disease, integrated gene, pathway, and systems biology analyses were performed in human primary RC disease skeletal muscle and fibroblast transcriptomes. Significant changes were evident in muscle across diverse RC complex and genetic etiologies that were consistent with prior reports in other primary RC disease models and involved dysregulation of genes involved in RNA processing, protein translation, transport, and degradation, and muscle structure. Global transcriptional and post-transcriptional dysregulation was also found to occur in a highly tissue-specific fashion. In particular, RC disease muscle had decreased transcription of cytosolic ribosomal proteins suggestive of reduced anabolic processes, increased transcription of mitochondrial ribosomal proteins, shorter 5′-UTRs that likely improve translational efficiency, and stabilization of 3′-UTRs containing AU-rich elements. RC disease fibroblasts showed a strikingly similar pattern of global transcriptome dysregulation in a reverse direction. In parallel with these transcriptional effects, RC disease dysregulated the integrated nutrient-sensing signaling network involving FOXO, PPAR, sirtuins, AMPK, and mTORC1, which collectively sense nutrient availability and regulate cellular growth. Altered activities of central nodes in the nutrient-sensing signaling network were validated by phosphokinase immunoblot analysis in RC inhibited cells. Remarkably, treating RC mutant fibroblasts with nicotinic acid to enhance sirtuin and PPAR activity also normalized mTORC1 and AMPK signaling, restored NADH/NAD+ redox balance, and improved cellular respiratory capacity. These data specifically highlight a common pathogenesis extending across different molecular and biochemical etiologies of individual RC disorders that involves global transcriptome modifications. We further identify the integrated nutrient-sensing signaling network as a common cellular response that mediates, and may be amenable to targeted therapies for, tissue-specific sequelae of primary mitochondrial RC disease. PMID:23894440

  3. Road Nail: Experimental Solar Powered Intelligent Road Marking System

    NASA Astrophysics Data System (ADS)

    Samardžija, Dragan; Teslić, Nikola; Todorović, Branislav M.; Kovač, Erne; Isailović, Đorđe; Miladinović, Bojan

    2012-03-01

    Driving in low visibility conditions (night time, fog or heavy precipitation) is particularly challenging task with an increased probability of traffic accidents and possible injuries. Road Nail is a solar powered intelligent road marking system of wirelessly networked signaling devices that improve driver safety in low visibility conditions along hazardous roadways. Nails or signaling devices are autonomous nodes with capability to accumulate energy, exchange wireless messages, detect approaching vehicles and emit signalization light. We have built an experimental test-bed that consists of 20 nodes and a cellular gateway. Implementation details of the above system, including extensive measurements and performance evaluations in realistic field deployments are presented. A novel distributed network topology discovery scheme is proposed which integrates both sensor and wireless communication aspects, where nodes act autonomously. Finally, integration of the Road Nail system with the cellular network and the Internet is described.

  4. In vitro and in vivo analysis and characterization of engineered spinal neural implants (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Shor, Erez; Shoham, Shy; Levenberg, Shulamit

    2016-03-01

    Spinal cord injury is a devastating medical condition. Recent developments in pre-clinical and clinical research have started to yield neural implants inducing functional recovery after spinal cord transection injury. However, the functional performance of the transplants was assessed using histology and behavioral experiments which are unable to study cell dynamics and the therapeutic response. Here, we use neurophotonic tools and optogenetic probes to investigate cellular level morphology and activity characteristics of neural implants over time at the cellular level. These methods were used in-vitro and in-vivo, in a mouse spinal cord injury implant model. Following previous attempts to induce recovery after spinal cord injury, we engineered a pre-vascularized implant to obtain better functional performance. To image network activity of a construct implanted in a mouse spinal cord, we transfected the implant to express GCaMP6 calcium activity indicators and implanted these constructs under a spinal cord chamber enabling 2-photon chronic in vivo neural activity imaging. Activity and morphology analysis image processing software was developed to automatically quantify the behavior of the neural and vascular networks. Our experimental results and analyses demonstrate that vascularized and non-vascularized constructs exhibit very different morphologic and activity patterns at the cellular level. This work enables further optimization of neural implants and also provides valuable tools for continuous cellular level monitoring and evaluation of transplants designed for various neurodegenerative disease models.

  5. Cellular telephone interference with medical equipment.

    PubMed

    Tri, Jeffrey L; Severson, Rodney P; Firl, Allen R; Hayes, David L; Abenstein, John P

    2005-10-01

    To assess the potential electromagnetic interference (EMI) effects that new or current-generation cellular telephones have on medical devices. For this study, performed at the Mayo Clinic in Rochester, Minn, between March 9, 2004, and April 24, 2004, we tested 16 different medical devices with 6 cellular telephones to assess the potential for EMI. Two of the medical devices were tested with both new and old interface modules. The 6 cellular telephones chosen represent the different cellular technology protocols in use: Code Division Multiple Access (2 models), Global System for Mobile communications, Integrated Digital Enhanced Network, Time Division Multiple Access, and analog. The cellular telephones were tested when operating at or near their maximum power output. The medical devices, connected to clinical simulators during testing, were monitored by observing the device displays and alarms. Of 510 tests performed, the incidence of clinically important interference was 1.2%; EMI was Induced in 108 tests (21.2%). Interference occurred in 7 (44%) of the 16 devices tested. Cellular telephones can interfere with medical equipment. Technology changes in both cellular telephones and medical equipment may continue to mitigate or may worsen clinically relevant interference. Compared with cellular telephones tested in previous studies, those currently in use must be closer to medical devices before any interference is noticed. However, periodic testing of cellular telephones to determine their effects on medical equipment will be required.

  6. 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

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

    PubMed Central

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

    2013-01-01

    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. PMID:24154593

  8. System-Level Performance of Antenna Arrays in CDMA-Based Cellular Mobile Radio Systems

    NASA Astrophysics Data System (ADS)

    Czylwik, Andreas; Dekorsy, Armin

    2004-12-01

    Smart antennas exploit the inherent spatial diversity of the mobile radio channel, provide an antenna gain, and also enable spatial interference suppression leading to reduced intracell as well as intercell interference. Especially, for the downlink of future CDMA-based mobile communications systems, transmit beamforming is seen as a well-promising smart antenna technique. The main objective of this paper is to study the performance of diverse antenna array topologies when applied for transmit beamforming in the downlink of CDMA-based networks. In this paper, we focus on uniform linear array (ULA) and uniform circular array (UCA) topologies. For the ULA, we consider three-sector base stations with one linear array per sector. While recent research on downlink beamforming is often restricted to one single cell, this study takes into account the important impact of intercell interference on the performance by evaluating complete networks. Especially, from the operator perspective, system capacity and system coverage are very essential parameters of a cellular system so that there is a clear necessity of intensive system level investigations. Apart from delivering assessments on the performance of the diverse antenna array topologies, in the paper also different antenna array parameters, such as element spacing and beamwidth of the sector antennas, are optimized. Although we focus on the network level, fast channel fluctuations are taken into account by including them analytically into the signal-to-interference calculation.

  9. A multi-scale convolutional neural network for phenotyping high-content cellular images.

    PubMed

    Godinez, William J; Hossain, Imtiaz; Lazic, Stanley E; Davies, John W; Zhang, Xian

    2017-07-01

    Identifying phenotypes based on high-content cellular images is challenging. Conventional image analysis pipelines for phenotype identification comprise multiple independent steps, with each step requiring method customization and adjustment of multiple parameters. Here, we present an approach based on a multi-scale convolutional neural network (M-CNN) that classifies, in a single cohesive step, cellular images into phenotypes by using directly and solely the images' pixel intensity values. The only parameters in the approach are the weights of the neural network, which are automatically optimized based on training images. The approach requires no a priori knowledge or manual customization, and is applicable to single- or multi-channel images displaying single or multiple cells. We evaluated the classification performance of the approach on eight diverse benchmark datasets. The approach yielded overall a higher classification accuracy compared with state-of-the-art results, including those of other deep CNN architectures. In addition to using the network to simply obtain a yes-or-no prediction for a given phenotype, we use the probability outputs calculated by the network to quantitatively describe the phenotypes. This study shows that these probability values correlate with chemical treatment concentrations. This finding validates further our approach and enables chemical treatment potency estimation via CNNs. The network specifications and solver definitions are provided in Supplementary Software 1. william_jose.godinez_navarro@novartis.com or xian-1.zhang@novartis.com. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  10. Analysis And Augmentation Of Timing Advance Based Geolocation In Lte Cellular Networks

    DTIC Science & Technology

    2016-12-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA DISSERTATION ANALYSIS AND AUGMENTATION OF TIMING ADVANCE-BASED GEOLOCATION IN LTE CELLULAR NETWORKS by...estimated to average 1 hour per response, including the time for reviewing instruction, searching existing data sources, gathering and maintaining the...AND SUBTITLE ANALYSIS AND AUGMENTATION OF TIMING ADVANCE-BASED GEOLOCA- TION IN LTE CELLULAR NETWORKS 5. FUNDING NUMBERS 6. AUTHOR(S) John D. Roth 7

  11. Clustering Single-Cell Expression Data Using Random Forest Graphs.

    PubMed

    Pouyan, Maziyar Baran; Nourani, Mehrdad

    2017-07-01

    Complex tissues such as brain and bone marrow are made up of multiple cell types. As the study of biological tissue structure progresses, the role of cell-type-specific research becomes increasingly important. Novel sequencing technology such as single-cell cytometry provides researchers access to valuable biological data. Applying machine-learning techniques to these high-throughput datasets provides deep insights into the cellular landscape of the tissue where those cells are a part of. In this paper, we propose the use of random-forest-based single-cell profiling, a new machine-learning-based technique, to profile different cell types of intricate tissues using single-cell cytometry data. Our technique utilizes random forests to capture cell marker dependences and model the cellular populations using the cell network concept. This cellular network helps us discover what cell types are in the tissue. Our experimental results on public-domain datasets indicate promising performance and accuracy of our technique in extracting cell populations of complex tissues.

  12. Remote Energy Monitoring System via Cellular Network

    NASA Astrophysics Data System (ADS)

    Yunoki, Shoji; Tamaki, Satoshi; Takada, May; Iwaki, Takashi

    Recently, improvement on power saving and cost efficiency by monitoring the operation status of various facilities over the network has gained attention. Wireless network, especially cellular network, has advantage in mobility, coverage, and scalability. On the other hand, it has disadvantage of low reliability, due to rapid changes in the available bandwidth. We propose a transmission control scheme based on data priority and instantaneous available bandwidth to realize a highly reliable remote monitoring system via cellular network. We have developed our proposed monitoring system and evaluated the effectiveness of our scheme, and proved it reduces the maximum transmission delay of sensor status to 1/10 compared to best effort transmission.

  13. Convergence behavior of delayed discrete cellular neural network without periodic coefficients.

    PubMed

    Wang, Jinling; Jiang, Haijun; Hu, Cheng; Ma, Tianlong

    2014-05-01

    In this paper, we study convergence behaviors of delayed discrete cellular neural networks without periodic coefficients. Some sufficient conditions are derived to ensure all solutions of delayed discrete cellular neural network without periodic coefficients converge to a periodic function, by applying mathematical analysis techniques and the properties of inequalities. Finally, some examples showing the effectiveness of the provided criterion are given. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. 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.

  15. A design of wireless sensor networks for a power quality monitoring system.

    PubMed

    Lim, Yujin; Kim, Hak-Man; Kang, Sanggil

    2010-01-01

    Power grids deal with the business of generation, transmission, and distribution of electric power. Recently, interest in power quality in electrical distribution systems has increased rapidly. In Korea, the communication network to deliver voltage, current, and temperature measurements gathered from pole transformers to remote monitoring centers employs cellular mobile technology. Due to high cost of the cellular mobile technology, power quality monitoring measurements are limited and data gathering intervals are large. This causes difficulties in providing the power quality monitoring service. To alleviate the problems, in this paper we present a communication infrastructure to provide low cost, reliable data delivery. The communication infrastructure consists of wired connections between substations and monitoring centers, and wireless connections between pole transformers and substations. For the wireless connection, we employ a wireless sensor network and design its corresponding data forwarding protocol to improve the quality of data delivery. For the design, we adopt a tree-based data forwarding protocol in order to customize the distribution pattern of the power quality information. We verify the performance of the proposed data forwarding protocol quantitatively using the NS-2 network simulator.

  16. High-performance, polymer-based direct cellular interfaces for electrical stimulation and recording

    NASA Astrophysics Data System (ADS)

    Kim, Seong-Min; Kim, Nara; Kim, Youngseok; Baik, Min-Seo; Yoo, Minsu; Kim, Dongyoon; Lee, Won-June; Kang, Dong-Hee; Kim, Sohee; Lee, Kwanghee; Yoon, Myung-Han

    2018-04-01

    Due to the trade-off between their electrical/electrochemical performance and underwater stability, realizing polymer-based, high-performance direct cellular interfaces for electrical stimulation and recording has been very challenging. Herein, we developed transparent and conductive direct cellular interfaces based on a water-stable, high-performance poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) film via solvent-assisted crystallization. The crystallized PEDOT:PSS on a polyethylene terephthalate (PET) substrate exhibited excellent electrical/electrochemical/optical characteristics, long-term underwater stability without film dissolution/delamination, and good viability for primarily cultured cardiomyocytes and neurons over several weeks. Furthermore, the highly crystallized, nanofibrillar PEDOT:PSS networks enabled dramatically enlarged surface areas and electrochemical activities, which were successfully employed to modulate cardiomyocyte beating via direct electrical stimulation. Finally, the high-performance PEDOT:PSS layer was seamlessly incorporated into transparent microelectrode arrays for efficient, real-time recording of cardiomyocyte action potentials with a high signal fidelity. All these results demonstrate the strong potential of crystallized PEDOT:PSS as a crucial component for a variety of versatile bioelectronic interfaces.

  17. Performance of cellular frequency-hopped spread-spectrum radio networks

    NASA Astrophysics Data System (ADS)

    Gluck, Jeffrey W.; Geraniotis, Evaggelos

    1989-10-01

    Multiple access interference is characterized for cellular mobile networks, in which users are assumed to be Poisson-distributed in the plane and employ frequency-hopped spread-spectrum signaling with transmitter-oriented assignment of frequency-hopping patterns. Exact expressions for the bit error probabilities are derived for binary coherently demodulated systems without coding. Approximations for the packet error probability are derived for coherent and noncoherent systems and these approximations are applied when forward-error-control coding is employed. In all cases, the effects of varying interference power are accurately taken into account according to some propagation law. Numerical results are given in terms of bit error probability for the exact case and throughput for the approximate analyses. Comparisons are made with previously derived bounds and it is shown that these tend to be very pessimistic.

  18. Searching for cellular partners of hantaviral nonstructural protein NSs: Y2H screening of mouse cDNA library and analysis of cellular interactome.

    PubMed

    Rönnberg, Tuomas; Jääskeläinen, Kirsi; Blot, Guillaume; Parviainen, Ville; Vaheri, Antti; Renkonen, Risto; Bouloy, Michele; Plyusnin, Alexander

    2012-01-01

    Hantaviruses (Bunyaviridae) are negative-strand RNA viruses with a tripartite genome. The small (S) segment encodes the nucleocapsid protein and, in some hantaviruses, also the nonstructural protein (NSs). The aim of this study was to find potential cellular partners for the hantaviral NSs protein. Toward this aim, yeast two-hybrid (Y2H) screening of mouse cDNA library was performed followed by a search for potential NSs protein counterparts via analyzing a cellular interactome. The resulting interaction network was shown to form logical, clustered structures. Furthermore, several potential binding partners for the NSs protein, for instance ACBD3, were identified and, to prove the principle, interaction between NSs and ACBD3 proteins was demonstrated biochemically.

  19. Listening to the noise: random fluctuations reveal gene network parameters

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Munsky, Brian; Khammash, Mustafa

    2009-01-01

    The cellular environment is abuzz with noise. The origin of this noise is attributed to the inherent random motion of reacting molecules that take part in gene expression and post expression interactions. In this noisy environment, clonal populations of cells exhibit cell-to-cell variability that frequently manifests as significant phenotypic differences within the cellular population. The stochastic fluctuations in cellular constituents induced by noise can be measured and their statistics quantified. We show that these random fluctuations carry within them valuable information about the underlying genetic network. Far from being a nuisance, the ever-present cellular noise acts as a rich sourcemore » of excitation that, when processed through a gene network, carries its distinctive fingerprint that encodes a wealth of information about that network. We demonstrate that in some cases the analysis of these random fluctuations enables the full identification of network parameters, including those that may otherwise be difficult to measure. This establishes a potentially powerful approach for the identification of gene networks and offers a new window into the workings of these networks.« less

  20. Self-organizing feature maps for dynamic control of radio resources in CDMA microcellular networks

    NASA Astrophysics Data System (ADS)

    Hortos, William S.

    1998-03-01

    The application of artificial neural networks to the channel assignment problem for cellular code-division multiple access (CDMA) cellular networks has previously been investigated. 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. To satisfy the high demands for new services and improved connectivity for mobile communications, microcellular and picocellular systems are being introduced. For these systems, there is a need to develop robust and efficient management procedures for the allocation of power and spectrum to maximize radio capacity. Topology-conserving mappings play an important role in the biological processing of sensory inputs. The same principles underlying Kohonen's self-organizing feature maps (SOFMs) are applied to the adaptive control of radio resources to minimize interference, hence, maximize capacity in direct-sequence (DS) CDMA networks. The approach based on SOFMs is applied to some published examples of both theoretical and empirical models of DS/CDMA microcellular networks in metropolitan areas. The results of the approach for these examples are informally compared to the performance of algorithms, based on Hopfield- Tank neural networks and on genetic algorithms, for the channel assignment problem.

  1. Toxicological Tipping Points: Learning Boolean Networks from High-Content Imaging Data. (BOSC meeting)

    EPA Science Inventory

    The objective of this work is to elucidate biological networks underlying cellular tipping points using time-course data. We discretized the high-content imaging (HCI) data and inferred Boolean networks (BNs) that could accurately predict dynamic cellular trajectories. We found t...

  2. Simple platform for chronic imaging of hippocampal activity during spontaneous behaviour in an awake mouse

    PubMed Central

    Villette, Vincent; Levesque, Mathieu; Miled, Amine; Gosselin, Benoit; Topolnik, Lisa

    2017-01-01

    Chronic electrophysiological recordings of neuronal activity combined with two-photon Ca2+ imaging give access to high resolution and cellular specificity. In addition, awake drug-free experimentation is required for investigating the physiological mechanisms that operate in the brain. Here, we developed a simple head fixation platform, which allows simultaneous chronic imaging and electrophysiological recordings to be obtained from the hippocampus of awake mice. We performed quantitative analyses of spontaneous animal behaviour, the associated network states and the cellular activities in the dorsal hippocampus as well as estimated the brain stability limits to image dendritic processes and individual axonal boutons. Ca2+ imaging recordings revealed a relatively stereotyped hippocampal activity despite a high inter-animal and inter-day variability in the mouse behavior. In addition to quiet state and locomotion behavioural patterns, the platform allowed the reliable detection of walking steps and fine speed variations. The brain motion during locomotion was limited to ~1.8 μm, thus allowing for imaging of small sub-cellular structures to be performed in parallel with recordings of network and behavioural states. This simple device extends the drug-free experimentation in vivo, enabling high-stability optophysiological experiments with single-bouton resolution in the mouse awake brain. PMID:28240275

  3. Measurements and modelling of base station power consumption under real traffic loads.

    PubMed

    Lorincz, Josip; Garma, Tonko; Petrovic, Goran

    2012-01-01

    Base stations represent the main contributor to the energy consumption of a mobile cellular network. Since traffic load in mobile networks significantly varies during a working or weekend day, it is important to quantify the influence of these variations on the base station power consumption. Therefore, this paper investigates changes in the instantaneous power consumption of GSM (Global System for Mobile Communications) and UMTS (Universal Mobile Telecommunications System) base stations according to their respective traffic load. The real data in terms of the power consumption and traffic load have been obtained from continuous measurements performed on a fully operated base station site. Measurements show the existence of a direct relationship between base station traffic load and power consumption. According to this relationship, we develop a linear power consumption model for base stations of both technologies. This paper also gives an overview of the most important concepts which are being proposed to make cellular networks more energy-efficient.

  4. Measurements and Modelling of Base Station Power Consumption under Real Traffic Loads †

    PubMed Central

    Lorincz, Josip; Garma, Tonko; Petrovic, Goran

    2012-01-01

    Base stations represent the main contributor to the energy consumption of a mobile cellular network. Since traffic load in mobile networks significantly varies during a working or weekend day, it is important to quantify the influence of these variations on the base station power consumption. Therefore, this paper investigates changes in the instantaneous power consumption of GSM (Global System for Mobile Communications) and UMTS (Universal Mobile Telecommunications System) base stations according to their respective traffic load. The real data in terms of the power consumption and traffic load have been obtained from continuous measurements performed on a fully operated base station site. Measurements show the existence of a direct relationship between base station traffic load and power consumption. According to this relationship, we develop a linear power consumption model for base stations of both technologies. This paper also gives an overview of the most important concepts which are being proposed to make cellular networks more energy-efficient. PMID:22666026

  5. Novel method for water vapour monitoring using wireless communication networks measurements

    NASA Astrophysics Data System (ADS)

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

    2010-09-01

    We propose a new technique for monitoring near-surface water vapour, by estimating humidity from data collected through existing wireless communication networks. Weather conditions and atmospheric phenomena affect the electromagnetic channel, causing attenuations to the radio signals. Thus, wireless communication networks are in effect built-in environmental monitoring facilities. The wireless microwave links, used in these networks, are widely deployed by cellular providers for backhaul communication between base stations, a few tens of meters above ground level. As a result, if all available measurements are used, the proposed method can provide moisture observations with high spatial resolution and potentially high temporal resolution. Further, the implementation cost is minimal, since the data used are already collected and saved by the cellular operators. In addition - many of these links are installed in areas where access is difficult such as orographic terrain and complex topography. As such, our method enables measurements in places that have been hard to measure in the past, or have never been measured before. The technique is restricted to weather conditions which exclude rain, fog or clouds along the propagation path. Strong winds that may cause movement of the link transmitter or receiver (or both) may also interfere with the ability to conduct accurate measurements. We present results from real-data measurements taken from microwave links used in a backhaul cellular network that show very good correlation with surface station humidity measurements (comparisons were performed for several links, found at different locations, during different time periods, showing correlations in the range of 0.5-0.9).

  6. Capacity on wireless quantum cellular communication system

    NASA Astrophysics Data System (ADS)

    Zhou, Xiang-Zhen; Yu, Xu-Tao; Zhang, Zai-Chen

    2018-03-01

    Quantum technology is making excellent prospects in future communication networks. Entanglement generation and purification are two major components in quantum networks. Combining these two techniques with classical cellular mobile communication, we proposed a novel wireless quantum cellular(WQC) communication system which is possible to realize commercial mobile quantum communication. In this paper, the architecture and network topology of WQC communication system are discussed, the mathematical model of WQC system is extracted and the serving capacity, indicating the ability to serve customers, is defined and calculated under certain circumstances.

  7. 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.

  8. Modeling integrated cellular machinery using hybrid Petri-Boolean networks.

    PubMed

    Berestovsky, Natalie; Zhou, Wanding; Nagrath, Deepak; Nakhleh, Luay

    2013-01-01

    The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM) that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them using such more detailed mathematical models.

  9. Modeling Integrated Cellular Machinery Using Hybrid Petri-Boolean Networks

    PubMed Central

    Berestovsky, Natalie; Zhou, Wanding; Nagrath, Deepak; Nakhleh, Luay

    2013-01-01

    The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM) that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them using such more detailed mathematical models. PMID:24244124

  10. CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Information Feedback Strategies in a Signal Controlled Network with Overlapped Routes

    NASA Astrophysics Data System (ADS)

    Tian, Li-Jun; Huang, Hai-Jun; Liu, Tian-Liang

    2009-07-01

    We investigate the effects of four different information feedback strategies on the dynamics of traffic, travelers' route choice and the resultant system performance in a signal controlled network with overlapped routes. Simulation results given by the cellular automaton model show that the system purpose-based mean velocity feedback strategy and the congestion coefficient feedback strategy have more advantages in improving network utilization efficiency and reducing travelers' travel times. The travel time feedback strategy and the individual purposed-based mean velocity feedback strategy behave slightly better to ensure user equity.

  11. Elementary Mode Analysis: A Useful Metabolic Pathway Analysis Tool for Characterizing Cellular Metabolism

    PubMed Central

    Trinh, Cong T.; Wlaschin, Aaron; Srienc, Friedrich

    2010-01-01

    Elementary Mode Analysis is a useful Metabolic Pathway Analysis tool to identify the structure of a metabolic network that links the cellular phenotype to the corresponding genotype. The analysis can decompose the intricate metabolic network comprised of highly interconnected reactions into uniquely organized pathways. These pathways consisting of a minimal set of enzymes that can support steady state operation of cellular metabolism represent independent cellular physiological states. Such pathway definition provides a rigorous basis to systematically characterize cellular phenotypes, metabolic network regulation, robustness, and fragility that facilitate understanding of cell physiology and implementation of metabolic engineering strategies. This mini-review aims to overview the development and application of elementary mode analysis as a metabolic pathway analysis tool in studying cell physiology and as a basis of metabolic engineering. PMID:19015845

  12. Analysis and Synthesis of Adaptive Neural Elements and Assemblies

    DTIC Science & Technology

    1992-12-14

    network, a learning rule (activity-dependent neuromodulation ), which has been proposed as a cellular mechanism for classical conditioning , was...activity-dependent neuromodulation ), which has been proposed as a cellular mechanism for classical conditioning, was demonstrated to support many...network, a learning rule (activity-dependent neuromodulation ), which has been proposed as a cellular mechanism for classical conditioning, was

  13. Gene regulatory and signaling networks exhibit distinct topological distributions of motifs

    NASA Astrophysics Data System (ADS)

    Ferreira, Gustavo Rodrigues; Nakaya, Helder Imoto; Costa, Luciano da Fontoura

    2018-04-01

    The biological processes of cellular decision making and differentiation involve a plethora of signaling pathways and gene regulatory circuits. These networks in turn exhibit a multitude of motifs playing crucial parts in regulating network activity. Here we compare the topological placement of motifs in gene regulatory and signaling networks and observe that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.

  14. Mobile Videoconferencing Apps for Telemedicine

    PubMed Central

    Liu, Wei-Li; Locatis, Craig; Ackerman, Michael

    2016-01-01

    Abstract Introduction: The quality and performance of several videoconferencing applications (apps) tested on iOS (Apple, Cupertino, CA) and Android™ (Google, Mountain View, CA) mobile platforms using Wi-Fi (802.11), third-generation (3G), and fourth-generation (4G) cellular networks are described. Materials and Methods: The tests were done to determine how well apps perform compared with videoconferencing software installed on computers or with more traditional videoconferencing using dedicated hardware. The rationale for app assessment and the testing methodology are described. Results: Findings are discussed in relation to operating system platform (iOS or Android) for which the apps were designed and the type of network (Wi-Fi, 3G, or 4G) used. The platform, network, and apps interact, and it is impossible to discuss videoconferencing experienced on mobile devices in relation to one of these factors without referencing the others. Conclusions: Apps for mobile devices can vary significantly from other videoconferencing software or hardware. App performance increased over the testing period due to improvements in network infrastructure and how apps manage bandwidth. PMID:26204322

  15. Mobile Videoconferencing Apps for Telemedicine.

    PubMed

    Zhang, Kai; Liu, Wei-Li; Locatis, Craig; Ackerman, Michael

    2016-01-01

    The quality and performance of several videoconferencing applications (apps) tested on iOS (Apple, Cupertino, CA) and Android (Google, Mountain View, CA) mobile platforms using Wi-Fi (802.11), third-generation (3G), and fourth-generation (4G) cellular networks are described. The tests were done to determine how well apps perform compared with videoconferencing software installed on computers or with more traditional videoconferencing using dedicated hardware. The rationale for app assessment and the testing methodology are described. Findings are discussed in relation to operating system platform (iOS or Android) for which the apps were designed and the type of network (Wi-Fi, 3G, or 4G) used. The platform, network, and apps interact, and it is impossible to discuss videoconferencing experienced on mobile devices in relation to one of these factors without referencing the others. Apps for mobile devices can vary significantly from other videoconferencing software or hardware. App performance increased over the testing period due to improvements in network infrastructure and how apps manage bandwidth.

  16. Telecommunication Platforms for Transmitting Sensor Data over Communication Networks-State of the Art and Challenges.

    PubMed

    Staniec, Kamil; Habrych, Marcin

    2016-07-19

    The importance of constructing wide-area sensor networks for holistic environmental state evaluation has been demonstrated. A general structure of such a network has been presented with distinction of three segments: local (based on ZigBee, Ethernet and ModBus techniques), core (base on cellular technologies) and the storage/application. The implementation of these techniques requires knowledge of their technical limitations and electromagnetic compatibility issues. The former refer to ZigBee performance degradation in multi-hop transmission, whereas the latter are associated with the common electromagnetic spectrum sharing with other existing technologies or with undesired radiated emissions generated by the radio modules of the sensor network. In many cases, it is also necessary to provide a measurement station with autonomous energy source, such as solar. As stems from measurements of the energetic efficiency of these sources, one should apply them with care and perform detailed power budget since their real performance may turn out to be far from expected. This, in turn, may negatively affect-in particular-the operation of chemical sensors implemented in the network as they often require additional heating.

  17. A high performance parallel computing architecture for robust image features

    NASA Astrophysics Data System (ADS)

    Zhou, Renyan; Liu, Leibo; Wei, Shaojun

    2014-03-01

    A design of parallel architecture for image feature detection and description is proposed in this article. The major component of this architecture is a 2D cellular network composed of simple reprogrammable processors, enabling the Hessian Blob Detector and Haar Response Calculation, which are the most computing-intensive stage of the Speeded Up Robust Features (SURF) algorithm. Combining this 2D cellular network and dedicated hardware for SURF descriptors, this architecture achieves real-time image feature detection with minimal software in the host processor. A prototype FPGA implementation of the proposed architecture achieves 1318.9 GOPS general pixel processing @ 100 MHz clock and achieves up to 118 fps in VGA (640 × 480) image feature detection. The proposed architecture is stand-alone and scalable so it is easy to be migrated into VLSI implementation.

  18. 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

  19. 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.

  20. 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

  1. A physical sciences network characterization of non-tumorigenic and metastatic cells

    PubMed Central

    Agus, David B.; Alexander, Jenolyn F.; Arap, Wadih; Ashili, Shashanka; Aslan, Joseph E.; Austin, Robert H.; Backman, Vadim; Bethel, Kelly J.; Bonneau, Richard; Chen, Wei-Chiang; Chen-Tanyolac, Chira; Choi, Nathan C.; Curley, Steven A.; Dallas, Matthew; Damania, Dhwanil; Davies, Paul C. W.; Decuzzi, Paolo; Dickinson, Laura; Estevez-Salmeron, Luis; Estrella, Veronica; Ferrari, Mauro; Fischbach, Claudia; Foo, Jasmine; Fraley, Stephanie I.; Frantz, Christian; Fuhrmann, Alexander; Gascard, Philippe; Gatenby, Robert A.; Geng, Yue; Gerecht, Sharon; Gillies, Robert J.; Godin, Biana; Grady, William M.; Greenfield, Alex; Hemphill, Courtney; Hempstead, Barbara L.; Hielscher, Abigail; Hillis, W. Daniel; Holland, Eric C.; Ibrahim-Hashim, Arig; Jacks, Tyler; Johnson, Roger H.; Joo, Ahyoung; Katz, Jonathan E.; Kelbauskas, Laimonas; Kesselman, Carl; King, Michael R.; Konstantopoulos, Konstantinos; Kraning-Rush, Casey M.; Kuhn, Peter; Kung, Kevin; Kwee, Brian; Lakins, Johnathon N.; Lambert, Guillaume; Liao, David; Licht, Jonathan D.; Liphardt, Jan T.; Liu, Liyu; Lloyd, Mark C.; Lyubimova, Anna; Mallick, Parag; Marko, John; McCarty, Owen J. T.; Meldrum, Deirdre R.; Michor, Franziska; Mumenthaler, Shannon M.; Nandakumar, Vivek; O’Halloran, Thomas V.; Oh, Steve; Pasqualini, Renata; Paszek, Matthew J.; Philips, Kevin G.; Poultney, Christopher S.; Rana, Kuldeepsinh; Reinhart-King, Cynthia A.; Ros, Robert; Semenza, Gregg L.; Senechal, Patti; Shuler, Michael L.; Srinivasan, Srimeenakshi; Staunton, Jack R.; Stypula, Yolanda; Subramanian, Hariharan; Tlsty, Thea D.; Tormoen, Garth W.; Tseng, Yiider; van Oudenaarden, Alexander; Verbridge, Scott S.; Wan, Jenny C.; Weaver, Valerie M.; Widom, Jonathan; Will, Christine; Wirtz, Denis; Wojtkowiak, Jonathan; Wu, Pei-Hsun

    2013-01-01

    To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis. PMID:23618955

  2. A physical sciences network characterization of non-tumorigenic and metastatic cells.

    PubMed

    Agus, David B; Alexander, Jenolyn F; Arap, Wadih; Ashili, Shashanka; Aslan, Joseph E; Austin, Robert H; Backman, Vadim; Bethel, Kelly J; Bonneau, Richard; Chen, Wei-Chiang; Chen-Tanyolac, Chira; Choi, Nathan C; Curley, Steven A; Dallas, Matthew; Damania, Dhwanil; Davies, Paul C W; Decuzzi, Paolo; Dickinson, Laura; Estevez-Salmeron, Luis; Estrella, Veronica; Ferrari, Mauro; Fischbach, Claudia; Foo, Jasmine; Fraley, Stephanie I; Frantz, Christian; Fuhrmann, Alexander; Gascard, Philippe; Gatenby, Robert A; Geng, Yue; Gerecht, Sharon; Gillies, Robert J; Godin, Biana; Grady, William M; Greenfield, Alex; Hemphill, Courtney; Hempstead, Barbara L; Hielscher, Abigail; Hillis, W Daniel; Holland, Eric C; Ibrahim-Hashim, Arig; Jacks, Tyler; Johnson, Roger H; Joo, Ahyoung; Katz, Jonathan E; Kelbauskas, Laimonas; Kesselman, Carl; King, Michael R; Konstantopoulos, Konstantinos; Kraning-Rush, Casey M; Kuhn, Peter; Kung, Kevin; Kwee, Brian; Lakins, Johnathon N; Lambert, Guillaume; Liao, David; Licht, Jonathan D; Liphardt, Jan T; Liu, Liyu; Lloyd, Mark C; Lyubimova, Anna; Mallick, Parag; Marko, John; McCarty, Owen J T; Meldrum, Deirdre R; Michor, Franziska; Mumenthaler, Shannon M; Nandakumar, Vivek; O'Halloran, Thomas V; Oh, Steve; Pasqualini, Renata; Paszek, Matthew J; Philips, Kevin G; Poultney, Christopher S; Rana, Kuldeepsinh; Reinhart-King, Cynthia A; Ros, Robert; Semenza, Gregg L; Senechal, Patti; Shuler, Michael L; Srinivasan, Srimeenakshi; Staunton, Jack R; Stypula, Yolanda; Subramanian, Hariharan; Tlsty, Thea D; Tormoen, Garth W; Tseng, Yiider; van Oudenaarden, Alexander; Verbridge, Scott S; Wan, Jenny C; Weaver, Valerie M; Widom, Jonathan; Will, Christine; Wirtz, Denis; Wojtkowiak, Jonathan; Wu, Pei-Hsun

    2013-01-01

    To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

  3. A physical sciences network characterization of non-tumorigenic and metastatic cells

    NASA Astrophysics Data System (ADS)

    Physical Sciences-Oncology Centers Network; Agus, David B.; Alexander, Jenolyn F.; Arap, Wadih; Ashili, Shashanka; Aslan, Joseph E.; Austin, Robert H.; Backman, Vadim; Bethel, Kelly J.; Bonneau, Richard; Chen, Wei-Chiang; Chen-Tanyolac, Chira; Choi, Nathan C.; Curley, Steven A.; Dallas, Matthew; Damania, Dhwanil; Davies, Paul C. W.; Decuzzi, Paolo; Dickinson, Laura; Estevez-Salmeron, Luis; Estrella, Veronica; Ferrari, Mauro; Fischbach, Claudia; Foo, Jasmine; Fraley, Stephanie I.; Frantz, Christian; Fuhrmann, Alexander; Gascard, Philippe; Gatenby, Robert A.; Geng, Yue; Gerecht, Sharon; Gillies, Robert J.; Godin, Biana; Grady, William M.; Greenfield, Alex; Hemphill, Courtney; Hempstead, Barbara L.; Hielscher, Abigail; Hillis, W. Daniel; Holland, Eric C.; Ibrahim-Hashim, Arig; Jacks, Tyler; Johnson, Roger H.; Joo, Ahyoung; Katz, Jonathan E.; Kelbauskas, Laimonas; Kesselman, Carl; King, Michael R.; Konstantopoulos, Konstantinos; Kraning-Rush, Casey M.; Kuhn, Peter; Kung, Kevin; Kwee, Brian; Lakins, Johnathon N.; Lambert, Guillaume; Liao, David; Licht, Jonathan D.; Liphardt, Jan T.; Liu, Liyu; Lloyd, Mark C.; Lyubimova, Anna; Mallick, Parag; Marko, John; McCarty, Owen J. T.; Meldrum, Deirdre R.; Michor, Franziska; Mumenthaler, Shannon M.; Nandakumar, Vivek; O'Halloran, Thomas V.; Oh, Steve; Pasqualini, Renata; Paszek, Matthew J.; Philips, Kevin G.; Poultney, Christopher S.; Rana, Kuldeepsinh; Reinhart-King, Cynthia A.; Ros, Robert; Semenza, Gregg L.; Senechal, Patti; Shuler, Michael L.; Srinivasan, Srimeenakshi; Staunton, Jack R.; Stypula, Yolanda; Subramanian, Hariharan; Tlsty, Thea D.; Tormoen, Garth W.; Tseng, Yiider; van Oudenaarden, Alexander; Verbridge, Scott S.; Wan, Jenny C.; Weaver, Valerie M.; Widom, Jonathan; Will, Christine; Wirtz, Denis; Wojtkowiak, Jonathan; Wu, Pei-Hsun

    2013-04-01

    To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

  4. Intrinsic Cellular Properties and Connectivity Density Determine Variable Clustering Patterns in Randomly Connected Inhibitory Neural Networks

    PubMed Central

    Rich, Scott; Booth, Victoria; Zochowski, Michal

    2016-01-01

    The plethora of inhibitory interneurons in the hippocampus and cortex play a pivotal role in generating rhythmic activity by clustering and synchronizing cell firing. Results of our simulations demonstrate that both the intrinsic cellular properties of neurons and the degree of network connectivity affect the characteristics of clustered dynamics exhibited in randomly connected, heterogeneous inhibitory networks. We quantify intrinsic cellular properties by the neuron's current-frequency relation (IF curve) and Phase Response Curve (PRC), a measure of how perturbations given at various phases of a neurons firing cycle affect subsequent spike timing. We analyze network bursting properties of networks of neurons with Type I or Type II properties in both excitability and PRC profile; Type I PRCs strictly show phase advances and IF curves that exhibit frequencies arbitrarily close to zero at firing threshold while Type II PRCs display both phase advances and delays and IF curves that have a non-zero frequency at threshold. Type II neurons whose properties arise with or without an M-type adaptation current are considered. We analyze network dynamics under different levels of cellular heterogeneity and as intrinsic cellular firing frequency and the time scale of decay of synaptic inhibition are varied. Many of the dynamics exhibited by these networks diverge from the predictions of the interneuron network gamma (ING) mechanism, as well as from results in all-to-all connected networks. Our results show that randomly connected networks of Type I neurons synchronize into a single cluster of active neurons while networks of Type II neurons organize into two mutually exclusive clusters segregated by the cells' intrinsic firing frequencies. Networks of Type II neurons containing the adaptation current behave similarly to networks of either Type I or Type II neurons depending on network parameters; however, the adaptation current creates differences in the cluster dynamics compared to those in networks of Type I or Type II neurons. To understand these results, we compute neuronal PRCs calculated with a perturbation matching the profile of the synaptic current in our networks. Differences in profiles of these PRCs across the different neuron types reveal mechanisms underlying the divergent network dynamics. PMID:27812323

  5. Smart Bandwidth Assignation in an Underlay Cellular Network for Internet of Vehicles.

    PubMed

    de la Iglesia, Idoia; Hernandez-Jayo, Unai; Osaba, Eneko; Carballedo, Roberto

    2017-09-27

    The evolution of the IoT (Internet of Things) paradigm applied to new scenarios as VANETs (Vehicular Ad Hoc Networks) has gained momentum in recent years. Both academia and industry have triggered advanced studies in the IoV (Internet of Vehicles), which is understood as an ecosystem where different types of users (vehicles, elements of the infrastructure, pedestrians) are connected. How to efficiently share the available radio resources among the different types of eligible users is one of the important issues to be addressed. This paper briefly analyzes various concepts presented hitherto in the literature and it proposes an enhanced algorithm for ensuring a robust co-existence of the aforementioned system users. Therefore, this paper introduces an underlay RRM (Radio Resource Management) methodology which is capable of (1) improving cellular spectral efficiency while making a minimal impact on cellular communications and (2) ensuring the different QoS (Quality of Service) requirements of ITS (Intelligent Transportation Systems) applications. Simulation results, where we compare the proposed algorithm to the other two RRM, show the promising spectral efficiency performance of the proposed RRM methodology.

  6. Smart Bandwidth Assignation in an Underlay Cellular Network for Internet of Vehicles

    PubMed Central

    de la Iglesia, Idoia; Hernandez-Jayo, Unai

    2017-01-01

    The evolution of the IoT (Internet of Things) paradigm applied to new scenarios as VANETs (Vehicular Ad Hoc Networks) has gained momentum in recent years. Both academia and industry have triggered advanced studies in the IoV (Internet of Vehicles), which is understood as an ecosystem where different types of users (vehicles, elements of the infrastructure, pedestrians) are connected. How to efficiently share the available radio resources among the different types of eligible users is one of the important issues to be addressed. This paper briefly analyzes various concepts presented hitherto in the literature and it proposes an enhanced algorithm for ensuring a robust co-existence of the aforementioned system users. Therefore, this paper introduces an underlay RRM (Radio Resource Management) methodology which is capable of (1) improving cellular spectral efficiency while making a minimal impact on cellular communications and (2) ensuring the different QoS (Quality of Service) requirements of ITS (Intelligent Transportation Systems) applications. Simulation results, where we compare the proposed algorithm to the other two RRM, show the promising spectral efficiency performance of the proposed RRM methodology. PMID:28953256

  7. Distributed sensor networks: a cellular nonlinear network perspective.

    PubMed

    Haenggi, Martin

    2003-12-01

    Large-scale networks of integrated wireless sensors become increasingly tractable. Advances in hardware technology and engineering design have led to dramatic reductions in size, power consumption, and cost for digital circuitry, and wireless communications. Networking, self-organization, and distributed operation are crucial ingredients to harness the sensing, computing, and computational capabilities of the nodes into a complete system. This article shows that those networks can be considered as cellular nonlinear networks (CNNs), and that their analysis and design may greatly benefit from the rich theoretical results available for CNNs.

  8. Molecular Signaling Network Motifs Provide a Mechanistic Basis for Cellular Threshold Responses

    PubMed Central

    Bhattacharya, Sudin; Conolly, Rory B.; Clewell, Harvey J.; Kaminski, Norbert E.; Andersen, Melvin E.

    2014-01-01

    Background: Increasingly, there is a move toward using in vitro toxicity testing to assess human health risk due to chemical exposure. As with in vivo toxicity testing, an important question for in vitro results is whether there are thresholds for adverse cellular responses. Empirical evaluations may show consistency with thresholds, but the main evidence has to come from mechanistic considerations. Objectives: Cellular response behaviors depend on the molecular pathway and circuitry in the cell and the manner in which chemicals perturb these circuits. Understanding circuit structures that are inherently capable of resisting small perturbations and producing threshold responses is an important step towards mechanistically interpreting in vitro testing data. Methods: Here we have examined dose–response characteristics for several biochemical network motifs. These network motifs are basic building blocks of molecular circuits underpinning a variety of cellular functions, including adaptation, homeostasis, proliferation, differentiation, and apoptosis. For each motif, we present biological examples and models to illustrate how thresholds arise from specific network structures. Discussion and Conclusion: Integral feedback, feedforward, and transcritical bifurcation motifs can generate thresholds. Other motifs (e.g., proportional feedback and ultrasensitivity)produce responses where the slope in the low-dose region is small and stays close to the baseline. Feedforward control may lead to nonmonotonic or hormetic responses. We conclude that network motifs provide a basis for understanding thresholds for cellular responses. Computational pathway modeling of these motifs and their combinations occurring in molecular signaling networks will be a key element in new risk assessment approaches based on in vitro cellular assays. Citation: Zhang Q, Bhattacharya S, Conolly RB, Clewell HJ III, Kaminski NE, Andersen ME. 2014. Molecular signaling network motifs provide a mechanistic basis for cellular threshold responses. Environ Health Perspect 122:1261–1270; http://dx.doi.org/10.1289/ehp.1408244 PMID:25117432

  9. Bio-Inspired Networking — Self-Organizing Networked Embedded Systems

    NASA Astrophysics Data System (ADS)

    Dressler, Falko

    The turn to nature has brought us many unforeseen great concepts and solutions. This course seems to hold on for many research domains. In this article, we study the applicability of biological mechanisms and techniques in the domain of communications. In particular, we study the behavior and the challenges in networked embedded systems that are meant to self-organize in large groups of nodes. Application examples include wireless sensor networks and sensor/actuator networks. Based on a review of the needs and requirements in such networks, we study selected bio-inspired networking approaches that claim to outperform other methods in specific domains. We study mechanisms in swarm intelligence, the artificial immune system, and approaches based on investigations on the cellular signaling pathways. As a major conclusion, we derive that bio-inspired networking techniques do have advantages compared to engineering methods. Nevertheless, selection and employment must be done carefully to achieve the desired performance gains.

  10. Traffic prediction using wireless cellular networks : final report.

    DOT National Transportation Integrated Search

    2016-03-01

    The major objective of this project is to obtain traffic information from existing wireless : infrastructure. : In this project freeway traffic is identified and modeled using data obtained from existing : wireless cellular networks. Most of the prev...

  11. Shunting inhibitory cellular neural networks with chaotic external inputs

    NASA Astrophysics Data System (ADS)

    Akhmet, M. U.; Fen, M. O.

    2013-06-01

    Taking advantage of external inputs, it is shown that shunting inhibitory cellular neural networks behave chaotically. The analysis is based on the Li-Yorke definition of chaos. Appropriate illustrations which support the theoretical results are depicted.

  12. Control of fluxes in metabolic networks

    PubMed Central

    Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

    2016-01-01

    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

  13. Least dissipation cost as a design principle for robustness and function of cellular networks

    NASA Astrophysics Data System (ADS)

    Han, Bo; Wang, Jin

    2008-03-01

    From a study of the budding yeast cell cycle, we found that the cellular network evolves to have the least cost for realizing its biological function. We quantify the cost in terms of the dissipation or heat loss characterized through the steady-state properties: the underlying landscape and the associated flux. We found that the dissipation cost is intimately related to the stability and robustness of the network. With the least dissipation cost, the network becomes most stable and robust under mutations and perturbations on the sharpness of the response from input to output as well as self-degradations. The least dissipation cost may provide a general design principle for the cellular network to survive from the evolution and realize the biological function.

  14. Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer

    NASA Astrophysics Data System (ADS)

    Damania, Dhwanil; Subramanian, Hariharan; Backman, Vadim; Anderson, Eric C.; Wong, Melissa H.; McCarty, Owen J. T.; Phillips, Kevin G.

    2014-01-01

    Cells contributing to the pathogenesis of cancer possess cytoplasmic and nuclear structural alterations that accompany their aberrant genetic, epigenetic, and molecular perturbations. Although it is known that architectural changes in primary and metastatic tumor cells can be quantified through variations in cellular density at the nanometer and micrometer spatial scales, the interdependent relationships among nuclear and cytoplasmic density as a function of tumorigenic potential has not been thoroughly investigated. We present a combined optical approach utilizing quantitative phase microscopy and partial wave spectroscopic microscopy to perform parallel structural characterizations of cellular architecture. Using the isogenic SW480 and SW620 cell lines as a model of pre and postmetastatic transition in colorectal cancer, we demonstrate that nuclear and cytoplasmic nanoscale disorder, micron-scale dry mass content, mean dry mass density, and shape metrics of the dry mass density histogram are uniquely correlated within and across different cellular compartments for a given cell type. The correlations of these physical parameters can be interpreted as networks whose nodal importance and level of connection independence differ according to disease stage. This work demonstrates how optically derived biophysical parameters are linked within and across different cellular compartments during the architectural orchestration of the metastatic phenotype.

  15. Interfacing cellular networks of S. cerevisiae and E. coli: Connecting dynamic and genetic information

    PubMed Central

    2013-01-01

    Background In recent years, various types of cellular networks have penetrated biology and are nowadays used omnipresently for studying eukaryote and prokaryote organisms. Still, the relation and the biological overlap among phenomenological and inferential gene networks, e.g., between the protein interaction network and the gene regulatory network inferred from large-scale transcriptomic data, is largely unexplored. Results We provide in this study an in-depth analysis of the structural, functional and chromosomal relationship between a protein-protein network, a transcriptional regulatory network and an inferred gene regulatory network, for S. cerevisiae and E. coli. Further, we study global and local aspects of these networks and their biological information overlap by comparing, e.g., the functional co-occurrence of Gene Ontology terms by exploiting the available interaction structure among the genes. Conclusions Although the individual networks represent different levels of cellular interactions with global structural and functional dissimilarities, we observe crucial functions of their network interfaces for the assembly of protein complexes, proteolysis, transcription, translation, metabolic and regulatory interactions. Overall, our results shed light on the integrability of these networks and their interfacing biological processes. PMID:23663484

  16. Discrepancy between mRNA and protein abundance: Insight from information retrieval process in computers

    PubMed Central

    Wang, Degeng

    2008-01-01

    Discrepancy between the abundance of cognate protein and RNA molecules is frequently observed. A theoretical understanding of this discrepancy remains elusive, and it is frequently described as surprises and/or technical difficulties in the literature. Protein and RNA represent different steps of the multi-stepped cellular genetic information flow process, in which they are dynamically produced and degraded. This paper explores a comparison with a similar process in computers - multi-step information flow from storage level to the execution level. Functional similarities can be found in almost every facet of the retrieval process. Firstly, common architecture is shared, as the ribonome (RNA space) and the proteome (protein space) are functionally similar to the computer primary memory and the computer cache memory respectively. Secondly, the retrieval process functions, in both systems, to support the operation of dynamic networks – biochemical regulatory networks in cells and, in computers, the virtual networks (of CPU instructions) that the CPU travels through while executing computer programs. Moreover, many regulatory techniques are implemented in computers at each step of the information retrieval process, with a goal of optimizing system performance. Cellular counterparts can be easily identified for these regulatory techniques. In other words, this comparative study attempted to utilize theoretical insight from computer system design principles as catalysis to sketch an integrative view of the gene expression process, that is, how it functions to ensure efficient operation of the overall cellular regulatory network. In context of this bird’s-eye view, discrepancy between protein and RNA abundance became a logical observation one would expect. It was suggested that this discrepancy, when interpreted in the context of system operation, serves as a potential source of information to decipher regulatory logics underneath biochemical network operation. PMID:18757239

  17. The underlying pathway structure of biochemical reaction networks

    PubMed Central

    Schilling, Christophe H.; Palsson, Bernhard O.

    1998-01-01

    Bioinformatics is yielding extensive, and in some cases complete, genetic and biochemical information about individual cell types and cellular processes, providing the composition of living cells and the molecular structure of its components. These components together perform integrated cellular functions that now need to be analyzed. In particular, the functional definition of biochemical pathways and their role in the context of the whole cell is lacking. In this study, we show how the mass balance constraints that govern the function of biochemical reaction networks lead to the translation of this problem into the realm of linear algebra. The functional capabilities of biochemical reaction networks, and thus the choices that cells can make, are reflected in the null space of their stoichiometric matrix. The null space is spanned by a finite number of basis vectors. We present an algorithm for the synthesis of a set of basis vectors for spanning the null space of the stoichiometric matrix, in which these basis vectors represent the underlying biochemical pathways that are fundamental to the corresponding biochemical reaction network. In other words, all possible flux distributions achievable by a defined set of biochemical reactions are represented by a linear combination of these basis pathways. These basis pathways thus represent the underlying pathway structure of the defined biochemical reaction network. This development is significant from a fundamental and conceptual standpoint because it yields a holistic definition of biochemical pathways in contrast to definitions that have arisen from the historical development of our knowledge about biochemical processes. Additionally, this new conceptual framework will be important in defining, characterizing, and studying biochemical pathways from the rapidly growing information on cellular function. PMID:9539712

  18. Discrepancy between mRNA and protein abundance: insight from information retrieval process in computers.

    PubMed

    Wang, Degeng

    2008-12-01

    Discrepancy between the abundance of cognate protein and RNA molecules is frequently observed. A theoretical understanding of this discrepancy remains elusive, and it is frequently described as surprises and/or technical difficulties in the literature. Protein and RNA represent different steps of the multi-stepped cellular genetic information flow process, in which they are dynamically produced and degraded. This paper explores a comparison with a similar process in computers-multi-step information flow from storage level to the execution level. Functional similarities can be found in almost every facet of the retrieval process. Firstly, common architecture is shared, as the ribonome (RNA space) and the proteome (protein space) are functionally similar to the computer primary memory and the computer cache memory, respectively. Secondly, the retrieval process functions, in both systems, to support the operation of dynamic networks-biochemical regulatory networks in cells and, in computers, the virtual networks (of CPU instructions) that the CPU travels through while executing computer programs. Moreover, many regulatory techniques are implemented in computers at each step of the information retrieval process, with a goal of optimizing system performance. Cellular counterparts can be easily identified for these regulatory techniques. In other words, this comparative study attempted to utilize theoretical insight from computer system design principles as catalysis to sketch an integrative view of the gene expression process, that is, how it functions to ensure efficient operation of the overall cellular regulatory network. In context of this bird's-eye view, discrepancy between protein and RNA abundance became a logical observation one would expect. It was suggested that this discrepancy, when interpreted in the context of system operation, serves as a potential source of information to decipher regulatory logics underneath biochemical network operation.

  19. Architectures and protocols for an integrated satellite-terrestrial mobile system

    NASA Technical Reports Server (NTRS)

    Delre, E.; Dellipriscoli, F.; Iannucci, P.; Menolascino, R.; Settimo, F.

    1993-01-01

    This paper aims to depict some basic concepts related to the definition of an integrated system for mobile communications, consisting of a satellite network and a terrestrial cellular network. In particular three aspects are discussed: (1) architecture definition for the satellite network; (2) assignment strategy of the satellite channels; and (3) definition of 'internetworking procedures' between cellular and satellite network, according to the selected architecture and the satellite channel assignment strategy.

  20. The large-scale organization of metabolic networks

    NASA Astrophysics Data System (ADS)

    Jeong, H.; Tombor, B.; Albert, R.; Oltvai, Z. N.; Barabási, A.-L.

    2000-10-01

    In a cell or microorganism, the processes that generate mass, energy, information transfer and cell-fate specification are seamlessly integrated through a complex network of cellular constituents and reactions. However, despite the key role of these networks in sustaining cellular functions, their large-scale structure is essentially unknown. Here we present a systematic comparative mathematical analysis of the metabolic networks of 43 organisms representing all three domains of life. We show that, despite significant variation in their individual constituents and pathways, these metabolic networks have the same topological scaling properties and show striking similarities to the inherent organization of complex non-biological systems. This may indicate that metabolic organization is not only identical for all living organisms, but also complies with the design principles of robust and error-tolerant scale-free networks, and may represent a common blueprint for the large-scale organization of interactions among all cellular constituents.

  1. Performance Evaluation of Hyperbolic Position Location Technique in Cellular Wireless Networks

    DTIC Science & Technology

    2002-03-13

    number of applications called location - based services which can be defined as value added services that utilize the knowledge of the mobile user’s... Location based services “4-1-1”, location specific information such as local weather, mobile yellow pages, etc. and • Mobile e-commerce, wireless

  2. 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.

  3. Design of cryptographically secure AES like S-Box using second-order reversible cellular automata for wireless body area network applications.

    PubMed

    Gangadari, Bhoopal Rao; Rafi Ahamed, Shaik

    2016-09-01

    In biomedical, data security is the most expensive resource for wireless body area network applications. Cryptographic algorithms are used in order to protect the information against unauthorised access. Advanced encryption standard (AES) cryptographic algorithm plays a vital role in telemedicine applications. The authors propose a novel approach for design of substitution bytes (S-Box) using second-order reversible one-dimensional cellular automata (RCA 2 ) as a replacement to the classical look-up-table (LUT) based S-Box used in AES algorithm. The performance of proposed RCA 2 based S-Box and conventional LUT based S-Box is evaluated in terms of security using the cryptographic properties such as the nonlinearity, correlation immunity bias, strict avalanche criteria and entropy. Moreover, it is also shown that RCA 2 based S-Boxes are dynamic in nature, invertible and provide high level of security. Further, it is also found that the RCA 2 based S-Box have comparatively better performance than that of conventional LUT based S-Box.

  4. 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

    2015-09-04

    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.

  5. Design of cryptographically secure AES like S-Box using second-order reversible cellular automata for wireless body area network applications

    PubMed Central

    Rafi Ahamed, Shaik

    2016-01-01

    In biomedical, data security is the most expensive resource for wireless body area network applications. Cryptographic algorithms are used in order to protect the information against unauthorised access. Advanced encryption standard (AES) cryptographic algorithm plays a vital role in telemedicine applications. The authors propose a novel approach for design of substitution bytes (S-Box) using second-order reversible one-dimensional cellular automata (RCA2) as a replacement to the classical look-up-table (LUT) based S-Box used in AES algorithm. The performance of proposed RCA2 based S-Box and conventional LUT based S-Box is evaluated in terms of security using the cryptographic properties such as the nonlinearity, correlation immunity bias, strict avalanche criteria and entropy. Moreover, it is also shown that RCA2 based S-Boxes are dynamic in nature, invertible and provide high level of security. Further, it is also found that the RCA2 based S-Box have comparatively better performance than that of conventional LUT based S-Box. PMID:27733924

  6. Optimal Objective-Based Experimental Design for Uncertain Dynamical Gene Networks with Experimental Error.

    PubMed

    Mohsenizadeh, Daniel N; Dehghannasiri, Roozbeh; Dougherty, Edward R

    2018-01-01

    In systems biology, network models are often used to study interactions among cellular components, a salient aim being to develop drugs and therapeutic mechanisms to change the dynamical behavior of the network to avoid undesirable phenotypes. Owing to limited knowledge, model uncertainty is commonplace and network dynamics can be updated in different ways, thereby giving multiple dynamic trajectories, that is, dynamics uncertainty. In this manuscript, we propose an experimental design method that can effectively reduce the dynamics uncertainty and improve performance in an interaction-based network. Both dynamics uncertainty and experimental error are quantified with respect to the modeling objective, herein, therapeutic intervention. The aim of experimental design is to select among a set of candidate experiments the experiment whose outcome, when applied to the network model, maximally reduces the dynamics uncertainty pertinent to the intervention objective.

  7. A secure mobile multimedia system to assist emergency response teams.

    PubMed

    Belala, Yacine; Issa, Omneya; Gregoire, Jean-Charles; Wong, James

    2008-08-01

    Long wait times after injury and greater distances to travel between accident scenes and medical facilities contribute to increased, possibly unnecessary deaths. This paper describes a mobile emergency system aimed at reducing mortality by improving the readiness of hospital personnel, therefore allowing for more efficient treatment procedures to be performed when the victim arrives. The system is designed to provide a secure transmission of voice, medical data, and video in real-time over third-generation cellular networks. Test results obtained on a commercial network under real-life conditions demonstrate the ability to effectively transmit medical data over 3G networks, making them a viable option available to healthcare professionals.

  8. 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.

  9. Engineering microbial phenotypes through rewiring of genetic networks

    PubMed Central

    Rodrigues, Rui T.L.; Lee, Sangjin; Haines, Matthew

    2017-01-01

    Abstract The ability to program cellular behaviour is a major goal of synthetic biology, with applications in health, agriculture and chemicals production. Despite efforts to build ‘orthogonal’ systems, interactions between engineered genetic circuits and the endogenous regulatory network of a host cell can have a significant impact on desired functionality. We have developed a strategy to rewire the endogenous cellular regulatory network of yeast to enhance compatibility with synthetic protein and metabolite production. We found that introducing novel connections in the cellular regulatory network enabled us to increase the production of heterologous proteins and metabolites. This strategy is demonstrated in yeast strains that show significantly enhanced heterologous protein expression and higher titers of terpenoid production. Specifically, we found that the addition of transcriptional regulation between free radical induced signalling and nitrogen regulation provided robust improvement of protein production. Assessment of rewired networks revealed the importance of key topological features such as high betweenness centrality. The generation of rewired transcriptional networks, selection for specific phenotypes, and analysis of resulting library members is a powerful tool for engineering cellular behavior and may enable improved integration of heterologous protein and metabolite pathways. PMID:28369627

  10. Interconnectivity of human cellular metabolism and disease prevalence

    NASA Astrophysics Data System (ADS)

    Lee, Deok-Sun

    2010-12-01

    Fluctuations of metabolic reaction fluxes may cause abnormal concentrations of toxic or essential metabolites, possibly leading to metabolic diseases. The mutual binding of enzymatic proteins and ones involving common metabolites enforces distinct coupled reactions, by which local perturbations may spread through the cellular network. Such network effects at the molecular interaction level in human cellular metabolism can reappear in the patterns of disease occurrence. Here we construct the enzyme-reaction network and the metabolite-reaction network, capturing the flux coupling of metabolic reactions caused by the interacting enzymes and the shared metabolites, respectively. Diseases potentially caused by the failure of individual metabolic reactions can be identified by using the known disease-gene association, which allows us to derive the probability of an inactivated reaction causing diseases from the disease records at the population level. We find that the greater the number of proteins that catalyze a reaction, the higher the mean prevalence of its associated diseases. Moreover, the number of connected reactions and the mean size of the avalanches in the networks constructed are also shown to be positively correlated with the disease prevalence. These findings illuminate the impact of the cellular network topology on disease development, suggesting that the global organization of the molecular interaction network should be understood to assist in disease diagnosis, treatment, and drug discovery.

  11. 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.

  12. [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. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  13. 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

  14. 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.

  15. Towards a comprehensive understanding of emerging dynamics and function of pancreatic islets: A complex network approach. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

    NASA Astrophysics Data System (ADS)

    Loppini, Alessandro

    2018-03-01

    Complex network theory represents a comprehensive mathematical framework to investigate biological systems, ranging from sub-cellular and cellular scales up to large-scale networks describing species interactions and ecological systems. In their exhaustive and comprehensive work [1], Gosak et al. discuss several scenarios in which the network approach was able to uncover general properties and underlying mechanisms of cells organization and regulation, tissue functions and cell/tissue failure in pathology, by the study of chemical reaction networks, structural networks and functional connectivities.

  16. PDA-phone-based instant transmission of radiological images over a CDMA network by combining the PACS screen with a Bluetooth-interfaced local wireless link.

    PubMed

    Kim, Dong Keun; Yoo, Sun K; Park, Jeong Jin; Kim, Sun Ho

    2007-06-01

    Remote teleconsultation by specialists is important for timely, correct, and specialized emergency surgical and medical decision making. In this paper, we designed a new personal digital assistant (PDA)-phone-based emergency teleradiology system by combining cellular communication with Bluetooth-interfaced local wireless links. The mobility and portability resulting from the use of PDAs and wireless communication can provide a more effective means of emergency teleconsultation without requiring the user to be limited to a fixed location. Moreover, it enables synchronized radiological image sharing between the attending physician in the emergency room and the remote specialist on picture archiving and communication system terminals without distorted image acquisition. To enable rapid and fine-quality radiological image transmission over a cellular network in a secure manner, progressive compression and security mechanisms have been incorporated. The proposed system is tested over a code division Multiple Access 1x-Evolution Data-Only network to evaluate the performance and to demonstrate the feasibility of this system in a real-world setting.

  17. Developmental Progression in the Coral Acropora digitifera Is Controlled by Differential Expression of Distinct Regulatory Gene Networks

    PubMed Central

    Reyes-Bermudez, Alejandro; Villar-Briones, Alejandro; Ramirez-Portilla, Catalina; Hidaka, Michio; Mikheyev, Alexander S.

    2016-01-01

    Corals belong to the most basal class of the Phylum Cnidaria, which is considered the sister group of bilaterian animals, and thus have become an emerging model to study the evolution of developmental mechanisms. Although cell renewal, differentiation, and maintenance of pluripotency are cellular events shared by multicellular animals, the cellular basis of these fundamental biological processes are still poorly understood. To understand how changes in gene expression regulate morphogenetic transitions at the base of the eumetazoa, we performed quantitative RNA-seq analysis during Acropora digitifera’s development. We collected embryonic, larval, and adult samples to characterize stage-specific transcription profiles, as well as broad expression patterns. Transcription profiles reconstructed development revealing two main expression clusters. The first cluster grouped blastula and gastrula and the second grouped subsequent developmental time points. Consistently, we observed clear differences in gene expression between early and late developmental transitions, with higher numbers of differentially expressed genes and fold changes around gastrulation. Furthermore, we identified three coexpression clusters that represented discrete gene expression patterns. During early transitions, transcriptional networks seemed to regulate cellular fate and morphogenesis of the larval body. In late transitions, these networks seemed to play important roles preparing planulae for switch in lifestyle and regulation of adult processes. Although developmental progression in A. digitifera is regulated to some extent by differential coexpression of well-defined gene networks, stage-specific transcription profiles appear to be independent entities. While negative regulation of transcription is predominant in early development, cell differentiation was upregulated in larval and adult stages. PMID:26941230

  18. Triangles bridge the scales: Quantifying cellular contributions to tissue deformation

    NASA Astrophysics Data System (ADS)

    Merkel, Matthias; Etournay, Raphaël; Popović, Marko; Salbreux, Guillaume; Eaton, Suzanne; Jülicher, Frank

    2017-03-01

    In this article, we propose a general framework to study the dynamics and topology of cellular networks that capture the geometry of cell packings in two-dimensional tissues. Such epithelia undergo large-scale deformation during morphogenesis of a multicellular organism. Large-scale deformations emerge from many individual cellular events such as cell shape changes, cell rearrangements, cell divisions, and cell extrusions. Using a triangle-based representation of cellular network geometry, we obtain an exact decomposition of large-scale material deformation. Interestingly, our approach reveals contributions of correlations between cellular rotations and elongation as well as cellular growth and elongation to tissue deformation. Using this triangle method, we discuss tissue remodeling in the developing pupal wing of the fly Drosophila melanogaster.

  19. MSAT and cellular hybrid networking

    NASA Astrophysics Data System (ADS)

    Baranowsky, Patrick W., II

    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.

  20. Network Analysis Reveals a Common Host-Pathogen Interaction Pattern in Arabidopsis Immune Responses.

    PubMed

    Li, Hong; Zhou, Yuan; Zhang, Ziding

    2017-01-01

    Many plant pathogens secrete virulence effectors into host cells to target important proteins in host cellular network. However, the dynamic interactions between effectors and host cellular network have not been fully understood. Here, an integrative network analysis was conducted by combining Arabidopsis thaliana protein-protein interaction network, known targets of Pseudomonas syringae and Hyaloperonospora arabidopsidis effectors, and gene expression profiles in the immune response. In particular, we focused on the characteristic network topology of the effector targets and differentially expressed genes (DEGs). We found that effectors tended to manipulate key network positions with higher betweenness centrality. The effector targets, especially those that are common targets of an individual effector, tended to be clustered together in the network. Moreover, the distances between the effector targets and DEGs increased over time during infection. In line with this observation, pathogen-susceptible mutants tended to have more DEGs surrounding the effector targets compared with resistant mutants. Our results suggest a common plant-pathogen interaction pattern at the cellular network level, where pathogens employ potent local impact mode to interfere with key positions in the host network, and plant organizes an in-depth defense by sequentially activating genes distal to the effector targets.

  1. Inferring Broad Regulatory Biology from Time Course Data: Have We Reached an Upper Bound under Constraints Typical of In Vivo Studies?

    PubMed Central

    Craddock, Travis J. A.; Fletcher, Mary Ann; Klimas, Nancy G.

    2015-01-01

    There is a growing appreciation for the network biology that regulates the coordinated expression of molecular and cellular markers however questions persist regarding the identifiability of these networks. Here we explore some of the issues relevant to recovering directed regulatory networks from time course data collected under experimental constraints typical of in vivo studies. NetSim simulations of sparsely connected biological networks were used to evaluate two simple feature selection techniques used in the construction of linear Ordinary Differential Equation (ODE) models, namely truncation of terms versus latent vector projection. Performance was compared with ODE-based Time Series Network Identification (TSNI) integral, and the information-theoretic Time-Delay ARACNE (TD-ARACNE). Projection-based techniques and TSNI integral outperformed truncation-based selection and TD-ARACNE on aggregate networks with edge densities of 10-30%, i.e. transcription factor, protein-protein cliques and immune signaling networks. All were more robust to noise than truncation-based feature selection. Performance was comparable on the in silico 10-node DREAM 3 network, a 5-node Yeast synthetic network designed for In vivo Reverse-engineering and Modeling Assessment (IRMA) and a 9-node human HeLa cell cycle network of similar size and edge density. Performance was more sensitive to the number of time courses than to sample frequency and extrapolated better to larger networks by grouping experiments. In all cases performance declined rapidly in larger networks with lower edge density. Limited recovery and high false positive rates obtained overall bring into question our ability to generate informative time course data rather than the design of any particular reverse engineering algorithm. PMID:25984725

  2. MIDER: Network Inference with Mutual Information Distance and Entropy Reduction

    PubMed Central

    Villaverde, Alejandro F.; Ross, John; Morán, Federico; Banga, Julio R.

    2014-01-01

    The prediction of links among variables from a given dataset is a task referred to as network inference or reverse engineering. It is an open problem in bioinformatics and systems biology, as well as in other areas of science. Information theory, which uses concepts such as mutual information, provides a rigorous framework for addressing it. While a number of information-theoretic methods are already available, most of them focus on a particular type of problem, introducing assumptions that limit their generality. Furthermore, many of these methods lack a publicly available implementation. Here we present MIDER, a method for inferring network structures with information theoretic concepts. It consists of two steps: first, it provides a representation of the network in which the distance among nodes indicates their statistical closeness. Second, it refines the prediction of the existing links to distinguish between direct and indirect interactions and to assign directionality. The method accepts as input time-series data related to some quantitative features of the network nodes (such as e.g. concentrations, if the nodes are chemical species). It takes into account time delays between variables, and allows choosing among several definitions and normalizations of mutual information. It is general purpose: it may be applied to any type of network, cellular or otherwise. A Matlab implementation including source code and data is freely available (http://www.iim.csic.es/~gingproc/mider.html). The performance of MIDER has been evaluated on seven different benchmark problems that cover the main types of cellular networks, including metabolic, gene regulatory, and signaling. Comparisons with state of the art information–theoretic methods have demonstrated the competitive performance of MIDER, as well as its versatility. Its use does not demand any a priori knowledge from the user; the default settings and the adaptive nature of the method provide good results for a wide range of problems without requiring tuning. PMID:24806471

  3. MIDER: network inference with mutual information distance and entropy reduction.

    PubMed

    Villaverde, Alejandro F; Ross, John; Morán, Federico; Banga, Julio R

    2014-01-01

    The prediction of links among variables from a given dataset is a task referred to as network inference or reverse engineering. It is an open problem in bioinformatics and systems biology, as well as in other areas of science. Information theory, which uses concepts such as mutual information, provides a rigorous framework for addressing it. While a number of information-theoretic methods are already available, most of them focus on a particular type of problem, introducing assumptions that limit their generality. Furthermore, many of these methods lack a publicly available implementation. Here we present MIDER, a method for inferring network structures with information theoretic concepts. It consists of two steps: first, it provides a representation of the network in which the distance among nodes indicates their statistical closeness. Second, it refines the prediction of the existing links to distinguish between direct and indirect interactions and to assign directionality. The method accepts as input time-series data related to some quantitative features of the network nodes (such as e.g. concentrations, if the nodes are chemical species). It takes into account time delays between variables, and allows choosing among several definitions and normalizations of mutual information. It is general purpose: it may be applied to any type of network, cellular or otherwise. A Matlab implementation including source code and data is freely available (http://www.iim.csic.es/~gingproc/mider.html). The performance of MIDER has been evaluated on seven different benchmark problems that cover the main types of cellular networks, including metabolic, gene regulatory, and signaling. Comparisons with state of the art information-theoretic methods have demonstrated the competitive performance of MIDER, as well as its versatility. Its use does not demand any a priori knowledge from the user; the default settings and the adaptive nature of the method provide good results for a wide range of problems without requiring tuning.

  4. Discrete Logic Modelling Optimization to Contextualize Prior Knowledge Networks Using PRUNET

    PubMed Central

    Androsova, Ganna; del Sol, Antonio

    2015-01-01

    High-throughput technologies have led to the generation of an increasing amount of data in different areas of biology. Datasets capturing the cell’s response to its intra- and extra-cellular microenvironment allows such data to be incorporated as signed and directed graphs or influence networks. These prior knowledge networks (PKNs) represent our current knowledge of the causality of cellular signal transduction. New signalling data is often examined and interpreted in conjunction with PKNs. However, different biological contexts, such as cell type or disease states, may have distinct variants of signalling pathways, resulting in the misinterpretation of new data. The identification of inconsistencies between measured data and signalling topologies, as well as the training of PKNs using context specific datasets (PKN contextualization), are necessary conditions to construct reliable, predictive models, which are current challenges in the systems biology of cell signalling. Here we present PRUNET, a user-friendly software tool designed to address the contextualization of a PKNs to specific experimental conditions. As the input, the algorithm takes a PKN and the expression profile of two given stable steady states or cellular phenotypes. The PKN is iteratively pruned using an evolutionary algorithm to perform an optimization process. This optimization rests in a match between predicted attractors in a discrete logic model (Boolean) and a Booleanized representation of the phenotypes, within a population of alternative subnetworks that evolves iteratively. We validated the algorithm applying PRUNET to four biological examples and using the resulting contextualized networks to predict missing expression values and to simulate well-characterized perturbations. PRUNET constitutes a tool for the automatic curation of a PKN to make it suitable for describing biological processes under particular experimental conditions. The general applicability of the implemented algorithm makes PRUNET suitable for a variety of biological processes, for instance cellular reprogramming or transitions between healthy and disease states. PMID:26058016

  5. Telecommunication Platforms for Transmitting Sensor Data over Communication Networks—State of the Art and Challenges

    PubMed Central

    Staniec, Kamil; Habrych, Marcin

    2016-01-01

    The importance of constructing wide-area sensor networks for holistic environmental state evaluation has been demonstrated. A general structure of such a network has been presented with distinction of three segments: local (based on ZigBee, Ethernet and ModBus techniques), core (base on cellular technologies) and the storage/application. The implementation of these techniques requires knowledge of their technical limitations and electromagnetic compatibility issues. The former refer to ZigBee performance degradation in multi-hop transmission, whereas the latter are associated with the common electromagnetic spectrum sharing with other existing technologies or with undesired radiated emissions generated by the radio modules of the sensor network. In many cases, it is also necessary to provide a measurement station with autonomous energy source, such as solar. As stems from measurements of the energetic efficiency of these sources, one should apply them with care and perform detailed power budget since their real performance may turn out to be far from expected. This, in turn, may negatively affect—in particular—the operation of chemical sensors implemented in the network as they often require additional heating. PMID:27447633

  6. 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

  7. 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. © 2016 Basler et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Reverse Engineering Validation using a Benchmark Synthetic Gene Circuit in Human Cells

    PubMed Central

    Kang, Taek; White, Jacob T.; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas

    2013-01-01

    Multi-component biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network. PMID:23654266

  9. Reverse engineering validation using a benchmark synthetic gene circuit in human cells.

    PubMed

    Kang, Taek; White, Jacob T; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas

    2013-05-17

    Multicomponent biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network.

  10. Genetic networks and soft computing.

    PubMed

    Mitra, Sushmita; Das, Ranajit; Hayashi, Yoichi

    2011-01-01

    The analysis of gene regulatory networks provides enormous information on various fundamental cellular processes involving growth, development, hormone secretion, and cellular communication. Their extraction from available gene expression profiles is a challenging problem. Such reverse engineering of genetic networks offers insight into cellular activity toward prediction of adverse effects of new drugs or possible identification of new drug targets. Tasks such as classification, clustering, and feature selection enable efficient mining of knowledge about gene interactions in the form of networks. It is known that biological data is prone to different kinds of noise and ambiguity. Soft computing tools, such as fuzzy sets, evolutionary strategies, and neurocomputing, have been found to be helpful in providing low-cost, acceptable solutions in the presence of various types of uncertainties. In this paper, we survey the role of these soft methodologies and their hybridizations, for the purpose of generating genetic networks.

  11. 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.

  12. Serotonin targets inhibitory synapses to induce modulation of network functions

    PubMed Central

    Manzke, Till; Dutschmann, Mathias; Schlaf, Gerald; Mörschel, Michael; Koch, Uwe R.; Ponimaskin, Evgeni; Bidon, Olivier; Lalley, Peter M.; Richter, Diethelm W.

    2009-01-01

    The cellular effects of serotonin (5-HT), a neuromodulator with widespread influences in the central nervous system, have been investigated. Despite detailed knowledge about the molecular biology of cellular signalling, it is not possible to anticipate the responses of neuronal networks to a global action of 5-HT. Heterogeneous expression of various subtypes of serotonin receptors (5-HTR) in a variety of neurons differently equipped with cell-specific transmitter receptors and ion channel assemblies can provoke diverse cellular reactions resulting in various forms of network adjustment and, hence, motor behaviour. Using the respiratory network as a model for reciprocal synaptic inhibition, we demonstrate that 5-HT1AR modulation primarily affects inhibition through glycinergic synapses. Potentiation of glycinergic inhibition of both excitatory and inhibitory neurons induces a functional reorganization of the network leading to a characteristic change of motor output. The changes in network operation are robust and help to overcome opiate-induced respiratory depression. Hence, 5-HT1AR activation stabilizes the rhythmicity of breathing during opiate medication of pain. PMID:19651659

  13. Resource Sharing via Planed Relay for [InlineEquation not available: see fulltext.

    NASA Astrophysics Data System (ADS)

    Shen, Chong; Rea, Susan; Pesch, Dirk

    2008-12-01

    We present an improved version of adaptive distributed cross-layer routing algorithm (ADCR) for hybrid wireless network with dedicated relay stations ([InlineEquation not available: see fulltext.]) in this paper. A mobile terminal (MT) may borrow radio resources that are available thousands mile away via secure multihop RNs, where RNs are placed at pre-engineered locations in the network. In rural places such as mountain areas, an MT may also communicate with the core network, when intermediate MTs act as relay node with mobility. To address cross-layer network layers routing issues, the cascaded ADCR establishes routing paths across MTs, RNs, and cellular base stations (BSs) and provides appropriate quality of service (QoS). We verify the routing performance benefits of [InlineEquation not available: see fulltext.] over other networks by intensive simulation.

  14. Resource Allocation Algorithms for the Next Generation Cellular Networks

    NASA Astrophysics Data System (ADS)

    Amzallag, David; Raz, Danny

    This chapter describes recent results addressing resource allocation problems in the context of current and future cellular technologies. We present models that capture several fundamental aspects of planning and operating these networks, and develop new approximation algorithms providing provable good solutions for the corresponding optimization problems. We mainly focus on two families of problems: cell planning and cell selection. Cell planning deals with choosing a network of base stations that can provide the required coverage of the service area with respect to the traffic requirements, available capacities, interference, and the desired QoS. Cell selection is the process of determining the cell(s) that provide service to each mobile station. Optimizing these processes is an important step towards maximizing the utilization of current and future cellular networks.

  15. The statistical mechanics of complex signaling networks: nerve growth factor signaling

    NASA Astrophysics Data System (ADS)

    Brown, K. S.; Hill, C. C.; Calero, G. A.; Myers, C. R.; Lee, K. H.; Sethna, J. P.; Cerione, R. A.

    2004-10-01

    The inherent complexity of cellular signaling networks and their importance to a wide range of cellular functions necessitates the development of modeling methods that can be applied toward making predictions and highlighting the appropriate experiments to test our understanding of how these systems are designed and function. We use methods of statistical mechanics to extract useful predictions for complex cellular signaling networks. A key difficulty with signaling models is that, while significant effort is being made to experimentally measure the rate constants for individual steps in these networks, many of the parameters required to describe their behavior remain unknown or at best represent estimates. To establish the usefulness of our approach, we have applied our methods toward modeling the nerve growth factor (NGF)-induced differentiation of neuronal cells. In particular, we study the actions of NGF and mitogenic epidermal growth factor (EGF) in rat pheochromocytoma (PC12) cells. Through a network of intermediate signaling proteins, each of these growth factors stimulates extracellular regulated kinase (Erk) phosphorylation with distinct dynamical profiles. Using our modeling approach, we are able to predict the influence of specific signaling modules in determining the integrated cellular response to the two growth factors. Our methods also raise some interesting insights into the design and possible evolution of cellular systems, highlighting an inherent property of these systems that we call 'sloppiness.'

  16. Dynamic Call Admission Control Scheme Based on Predictive User Mobility Behavior for Cellular Networks

    NASA Astrophysics Data System (ADS)

    Intarasothonchun, Silada; Thipchaksurat, Sakchai; Varakulsiripunth, Ruttikorn; Onozato, Yoshikuni

    In this paper, we propose a modified scheme of MSODB and PMS, called Predictive User Mobility Behavior (PUMB) to improve performance of resource reservation and call admission control for cellular networks. This algorithm is proposed in which bandwidth is allocated more efficiently to neighboring cells by key mobility parameters in order to provide QoS guarantees for transferring traffic. The probability is used to form a cluster of cells and the shadow cluster, where a mobile unit is likely to visit. When a mobile unit may change the direction and migrate to the cell that does not belong to its shadow cluster, we can support it by making efficient use of predicted nonconforming call. Concomitantly, to ensure continuity of on-going calls with better utilization of resources, bandwidth is borrowed from predicted nonconforming calls and existing adaptive calls without affecting the minimum QoS guarantees. The performance of the PUMB is demonstrated by simulation results in terms of new call blocking probability, handoff call dropping probability, bandwidth utilization, call successful probability, and overhead message transmission when arrival rate and speed of mobile units are varied. Our results show that PUMB provides the better performances comparing with those of MSODB and PMS under different traffic conditions.

  17. Software-Reconfigurable Processors for Spacecraft

    NASA Technical Reports Server (NTRS)

    Farrington, Allen; Gray, Andrew; Bell, Bryan; Stanton, Valerie; Chong, Yong; Peters, Kenneth; Lee, Clement; Srinivasan, Jeffrey

    2005-01-01

    A report presents an overview of an architecture for a software-reconfigurable network data processor for a spacecraft engaged in scientific exploration. When executed on suitable electronic hardware, the software performs the functions of a physical layer (in effect, acts as a software radio in that it performs modulation, demodulation, pulse-shaping, error correction, coding, and decoding), a data-link layer, a network layer, a transport layer, and application-layer processing of scientific data. The software-reconfigurable network processor is undergoing development to enable rapid prototyping and rapid implementation of communication, navigation, and scientific signal-processing functions; to provide a long-lived communication infrastructure; and to provide greatly improved scientific-instrumentation and scientific-data-processing functions by enabling science-driven in-flight reconfiguration of computing resources devoted to these functions. This development is an extension of terrestrial radio and network developments (e.g., in the cellular-telephone industry) implemented in software running on such hardware as field-programmable gate arrays, digital signal processors, traditional digital circuits, and mixed-signal application-specific integrated circuits (ASICs).

  18. Active module identification in intracellular networks using a memetic algorithm with a new binary decoding scheme.

    PubMed

    Li, Dong; Pan, Zhisong; Hu, Guyu; Zhu, Zexuan; He, Shan

    2017-03-14

    Active modules are connected regions in biological network which show significant changes in expression over particular conditions. The identification of such modules is important since it may reveal the regulatory and signaling mechanisms that associate with a given cellular response. In this paper, we propose a novel active module identification algorithm based on a memetic algorithm. We propose a novel encoding/decoding scheme to ensure the connectedness of the identified active modules. Based on the scheme, we also design and incorporate a local search operator into the memetic algorithm to improve its performance. The effectiveness of proposed algorithm is validated on both small and large protein interaction networks.

  19. Novel Method for Detection of Air Pollution using Cellular Communication Networks

    NASA Astrophysics Data System (ADS)

    David, N.; Gao, O. H.

    2016-12-01

    Air pollution can lead to a wide spectrum of severe and chronic health impacts. Conventional tools for monitoring the phenomenon do not provide a sufficient monitoring solution in a global scale since they are, for example, not representative of the larger space or due to limited deployment as a result of practical limitations, such as: acquisition, installation, and ongoing maintenance costs. Near ground temperature inversions are directly identified with air pollution events since they suppress vertical atmospheric movement and trap pollutants near the ground. Wireless telecommunication links that comprise the data transfer infrastructure in cellular communication networks operate at frequencies of tens of GHz and are affected by different atmospheric phenomena. These systems are deployed near ground level across the globe, including in developing countries such as India, countries in Africa, etc. Many cellular providers routinely store data regarding the received signal levels in the network for quality assurance needs. Temperature inversions cause atmospheric layering, and change the refractive index of the air when compared to standard conditions. As a result, the ducts that are formed can operate, in essence, as atmospheric wave guides, and cause interference (signal amplification / attenuation) in the microwaves measured by the wireless network. Thus, this network is in effect, an existing system of environmental sensors for monitoring temperature inversions and the episodes of air pollution identified with them. This work presents the novel idea, and demonstrates it, in operation, over several events of air pollution which were detected by a standard cellular communication network during routine operation. Reference: David, N. and Gao, H.O. Using cellular communication networks to detect air pollution, Environmental Science & Technology, 2016 (accepted).

  20. Computational Model of Secondary Palate Fusion and Disruption

    EPA Science Inventory

    Morphogenetic events are driven by cell-generated physical forces and complex cellular dynamics. To improve our capacity to predict developmental effects from cellular alterations, we built a multi-cellular agent-based model in CompuCell3D that recapitulates the cellular networks...

  1. Architecture of the human interactome defines protein communities and disease networks

    PubMed Central

    Huttlin, Edward L.; Bruckner, Raphael J.; Paulo, Joao A.; Cannon, Joe R.; Ting, Lily; Baltier, Kurt; Colby, Greg; Gebreab, Fana; Gygi, Melanie P.; Parzen, Hannah; Szpyt, John; Tam, Stanley; Zarraga, Gabriela; Pontano-Vaites, Laura; Swarup, Sharan; White, Anne E.; Schweppe, Devin K.; Rad, Ramin; Erickson, Brian K.; Obar, Robert A.; Guruharsha, K.G.; Li, Kejie; Artavanis-Tsakonas, Spyros; Gygi, Steven P.; Harper, J. Wade

    2017-01-01

    The physiology of a cell can be viewed as the product of thousands of proteins acting in concert to shape the cellular response. Coordination is achieved in part through networks of protein-protein interactions that assemble functionally related proteins into complexes, organelles, and signal transduction pathways. Understanding the architecture of the human proteome has the potential to inform cellular, structural, and evolutionary mechanisms and is critical to elucidation of how genome variation contributes to disease1–3. Here, we present BioPlex 2.0 (Biophysical Interactions of ORFEOME-derived complexes), which employs robust affinity purification-mass spectrometry (AP-MS) methodology4 to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein coding genes from the human genome, and constitutes the largest such network to date. With >56,000 candidate interactions, BioPlex 2.0 contains >29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins while enhancing network-based analyses of domain associations, subcellular localization, and co-complex formation. Unsupervised Markov clustering (MCL)5 of interacting proteins identified more than 1300 protein communities representing diverse cellular activities. Genes essential for cell fitness6,7 are enriched within 53 communities representing central cellular functions. Moreover, we identified 442 communities associated with more than 2000 disease annotations, placing numerous candidate disease genes into a cellular framework. BioPlex 2.0 exceeds previous experimentally derived interaction networks in depth and breadth, and will be a valuable resource for exploring the biology of incompletely characterized proteins and for elucidating larger-scale patterns of proteome organization. PMID:28514442

  2. Predicting multicellular function through multi-layer tissue networks

    PubMed Central

    Zitnik, Marinka; Leskovec, Jure

    2017-01-01

    Abstract Motivation: Understanding functions of proteins in specific human tissues is essential for insights into disease diagnostics and therapeutics, yet prediction of tissue-specific cellular function remains a critical challenge for biomedicine. Results: Here, we present OhmNet, a hierarchy-aware unsupervised node feature learning approach for multi-layer networks. We build a multi-layer network, where each layer represents molecular interactions in a different human tissue. OhmNet then automatically learns a mapping of proteins, represented as nodes, to a neural embedding-based low-dimensional space of features. OhmNet encourages sharing of similar features among proteins with similar network neighborhoods and among proteins activated in similar tissues. The algorithm generalizes prior work, which generally ignores relationships between tissues, by modeling tissue organization with a rich multiscale tissue hierarchy. We use OhmNet to study multicellular function in a multi-layer protein interaction network of 107 human tissues. In 48 tissues with known tissue-specific cellular functions, OhmNet provides more accurate predictions of cellular function than alternative approaches, and also generates more accurate hypotheses about tissue-specific protein actions. We show that taking into account the tissue hierarchy leads to improved predictive power. Remarkably, we also demonstrate that it is possible to leverage the tissue hierarchy in order to effectively transfer cellular functions to a functionally uncharacterized tissue. Overall, OhmNet moves from flat networks to multiscale models able to predict a range of phenotypes spanning cellular subsystems. Availability and implementation: Source code and datasets are available at http://snap.stanford.edu/ohmnet. Contact: jure@cs.stanford.edu PMID:28881986

  3. Heat acclimation and cross-tolerance against novel stressors: genomic-physiological linkage.

    PubMed

    Horowitz, Michal

    2007-01-01

    Heat acclimation (AC) is a "within lifetime" reversible phenotypic adaptation, enhancing thermotolerance and heat endurance via a transition to "efficient" cellular performance when acclimatory homeostasis is reached. An inseparable outcome of AC is the development of cross-tolerance (C-T) against novel stressors. This chapter focuses on central plasticity and the molecular-physiological linkage of acclimatory and C-T responses. A drop in temperature thresholds (T-Tsh) for activation of heat-dissipation mechanisms and an elevated T-Tsh for thermal injury development imply autonomic nervous system (ANS) and cytoprotective network involvement in these processes. During acclimation, the changes in T-Tsh for heat dissipation are biphasic. Initially T-Tsh drops, signifying the early autonomic response, and is associated with perturbed peripheral effector cellular performance. Pre-acclimation values return when acclimatory homeostasis is achieved. The changes in the ANS suggest that acclimatory plasticity involves molecular and cellular changes. These changes are manifested by the activation of central peripheral molecular networks and post-translational modifications. Sympathetic induction of elevated HSP 72 reservoirs, with faster heat shock response, is only one example of this. The global genomic response, detected using gene-chips and cluster analyses imply upregulation of genes encoding ion channels, pumps, and transporters (markers for neuronal excitability) in the hypothalamus at the onset of AC and down regulation of metabotrophic genes upon long term AC. Peripherally, the transcriptional program indicates a two-tier defense strategy. The immediate transient response is associated with the maintenance of DNA and cellular integrity. The sustained response correlates with long-lasting cytoprotective-signaling networks. C-T is recorded against cerebral hypoxia, hyperoxia, and traumatic brain injury. Using the highly developed ischemic/reperfused heart model as a baseline, it is evident that C-T stems via protective shared pathways developed with AC. These comprise constitutive elevation of HIF 1alpha and associated target pathways, HSPs, anti-apoptosis, and antioxidative pathways. Collectively the master regulators of AC and C-T are still enigmatic; however, cutting-edge investigative techniques, using a broad molecular approach, challenge current ideas, and the data accumulated will pinpoint novel pathways and provide new perspectives.

  4. Towards a magnetoresistive platform for neural signal recording

    NASA Astrophysics Data System (ADS)

    Sharma, P. P.; Gervasoni, G.; Albisetti, E.; D'Ercoli, F.; Monticelli, M.; Moretti, D.; Forte, N.; Rocchi, A.; Ferrari, G.; Baldelli, P.; Sampietro, M.; Benfenati, F.; Bertacco, R.; Petti, D.

    2017-05-01

    A promising strategy to get deeper insight on brain functionalities relies on the investigation of neural activities at the cellular and sub-cellular level. In this framework, methods for recording neuron electrical activity have gained interest over the years. Main technological challenges are associated to finding highly sensitive detection schemes, providing considerable spatial and temporal resolution. Moreover, the possibility to perform non-invasive assays would constitute a noteworthy benefit. In this work, we present a magnetoresistive platform for the detection of the action potential propagation in neural cells. Such platform allows, in perspective, the in vitro recording of neural signals arising from single neurons, neural networks and brain slices.

  5. The Development of Design Tools for Fault Tolerant Quantum Dot Cellular Automata Based Logic

    NASA Technical Reports Server (NTRS)

    Armstrong, Curtis D.; Humphreys, William M.

    2003-01-01

    We are developing software to explore the fault tolerance of quantum dot cellular automata gate architectures in the presence of manufacturing variations and device defects. The Topology Optimization Methodology using Applied Statistics (TOMAS) framework extends the capabilities of the A Quantum Interconnected Network Array Simulator (AQUINAS) by adding front-end and back-end software and creating an environment that integrates all of these components. The front-end tools establish all simulation parameters, configure the simulation system, automate the Monte Carlo generation of simulation files, and execute the simulation of these files. The back-end tools perform automated data parsing, statistical analysis and report generation.

  6. Classifying and Analyzing 3d Cell Motion in Jammed Microgels

    NASA Astrophysics Data System (ADS)

    Bhattacharjee, Tapomoy; Sawyer, W. Gregory; Angelini, Thomas

    Soft granular polyelectrolyte microgels swell in liquid cell growth media to form a continuous elastic solid that can easily transition between solid to fluid state under a low shear stress. Such Liquid-like solids (LLS) have recently been used to create 3D cellular constructs as well as to support, culture and harvest cells in 3D. Current understanding of cell migration mechanics in 3D was established from experiments performed in natural and synthetic polymer networks. Spatial variation in network structure and the transience of degradable gels limit their usefulness in quantitative cell mechanics studies. By contrast, LLS growth media approximates a homogeneous continuum, enabling tractable cell mechanics measurements to be performed in 3D. Here, we introduce a process to understand and classify cytotoxic T cell motion in 3D by studying cellular motility in LLS media. General classification of T cell motion can be achieved with a very traditional statistical approach: the cell's mean squared displacement (MSD) as a function of delay time. We will also use Langevin approaches combined with the constitutive equations of the LLS medium to predict the statistics of T cell motion. National Science Foundation under Grant No. DMR-1352043.

  7. Optimizing network connectivity for mobile health technologies in sub-Saharan Africa.

    PubMed

    Siedner, Mark J; Lankowski, Alexander; Musinga, Derrick; Jackson, Jonathon; Muzoora, Conrad; Hunt, Peter W; Martin, Jeffrey N; Bangsberg, David R; Haberer, Jessica E

    2012-01-01

    Mobile health (mHealth) technologies hold incredible promise to improve healthcare delivery in resource-limited settings. Network reliability across large catchment areas can be a major challenge. We performed an analysis of network failure frequency as part of a study of real-time adherence monitoring in rural Uganda. We hypothesized that the addition of short messaging service (SMS+GPRS) to the standard cellular network modality (GPRS) would reduce network disruptions and improve transmission of data. Participants were enrolled in a study of real-time adherence monitoring in southwest Uganda. In June 2011, we began using Wisepill devices that transmit data each time the pill bottle is opened. We defined network failures as medication interruptions of >48 hours duration that were transmitted when network connectivity was re-established. During the course of the study, we upgraded devices from GPRS to GPRS+SMS compatibility. We compared network failure rates between GPRS and GPRS+SMS periods and created geospatial maps to graphically demonstrate patterns of connectivity. One hundred fifty-seven participants met inclusion criteria of seven days of SMS and seven days of SMS+GPRS observation time. Seventy-three percent were female, median age was 40 years (IQR 33-46), 39% reported >1-hour travel time to clinic and 17% had home electricity. One hundred one had GPS coordinates recorded and were included in the geospatial maps. The median number of network failures per person-month for the GPRS and GPRS+SMS modalities were 1.5 (IQR 1.0-2.2) and 0.3 (IQR 0-0.9) respectively, (mean difference 1.2, 95%CI 1.0-1.3, p-value<0.0001). Improvements in network connectivity were notable throughout the region. Study costs increased by approximately $1USD per person-month. Addition of SMS to standard GPRS cellular network connectivity can significantly reduce network connection failures for mobile health applications in remote areas. Projects depending on mobile health data in resource-limited settings should consider this upgrade to optimize mHealth applications.

  8. Endoplasmic reticulum mediated signaling in cellular microdomains

    PubMed Central

    Biwer, Lauren; Isakson, Brant E

    2016-01-01

    The endoplasmic reticulum (ER) is a prime mediator of cellular signaling due to its functions as an internal cellular store for calcium, as well as a site for synthesis of proteins and lipids. Its peripheral network of sheets and tubules facilitate calcium and lipid signaling, especially in areas of the cell that are more distant to the main cytoplasmic network. Specific membrane proteins shape the peripheral ER architecture and influence the network stability in order to project into restricted spaces. The signaling microdomains are anatomically separate from the cytoplasm as a whole and exhibit localized protein, ion channel and cytoskeletal element expression. Signaling can also occur between the ER and other organelles, such as the Golgi or mitochondria. Lipids made in the ER membrane can be sent to the Golgi via specialized transfer proteins and specific phospholipid synthases are enriched at ER-mitochondria junctions to more efficiently expedite phospholipid transfer. As a hub for protein and lipid synthesis, a store for intracellular calcium [Ca2+]i, and a mediator of cellular stress, the ER is an important cellular organelle. Its ability to organize into tubules and project into restricted spaces allows for discrete and temporal signaling, which is important for cellular physiology and organism homeostasis. PMID:26973141

  9. Viruses Associated with Human Cancer

    PubMed Central

    McLaughlin-Drubin, Margaret E.; Munger, Karl

    2008-01-01

    It is estimated that viral infections contribute to 15–20% of all human cancers. As obligatory intracellular parasites, viruses encode proteins that reprogram host cellular signaling pathways that control proliferation, differentiation, cell death, genomic integrity, and recognition by the immune system. These cellular processes are governed by complex and redundant regulatory networks and are surveyed by sentinel mechanisms that ensure that aberrant cells are removed from the proliferative pool. Given that the genome size of a virus is highly restricted to ensure packaging within an infectious structure, viruses must target cellular regulatory nodes with limited redundancy and need to inactivate surveillance mechanisms that would normally recognize and extinguish such abnormal cells. In many cases, key proteins in these same regulatory networks are subject to mutation in non-virally associated diseases and cancers. Oncogenic viruses have thus served as important experimental models to identify and molecularly investigate such cellular networks. These include the discovery of oncogenes and tumor suppressors, identification of regulatory networks that are critical for maintenance of genomic integrity, and processes that govern immune surveillance. PMID:18201576

  10. Resource constrained flux balance analysis predicts selective pressure on the global structure of metabolic networks.

    PubMed

    Abedpour, Nima; Kollmann, Markus

    2015-11-23

    A universal feature of metabolic networks is their hourglass or bow-tie structure on cellular level. This architecture reflects the conversion of multiple input nutrients into multiple biomass components via a small set of precursor metabolites. However, it is yet unclear to what extent this structural feature is the result of natural selection. We extend flux balance analysis to account for limited cellular resources. Using this model, optimal structure of metabolic networks can be calculated for different environmental conditions. We observe a significant structural reshaping of metabolic networks for a toy-network and E. coli core metabolism if we increase the share of invested resources for switching between different nutrient conditions. Here, hub nodes emerge and the optimal network structure becomes bow-tie-like as a consequence of limited cellular resource constraint. We confirm this theoretical finding by comparing the reconstructed metabolic networks of bacterial species with respect to their lifestyle. We show that bow-tie structure can give a system-level fitness advantage to organisms that live in highly competitive and fluctuating environments. Here, limitation of cellular resources can lead to an efficiency-flexibility tradeoff where it pays off for the organism to shorten catabolic pathways if they are frequently activated and deactivated. As a consequence, generalists that shuttle between diverse environmental conditions should have a more predominant bow-tie structure than specialists that visit just a few isomorphic habitats during their life cycle.

  11. Functional modules by relating protein interaction networks and gene expression.

    PubMed

    Tornow, Sabine; Mewes, H W

    2003-11-01

    Genes and proteins are organized on the basis of their particular mutual relations or according to their interactions in cellular and genetic networks. These include metabolic or signaling pathways and protein interaction, regulatory or co-expression networks. Integrating the information from the different types of networks may lead to the notion of a functional network and functional modules. To find these modules, we propose a new technique which is based on collective, multi-body correlations in a genetic network. We calculated the correlation strength of a group of genes (e.g. in the co-expression network) which were identified as members of a module in a different network (e.g. in the protein interaction network) and estimated the probability that this correlation strength was found by chance. Groups of genes with a significant correlation strength in different networks have a high probability that they perform the same function. Here, we propose evaluating the multi-body correlations by applying the superparamagnetic approach. We compare our method to the presently applied mean Pearson correlations and show that our method is more sensitive in revealing functional relationships.

  12. Functional modules by relating protein interaction networks and gene expression

    PubMed Central

    Tornow, Sabine; Mewes, H. W.

    2003-01-01

    Genes and proteins are organized on the basis of their particular mutual relations or according to their interactions in cellular and genetic networks. These include metabolic or signaling pathways and protein interaction, regulatory or co-expression networks. Integrating the information from the different types of networks may lead to the notion of a functional network and functional modules. To find these modules, we propose a new technique which is based on collective, multi-body correlations in a genetic network. We calculated the correlation strength of a group of genes (e.g. in the co-expression network) which were identified as members of a module in a different network (e.g. in the protein interaction network) and estimated the probability that this correlation strength was found by chance. Groups of genes with a significant correlation strength in different networks have a high probability that they perform the same function. Here, we propose evaluating the multi-body correlations by applying the superparamagnetic approach. We compare our method to the presently applied mean Pearson correlations and show that our method is more sensitive in revealing functional relationships. PMID:14576317

  13. Graph Curvature for Differentiating Cancer Networks

    PubMed Central

    Sandhu, Romeil; Georgiou, Tryphon; Reznik, Ed; Zhu, Liangjia; Kolesov, Ivan; Senbabaoglu, Yasin; Tannenbaum, Allen

    2015-01-01

    Cellular interactions can be modeled as complex dynamical systems represented by weighted graphs. The functionality of such networks, including measures of robustness, reliability, performance, and efficiency, are intrinsically tied to the topology and geometry of the underlying graph. Utilizing recently proposed geometric notions of curvature on weighted graphs, we investigate the features of gene co-expression networks derived from large-scale genomic studies of cancer. We find that the curvature of these networks reliably distinguishes between cancer and normal samples, with cancer networks exhibiting higher curvature than their normal counterparts. We establish a quantitative relationship between our findings and prior investigations of network entropy. Furthermore, we demonstrate how our approach yields additional, non-trivial pair-wise (i.e. gene-gene) interactions which may be disrupted in cancer samples. The mathematical formulation of our approach yields an exact solution to calculating pair-wise changes in curvature which was computationally infeasible using prior methods. As such, our findings lay the foundation for an analytical approach to studying complex biological networks. PMID:26169480

  14. Protein complex prediction in large ontology attributed protein-protein interaction networks.

    PubMed

    Zhang, Yijia; Lin, Hongfei; Yang, Zhihao; Wang, Jian; Li, Yanpeng; Xu, Bo

    2013-01-01

    Protein complexes are important for unraveling the secrets of cellular organization and function. Many computational approaches have been developed to predict protein complexes in protein-protein interaction (PPI) networks. However, most existing approaches focus mainly on the topological structure of PPI networks, and largely ignore the gene ontology (GO) annotation information. In this paper, we constructed ontology attributed PPI networks with PPI data and GO resource. After constructing ontology attributed networks, we proposed a novel approach called CSO (clustering based on network structure and ontology attribute similarity). Structural information and GO attribute information are complementary in ontology attributed networks. CSO can effectively take advantage of the correlation between frequent GO annotation sets and the dense subgraph for protein complex prediction. Our proposed CSO approach was applied to four different yeast PPI data sets and predicted many well-known protein complexes. The experimental results showed that CSO was valuable in predicting protein complexes and achieved state-of-the-art performance.

  15. Graph Theory-Based Analysis of the Lymph Node Fibroblastic Reticular Cell Network.

    PubMed

    Novkovic, Mario; Onder, Lucas; Bocharov, Gennady; Ludewig, Burkhard

    2017-01-01

    Secondary lymphoid organs have developed segregated niches that are able to initiate and maintain effective immune responses. Such global organization requires tight control of diverse cellular components, specifically those that regulate lymphocyte trafficking. Fibroblastic reticular cells (FRCs) form a densely interconnected network in lymph nodes and provide key factors necessary for T cell migration and retention, and foster subsequent interactions between T cells and dendritic cells. Development of integrative systems biology approaches has made it possible to elucidate this multilevel complexity of the immune system. Here, we present a graph theory-based analysis of the FRC network in murine lymph nodes, where generation of the network topology is performed using high-resolution confocal microscopy and 3D reconstruction. This approach facilitates the analysis of physical cell-to-cell connectivity, and estimation of topological robustness and global behavior of the network when it is subjected to perturbation in silico.

  16. Effect of noise in intelligent cellular decision making.

    PubMed

    Bates, Russell; Blyuss, Oleg; Alsaedi, Ahmed; Zaikin, Alexey

    2015-01-01

    Similar to intelligent multicellular neural networks controlling human brains, even single cells, surprisingly, are able to make intelligent decisions to classify several external stimuli or to associate them. This happens because of the fact that gene regulatory networks can perform as perceptrons, simple intelligent schemes known from studies on Artificial Intelligence. We study the role of genetic noise in intelligent decision making at the genetic level and show that noise can play a constructive role helping cells to make a proper decision. We show this using the example of a simple genetic classifier able to classify two external stimuli.

  17. Cooperative Game-Based Energy Efficiency Management over Ultra-Dense Wireless Cellular Networks

    PubMed Central

    Li, Ming; Chen, Pengpeng; Gao, Shouwan

    2016-01-01

    Ultra-dense wireless cellular networks have been envisioned as a promising technique for handling the explosive increase of wireless traffic volume. With the extensive deployment of small cells in wireless cellular networks, the network spectral efficiency (SE) is improved with the use of limited frequency. However, the mutual inter-tier and intra-tier interference between or among small cells and macro cells becomes serious. On the other hand, more chances for potential cooperation among different cells are introduced. Energy efficiency (EE) has become one of the most important problems for future wireless networks. This paper proposes a cooperative bargaining game-based method for comprehensive EE management in an ultra-dense wireless cellular network, which highlights the complicated interference influence on energy-saving challenges and the power-coordination process among small cells and macro cells. Especially, a unified EE utility with the consideration of the interference mitigation is proposed to jointly address the SE, the deployment efficiency (DE), and the EE. In particular, closed-form power-coordination solutions for the optimal EE are derived to show the convergence property of the algorithm. Moreover, a simplified algorithm is presented to reduce the complexity of the signaling overhead, which is significant for ultra-dense small cells. Finally, numerical simulations are provided to illustrate the efficiency of the proposed cooperative bargaining game-based and simplified schemes. PMID:27649170

  18. Cooperative Game-Based Energy Efficiency Management over Ultra-Dense Wireless Cellular Networks.

    PubMed

    Li, Ming; Chen, Pengpeng; Gao, Shouwan

    2016-09-13

    Ultra-dense wireless cellular networks have been envisioned as a promising technique for handling the explosive increase of wireless traffic volume. With the extensive deployment of small cells in wireless cellular networks, the network spectral efficiency (SE) is improved with the use of limited frequency. However, the mutual inter-tier and intra-tier interference between or among small cells and macro cells becomes serious. On the other hand, more chances for potential cooperation among different cells are introduced. Energy efficiency (EE) has become one of the most important problems for future wireless networks. This paper proposes a cooperative bargaining game-based method for comprehensive EE management in an ultra-dense wireless cellular network, which highlights the complicated interference influence on energy-saving challenges and the power-coordination process among small cells and macro cells. Especially, a unified EE utility with the consideration of the interference mitigation is proposed to jointly address the SE, the deployment efficiency (DE), and the EE. In particular, closed-form power-coordination solutions for the optimal EE are derived to show the convergence property of the algorithm. Moreover, a simplified algorithm is presented to reduce the complexity of the signaling overhead, which is significant for ultra-dense small cells. Finally, numerical simulations are provided to illustrate the efficiency of the proposed cooperative bargaining game-based and simplified schemes.

  19. On the holistic approach in cellular and cancer biology: nonlinearity, complexity, and quasi-determinism of the dynamic cellular network.

    PubMed

    Waliszewski, P; Molski, M; Konarski, J

    1998-06-01

    A keystone of the molecular reductionist approach to cellular biology is a specific deductive strategy relating genotype to phenotype-two distinct categories. This relationship is based on the assumption that the intermediary cellular network of actively transcribed genes and their regulatory elements is deterministic (i.e., a link between expression of a gene and a phenotypic trait can always be identified, and evolution of the network in time is predetermined). However, experimental data suggest that the relationship between genotype and phenotype is nonbijective (i.e., a gene can contribute to the emergence of more than just one phenotypic trait or a phenotypic trait can be determined by expression of several genes). This implies nonlinearity (i.e., lack of the proportional relationship between input and the outcome), complexity (i.e. emergence of the hierarchical network of multiple cross-interacting elements that is sensitive to initial conditions, possesses multiple equilibria, organizes spontaneously into different morphological patterns, and is controlled in dispersed rather than centralized manner), and quasi-determinism (i.e., coexistence of deterministic and nondeterministic events) of the network. Nonlinearity within the space of the cellular molecular events underlies the existence of a fractal structure within a number of metabolic processes, and patterns of tissue growth, which is measured experimentally as a fractal dimension. Because of its complexity, the same phenotype can be associated with a number of alternative sequences of cellular events. Moreover, the primary cause initiating phenotypic evolution of cells such as malignant transformation can be favored probabilistically, but not identified unequivocally. Thermodynamic fluctuations of energy rather than gene mutations, the material traits of the fluctuations alter both the molecular and informational structure of the network. Then, the interplay between deterministic chaos, complexity, self-organization, and natural selection drives formation of malignant phenotype. This concept offers a novel perspective for investigation of tumorigenesis without invalidating current molecular findings. The essay integrates the ideas of the sciences of complexity in a biological context.

  20. Computation of Steady-State Probability Distributions in Stochastic Models of Cellular Networks

    PubMed Central

    Hallen, Mark; Li, Bochong; Tanouchi, Yu; Tan, Cheemeng; West, Mike; You, Lingchong

    2011-01-01

    Cellular processes are “noisy”. In each cell, concentrations of molecules are subject to random fluctuations due to the small numbers of these molecules and to environmental perturbations. While noise varies with time, it is often measured at steady state, for example by flow cytometry. When interrogating aspects of a cellular network by such steady-state measurements of network components, a key need is to develop efficient methods to simulate and compute these distributions. We describe innovations in stochastic modeling coupled with approaches to this computational challenge: first, an approach to modeling intrinsic noise via solution of the chemical master equation, and second, a convolution technique to account for contributions of extrinsic noise. We show how these techniques can be combined in a streamlined procedure for evaluation of different sources of variability in a biochemical network. Evaluation and illustrations are given in analysis of two well-characterized synthetic gene circuits, as well as a signaling network underlying the mammalian cell cycle entry. PMID:22022252

  1. The brain as a system of nested but partially overlapping networks. Heuristic relevance of the model for brain physiology and pathology.

    PubMed

    Agnati, L F; Guidolin, D; Fuxe, K

    2007-01-01

    A new model of the brain organization is proposed. The model is based on the assumption that a global molecular network enmeshes the entire central nervous system. Thus, brain extra-cellular and intra-cellular molecular networks are proposed to communicate at the level of special plasma membrane regions (e.g., the lipid rafts) where horizontal molecular networks can represent input/output regions allowing the cell to have informational exchanges with the extracellular environment. Furthermore, some "pervasive signals" such as field potentials, pressure waves and thermal gradients that affect large parts of the brain cellular and molecular networks are discussed. Finally, at least two learning paradigms are analyzed taking into account the possible role of Volume Transmission: the so-called model of "temporal difference learning" and the "Turing B-unorganised machine". The relevance of this new view of brain organization for a deeper understanding of some neurophysiological and neuropathological aspects of its function is briefly discussed.

  2. Hacking the Cell: Network Intrusion and Exploitation by Adenovirus E1A.

    PubMed

    King, Cason R; Zhang, Ali; Tessier, Tanner M; Gameiro, Steven F; Mymryk, Joe S

    2018-05-01

    As obligate intracellular parasites, viruses are dependent on their infected hosts for survival. Consequently, viruses are under enormous selective pressure to utilize available cellular components and processes to their own advantage. As most, if not all, cellular activities are regulated at some level via protein interactions, host protein interaction networks are particularly vulnerable to viral exploitation. Indeed, viral proteins frequently target highly connected "hub" proteins to "hack" the cellular network, defining the molecular basis for viral control over the host. This widespread and successful strategy of network intrusion and exploitation has evolved convergently among numerous genetically distinct viruses as a result of the endless evolutionary arms race between pathogens and hosts. Here we examine the means by which a particularly well-connected viral hub protein, human adenovirus E1A, compromises and exploits the vulnerabilities of eukaryotic protein interaction networks. Importantly, these interactions identify critical regulatory hubs in the human proteome and help define the molecular basis of their function. Copyright © 2018 King et al.

  3. Discrete dynamic modeling of cellular signaling networks.

    PubMed

    Albert, Réka; Wang, Rui-Sheng

    2009-01-01

    Understanding signal transduction in cellular systems is a central issue in systems biology. Numerous experiments from different laboratories generate an abundance of individual components and causal interactions mediating environmental and developmental signals. However, for many signal transduction systems there is insufficient information on the overall structure and the molecular mechanisms involved in the signaling network. Moreover, lack of kinetic and temporal information makes it difficult to construct quantitative models of signal transduction pathways. Discrete dynamic modeling, combined with network analysis, provides an effective way to integrate fragmentary knowledge of regulatory interactions into a predictive mathematical model which is able to describe the time evolution of the system without the requirement for kinetic parameters. This chapter introduces the fundamental concepts of discrete dynamic modeling, particularly focusing on Boolean dynamic models. We describe this method step-by-step in the context of cellular signaling networks. Several variants of Boolean dynamic models including threshold Boolean networks and piecewise linear systems are also covered, followed by two examples of successful application of discrete dynamic modeling in cell biology.

  4. Hacking the Cell: Network Intrusion and Exploitation by Adenovirus E1A

    PubMed Central

    King, Cason R.; Zhang, Ali; Tessier, Tanner M.; Gameiro, Steven F.

    2018-01-01

    ABSTRACT As obligate intracellular parasites, viruses are dependent on their infected hosts for survival. Consequently, viruses are under enormous selective pressure to utilize available cellular components and processes to their own advantage. As most, if not all, cellular activities are regulated at some level via protein interactions, host protein interaction networks are particularly vulnerable to viral exploitation. Indeed, viral proteins frequently target highly connected “hub” proteins to “hack” the cellular network, defining the molecular basis for viral control over the host. This widespread and successful strategy of network intrusion and exploitation has evolved convergently among numerous genetically distinct viruses as a result of the endless evolutionary arms race between pathogens and hosts. Here we examine the means by which a particularly well-connected viral hub protein, human adenovirus E1A, compromises and exploits the vulnerabilities of eukaryotic protein interaction networks. Importantly, these interactions identify critical regulatory hubs in the human proteome and help define the molecular basis of their function. PMID:29717008

  5. Listening to the Noise: Random Fluctuations Reveal Gene Network Parameters

    NASA Astrophysics Data System (ADS)

    Munsky, Brian; Trinh, Brooke; Khammash, Mustafa

    2010-03-01

    The cellular environment is abuzz with noise originating from the inherent random motion of reacting molecules in the living cell. In this noisy environment, clonal cell populations exhibit cell-to-cell variability that can manifest significant prototypical differences. Noise induced stochastic fluctuations in cellular constituents can be measured and their statistics quantified using flow cytometry, single molecule fluorescence in situ hybridization, time lapse fluorescence microscopy and other single cell and single molecule measurement techniques. We show that these random fluctuations carry within them valuable information about the underlying genetic network. Far from being a nuisance, the ever-present cellular noise acts as a rich source of excitation that, when processed through a gene network, carries its distinctive fingerprint that encodes a wealth of information about that network. We demonstrate that in some cases the analysis of these random fluctuations enables the full identification of network parameters, including those that may otherwise be difficult to measure. We use theoretical investigations to establish experimental guidelines for the identification of gene regulatory networks, and we apply these guideline to experimentally identify predictive models for different regulatory mechanisms in bacteria and yeast.

  6. Functional Genomics Assistant (FUGA): a toolbox for the analysis of complex biological networks

    PubMed Central

    2011-01-01

    Background Cellular constituents such as proteins, DNA, and RNA form a complex web of interactions that regulate biochemical homeostasis and determine the dynamic cellular response to external stimuli. It follows that detailed understanding of these patterns is critical for the assessment of fundamental processes in cell biology and pathology. Representation and analysis of cellular constituents through network principles is a promising and popular analytical avenue towards a deeper understanding of molecular mechanisms in a system-wide context. Findings We present Functional Genomics Assistant (FUGA) - an extensible and portable MATLAB toolbox for the inference of biological relationships, graph topology analysis, random network simulation, network clustering, and functional enrichment statistics. In contrast to conventional differential expression analysis of individual genes, FUGA offers a framework for the study of system-wide properties of biological networks and highlights putative molecular targets using concepts of systems biology. Conclusion FUGA offers a simple and customizable framework for network analysis in a variety of systems biology applications. It is freely available for individual or academic use at http://code.google.com/p/fuga. PMID:22035155

  7. 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

  8. Dietary antioxidants and exercise.

    PubMed

    Powers, Scott K; DeRuisseau, Keith C; Quindry, John; Hamilton, Karyn L

    2004-01-01

    Muscular exercise promotes the production of radicals and other reactive oxygen species in the working muscle. Growing evidence indicates that reactive oxygen species are responsible for exercise-induced protein oxidation and contribute to muscle fatigue. To protect against exercise-induced oxidative injury, muscle cells contain complex endogenous cellular defence mechanisms (enzymatic and non-enzymatic antioxidants) to eliminate reactive oxygen species. Furthermore, exogenous dietary antioxidants interact with endogenous antioxidants to form a cooperative network of cellular antioxidants. Knowledge that exercise-induced oxidant formation can contribute to muscle fatigue has resulted in numerous investigations examining the effects of antioxidant supplementation on human exercise performance. To date, there is limited evidence that dietary supplementation with antioxidants will improve human performance. Furthermore, it is currently unclear whether regular vigorous exercise increases the need for dietary intake of antioxidants. Clearly, additional research that analyses the antioxidant requirements of individual athletes is needed.

  9. 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…

  10. A positive feedback at the cellular level promotes robustness and modulation at the circuit level

    PubMed Central

    Dethier, Julie; Drion, Guillaume; Franci, Alessio

    2015-01-01

    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

  11. A Systematic Analysis of a Deep Mouse Epididymal Sperm Proteome

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chauvin, Theodore; Xie, Fang; Liu, Tao

    Spermatozoa are highly specialized cells that, when mature, are capable of navigating the female reproductive tract and fertilizing an oocyte. The sperm cell is thought to be largely quiescent in terms of transcriptional and translational activity. As a result, once it has left the male reproductive tract, the sperm cell is essentially operating with a static population of proteins. It is therefore theoretically possible to understand the protein networks contained in a sperm cell and to deduce its cellular function capabilities. To this end we have performed a proteomic analysis of mouse sperm isolated from the cauda epididymis and havemore » confidently identified 2,850 proteins, which is the most comprehensive sperm proteome for any species reported to date. These proteins comprise many complete cellular pathways, including those for energy production via glycolysis, β-oxidation and oxidative phosphorylation, protein folding and transport, and cell signaling systems. This proteome should prove a useful tool for assembly and testing of protein networks important for sperm function.« less

  12. Image processing for navigation on a mobile embedded platform

    NASA Astrophysics Data System (ADS)

    Preuss, Thomas; Gentsch, Lars; Rambow, Mark

    2006-02-01

    Mobile computing devices such as PDAs or cellular phones may act as "Personal Multimedia Exchanges", but they are limited in their processing power as well as in their connectivity. Sensors as well as cellular phones and PDAs are able to gather multimedia data, e. g. images, but leak computing power to process that data on their own. Therefore, it is necessary, that these devices connect to devices with more performance, which provide e.g. image processing services. In this paper, a generic approach is presented that connects different kinds of clients with each other and allows them to interact with more powerful devices. This architecture, called BOSPORUS, represents a communication framework for dynamic peer-to-peer computing. Each peer offers and uses services in this network and communicates loosely coupled and asynchronously with the others. These features make BOSPORUS a service oriented network architecture (SONA). A mobile embedded system, which uses external services for image processing based on the BOSPORUS Framework is shown as an application of the BOSPORUS framework.

  13. Beamforming design with proactive interference cancelation in MISO interference channels

    NASA Astrophysics Data System (ADS)

    Li, Yang; Tian, Yafei; Yang, Chenyang

    2015-12-01

    In this paper, we design coordinated beamforming at base stations (BSs) to facilitate interference cancelation at users in interference networks, where each BS is equipped with multiple antennas and each user is with a single antenna. By assuming that each user can select the best decoding strategy to mitigate the interference, either canceling the interference after decoding when it is strong or treating it as noise when it is weak, we optimize the beamforming vectors that maximize the sum rate for the networks under different interference scenarios and find the solutions of beamforming with closed-form expressions. The inherent design principles are then analyzed, and the performance gain over passive interference cancelation is demonstrated through simulations in heterogeneous cellular networks.

  14. Protein intrinsic disorder in plants.

    PubMed

    Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto

    2013-09-12

    To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

  15. Protein intrinsic disorder in plants

    PubMed Central

    Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A.; Solano, Roberto

    2013-01-01

    To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks. PMID:24062761

  16. Bioinformatics analysis on molecular mechanism of rheum officinale in treatment of jaundice

    NASA Astrophysics Data System (ADS)

    Shan, Si; Tu, Jun; Nie, Peng; Yan, Xiaojun

    2017-01-01

    Objective: To study the molecular mechanism of Rheum officinale in the treatment of Jaundice by building molecular networks and comparing canonical pathways. Methods: Target proteins of Rheum officinale and related genes of Jaundice were searched from Pubchem and Gene databases online respectively. Molecular networks and canonical pathways comparison analyses were performed by Ingenuity Pathway Analysis (IPA). Results: The molecular networks of Rheum officinale and Jaundice were complex and multifunctional. The 40 target proteins of Rheum officinale and 33 Homo sapiens genes of Jaundice were found in databases. There were 19 common pathways both related networks. Rheum officinale could regulate endothelial differentiation, Interleukin-1B (IL-1B) and Tumor Necrosis Factor (TNF) in these pathways. Conclusions: Rheum officinale treat Jaundice by regulating many effective nodes of Apoptotic pathway and cellular immunity related pathways.

  17. 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.

  18. Genome-wide differential gene expression in immortalized DF-1 chicken embryo fibroblast cell line

    PubMed Central

    2011-01-01

    Background When compared to primary chicken embryo fibroblast (CEF) cells, the immortal DF-1 CEF line exhibits enhanced growth rates and susceptibility to oxidative stress. Although genes responsible for cell cycle regulation and antioxidant functions have been identified, the genome-wide transcription profile of immortal DF-1 CEF cells has not been previously reported. Global gene expression in primary CEF and DF-1 cells was performed using a 4X44K chicken oligo microarray. Results A total of 3876 differentially expressed genes were identified with a 2 fold level cutoff that included 1706 up-regulated and 2170 down-regulated genes in DF-1 cells. Network and functional analyses using Ingenuity Pathways Analysis (IPA, Ingenuity® Systems, http://www.ingenuity.com) revealed that 902 of 3876 differentially expressed genes were classified into a number of functional groups including cellular growth and proliferation, cell cycle, cellular movement, cancer, genetic disorders, and cell death. Also, the top 5 gene networks with intermolecular connections were identified. Bioinformatic analyses suggested that DF-1 cells were characterized by enhanced molecular mechanisms for cell cycle progression and proliferation, suppressing cell death pathways, altered cellular morphogenesis, and accelerated capacity for molecule transport. Key molecules for these functions include E2F1, BRCA1, SRC, CASP3, and the peroxidases. Conclusions The global gene expression profiles provide insight into the cellular mechanisms that regulate the unique characteristics observed in immortal DF-1 CEF cells. PMID:22111699

  19. A Multi-Method Approach for Proteomic Network Inference in 11 Human Cancers.

    PubMed

    Şenbabaoğlu, Yasin; Sümer, Selçuk Onur; Sánchez-Vega, Francisco; Bemis, Debra; Ciriello, Giovanni; Schultz, Nikolaus; Sander, Chris

    2016-02-01

    Protein expression and post-translational modification levels are tightly regulated in neoplastic cells to maintain cellular processes known as 'cancer hallmarks'. The first Pan-Cancer initiative of The Cancer Genome Atlas (TCGA) Research Network has aggregated protein expression profiles for 3,467 patient samples from 11 tumor types using the antibody based reverse phase protein array (RPPA) technology. The resultant proteomic data can be utilized to computationally infer protein-protein interaction (PPI) networks and to study the commonalities and differences across tumor types. In this study, we compare the performance of 13 established network inference methods in their capacity to retrieve the curated Pathway Commons interactions from RPPA data. We observe that no single method has the best performance in all tumor types, but a group of six methods, including diverse techniques such as correlation, mutual information, and regression, consistently rank highly among the tested methods. We utilize the high performing methods to obtain a consensus network; and identify four robust and densely connected modules that reveal biological processes as well as suggest antibody-related technical biases. Mapping the consensus network interactions to Reactome gene lists confirms the pan-cancer importance of signal transduction pathways, innate and adaptive immune signaling, cell cycle, metabolism, and DNA repair; and also suggests several biological processes that may be specific to a subset of tumor types. Our results illustrate the utility of the RPPA platform as a tool to study proteomic networks in cancer.

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

    PubMed

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

    2015-10-30

    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. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Differential network entropy reveals cancer system hallmarks

    PubMed Central

    West, James; Bianconi, Ginestra; Severini, Simone; Teschendorff, Andrew E.

    2012-01-01

    The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network we here demonstrate that cancer cells are characterised by an increase in network entropy. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local network entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local correlation patterns. In particular, we find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in network entropy. These findings may have potential implications for identifying novel drug targets. PMID:23150773

  2. Age gene expression and coexpression progressive signatures in peripheral blood leukocytes.

    PubMed

    Irizar, Haritz; Goñi, Joaquín; Alzualde, Ainhoa; Castillo-Triviño, Tamara; Olascoaga, Javier; Lopez de Munain, Adolfo; Otaegui, David

    2015-12-01

    Both cellular senescence and organismic aging are known to be dynamic processes that start early in life and progress constantly during the whole life of the individual. In this work, with the objective of identifying signatures of age-related progressive change at the transcriptomic level, we have performed a whole-genome gene expression analysis of peripheral blood leukocytes in a group of healthy individuals with ages ranging from 14 to 93 years. A set of genes with progressively changing gene expression (either increase or decrease with age) has been identified and contextualized in a coexpression network. A modularity analysis has been performed on this network and biological-term and pathway enrichment analyses have been used for biological interpretation of each module. In summary, the results of the present work reveal the existence of a transcriptomic component that shows progressive expression changes associated to age in peripheral blood leukocytes, highlighting both the dynamic nature of the process and the need to complement young vs. elder studies with longitudinal studies that include middle aged individuals. From the transcriptional point of view, immunosenescence seems to be occurring from a relatively early age, at least from the late 20s/early 30s, and the 49-56 year old age-range appears to be critical. In general, the genes that, according to our results, show progressive expression changes with aging are involved in pathogenic/cellular processes that have classically been linked to aging in humans: cancer, immune processes and cellular growth vs. maintenance. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Development and Performance Analysis of a Photonics-Assisted RF Converter for 5G Applications

    NASA Astrophysics Data System (ADS)

    Borges, Ramon Maia; Muniz, André Luiz Marques; Sodré Junior, Arismar Cerqueira

    2017-03-01

    This article presents a simple, ultra-wideband and tunable radiofrequency (RF) converter for 5G cellular networks. The proposed optoelectronic device performs broadband photonics-assisted upconversion and downconversion using a single optical modulator. Experimental results demonstrate RF conversion from DC to millimeter waves, including 28 and 38 GHz that are potential frequency bands for 5G applications. Narrow linewidth and low phase noise characteristics are observed in all generated RF carriers. An experimental digital performance analysis using different modulation schemes illustrates the applicability of the proposed photonics-based device in reconfigurable optical wireless communications.

  4. Adapting to stress - chaperome networks in cancer.

    PubMed

    Joshi, Suhasini; Wang, Tai; Araujo, Thaís L S; Sharma, Sahil; Brodsky, Jeffrey L; Chiosis, Gabriela

    2018-05-23

    In this Opinion article, we aim to address how cells adapt to stress and the repercussions chronic stress has on cellular function. We consider acute and chronic stress-induced changes at the cellular level, with a focus on a regulator of cellular stress, the chaperome, which is a protein assembly that encompasses molecular chaperones, co-chaperones and other co-factors. We discuss how the chaperome takes on distinct functions under conditions of stress that are executed in ways that differ from the one-on-one cyclic, dynamic functions exhibited by distinct molecular chaperones. We argue that through the formation of multimeric stable chaperome complexes, a state of chaperome hyperconnectivity, or networking, is gained. The role of these chaperome networks is to act as multimolecular scaffolds, a particularly important function in cancer, where they increase the efficacy and functional diversity of several cellular processes. We predict that these concepts will change how we develop and implement drugs targeting the chaperome to treat cancer.

  5. Mapping biological process relationships and disease perturbations within a pathway network.

    PubMed

    Stoney, Ruth; Robertson, David L; Nenadic, Goran; Schwartz, Jean-Marc

    2018-01-01

    Molecular interaction networks are routinely used to map the organization of cellular function. Edges represent interactions between genes, proteins, or metabolites. However, in living cells, molecular interactions are dynamic, necessitating context-dependent models. Contextual information can be integrated into molecular interaction networks through the inclusion of additional molecular data, but there are concerns about completeness and relevance of this data. We developed an approach for representing the organization of human cellular processes using pathways as the nodes in a network. Pathways represent spatial and temporal sets of context-dependent interactions, generating a high-level network when linked together, which incorporates contextual information without the need for molecular interaction data. Analysis of the pathway network revealed linked communities representing functional relationships, comparable to those found in molecular networks, including metabolism, signaling, immunity, and the cell cycle. We mapped a range of diseases onto this network and find that pathways associated with diseases tend to be functionally connected, highlighting the perturbed functions that result in disease phenotypes. We demonstrated that disease pathways cluster within the network. We then examined the distribution of cancer pathways and showed that cancer pathways tend to localize within the signaling, DNA processes and immune modules, although some cancer-associated nodes are found in other network regions. Altogether, we generated a high-confidence functional network, which avoids some of the shortcomings faced by conventional molecular models. Our representation provides an intuitive functional interpretation of cellular organization, which relies only on high-quality pathway and Gene Ontology data. The network is available at https://data.mendeley.com/datasets/3pbwkxjxg9/1.

  6. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular mobile revenue. 32.5003 Section 32... mobile revenue. This account shall include message revenue derived from cellular mobile telecommunications systems connected to the public switched network placed between mobile units and other stations...

  7. Reconstruction of cellular signal transduction networks using perturbation assays and linear programming.

    PubMed

    Knapp, Bettina; Kaderali, Lars

    2013-01-01

    Perturbation experiments for example using RNA interference (RNAi) offer an attractive way to elucidate gene function in a high throughput fashion. The placement of hit genes in their functional context and the inference of underlying networks from such data, however, are challenging tasks. One of the problems in network inference is the exponential number of possible network topologies for a given number of genes. Here, we introduce a novel mathematical approach to address this question. We formulate network inference as a linear optimization problem, which can be solved efficiently even for large-scale systems. We use simulated data to evaluate our approach, and show improved performance in particular on larger networks over state-of-the art methods. We achieve increased sensitivity and specificity, as well as a significant reduction in computing time. Furthermore, we show superior performance on noisy data. We then apply our approach to study the intracellular signaling of human primary nave CD4(+) T-cells, as well as ErbB signaling in trastuzumab resistant breast cancer cells. In both cases, our approach recovers known interactions and points to additional relevant processes. In ErbB signaling, our results predict an important role of negative and positive feedback in controlling the cell cycle progression.

  8. Design and performance of mobile terminal for North American MSAT network

    NASA Technical Reports Server (NTRS)

    Fuji, Tsuyoshi; Tsuchiya, Makio; Isota, Yoji; Aoki, Katsuhiko

    1995-01-01

    The mobile terminal (MT), which can be selected for various applications, i.e. land mobile, transportable, fixed site, and maritime use, has been developed. Medium gain and high gain antennas are available. The MT can support circuit switched voice and data service. Additionally, cellular roaming service, net radio, and Group 3 facsimile services are optionally provided. A Mitsubishi handheld portable phone can be used as a stand-alone portable cellular-only phone or it can provide MSAT voice service when connected to MT. The MT which operates in L-band (1.5 GHz/1.6 GHz) satisfies equivalent isotropically radiated power (EIRP) of 12.5 dBW minimum and G/T of -16 dB/K minimum for medium gain system and -12 dB/K for high gain system. The excellent performance of transmit phase noise and bit error rate is achieved by using new technologies.

  9. Action of lytic polysaccharide monooxygenase on plant tissue is governed by cellular type.

    PubMed

    Chabbert, Brigitte; Habrant, Anouck; Herbaut, Mickaël; Foulon, Laurence; Aguié-Béghin, Véronique; Garajova, Sona; Grisel, Sacha; Bennati-Granier, Chloé; Gimbert-Herpoël, Isabelle; Jamme, Frédéric; Réfrégiers, Matthieu; Sandt, Christophe; Berrin, Jean-Guy; Paës, Gabriel

    2017-12-19

    Lignocellulosic biomass bioconversion is hampered by the structural and chemical complexity of the network created by cellulose, hemicellulose and lignin. Biological conversion of lignocellulose involves synergistic action of a large array of enzymes including the recently discovered lytic polysaccharide monooxygenases (LPMOs) that perform oxidative cleavage of cellulose. Using in situ imaging by synchrotron UV fluorescence, we have shown that the addition of AA9 LPMO (from Podospora anserina) to cellulases cocktail improves the progression of enzymes in delignified Miscanthus x giganteus as observed at tissular levels. In situ chemical monitoring of cell wall modifications performed by synchrotron infrared spectroscopy during enzymatic hydrolysis demonstrated that the boosting effect of the AA9 LPMO was dependent on the cellular type indicating contrasted recalcitrance levels in plant tissues. Our study provides a useful strategy for investigating enzyme dynamics and activity in plant cell wall to improve enzymatic cocktails aimed at expanding lignocelluloses biorefinery.

  10. CellNetVis: a web tool for visualization of biological networks using force-directed layout constrained by cellular components.

    PubMed

    Heberle, Henry; Carazzolle, Marcelo Falsarella; Telles, Guilherme P; Meirelles, Gabriela Vaz; Minghim, Rosane

    2017-09-13

    The advent of "omics" science has brought new perspectives in contemporary biology through the high-throughput analyses of molecular interactions, providing new clues in protein/gene function and in the organization of biological pathways. Biomolecular interaction networks, or graphs, are simple abstract representations where the components of a cell (e.g. proteins, metabolites etc.) are represented by nodes and their interactions are represented by edges. An appropriate visualization of data is crucial for understanding such networks, since pathways are related to functions that occur in specific regions of the cell. The force-directed layout is an important and widely used technique to draw networks according to their topologies. Placing the networks into cellular compartments helps to quickly identify where network elements are located and, more specifically, concentrated. Currently, only a few tools provide the capability of visually organizing networks by cellular compartments. Most of them cannot handle large and dense networks. Even for small networks with hundreds of nodes the available tools are not able to reposition the network while the user is interacting, limiting the visual exploration capability. Here we propose CellNetVis, a web tool to easily display biological networks in a cell diagram employing a constrained force-directed layout algorithm. The tool is freely available and open-source. It was originally designed for networks generated by the Integrated Interactome System and can be used with networks from others databases, like InnateDB. CellNetVis has demonstrated to be applicable for dynamic investigation of complex networks over a consistent representation of a cell on the Web, with capabilities not matched elsewhere.

  11. Evolution of the Max and Mlx networks in animals.

    PubMed

    McFerrin, Lisa G; Atchley, William R

    2011-01-01

    Transcription factors (TFs) are essential for the regulation of gene expression and often form emergent complexes to perform vital roles in cellular processes. In this paper, we focus on the parallel Max and Mlx networks of TFs because of their critical involvement in cell cycle regulation, proliferation, growth, metabolism, and apoptosis. A basic-helix-loop-helix-zipper (bHLHZ) domain mediates the competitive protein dimerization and DNA binding among Max and Mlx network members to form a complex system of cell regulation. To understand the importance of these network interactions, we identified the bHLHZ domain of Max and Mlx network proteins across the animal kingdom and carried out several multivariate statistical analyses. The presence and conservation of Max and Mlx network proteins in animal lineages stemming from the divergence of Metazoa indicate that these networks have ancient and essential functions. Phylogenetic analysis of the bHLHZ domain identified clear relationships among protein families with distinct points of radiation and divergence. Multivariate discriminant analysis further isolated specific amino acid changes within the bHLHZ domain that classify proteins, families, and network configurations. These analyses on Max and Mlx network members provide a model for characterizing the evolution of TFs involved in essential networks.

  12. 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.

  13. Cellular and synaptic network defects in autism

    PubMed Central

    Peça, João; Feng, Guoping

    2012-01-01

    Many candidate genes are now thought to confer susceptibility to autism spectrum disorder (ASD). Here we review four interrelated complexes, each composed of multiple families of genes that functionally coalesce on common cellular pathways. We illustrate a common thread in the organization of glutamatergic synapses and suggest a link between genes involved in Tuberous Sclerosis Complex, Fragile X syndrome, Angelman syndrome and several synaptic ASD candidate genes. When viewed in this context, progress in deciphering the molecular architecture of cellular protein-protein interactions together with the unraveling of synaptic dysfunction in neural networks may prove pivotal to advancing our understanding of ASDs. PMID:22440525

  14. The modeling and simulation of visuospatial working memory

    PubMed Central

    Liang, Lina; Zhang, Zhikang

    2010-01-01

    Camperi and Wang (Comput Neurosci 5:383–405, 1998) presented a network model for working memory that combines intrinsic cellular bistability with the recurrent network architecture of the neocortex. While Fall and Rinzel (Comput Neurosci 20:97–107, 2006) replaced this intrinsic bistability with a biological mechanism-Ca2+ release subsystem. In this study, we aim to further expand the above work. We integrate the traditional firing-rate network with Ca2+ subsystem-induced bistability, amend the synaptic weights and suggest that Ca2+ concentration only increase the efficacy of synaptic input but has nothing to do with the external input for the transient cue. We found that our network model maintained the persistent activity in response to a brief transient stimulus like that of the previous two models and the working memory performance was resistant to noise and distraction stimulus if Ca2+ subsystem was tuned to be bistable. PMID:22132045

  15. Principles of Protein Recognition and Properties of Protein-protein Interfaces

    NASA Astrophysics Data System (ADS)

    Keskin, Ozlem; Gursoy, Attila; Nussinov, Ruth

    In this chapter we address two aspects - the static physical interactions which allow the information transfer for the function to be performed; and the dynamic, i.e. how the information is transmitted between the binding sites in the single protein molecule and in the network. We describe the single protein molecules and their complexes; and the analogy between protein folding and protein binding. Eventually, to fully understand the interactome and how it performs the essential cellular functions, we have to put all together - and hierarchically progress through the system.

  16. Determining Regulatory Networks Governing the Differentiation of Embryonic Stem Cells to Pancreatic Lineage

    NASA Astrophysics Data System (ADS)

    Banerjee, Ipsita

    2009-03-01

    Knowledge of pathways governing cellular differentiation to specific phenotype will enable generation of desired cell fates by careful alteration of the governing network by adequate manipulation of the cellular environment. With this aim, we have developed a novel method to reconstruct the underlying regulatory architecture of a differentiating cell population from discrete temporal gene expression data. We utilize an inherent feature of biological networks, that of sparsity, in formulating the network reconstruction problem as a bi-level mixed-integer programming problem. The formulation optimizes the network topology at the upper level and the network connectivity strength at the lower level. The method is first validated by in-silico data, before applying it to the complex system of embryonic stem (ES) cell differentiation. This formulation enables efficient identification of the underlying network topology which could accurately predict steps necessary for directing differentiation to subsequent stages. Concurrent experimental verification demonstrated excellent agreement with model prediction.

  17. Semi-Automated Curation Allows Causal Network Model Building for the Quantification of Age-Dependent Plaque Progression in ApoE-/- Mouse.

    PubMed

    Szostak, Justyna; Martin, Florian; Talikka, Marja; Peitsch, Manuel C; Hoeng, Julia

    2016-01-01

    The cellular and molecular mechanisms behind the process of atherosclerotic plaque destabilization are complex, and molecular data from aortic plaques are difficult to interpret. Biological network models may overcome these difficulties and precisely quantify the molecular mechanisms impacted during disease progression. The atherosclerosis plaque destabilization biological network model was constructed with the semiautomated curation pipeline, BELIEF. Cellular and molecular mechanisms promoting plaque destabilization or rupture were captured in the network model. Public transcriptomic data sets were used to demonstrate the specificity of the network model and to capture the different mechanisms that were impacted in ApoE -/- mouse aorta at 6 and 32 weeks. We concluded that network models combined with the network perturbation amplitude algorithm provide a sensitive, quantitative method to follow disease progression at the molecular level. This approach can be used to investigate and quantify molecular mechanisms during plaque progression.

  18. φ-evo: A program to evolve phenotypic models of biological networks.

    PubMed

    Henry, Adrien; Hemery, Mathieu; François, Paul

    2018-06-01

    Molecular networks are at the core of most cellular decisions, but are often difficult to comprehend. Reverse engineering of network architecture from their functions has proved fruitful to classify and predict the structure and function of molecular networks, suggesting new experimental tests and biological predictions. We present φ-evo, an open-source program to evolve in silico phenotypic networks performing a given biological function. We include implementations for evolution of biochemical adaptation, adaptive sorting for immune recognition, metazoan development (somitogenesis, hox patterning), as well as Pareto evolution. We detail the program architecture based on C, Python 3, and a Jupyter interface for project configuration and network analysis. We illustrate the predictive power of φ-evo by first recovering the asymmetrical structure of the lac operon regulation from an objective function with symmetrical constraints. Second, we use the problem of hox-like embryonic patterning to show how a single effective fitness can emerge from multi-objective (Pareto) evolution. φ-evo provides an efficient approach and user-friendly interface for the phenotypic prediction of networks and the numerical study of evolution itself.

  19. A Compact Synchronous Cellular Model of Nonlinear Calcium Dynamics: Simulation and FPGA Synthesis Results.

    PubMed

    Soleimani, Hamid; Drakakis, Emmanuel M

    2017-06-01

    Recent studies have demonstrated that calcium is a widespread intracellular ion that controls a wide range of temporal dynamics in the mammalian body. The simulation and validation of such studies using experimental data would benefit from a fast large scale simulation and modelling tool. This paper presents a compact and fully reconfigurable cellular calcium model capable of mimicking Hopf bifurcation phenomenon and various nonlinear responses of the biological calcium dynamics. The proposed cellular model is synthesized on a digital platform for a single unit and a network model. Hardware synthesis, physical implementation on FPGA, and theoretical analysis confirm that the proposed cellular model can mimic the biological calcium behaviors with considerably low hardware overhead. The approach has the potential to speed up large-scale simulations of slow intracellular dynamics by sharing more cellular units in real-time. To this end, various networks constructed by pipelining 10 k to 40 k cellular calcium units are compared with an equivalent simulation run on a standard PC workstation. Results show that the cellular hardware model is, on average, 83 times faster than the CPU version.

  20. A Game Theoretic Optimization Method for Energy Efficient Global Connectivity in Hybrid Wireless Sensor Networks

    PubMed Central

    Lee, JongHyup; Pak, Dohyun

    2016-01-01

    For practical deployment of wireless sensor networks (WSN), WSNs construct clusters, where a sensor node communicates with other nodes in its cluster, and a cluster head support connectivity between the sensor nodes and a sink node. In hybrid WSNs, cluster heads have cellular network interfaces for global connectivity. However, when WSNs are active and the load of cellular networks is high, the optimal assignment of cluster heads to base stations becomes critical. Therefore, in this paper, we propose a game theoretic model to find the optimal assignment of base stations for hybrid WSNs. Since the communication and energy cost is different according to cellular systems, we devise two game models for TDMA/FDMA and CDMA systems employing power prices to adapt to the varying efficiency of recent wireless technologies. The proposed model is defined on the assumptions of the ideal sensing field, but our evaluation shows that the proposed model is more adaptive and energy efficient than local selections. PMID:27589743

  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. 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

  3. Derivation of large-scale cellular regulatory networks from biological time series data.

    PubMed

    de Bivort, Benjamin L

    2010-01-01

    Pharmacological agents and other perturbants of cellular homeostasis appear to nearly universally affect the activity of many genes, proteins, and signaling pathways. While this is due in part to nonspecificity of action of the drug or cellular stress, the large-scale self-regulatory behavior of the cell may also be responsible, as this typically means that when a cell switches states, dozens or hundreds of genes will respond in concert. If many genes act collectively in the cell during state transitions, rather than every gene acting independently, models of the cell can be created that are comprehensive of the action of all genes, using existing data, provided that the functional units in the model are collections of genes. Techniques to develop these large-scale cellular-level models are provided in detail, along with methods of analyzing them, and a brief summary of major conclusions about large-scale cellular networks to date.

  4. From neural-based object recognition toward microelectronic eyes

    NASA Technical Reports Server (NTRS)

    Sheu, Bing J.; Bang, Sa Hyun

    1994-01-01

    Engineering neural network systems are best known for their abilities to adapt to the changing characteristics of the surrounding environment by adjusting system parameter values during the learning process. Rapid advances in analog current-mode design techniques have made possible the implementation of major neural network functions in custom VLSI chips. An electrically programmable analog synapse cell with large dynamic range can be realized in a compact silicon area. New designs of the synapse cells, neurons, and analog processor are presented. A synapse cell based on Gilbert multiplier structure can perform the linear multiplication for back-propagation networks. A double differential-pair synapse cell can perform the Gaussian function for radial-basis network. The synapse cells can be biased in the strong inversion region for high-speed operation or biased in the subthreshold region for low-power operation. The voltage gain of the sigmoid-function neurons is externally adjustable which greatly facilitates the search of optimal solutions in certain networks. Various building blocks can be intelligently connected to form useful industrial applications. Efficient data communication is a key system-level design issue for large-scale networks. We also present analog neural processors based on perceptron architecture and Hopfield network for communication applications. Biologically inspired neural networks have played an important role towards the creation of powerful intelligent machines. Accuracy, limitations, and prospects of analog current-mode design of the biologically inspired vision processing chips and cellular neural network chips are key design issues.

  5. 2D reentrant auxetic structures of graphene/CNT networks for omnidirectionally stretchable supercapacitors.

    PubMed

    Kim, Byoung Soo; Lee, Kangsuk; Kang, Seulki; Lee, Soyeon; Pyo, Jun Beom; Choi, In Suk; Char, Kookheon; Park, Jong Hyuk; Lee, Sang-Soo; Lee, Jonghwi; Son, Jeong Gon

    2017-09-14

    Stretchable energy storage systems are essential for the realization of implantable and epidermal electronics. However, high-performance stretchable supercapacitors have received less attention because currently available processing techniques and material structures are too limited to overcome the trade-off relationship among electrical conductivity, ion-accessible surface area, and stretchability of electrodes. Herein, we introduce novel 2D reentrant cellular structures of porous graphene/CNT networks for omnidirectionally stretchable supercapacitor electrodes. Reentrant structures, with inwardly protruded frameworks in porous networks, were fabricated by the radial compression of vertically aligned honeycomb-like rGO/CNT networks, which were prepared by a directional crystallization method. Unlike typical porous graphene structures, the reentrant structure provided structure-assisted stretchability, such as accordion and origami structures, to otherwise unstretchable materials. The 2D reentrant structures of graphene/CNT networks maintained excellent electrical conductivities under biaxial stretching conditions and showed a slightly negative or near-zero Poisson's ratio over a wide strain range because of their structural uniqueness. For practical applications, we fabricated all-solid-state supercapacitors based on 2D auxetic structures. A radial compression process up to 1/10 th densified the electrode, significantly increasing the areal and volumetric capacitances of the electrodes. Additionally, vertically aligned graphene/CNT networks provided a plentiful surface area and induced sufficient ion transport pathways for the electrodes. Therefore, they exhibited high gravimetric and areal capacitance values of 152.4 F g -1 and 2.9 F cm -2 , respectively, and had an excellent retention ratio of 88% under a biaxial strain of 100%. Auxetic cellular and vertically aligned structures provide a new strategy for the preparation of robust platforms for stretchable energy storage electrodes.

  6. Issues in PCS interoperability and Internetworking

    NASA Technical Reports Server (NTRS)

    Dean, Richard A.; Estabrook, Polly

    1995-01-01

    This paper is an expansion of an earlier paper on Satellite/Terrestrial PCS which addressed issues for interoperability that included Networks, Services, Voice Coders and Mobility/Security. This paper focuses on the narrower topic of Network Reference Models and associated interfaces and protocols. The network reference models are addressed from the perspective of the User, the Cellular Carrier, the PSN Carrier, and the Radio Vendor. Each perspective is presented in the way these systems have evolved. The TIA TR46/GSM reference model will be reviewed. Variations in the use of this model that are prevalent in the industry will be discussed. These are the North American Cellular networks, the GSM networks, and the North American Carriers/Bellcore perspective. The paper concludes with the presentation of issues that develop from looking at merging satellite service into a world of many different networks.

  7. Numerical Analysis of the Performance of Millimeter-Wave RoF-Based Cellular Backhaul Links

    NASA Astrophysics Data System (ADS)

    Pham, Thu A.; Pham, Hien T. T.; Le, Hai-Chau; Dang, Ngoc T.

    2017-08-01

    In this paper, we study the performance of a next-generation cellular backhaul network that is based on a hybrid architecture using radio-over-fiber (RoF) and millimeter-wave (MMW) techniques. We develop a mathematic model and comprehensively analyze the performance of a MMW/RoF-based backhaul downlink under the impacts of various physical layer impairments originated from both optical fiber and wireless links. More specifically, the effects of nonlinear distortion, chromatic dispersion, fading, and many types of noises including shot noise, thermal noise, amplifier noise, and relative intensity noise are investigated. The numerical results show that the nonlinear distortion, fiber dispersion, and wireless fading are key factors that limit the system performance. Setting the modulation index properly helps minimize the effect of nonlinear distortion while implementing dispersion shifted optical fibers could be used to reduce the impact of dispersion and as a result, they can improve the bit-error rate. Moreover, it is also verified that, to mitigate the effect of multipath fading, remote radio heads should be located as near the remote antenna units as possible.

  8. Cell segmentation in histopathological images with deep learning algorithms by utilizing spatial relationships.

    PubMed

    Hatipoglu, Nuh; Bilgin, Gokhan

    2017-10-01

    In many computerized methods for cell detection, segmentation, and classification in digital histopathology that have recently emerged, the task of cell segmentation remains a chief problem for image processing in designing computer-aided diagnosis (CAD) systems. In research and diagnostic studies on cancer, pathologists can use CAD systems as second readers to analyze high-resolution histopathological images. Since cell detection and segmentation are critical for cancer grade assessments, cellular and extracellular structures should primarily be extracted from histopathological images. In response, we sought to identify a useful cell segmentation approach with histopathological images that uses not only prominent deep learning algorithms (i.e., convolutional neural networks, stacked autoencoders, and deep belief networks), but also spatial relationships, information of which is critical for achieving better cell segmentation results. To that end, we collected cellular and extracellular samples from histopathological images by windowing in small patches with various sizes. In experiments, the segmentation accuracies of the methods used improved as the window sizes increased due to the addition of local spatial and contextual information. Once we compared the effects of training sample size and influence of window size, results revealed that the deep learning algorithms, especially convolutional neural networks and partly stacked autoencoders, performed better than conventional methods in cell segmentation.

  9. Dynamic self-guiding analysis of Alzheimer's disease

    PubMed Central

    Kurakin, Alexei; Bredesen, Dale E.

    2015-01-01

    We applied a self-guiding evolutionary algorithm to initiate the synthesis of the Alzheimer's disease-related data and literature. A protein interaction network associated with amyloid-beta precursor protein (APP) and a seed model that treats Alzheimer's disease as progressive dysregulation of APP-associated signaling were used as dynamic “guides” and structural “filters” in the recursive search, analysis, and assimilation of data to drive the evolution of the seed model in size, detail, and complexity. Analysis of data and literature across sub-disciplines and system-scale discovery platforms suggests a key role of dynamic cytoskeletal connectivity in the stability, plasticity, and performance of multicellular networks and architectures. Chronic impairment and/or dysregulation of cell adhesions/synapses, cytoskeletal networks, and/or reversible epithelial-to-mesenchymal-like transitions, which enable and mediate the stable and coherent yet dynamic and reconfigurable multicellular architectures, may lead to the emergence and persistence of the disordered, wound-like pockets/microenvironments of chronically disconnected cells. Such wound-like microenvironments support and are supported by pro-inflammatory, pro-secretion, de-differentiated cellular phenotypes with altered metabolism and signaling. The co-evolution of wound-like microenvironments and their inhabitants may lead to the selection and stabilization of degenerated cellular phenotypes, via acquisition of epigenetic modifications and mutations, which eventually result in degenerative disorders such as cancer and Alzheimer's disease. PMID:26041885

  10. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions.

    PubMed

    Roy, Raktim; Shilpa, P Phani; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level. Systems biology-Microgravity-Pathways and networks-Bacteria. Astrobiology 16, 677-689.

  11. Interaction Network of Proteins Associated with Human Cytomegalovirus IE2-p86 Protein during Infection: A Proteomic Analysis

    PubMed Central

    Du, Guixin; Stinski, Mark F.

    2013-01-01

    Human cytomegalovirus protein IE2-p86 exerts its functions through interaction with other viral and cellular proteins. To further delineate its protein interaction network, we generated a recombinant virus expressing SG-tagged IE2-p86 and used tandem affinity purification coupled with mass spectrometry. A total of 9 viral proteins and 75 cellular proteins were found to associate with IE2-p86 protein during the first 48 hours of infection. The protein profile at 8, 24, and 48 h post infection revealed that UL84 tightly associated with IE2-p86, and more viral and cellular proteins came into association with IE2-p86 with the progression of virus infection. A computational analysis of the protein-protein interaction network indicated that all of the 9 viral proteins and most of the cellular proteins identified in the study are interconnected to varying degrees. Of the cellular proteins that were confirmed to associate with IE2-p86 by immunoprecipitation, C1QBP was further shown to be upregulated by HCMV infection and colocalized with IE2-p86, UL84 and UL44 in the virus replication compartment of the nucleus. The IE2-p86 interactome network demonstrated the temporal development of stable and abundant protein complexes that associate with IE2-p86 and provided a framework to benefit future studies of various protein complexes during HCMV infection. PMID:24358118

  12. Algorithm to Identify Frequent Coupled Modules from Two-Layered Network Series: Application to Study Transcription and Splicing Coupling

    PubMed Central

    Li, Wenyuan; Dai, Chao; Liu, Chun-Chi

    2012-01-01

    Abstract Current network analysis methods all focus on one or multiple networks of the same type. However, cells are organized by multi-layer networks (e.g., transcriptional regulatory networks, splicing regulatory networks, protein-protein interaction networks), which interact and influence each other. Elucidating the coupling mechanisms among those different types of networks is essential in understanding the functions and mechanisms of cellular activities. In this article, we developed the first computational method for pattern mining across many two-layered graphs, with the two layers representing different types yet coupled biological networks. We formulated the problem of identifying frequent coupled clusters between the two layers of networks into a tensor-based computation problem, and proposed an efficient solution to solve the problem. We applied the method to 38 two-layered co-transcription and co-splicing networks, derived from 38 RNA-seq datasets. With the identified atlas of coupled transcription-splicing modules, we explored to what extent, for which cellular functions, and by what mechanisms transcription-splicing coupling takes place. PMID:22697243

  13. Cellular-based modeling of oscillatory dynamics in brain networks.

    PubMed

    Skinner, Frances K

    2012-08-01

    Oscillatory, population activities have long been known to occur in our brains during different behavioral states. We know that many different cell types exist and that they contribute in distinct ways to the generation of these activities. I review recent papers that involve cellular-based models of brain networks, most of which include theta, gamma and sharp wave-ripple activities. To help organize the modeling work, I present it from a perspective of three different types of cellular-based modeling: 'Generic', 'Biophysical' and 'Linking'. Cellular-based modeling is taken to encompass the four features of experiment, model development, theory/analyses, and model usage/computation. The three modeling types are shown to include these features and interactions in different ways. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Tracking of time-varying genomic regulatory networks with a LASSO-Kalman smoother

    PubMed Central

    2014-01-01

    It is widely accepted that cellular requirements and environmental conditions dictate the architecture of genetic regulatory networks. Nonetheless, the status quo in regulatory network modeling and analysis assumes an invariant network topology over time. In this paper, we refocus on a dynamic perspective of genetic networks, one that can uncover substantial topological changes in network structure during biological processes such as developmental growth. We propose a novel outlook on the inference of time-varying genetic networks, from a limited number of noisy observations, by formulating the network estimation as a target tracking problem. We overcome the limited number of observations (small n large p problem) by performing tracking in a compressed domain. Assuming linear dynamics, we derive the LASSO-Kalman smoother, which recursively computes the minimum mean-square sparse estimate of the network connectivity at each time point. The LASSO operator, motivated by the sparsity of the genetic regulatory networks, allows simultaneous signal recovery and compression, thereby reducing the amount of required observations. The smoothing improves the estimation by incorporating all observations. We track the time-varying networks during the life cycle of the Drosophila melanogaster. The recovered networks show that few genes are permanent, whereas most are transient, acting only during specific developmental phases of the organism. PMID:24517200

  15. Oscillatory Protein Expression Dynamics Endows Stem Cells with Robust Differentiation Potential

    PubMed Central

    Kaneko, Kunihiko

    2011-01-01

    The lack of understanding of stem cell differentiation and proliferation is a fundamental problem in developmental biology. Although gene regulatory networks (GRNs) for stem cell differentiation have been partially identified, the nature of differentiation dynamics and their regulation leading to robust development remain unclear. Herein, using a dynamical system modeling cell approach, we performed simulations of the developmental process using all possible GRNs with a few genes, and screened GRNs that could generate cell type diversity through cell-cell interactions. We found that model stem cells that both proliferated and differentiated always exhibited oscillatory expression dynamics, and the differentiation frequency of such stem cells was regulated, resulting in a robust number distribution. Moreover, we uncovered the common regulatory motifs for stem cell differentiation, in which a combination of regulatory motifs that generated oscillatory expression dynamics and stabilized distinct cellular states played an essential role. These findings may explain the recently observed heterogeneity and dynamic equilibrium in cellular states of stem cells, and can be used to predict regulatory networks responsible for differentiation in stem cell systems. PMID:22073296

  16. Computational analysis of multimorbidity between asthma, eczema and rhinitis

    PubMed Central

    Aguilar, Daniel; Pinart, Mariona; Koppelman, Gerard H.; Saeys, Yvan; Nawijn, Martijn C.; Postma, Dirkje S.; Akdis, Mübeccel; Auffray, Charles; Ballereau, Stéphane; Benet, Marta; García-Aymerich, Judith; González, Juan Ramón; Guerra, Stefano; Keil, Thomas; Kogevinas, Manolis; Lambrecht, Bart; Lemonnier, Nathanael; Melen, Erik; Sunyer, Jordi; Valenta, Rudolf; Valverde, Sergi; Wickman, Magnus; Bousquet, Jean; Oliva, Baldo; Antó, Josep M.

    2017-01-01

    Background The mechanisms explaining the co-existence of asthma, eczema and rhinitis (allergic multimorbidity) are largely unknown. We investigated the mechanisms underlying multimorbidity between three main allergic diseases at a molecular level by identifying the proteins and cellular processes that are common to them. Methods An in silico study based on computational analysis of the topology of the protein interaction network was performed in order to characterize the molecular mechanisms of multimorbidity of asthma, eczema and rhinitis. As a first step, proteins associated to either disease were identified using data mining approaches, and their overlap was calculated. Secondly, a functional interaction network was built, allowing to identify cellular pathways involved in allergic multimorbidity. Finally, a network-based algorithm generated a ranked list of newly predicted multimorbidity-associated proteins. Results Asthma, eczema and rhinitis shared a larger number of associated proteins than expected by chance, and their associated proteins exhibited a significant degree of interconnectedness in the interaction network. There were 15 pathways involved in the multimorbidity of asthma, eczema and rhinitis, including IL4 signaling and GATA3-related pathways. A number of proteins potentially associated to these multimorbidity processes were also obtained. Conclusions These results strongly support the existence of an allergic multimorbidity cluster between asthma, eczema and rhinitis, and suggest that type 2 signaling pathways represent a relevant multimorbidity mechanism of allergic diseases. Furthermore, we identified new candidates contributing to multimorbidity that may assist in identifying new targets for multimorbid allergic diseases. PMID:28598986

  17. Computational analysis of multimorbidity between asthma, eczema and rhinitis.

    PubMed

    Aguilar, Daniel; Pinart, Mariona; Koppelman, Gerard H; Saeys, Yvan; Nawijn, Martijn C; Postma, Dirkje S; Akdis, Mübeccel; Auffray, Charles; Ballereau, Stéphane; Benet, Marta; García-Aymerich, Judith; González, Juan Ramón; Guerra, Stefano; Keil, Thomas; Kogevinas, Manolis; Lambrecht, Bart; Lemonnier, Nathanael; Melen, Erik; Sunyer, Jordi; Valenta, Rudolf; Valverde, Sergi; Wickman, Magnus; Bousquet, Jean; Oliva, Baldo; Antó, Josep M

    2017-01-01

    The mechanisms explaining the co-existence of asthma, eczema and rhinitis (allergic multimorbidity) are largely unknown. We investigated the mechanisms underlying multimorbidity between three main allergic diseases at a molecular level by identifying the proteins and cellular processes that are common to them. An in silico study based on computational analysis of the topology of the protein interaction network was performed in order to characterize the molecular mechanisms of multimorbidity of asthma, eczema and rhinitis. As a first step, proteins associated to either disease were identified using data mining approaches, and their overlap was calculated. Secondly, a functional interaction network was built, allowing to identify cellular pathways involved in allergic multimorbidity. Finally, a network-based algorithm generated a ranked list of newly predicted multimorbidity-associated proteins. Asthma, eczema and rhinitis shared a larger number of associated proteins than expected by chance, and their associated proteins exhibited a significant degree of interconnectedness in the interaction network. There were 15 pathways involved in the multimorbidity of asthma, eczema and rhinitis, including IL4 signaling and GATA3-related pathways. A number of proteins potentially associated to these multimorbidity processes were also obtained. These results strongly support the existence of an allergic multimorbidity cluster between asthma, eczema and rhinitis, and suggest that type 2 signaling pathways represent a relevant multimorbidity mechanism of allergic diseases. Furthermore, we identified new candidates contributing to multimorbidity that may assist in identifying new targets for multimorbid allergic diseases.

  18. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions

    NASA Astrophysics Data System (ADS)

    Roy, Raktim; Phani Shilpa, P.; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level.

  19. CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Noise effect in metabolic networks

    NASA Astrophysics Data System (ADS)

    Li, Zheng-Yan; Xie, Zheng-Wei; Chen, Tong; Ouyang, Qi

    2009-12-01

    Constraint-based models such as flux balance analysis (FBA) are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term 'noise', and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states.

  20. Cellular structures with interconnected microchannels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shaefer, Robert Shahram; Ghoniem, Nasr M.; Williams, Brian

    A method for fabricating a cellular tritium breeder component includes obtaining a reticulated carbon foam skeleton comprising a network of interconnected ligaments. The foam skeleton is then melt-infiltrated with a tritium breeder material, for example, lithium zirconate or lithium titanate. The foam skeleton is then removed to define a cellular breeder component having a network of interconnected tritium purge channels. In an embodiment the ligaments of the foam skeleton are enlarged by adding carbon using chemical vapor infiltration (CVI) prior to melt-infiltration. In an embodiment the foam skeleton is coated with a refractory material, for example, tungsten, prior to meltmore » infiltration.« less

  1. Spatial localization of the first and last enzymes effectively connects active metabolic pathways in bacteria.

    PubMed

    Meyer, Pablo; Cecchi, Guillermo; Stolovitzky, Gustavo

    2014-12-14

    Although much is understood about the enzymatic cascades that underlie cellular biosynthesis, comparatively little is known about the rules that determine their cellular organization. We performed a detailed analysis of the localization of E.coli GFP-tagged enzymes for cells growing exponentially. We found that out of 857 globular enzymes, at least 219 have a discrete punctuate localization in the cytoplasm and catalyze the first or the last reaction in 60% of biosynthetic pathways. A graph-theoretic analysis of E.coli's metabolic network shows that localized enzymes, in contrast to non-localized ones, form a tree-like hierarchical structure, have a higher within-group connectivity, and are traversed by a higher number of feed-forward and feedback loops than their non-localized counterparts. A Gene Ontology analysis of these enzymes reveals an enrichment of terms related to essential metabolic functions in growing cells. Given that these findings suggest a distinct metabolic role for localization, we studied the dynamics of cellular localization of the cell wall synthesizing enzymes in B. subtilis and found that enzymes localize during exponential growth but not during stationary growth. We conclude that active biochemical pathways inside the cytoplasm are organized spatially following a rule where their first or their last enzymes localize to effectively connect the different active pathways and thus could reflect the activity state of the cell's metabolic network.

  2. 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.

  3. Cellular automata simulation of topological effects on the dynamics of feed-forward motifs

    PubMed Central

    Apte, Advait A; Cain, John W; Bonchev, Danail G; Fong, Stephen S

    2008-01-01

    Background Feed-forward motifs are important functional modules in biological and other complex networks. The functionality of feed-forward motifs and other network motifs is largely dictated by the connectivity of the individual network components. While studies on the dynamics of motifs and networks are usually devoted to the temporal or spatial description of processes, this study focuses on the relationship between the specific architecture and the overall rate of the processes of the feed-forward family of motifs, including double and triple feed-forward loops. The search for the most efficient network architecture could be of particular interest for regulatory or signaling pathways in biology, as well as in computational and communication systems. Results Feed-forward motif dynamics were studied using cellular automata and compared with differential equation modeling. The number of cellular automata iterations needed for a 100% conversion of a substrate into a target product was used as an inverse measure of the transformation rate. Several basic topological patterns were identified that order the specific feed-forward constructions according to the rate of dynamics they enable. At the same number of network nodes and constant other parameters, the bi-parallel and tri-parallel motifs provide higher network efficacy than single feed-forward motifs. Additionally, a topological property of isodynamicity was identified for feed-forward motifs where different network architectures resulted in the same overall rate of the target production. Conclusion It was shown for classes of structural motifs with feed-forward architecture that network topology affects the overall rate of a process in a quantitatively predictable manner. These fundamental results can be used as a basis for simulating larger networks as combinations of smaller network modules with implications on studying synthetic gene circuits, small regulatory systems, and eventually dynamic whole-cell models. PMID:18304325

  4. Adaptive Control Model Reveals Systematic Feedback and Key Molecules in Metabolic Pathway Regulation

    PubMed Central

    Moffitt, Richard A.; Merrill, Alfred H.; Wang, May D.

    2011-01-01

    Abstract Robust behavior in metabolic pathways resembles stabilized performance in systems under autonomous control. This suggests we can apply control theory to study existing regulation in these cellular networks. Here, we use model-reference adaptive control (MRAC) to investigate the dynamics of de novo sphingolipid synthesis regulation in a combined theoretical and experimental case study. The effects of serine palmitoyltransferase over-expression on this pathway are studied in vitro using human embryonic kidney cells. We report two key results from comparing numerical simulations with observed data. First, MRAC simulations of pathway dynamics are comparable to simulations from a standard model using mass action kinetics. The root-sum-square (RSS) between data and simulations in both cases differ by less than 5%. Second, MRAC simulations suggest systematic pathway regulation in terms of adaptive feedback from individual molecules. In response to increased metabolite levels available for de novo sphingolipid synthesis, feedback from molecules along the main artery of the pathway is regulated more frequently and with greater amplitude than from other molecules along the branches. These biological insights are consistent with current knowledge while being new that they may guide future research in sphingolipid biology. In summary, we report a novel approach to study regulation in cellular networks by applying control theory in the context of robust metabolic pathways. We do this to uncover potential insight into the dynamics of regulation and the reverse engineering of cellular networks for systems biology. This new modeling approach and the implementation routines designed for this case study may be extended to other systems. Supplementary Material is available at www.liebertonline.com/cmb. PMID:21314456

  5. Estimating phase synchronization in dynamical systems using cellular nonlinear networks

    NASA Astrophysics Data System (ADS)

    Sowa, Robert; Chernihovskyi, Anton; Mormann, Florian; Lehnertz, Klaus

    2005-06-01

    We propose a method for estimating phase synchronization between time series using the parallel computing architecture of cellular nonlinear networks (CNN’s). Applying this method to time series of coupled nonlinear model systems and to electroencephalographic time series from epilepsy patients, we show that an accurate approximation of the mean phase coherence R —a bivariate measure for phase synchronization—can be achieved with CNN’s using polynomial-type templates.

  6. CellNet: Network Biology Applied to Stem Cell Engineering

    PubMed Central

    Cahan, Patrick; Li, Hu; Morris, Samantha A.; da Rocha, Edroaldo Lummertz; Daley, George Q.; Collins, James J.

    2014-01-01

    SUMMARY Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population, and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. PMID:25126793

  7. Understanding Biological Regulation Through Synthetic Biology.

    PubMed

    Bashor, Caleb J; Collins, James J

    2018-05-20

    Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.

  8. Integration of Mobil Satellite and Cellular Systems

    NASA Technical Reports Server (NTRS)

    Drucker, E. H.; Estabrook, P.; Pinck, D.; Ekroot, L.

    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.

  9. Inference of Gene Regulatory Networks Using Time-Series Data: A Survey

    PubMed Central

    Sima, Chao; Hua, Jianping; Jung, Sungwon

    2009-01-01

    The advent of high-throughput technology like microarrays has provided the platform for studying how different cellular components work together, thus created an enormous interest in mathematically modeling biological network, particularly gene regulatory network (GRN). Of particular interest is the modeling and inference on time-series data, which capture a more thorough picture of the system than non-temporal data do. We have given an extensive review of methodologies that have been used on time-series data. In realizing that validation is an impartible part of the inference paradigm, we have also presented a discussion on the principles and challenges in performance evaluation of different methods. This survey gives a panoramic view on these topics, with anticipation that the readers will be inspired to improve and/or expand GRN inference and validation tool repository. PMID:20190956

  10. Non-Orthogonal Multiple Access for Ubiquitous Wireless Sensor Networks.

    PubMed

    Anwar, Asim; Seet, Boon-Chong; Ding, Zhiguo

    2018-02-08

    Ubiquitous wireless sensor networks (UWSNs) have become a critical technology for enabling smart cities and other ubiquitous monitoring applications. Their deployment, however, can be seriously hampered by the spectrum available to the sheer number of sensors for communication. To support the communication needs of UWSNs without requiring more spectrum resources, the power-domain non-orthogonal multiple access (NOMA) technique originally proposed for 5th Generation (5G) cellular networks is investigated for UWSNs for the first time in this paper. However, unlike 5G networks that operate in the licensed spectrum, UWSNs mostly operate in unlicensed spectrum where sensors also experience cross-technology interferences from other devices sharing the same spectrum. In this paper, we model the interferences from various sources at the sensors using stochastic geometry framework. To evaluate the performance, we derive a theorem and present new closed form expression for the outage probability of the sensors in a downlink scenario under interference limited environment. In addition, diversity analysis for the ordered NOMA users is performed. Based on the derived outage probability, we evaluate the average link throughput and energy consumption efficiency of NOMA against conventional orthogonal multiple access (OMA) technique in UWSNs. Further, the required computational complexity for the NOMA users is presented.

  11. Dynamical analysis of cellular ageing by modeling of gene regulatory network based attractor landscape.

    PubMed

    Chong, Ket Hing; Zhang, Xiaomeng; Zheng, Jie

    2018-01-01

    Ageing is a natural phenomenon that is inherently complex and remains a mystery. Conceptual model of cellular ageing landscape was proposed for computational studies of ageing. However, there is a lack of quantitative model of cellular ageing landscape. This study aims to investigate the mechanism of cellular ageing in a theoretical model using the framework of Waddington's epigenetic landscape. We construct an ageing gene regulatory network (GRN) consisting of the core cell cycle regulatory genes (including p53). A model parameter (activation rate) is used as a measure of the accumulation of DNA damage. Using the bifurcation diagrams to estimate the parameter values that lead to multi-stability, we obtained a conceptual model for capturing three distinct stable steady states (or attractors) corresponding to homeostasis, cell cycle arrest, and senescence or apoptosis. In addition, we applied a Monte Carlo computational method to quantify the potential landscape, which displays: I) one homeostasis attractor for low accumulation of DNA damage; II) two attractors for cell cycle arrest and senescence (or apoptosis) in response to high accumulation of DNA damage. Using the Waddington's epigenetic landscape framework, the process of ageing can be characterized by state transitions from landscape I to II. By in silico perturbations, we identified the potential landscape of a perturbed network (inactivation of p53), and thereby demonstrated the emergence of a cancer attractor. The simulated dynamics of the perturbed network displays a landscape with four basins of attraction: homeostasis, cell cycle arrest, senescence (or apoptosis) and cancer. Our analysis also showed that for the same perturbed network with low DNA damage, the landscape displays only the homeostasis attractor. The mechanistic model offers theoretical insights that can facilitate discovery of potential strategies for network medicine of ageing-related diseases such as cancer.

  12. 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...

  13. A global interaction network maps a wiring diagram of cellular function

    PubMed Central

    Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles

    2017-01-01

    We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008

  14. Independence screening for high dimensional nonlinear additive ODE models with applications to dynamic gene regulatory networks.

    PubMed

    Xue, Hongqi; Wu, Shuang; Wu, Yichao; Ramirez Idarraga, Juan C; Wu, Hulin

    2018-05-02

    Mechanism-driven low-dimensional ordinary differential equation (ODE) models are often used to model viral dynamics at cellular levels and epidemics of infectious diseases. However, low-dimensional mechanism-based ODE models are limited for modeling infectious diseases at molecular levels such as transcriptomic or proteomic levels, which is critical to understand pathogenesis of diseases. Although linear ODE models have been proposed for gene regulatory networks (GRNs), nonlinear regulations are common in GRNs. The reconstruction of large-scale nonlinear networks from time-course gene expression data remains an unresolved issue. Here, we use high-dimensional nonlinear additive ODEs to model GRNs and propose a 4-step procedure to efficiently perform variable selection for nonlinear ODEs. To tackle the challenge of high dimensionality, we couple the 2-stage smoothing-based estimation method for ODEs and a nonlinear independence screening method to perform variable selection for the nonlinear ODE models. We have shown that our method possesses the sure screening property and it can handle problems with non-polynomial dimensionality. Numerical performance of the proposed method is illustrated with simulated data and a real data example for identifying the dynamic GRN of Saccharomyces cerevisiae. Copyright © 2018 John Wiley & Sons, Ltd.

  15. Message Efficient Checkpointing and Rollback Recovery in Heterogeneous Mobile Networks

    NASA Astrophysics Data System (ADS)

    Jaggi, Parmeet Kaur; Singh, Awadhesh Kumar

    2016-06-01

    Heterogeneous networks provide an appealing way of expanding the computing capability of mobile networks by combining infrastructure-less mobile ad-hoc networks with the infrastructure-based cellular mobile networks. The nodes in such a network range from low-power nodes to macro base stations and thus, vary greatly in their capabilities such as computation power and battery power. The nodes are susceptible to different types of transient and permanent failures and therefore, the algorithms designed for such networks need to be fault-tolerant. The article presents a checkpointing algorithm for the rollback recovery of mobile hosts in a heterogeneous mobile network. Checkpointing is a well established approach to provide fault tolerance in static and cellular mobile distributed systems. However, the use of checkpointing for fault tolerance in a heterogeneous environment remains to be explored. The proposed protocol is based on the results of zigzag paths and zigzag cycles by Netzer-Xu. Considering the heterogeneity prevalent in the network, an uncoordinated checkpointing technique is employed. Yet, useless checkpoints are avoided without causing a high message overhead.

  16. Parallel multipoint recording of aligned and cultured neurons on micro channel array toward cellular network analysis.

    PubMed

    Tonomura, Wataru; Moriguchi, Hiroyuki; Jimbo, Yasuhiko; Konishi, Satoshi

    2010-08-01

    This paper describes an advanced Micro Channel Array (MCA) for recording electrophysiological signals of neuronal networks at multiple points simultaneously. The developed MCA is designed for neuronal network analysis which has been studied by the co-authors using the Micro Electrode Arrays (MEA) system, and employs the principles of extracellular recordings. A prerequisite for extracellular recordings with good signal-to-noise ratio is a tight contact between cells and electrodes. The MCA described herein has the following advantages. The electrodes integrated around individual micro channels are electrically isolated to enable parallel multipoint recording. Reliable clamping of a targeted cell through micro channels is expected to improve the cellular selectivity and the attachment between the cell and the electrode toward steady electrophysiological recordings. We cultured hippocampal neurons on the developed MCA. As a result, the spontaneous and evoked spike potentials could be recorded by sucking and clamping the cells at multiple points. In this paper, we describe the design and fabrication of the MCA and the successful electrophysiological recordings leading to the development of an effective cellular network analysis device.

  17. Inter-cellular forces orchestrate contact inhibition of locomotion.

    PubMed

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

    2015-04-09

    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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Protein complex prediction for large protein protein interaction networks with the Core&Peel method.

    PubMed

    Pellegrini, Marco; Baglioni, Miriam; Geraci, Filippo

    2016-11-08

    Biological networks play an increasingly important role in the exploration of functional modularity and cellular organization at a systemic level. Quite often the first tools used to analyze these networks are clustering algorithms. We concentrate here on the specific task of predicting protein complexes (PC) in large protein-protein interaction networks (PPIN). Currently, many state-of-the-art algorithms work well for networks of small or moderate size. However, their performance on much larger networks, which are becoming increasingly common in modern proteome-wise studies, needs to be re-assessed. We present a new fast algorithm for clustering large sparse networks: Core&Peel, which runs essentially in time and storage O(a(G)m+n) for a network G of n nodes and m arcs, where a(G) is the arboricity of G (which is roughly proportional to the maximum average degree of any induced subgraph in G). We evaluated Core&Peel on five PPI networks of large size and one of medium size from both yeast and homo sapiens, comparing its performance against those of ten state-of-the-art methods. We demonstrate that Core&Peel consistently outperforms the ten competitors in its ability to identify known protein complexes and in the functional coherence of its predictions. Our method is remarkably robust, being quite insensible to the injection of random interactions. Core&Peel is also empirically efficient attaining the second best running time over large networks among the tested algorithms. Our algorithm Core&Peel pushes forward the state-of the-art in PPIN clustering providing an algorithmic solution with polynomial running time that attains experimentally demonstrable good output quality and speed on challenging large real networks.

  19. Utilization of Concurrent Buffers to Facilitate Seamless Data Transition in Tactical Cellular Communications

    DTIC Science & Technology

    2015-09-01

    INTENTIONALLY LEFT BLANK xiii LIST OF ACRONYMS AND ABBREVIATIONS 2G 2nd Generation 3G 3rd Generation 3GPP 3rd Generation Partnership Project 4G 4th...System (UMTS) is the standard that governs 3rd Generation ( 3G ) migration of Global Services for Mobile (GSM) networks. It defines packet-based...network may assist or mitigate. 14. SUBJECT TERMS IEEE, 802.21, Media Independent Handover, mobile , communications, cyber, tactical, buffer, cellular

  20. Almost periodic cellular neural networks with neutral-type proportional delays

    NASA Astrophysics Data System (ADS)

    Xiao, Songlin

    2018-03-01

    This paper presents a new result on the existence, uniqueness and generalised exponential stability of almost periodic solutions for cellular neural networks with neutral-type proportional delays and D operator. Based on some novel differential inequality techniques, a testable condition is derived to ensure that all the state trajectories of the system converge to an almost periodic solution with a positive exponential convergence rate. The effectiveness of the obtained result is illustrated by a numerical example.

  1. Resveratrol stimulates mitochondrial fusion by a mechanism requiring mitofusin-2.

    PubMed

    Robb, Ellen L; Moradi, Fereshteh; Maddalena, Lucas A; Valente, Andrew J F; Fonseca, Joao; Stuart, Jeffrey A

    2017-04-01

    Resveratrol (RES) is a plant-derived stilbene associated with a wide range of health benefits. Mitochondria are a key downstream target of RES, and in some cell types RES promotes mitochondrial biogenesis, altered cellular redox status, and a shift toward oxidative metabolism. Mitochondria exist as a dynamic network that continually remodels via fusion and fission processes, and the extent of fusion is related to cellular redox status and metabolism. We investigated RES's effects on mitochondrial network morphology in several cell lines using a quantitative approach to measure the extent of network fusion. 48 h continuous treatment with 10-20 μM RES stimulated mitochondrial fusion in C2C12 myoblasts, PC3 cancer cells, and mouse embryonic fibroblasts stimulated significant increases in fusion in all instances, resulting in larger and more highly branched mitochondrial networks. Mitofusin-2 (Mfn2) is a key protein facilitating mitochondrial fusion, and its expression was also stimulated by RES. Using Mfn2-null cells we demonstrated that RES's effects on mitochondrial fusion, cellular respiration rates, and cell growth are all dependent upon the presence of Mfn2. Taken together, these results demonstrate that Mfn2 and mitochondrial fusion are affected by RES in ways that appear to relate to RES's known effects on cellular metabolism and growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Cellular computational generalized neuron network for frequency situational intelligence in a multi-machine power system.

    PubMed

    Wei, Yawei; Venayagamoorthy, Ganesh Kumar

    2017-09-01

    To prevent large interconnected power system from a cascading failure, brownout or even blackout, grid operators require access to faster than real-time information to make appropriate just-in-time control decisions. However, the communication and computational system limitations of currently used supervisory control and data acquisition (SCADA) system can only deliver delayed information. However, the deployment of synchrophasor measurement devices makes it possible to capture and visualize, in near-real-time, grid operational data with extra granularity. In this paper, a cellular computational network (CCN) approach for frequency situational intelligence (FSI) in a power system is presented. The distributed and scalable computing unit of the CCN framework makes it particularly flexible for customization for a particular set of prediction requirements. Two soft-computing algorithms have been implemented in the CCN framework: a cellular generalized neuron network (CCGNN) and a cellular multi-layer perceptron network (CCMLPN), for purposes of providing multi-timescale frequency predictions, ranging from 16.67 ms to 2 s. These two developed CCGNN and CCMLPN systems were then implemented on two different scales of power systems, one of which installed a large photovoltaic plant. A real-time power system simulator at weather station within the Real-Time Power and Intelligent Systems (RTPIS) laboratory at Clemson, SC, was then used to derive typical FSI results. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Computational study of noise in a large signal transduction network.

    PubMed

    Intosalmi, Jukka; Manninen, Tiina; Ruohonen, Keijo; Linne, Marja-Leena

    2011-06-21

    Biochemical systems are inherently noisy due to the discrete reaction events that occur in a random manner. Although noise is often perceived as a disturbing factor, the system might actually benefit from it. In order to understand the role of noise better, its quality must be studied in a quantitative manner. Computational analysis and modeling play an essential role in this demanding endeavor. We implemented a large nonlinear signal transduction network combining protein kinase C, mitogen-activated protein kinase, phospholipase A2, and β isoform of phospholipase C networks. We simulated the network in 300 different cellular volumes using the exact Gillespie stochastic simulation algorithm and analyzed the results in both the time and frequency domain. In order to perform simulations in a reasonable time, we used modern parallel computing techniques. The analysis revealed that time and frequency domain characteristics depend on the system volume. The simulation results also indicated that there are several kinds of noise processes in the network, all of them representing different kinds of low-frequency fluctuations. In the simulations, the power of noise decreased on all frequencies when the system volume was increased. We concluded that basic frequency domain techniques can be applied to the analysis of simulation results produced by the Gillespie stochastic simulation algorithm. This approach is suited not only to the study of fluctuations but also to the study of pure noise processes. Noise seems to have an important role in biochemical systems and its properties can be numerically studied by simulating the reacting system in different cellular volumes. Parallel computing techniques make it possible to run massive simulations in hundreds of volumes and, as a result, accurate statistics can be obtained from computational studies. © 2011 Intosalmi et al; licensee BioMed Central Ltd.

  4. Analyzing mobile WiMAX base station deployment under different frequency planning strategies

    NASA Astrophysics Data System (ADS)

    Salman, M. K.; Ahmad, R. B.; Ali, Ziad G.; Aldhaibani, Jaafar A.; Fayadh, Rashid A.

    2015-05-01

    The frequency spectrum is a precious resource and scarce in the communication markets. Therefore, different techniques are adopted to utilize the available spectrum in deploying WiMAX base stations (BS) in cellular networks. In this paper several types of frequency planning techniques are illustrated, and a comprehensive comparative study between conventional frequency reuse of 1 (FR of 1) and fractional frequency reuse (FFR) is presented. These techniques are widely used in network deployment, because they employ universal frequency (using all the available bandwidth) in their base station installation/configuration within network system. This paper presents a network model of 19 base stations in order to be employed in the comparison of the aforesaid frequency planning techniques. Users are randomly distributed within base stations, users' resource mapping and their burst profile selection are based on the measured signal to interference plus-noise ratio (SINR). Simulation results reveal that the FFR has advantages over the conventional FR of 1 in various metrics. 98 % of downlink resources (slots) are exploited when FFR is applied, whilst it is 81 % at FR of 1. Data rate of FFR has been increased to 10.6 Mbps, while it is 7.98 Mbps at FR of 1. The spectral efficiency is better enhanced (1.072 bps/Hz) at FR of 1 than FFR (0.808 bps/Hz), since FR of 1 exploits all the Bandwidth. The subcarrier efficiency shows how many data bits that can be carried by subcarriers under different frequency planning techniques, the system can carry more data bits under FFR (2.40 bit/subcarrier) than FR of 1 (1.998 bit/subcarrier). This study confirms that FFR can perform better than conventional frequency planning (FR of 1) which made it a strong candidate for WiMAX BS deployment in cellular networks.

  5. Exploring Spatio-temporal Dynamics of Cellular Automata for Pattern Recognition in Networks.

    PubMed

    Miranda, Gisele Helena Barboni; Machicao, Jeaneth; Bruno, Odemir Martinez

    2016-11-22

    Network science is an interdisciplinary field which provides an integrative approach for the study of complex systems. In recent years, network modeling has been used for the study of emergent phenomena in many real-world applications. Pattern recognition in networks has been drawing attention to the importance of network characterization, which may lead to understanding the topological properties that are related to the network model. In this paper, the Life-Like Network Automata (LLNA) method is introduced, which was designed for pattern recognition in networks. LLNA uses the network topology as a tessellation of Cellular Automata (CA), whose dynamics produces a spatio-temporal pattern used to extract the feature vector for network characterization. The method was evaluated using synthetic and real-world networks. In the latter, three pattern recognition applications were used: (i) identifying organisms from distinct domains of life through their metabolic networks, (ii) identifying online social networks and (iii) classifying stomata distribution patterns varying according to different lighting conditions. LLNA was compared to structural measurements and surpasses them in real-world applications, achieving improvement in the classification rate as high as 23%, 4% and 7% respectively. Therefore, the proposed method is a good choice for pattern recognition applications using networks and demonstrates potential for general applicability.

  6. Exploring Spatio-temporal Dynamics of Cellular Automata for Pattern Recognition in Networks

    PubMed Central

    Miranda, Gisele Helena Barboni; Machicao, Jeaneth; Bruno, Odemir Martinez

    2016-01-01

    Network science is an interdisciplinary field which provides an integrative approach for the study of complex systems. In recent years, network modeling has been used for the study of emergent phenomena in many real-world applications. Pattern recognition in networks has been drawing attention to the importance of network characterization, which may lead to understanding the topological properties that are related to the network model. In this paper, the Life-Like Network Automata (LLNA) method is introduced, which was designed for pattern recognition in networks. LLNA uses the network topology as a tessellation of Cellular Automata (CA), whose dynamics produces a spatio-temporal pattern used to extract the feature vector for network characterization. The method was evaluated using synthetic and real-world networks. In the latter, three pattern recognition applications were used: (i) identifying organisms from distinct domains of life through their metabolic networks, (ii) identifying online social networks and (iii) classifying stomata distribution patterns varying according to different lighting conditions. LLNA was compared to structural measurements and surpasses them in real-world applications, achieving improvement in the classification rate as high as 23%, 4% and 7% respectively. Therefore, the proposed method is a good choice for pattern recognition applications using networks and demonstrates potential for general applicability. PMID:27874024

  7. Exploring Spatio-temporal Dynamics of Cellular Automata for Pattern Recognition in Networks

    NASA Astrophysics Data System (ADS)

    Miranda, Gisele Helena Barboni; Machicao, Jeaneth; Bruno, Odemir Martinez

    2016-11-01

    Network science is an interdisciplinary field which provides an integrative approach for the study of complex systems. In recent years, network modeling has been used for the study of emergent phenomena in many real-world applications. Pattern recognition in networks has been drawing attention to the importance of network characterization, which may lead to understanding the topological properties that are related to the network model. In this paper, the Life-Like Network Automata (LLNA) method is introduced, which was designed for pattern recognition in networks. LLNA uses the network topology as a tessellation of Cellular Automata (CA), whose dynamics produces a spatio-temporal pattern used to extract the feature vector for network characterization. The method was evaluated using synthetic and real-world networks. In the latter, three pattern recognition applications were used: (i) identifying organisms from distinct domains of life through their metabolic networks, (ii) identifying online social networks and (iii) classifying stomata distribution patterns varying according to different lighting conditions. LLNA was compared to structural measurements and surpasses them in real-world applications, achieving improvement in the classification rate as high as 23%, 4% and 7% respectively. Therefore, the proposed method is a good choice for pattern recognition applications using networks and demonstrates potential for general applicability.

  8. Cellular computational platform and neurally inspired elements thereof

    DOEpatents

    Okandan, Murat

    2016-11-22

    A cellular computational platform is disclosed that includes a multiplicity of functionally identical, repeating computational hardware units that are interconnected electrically and optically. Each computational hardware unit includes a reprogrammable local memory and has interconnections to other such units that have reconfigurable weights. Each computational hardware unit is configured to transmit signals into the network for broadcast in a protocol-less manner to other such units in the network, and to respond to protocol-less broadcast messages that it receives from the network. Each computational hardware unit is further configured to reprogram the local memory in response to incoming electrical and/or optical signals.

  9. Integration of Optical Manipulation and Electrophysiological Tools to Modulate and Record Activity in Neural Networks

    NASA Astrophysics Data System (ADS)

    Difato, F.; Schibalsky, L.; Benfenati, F.; Blau, A.

    2011-07-01

    We present an optical system that combines IR (1064 nm) holographic optical tweezers with a sub-nanosecond-pulsed UV (355 nm) laser microdissector for the optical manipulation of single neurons and entire networks both on transparent and non-transparent substrates in vitro. The phase-modulated laser beam can illuminate the sample concurrently or independently from above or below assuring compatibility with different types of microelectrode array and patch-clamp electrophysiology. By combining electrophysiological and optical tools, neural activity in response to localized stimuli or injury can be studied and quantified at sub-cellular, cellular, and network level.

  10. Proteome-scale human interactomics

    PubMed Central

    Luck, Katja; Sheynkman, Gloria M.; Zhang, Ivy; Vidal, Marc

    2017-01-01

    Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome-scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life. PMID:28284537

  11. Nuclear traffic and peloton formation in fungal networks

    NASA Astrophysics Data System (ADS)

    Roper, Marcus; Hickey, Patrick; Lewkiewicz, Stephanie; Dressaire, Emilie; Read, Nick

    2013-11-01

    Hyphae, the network of microfluidic pipes that make up a growing fungal cell, must balance their function as conduits for the transport of nuclei with other cellular functions including secretion and growth. Constant flow of nuclei may interfere with the protein traffic that enables other functions to be performed. Live-cell imaging reveals that nuclear flows are anti-congestive; that groups of nuclei flow faster than single nuclei, and that nuclei sweep through the colony in dense clumps. We call these clumps pelotons, after the term used to describe groups of cycle racers slip-streaming off each other. Because of the pelotons, individual hyphae transport nuclei only intermittently, producing long intervals in which hyphae can perform their other functions. Modeling reveals how pelotons are created by interactions between nuclei and the hyphal cytoskeleton, and reveal the control that the fungus enjoys over peloton assembly and timing.

  12. Inference of Gene Regulatory Networks Using Bayesian Nonparametric Regression and Topology Information.

    PubMed

    Fan, Yue; Wang, Xiao; Peng, Qinke

    2017-01-01

    Gene regulatory networks (GRNs) play an important role in cellular systems and are important for understanding biological processes. Many algorithms have been developed to infer the GRNs. However, most algorithms only pay attention to the gene expression data but do not consider the topology information in their inference process, while incorporating this information can partially compensate for the lack of reliable expression data. Here we develop a Bayesian group lasso with spike and slab priors to perform gene selection and estimation for nonparametric models. B-spline basis functions are used to capture the nonlinear relationships flexibly and penalties are used to avoid overfitting. Further, we incorporate the topology information into the Bayesian method as a prior. We present the application of our method on DREAM3 and DREAM4 datasets and two real biological datasets. The results show that our method performs better than existing methods and the topology information prior can improve the result.

  13. Bayesian networks in neuroscience: a survey.

    PubMed

    Bielza, Concha; Larrañaga, Pedro

    2014-01-01

    Bayesian networks are a type of probabilistic graphical models lie at the intersection between statistics and machine learning. They have been shown to be powerful tools to encode dependence relationships among the variables of a domain under uncertainty. Thanks to their generality, Bayesian networks can accommodate continuous and discrete variables, as well as temporal processes. In this paper we review Bayesian networks and how they can be learned automatically from data by means of structure learning algorithms. Also, we examine how a user can take advantage of these networks for reasoning by exact or approximate inference algorithms that propagate the given evidence through the graphical structure. Despite their applicability in many fields, they have been little used in neuroscience, where they have focused on specific problems, like functional connectivity analysis from neuroimaging data. Here we survey key research in neuroscience where Bayesian networks have been used with different aims: discover associations between variables, perform probabilistic reasoning over the model, and classify new observations with and without supervision. The networks are learned from data of any kind-morphological, electrophysiological, -omics and neuroimaging-, thereby broadening the scope-molecular, cellular, structural, functional, cognitive and medical- of the brain aspects to be studied.

  14. 5G: The Convergence of Wireless Communications.

    PubMed

    Chávez-Santiago, Raúl; Szydełko, Michał; Kliks, Adrian; Foukalas, Fotis; Haddad, Yoram; Nolan, Keith E; Kelly, Mark Y; Masonta, Moshe T; Balasingham, Ilangko

    As the rollout of 4G mobile communication networks takes place, representatives of industry and academia have started to look into the technological developments toward the next generation (5G). Several research projects involving key international mobile network operators, infrastructure manufacturers, and academic institutions, have been launched recently to set the technological foundations of 5G. However, the architecture of future 5G systems, their performance, and mobile services to be provided have not been clearly defined. In this paper, we put forth the vision for 5G as the convergence of evolved versions of current cellular networks with other complementary radio access technologies. Therefore, 5G may not be a single radio access interface but rather a "network of networks". Evidently, the seamless integration of a variety of air interfaces, protocols, and frequency bands, requires paradigm shifts in the way networks cooperate and complement each other to deliver data rates of several Gigabits per second with end-to-end latency of a few milliseconds. We provide an overview of the key radio technologies that will play a key role in the realization of this vision for the next generation of mobile communication networks. We also introduce some of the research challenges that need to be addressed.

  15. Bayesian networks in neuroscience: a survey

    PubMed Central

    Bielza, Concha; Larrañaga, Pedro

    2014-01-01

    Bayesian networks are a type of probabilistic graphical models lie at the intersection between statistics and machine learning. They have been shown to be powerful tools to encode dependence relationships among the variables of a domain under uncertainty. Thanks to their generality, Bayesian networks can accommodate continuous and discrete variables, as well as temporal processes. In this paper we review Bayesian networks and how they can be learned automatically from data by means of structure learning algorithms. Also, we examine how a user can take advantage of these networks for reasoning by exact or approximate inference algorithms that propagate the given evidence through the graphical structure. Despite their applicability in many fields, they have been little used in neuroscience, where they have focused on specific problems, like functional connectivity analysis from neuroimaging data. Here we survey key research in neuroscience where Bayesian networks have been used with different aims: discover associations between variables, perform probabilistic reasoning over the model, and classify new observations with and without supervision. The networks are learned from data of any kind–morphological, electrophysiological, -omics and neuroimaging–, thereby broadening the scope–molecular, cellular, structural, functional, cognitive and medical– of the brain aspects to be studied. PMID:25360109

  16. Objective Speech Quality Assessment Based on Payload Discrimination of Lost Packets for Cellular Phones in NGN Environment

    NASA Astrophysics Data System (ADS)

    Uemura, Satoshi; Fukumoto, Norihiro; Yamada, Hideaki; Nakamura, Hajime

    A feature of services provided in a Next Generation Network (NGN) is that the end-to-end quality is guaranteed. This is quite a challenging issue, given the considerable fluctuation in network conditions within a Fixed Mobile Convergence (FMC) network. Therefore, a novel approach, whereby a network node and a mobile terminal such as a cellular phone cooperate with each other to control service quality is essential. In order to achieve such cooperation, the mobile terminal needs to become more intelligent so it can estimate the service quality, including the user's perceptual quality, and notify the measurement result to the network node. Subsequently, the network node implements some kind of service control function, such as a resource and admission control function, based on the notification from the mobile terminal. In this paper, the role of the mobile terminal in such collaborative system is focused on. As a part of a QoS/QoE measurement system, we describe an objective speech quality assessment with payload discrimination of lost packets to measure the user's perceptual quality of VoIP. The proposed assessment is so simple that it can be implemented on a cellular phone. We therefore did this as part of the QoS/QoE measurement system. By using the implemented system, we can measure the user's perceptual quality of VoIP as well as the network QoS metrics, in terms of criteria such as packet loss rate, jitter and burstiness in real time.

  17. Combining the Finite Element Method with Structural Connectome-based Analysis for Modeling Neurotrauma: Connectome Neurotrauma Mechanics

    PubMed Central

    Kraft, Reuben H.; Mckee, Phillip Justin; Dagro, Amy M.; Grafton, Scott T.

    2012-01-01

    This article presents the integration of brain injury biomechanics and graph theoretical analysis of neuronal connections, or connectomics, to form a neurocomputational model that captures spatiotemporal characteristics of trauma. We relate localized mechanical brain damage predicted from biofidelic finite element simulations of the human head subjected to impact with degradation in the structural connectome for a single individual. The finite element model incorporates various length scales into the full head simulations by including anisotropic constitutive laws informed by diffusion tensor imaging. Coupling between the finite element analysis and network-based tools is established through experimentally-based cellular injury thresholds for white matter regions. Once edges are degraded, graph theoretical measures are computed on the “damaged” network. For a frontal impact, the simulations predict that the temporal and occipital regions undergo the most axonal strain and strain rate at short times (less than 24 hrs), which leads to cellular death initiation, which results in damage that shows dependence on angle of impact and underlying microstructure of brain tissue. The monotonic cellular death relationships predict a spatiotemporal change of structural damage. Interestingly, at 96 hrs post-impact, computations predict no network nodes were completely disconnected from the network, despite significant damage to network edges. At early times () network measures of global and local efficiency were degraded little; however, as time increased to 96 hrs the network properties were significantly reduced. In the future, this computational framework could help inform functional networks from physics-based structural brain biomechanics to obtain not only a biomechanics-based understanding of injury, but also neurophysiological insight. PMID:22915997

  18. APRON: A Cellular Processor Array Simulation and Hardware Design Tool

    NASA Astrophysics Data System (ADS)

    Barr, David R. W.; Dudek, Piotr

    2009-12-01

    We present a software environment for the efficient simulation of cellular processor arrays (CPAs). This software (APRON) is used to explore algorithms that are designed for massively parallel fine-grained processor arrays, topographic multilayer neural networks, vision chips with SIMD processor arrays, and related architectures. The software uses a highly optimised core combined with a flexible compiler to provide the user with tools for the design of new processor array hardware architectures and the emulation of existing devices. We present performance benchmarks for the software processor array implemented on standard commodity microprocessors. APRON can be configured to use additional processing hardware if necessary and can be used as a complete graphical user interface and development environment for new or existing CPA systems, allowing more users to develop algorithms for CPA systems.

  19. 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…

  20. 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

  1. Trans-species learning of cellular signaling systems with bimodal deep belief networks

    PubMed Central

    Chen, Lujia; Cai, Chunhui; Chen, Vicky; Lu, Xinghua

    2015-01-01

    Motivation: Model organisms play critical roles in biomedical research of human diseases and drug development. An imperative task is to translate information/knowledge acquired from model organisms to humans. In this study, we address a trans-species learning problem: predicting human cell responses to diverse stimuli, based on the responses of rat cells treated with the same stimuli. Results: We hypothesized that rat and human cells share a common signal-encoding mechanism but employ different proteins to transmit signals, and we developed a bimodal deep belief network and a semi-restricted bimodal deep belief network to represent the common encoding mechanism and perform trans-species learning. These ‘deep learning’ models include hierarchically organized latent variables capable of capturing the statistical structures in the observed proteomic data in a distributed fashion. The results show that the models significantly outperform two current state-of-the-art classification algorithms. Our study demonstrated the potential of using deep hierarchical models to simulate cellular signaling systems. Availability and implementation: The software is available at the following URL: http://pubreview.dbmi.pitt.edu/TransSpeciesDeepLearning/. The data are available through SBV IMPROVER website, https://www.sbvimprover.com/challenge-2/overview, upon publication of the report by the organizers. Contact: xinghua@pitt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25995230

  2. Trans-species learning of cellular signaling systems with bimodal deep belief networks.

    PubMed

    Chen, Lujia; Cai, Chunhui; Chen, Vicky; Lu, Xinghua

    2015-09-15

    Model organisms play critical roles in biomedical research of human diseases and drug development. An imperative task is to translate information/knowledge acquired from model organisms to humans. In this study, we address a trans-species learning problem: predicting human cell responses to diverse stimuli, based on the responses of rat cells treated with the same stimuli. We hypothesized that rat and human cells share a common signal-encoding mechanism but employ different proteins to transmit signals, and we developed a bimodal deep belief network and a semi-restricted bimodal deep belief network to represent the common encoding mechanism and perform trans-species learning. These 'deep learning' models include hierarchically organized latent variables capable of capturing the statistical structures in the observed proteomic data in a distributed fashion. The results show that the models significantly outperform two current state-of-the-art classification algorithms. Our study demonstrated the potential of using deep hierarchical models to simulate cellular signaling systems. The software is available at the following URL: http://pubreview.dbmi.pitt.edu/TransSpeciesDeepLearning/. The data are available through SBV IMPROVER website, https://www.sbvimprover.com/challenge-2/overview, upon publication of the report by the organizers. xinghua@pitt.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Cache-enabled small cell networks: modeling and tradeoffs.

    PubMed

    Baştuǧ, Ejder; Bennis, Mehdi; Kountouris, Marios; Debbah, Mérouane

    We consider a network model where small base stations (SBSs) have caching capabilities as a means to alleviate the backhaul load and satisfy users' demand. The SBSs are stochastically distributed over the plane according to a Poisson point process (PPP) and serve their users either (i) by bringing the content from the Internet through a finite rate backhaul or (ii) by serving them from the local caches. We derive closed-form expressions for the outage probability and the average delivery rate as a function of the signal-to-interference-plus-noise ratio (SINR), SBS density, target file bitrate, storage size, file length, and file popularity. We then analyze the impact of key operating parameters on the system performance. It is shown that a certain outage probability can be achieved either by increasing the number of base stations or the total storage size. Our results and analysis provide key insights into the deployment of cache-enabled small cell networks (SCNs), which are seen as a promising solution for future heterogeneous cellular networks.

  4. Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis.

    PubMed

    Frey, Olivier; Misun, Patrick M; Fluri, David A; Hengstler, Jan G; Hierlemann, Andreas

    2014-06-30

    Integration of multiple three-dimensional microtissues into microfluidic networks enables new insights in how different organs or tissues of an organism interact. Here, we present a platform that extends the hanging-drop technology, used for multi-cellular spheroid formation, to multifunctional complex microfluidic networks. Engineered as completely open, 'hanging' microfluidic system at the bottom of a substrate, the platform features high flexibility in microtissue arrangements and interconnections, while fabrication is simple and operation robust. Multiple spheroids of different cell types are formed in parallel on the same platform; the different tissues are then connected in physiological order for multi-tissue experiments through reconfiguration of the fluidic network. Liquid flow is precisely controlled through the hanging drops, which enable nutrient supply, substance dosage and inter-organ metabolic communication. The possibility to perform parallelized microtissue formation on the same chip that is subsequently used for complex multi-tissue experiments renders the developed platform a promising technology for 'body-on-a-chip'-related research.

  5. Pithy Review on Routing Protocols in Wireless Sensor Networks and Least Routing Time Opportunistic Technique in WSN

    NASA Astrophysics Data System (ADS)

    Salman Arafath, Mohammed; Rahman Khan, Khaleel Ur; Sunitha, K. V. N.

    2018-01-01

    Nowadays due to most of the telecommunication standard development organizations focusing on using device-to-device communication so that they can provide proximity-based services and add-on services on top of the available cellular infrastructure. An Oppnets and wireless sensor network play a prominent role here. Routing in these networks plays a significant role in fields such as traffic management, packet delivery etc. Routing is a prodigious research area with diverse unresolved issues. This paper firstly focuses on the importance of Opportunistic routing and its concept then focus is shifted to prime aspect i.e. on packet reception ratio which is one of the highest QoS Awareness parameters. This paper discusses the two important functions of routing in wireless sensor networks (WSN) namely route selection using least routing time algorithm (LRTA) and data forwarding using clustering technique. Finally, the simulation result reveals that LRTA performs relatively better than the existing system in terms of average packet reception ratio and connectivity.

  6. Modes of Interaction between Individuals Dominate the Topologies of Real World Networks

    PubMed Central

    Lee, Insuk; Kim, Eiru; Marcotte, Edward M.

    2015-01-01

    We find that the topologies of real world networks, such as those formed within human societies, by the Internet, or among cellular proteins, are dominated by the mode of the interactions considered among the individuals. Specifically, a major dichotomy in previously studied networks arises from modeling networks in terms of pairwise versus group tasks. The former often intrinsically give rise to scale-free, disassortative, hierarchical networks, whereas the latter often give rise to single- or broad-scale, assortative, nonhierarchical networks. These dependencies explain contrasting observations among previous topological analyses of real world complex systems. We also observe this trend in systems with natural hierarchies, in which alternate representations of the same networks, but which capture different levels of the hierarchy, manifest these signature topological differences. For example, in both the Internet and cellular proteomes, networks of lower-level system components (routers within domains or proteins within biological processes) are assortative and nonhierarchical, whereas networks of upper-level system components (internet domains or biological processes) are disassortative and hierarchical. Our results demonstrate that network topologies of complex systems must be interpreted in light of their hierarchical natures and interaction types. PMID:25793969

  7. 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.

  8. Evolution of a designless nanoparticle network into reconfigurable Boolean logic

    NASA Astrophysics Data System (ADS)

    Bose, S. K.; Lawrence, C. P.; Liu, Z.; Makarenko, K. S.; van Damme, R. M. J.; Broersma, H. J.; van der Wiel, W. G.

    2015-12-01

    Natural computers exploit the emergent properties and massive parallelism of interconnected networks of locally active components. Evolution has resulted in systems that compute quickly and that use energy efficiently, utilizing whatever physical properties are exploitable. Man-made computers, on the other hand, are based on circuits of functional units that follow given design rules. Hence, potentially exploitable physical processes, such as capacitive crosstalk, to solve a problem are left out. Until now, designless nanoscale networks of inanimate matter that exhibit robust computational functionality had not been realized. Here we artificially evolve the electrical properties of a disordered nanomaterials system (by optimizing the values of control voltages using a genetic algorithm) to perform computational tasks reconfigurably. We exploit the rich behaviour that emerges from interconnected metal nanoparticles, which act as strongly nonlinear single-electron transistors, and find that this nanoscale architecture can be configured in situ into any Boolean logic gate. This universal, reconfigurable gate would require about ten transistors in a conventional circuit. Our system meets the criteria for the physical realization of (cellular) neural networks: universality (arbitrary Boolean functions), compactness, robustness and evolvability, which implies scalability to perform more advanced tasks. Our evolutionary approach works around device-to-device variations and the accompanying uncertainties in performance. Moreover, it bears a great potential for more energy-efficient computation, and for solving problems that are very hard to tackle in conventional architectures.

  9. A network property necessary for concentration robustness

    NASA Astrophysics Data System (ADS)

    Eloundou-Mbebi, Jeanne M. O.; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

    2016-10-01

    Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications.

  10. A network property necessary for concentration robustness.

    PubMed

    Eloundou-Mbebi, Jeanne M O; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

    2016-10-19

    Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications.

  11. A network property necessary for concentration robustness

    PubMed Central

    Eloundou-Mbebi, Jeanne M. O.; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

    2016-01-01

    Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications. PMID:27759015

  12. The role of the interaction network in the emergence of diversity of behavior

    PubMed Central

    Tabacof, Pedro; Von Zuben, Fernando J.

    2017-01-01

    How can systems in which individuals’ inner workings are very similar to each other, as neural networks or ant colonies, produce so many qualitatively different behaviors, giving rise to roles and specialization? In this work, we bring new perspectives to this question by focusing on the underlying network that defines how individuals in these systems interact. We applied a genetic algorithm to optimize rules and connections of cellular automata in order to solve the density classification task, a classical problem used to study emergent behaviors in decentralized computational systems. The networks used were all generated by the introduction of shortcuts in an originally regular topology, following the small-world model. Even though all cells follow the exact same rules, we observed the existence of different classes of cells’ behaviors in the best cellular automata found—most cells were responsible for memory and others for integration of information. Through the analysis of structural measures and patterns of connections (motifs) in successful cellular automata, we observed that the distribution of shortcuts between distant regions and the speed in which a cell can gather information from different parts of the system seem to be the main factors for the specialization we observed, demonstrating how heterogeneity in a network can create heterogeneity of behavior. PMID:28234962

  13. Network Analysis of Epidermal Growth Factor Signaling Using Integrated Genomic, Proteomic and Phosphorylation Data

    PubMed Central

    Waters, Katrina M.; Liu, Tao; Quesenberry, Ryan D.; Willse, Alan R.; Bandyopadhyay, Somnath; Kathmann, Loel E.; Weber, Thomas J.; Smith, Richard D.; Wiley, H. Steven; Thrall, Brian D.

    2012-01-01

    To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF) using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response. PMID:22479638

  14. Attractor Structures of Signaling Networks: Consequences of Different Conformational Barcode Dynamics and Their Relations to Network-Based Drug Design.

    PubMed

    Szalay, Kristóf Z; Nussinov, Ruth; Csermely, Peter

    2014-06-01

    Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10 % noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Overload Control for Signaling Congestion of Machine Type Communications in 3GPP Networks

    PubMed Central

    Lu, Zhaoming; Pan, Qi; Wang, Luhan; Wen, Xiangming

    2016-01-01

    Because of the limited resources on radio access channels of third generation partnership projection (3GPP) network, one of the most challenging tasks posted by 3GPP cellular-based machine type communications (MTC) is congestion due to massive requests for connection to radio access network (RAN). In this paper, an overload control algorithm in 3GPP RAN is proposed, which proactively disperses the simultaneous access attempts in evenly distributed time window. Through periodic reservation strategy, massive access requests of MTC devices are dispersed in time, which reduces the probability of confliction of signaling. By the compensation and prediction mechanism, each device can communicate with MTC server with dynamic load of air interface. Numerical results prove that proposed method makes MTC applications friendly to 3GPP cellular network. PMID:27936011

  16. Overload Control for Signaling Congestion of Machine Type Communications in 3GPP Networks.

    PubMed

    Lu, Zhaoming; Pan, Qi; Wang, Luhan; Wen, Xiangming

    2016-01-01

    Because of the limited resources on radio access channels of third generation partnership projection (3GPP) network, one of the most challenging tasks posted by 3GPP cellular-based machine type communications (MTC) is congestion due to massive requests for connection to radio access network (RAN). In this paper, an overload control algorithm in 3GPP RAN is proposed, which proactively disperses the simultaneous access attempts in evenly distributed time window. Through periodic reservation strategy, massive access requests of MTC devices are dispersed in time, which reduces the probability of confliction of signaling. By the compensation and prediction mechanism, each device can communicate with MTC server with dynamic load of air interface. Numerical results prove that proposed method makes MTC applications friendly to 3GPP cellular network.

  17. Modeling formalisms in Systems Biology

    PubMed Central

    2011-01-01

    Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future. PMID:22141422

  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. Systematic identification of an integrative network module during senescence from time-series gene expression.

    PubMed

    Park, Chihyun; Yun, So Jeong; Ryu, Sung Jin; Lee, Soyoung; Lee, Young-Sam; Yoon, Youngmi; Park, Sang Chul

    2017-03-15

    Cellular senescence irreversibly arrests growth of human diploid cells. In addition, recent studies have indicated that senescence is a multi-step evolving process related to important complex biological processes. Most studies analyzed only the genes and their functions representing each senescence phase without considering gene-level interactions and continuously perturbed genes. It is necessary to reveal the genotypic mechanism inferred by affected genes and their interaction underlying the senescence process. We suggested a novel computational approach to identify an integrative network which profiles an underlying genotypic signature from time-series gene expression data. The relatively perturbed genes were selected for each time point based on the proposed scoring measure denominated as perturbation scores. Then, the selected genes were integrated with protein-protein interactions to construct time point specific network. From these constructed networks, the conserved edges across time point were extracted for the common network and statistical test was performed to demonstrate that the network could explain the phenotypic alteration. As a result, it was confirmed that the difference of average perturbation scores of common networks at both two time points could explain the phenotypic alteration. We also performed functional enrichment on the common network and identified high association with phenotypic alteration. Remarkably, we observed that the identified cell cycle specific common network played an important role in replicative senescence as a key regulator. Heretofore, the network analysis from time series gene expression data has been focused on what topological structure was changed over time point. Conversely, we focused on the conserved structure but its context was changed in course of time and showed it was available to explain the phenotypic changes. We expect that the proposed method will help to elucidate the biological mechanism unrevealed by the existing approaches.

  20. E3Net: a system for exploring E3-mediated regulatory networks of cellular functions.

    PubMed

    Han, Youngwoong; Lee, Hodong; Park, Jong C; Yi, Gwan-Su

    2012-04-01

    Ubiquitin-protein ligase (E3) is a key enzyme targeting specific substrates in diverse cellular processes for ubiquitination and degradation. The existing findings of substrate specificity of E3 are, however, scattered over a number of resources, making it difficult to study them together with an integrative view. Here we present E3Net, a web-based system that provides a comprehensive collection of available E3-substrate specificities and a systematic framework for the analysis of E3-mediated regulatory networks of diverse cellular functions. Currently, E3Net contains 2201 E3s and 4896 substrates in 427 organisms and 1671 E3-substrate specific relations between 493 E3s and 1277 substrates in 42 organisms, extracted mainly from MEDLINE abstracts and UniProt comments with an automatic text mining method and additional manual inspection and partly from high throughput experiment data and public ubiquitination databases. The significant functions and pathways of the extracted E3-specific substrate groups were identified from a functional enrichment analysis with 12 functional category resources for molecular functions, protein families, protein complexes, pathways, cellular processes, cellular localization, and diseases. E3Net includes interactive analysis and navigation tools that make it possible to build an integrative view of E3-substrate networks and their correlated functions with graphical illustrations and summarized descriptions. As a result, E3Net provides a comprehensive resource of E3s, substrates, and their functional implications summarized from the regulatory network structures of E3-specific substrate groups and their correlated functions. This resource will facilitate further in-depth investigation of ubiquitination-dependent regulatory mechanisms. E3Net is freely available online at http://pnet.kaist.ac.kr/e3net.

  1. Drug-therapy networks and the prediction of novel drug targets

    PubMed Central

    Spiro, Zoltan; Kovacs, Istvan A; Csermely, Peter

    2008-01-01

    A recent study in BMC Pharmacology presents a network of drugs and the therapies in which they are used. Network approaches open new ways of predicting novel drug targets and overcoming the cellular robustness that can prevent drugs from working. PMID:18710588

  2. Mobile Computing and Ubiquitous Networking: Concepts, Technologies and Challenges.

    ERIC Educational Resources Information Center

    Pierre, Samuel

    2001-01-01

    Analyzes concepts, technologies and challenges related to mobile computing and networking. Defines basic concepts of cellular systems. Describes the evolution of wireless technologies that constitute the foundations of mobile computing and ubiquitous networking. Presents characterization and issues of mobile computing. Analyzes economical and…

  3. Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior.

    PubMed

    Portugues, Ruben; Feierstein, Claudia E; Engert, Florian; Orger, Michael B

    2014-03-19

    Most behaviors, even simple innate reflexes, are mediated by circuits of neurons spanning areas throughout the brain. However, in most cases, the distribution and dynamics of firing patterns of these neurons during behavior are not known. We imaged activity, with cellular resolution, throughout the whole brains of zebrafish performing the optokinetic response. We found a sparse, broadly distributed network that has an elaborate but ordered pattern, with a bilaterally symmetrical organization. Activity patterns fell into distinct clusters reflecting sensory and motor processing. By correlating neuronal responses with an array of sensory and motor variables, we find that the network can be clearly divided into distinct functional modules. Comparing aligned data from multiple fish, we find that the spatiotemporal activity dynamics and functional organization are highly stereotyped across individuals. These experiments systematically reveal the functional architecture of neural circuits underlying a sensorimotor behavior in a vertebrate brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior

    PubMed Central

    Portugues, Ruben; Feierstein, Claudia E.; Engert, Florian; Orger, Michael B.

    2014-01-01

    Summary Most behaviors, even simple innate reflexes, are mediated by circuits of neurons spanning areas throughout the brain. However, in most cases, the distribution and dynamics of firing patterns of these neurons during behavior are not known. We imaged activity, with cellular resolution, throughout the whole brains of zebrafish performing the optokinetic response. We found a sparse, broadly distributed network that has an elaborate, but ordered, pattern, with a bilaterally symmetrical organization. Activity patterns fell into distinct clusters reflecting sensory and motor processing. By correlating neuronal responses with an array of sensory and motor variables, we find that the network can be clearly divided into distinct functional modules. Comparing aligned data from multiple fish, we find that the spatiotemporal activity dynamics and functional organization are highly stereotyped across individuals. These experiments reveal, for the first time in a vertebrate, the comprehensive functional architecture of the neural circuits underlying a sensorimotor behavior. PMID:24656252

  5. The BioPlex Network: A Systematic Exploration of the Human Interactome.

    PubMed

    Huttlin, Edward L; Ting, Lily; Bruckner, Raphael J; Gebreab, Fana; Gygi, Melanie P; Szpyt, John; Tam, Stanley; Zarraga, Gabriela; Colby, Greg; Baltier, Kurt; Dong, Rui; Guarani, Virginia; Vaites, Laura Pontano; Ordureau, Alban; Rad, Ramin; Erickson, Brian K; Wühr, Martin; Chick, Joel; Zhai, Bo; Kolippakkam, Deepak; Mintseris, Julian; Obar, Robert A; Harris, Tim; Artavanis-Tsakonas, Spyros; Sowa, Mathew E; De Camilli, Pietro; Paulo, Joao A; Harper, J Wade; Gygi, Steven P

    2015-07-16

    Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. Finally, BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. The BioPlex Network: A Systematic Exploration of the Human Interactome

    PubMed Central

    Huttlin, Edward L.; Ting, Lily; Bruckner, Raphael J.; Gebreab, Fana; Gygi, Melanie P.; Szpyt, John; Tam, Stanley; Zarraga, Gabriela; Colby, Greg; Baltier, Kurt; Dong, Rui; Guarani, Virginia; Vaites, Laura Pontano; Ordureau, Alban; Rad, Ramin; Erickson, Brian K.; Wühr, Martin; Chick, Joel; Zhai, Bo; Kolippakkam, Deepak; Mintseris, Julian; Obar, Robert A.; Harris, Tim; Artavanis-Tsakonas, Spyros; Sowa, Mathew E.; DeCamilli, Pietro; Paulo, Joao A.; Harper, J. Wade; Gygi, Steven P.

    2015-01-01

    SUMMARY Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally-related proteins. Finally, BioPlex, in combination with other approaches can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial Amyotrophic Lateral Sclerosis perturb a defined community of interactors. PMID:26186194

  7. Network Analysis of Rodent Transcriptomes in Spaceflight

    NASA Technical Reports Server (NTRS)

    Ramachandran, Maya; Fogle, Homer; Costes, Sylvain

    2017-01-01

    Network analysis methods leverage prior knowledge of cellular systems and the statistical and conceptual relationships between analyte measurements to determine gene connectivity. Correlation and conditional metrics are used to infer a network topology and provide a systems-level context for cellular responses. Integration across multiple experimental conditions and omics domains can reveal the regulatory mechanisms that underlie gene expression. GeneLab has assembled rich multi-omic (transcriptomics, proteomics, epigenomics, and epitranscriptomics) datasets for multiple murine tissues from the Rodent Research 1 (RR-1) experiment. RR-1 assesses the impact of 37 days of spaceflight on gene expression across a variety of tissue types, such as adrenal glands, quadriceps, gastrocnemius, tibalius anterior, extensor digitorum longus, soleus, eye, and kidney. Network analysis is particularly useful for RR-1 -omics datasets because it reinforces subtle relationships that may be overlooked in isolated analyses and subdues confounding factors. Our objective is to use network analysis to determine potential target nodes for therapeutic intervention and identify similarities with existing disease models. Multiple network algorithms are used for a higher confidence consensus.

  8. Broadband network selection issues

    NASA Astrophysics Data System (ADS)

    Leimer, Michael E.

    1996-01-01

    Selecting the best network for a given cable or telephone company provider is not as obvious as it appears. The cost and performance trades between Hybrid Fiber Coax (HFC), Fiber to the Curb (FTTC) and Asymmetric Digital Subscriber Line networks lead to very different choices based on the existing plant and the expected interactive subscriber usage model. This paper presents some of the issues and trades that drive network selection. The majority of the Interactive Television trials currently underway or planned are based on HFC networks. As a throw away market trial or a short term strategic incursion into a cable market, HFC may make sense. In the long run, if interactive services see high demand, HFC costs per node and an ever shrinking neighborhood node size to service large numbers of subscribers make FTTC appear attractive. For example, thirty-three 64-QAM modulators are required to fill the 550 MHz to 750 MHz spectrum with compressed video streams in 6 MHz channels. This large amount of hardware at each node drives not only initial build-out costs, but operations and maintenance costs as well. FTTC, with its potential for digitally switching large amounts of bandwidth to an given home, offers the potential to grow with the interactive subscriber base with less downstream cost. Integrated telephony on these networks is an issue that appears to be an afterthought for most of the networks being selected at the present time. The major players seem to be videocentric and include telephony as a simple add-on later. This may be a reasonable view point for the telephone companies that plan to leave their existing phone networks untouched. However, a phone company planning a network upgrade or a cable company jumping into the telephony business needs to carefully weigh the cost and performance issues of the various network choices. Each network type provides varying capability in both upstream and downstream bandwidth for voice channels. The noise characteristics 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.

  9. Mobile visual communications and displays

    NASA Astrophysics Data System (ADS)

    Valliath, George T.

    2004-09-01

    The different types of mobile visual communication modes and the types of displays needed in cellular handsets are explored. The well-known 2-way video conferencing is only one of the possible modes. Some modes are already supported on current handsets while others need the arrival of advanced network capabilities to be supported. Displays for devices that support these visual communication modes need to deliver the required visual experience. Over the last 20 years the display has grown in size while the rest of the handset has shrunk. However, the display is still not large enough - the processor performance and network capabilities continue to outstrip the display ability. This makes the display a bottleneck. This paper will explore potential solutions to a small large image on a small handset.

  10. Integration between terrestrial-based and satellite-based land mobile communications systems

    NASA Technical Reports Server (NTRS)

    Arcidiancono, Antonio

    1990-01-01

    A survey is given of several approaches to improving the performance and marketability of mobile satellite systems (MSS). The provision of voice/data services in the future regional European Land Mobile Satellite System (LMSS), network integration between the Digital Cellular Mobile System (GSM) and LMSS, the identification of critical areas for the implementation of integrated GSM/LMSS areas, space segment scenarios, LMSS for digital trunked private mobile radio (PMR) services, and code division multiple access (CDMA) techniques for a terrestrial/satellite system are covered.

  11. CellNet: network biology applied to stem cell engineering.

    PubMed

    Cahan, Patrick; Li, Hu; Morris, Samantha A; Lummertz da Rocha, Edroaldo; Daley, George Q; Collins, James J

    2014-08-14

    Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Proteome-Scale Human Interactomics.

    PubMed

    Luck, Katja; Sheynkman, Gloria M; Zhang, Ivy; Vidal, Marc

    2017-05-01

    Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Reverse engineering and analysis of large genome-scale gene networks

    PubMed Central

    Aluru, Maneesha; Zola, Jaroslaw; Nettleton, Dan; Aluru, Srinivas

    2013-01-01

    Reverse engineering the whole-genome networks of complex multicellular organisms continues to remain a challenge. While simpler models easily scale to large number of genes and gene expression datasets, more accurate models are compute intensive limiting their scale of applicability. To enable fast and accurate reconstruction of large networks, we developed Tool for Inferring Network of Genes (TINGe), a parallel mutual information (MI)-based program. The novel features of our approach include: (i) B-spline-based formulation for linear-time computation of MI, (ii) a novel algorithm for direct permutation testing and (iii) development of parallel algorithms to reduce run-time and facilitate construction of large networks. We assess the quality of our method by comparison with ARACNe (Algorithm for the Reconstruction of Accurate Cellular Networks) and GeneNet and demonstrate its unique capability by reverse engineering the whole-genome network of Arabidopsis thaliana from 3137 Affymetrix ATH1 GeneChips in just 9 min on a 1024-core cluster. We further report on the development of a new software Gene Network Analyzer (GeNA) for extracting context-specific subnetworks from a given set of seed genes. Using TINGe and GeNA, we performed analysis of 241 Arabidopsis AraCyc 8.0 pathways, and the results are made available through the web. PMID:23042249

  14. Dual phosphoproteomics and chemical proteomics analysis of erlotinib and gefitinib interference in acute myeloid leukemia cells.

    PubMed

    Weber, Christoph; Schreiber, Thiemo B; Daub, Henrik

    2012-02-02

    Small molecule inhibitors of protein kinases have emerged as a major class of therapeutic agents for the treatment of hematological malignancies. Both in vitro studies and patient case reports suggest therapeutic potential of the clinical kinase inhibitors erlotinib and gefitinib in acute myeloid leukemia (AML). The drugs' cellular modes of action in AML warrant further investigation as their primary therapeutic target, the epidermal growth factor receptor, is not expressed. We therefore performed SILAC-based quantitative mass spectrometry analyses to a depth of 10,975 distinct phosphorylation sites to characterize the phosphoproteome of KG1 AML cells and its regulation upon erlotinib and gefitinib treatment. Less than 50 site-specific phosphorylations changed significantly, indicating rather specific interference with AML cell signaling. Many drug-induced changes occurred within a network of tyrosine phosphorylated proteins that included Src family kinases (SFKs) and the tyrosine kinases Btk and Syk. We further performed quantitative chemical proteomics in KG1 cell extracts and identified SFKs and Btk as direct cellular targets of both erlotinib and gefitinib. Taken together, our data suggest that cellular perturbation of SFKs and/or Btk translates into rather specific signal transduction inhibition, which in turn contributes to the antileukemic activity of erlotinib and gefitinib in AML. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Collective dynamics in heterogeneous networks of neuronal cellular automata

    NASA Astrophysics Data System (ADS)

    Manchanda, Kaustubh; Bose, Amitabha; Ramaswamy, Ramakrishna

    2017-12-01

    We examine the collective dynamics of heterogeneous random networks of model neuronal cellular automata. Each automaton has b active states, a single silent state and r - b - 1 refractory states, and can show 'spiking' or 'bursting' behavior, depending on the values of b. We show that phase transitions that occur in the dynamical activity can be related to phase transitions in the structure of Erdõs-Rényi graphs as a function of edge probability. Different forms of heterogeneity allow distinct structural phase transitions to become relevant. We also show that the dynamics on the network can be described by a semi-annealed process and, as a result, can be related to the Boolean Lyapunov exponent.

  16. Evidence for network evolution in an arabidopsis interactome map

    USDA-ARS?s Scientific Manuscript database

    Plants have unique features that evolved in response to their environments and ecosystems. A full account of the complex cellular networks that underlie plant-specific functions is still missing. We describe a proteome-wide binary protein-protein interaction map for the interactome network of the pl...

  17. Dynamic Spectrum Access for Internet of Things Service in Cognitive Radio-Enabled LPWANs

    PubMed Central

    Moon, Bongkyo

    2017-01-01

    In this paper, we focus on a dynamic spectrum access strategy for Internet of Things (IoT) applications in two types of radio systems: cellular networks and cognitive radio-enabled low power wide area networks (CR-LPWANs). The spectrum channel contention between the licensed cellular networks and the unlicensed CR-LPWANs, which work with them, only takes place within the cellular radio spectrum range. Our aim is to maximize the spectrum capacity for the unlicensed users while ensuring that it never interferes with the licensed network. Therefore, in this paper we propose a dynamic spectrum access strategy for CR-LPWANs operating in both licensed and unlicensed bands. The simulation and the numerical analysis by using a matrix geometric approach for the strategy are presented. Finally, we obtain the blocking probability of the licensed users, the mean dwell time of the unlicensed user, and the total carried traffic and combined service quality for the licensed and unlicensed users. The results show that the proposed strategy can maximize the spectrum capacity for the unlicensed users using IoT applications as well as keep the service quality of the licensed users independent of them. PMID:29206215

  18. Dynamic Spectrum Access for Internet of Things Service in Cognitive Radio-Enabled LPWANs.

    PubMed

    Moon, Bongkyo

    2017-12-05

    In this paper, we focus on a dynamic spectrum access strategy for Internet of Things (IoT) applications in two types of radio systems: cellular networks and cognitive radio-enabled low power wide area networks (CR-LPWANs). The spectrum channel contention between the licensed cellular networks and the unlicensed CR-LPWANs, which work with them, only takes place within the cellular radio spectrum range. Our aim is to maximize the spectrum capacity for the unlicensed users while ensuring that it never interferes with the licensed network. Therefore, in this paper we propose a dynamic spectrum access strategy for CR-LPWANs operating in both licensed and unlicensed bands. The simulation and the numerical analysis by using a matrix geometric approach for the strategy are presented. Finally, we obtain the blocking probability of the licensed users, the mean dwell time of the unlicensed user, and the total carried traffic and combined service quality for the licensed and unlicensed users. The results show that the proposed strategy can maximize the spectrum capacity for the unlicensed users using IoT applications as well as keep the service quality of the licensed users independent of them.

  19. Plectin isoforms as organizers of intermediate filament cytoarchitecture

    PubMed Central

    Winter, Lilli

    2011-01-01

    Intermediate filaments (IFs) form cytoplamic and nuclear networks that provide cells with mechanical strength. Perturbation of this structural support causes cell and tissue fragility and accounts for a number of human genetic diseases. In recent years, important additional roles, nonmechanical in nature, were ascribed to IFs, including regulation of signaling pathways that control survival and growth of the cells, and vectorial processes such as protein targeting in polarized cellular settings. The cytolinker protein plectin anchors IF networks to junctional complexes, the nuclear envelope and cytoplasmic organelles and it mediates their cross talk with the actin and tubulin cytoskeleton. These functions empower plectin to wield significant influence over IF network cytoarchitecture. Moreover, the unusual diversity of plectin isoforms with different N termini and a common IF-binding (C-terminal) domain enables these isoforms to specifically associate with and thereby bridge IF networks to distinct cellular structures. Here we review the evidence for IF cytoarchitecture being controlled by specific plectin isoforms in different cell systems, including fibroblasts, endothelial cells, lens fibers, lymphocytes, myocytes, keratinocytes, neurons and astrocytes, and discuss what impact the absence of these isoforms has on IF cytoarchitecture-dependent cellular functions. PMID:21866256

  20. Capacity-Delay Trade-Off in Collaborative Hybrid Ad-Hoc Networks with Coverage Sensing.

    PubMed

    Chen, Lingyu; Luo, Wenbin; Liu, Chen; Hong, Xuemin; Shi, Jianghong

    2017-01-26

    The integration of ad hoc device-to-device (D2D) communications and open-access small cells can result in a networking paradigm called hybrid the ad hoc network, which is particularly promising in delivering delay-tolerant data. The capacity-delay performance of hybrid ad hoc networks has been studied extensively under a popular framework called scaling law analysis. These studies, however, do not take into account aspects of interference accumulation and queueing delay and, therefore, may lead to over-optimistic results. Moreover, focusing on the average measures, existing works fail to give finer-grained insights into the distribution of delays. This paper proposes an alternative analytical framework based on queueing theoretic models and physical interference models. We apply this framework to study the capacity-delay performance of a collaborative cellular D2D network with coverage sensing and two-hop relay. The new framework allows us to fully characterize the delay distribution in the transform domain and pinpoint the impacts of coverage sensing, user and base station densities, transmit power, user mobility and packet size on the capacity-delay trade-off. We show that under the condition of queueing equilibrium, the maximum throughput capacity per device saturates to an upper bound of 0.7239 λ b / λ u bits/s/Hz, where λ b and λ u are the densities of base stations and mobile users, respectively.

  1. Capacity-Delay Trade-Off in Collaborative Hybrid Ad-Hoc Networks with Coverage Sensing

    PubMed Central

    Chen, Lingyu; Luo, Wenbin; Liu, Chen; Hong, Xuemin; Shi, Jianghong

    2017-01-01

    The integration of ad hoc device-to-device (D2D) communications and open-access small cells can result in a networking paradigm called hybrid the ad hoc network, which is particularly promising in delivering delay-tolerant data. The capacity-delay performance of hybrid ad hoc networks has been studied extensively under a popular framework called scaling law analysis. These studies, however, do not take into account aspects of interference accumulation and queueing delay and, therefore, may lead to over-optimistic results. Moreover, focusing on the average measures, existing works fail to give finer-grained insights into the distribution of delays. This paper proposes an alternative analytical framework based on queueing theoretic models and physical interference models. We apply this framework to study the capacity-delay performance of a collaborative cellular D2D network with coverage sensing and two-hop relay. The new framework allows us to fully characterize the delay distribution in the transform domain and pinpoint the impacts of coverage sensing, user and base station densities, transmit power, user mobility and packet size on the capacity-delay trade-off. We show that under the condition of queueing equilibrium, the maximum throughput capacity per device saturates to an upper bound of 0.7239 λb/λu bits/s/Hz, where λb and λu are the densities of base stations and mobile users, respectively. PMID:28134769

  2. 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.

  3. RAID: a comprehensive resource for human RNA-associated (RNA–RNA/RNA–protein) interaction

    PubMed Central

    Zhang, Xiaomeng; Wu, Deng; Chen, Liqun; Li, Xiang; Yang, Jinxurong; Fan, Dandan; Dong, Tingting; Liu, Mingyue; Tan, Puwen; Xu, Jintian; Yi, Ying; Wang, Yuting; Zou, Hua; Hu, Yongfei; Fan, Kaili; Kang, Juanjuan; Huang, Yan; Miao, Zhengqiang; Bi, Miaoman; Jin, Nana; Li, Kongning; Li, Xia; Xu, Jianzhen; Wang, Dong

    2014-01-01

    Transcriptomic analyses have revealed an unexpected complexity in the eukaryote transcriptome, which includes not only protein-coding transcripts but also an expanding catalog of noncoding RNAs (ncRNAs). Diverse coding and noncoding RNAs (ncRNAs) perform functions through interaction with each other in various cellular processes. In this project, we have developed RAID (http://www.rna-society.org/raid), an RNA-associated (RNA–RNA/RNA–protein) interaction database. RAID intends to provide the scientific community with all-in-one resources for efficient browsing and extraction of the RNA-associated interactions in human. This version of RAID contains more than 6100 RNA-associated interactions obtained by manually reviewing more than 2100 published papers, including 4493 RNA–RNA interactions and 1619 RNA–protein interactions. Each entry contains detailed information on an RNA-associated interaction, including RAID ID, RNA/protein symbol, RNA/protein categories, validated method, expressing tissue, literature references (Pubmed IDs), and detailed functional description. Users can query, browse, analyze, and manipulate RNA-associated (RNA–RNA/RNA–protein) interaction. RAID provides a comprehensive resource of human RNA-associated (RNA–RNA/RNA–protein) interaction network. Furthermore, this resource will help in uncovering the generic organizing principles of cellular function network. PMID:24803509

  4. Investigation of OSL signal of resistors from mobile phones for accidental dosimetry

    NASA Astrophysics Data System (ADS)

    Mrozik, A.; Marczewska, B.; Bilski, P.; Gieszczyk, W.

    2014-12-01

    Resistors from mobile phones, usually located near the human body, are considered as individual dosimeters of ionizing radiation in emergency situations. The resistors contain Al2O3, which is optically stimulated luminescence (OSL) material sensitive to ionizing radiation. This work is focused on determination of dose homogeneity within a mobile phones which was carried out by OSL measurements of resistors placed in different parts inside the mobile phone. Separate, commercially available resistors, similar in the shape and size to the resistors from circuit board of the studied mobile phone, were situated in different locations inside it. The irradiations were performed in uniform 60Co and 137Cs radiation fields, with the mobile phones connected and not connected to the cellular network. The dose decrease of 9% was measured for original resistors situated between layer of copper-clad laminate and battery, in comparison to the dose at the front of the phone. The resistors showed the lower signal when the mobile phone was connected to the cellular network, due to higher temperature inside the housing. The profile of fading was investigated within 3 month period for resistors irradiated with 1 Gy of gamma rays to estimate of the fading coefficient.

  5. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kuruganti, Phani Teja

    The smart grid is a combined process of revitalizing the traditional power grid applications and introducing new applications to improve the efficiency of power generation, transmission and distribution. This can be achieved by leveraging advanced communication and networking technologies. Therefore the selection of the appropriate communication technology for different smart grid applications has been debated a lot in the recent past. After comparing different possible technologies, a recent research study has arrived at a conclusion that the 3G cellular technology is the right choice for distribution side smart grid applications like smart metering, advanced distribution automation and demand response managementmore » system. In this paper, we argue that the current 3G/4G cellular technologies are not an appropriate choice for smart grid distribution applications and propose a Hybrid Spread Spectrum (HSS) based Advanced Metering Infrastructure (AMI) as one of the alternatives to 3G/4G technologies. We present a preliminary PHY and MAC layer design of a HSS based AMI network and evaluate their performance using matlab and NS2 simulations. Also, we propose a time hierarchical scheme that can significantly reduce the volume of random access traffic generated during blackouts and the delay in power outage reporting.« less

  6. Encapsulating Networks of Droplet Interface Bilayers in a Thermoreversible Organogel.

    PubMed

    Challita, Elio J; Najem, Joseph S; Monroe, Rachel; Leo, Donald J; Freeman, Eric C

    2018-04-24

    The development of membrane-based materials that exhibit the range and robustness of autonomic functions found in biological systems remains elusive. Droplet interface bilayers (DIBs) have been proposed as building blocks for such materials, owing to their simplicity, geometry, and capability for replicating cellular phenomena. Similar to how individual cells operate together to perform complex tasks and functions in tissues, networks of functionalized DIBs have been assembled in modular/scalable networks. Here we present the printing of different configurations of picoliter aqueous droplets in a bath of thermoreversible organogel consisting of hexadecane and SEBS triblock copolymers. The droplets are connected by means of lipid bilayers, creating a network of aqueous subcompartments capable of communicating and hosting various types of chemicals and biomolecules. Upon cooling, the encapsulating organogel solidifies to form self-supported liquid-in-gel, tissue-like materials that are robust and durable. To test the biomolecular networks, we functionalized the network with alamethicin peptides and alpha-hemolysin (αHL) channels. Both channels responded to external voltage inputs, indicating the assembly process does not damage the biomolecules. Moreover, we show that the membrane properties may be regulated through the deformation of the surrounding gel.

  7. Identification and Analyses of AUX-IAA target genes controlling multiple pathways in developing fiber cells of Gossypium hirsutum L

    PubMed Central

    Nigam, Deepti; Sawant, Samir V

    2013-01-01

    Technological development led to an increased interest in systems biological approaches in plants to characterize developmental mechanism and candidate genes relevant to specific tissue or cell morphology. AUX-IAA proteins are important plant-specific putative transcription factors. There are several reports on physiological response of this family in Arabidopsis but in cotton fiber the transcriptional network through which AUX-IAA regulated its target genes is still unknown. in-silico modelling of cotton fiber development specific gene expression data (108 microarrays and 22,737 genes) using Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) reveals 3690 putative AUX-IAA target genes of which 139 genes were known to be AUX-IAA co-regulated within Arabidopsis. Further AUX-IAA targeted gene regulatory network (GRN) had substantial impact on the transcriptional dynamics of cotton fiber, as showed by, altered TF networks, and Gene Ontology (GO) biological processes and metabolic pathway associated with its target genes. Analysis of the AUX-IAA-correlated gene network reveals multiple functions for AUX-IAA target genes such as unidimensional cell growth, cellular nitrogen compound metabolic process, nucleosome organization, DNA-protein complex and process related to cell wall. These candidate networks/pathways have a variety of profound impacts on such cellular functions as stress response, cell proliferation, and cell differentiation. While these functions are fairly broad, their underlying TF networks may provide a global view of AUX-IAA regulated gene expression and a GRN that guides future studies in understanding role of AUX-IAA box protein and its targets regulating fiber development. PMID:24497725

  8. ProteoLens: a visual analytic tool for multi-scale database-driven biological network data mining.

    PubMed

    Huan, Tianxiao; Sivachenko, Andrey Y; Harrison, Scott H; Chen, Jake Y

    2008-08-12

    New systems biology studies require researchers to understand how interplay among myriads of biomolecular entities is orchestrated in order to achieve high-level cellular and physiological functions. Many software tools have been developed in the past decade to help researchers visually navigate large networks of biomolecular interactions with built-in template-based query capabilities. To further advance researchers' ability to interrogate global physiological states of cells through multi-scale visual network explorations, new visualization software tools still need to be developed to empower the analysis. A robust visual data analysis platform driven by database management systems to perform bi-directional data processing-to-visualizations with declarative querying capabilities is needed. We developed ProteoLens as a JAVA-based visual analytic software tool for creating, annotating and exploring multi-scale biological networks. It supports direct database connectivity to either Oracle or PostgreSQL database tables/views, on which SQL statements using both Data Definition Languages (DDL) and Data Manipulation languages (DML) may be specified. The robust query languages embedded directly within the visualization software help users to bring their network data into a visualization context for annotation and exploration. ProteoLens supports graph/network represented data in standard Graph Modeling Language (GML) formats, and this enables interoperation with a wide range of other visual layout tools. The architectural design of ProteoLens enables the de-coupling of complex network data visualization tasks into two distinct phases: 1) creating network data association rules, which are mapping rules between network node IDs or edge IDs and data attributes such as functional annotations, expression levels, scores, synonyms, descriptions etc; 2) applying network data association rules to build the network and perform the visual annotation of graph nodes and edges according to associated data values. We demonstrated the advantages of these new capabilities through three biological network visualization case studies: human disease association network, drug-target interaction network and protein-peptide mapping network. The architectural design of ProteoLens makes it suitable for bioinformatics expert data analysts who are experienced with relational database management to perform large-scale integrated network visual explorations. ProteoLens is a promising visual analytic platform that will facilitate knowledge discoveries in future network and systems biology studies.

  9. 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 behavior as in cancer metastasis. In addition to stiffness, the local geometry or topography of the surface has been shown to modulate the movement, morphology, and cytoskeletal organization of cells. However, the effect of topography on fluctuations of intracellular structures, which arise from motor driven activity on a viscoelastic actin network are not known. I have used nanofabricated substrates with parallel ridges to show that the cell shape, the actin cytoskeleton and focal adhesions all align along the direction of the ridges, exhibiting a biphasic dependence on the spacing between ridges. I further demonstrated that palladin bands along actin stress fibers undergo a complex diffusive motion with velocities aligned along the direction of ridges. These results provide insight into the mechanisms of cellular mechanosensing of the environment, suggesting a complex interplay between the actin cytoskeleton and cellular adhesions in coordinating cellular response to surface topography. Overall, this work has advanced our understanding of mechanisms that govern cellular responses to their physical environment.

  10. A virus or more in (nearly) every cell: ubiquitous networks of virus-host interactions in extreme environments.

    PubMed

    Munson-McGee, Jacob H; Peng, Shengyun; Dewerff, Samantha; Stepanauskas, Ramunas; Whitaker, Rachel J; Weitz, Joshua S; Young, Mark J

    2018-06-01

    The application of viral and cellular metagenomics to natural environments has expanded our understanding of the structure, functioning, and diversity of microbial and viral communities. The high diversity of many communities, e.g., soils, surface ocean waters, and animal-associated microbiomes, make it difficult to establish virus-host associations at the single cell (rather than population) level, assign cellular hosts, or determine the extent of viral host range from metagenomics studies alone. Here, we combine single-cell sequencing with environmental metagenomics to characterize the structure of virus-host associations in a Yellowstone National Park (YNP) hot spring microbial community. Leveraging the relatively low diversity of the YNP environment, we are able to overlay evidence at the single-cell level with contextualized viral and cellular community structure. Combining evidence from hexanucelotide analysis, single cell read mapping, network-based analytics, and CRISPR-based inference, we conservatively estimate that >60% of cells contain at least one virus type and a majority of these cells contain two or more virus types. Of the detected virus types, nearly 50% were found in more than 2 cellular clades, indicative of a broad host range. The new lens provided by the combination of metaviromics and single-cell genomics reveals a network of virus-host interactions in extreme environments, provides evidence that extensive virus-host associations are common, and further expands the unseen impact of viruses on cellular life.

  11. Intercellular communication via gap junctions affected by mechanical load in the bovine annulus fibrosus.

    PubMed

    Desrochers, Jane; Duncan, Neil A

    2014-01-01

    Cells in the intervertebral disc, as in other connective tissues including tendon, ligament and bone, form interconnected cellular networks that are linked via functional gap junctions. These cellular networks may be necessary to affect a coordinated response to mechanical and environmental stimuli. Using confocal microscopy with fluorescence recovery after photobleaching methods, we explored the in situ strain environment of the outer annulus of an intact bovine disc and the effect of high-level flexion on gap junction signalling. The in situ strain environment in the extracellular matrix of the outer annulus under high flexion load was observed to be non-uniform with the extensive cellular processes remaining crimped sometimes at flexion angles greater than 25°. A significant transient disruption of intercellular communication via functional gap junctions was measured after 10 and 20 min under high flexion load. This study illustrates that in healthy annulus fibrosus tissue, high mechanical loads can impede the functioning of the gap junctions. Future studies will explore more complex loading conditions to determine whether losses in intercellular communication can be permanent and whether gap junctions in aged and degenerated tissues become more susceptible to load. The current research suggests that cellular structures such as gap junctions and intercellular networks, as well as other cell-cell and cell-matrix interconnections, need to be considered in computational models in order to fully understand how macroscale mechanical signals are transmitted across scales to the microscale and ultimately into a cellular biosynthetic response in collagenous tissues.

  12. Enhanced Communication Network Solution for Positive Train Control Implementation

    NASA Technical Reports Server (NTRS)

    Fatehi, M. T.; Simon, J.; Chang, W.; Chow, E. T.; Burleigh, S. C.

    2011-01-01

    The commuter and freight railroad industry is required to implement Positive Train Control (PTC) by 2015 (2012 for Metrolink), a challenging network communications problem. This paper will discuss present technologies developed by the National Aeronautics and Space Administration (NASA) to overcome comparable communication challenges encountered in deep space mission operations. PTC will be based on a new cellular wireless packet Internet Protocol (IP) network. However, ensuring reliability in such a network is difficult due to the "dead zones" and transient disruptions we commonly experience when we lose calls in commercial cellular networks. These disruptions make it difficult to meet PTC s stringent reliability (99.999%) and safety requirements, deployment deadlines, and budget. This paper proposes innovative solutions based on space-proven technologies that would help meet these challenges: (1) Delay Tolerant Networking (DTN) technology, designed for use in resource-constrained, embedded systems and currently in use on the International Space Station, enables reliable communication over networks in which timely data acknowledgments might not be possible due to transient link outages. (2) Policy-Based Management (PBM) provides dynamic management capabilities, allowing vital data to be exchanged selectively (with priority) by utilizing alternative communication resources. The resulting network may help railroads implement PTC faster, cheaper, and more reliably.

  13. A Reinforcement Sensor Embedded Vertical Handoff Controller for Vehicular Heterogeneous Wireless Networks

    PubMed Central

    Li, Limin; Xu, Yubin; Soong, Boon-Hee; Ma, Lin

    2013-01-01

    Vehicular communication platforms that provide real-time access to wireless networks have drawn more and more attention in recent years. IEEE 802.11p is the main radio access technology that supports communication for high mobility terminals, however, due to its limited coverage, IEEE 802.11p is usually deployed by coupling with cellular networks to achieve seamless mobility. In a heterogeneous cellular/802.11p network, vehicular communication is characterized by its short time span in association with a wireless local area network (WLAN). Moreover, for the media access control (MAC) scheme used for WLAN, the network throughput dramatically decreases with increasing user quantity. In response to these compelling problems, we propose a reinforcement sensor (RFS) embedded vertical handoff control strategy to support mobility management. The RFS has online learning capability and can provide optimal handoff decisions in an adaptive fashion without prior knowledge. The algorithm integrates considerations including vehicular mobility, traffic load, handoff latency, and network status. Simulation results verify that the proposed algorithm can adaptively adjust the handoff strategy, allowing users to stay connected to the best network. Furthermore, the algorithm can ensure that RSUs are adequate, thereby guaranteeing a high quality user experience. PMID:24193101

  14. Interwoven Aligned Conductive Nanofiber Yarn/Hydrogel Composite Scaffolds for Engineered 3D Cardiac Anisotropy.

    PubMed

    Wu, Yaobin; Wang, Ling; Guo, Baolin; Ma, Peter X

    2017-06-27

    Mimicking the anisotropic cardiac structure and guiding 3D cellular orientation play a critical role in designing scaffolds for cardiac tissue regeneration. Significant advances have been achieved to control cellular alignment and elongation, but it remains an ongoing challenge for engineering 3D cardiac anisotropy using these approaches. Here, we present a 3D hybrid scaffold based on aligned conductive nanofiber yarns network (NFYs-NET, composition: polycaprolactone, silk fibroin, and carbon nanotubes) within a hydrogel shell for mimicking the native cardiac tissue structure, and further demonstrate their great potential for engineering 3D cardiac anisotropy for cardiac tissue engineering. The NFYs-NET structures are shown to control cellular orientation and enhance cardiomyocytes (CMs) maturation. 3D hybrid scaffolds were then fabricated by encapsulating NFYs-NET layers within hydrogel shell, and these 3D scaffolds performed the ability to promote aligned and elongated CMs maturation on each layer and individually control cellular orientation on different layers in a 3D environment. Furthermore, endothelialized myocardium was constructed by using this hybrid strategy via the coculture of CMs on NFYs-NET layer and endothelial cells within hydrogel shell. Therefore, these 3D hybrid scaffolds, containing NFYs-NET layer inducing cellular orientation, maturation, and anisotropy and hydrogel shell providing a suitable 3D environment for endothelialization, has great potential in engineering 3D cardiac anisotropy.

  15. Linear matrix inequality approach to exponential synchronization of a class of chaotic neural networks with time-varying delays

    NASA Astrophysics Data System (ADS)

    Wu, Wei; Cui, Bao-Tong

    2007-07-01

    In this paper, a synchronization scheme for a class of chaotic neural networks with time-varying delays is presented. This class of chaotic neural networks covers several well-known neural networks, such as Hopfield neural networks, cellular neural networks, and bidirectional associative memory networks. The obtained criteria are expressed in terms of linear matrix inequalities, thus they can be efficiently verified. A comparison between our results and the previous results shows that our results are less restrictive.

  16. 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...

  17. Attractor Metabolic Networks

    PubMed Central

    De la Fuente, Ildefonso M.; Cortes, Jesus M.; Pelta, David A.; Veguillas, Juan

    2013-01-01

    Background The experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a Systemic Metabolic Structure in the cell, characterized by a set of different enzymatic reactions always locked into active states (metabolic core) while the rest of the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordance with these observations, the cell can be considered a complex metabolic network which mainly integrates a large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, where multiple autonomous oscillatory and quasi-stationary catalytic patterns simultaneously emerge. The network adjusts the internal metabolic activities to the external change by means of flux plasticity and structural plasticity. Methodology/Principal Findings In order to research the systemic mechanisms involved in the regulation of the cellular enzymatic activity we have studied different catalytic activities of a dissipative metabolic network under different external stimuli. The emergent biochemical data have been analysed using statistical mechanic tools, studying some macroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann machine. Our main result shows that the dissipative metabolic network can behave as an attractor metabolic network. Conclusions/Significance We have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns, modify the efficiency in the connection between the multienzymatic complexes, and stably retain these modifications. Here for the first time, we have introduced the general concept of attractor metabolic network, in which this dynamic behavior is observed. PMID:23554883

  18. Focus on the emerging new fields of network physiology and network medicine

    NASA Astrophysics Data System (ADS)

    Ivanov, Plamen Ch; Liu, Kang K. L.; Bartsch, Ronny P.

    2016-10-01

    Despite the vast progress and achievements in systems biology and integrative physiology in the last decades, there is still a significant gap in understanding the mechanisms through which (i) genomic, proteomic and metabolic factors and signaling pathways impact vertical processes across cells, tissues and organs leading to the expression of different disease phenotypes and influence the functional and clinical associations between diseases, and (ii) how diverse physiological systems and organs coordinate their functions over a broad range of space and time scales and horizontally integrate to generate distinct physiologic states at the organism level. Two emerging fields, network medicine and network physiology, aim to address these fundamental questions. Novel concepts and approaches derived from recent advances in network theory, coupled dynamical systems, statistical and computational physics show promise to provide new insights into the complexity of physiological structure and function in health and disease, bridging the genetic and sub-cellular level with inter-cellular interactions and communications among integrated organ systems and sub-systems. These advances form first building blocks in the methodological formalism and theoretical framework necessary to address fundamental problems and challenges in physiology and medicine. This ‘focus on’ issue contains 26 articles representing state-of-the-art contributions covering diverse systems from the sub-cellular to the organism level where physicists have key role in laying the foundations of these new fields.

  19. 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)

  20. Evolution, learning, and cognition

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Y.C.

    1988-01-01

    The book comprises more than fifteen articles in the areas of neural networks and connectionist systems, classifier systems, adaptive network systems, genetic algorithm, cellular automata, artificial immune systems, evolutionary genetics, cognitive science, optical computing, combinatorial optimization, and cybernetics.

  1. Interactome Networks and Human Disease

    PubMed Central

    Vidal, Marc; Cusick, Michael E.; Barabási, Albert-László

    2011-01-01

    Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease. PMID:21414488

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Palazzo, S.; Vagliasindi, G.; Arena, P.

    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 inmore » 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.« less

  3. Early warning of illegal development for protected areas by integrating cellular automata with neural networks.

    PubMed

    Li, Xia; Lao, Chunhua; Liu, Yilun; Liu, Xiaoping; Chen, Yimin; Li, Shaoying; Ai, Bing; He, Zijian

    2013-11-30

    Ecological security has become a major issue under fast urbanization in China. As the first two cities in this country, Shenzhen and Dongguan issued the ordinance of Eco-designated Line of Control (ELC) to "wire" ecologically important areas for strict protection in 2005 and 2009 respectively. Early warning systems (EWS) are a useful tool for assisting the implementation ELC. In this study, a multi-model approach is proposed for the early warning of illegal development by integrating cellular automata (CA) and artificial neural networks (ANN). The objective is to prevent the ecological risks or catastrophe caused by such development at an early stage. The integrated model is calibrated by using the empirical information from both remote sensing and handheld GPS (global positioning systems). The MAR indicator which is the ratio of missing alarms to all the warnings is proposed for better assessment of the model performance. It is found that the fast urban development has caused significant threats to natural-area protection in the study area. The integration of CA, ANN and GPS provides a powerful tool for describing and predicting illegal development which is in highly non-linear and fragmented forms. The comparison shows that this multi-model approach has much better performances than the single-model approach for the early warning. Compared with the single models of CA and ANN, this integrated multi-model can improve the value of MAR by 65.48% and 5.17% respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. A low-cost, tablet-based option for prehospital neurologic assessment: The iTREAT Study.

    PubMed

    Chapman Smith, Sherita N; Govindarajan, Prasanthi; Padrick, Matthew M; Lippman, Jason M; McMurry, Timothy L; Resler, Brian L; Keenan, Kevin; Gunnell, Brian S; Mehndiratta, Prachi; Chee, Christina Y; Cahill, Elizabeth A; Dietiker, Cameron; Cattell-Gordon, David C; Smith, Wade S; Perina, Debra G; Solenski, Nina J; Worrall, Bradford B; Southerland, Andrew M

    2016-07-05

    In this 2-center study, we assessed the technical feasibility and reliability of a low cost, tablet-based mobile telestroke option for ambulance transport and hypothesized that the NIH Stroke Scale (NIHSS) could be performed with similar reliability between remote and bedside examinations. We piloted our mobile telemedicine system in 2 geographic regions, central Virginia and the San Francisco Bay Area, utilizing commercial cellular networks for videoconferencing transmission. Standardized patients portrayed scripted stroke scenarios during ambulance transport and were evaluated by independent raters comparing bedside to remote mobile telestroke assessments. We used a mixed-effects regression model to determine intraclass correlation of the NIHSS between bedside and remote examinations (95% confidence interval). We conducted 27 ambulance runs at both sites and successfully completed the NIHSS for all prehospital assessments without prohibitive technical interruption. The mean difference between bedside (face-to-face) and remote (video) NIHSS scores was 0.25 (1.00 to -0.50). Overall, correlation of the NIHSS between bedside and mobile telestroke assessments was 0.96 (0.92-0.98). In the mixed-effects regression model, there were no statistically significant differences accounting for method of evaluation or differences between sites. Utilizing a low-cost, tablet-based platform and commercial cellular networks, we can reliably perform prehospital neurologic assessments in both rural and urban settings. Further research is needed to establish the reliability and validity of prehospital mobile telestroke assessment in live patients presenting with acute neurologic symptoms. © 2016 American Academy of Neurology.

  5. A low-cost, tablet-based option for prehospital neurologic assessment

    PubMed Central

    Chapman Smith, Sherita N.; Govindarajan, Prasanthi; Padrick, Matthew M.; Lippman, Jason M.; McMurry, Timothy L.; Resler, Brian L.; Keenan, Kevin; Gunnell, Brian S.; Mehndiratta, Prachi; Chee, Christina Y.; Cahill, Elizabeth A.; Dietiker, Cameron; Cattell-Gordon, David C.; Smith, Wade S.; Perina, Debra G.; Solenski, Nina J.; Worrall, Bradford B.

    2016-01-01

    Objectives: In this 2-center study, we assessed the technical feasibility and reliability of a low cost, tablet-based mobile telestroke option for ambulance transport and hypothesized that the NIH Stroke Scale (NIHSS) could be performed with similar reliability between remote and bedside examinations. Methods: We piloted our mobile telemedicine system in 2 geographic regions, central Virginia and the San Francisco Bay Area, utilizing commercial cellular networks for videoconferencing transmission. Standardized patients portrayed scripted stroke scenarios during ambulance transport and were evaluated by independent raters comparing bedside to remote mobile telestroke assessments. We used a mixed-effects regression model to determine intraclass correlation of the NIHSS between bedside and remote examinations (95% confidence interval). Results: We conducted 27 ambulance runs at both sites and successfully completed the NIHSS for all prehospital assessments without prohibitive technical interruption. The mean difference between bedside (face-to-face) and remote (video) NIHSS scores was 0.25 (1.00 to −0.50). Overall, correlation of the NIHSS between bedside and mobile telestroke assessments was 0.96 (0.92–0.98). In the mixed-effects regression model, there were no statistically significant differences accounting for method of evaluation or differences between sites. Conclusions: Utilizing a low-cost, tablet-based platform and commercial cellular networks, we can reliably perform prehospital neurologic assessments in both rural and urban settings. Further research is needed to establish the reliability and validity of prehospital mobile telestroke assessment in live patients presenting with acute neurologic symptoms. PMID:27281534

  6. The Neurona at Home project: Simulating a large-scale cellular automata brain in a distributed computing environment

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

    The Berkeley Open Infrastructure for Network Computing (BOINC) has become the standard open source solution for grid computing in the Internet. Volunteers use their computers to complete an small part of the task assigned by a dedicated server. We have developed a BOINC project called Neurona@Home whose objective is to simulate a cellular automata random network with, at least, one million neurons. We consider a cellular automata version of the integrate-and-fire model in which excitatory and inhibitory nodes can activate or deactivate neighbor nodes according to a set of probabilistic rules. Our aim is to determine the phase diagram of the model and its behaviour and to compare it with the electroencephalographic signals measured in real brains.

  7. A Global Protein Kinase and Phosphatase Interaction Network in Yeast

    PubMed Central

    Breitkreutz, Ashton; Choi, Hyungwon; Sharom, Jeffrey R.; Boucher, Lorrie; Neduva, Victor; Larsen, Brett; Lin, Zhen-Yuan; Breitkreutz, Bobby-Joe; Stark, Chris; Liu, Guomin; Ahn, Jessica; Dewar-Darch, Danielle; Reguly, Teresa; Tang, Xiaojing; Almeida, Ricardo; Qin, Zhaohui Steve; Pawson, Tony; Gingras, Anne-Claude; Nesvizhskii, Alexey I.; Tyers, Mike

    2011-01-01

    The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. PMID:20489023

  8. 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.).

  9. 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.

  10. Murine Hyperglycemic Vasculopathy and Cardiomyopathy: Whole-Genome Gene Expression Analysis Predicts Cellular Targets and Regulatory Networks Influenced by Mannose Binding Lectin

    PubMed Central

    Zou, Chenhui; La Bonte, Laura R.; Pavlov, Vasile I.; Stahl, Gregory L.

    2012-01-01

    Hyperglycemia, in the absence of type 1 or 2 diabetes, is an independent risk factor for cardiovascular disease. We have previously demonstrated a central role for mannose binding lectin (MBL)-mediated cardiac dysfunction in acute hyperglycemic mice. In this study, we applied whole-genome microarray data analysis to investigate MBL’s role in systematic gene expression changes. The data predict possible intracellular events taking place in multiple cellular compartments such as enhanced insulin signaling pathway sensitivity, promoted mitochondrial respiratory function, improved cellular energy expenditure and protein quality control, improved cytoskeleton structure, and facilitated intracellular trafficking, all of which may contribute to the organismal health of MBL null mice against acute hyperglycemia. Our data show a tight association between gene expression profile and tissue function which might be a very useful tool in predicting cellular targets and regulatory networks connected with in vivo observations, providing clues for further mechanistic studies. PMID:22375142

  11. System-wide organization of actin cytoskeleton determines organelle transport in hypocotyl plant cells

    PubMed Central

    Nowak, Jacqueline; Ivakov, Alexander; Somssich, Marc; Persson, Staffan; Nikoloski, Zoran

    2017-01-01

    The actin cytoskeleton is an essential intracellular filamentous structure that underpins cellular transport and cytoplasmic streaming in plant cells. However, the system-level properties of actin-based cellular trafficking remain tenuous, largely due to the inability to quantify key features of the actin cytoskeleton. Here, we developed an automated image-based, network-driven framework to accurately segment and quantify actin cytoskeletal structures and Golgi transport. We show that the actin cytoskeleton in both growing and elongated hypocotyl cells has structural properties facilitating efficient transport. Our findings suggest that the erratic movement of Golgi is a stable cellular phenomenon that might optimize distribution efficiency of cell material. Moreover, we demonstrate that Golgi transport in hypocotyl cells can be accurately predicted from the actin network topology alone. Thus, our framework provides quantitative evidence for system-wide coordination of cellular transport in plant cells and can be readily applied to investigate cytoskeletal organization and transport in other organisms. PMID:28655850

  12. Calcium and ROS: A mutual interplay

    PubMed Central

    Görlach, Agnes; Bertram, Katharina; Hudecova, Sona; Krizanova, Olga

    2015-01-01

    Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions. The Ca2+ signaling network works in many different ways to regulate cellular processes that function over a wide dynamic range due to the action of buffers, pumps and exchangers on the plasma membrane as well as in internal stores. Calcium signaling pathways interact with other cellular signaling systems such as reactive oxygen species (ROS). Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death. Increasing evidence suggests a mutual interplay between calcium and ROS signaling systems which seems to have important implications for fine tuning cellular signaling networks. However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders. PMID:26296072

  13. Wavefront cellular learning automata.

    PubMed

    Moradabadi, Behnaz; Meybodi, Mohammad Reza

    2018-02-01

    This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

  14. Wavefront cellular learning automata

    NASA Astrophysics Data System (ADS)

    Moradabadi, Behnaz; Meybodi, Mohammad Reza

    2018-02-01

    This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

  15. 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

  16. 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

    2016-06-14

    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.

  17. TimeXNet Web: Identifying cellular response networks from diverse omics time-course data.

    PubMed

    Tan, Phit Ling; López, Yosvany; Nakai, Kenta; Patil, Ashwini

    2018-05-14

    Condition-specific time-course omics profiles are frequently used to study cellular response to stimuli and identify associated signaling pathways. However, few online tools allow users to analyze multiple types of high-throughput time-course data. TimeXNet Web is a web server that extracts a time-dependent gene/protein response network from time-course transcriptomic, proteomic or phospho-proteomic data, and an input interaction network. It classifies the given genes/proteins into time-dependent groups based on the time of their highest activity and identifies the most probable paths connecting genes/proteins in consecutive groups. The response sub-network is enriched in activated genes/proteins and contains novel regulators that do not show any observable change in the input data. Users can view the resultant response network and analyze it for functional enrichment. TimeXNet Web supports the analysis of high-throughput data from multiple species by providing high quality, weighted protein-protein interaction networks for 12 model organisms. http://txnet.hgc.jp/. ashwini@hgc.jp. Supplementary data are available at Bioinformatics online.

  18. Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems.

    PubMed

    Bashor, Caleb J; Horwitz, Andrew A; Peisajovich, Sergio G; Lim, Wendell A

    2010-01-01

    The living cell is an incredibly complex entity, and the goal of predictively and quantitatively understanding its function is one of the next great challenges in biology. Much of what we know about the cell concerns its constituent parts, but to a great extent we have yet to decode how these parts are organized to yield complex physiological function. Classically, we have learned about the organization of cellular networks by disrupting them through genetic or chemical means. The emerging discipline of synthetic biology offers an additional, powerful approach to study systems. By rearranging the parts that comprise existing networks, we can gain valuable insight into the hierarchical logic of the networks and identify the modular building blocks that evolution uses to generate innovative function. In addition, by building minimal toy networks, one can systematically explore the relationship between network structure and function. Here, we outline recent work that uses synthetic biology approaches to investigate the organization and function of cellular networks, and describe a vision for a synthetic biology toolkit that could be used to interrogate the design principles of diverse systems.

  19. An FD-LC-MS/MS Proteomic Strategy for Revealing Cellular Protein Networks: A Conditional Superoxide Dismutase 1 Knockout Cells

    PubMed Central

    Ichibangase, Tomoko; Sugawara, Yasuhiro; Yamabe, Akio; Koshiyama, Akiyo; Yoshimura, Akari; Enomoto, Takemi; Imai, Kazuhiro

    2012-01-01

    Systems biology aims to understand biological phenomena in terms of complex biological and molecular interactions, and thus proteomics plays an important role in elucidating protein networks. However, many proteomic methods have suffered from their high variability, resulting in only showing altered protein names. Here, we propose a strategy for elucidating cellular protein networks based on an FD-LC-MS/MS proteomic method. The strategy permits reproducible relative quantitation of differences in protein levels between different cell populations and allows for integration of the data with those obtained through other methods. We demonstrate the validity of the approach through a comparison of differential protein expression in normal and conditional superoxide dismutase 1 gene knockout cells and believe that beginning with an FD-LC-MS/MS proteomic approach will enable researchers to elucidate protein networks more easily and comprehensively. PMID:23029042

  20. Cytoskeletal Network Morphology Regulates Intracellular Transport Dynamics

    PubMed Central

    Ando, David; Korabel, Nickolay; Huang, Kerwyn Casey; Gopinathan, Ajay

    2015-01-01

    Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design. PMID:26488648

  1. Energy-efficient downlink resource management in self-organized OFDMA-based two-tier femtocell networks

    NASA Astrophysics Data System (ADS)

    Shahid, Adnan; Aslam, Saleem; Kim, Hyung Seok; Lee, Kyung-Geun

    2015-12-01

    Femtocell is a novel technology that is used for escalating indoor coverage as well as the capacity of traditional cellular networks. However, interference is the limiting factor for performance improvement due to co-channel deployment between macrocells and femtocells. The traditional network planning is not feasible because of the random deployment of femtocells. Therefore, self-organization approaches are the key to having successful deployment of femtocells. This study presents the joint resource block (RB) and power allocation task for the two-tier femtocell network in a self-organizing manner, with the concern to minimizing the impact of interference and maximizing the energy efficiency. In this study, we analyze the performance of the system in terms of the energy efficiency, which is composed of both the transmission and circuit power. Most of the previous studies investigate the performance regarding the throughput requirement of the two-tier femtocell network while the energy efficiency aspect is largely ignored. Here, the joint allocation task is modeled as a non-cooperative game which is demonstrated to exhibit pure and unique Nash equilibrium. In order to reduce the complexity of the proposed non-cooperative game, the joint RB and power allocation task is divided into two subproblems: an RB allocation and a particle swarm optimization-based power allocation. The analysis of the proposed game is carried out in terms of not only energy efficiency but also throughput. With practical 3rd Generation Partnership Project (3GPP) Long-Term Evolution (LTE) parameters, the simulation results illustrate the superior performance of the proposed game as compared to the traditional methods. Also, the comparison is carried out with the joint allocation scheme which only considers the throughput as the objective function. The results illustrate that significant performance improvement is achieved in terms of energy efficiency with slight loss in the throughput. The analysis in regard to energy efficiency and throughput of the two-tier femtocell network is carried out in terms of the performance metrics, which include convergence, impact of varying RBs, impact of femtocell density, and the fairness index.

  2. Network models provide insights into how oriens–lacunosum-moleculare and bistratified cell interactions influence the power of local hippocampal CA1 theta oscillations

    PubMed Central

    Ferguson, Katie A.; Huh, Carey Y. L.; Amilhon, Bénédicte; Manseau, Frédéric; Williams, Sylvain; Skinner, Frances K.

    2015-01-01

    Hippocampal theta is a 4–12 Hz rhythm associated with episodic memory, and although it has been studied extensively, the cellular mechanisms underlying its generation are unclear. The complex interactions between different interneuron types, such as those between oriens–lacunosum-moleculare (OLM) interneurons and bistratified cells (BiCs), make their contribution to network rhythms difficult to determine experimentally. We created network models that are tied to experimental work at both cellular and network levels to explore how these interneuron interactions affect the power of local oscillations. Our cellular models were constrained with properties from patch clamp recordings in the CA1 region of an intact hippocampus preparation in vitro. Our network models are composed of three different types of interneurons: parvalbumin-positive (PV+) basket and axo-axonic cells (BC/AACs), PV+ BiCs, and somatostatin-positive OLM cells. Also included is a spatially extended pyramidal cell model to allow for a simplified local field potential representation, as well as experimentally-constrained, theta frequency synaptic inputs to the interneurons. The network size, connectivity, and synaptic properties were constrained with experimental data. To determine how the interactions between OLM cells and BiCs could affect local theta power, we explored how the number of OLM-BiC connections and connection strength affected local theta power. We found that our models operate in regimes that could be distinguished by whether OLM cells minimally or strongly affected the power of network theta oscillations due to balances that, respectively, allow compensatory effects or not. Inactivation of OLM cells could result in no change or even an increase in theta power. We predict that the dis-inhibitory effect of OLM cells to BiCs to pyramidal cell interactions plays a critical role in the resulting power of network theta oscillations. Overall, our network models reveal a dynamic interplay between different classes of interneurons in influencing local theta power. PMID:26300744

  3. Geolocation of WiMAX Subscriber Stations Based on the Timing Adjust Ranging Parameter

    DTIC Science & Technology

    2009-12-01

    to cellular networks hoping to offer location based services and to emergency response and tactical personnel who may need to locate mobile persons...applications. Location - based services have grown increasingly popular in the current generation of cellular phones, providing weather, traffic, and

  4. SigFlux: a novel network feature to evaluate the importance of proteins in signal transduction networks.

    PubMed

    Liu, Wei; Li, Dong; Zhang, Jiyang; Zhu, Yunping; He, Fuchu

    2006-11-27

    Measuring each protein's importance in signaling networks helps to identify the crucial proteins in a cellular process, find the fragile portion of the biology system and further assist for disease therapy. However, there are relatively few methods to evaluate the importance of proteins in signaling networks. We developed a novel network feature to evaluate the importance of proteins in signal transduction networks, that we call SigFlux, based on the concept of minimal path sets (MPSs). An MPS is a minimal set of nodes that can perform the signal propagation from ligands to target genes or feedback loops. We define SigFlux as the number of MPSs in which each protein is involved. We applied this network feature to the large signal transduction network in the hippocampal CA1 neuron of mice. Significant correlations were simultaneously observed between SigFlux and both the essentiality and evolutionary rate of genes. Compared with another commonly used network feature, connectivity, SigFlux has similar or better ability as connectivity to reflect a protein's essentiality. Further classification according to protein function demonstrates that high SigFlux, low connectivity proteins are abundant in receptors and transcriptional factors, indicating that SigFlux candescribe the importance of proteins within the context of the entire network. SigFlux is a useful network feature in signal transduction networks that allows the prediction of the essentiality and conservation of proteins. With this novel network feature, proteins that participate in more pathways or feedback loops within a signaling network are proved far more likely to be essential and conserved during evolution than their counterparts.

  5. 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.

  6. 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.

  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. 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

  9. 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

    2016-06-25

    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.

  10. 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.

  11. 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.

  12. Integration of mobile satellite and cellular systems

    NASA Astrophysics Data System (ADS)

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

    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.

  13. Computational Characterization of Type I collagen-based Extra-cellular Matrix

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    A model of extracellular matrix (ECM) of collagen fibers has been built, in which cells could communicate with distant partners via fiber-mediated long-range-transmitted stress states. The ECM is modeled as a spring-like fiber network derived from skeletonized confocal microscopy data. Different local and global perturbations have been performed on the network, each followed by an optimized global Monte-Carlo (MC) energy minimization leading to the deformed network in response to the perturbations. In the optimization, a highly efficient local energy update procedure is employed and force-directed MC moves are used, which results in a convergence to the energy minimum state 20 times faster than the commonly used random displacement trial moves in MC. Further analysis and visualization of the distribution and correlation of the resulting force network reveal that local perturbations can give rise to global impacts: the force chains formed with a linear extent much further than the characteristic length scale associated with the perturbation sites and average fiber length. This behavior provides a strong evidence for our hypothesis of fiber-mediated long-range force transmission in ECM networks and the resulting long-range cell-cell mechanical signaling. ASU Seed Grant.

  14. 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

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

    PubMed

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

    2016-03-14

    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.

  16. Implementation of a Synchronized Oscillator Circuit for Fast Sensing and Labeling of Image Objects

    PubMed Central

    Kowalski, Jacek; Strzelecki, Michal; Kim, Hyongsuk

    2011-01-01

    We present an application-specific integrated circuit (ASIC) CMOS chip that implements a synchronized oscillator cellular neural network with a matrix size of 32 × 32 for object sensing and labeling in binary images. Networks of synchronized oscillators are a recently developed tool for image segmentation and analysis. Its parallel network operation is based on a “temporary correlation” theory that attempts to describe scene recognition as if performed by the human brain. The synchronized oscillations of neuron groups attract a person’s attention if he or she is focused on a coherent stimulus (image object). For more than one perceived stimulus, these synchronized patterns switch in time between different neuron groups, thus forming temporal maps that code several features of the analyzed scene. In this paper, a new oscillator circuit based on a mathematical model is proposed, and the network architecture and chip functional blocks are presented and discussed. The proposed chip is implemented in AMIS 0.35 μm C035M-D 5M/1P technology. An application of the proposed network chip for the segmentation of insulin-producing pancreatic islets in magnetic resonance liver images is presented. PMID:22163803

  17. A cryptographic hash function based on chaotic network automata

    NASA Astrophysics Data System (ADS)

    Machicao, Jeaneth; Bruno, Odemir M.

    2017-12-01

    Chaos theory has been used to develop several cryptographic methods relying on the pseudo-random properties extracted from simple nonlinear systems such as cellular automata (CA). Cryptographic hash functions (CHF) are commonly used to check data integrity. CHF “compress” arbitrary long messages (input) into much smaller representations called hash values or message digest (output), designed to prevent the ability to reverse the hash values into the original message. This paper proposes a chaos-based CHF inspired on an encryption method based on chaotic CA rule B1357-S2468. Here, we propose an hybrid model that combines CA and networks, called network automata (CNA), whose chaotic spatio-temporal outputs are used to compute a hash value. Following the Merkle and Damgård model of construction, a portion of the message is entered as the initial condition of the network automata, so that the rest parts of messages are iteratively entered to perturb the system. The chaotic network automata shuffles the message using flexible control parameters, so that the generated hash value is highly sensitive to the message. As demonstrated in our experiments, the proposed model has excellent pseudo-randomness and sensitivity properties with acceptable performance when compared to conventional hash functions.

  18. Hypertonic stress induces rapid and widespread protein damage in C. elegans

    PubMed Central

    Burkewitz, Kris; Choe, Keith

    2011-01-01

    Proteostasis is defined as the homeostatic mechanisms that maintain the function of all cytoplasmic proteins. We recently demonstrated that the capacity of the proteostasis network is a critical factor that defines the limits of cellular and organismal survival in hypertonic environments. The current studies were performed to determine the extent of protein damage induced by cellular water loss. Using worm strains expressing fluorescently tagged foreign and endogenous proteins and proteins with temperature-sensitive point mutations, we demonstrate that hypertonic stress causes aggregation and misfolding of diverse proteins in multiple cell types. Protein damage is rapid. Aggregation of a polyglutamine yellow fluorescent protein reporter is observable with <1 h of hypertonic stress, and aggregate volume doubles approximately every 10 min. Aggregate formation is irreversible and occurs after as little as 10 min of exposure to hypertonic conditions. To determine whether endogenous proteins are aggregated by hypertonic stress, we quantified the relative amount of total cellular protein present in detergent-insoluble extracts. Exposure for 4 h to 400 mM or 500 mM NaCl induced a 55–120% increase in endogenous protein aggregation. Inhibition of insulin signaling or acclimation to mild hypertonic stress increased survival under extreme hypertonic conditions and prevented aggregation of endogenous proteins. Our results demonstrate that hypertonic stress causes widespread and dramatic protein damage and that cells have a significant capacity to remodel the network of proteins that function to maintain proteostasis. These findings have important implications for understanding how cells cope with hypertonic stress and other protein-damaging stressors. PMID:21613604

  19. Wireless data communication alternatives for small public safety agencies: how one community cost-effectively solved its expanding field data requirements

    NASA Astrophysics Data System (ADS)

    Canning, Ryan M.; Lefebvre, Eric

    2005-06-01

    A growing number of Public Safety agencies have begun leveraging wireless data communication technology to improve tactical response capabilities as well as overall productivity. For years police departments subscribed to CDPD (Cellular Digital Packet Data) services to provide officers with basic dispatch data and criminal database access. Now as cellular carriers have deactivated CDPD and shifted to 2.5G and 3G data services such as 1xRTT, GPRS and EDGE, police departments are scrambling to fill the void. Not surprisingly, the extraordinary investments cellular carriers made to upgrade their infrastructures have been transferred to the customer, with monthly fees running as high as $80 a month per user. It's no wonder public safety agencies have been reluctant to adopt these services. Lost in the fray are those smaller police departments which account for nearly 90% of the nation's total. This group has increasingly sought out alternative data communication solutions that are not predicated on budget-busting monthly access fees. One such example is the Marco Island Police Department (MIPD) in Southwestern Florida that received a Federal grant to augment its existing voice communications with data. After evaluating several different technologies and vendors, MIPD chose a 900 MHz ad hoc mesh network solution based on its ability to provide reliable, high-speed and secure IP-based data communications over extensive distances. This paper will discuss technical details of Marco Island's mobile mesh network implementation; including: coverage area with 900 MHz spread spectrum radios, strategic repeater tower placement, interference, throughput performance, and the necessity for application-persistence software.

  20. Long-range interactions and parallel scalability in molecular simulations

    NASA Astrophysics Data System (ADS)

    Patra, Michael; Hyvönen, Marja T.; Falck, Emma; Sabouri-Ghomi, Mohsen; Vattulainen, Ilpo; Karttunen, Mikko

    2007-01-01

    Typical biomolecular systems such as cellular membranes, DNA, and protein complexes are highly charged. Thus, efficient and accurate treatment of electrostatic interactions is of great importance in computational modeling of such systems. We have employed the GROMACS simulation package to perform extensive benchmarking of different commonly used electrostatic schemes on a range of computer architectures (Pentium-4, IBM Power 4, and Apple/IBM G5) for single processor and parallel performance up to 8 nodes—we have also tested the scalability on four different networks, namely Infiniband, GigaBit Ethernet, Fast Ethernet, and nearly uniform memory architecture, i.e. communication between CPUs is possible by directly reading from or writing to other CPUs' local memory. It turns out that the particle-mesh Ewald method (PME) performs surprisingly well and offers competitive performance unless parallel runs on PC hardware with older network infrastructure are needed. Lipid bilayers of sizes 128, 512 and 2048 lipid molecules were used as the test systems representing typical cases encountered in biomolecular simulations. Our results enable an accurate prediction of computational speed on most current computing systems, both for serial and parallel runs. These results should be helpful in, for example, choosing the most suitable configuration for a small departmental computer cluster.

  1. Identification of infection- and defense-related genes via a dynamic host-pathogen interaction network using a Candida albicans-zebrafish infection model.

    PubMed

    Kuo, Zong-Yu; Chuang, Yung-Jen; Chao, Chun-Cheih; Liu, Fu-Chen; Lan, Chung-Yu; Chen, Bor-Sen

    2013-01-01

    Candida albicans infections and candidiasis are difficult to treat and create very serious therapeutic challenges. In this study, based on interactive time profile microarray data of C. albicans and zebrafish during infection, the infection-related protein-protein interaction (PPI) networks of the two species and the intercellular PPI network between host and pathogen were simultaneously constructed by a dynamic interaction model, modeled as an integrated network consisting of intercellular invasion and cellular defense processes during infection. The signal transduction pathways in regulating morphogenesis and hyphal growth of C. albicans were further investigated based on significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins from which we can gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. The hyphal growth PPI network, zebrafish PPI network and host-pathogen intercellular PPI network were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host, and may help improve medical therapies and facilitate the development of new antifungal drugs. Copyright © 2013 S. Karger AG, Basel.

  2. Computational Systems Toxicology: recapitulating the logistical dynamics of cellular response networks in virtual tissue models (Eurotox_2017)

    EPA Science Inventory

    Translating in vitro data and biological information into a predictive model for human toxicity poses a significant challenge. This is especially true for complex adaptive systems such as the embryo where cellular dynamics are precisely orchestrated in space and time. Computer ce...

  3. 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…

  4. Mapping the physical network of cellular interactions.

    PubMed

    Boisset, Jean-Charles; Vivié, Judith; Grün, Dominic; Muraro, Mauro J; Lyubimova, Anna; van Oudenaarden, Alexander

    2018-05-21

    A cell's function is influenced by the environment, or niche, in which it resides. Studies of niches usually require assumptions about the cell types present, which impedes the discovery of new cell types or interactions. Here we describe ProximID, an approach for building a cellular network based on physical cell interaction and single-cell mRNA sequencing, and show that it can be used to discover new preferential cellular interactions without prior knowledge of component cell types. ProximID found specific interactions between megakaryocytes and mature neutrophils and between plasma cells and myeloblasts and/or promyelocytes (precursors of neutrophils) in mouse bone marrow, and it identified a Tac1 + enteroendocrine cell-Lgr5 + stem cell interaction in small intestine crypts. This strategy can be used to discover new niches or preferential interactions in a variety of organs.

  5. Strange non-chaotic attractors in a state controlled-cellular neural network-based quasiperiodically forced MLC circuit

    NASA Astrophysics Data System (ADS)

    Ezhilarasu, P. Megavarna; Inbavalli, M.; Murali, K.; Thamilmaran, K.

    2018-07-01

    In this paper, we report the dynamical transitions to strange non-chaotic attractors in a quasiperiodically forced state controlled-cellular neural network (SC-CNN)-based MLC circuit via two different mechanisms, namely the Heagy-Hammel route and the gradual fractalisation route. These transitions were observed through numerical simulations and hardware experiments and confirmed using statistical tools, such as maximal Lyapunov exponent spectrum and its variance and singular continuous spectral analysis. We find that there is a remarkable agreement of the results from both numerical simulations as well as from hardware experiments.

  6. 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.

  7. 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.

  8. Genome Scale Modeling in Systems Biology: Algorithms and Resources

    PubMed Central

    Najafi, Ali; Bidkhori, Gholamreza; Bozorgmehr, Joseph H.; Koch, Ina; Masoudi-Nejad, Ali

    2014-01-01

    In recent years, in silico studies and trial simulations have complemented experimental procedures. A model is a description of a system, and a system is any collection of interrelated objects; an object, moreover, is some elemental unit upon which observations can be made but whose internal structure either does not exist or is ignored. Therefore, any network analysis approach is critical for successful quantitative modeling of biological systems. This review highlights some of most popular and important modeling algorithms, tools, and emerging standards for representing, simulating and analyzing cellular networks in five sections. Also, we try to show these concepts by means of simple example and proper images and graphs. Overall, systems biology aims for a holistic description and understanding of biological processes by an integration of analytical experimental approaches along with synthetic computational models. In fact, biological networks have been developed as a platform for integrating information from high to low-throughput experiments for the analysis of biological systems. We provide an overview of all processes used in modeling and simulating biological networks in such a way that they can become easily understandable for researchers with both biological and mathematical backgrounds. Consequently, given the complexity of generated experimental data and cellular networks, it is no surprise that researchers have turned to computer simulation and the development of more theory-based approaches to augment and assist in the development of a fully quantitative understanding of cellular dynamics. PMID:24822031

  9. An end-to-end workflow for engineering of biological networks from high-level specifications.

    PubMed

    Beal, Jacob; Weiss, Ron; Densmore, Douglas; Adler, Aaron; Appleton, Evan; Babb, Jonathan; Bhatia, Swapnil; Davidsohn, Noah; Haddock, Traci; Loyall, Joseph; Schantz, Richard; Vasilev, Viktor; Yaman, Fusun

    2012-08-17

    We present a workflow for the design and production of biological networks from high-level program specifications. The workflow is based on a sequence of intermediate models that incrementally translate high-level specifications into DNA samples that implement them. We identify algorithms for translating between adjacent models and implement them as a set of software tools, organized into a four-stage toolchain: Specification, Compilation, Part Assignment, and Assembly. The specification stage begins with a Boolean logic computation specified in the Proto programming language. The compilation stage uses a library of network motifs and cellular platforms, also specified in Proto, to transform the program into an optimized Abstract Genetic Regulatory Network (AGRN) that implements the programmed behavior. The part assignment stage assigns DNA parts to the AGRN, drawing the parts from a database for the target cellular platform, to create a DNA sequence implementing the AGRN. Finally, the assembly stage computes an optimized assembly plan to create the DNA sequence from available part samples, yielding a protocol for producing a sample of engineered plasmids with robotics assistance. Our workflow is the first to automate the production of biological networks from a high-level program specification. Furthermore, the workflow's modular design allows the same program to be realized on different cellular platforms simply by swapping workflow configurations. We validated our workflow by specifying a small-molecule sensor-reporter program and verifying the resulting plasmids in both HEK 293 mammalian cells and in E. coli bacterial cells.

  10. An Automated Design Framework for Multicellular Recombinase Logic.

    PubMed

    Guiziou, Sarah; Ulliana, Federico; Moreau, Violaine; Leclere, Michel; Bonnet, Jerome

    2018-05-18

    Tools to systematically reprogram cellular behavior are crucial to address pressing challenges in manufacturing, environment, or healthcare. Recombinases can very efficiently encode Boolean and history-dependent logic in many species, yet current designs are performed on a case-by-case basis, limiting their scalability and requiring time-consuming optimization. Here we present an automated workflow for designing recombinase logic devices executing Boolean functions. Our theoretical framework uses a reduced library of computational devices distributed into different cellular subpopulations, which are then composed in various manners to implement all desired logic functions at the multicellular level. Our design platform called CALIN (Composable Asynchronous Logic using Integrase Networks) is broadly accessible via a web server, taking truth tables as inputs and providing corresponding DNA designs and sequences as outputs (available at http://synbio.cbs.cnrs.fr/calin ). We anticipate that this automated design workflow will streamline the implementation of Boolean functions in many organisms and for various applications.

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

    DOEpatents

    Craig, William W [Pittsburg, CA; Labov, Simon E [Berkeley, CA

    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.

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

    DOEpatents

    Craig, William W [Pittsburg, CA; Labov, Simon E [Berkeley, CA

    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.

  13. Towards the understanding of network information processing in biology

    NASA Astrophysics Data System (ADS)

    Singh, Vijay

    Living organisms perform incredibly well in detecting a signal present in the environment. This information processing is achieved near optimally and quite reliably, even though the sources of signals are highly variable and complex. The work in the last few decades has given us a fair understanding of how individual signal processing units like neurons and cell receptors process signals, but the principles of collective information processing on biological networks are far from clear. Information processing in biological networks, like the brain, metabolic circuits, cellular-signaling circuits, etc., involves complex interactions among a large number of units (neurons, receptors). The combinatorially large number of states such a system can exist in makes it impossible to study these systems from the first principles, starting from the interactions between the basic units. The principles of collective information processing on such complex networks can be identified using coarse graining approaches. This could provide insights into the organization and function of complex biological networks. Here I study models of biological networks using continuum dynamics, renormalization, maximum likelihood estimation and information theory. Such coarse graining approaches identify features that are essential for certain processes performed by underlying biological networks. We find that long-range connections in the brain allow for global scale feature detection in a signal. These also suppress the noise and remove any gaps present in the signal. Hierarchical organization with long-range connections leads to large-scale connectivity at low synapse numbers. Time delays can be utilized to separate a mixture of signals with temporal scales. Our observations indicate that the rules in multivariate signal processing are quite different from traditional single unit signal processing.

  14. Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae.

    PubMed

    Arlia-Ciommo, Anthony; Leonov, Anna; Piano, Amanda; Svistkova, Veronika; Titorenko, Vladimir I

    2014-05-27

    A body of evidence supports the view that the signaling pathways governing cellular aging - as well as mechanisms of their modulation by longevity-extending genetic, dietary and pharmacological interventions - are conserved across species. The scope of this review is to critically analyze recent advances in our understanding of cell-autonomous mechanisms of chronological aging in the budding yeast Saccharomyces cerevisiae . Based on our analysis, we propose a concept of a biomolecular network underlying the chronology of cellular aging in yeast. The concept posits that such network progresses through a series of lifespan checkpoints. At each of these checkpoints, the intracellular concentrations of some key intermediates and products of certain metabolic pathways - as well as the rates of coordinated flow of such metabolites within an intricate network of intercompartmental communications - are monitored by some checkpoint-specific "master regulator" proteins. The concept envisions that a synergistic action of these master regulator proteins at certain early-life and late-life checkpoints modulates the rates and efficiencies of progression of such processes as cell metabolism, growth, proliferation, stress resistance, macromolecular homeostasis, survival and death. The concept predicts that, by modulating these vital cellular processes throughout lifespan (i.e., prior to an arrest of cell growth and division, and following such arrest), the checkpoint-specific master regulator proteins orchestrate the development and maintenance of a pro- or anti-aging cellular pattern and, thus, define longevity of chronologically aging yeast.

  15. CNN universal machine as classificaton platform: an art-like clustering algorithm.

    PubMed

    Bálya, David

    2003-12-01

    Fast and robust classification of feature vectors is a crucial task in a number of real-time systems. A cellular neural/nonlinear network universal machine (CNN-UM) can be very efficient as a feature detector. The next step is to post-process the results for object recognition. This paper shows how a robust classification scheme based on adaptive resonance theory (ART) can be mapped to the CNN-UM. Moreover, this mapping is general enough to include different types of feed-forward neural networks. The designed analogic CNN algorithm is capable of classifying the extracted feature vectors keeping the advantages of the ART networks, such as robust, plastic and fault-tolerant behaviors. An analogic algorithm is presented for unsupervised classification with tunable sensitivity and automatic new class creation. The algorithm is extended for supervised classification. The presented binary feature vector classification is implemented on the existing standard CNN-UM chips for fast classification. The experimental evaluation shows promising performance after 100% accuracy on the training set.

  16. Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts.

    PubMed

    Cellot, Giada; Cilia, Emanuele; Cipollone, Sara; Rancic, Vladimir; Sucapane, Antonella; Giordani, Silvia; Gambazzi, Luca; Markram, Henry; Grandolfo, Micaela; Scaini, Denis; Gelain, Fabrizio; Casalis, Loredana; Prato, Maurizio; Giugliano, Michele; Ballerini, Laura

    2009-02-01

    Carbon nanotubes have been applied in several areas of nerve tissue engineering to probe and augment cell behaviour, to label and track subcellular components, and to study the growth and organization of neural networks. Recent reports show that nanotubes can sustain and promote neuronal electrical activity in networks of cultured cells, but the ways in which they affect cellular function are still poorly understood. Here, we show, using single-cell electrophysiology techniques, electron microscopy analysis and theoretical modelling, that nanotubes improve the responsiveness of neurons by forming tight contacts with the cell membranes that might favour electrical shortcuts between the proximal and distal compartments of the neuron. We propose the 'electrotonic hypothesis' to explain the physical interactions between the cell and nanotube, and the mechanisms of how carbon nanotubes might affect the collective electrical activity of cultured neuronal networks. These considerations offer a perspective that would allow us to predict or engineer interactions between neurons and carbon nanotubes.

  17. RAID: a comprehensive resource for human RNA-associated (RNA-RNA/RNA-protein) interaction.

    PubMed

    Zhang, Xiaomeng; Wu, Deng; Chen, Liqun; Li, Xiang; Yang, Jinxurong; Fan, Dandan; Dong, Tingting; Liu, Mingyue; Tan, Puwen; Xu, Jintian; Yi, Ying; Wang, Yuting; Zou, Hua; Hu, Yongfei; Fan, Kaili; Kang, Juanjuan; Huang, Yan; Miao, Zhengqiang; Bi, Miaoman; Jin, Nana; Li, Kongning; Li, Xia; Xu, Jianzhen; Wang, Dong

    2014-07-01

    Transcriptomic analyses have revealed an unexpected complexity in the eukaryote transcriptome, which includes not only protein-coding transcripts but also an expanding catalog of noncoding RNAs (ncRNAs). Diverse coding and noncoding RNAs (ncRNAs) perform functions through interaction with each other in various cellular processes. In this project, we have developed RAID (http://www.rna-society.org/raid), an RNA-associated (RNA-RNA/RNA-protein) interaction database. RAID intends to provide the scientific community with all-in-one resources for efficient browsing and extraction of the RNA-associated interactions in human. This version of RAID contains more than 6100 RNA-associated interactions obtained by manually reviewing more than 2100 published papers, including 4493 RNA-RNA interactions and 1619 RNA-protein interactions. Each entry contains detailed information on an RNA-associated interaction, including RAID ID, RNA/protein symbol, RNA/protein categories, validated method, expressing tissue, literature references (Pubmed IDs), and detailed functional description. Users can query, browse, analyze, and manipulate RNA-associated (RNA-RNA/RNA-protein) interaction. RAID provides a comprehensive resource of human RNA-associated (RNA-RNA/RNA-protein) interaction network. Furthermore, this resource will help in uncovering the generic organizing principles of cellular function network. © 2014 Zhang et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  18. Altered Pathway Analyzer: A gene expression dataset analysis tool for identification and prioritization of differentially regulated and network rewired pathways

    PubMed Central

    Kaushik, Abhinav; Ali, Shakir; Gupta, Dinesh

    2017-01-01

    Gene connection rewiring is an essential feature of gene network dynamics. Apart from its normal functional role, it may also lead to dysregulated functional states by disturbing pathway homeostasis. Very few computational tools measure rewiring within gene co-expression and its corresponding regulatory networks in order to identify and prioritize altered pathways which may or may not be differentially regulated. We have developed Altered Pathway Analyzer (APA), a microarray dataset analysis tool for identification and prioritization of altered pathways, including those which are differentially regulated by TFs, by quantifying rewired sub-network topology. Moreover, APA also helps in re-prioritization of APA shortlisted altered pathways enriched with context-specific genes. We performed APA analysis of simulated datasets and p53 status NCI-60 cell line microarray data to demonstrate potential of APA for identification of several case-specific altered pathways. APA analysis reveals several altered pathways not detected by other tools evaluated by us. APA analysis of unrelated prostate cancer datasets identifies sample-specific as well as conserved altered biological processes, mainly associated with lipid metabolism, cellular differentiation and proliferation. APA is designed as a cross platform tool which may be transparently customized to perform pathway analysis in different gene expression datasets. APA is freely available at http://bioinfo.icgeb.res.in/APA. PMID:28084397

  19. An Interference Mitigation Scheme of Device-to-Device Communications for Sensor Networks Underlying LTE-A

    PubMed Central

    Kim, Jeehyeong; Karim, Nzabanita Abdoul; Cho, Sunghyun

    2017-01-01

    Device-to-Device (D2D) communication technology has become a key factor in wireless sensor networks to form autonomous communication links among sensor nodes. Many research results for D2D have been presented to resolve different technical issues of D2D. Nevertheless, the previous works have not resolved the shortage of data rate and limited coverage of wireless sensor networks. Due to bandwidth shortages and limited communication coverage, 3rd Generation Partnership Project (3GPP) has introduced a new Device-to-Device (D2D) communication technique underlying cellular networks, which can improve spectral efficiencies by enabling the direct communication of devices in proximity without passing through enhanced-NodeB (eNB). However, to enable D2D communication in a cellular network presents a challenge with regard to radio resource management since D2D links reuse the uplink radio resources of cellular users and it can cause interference to the receiving channels of D2D user equipment (DUE). In this paper, a hybrid mechanism is proposed that uses Fractional Frequency Reuse (FFR) and Almost Blank Sub-frame (ABS) schemes to handle inter-cell interference caused by cellular user equipments (CUEs) to D2D receivers (DUE-Rxs), reusing the same resources at the cell edge area. In our case, DUE-Rxs are considered as victim nodes and CUEs as aggressor nodes, since our primary target is to minimize inter-cell interference in order to increase the signal to interference and noise ratio (SINR) of the target DUE-Rx at the cell edge area. The numerical results show that the interference level of the target D2D receiver (DUE-Rx) decreases significantly compared to the conventional FFR at the cell edge. In addition, the system throughput of the proposed scheme can be increased up to 60% compared to the conventional FFR. PMID:28489064

  20. An Interference Mitigation Scheme of Device-to-Device Communications for Sensor Networks Underlying LTE-A.

    PubMed

    Kim, Jeehyeong; Karim, Nzabanita Abdoul; Cho, Sunghyun

    2017-05-10

    Device-to-Device (D2D) communication technology has become a key factor in wireless sensor networks to form autonomous communication links among sensor nodes. Many research results for D2D have been presented to resolve different technical issues of D2D. Nevertheless, the previous works have not resolved the shortage of data rate and limited coverage of wireless sensor networks. Due to bandwidth shortages and limited communication coverage, 3rd Generation Partnership Project (3GPP) has introduced a new Device-to-Device (D2D) communication technique underlying cellular networks, which can improve spectral efficiencies by enabling the direct communication of devices in proximity without passing through enhanced-NodeB (eNB). However, to enable D2D communication in a cellular network presents a challenge with regard to radio resource management since D2D links reuse the uplink radio resources of cellular users and it can cause interference to the receiving channels of D2D user equipment (DUE). In this paper, a hybrid mechanism is proposed that uses Fractional Frequency Reuse (FFR) and Almost Blank Sub-frame (ABS) schemes to handle inter-cell interference caused by cellular user equipments (CUEs) to D2D receivers (DUE-Rxs), reusing the same resources at the cell edge area. In our case, DUE-Rxs are considered as victim nodes and CUEs as aggressor nodes, since our primary target is to minimize inter-cell interference in order to increase the signal to interference and noise ratio (SINR) of the target DUE-Rx at the cell edge area. The numerical results show that the interference level of the target D2D receiver (DUE-Rx) decreases significantly compared to the conventional FFR at the cell edge. In addition, the system throughput of the proposed scheme can be increased up to 60% compared to the conventional FFR.

  1. 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 sequence of events underlying AD. Indeed, studies of models of AD in simple organisms, differentiated cells in culture and rodents are beginning to offer hope that the onset and progression of AD, if detected at an early stage, may be stopped, delayed, or even reversed, by activating or modulating networks involved in proteostasis and the clearance of toxic species. In practice, the incorporation of next-generation neuroimaging, high-throughput and computational approaches are opening the way towards early diagnosis well before irreversible cell death. Thus, the presence or co-occurrence of: (a) accumulation of toxic Aβ oligomers and tau species; (b) altered splicing and transcriptome patterns; (c) impaired redox, proteostatic, and metabolic networks together with, (d) compromised homeostatic capacities may constitute relevant 'AD hallmarks at the cellular level' towards reliable and early diagnosis. From here, preventive lifestyle changes and tailored therapies may be investigated, such as combined strategies aimed at both lowering the production of toxic species and potentiating homeostatic responses, in order to prevent or delay the onset, and arrest, alleviate, or even reverse the progression of the disease.

  2. 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.

  3. Cytoskeletal Network Morphology Regulates Intracellular Transport Dynamics.

    PubMed

    Ando, David; Korabel, Nickolay; Huang, Kerwyn Casey; Gopinathan, Ajay

    2015-10-20

    Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. A Three-Dimensional Computational Model of Collagen Network Mechanics

    PubMed Central

    Lee, Byoungkoo; Zhou, Xin; Riching, Kristin; Eliceiri, Kevin W.; Keely, Patricia J.; Guelcher, Scott A.; Weaver, Alissa M.; Jiang, Yi

    2014-01-01

    Extracellular matrix (ECM) strongly influences cellular behaviors, including cell proliferation, adhesion, and particularly migration. In cancer, the rigidity of the stromal collagen environment is thought to control tumor aggressiveness, and collagen alignment has been linked to tumor cell invasion. While the mechanical properties of collagen at both the single fiber scale and the bulk gel scale are quite well studied, how the fiber network responds to local stress or deformation, both structurally and mechanically, is poorly understood. This intermediate scale knowledge is important to understanding cell-ECM interactions and is the focus of this study. We have developed a three-dimensional elastic collagen fiber network model (bead-and-spring model) and studied fiber network behaviors for various biophysical conditions: collagen density, crosslinker strength, crosslinker density, and fiber orientation (random vs. prealigned). We found the best-fit crosslinker parameter values using shear simulation tests in a small strain region. Using this calibrated collagen model, we simulated both shear and tensile tests in a large linear strain region for different network geometry conditions. The results suggest that network geometry is a key determinant of the mechanical properties of the fiber network. We further demonstrated how the fiber network structure and mechanics evolves with a local formation, mimicking the effect of pulling by a pseudopod during cell migration. Our computational fiber network model is a step toward a full biomechanical model of cellular behaviors in various ECM conditions. PMID:25386649

  5. Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA interaction network regulating intestinal epithelial cellular pathways using R programming.

    PubMed

    Robinson, J M; Henderson, W A

    2018-01-12

    We report a method using functional-molecular databases and network modelling to identify hypothetical mRNA-miRNA interaction networks regulating intestinal epithelial barrier function. The model forms a data-analysis component of our cell culture experiments, which produce RNA expression data from Nanostring Technologies nCounter ® system. The epithelial tight-junction (TJ) and actin cytoskeleton interact as molecular components of the intestinal epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is effected by the Rac/Rock/Rho signaling pathway and other associated pathways which may be activated or suppressed by extracellular signaling from growth factors, hormones, and immune receptors. Pathway activations affect epithelial homeostasis, contributing to degradation of the epithelial barrier associated with osmotic dysregulation, inflammation, and tumor development. The complexity underlying miRNA-mRNA interaction networks represents a roadblock for prediction and validation of competing-endogenous RNA network function. We developed a network model to identify hypothetical co-regulatory motifs in a miRNA-mRNA interaction network related to epithelial function. A mRNA-miRNA interaction list was generated using KEGG and miRWalk2.0 databases. R-code was developed to quantify and visualize inherent network structures. We identified a sub-network with a high number of shared, targeting miRNAs, of genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D.

  6. Water deficit-induced changes in transcription factor expression in maize seedlings

    USDA-ARS?s Scientific Manuscript database

    Plants tolerate water deficits by regulating gene networks controlling cellular and physiological traits to modify growth and development. Transcription factor (TFs) directed regulation of transcription within these gene networks is key to eliciting appropriate responses. In this study, reverse tran...

  7. Survey on Monitoring and Quality Controlling of the Mobile Biosignal Delivery.

    PubMed

    Pawar, Pravin A; Edla, Damodar R; Edoh, Thierry; Shinde, Vijay; van Beijnum, Bert-Jan

    2017-10-31

    A Mobile Patient Monitoring System (MPMS) acquires patient's biosignals and transmits them using wireless network connection to the decision-making module or healthcare professional for the assessment of patient's condition. A variety of wireless network technologies such as wireless personal area networks (e.g., Bluetooth), mobile ad-hoc networks (MANET), and infrastructure-based networks (e.g., WLAN and cellular networks) are in practice for biosignals delivery. The wireless network quality-of-service (QoS) requirements of biosignals delivery are mainly specified in terms of required bandwidth, acceptable delay, and tolerable error rate. An important research challenge in the MPMS is how to satisfy QoS requirements of biosignals delivery in the environment characterized by patient mobility, deployment of multiple wireless network technologies, and variable QoS characteristics of the wireless networks. QoS requirements are mainly application specific, while available QoS is largely dependent on QoS provided by wireless network in use. QoS provisioning refers to providing support for improving QoS experience of networked applications. In resource poor conditions, application adaptation may also be required to make maximum use of available wireless network QoS. This survey paper presents a survey of recent developments in the area of QoS provisioning for MPMS. In particular, our contributions are as follows: (1) overview of wireless networks and network QoS requirements of biosignals delivery; (2) survey of wireless networks' QoS performance evaluation for the transmission of biosignals; and (3) survey of QoS provisioning mechanisms for biosignals delivery in MPMS. We also propose integrating end-to-end QoS monitoring and QoS provisioning strategies in a mobile patient monitoring system infrastructure to support optimal delivery of biosignals to the healthcare professionals.

  8. Realistic modeling of neurons and networks: towards brain simulation.

    PubMed

    D'Angelo, Egidio; Solinas, Sergio; Garrido, Jesus; Casellato, Claudia; Pedrocchi, Alessandra; Mapelli, Jonathan; Gandolfi, Daniela; Prestori, Francesca

    2013-01-01

    Realistic modeling is a new advanced methodology for investigating brain functions. Realistic modeling is based on a detailed biophysical description of neurons and synapses, which can be integrated into microcircuits. The latter can, in turn, be further integrated to form large-scale brain networks and eventually to reconstruct complex brain systems. Here we provide a review of the realistic simulation strategy and use the cerebellar network as an example. This network has been carefully investigated at molecular and cellular level and has been the object of intense theoretical investigation. The cerebellum is thought to lie at the core of the forward controller operations of the brain and to implement timing and sensory prediction functions. The cerebellum is well described and provides a challenging field in which one of the most advanced realistic microcircuit models has been generated. We illustrate how these models can be elaborated and embedded into robotic control systems to gain insight into how the cellular properties of cerebellar neurons emerge in integrated behaviors. Realistic network modeling opens up new perspectives for the investigation of brain pathologies and for the neurorobotic field.

  9. Realistic modeling of neurons and networks: towards brain simulation

    PubMed Central

    D’Angelo, Egidio; Solinas, Sergio; Garrido, Jesus; Casellato, Claudia; Pedrocchi, Alessandra; Mapelli, Jonathan; Gandolfi, Daniela; Prestori, Francesca

    Summary Realistic modeling is a new advanced methodology for investigating brain functions. Realistic modeling is based on a detailed biophysical description of neurons and synapses, which can be integrated into microcircuits. The latter can, in turn, be further integrated to form large-scale brain networks and eventually to reconstruct complex brain systems. Here we provide a review of the realistic simulation strategy and use the cerebellar network as an example. This network has been carefully investigated at molecular and cellular level and has been the object of intense theoretical investigation. The cerebellum is thought to lie at the core of the forward controller operations of the brain and to implement timing and sensory prediction functions. The cerebellum is well described and provides a challenging field in which one of the most advanced realistic microcircuit models has been generated. We illustrate how these models can be elaborated and embedded into robotic control systems to gain insight into how the cellular properties of cerebellar neurons emerge in integrated behaviors. Realistic network modeling opens up new perspectives for the investigation of brain pathologies and for the neurorobotic field. PMID:24139652

  10. Analysis and Synthesis of Adaptive Neural Elements and Assembles

    DTIC Science & Technology

    1990-12-12

    that neuron-like elements and network architectures that reflect the cellular processes contributing to activity- dependent neuromodulation can simulate...conditioning. Therefore, we were interested in determining whether a small network containing elements with the activity-dependent neuromodulation learning...network that are capable of activity- dependent neuromodulation (i.e., associative enhancement of synaptic strength). The motor elements (MNA and MNB) were

  11. High-resolution CMOS MEA platform to study neurons at subcellular, cellular, and network levels†

    PubMed Central

    Müller, Jan; Ballini, Marco; Livi, Paolo; Chen, Yihui; Radivojevic, Milos; Shadmani, Amir; Viswam, Vijay; Jones, Ian L.; Fiscella, Michele; Diggelmann, Roland; Stettler, Alexander; Frey, Urs; Bakkum, Douglas J.; Hierlemann, Andreas

    2017-01-01

    Studies on information processing and learning properties of neuronal networks would benefit from simultaneous and parallel access to the activity of a large fraction of all neurons in such networks. Here, we present a CMOS-based device, capable of simultaneously recording the electrical activity of over a thousand cells in in vitro neuronal networks. The device provides sufficiently high spatiotemporal resolution to enable, at the same time, access to neuronal preparations on subcellular, cellular, and network level. The key feature is a rapidly reconfigurable array of 26 400 microelectrodes arranged at low pitch (17.5 μm) within a large overall sensing area (3.85 × 2.10 mm2). An arbitrary subset of the electrodes can be simultaneously connected to 1024 low-noise readout channels as well as 32 stimulation units. Each electrode or electrode subset can be used to electrically stimulate or record the signals of virtually any neuron on the array. We demonstrate the applicability and potential of this device for various different experimental paradigms: large-scale recordings from whole networks of neurons as well as investigations of axonal properties of individual neurons. PMID:25973786

  12. Phenotypic stability and plasticity in GMP-derived cells as determined by their underlying regulatory network.

    PubMed

    Ramírez, Carlos; Mendoza, Luis

    2018-04-01

    Blood cell formation has been recognized as a suitable system to study celular differentiation mainly because of its experimental accessibility, and because it shows characteristics such as hierarchical and gradual bifurcated patterns of commitment, which are present in several developmental processes. Although hematopoiesis has been extensively studied and there is a wealth of molecular and cellular data about it, it is not clear how the underlying molecular regulatory networks define or restrict cellular differentiation processes. Here, we infer the molecular regulatory network that controls the differentiation of a blood cell subpopulation derived from the granulocyte-monocyte precursor (GMP), comprising monocytes, neutrophils, eosinophils, basophils and mast cells. We integrate published qualitative experimental data into a model to describe temporal expression patterns observed in GMP-derived cells. The model is implemented as a Boolean network, and its dynamical behavior is studied. Steady states of the network can be clearly identified with the expression profiles of monocytes, mast cells, neutrophils, basophils, and eosinophils, under wild-type and mutant backgrounds. All scripts are publicly available at https://github.com/caramirezal/RegulatoryNetworkGMPModel. lmendoza@biomedicas.unam.mx. Supplementary data are available at Bioinformatics online.

  13. 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

  14. High-resolution CMOS MEA platform to study neurons at subcellular, cellular, and network levels.

    PubMed

    Müller, Jan; Ballini, Marco; Livi, Paolo; Chen, Yihui; Radivojevic, Milos; Shadmani, Amir; Viswam, Vijay; Jones, Ian L; Fiscella, Michele; Diggelmann, Roland; Stettler, Alexander; Frey, Urs; Bakkum, Douglas J; Hierlemann, Andreas

    2015-07-07

    Studies on information processing and learning properties of neuronal networks would benefit from simultaneous and parallel access to the activity of a large fraction of all neurons in such networks. Here, we present a CMOS-based device, capable of simultaneously recording the electrical activity of over a thousand cells in in vitro neuronal networks. The device provides sufficiently high spatiotemporal resolution to enable, at the same time, access to neuronal preparations on subcellular, cellular, and network level. The key feature is a rapidly reconfigurable array of 26 400 microelectrodes arranged at low pitch (17.5 μm) within a large overall sensing area (3.85 × 2.10 mm(2)). An arbitrary subset of the electrodes can be simultaneously connected to 1024 low-noise readout channels as well as 32 stimulation units. Each electrode or electrode subset can be used to electrically stimulate or record the signals of virtually any neuron on the array. We demonstrate the applicability and potential of this device for various different experimental paradigms: large-scale recordings from whole networks of neurons as well as investigations of axonal properties of individual neurons.

  15. Spatial and temporal structure of the clinical research based on mesenchymal stromal cells: A network analysis.

    PubMed

    Monsarrat, Paul; Kemoun, Philippe; Vergnes, Jean-Noel; Sensebe, Luc; Casteilla, Louis; Planat-Benard, Valerie

    2017-01-01

    Using innovative tools derived from social network analysis, the aims of this study were (i) to decipher the spatial and temporal structure of the research centers network dedicated to the therapeutic uses of mesenchymal stromal cells (MSCs) and (ii) to measure the influence of fields of applications, cellular sources and industry funding on network topography. From each trial using MSCs reported on ClinicalTrials.gov, all research centers were extracted. Networks were generated using Cytoscape 3.2.2, where each center was assimilated to a node, and one trial to an edge connecting two nodes. The analysis included 563 studies. An independent segregation was obvious between continents. Asian, South American and African centers were significantly more isolated than other centers. Isolated centers had fewer advanced phases (P <0.001), completed studies (P = 0.01) and industry-supported studies (P <0.001). Various thematic priorities among continents were identified: the cardiovascular, digestive and nervous system diseases were strongly studied by North America, Europe and Asia, respectively. The choice of cellular sources also affected the network topography; North America was primarily involved in bone-marrow-derived MSC research, whereas Europe and Asia dominated the use of adipose-derived MSCs. Industrial funding was the highest for North American centers (90.5%). Strengthening of international standards and statements with institutional, federal and industrial partners is necessary. More connections would facilitate the transfer of knowledge, sharing of resources, mobility of researchers and advancement of trials. Developing partnerships between industry and academic centers seems beneficial to the advancement of trials across different phases and would facilitate the translation of research discoveries. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  16. Scale-space measures for graph topology link protein network architecture to function.

    PubMed

    Hulsman, Marc; Dimitrakopoulos, Christos; de Ridder, Jeroen

    2014-06-15

    The network architecture of physical protein interactions is an important determinant for the molecular functions that are carried out within each cell. To study this relation, the network architecture can be characterized by graph topological characteristics such as shortest paths and network hubs. These characteristics have an important shortcoming: they do not take into account that interactions occur across different scales. This is important because some cellular functions may involve a single direct protein interaction (small scale), whereas others require more and/or indirect interactions, such as protein complexes (medium scale) and interactions between large modules of proteins (large scale). In this work, we derive generalized scale-aware versions of known graph topological measures based on diffusion kernels. We apply these to characterize the topology of networks across all scales simultaneously, generating a so-called graph topological scale-space. The comprehensive physical interaction network in yeast is used to show that scale-space based measures consistently give superior performance when distinguishing protein functional categories and three major types of functional interactions-genetic interaction, co-expression and perturbation interactions. Moreover, we demonstrate that graph topological scale spaces capture biologically meaningful features that provide new insights into the link between function and protein network architecture. Matlab(TM) code to calculate the scale-aware topological measures (STMs) is available at http://bioinformatics.tudelft.nl/TSSA © The Author 2014. Published by Oxford University Press.

  17. Metabolism Goes Viral

    PubMed Central

    Miyake-Stoner, Shigeki J.; O’Shea, Clodagh C.

    2014-01-01

    Viral and cellular oncogenes converge in targeting critical protein interaction networks to reprogram the cellular DNA and protein replication machinery for pathological replication. In this issue, Thai et al. (2014) show that adenovirus E4ORF1 activates MYC glycolytic targets to induce a Warburg-like effect that converts glucose into nucleotides for viral replication. PMID:24703688

  18. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Endele, Max; Etzrodt, Martin; Schroeder, Timm, E-mail: timm.schroeder@bsse.ethz.ch

    Hematopoiesis is the cumulative consequence of finely tuned signaling pathways activated through extrinsic factors, such as local niche signals and systemic hematopoietic cytokines. Whether extrinsic factors actively instruct the lineage choice of hematopoietic stem and progenitor cells or are only selectively allowing survival and proliferation of already intrinsically lineage-committed cells has been debated over decades. Recent results demonstrated that cytokines can instruct lineage choice. However, the precise function of individual cytokine-triggered signaling molecules in inducing cellular events like proliferation, lineage choice, and differentiation remains largely elusive. Signal transduction pathways activated by different cytokine receptors are highly overlapping, but support themore » production of distinct hematopoietic lineages. Cellular context, signaling dynamics, and the crosstalk of different signaling pathways determine the cellular response of a given extrinsic signal. New tools to manipulate and continuously quantify signaling events at the single cell level are therefore required to thoroughly interrogate how dynamic signaling networks yield a specific cellular response. - Highlights: • Recent studies provided definite proof for lineage-instructive action of cytokines. • Signaling pathways involved in hematopoietic lineage instruction remain elusive. • New tools are emerging to quantitatively study dynamic signaling networks over time.« less

  19. Proceedings of the Workshop on Advanced Network and Technology Concepts for Mobile, Micro, and Personal Communications

    NASA Technical Reports Server (NTRS)

    Paul, Lori (Editor)

    1991-01-01

    The Workshop on Advanced Network and Technology Concepts for Mobile, Micro, and Personal Communications was held at NASA's JPL Laboratory on 30-31 May 1991. It provided a forum for reviewing the development of advanced network and technology concepts for turn-of-the-century telecommunications. The workshop was organized into three main categories: (1) Satellite-Based Networks (L-band, C-band, Ku-band, and Ka-band); (2) Terrestrial-Based Networks (cellular, CT2, PCN, GSM, and other networks); and (3) Hybrid Satellite/Terrestrial Networks. The proceedings contain presentation papers from each of the above categories.

  20. Nanofluidic interfaces in microfluidic networks

    DOE PAGES

    Millet, Larry J.; Doktycz, Mitchel John; Retterer, Scott T.

    2015-09-24

    The integration of nano- and microfluidic technologies enables the construction of tunable interfaces to physical and biological systems across relevant length scales. The ability to perform chemical manipulations of miniscule sample volumes is greatly enhanced through these technologies and extends the ability to manipulate and sample the local fluidic environments at subcellular, cellular and community or tissue scales. Here we describe the development of a flexible surface micromachining process for the creation of nanofluidic channel arrays integrated within SU-8 microfluidic networks. The use of a semi-porous, silicon rich, silicon nitride structural layer allows rapid release of the sacrificial silicon dioxidemore » during the nanochannel fabrication. Nanochannel openings that form the interface to biological samples are customized using focused ion beam milling. The compatibility of these interfaces with on-chip microbial culture is demonstrated.« less

  1. Drug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platform

    PubMed Central

    Chuang, Ryan; Hall, Benjamin A.; Benque, David; Cook, Byron; Ishtiaq, Samin; Piterman, Nir; Taylor, Alex; Vardi, Moshe; Koschmieder, Steffen; Gottgens, Berthold; Fisher, Jasmin

    2015-01-01

    Chronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3. PMID:25644994

  2. Drug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platform

    NASA Astrophysics Data System (ADS)

    Chuang, Ryan; Hall, Benjamin A.; Benque, David; Cook, Byron; Ishtiaq, Samin; Piterman, Nir; Taylor, Alex; Vardi, Moshe; Koschmieder, Steffen; Gottgens, Berthold; Fisher, Jasmin

    2015-02-01

    Chronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3.

  3. Detection of dysregulated protein-association networks by high-throughput proteomics predicts cancer vulnerabilities.

    PubMed

    Lapek, John D; Greninger, Patricia; Morris, Robert; Amzallag, Arnaud; Pruteanu-Malinici, Iulian; Benes, Cyril H; Haas, Wilhelm

    2017-10-01

    The formation of protein complexes and the co-regulation of the cellular concentrations of proteins are essential mechanisms for cellular signaling and for maintaining homeostasis. Here we use isobaric-labeling multiplexed proteomics to analyze protein co-regulation and show that this allows the identification of protein-protein associations with high accuracy. We apply this 'interactome mapping by high-throughput quantitative proteome analysis' (IMAHP) method to a panel of 41 breast cancer cell lines and show that deviations of the observed protein co-regulations in specific cell lines from the consensus network affects cellular fitness. Furthermore, these aberrant interactions serve as biomarkers that predict the drug sensitivity of cell lines in screens across 195 drugs. We expect that IMAHP can be broadly used to gain insight into how changing landscapes of protein-protein associations affect the phenotype of biological systems.

  4. Motifs, modules and games in bacteria.

    PubMed

    Wolf, Denise M; Arkin, Adam P

    2003-04-01

    Global explorations of regulatory network dynamics, organization and evolution have become tractable thanks to high-throughput sequencing and molecular measurement of bacterial physiology. From these, a nascent conceptual framework is developing, that views the principles of regulation in term of motifs, modules and games. Motifs are small, repeated, and conserved biological units ranging from molecular domains to small reaction networks. They are arranged into functional modules, genetically dissectible cellular functions such as the cell cycle, or different stress responses. The dynamical functioning of modules defines the organism's strategy to survive in a game, pitting cell against cell, and cell against environment. Placing pathway structure and dynamics into an evolutionary context begins to allow discrimination between those physical and molecular features that particularize a species to its surroundings, and those that provide core physiological function. This approach promises to generate a higher level understanding of cellular design, pathway evolution and cellular bioengineering.

  5. Motifs, modules and games in bacteria

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wolf, Denise M.; Arkin, Adam P.

    2003-04-01

    Global explorations of regulatory network dynamics, organization and evolution have become tractable thanks to high-throughput sequencing and molecular measurement of bacterial physiology. From these, a nascent conceptual framework is developing, that views the principles of regulation in term of motifs, modules and games. Motifs are small, repeated, and conserved biological units ranging from molecular domains to small reaction networks. They are arranged into functional modules, genetically dissectible cellular functions such as the cell cycle, or different stress responses. The dynamical functioning of modules defines the organism's strategy to survive in a game, pitting cell against cell, and cell against environment.more » Placing pathway structure and dynamics into an evolutionary context begins to allow discrimination between those physical and molecular features that particularize a species to its surroundings, and those that provide core physiological function. This approach promises to generate a higher level understanding of cellular design, pathway evolution and cellular bioengineering.« less

  6. A tree-like Bayesian structure learning algorithm for small-sample datasets from complex biological model systems.

    PubMed

    Yin, Weiwei; Garimalla, Swetha; Moreno, Alberto; Galinski, Mary R; Styczynski, Mark P

    2015-08-28

    There are increasing efforts to bring high-throughput systems biology techniques to bear on complex animal model systems, often with a goal of learning about underlying regulatory network structures (e.g., gene regulatory networks). However, complex animal model systems typically have significant limitations on cohort sizes, number of samples, and the ability to perform follow-up and validation experiments. These constraints are particularly problematic for many current network learning approaches, which require large numbers of samples and may predict many more regulatory relationships than actually exist. Here, we test the idea that by leveraging the accuracy and efficiency of classifiers, we can construct high-quality networks that capture important interactions between variables in datasets with few samples. We start from a previously-developed tree-like Bayesian classifier and generalize its network learning approach to allow for arbitrary depth and complexity of tree-like networks. Using four diverse sample networks, we demonstrate that this approach performs consistently better at low sample sizes than the Sparse Candidate Algorithm, a representative approach for comparison because it is known to generate Bayesian networks with high positive predictive value. We develop and demonstrate a resampling-based approach to enable the identification of a viable root for the learned tree-like network, important for cases where the root of a network is not known a priori. We also develop and demonstrate an integrated resampling-based approach to the reduction of variable space for the learning of the network. Finally, we demonstrate the utility of this approach via the analysis of a transcriptional dataset of a malaria challenge in a non-human primate model system, Macaca mulatta, suggesting the potential to capture indicators of the earliest stages of cellular differentiation during leukopoiesis. We demonstrate that by starting from effective and efficient approaches for creating classifiers, we can identify interesting tree-like network structures with significant ability to capture the relationships in the training data. This approach represents a promising strategy for inferring networks with high positive predictive value under the constraint of small numbers of samples, meeting a need that will only continue to grow as more high-throughput studies are applied to complex model systems.

  7. The Integrated Role of Wnt/β-Catenin, N-Glycosylation, and E-Cadherin-Mediated Adhesion in Network Dynamics

    PubMed Central

    Vargas, Diego A.; Sun, Meng; Sadykov, Khikmet; Kukuruzinska, Maria A.; Zaman, Muhammad H.

    2016-01-01

    The cellular network composed of the evolutionarily conserved metabolic pathways of protein N-glycosylation, Wnt/β-catenin signaling pathway, and E-cadherin-mediated cell-cell adhesion plays pivotal roles in determining the balance between cell proliferation and intercellular adhesion during development and in maintaining homeostasis in differentiated tissues. These pathways share a highly conserved regulatory molecule, β-catenin, which functions as both a structural component of E-cadherin junctions and as a co-transcriptional activator of the Wnt/β-catenin signaling pathway, whose target is the N-glycosylation-regulating gene, DPAGT1. Whereas these pathways have been studied independently, little is known about the dynamics of their interaction. Here we present the first numerical model of this network in MDCK cells. Since the network comprises a large number of molecules with varying cell context and time-dependent levels of expression, it can give rise to a wide range of plausible cellular states that are difficult to track. Using known kinetic parameters for individual reactions in the component pathways, we have developed a theoretical framework and gained new insights into cellular regulation of the network. Specifically, we developed a mathematical model to quantify the fold-change in concentration of any molecule included in the mathematical representation of the network in response to a simulated activation of the Wnt/ β-catenin pathway with Wnt3a under different conditions. We quantified the importance of protein N-glycosylation and synthesis of the DPAGT1 encoded enzyme, GPT, in determining the abundance of cytoplasmic β-catenin. We confirmed the role of axin in β-catenin degradation. Finally, our data suggest that cell-cell adhesion is insensitive to E-cadherin recycling in the cell. We validate the model by inhibiting β-catenin-mediated activation of DPAGT1 expression and predicting changes in cytoplasmic β-catenin concentration and stability of E-cadherin junctions in response to DPAGT1 inhibition. We show the impact of pathway dysregulation through measurements of cell migration in scratch-wound assays. Collectively, our results highlight the importance of numerical analyses of cellular networks dynamics to gain insights into physiological processes and potential design of therapeutic strategies to prevent epithelial cell invasion in cancer. PMID:27427963

  8. Reverse Engineering Cellular Networks with Information Theoretic Methods

    PubMed Central

    Villaverde, Alejandro F.; Ross, John; Banga, Julio R.

    2013-01-01

    Building mathematical models of cellular networks lies at the core of systems biology. It involves, among other tasks, the reconstruction of the structure of interactions between molecular components, which is known as network inference or reverse engineering. Information theory can help in the goal of extracting as much information as possible from the available data. A large number of methods founded on these concepts have been proposed in the literature, not only in biology journals, but in a wide range of areas. Their critical comparison is difficult due to the different focuses and the adoption of different terminologies. Here we attempt to review some of the existing information theoretic methodologies for network inference, and clarify their differences. While some of these methods have achieved notable success, many challenges remain, among which we can mention dealing with incomplete measurements, noisy data, counterintuitive behaviour emerging from nonlinear relations or feedback loops, and computational burden of dealing with large data sets. PMID:24709703

  9. Integrative systems control approach for reactivating Kaposi's sarcoma-associated herpesvirus (KSHV) with combinatory drugs

    PubMed Central

    Sun, Chien-Pin; Usui, Takane; Yu, Fuqu; Al-Shyoukh, Ibrahim; Shamma, Jeff; Sun, Ren; Ho, Chih-Ming

    2009-01-01

    Cells serve as basic units of life and represent intricate biological molecular systems. The vast number of cellular molecules with their signaling and regulatory circuitries forms an intertwined network. In this network, each pathway interacts non-linearly with others through different intermediates. Thus, the challenge of manipulating cellular functions for desired outcomes, such as cancer eradication and controlling viral infection lies within the integrative system of regulatory circuitries. By using a closed-loop system control scheme, we can efficiently analyze biological signaling networks and manipulate their behavior through multiple stimulations on a collection of pathways. Specifically, we aimed to maximize the reactivation of Kaposi's Sarcoma-associated Herpesvirus (KSHV) in a Primary Effusion Lymphoma cell line. The advantage of this approach is that it is well-suited to study complex integrated systems; it circumvents the need for detailed information of individual signaling components; and it investigates the network as a whole by utilizing key systemic outputs as indicators. PMID:19851479

  10. Integrative systems control approach for reactivating Kaposi's sarcoma-associated herpesvirus (KSHV) with combinatory drugs.

    PubMed

    Sun, Chien-Pin; Usui, Takane; Yu, Fuqu; Al-Shyoukh, Ibrahim; Shamma, Jeff; Sun, Ren; Ho, Chih-Ming

    2009-01-01

    Cells serve as basic units of life and represent intricate biological molecular systems. The vast number of cellular molecules with their signaling and regulatory circuitries forms an intertwined network. In this network, each pathway interacts non-linearly with others through different intermediates. Thus, the challenge of manipulating cellular functions for desired outcomes, such as cancer eradication and controlling viral infection lies within the integrative system of regulatory circuitries. By using a closed-loop system control scheme, we can efficiently analyze biological signaling networks and manipulate their behavior through multiple stimulations on a collection of pathways. Specifically, we aimed to maximize the reactivation of Kaposi's Sarcoma-associated Herpesvirus (KSHV) in a Primary Effusion Lymphoma cell line. The advantage of this approach is that it is well-suited to study complex integrated systems; it circumvents the need for detailed information of individual signaling components; and it investigates the network as a whole by utilizing key systemic outputs as indicators.

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

    PubMed Central

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

    2014-01-01

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

  12. Collective Calcium Signaling of Defective Multicellular Networks

    NASA Astrophysics Data System (ADS)

    Potter, Garrett; Sun, Bo

    2015-03-01

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

  13. Petri net-based method for the analysis of the dynamics of signal propagation in signaling pathways.

    PubMed

    Hardy, Simon; Robillard, Pierre N

    2008-01-15

    Cellular signaling networks are dynamic systems that propagate and process information, and, ultimately, cause phenotypical responses. Understanding the circuitry of the information flow in cells is one of the keys to understanding complex cellular processes. The development of computational quantitative models is a promising avenue for attaining this goal. Not only does the analysis of the simulation data based on the concentration variations of biological compounds yields information about systemic state changes, but it is also very helpful for obtaining information about the dynamics of signal propagation. This article introduces a new method for analyzing the dynamics of signal propagation in signaling pathways using Petri net theory. The method is demonstrated with the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) regulation network. The results constitute temporal information about signal propagation in the network, a simplified graphical representation of the network and of the signal propagation dynamics and a characterization of some signaling routes as regulation motifs.

  14. Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.

    PubMed

    Cheng, Feixiong; Murray, James L; Zhao, Junfei; Sheng, Jinsong; Zhao, Zhongming; Rubin, Donald H

    2016-09-01

    Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.

  15. A Self-organized MIMO-OFDM-based Cellular Network

    NASA Astrophysics Data System (ADS)

    Grünheid, Rainer; Fellenberg, Christian

    2012-05-01

    This paper presents a system proposal for a self-organized cellular network, which is based on the MIMO-OFDM transmission technique. Multicarrier transmission, combined with appropriate beamforming concepts, yields high bandwidth-efficiency and shows a robust behavior in multipath radio channels. Moreover, it provides a fine and tuneable granularity of space-time-frequency resources. Using a TDD approach and interference measurements in each cell, the Base Stations (BSs) decide autonomously which of the space-time-frequency resource blocks are allocated to the Mobile Terminals (MTs) in the cell, in order to fulfil certain Quality of Service (QoS) parameters. Since a synchronized Single Frequency Network (SFN), i.e., a re-use factor of one is applied, the resource blocks can be shared adaptively and flexibly among the cells, which is very advantageous in the case of a non-uniform MT distribution.

  16. A novel spatter detection algorithm based on typical cellular neural network operations for laser beam welding processes

    NASA Astrophysics Data System (ADS)

    Nicolosi, L.; Abt, F.; Blug, A.; Heider, A.; Tetzlaff, R.; Höfler, H.

    2012-01-01

    Real-time monitoring of laser beam welding (LBW) has increasingly gained importance in several manufacturing processes ranging from automobile production to precision mechanics. In the latter, a novel algorithm for the real-time detection of spatters was implemented in a camera based on cellular neural networks. The latter can be connected to the optics of commercially available laser machines leading to real-time monitoring of LBW processes at rates up to 15 kHz. Such high monitoring rates allow the integration of other image evaluation tasks such as the detection of the full penetration hole for real-time control of process parameters.

  17. Multilane Traffic Flow Modeling Using Cellular Automata Theory

    NASA Astrophysics Data System (ADS)

    Chechina, Antonina; Churbanova, Natalia; Trapeznikova, Marina

    2018-02-01

    The paper deals with the mathematical modeling of traffic flows on urban road networks using microscopic approach. The model is based on the cellular automata theory and presents a generalization of the Nagel-Schreckenberg model to a multilane case. The created program package allows to simulate traffic on various types of road fragments (T or X type intersection, strait road elements, etc.) and on road networks that consist of these elements. Besides that, it allows to predict the consequences of various decisions regarding road infrastructure changes, such as: number of lanes increasing/decreasing, putting new traffic lights into operation, building new roads, entrances/exits, road junctions.

  18. Multi-casting approach for vascular networks in cellularized hydrogels.

    PubMed

    Justin, Alexander W; Brooks, Roger A; Markaki, Athina E

    2016-12-01

    Vascularization is essential for living tissue and remains a major challenge in the field of tissue engineering. A lack of a perfusable channel network within a large and densely populated tissue engineered construct leads to necrotic core formation, preventing fabrication of functional tissues and organs. We report a new method for producing a hierarchical, three-dimensional (3D) and perfusable vasculature in a large, cellularized fibrin hydrogel. Bifurcating channels, varying in size from 1 mm to 200-250 µm, are formed using a novel process in which we convert a 3D printed thermoplastic material into a gelatin network template, by way of an intermediate alginate hydrogel. This enables a CAD-based model design, which is highly customizable, reproducible, and which can yield highly complex architectures, to be made into a removable material, which can be used in cellular environments. Our approach yields constructs with a uniform and high density of cells in the bulk, made from bioactive collagen and fibrin hydrogels. Using standard cell staining and immuno-histochemistry techniques, we showed good cell seeding and the presence of tight junctions between channel endothelial cells, and high cell viability and cell spreading in the bulk hydrogel. © 2016 The Authors.

  19. 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

  20. Coverage extension and balancing the transmitted power of the moving relay node at LTE-A cellular network.

    PubMed

    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.

  1. Detection of multiple perturbations in multi-omics biological networks.

    PubMed

    Griffin, Paula J; Zhang, Yuqing; Johnson, William Evan; Kolaczyk, Eric D

    2018-05-17

    Cellular mechanism-of-action is of fundamental concern in many biological studies. It is of particular interest for identifying the cause of disease and learning the way in which treatments act against disease. However, pinpointing such mechanisms is difficult, due to the fact that small perturbations to the cell can have wide-ranging downstream effects. Given a snapshot of cellular activity, it can be challenging to tell where a disturbance originated. The presence of an ever-greater variety of high-throughput biological data offers an opportunity to examine cellular behavior from multiple angles, but also presents the statistical challenge of how to effectively analyze data from multiple sources. In this setting, we propose a method for mechanism-of-action inference by extending network filtering to multi-attribute data. We first estimate a joint Gaussian graphical model across multiple data types using penalized regression and filter for network effects. We then apply a set of likelihood ratio tests to identify the most likely site of the original perturbation. In addition, we propose a conditional testing procedure to allow for detection of multiple perturbations. We demonstrate this methodology on paired gene expression and methylation data from The Cancer Genome Atlas (TCGA). © 2018, The International Biometric Society.

  2. Biconnectivity of the cellular metabolism: A cross-species study and its implication for human diseases

    PubMed Central

    Kim, P.; Lee, D.-S.; Kahng, B.

    2015-01-01

    The maintenance of stability during perturbations is essential for living organisms, and cellular networks organize multiple pathways to enable elements to remain connected and communicate, even when some pathways are broken. Here, we evaluated the biconnectivity of the metabolic networks of 506 species in terms of the clustering coefficients and the largest biconnected components (LBCs), wherein a biconnected component (BC) indicates a set of nodes in which every pair is connected by more than one path. Via comparison with the rewired networks, we illustrated how biconnectivity in cellular metabolism is achieved on small and large scales. Defining the biconnectivity of individual metabolic compounds by counting the number of species in which the compound belonged to the LBC, we demonstrated that biconnectivity is significantly correlated with the evolutionary age and functional importance of a compound. The prevalence of diseases associated with each metabolic compound quantifies the compounds vulnerability, i.e., the likelihood that it will cause a metabolic disorder. Moreover, the vulnerability depends on both the biconnectivity and the lethality of the compound. This fact can be used in drug discovery and medical treatments. PMID:26490723

  3. The Influence of Cold Temperature on Cellular Excitability of Hippocampal Networks

    PubMed Central

    Vara, Hugo; Caires, Rebeca; Ballesta, Juan J.; Belmonte, Carlos; Viana, Felix

    2012-01-01

    The hippocampus plays an important role in short term memory, learning and spatial navigation. A characteristic feature of the hippocampal region is its expression of different electrical population rhythms and activities during different brain states. Physiological fluctuations in brain temperature affect the activity patterns in hippocampus, but the underlying cellular mechanisms are poorly understood. In this work, we investigated the thermal modulation of hippocampal activity at the cellular network level. Primary cell cultures of mouse E17 hippocampus displayed robust network activation upon light cooling of the extracellular solution from baseline physiological temperatures. The activity generated was dependent on action potential firing and excitatory glutamatergic synaptic transmission. Involvement of thermosensitive channels from the transient receptor potential (TRP) family in network activation by temperature changes was ruled out, whereas pharmacological and immunochemical experiments strongly pointed towards the involvement of temperature-sensitive two-pore-domain potassium channels (K2P), TREK/TRAAK family. In hippocampal slices we could show an increase in evoked and spontaneous synaptic activity produced by mild cooling in the physiological range that was prevented by chloroform, a K2P channel opener. We propose that cold-induced closure of background TREK/TRAAK family channels increases the excitability of some hippocampal neurons, acting as a temperature-sensitive gate of network activation. Our findings in the hippocampus open the possibility that small temperature variations in the brain in vivo, associated with metabolism or blood flow oscillations, act as a switch mechanism of neuronal activity and determination of firing patterns through regulation of thermosensitive background potassium channel activity. PMID:23300680

  4. Spatial-Temporal Reasoning Applications of Computational Intelligence in the Game of Go and Computer Networks

    DTIC Science & Technology

    2012-01-01

    dimensionality, Tesauro used a backpropagation- based , three-layer neural network and implemented the outcome from a self-play game as the reinforcement signal...a school of fish, flock of birds, and colony of ants. Our literature review reveals that no one has used PSO to train the neural network ...trained with a variant of PSO called cellular PSO (CPSO). CSRN is a supervised learning neural network (SLNN). The proposed algorithm for the

  5. Sugar Influx Sensing by the Phosphotransferase System of Escherichia coli

    PubMed Central

    Somavanshi, Rahul; Ghosh, Bhaswar; Sourjik, Victor

    2016-01-01

    The phosphotransferase system (PTS) plays a pivotal role in the uptake of multiple sugars in Escherichia coli and many other bacteria. In the cell, individual sugar-specific PTS branches are interconnected through a series of phosphotransfer reactions, thus creating a global network that not only phosphorylates incoming sugars but also regulates a number of cellular processes. Despite the apparent importance of the PTS network in bacterial physiology, the holistic function of the network in the cell remains unclear. Here we used Förster resonance energy transfer (FRET) to investigate the PTS network in E. coli, including the dynamics of protein interactions and the processing of different stimuli and their transmission to the chemotaxis pathway. Our results demonstrate that despite the seeming complexity of the cellular PTS network, its core part operates in a strikingly simple way, sensing the overall influx of PTS sugars irrespective of the sugar identity and distributing this information equally through all studied branches of the network. Moreover, it also integrates several other specific metabolic inputs. The integrated output of the PTS network is then transmitted linearly to the chemotaxis pathway, in stark contrast to the amplification of conventional chemotactic stimuli. Finally, we observe that default uptake through the uninduced PTS network correlates well with the quality of the carbon source, apparently representing an optimal regulatory strategy. PMID:27557415

  6. Human immunodeficiency virus type 1 envelope proteins traffic toward virion assembly sites via a TBC1D20/Rab1-regulated pathway

    PubMed Central

    2012-01-01

    Background The cellular activity of many factors and pathways is required to execute the complex replication cycle of the human immunodeficiency virus type 1 (HIV-1). To reveal these cellular components, several extensive RNAi screens have been performed, listing numerous 'HIV-dependency factors'. However, only a small overlap between these lists exists, calling for further evaluation of the relevance of specific factors to HIV-1 replication and for the identification of additional cellular candidates. TBC1D20, the GTPase-activating protein (GAP) of Rab1, regulates endoplasmic reticulum (ER) to Golgi trafficking, was not identified in any of these screens, and its involvement in HIV-1 replication cycle is tested here. Findings Excessive TBC1D20 activity perturbs the early trafficking of HIV-1 envelope protein through the secretory pathway. Overexpression of TBC1D20 hampered envelope processing and reduced its association with detergent-resistant membranes, entailing a reduction in infectivity of HIV-1 virion like particles (VLPs). Conclusions These findings add TBC1D20 to the network of host factors regulating HIV replication cycle. PMID:22260459

  7. Organ reconstruction: Dream or reality for the future.

    PubMed

    Stoltz, J-F; Zhang, L; Ye, J S; De Isla, N

    2017-01-01

    The relevance of research on reconstructed organs is justified by the lack of organs available for transplant and the growing needs for the ageing population. The development of a reconstructed organ involves two parallel complementary steps: de-cellularization of the organ with the need to maintain the structural integrity of the extracellular matrix and vascular network and re-cellularization of the scaffold with stem cells or resident cells.Whole organ engineering for liver, heart, lung or kidneys, is particularly difficult because of the structural complexity of organs and heterogeneity of cells. Rodent, porcine and rhesus monkey organs have been de-cellularized to obtain a scaffold with preserved extracellular matrix and vascular network. As concern the cells for re-cellularization, embryonic, foetal, adult, progenitor stem cells and also iPS have been proposed.Heart construction could be an alternative option for the treatment of cardiac insufficiency. It is based on the use of an extra-cellular matrix coming from an animal's heart and seeded with cells likely to reconstruct a normal cardiac function. Though de-cellularization techniques now seem controlled, the issues posed by the selection of cells capable of generating the various components of cardiac tissue are not settled yet. In addition, the recolonisation of the matrix does not only depend on the phenotype of cells that are used, but it is also impacted by the nature of biochemical signals emitted.Recent researches have shown that it is possible to use decellularized whole liver treated by detergents as scaffold, which keeps the entire network of blood vessels and the integrated extracellular matrix (ECM). Beside of decellularized whole organ scaffold seeding cells selected to repopulate a decellularized liver scaffold are critical for the function of the bioengineered liver. At present, potential cell sources are hepatocyte, and mesenchymal stem cells.Pulmonary regeneration using engineering approaches is complex. In fact, several types of local progenitor cells that contribute to cell repair have been described at different levels of the respiratory tract. Moving towards the alveoles, one finds bronchioalveolar stem cells as well as epithelial cells and pneumocytes. A promising option to increase the donor organ pool is to use allogeneic or xenogeneic decellularized lungs as a scaffold to engineer functional lung tissue ex vivo.The kidney is certainly one of the most difficult organs to reconstruct due to its complex nature and the heterogeneous nature of the cells. There is relatively little research on auto-construction, and experiments have been performed on rats, pigs and monkeys.Nevertheless, before these therapeutic approaches can be applied in clinical practice, many researches are necessary to understand and in particular the behaviour of cells on the decellularized organs as well as the mechanisms of their interaction with the microenvironment. Current knowledges allow optimism for the future but definitive answers can only be given after long term animal studies and controlled clinical studies.

  8. The Security Aspects of Wireless Local Area Network (WLAN)

    DTIC Science & Technology

    2003-09-01

    by wireless links to enable devices to communicate. In a Bluetooth network, mobile routers control the changing network topologies of these... Bluetooth Bluetooth is a simple peer-to-peer protocol created to connect multiple consumer mobile information devices (cellular phones, laptops...technology [Ref 2]. Bluetooth enables mobile devices to avoid interference from other signals by hopping to a new frequency after transmitting or

  9. Novel High-Fidelity Screening of Environmental Chemicals and Carcinogens and Mechanisms in Colorectal Cancer.

    DTIC Science & Technology

    2016-09-01

    Chemical Promiscuity, Pharmacokinetics, Colorectal Cancer, N , N ’-disalicylidene-1,2-diaminopropane, Pyraclostrobin, Paclobutrazol, Vitamin D Receptor, Wnt...Environmental Chemicals, TOX-TMFS, CPTM, Cancer Cellular Network Model, Chemical Reactivity, Chemical Promiscuity, Pharmacokinetics, Colorectal Cancer, N , N ...network models were further enriched with oncologic disease OMIM profiles to create cancer-specific networks. The ECs N , N ’-disalicylidene- 1,2

  10. Designing Composite Resins in the 21st Century: Ending the End Group Fallacy

    DTIC Science & Technology

    2015-09-30

    unlimited. Network Automata • In correspondence with cellular automata , a system of differential equations describes the evolution of structures...LLNL). 11Distribution A: Approved for public release; distribution is unlimited. “State of the Art” Network Automata Example • Cure kinetics

  11. Exploring Neural Network Models with Hierarchical Memories and Their Use in Modeling Biological Systems

    NASA Astrophysics Data System (ADS)

    Pusuluri, Sai Teja

    Energy landscapes are often used as metaphors for phenomena in biology, social sciences and finance. Different methods have been implemented in the past for the construction of energy landscapes. Neural network models based on spin glass physics provide an excellent mathematical framework for the construction of energy landscapes. This framework uses a minimal number of parameters and constructs the landscape using data from the actual phenomena. In the past neural network models were used to mimic the storage and retrieval process of memories (patterns) in the brain. With advances in the field now, these models are being used in machine learning, deep learning and modeling of complex phenomena. Most of the past literature focuses on increasing the storage capacity and stability of stored patterns in the network but does not study these models from a modeling perspective or an energy landscape perspective. This dissertation focuses on neural network models both from a modeling perspective and from an energy landscape perspective. I firstly show how the cellular interconversion phenomenon can be modeled as a transition between attractor states on an epigenetic landscape constructed using neural network models. The model allows the identification of a reaction coordinate of cellular interconversion by analyzing experimental and simulation time course data. Monte Carlo simulations of the model show that the initial phase of cellular interconversion is a Poisson process and the later phase of cellular interconversion is a deterministic process. Secondly, I explore the static features of landscapes generated using neural network models, such as sizes of basins of attraction and densities of metastable states. The simulation results show that the static landscape features are strongly dependent on the correlation strength and correlation structure between patterns. Using different hierarchical structures of the correlation between patterns affects the landscape features. These results show how the static landscape features can be controlled by adjusting the correlations between patterns. Finally, I explore the dynamical features of landscapes generated using neural network models such as the stability of minima and the transition rates between minima. The results from this project show that the stability depends on the correlations between patterns. It is also found that the transition rates between minima strongly depend on the type of bias applied and the correlation between patterns. The results from this part of the dissertation can be useful in engineering an energy landscape without even having the complete information about the associated minima of the landscape.

  12. Reinforcement Learning of Two-Joint Virtual Arm Reaching in a Computer Model of Sensorimotor Cortex

    PubMed Central

    Neymotin, Samuel A.; Chadderdon, George L.; Kerr, Cliff C.; Francis, Joseph T.; Lytton, William W.

    2014-01-01

    Neocortical mechanisms of learning sensorimotor control involve a complex series of interactions at multiple levels, from synaptic mechanisms to cellular dynamics to network connectomics. We developed a model of sensory and motor neocortex consisting of 704 spiking model neurons. Sensory and motor populations included excitatory cells and two types of interneurons. Neurons were interconnected with AMPA/NMDA and GABAA synapses. We trained our model using spike-timing-dependent reinforcement learning to control a two-joint virtual arm to reach to a fixed target. For each of 125 trained networks, we used 200 training sessions, each involving 15 s reaches to the target from 16 starting positions. Learning altered network dynamics, with enhancements to neuronal synchrony and behaviorally relevant information flow between neurons. After learning, networks demonstrated retention of behaviorally relevant memories by using proprioceptive information to perform reach-to-target from multiple starting positions. Networks dynamically controlled which joint rotations to use to reach a target, depending on current arm position. Learning-dependent network reorganization was evident in both sensory and motor populations: learned synaptic weights showed target-specific patterning optimized for particular reach movements. Our model embodies an integrative hypothesis of sensorimotor cortical learning that could be used to interpret future electrophysiological data recorded in vivo from sensorimotor learning experiments. We used our model to make the following predictions: learning enhances synchrony in neuronal populations and behaviorally relevant information flow across neuronal populations, enhanced sensory processing aids task-relevant motor performance and the relative ease of a particular movement in vivo depends on the amount of sensory information required to complete the movement. PMID:24047323

  13. Extracellular matrix of adipogenically differentiated mesenchymal stem cells reveals a network of collagen filaments, mostly interwoven by hexagonal structural units.

    PubMed

    Ullah, Mujib; Sittinger, Michael; Ringe, Jochen

    2013-01-01

    Extracellular matrix (ECM) is the non-cellular component of tissues, which not only provides biological shelter but also takes part in the cellular decisions for diverse functions. Every tissue has an ECM with unique composition and topology that governs the process of determination, differentiation, proliferation, migration and regeneration of cells. Little is known about the structural organization of matrix especially of MSC-derived adipogenic ECM. Here, we particularly focus on the composition and architecture of the fat ECM to understand the cellular behavior on functional bases. Thus, mesenchymal stem cells (MSC) were adipogenically differentiated, then, were transferred to adipogenic propagation medium, whereas they started the release of lipid droplets leaving bare network of ECM. Microarray analysis was performed, to indentify the molecular machinery of matrix. Adipogenesis was verified by Oil Red O staining of lipid droplets and by qPCR of adipogenic marker genes PPARG and FABP4. Antibody staining demonstrated the presence of collagen type I, II and IV filaments, while alkaline phosphatase activity verified the ossified nature of these filaments. In the adipogenic matrix, the hexagonal structures were abundant followed by octagonal structures, whereas they interwoven in a crisscross manner. Regarding molecular machinery of adipogenic ECM, the bioinformatics analysis revealed the upregulated expression of COL4A1, ITGA7, ITGA7, SDC2, ICAM3, ADAMTS9, TIMP4, GPC1, GPC4 and downregulated expression of COL14A1, ADAMTS5, TIMP2, TIMP3, BGN, LAMA3, ITGA2, ITGA4, ITGB1, ITGB8, CLDN11. Moreover, genes associated with integrins, glycoproteins, laminins, fibronectins, cadherins, selectins and linked signaling pathways were found. Knowledge of the interactive-language between cells and matrix could be beneficial for the artificial designing of biomaterials and bioscaffolds. © 2013.

  14. Mapping Protein Interactions between Dengue Virus and Its Human and Insect Hosts

    PubMed Central

    Doolittle, Janet M.; Gomez, Shawn M.

    2011-01-01

    Background Dengue fever is an increasingly significant arthropod-borne viral disease, with at least 50 million cases per year worldwide. As with other viral pathogens, dengue virus is dependent on its host to perform the bulk of functions necessary for viral survival and replication. To be successful, dengue must manipulate host cell biological processes towards its own ends, while avoiding elimination by the immune system. Protein-protein interactions between the virus and its host are one avenue through which dengue can connect and exploit these host cellular pathways and processes. Methodology/Principal Findings We implemented a computational approach to predict interactions between Dengue virus (DENV) and both of its hosts, Homo sapiens and the insect vector Aedes aegypti. Our approach is based on structural similarity between DENV and host proteins and incorporates knowledge from the literature to further support a subset of the predictions. We predict over 4,000 interactions between DENV and humans, as well as 176 interactions between DENV and A. aegypti. Additional filtering based on shared Gene Ontology cellular component annotation reduced the number of predictions to approximately 2,000 for humans and 18 for A. aegypti. Of 19 experimentally validated interactions between DENV and humans extracted from the literature, this method was able to predict nearly half (9). Additional predictions suggest specific interactions between virus and host proteins relevant to interferon signaling, transcriptional regulation, stress, and the unfolded protein response. Conclusions/Significance Dengue virus manipulates cellular processes to its advantage through specific interactions with the host's protein interaction network. The interaction networks presented here provide a set of hypothesis for further experimental investigation into the DENV life cycle as well as potential therapeutic targets. PMID:21358811

  15. MINCR is a MYC-induced lncRNA able to modulate MYC's transcriptional network in Burkitt lymphoma cells.

    PubMed

    Doose, Gero; Haake, Andrea; Bernhart, Stephan H; López, Cristina; Duggimpudi, Sujitha; Wojciech, Franziska; Bergmann, Anke K; Borkhardt, Arndt; Burkhardt, Birgit; Claviez, Alexander; Dimitrova, Lora; Haas, Siegfried; Hoell, Jessica I; Hummel, Michael; Karsch, Dennis; Klapper, Wolfram; Kleo, Karsten; Kretzmer, Helene; Kreuz, Markus; Küppers, Ralf; Lawerenz, Chris; Lenze, Dido; Loeffler, Markus; Mantovani-Löffler, Luisa; Möller, Peter; Ott, German; Richter, Julia; Rohde, Marius; Rosenstiel, Philip; Rosenwald, Andreas; Schilhabel, Markus; Schneider, Markus; Scholz, Ingrid; Stilgenbauer, Stephan; Stunnenberg, Hendrik G; Szczepanowski, Monika; Trümper, Lorenz; Weniger, Marc A; Hoffmann, Steve; Siebert, Reiner; Iaccarino, Ingram

    2015-09-22

    Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC-positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes down-regulated after MINCR knockdown. Interestingly, these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of the MYC transcriptional program. Accordingly, MINCR knockdown was associated with a reduction in MYC binding to the promoters of selected cell cycle genes. Finally, we show that down-regulation of Aurora kinases A and B and chromatin licensing and DNA replication factor 1 may explain the reduction in cellular proliferation observed on MINCR knockdown. We, therefore, suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes.

  16. A network approach to the geometric structure of shallow cloud fields

    NASA Astrophysics Data System (ADS)

    Glassmeier, F.; Feingold, G.

    2017-12-01

    The representation of shallow clouds and their radiative impact is one of the largest challenges for global climate models. While the bulk properties of cloud fields, including effects of organization, are a very active area of research, the potential of the geometric arrangement of cloud fields for the development of new parameterizations has hardly been explored. Self-organized patterns are particularly evident in the cellular structure of Stratocumulus (Sc) clouds so readily visible in satellite imagery. Inspired by similar patterns in biology and physics, we approach pattern formation in Sc fields from the perspective of natural cellular networks. Our network analysis is based on large-eddy simulations of open- and closed-cell Sc cases. We find the network structure to be neither random nor characteristic to natural convection. It is independent of macroscopic cloud fields properties like the Sc regime (open vs closed) and its typical length scale (boundary layer height). The latter is a consequence of entropy maximization (Lewis's Law with parameter 0.16). The cellular pattern is on average hexagonal, where non-6 sided cells occur according to a neighbor-number distribution variance of about 2. Reflecting the continuously renewing dynamics of Sc fields, large (many-sided) cells tend to neighbor small (few-sided) cells (Aboav-Weaire Law with parameter 0.9). These macroscopic network properties emerge independent of the Sc regime because the different processes governing the evolution of closed as compared to open cells correspond to topologically equivalent network dynamics. By developing a heuristic model, we show that open and closed cell dynamics can both be mimicked by versions of cell division and cell disappearance and are biased towards the expansion of smaller cells. This model offers for the first time a fundamental and universal explanation for the geometric pattern of Sc clouds. It may contribute to the development of advanced Sc parameterizations. As an outlook, we discuss how a similar network approach can be applied to describe and quantify the geometric structure of shallow cumulus cloud fields.

  17. Studies on the structure of the boundary tissue of the white rat seminiferous tubules.

    PubMed

    Cieciura, L

    1988-01-01

    The studies on boundary tissue of the white rat seminiferous tubules with light and electron microscopy were carried out. The wall of the tubules consists of four layers: two cellular and two amorphous ones. In cellular external sheath the characteristic intercellular fissures a network of hexagonal meshes were seen resembling the honey-combs.

  18. Coordinating Center: Molecular and Cellular Findings of Screen-Detected Lesions | Division of Cancer Prevention

    Cancer.gov

    The Molecular and Cellular Characterization of Screen‐Detected Lesions ‐ Coordinating Center and Data Management Group will provide support for the participating studies responding to RFA CA14‐10. The coordinating center supports three main domains: network coordination, statistical support and computational analysis and protocol development and database support. Support for

  19. Metabolism goes viral.

    PubMed

    Miyake-Stoner, Shigeki J; O'Shea, Clodagh C

    2014-04-01

    Viral and cellular oncogenes converge in targeting critical protein interaction networks to reprogram the cellular DNA and protein replication machinery for pathological replication. In this issue, Thai et al. (2014) show that adenovirus E4ORF1 activates MYC glycolytic targets to induce a Warburg-like effect that converts glucose into nucleotides for viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Effects of Four Different Regulatory Mechanisms on the Dynamics of Gene Regulatory Cascades

    NASA Astrophysics Data System (ADS)

    Hansen, Sabine; Krishna, Sandeep; Semsey, Szabolcs; Lo Svenningsen, Sine

    2015-07-01

    Gene regulatory cascades (GRCs) are common motifs in cellular molecular networks. A given logical function in these cascades, such as the repression of the activity of a transcription factor, can be implemented by a number of different regulatory mechanisms. The potential consequences for the dynamic performance of the GRC of choosing one mechanism over another have not been analysed systematically. Here, we report the construction of a synthetic GRC in Escherichia coli, which allows us for the first time to directly compare and contrast the dynamics of four different regulatory mechanisms, affecting the transcription, translation, stability, or activity of a transcriptional repressor. We developed a biologically motivated mathematical model which is sufficient to reproduce the response dynamics determined by experimental measurements. Using the model, we explored the potential response dynamics that the constructed GRC can perform. We conclude that dynamic differences between regulatory mechanisms at an individual step in a GRC are often concealed in the overall performance of the GRC, and suggest that the presence of a given regulatory mechanism in a certain network environment does not necessarily mean that it represents a single optimal evolutionary solution.

  1. A report on upgraded seismic monitoring stations in Myanmar: Station performance and site response

    USGS Publications Warehouse

    Thiam, Hrin Nei; Min Htwe, Yin Myo; Kyaw, Tun Lin; Tun, Pa Pa; Min, Zaw; Htwe, Sun Hninn; Aung, Tin Myo; Lin, Kyaw Kyaw; Aung, Myat Min; De Cristofaro, Jason; Franke, Mathias; Radman, Stefan; Lepiten, Elouie; Wolin, Emily; Hough, Susan E.

    2017-01-01

    Myanmar is in a tectonically complex region between the eastern edge of the Himalayan collision zone and the northern end of the Sunda megathrust. Until recently, earthquake monitoring and research efforts have been hampered by a lack of modern instrumentation and communication infrastructure. In January 2016, a major upgrade of the Myanmar National Seismic Network (MNSN; network code MM) was undertaken to improve earthquake monitoring capability. We installed five permanent broadband and strong‐motion seismic stations and real‐time data telemetry using newly improved cellular networks. Data are telemetered to the MNSN hub in Nay Pyi Taw and archived at the Incorporated Research Institutions for Seismology Data Management Center. We analyzed station noise characteristics and site response using noise and events recorded over the first six months of station operation. Background noise characteristics vary across the array, but indicate that the new stations are performing well. MM stations recorded more than 20 earthquakes of M≥4.5 within Myanmar and its immediate surroundings, including an M 6.8 earthquake located northwest of Mandalay on 13 April 2016 and the Mw 6.8 Chauk event on 24 August 2016. We use this new dataset to calculate horizontal‐to‐vertical spectral ratios, which provide a preliminary characterization of site response of the upgraded MM stations.

  2. Hot Chips and Hot Interconnects for High End Computing Systems

    NASA Technical Reports Server (NTRS)

    Saini, Subhash

    2005-01-01

    I will discuss several processors: 1. The Cray proprietary processor used in the Cray X1; 2. The IBM Power 3 and Power 4 used in an IBM SP 3 and IBM SP 4 systems; 3. The Intel Itanium and Xeon, used in the SGI Altix systems and clusters respectively; 4. IBM System-on-a-Chip used in IBM BlueGene/L; 5. HP Alpha EV68 processor used in DOE ASCI Q cluster; 6. SPARC64 V processor, which is used in the Fujitsu PRIMEPOWER HPC2500; 7. An NEC proprietary processor, which is used in NEC SX-6/7; 8. Power 4+ processor, which is used in Hitachi SR11000; 9. NEC proprietary processor, which is used in Earth Simulator. The IBM POWER5 and Red Storm Computing Systems will also be discussed. The architectures of these processors will first be presented, followed by interconnection networks and a description of high-end computer systems based on these processors and networks. The performance of various hardware/programming model combinations will then be compared, based on latest NAS Parallel Benchmark results (MPI, OpenMP/HPF and hybrid (MPI + OpenMP). The tutorial will conclude with a discussion of general trends in the field of high performance computing, (quantum computing, DNA computing, cellular engineering, and neural networks).

  3. Performance Evaluation of LoRa Considering Scenario Conditions.

    PubMed

    Sanchez-Iborra, Ramon; Sanchez-Gomez, Jesus; Ballesta-Viñas, Juan; Cano, Maria-Dolores; Skarmeta, Antonio F

    2018-03-03

    New verticals within the Internet of Things (IoT) paradigm such as smart cities, smart farming, or goods monitoring, among many others, are demanding strong requirements to the Radio Access Network (RAN) in terms of coverage, end-node's power consumption, and scalability. The technologies employed so far to provide IoT scenarios with connectivity, e.g., wireless sensor network and cellular technologies, are not able to simultaneously cope with these three requirements. Thus, a novel solution known as Low Power - Wide Area Network (LP-WAN) has emerged as a promising alternative to provide with low-cost and low-power-consumption connectivity to end-nodes spread in a wide area. Concretely, the Long-Range Wide Area Network (LoRaWAN) technology is one of the LP-WAN platforms that is receiving greater attention from both the industry and the academia. For that reason, in this work, a comprehensive performance evaluation of LoRaWAN under different environmental conditions is presented. The results are obtained from three real scenarios, namely, urban, suburban, and rural, considering both dynamic and static conditions, hence a discussion about the most proper LoRaWAN physical-layer configuration for each scenario is provided. Besides, a theoretical coverage study is also conducted by the use of a radio planning tool considering topographic maps and a precise propagation model. From the attained results, it can be concluded that it is necessary to evaluate the propagation conditions of the deployment scenario prior to the system implantation in order to reach a compromise between the robustness of the network and the transmission data-rate.

  4. Performance Evaluation of LoRa Considering Scenario Conditions

    PubMed Central

    Sanchez-Gomez, Jesus; Ballesta-Viñas, Juan

    2018-01-01

    New verticals within the Internet of Things (IoT) paradigm such as smart cities, smart farming, or goods monitoring, among many others, are demanding strong requirements to the Radio Access Network (RAN) in terms of coverage, end-node’s power consumption, and scalability. The technologies employed so far to provide IoT scenarios with connectivity, e.g., wireless sensor network and cellular technologies, are not able to simultaneously cope with these three requirements. Thus, a novel solution known as Low Power - Wide Area Network (LP-WAN) has emerged as a promising alternative to provide with low-cost and low-power-consumption connectivity to end-nodes spread in a wide area. Concretely, the Long-Range Wide Area Network (LoRaWAN) technology is one of the LP-WAN platforms that is receiving greater attention from both the industry and the academia. For that reason, in this work, a comprehensive performance evaluation of LoRaWAN under different environmental conditions is presented. The results are obtained from three real scenarios, namely, urban, suburban, and rural, considering both dynamic and static conditions, hence a discussion about the most proper LoRaWAN physical-layer configuration for each scenario is provided. Besides, a theoretical coverage study is also conducted by the use of a radio planning tool considering topographic maps and a precise propagation model. From the attained results, it can be concluded that it is necessary to evaluate the propagation conditions of the deployment scenario prior to the system implantation in order to reach a compromise between the robustness of the network and the transmission data-rate. PMID:29510524

  5. Inferring Boolean network states from partial information

    PubMed Central

    2013-01-01

    Networks of molecular interactions regulate key processes in living cells. Therefore, understanding their functionality is a high priority in advancing biological knowledge. Boolean networks are often used to describe cellular networks mathematically and are fitted to experimental datasets. The fitting often results in ambiguities since the interpretation of the measurements is not straightforward and since the data contain noise. In order to facilitate a more reliable mapping between datasets and Boolean networks, we develop an algorithm that infers network trajectories from a dataset distorted by noise. We analyze our algorithm theoretically and demonstrate its accuracy using simulation and microarray expression data. PMID:24006954

  6. An FPGA Platform for Real-Time Simulation of Spiking Neuronal Networks

    PubMed Central

    Pani, Danilo; Meloni, Paolo; Tuveri, Giuseppe; Palumbo, Francesca; Massobrio, Paolo; Raffo, Luigi

    2017-01-01

    In the last years, the idea to dynamically interface biological neurons with artificial ones has become more and more urgent. The reason is essentially due to the design of innovative neuroprostheses where biological cell assemblies of the brain can be substituted by artificial ones. For closed-loop experiments with biological neuronal networks interfaced with in silico modeled networks, several technological challenges need to be faced, from the low-level interfacing between the living tissue and the computational model to the implementation of the latter in a suitable form for real-time processing. Field programmable gate arrays (FPGAs) can improve flexibility when simple neuronal models are required, obtaining good accuracy, real-time performance, and the possibility to create a hybrid system without any custom hardware, just programming the hardware to achieve the required functionality. In this paper, this possibility is explored presenting a modular and efficient FPGA design of an in silico spiking neural network exploiting the Izhikevich model. The proposed system, prototypically implemented on a Xilinx Virtex 6 device, is able to simulate a fully connected network counting up to 1,440 neurons, in real-time, at a sampling rate of 10 kHz, which is reasonable for small to medium scale extra-cellular closed-loop experiments. PMID:28293163

  7. Mechanisms Underlying Adaptation of Respiratory Network Activity to Modulatory Stimuli in the Mouse Embryo.

    PubMed

    Chevalier, Marc; De Sa, Rafaël; Cardoit, Laura; Thoby-Brisson, Muriel

    2016-01-01

    Breathing is a rhythmic behavior that requires organized contractions of respiratory effector muscles. This behavior must adapt to constantly changing conditions in order to ensure homeostasis, proper body oxygenation, and CO2/pH regulation. Respiratory rhythmogenesis is controlled by neural networks located in the brainstem. One area considered to be essential for generating the inspiratory phase of the respiratory rhythm is the preBötzinger complex (preBötC). Rhythmogenesis emerges from this network through the interplay between the activation of intrinsic cellular properties (pacemaker properties) and intercellular synaptic connections. Respiratory activity continuously changes under the impact of numerous modulatory substances depending on organismal needs and environmental conditions. The preBötC network has been shown to become active during the last third of gestation. But only little is known regarding the modulation of inspiratory rhythmicity at embryonic stages and even less on a possible role of pacemaker neurons in this functional flexibility during the prenatal period. By combining electrophysiology and calcium imaging performed on embryonic brainstem slice preparations, we provide evidence showing that embryonic inspiratory pacemaker neurons are already intrinsically sensitive to neuromodulation and external conditions (i.e., temperature) affecting respiratory network activity, suggesting a potential role of pacemaker neurons in mediating rhythm adaptation to modulatory stimuli in the embryo.

  8. Mechanisms Underlying Adaptation of Respiratory Network Activity to Modulatory Stimuli in the Mouse Embryo

    PubMed Central

    Chevalier, Marc; De Sa, Rafaël; Cardoit, Laura; Thoby-Brisson, Muriel

    2016-01-01

    Breathing is a rhythmic behavior that requires organized contractions of respiratory effector muscles. This behavior must adapt to constantly changing conditions in order to ensure homeostasis, proper body oxygenation, and CO2/pH regulation. Respiratory rhythmogenesis is controlled by neural networks located in the brainstem. One area considered to be essential for generating the inspiratory phase of the respiratory rhythm is the preBötzinger complex (preBötC). Rhythmogenesis emerges from this network through the interplay between the activation of intrinsic cellular properties (pacemaker properties) and intercellular synaptic connections. Respiratory activity continuously changes under the impact of numerous modulatory substances depending on organismal needs and environmental conditions. The preBötC network has been shown to become active during the last third of gestation. But only little is known regarding the modulation of inspiratory rhythmicity at embryonic stages and even less on a possible role of pacemaker neurons in this functional flexibility during the prenatal period. By combining electrophysiology and calcium imaging performed on embryonic brainstem slice preparations, we provide evidence showing that embryonic inspiratory pacemaker neurons are already intrinsically sensitive to neuromodulation and external conditions (i.e., temperature) affecting respiratory network activity, suggesting a potential role of pacemaker neurons in mediating rhythm adaptation to modulatory stimuli in the embryo. PMID:27239348

  9. High Definition Confocal Imaging Modalities for the Characterization of Tissue-Engineered Substitutes.

    PubMed

    Mayrand, Dominique; Fradette, Julie

    2018-01-01

    Optimal imaging methods are necessary in order to perform a detailed characterization of thick tissue samples from either native or engineered tissues. Tissue-engineered substitutes are featuring increasing complexity including multiple cell types and capillary-like networks. Therefore, technical approaches allowing the visualization of the inner structural organization and cellular composition of tissues are needed. This chapter describes an optical clearing technique which facilitates the detailed characterization of whole-mount samples from skin and adipose tissues (ex vivo tissues and in vitro tissue-engineered substitutes) when combined with spectral confocal microscopy and quantitative analysis on image renderings.

  10. PodNet, a protein-protein interaction network of the podocyte.

    PubMed

    Warsow, Gregor; Endlich, Nicole; Schordan, Eric; Schordan, Sandra; Chilukoti, Ravi K; Homuth, Georg; Moeller, Marcus J; Fuellen, Georg; Endlich, Karlhans

    2013-07-01

    Interactions between proteins crucially determine cellular structure and function. Differential analysis of the interactome may help elucidate molecular mechanisms during disease development; however, this analysis necessitates mapping of expression data on protein-protein interaction networks. These networks do not exist for the podocyte; therefore, we built PodNet, a literature-based mouse podocyte network in Cytoscape format. Using database protein-protein interactions, we expanded PodNet to XPodNet with enhanced connectivity. In order to test the performance of XPodNet in differential interactome analysis, we examined podocyte developmental differentiation and the effect of cell culture. Transcriptomes of podocytes in 10 different states were mapped on XPodNet and analyzed with the Cytoscape plugin ExprEssence, based on the law of mass action. Interactions between slit diaphragm proteins are most significantly upregulated during podocyte development and most significantly downregulated in culture. On the other hand, our analysis revealed that interactions lost during podocyte differentiation are not regained in culture, suggesting a loss rather than a reversal of differentiation for podocytes in culture. Thus, we have developed PodNet as a valuable tool for differential interactome analysis in podocytes, and we have identified established and unexplored regulated interactions in developing and cultured podocytes.

  11. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xia, Jing; Rocke, David M.; Perry, George

    In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

  12. Convolutional Neural Network for Histopathological Analysis of Osteosarcoma.

    PubMed

    Mishra, Rashika; Daescu, Ovidiu; Leavey, Patrick; Rakheja, Dinesh; Sengupta, Anita

    2018-03-01

    Pathologists often deal with high complexity and sometimes disagreement over osteosarcoma tumor classification due to cellular heterogeneity in the dataset. Segmentation and classification of histology tissue in H&E stained tumor image datasets is a challenging task because of intra-class variations, inter-class similarity, crowded context, and noisy data. In recent years, deep learning approaches have led to encouraging results in breast cancer and prostate cancer analysis. In this article, we propose convolutional neural network (CNN) as a tool to improve efficiency and accuracy of osteosarcoma tumor classification into tumor classes (viable tumor, necrosis) versus nontumor. The proposed CNN architecture contains eight learned layers: three sets of stacked two convolutional layers interspersed with max pooling layers for feature extraction and two fully connected layers with data augmentation strategies to boost performance. The use of a neural network results in higher accuracy of average 92% for the classification. We compare the proposed architecture with three existing and proven CNN architectures for image classification: AlexNet, LeNet, and VGGNet. We also provide a pipeline to calculate percentage necrosis in a given whole slide image. We conclude that the use of neural networks can assure both high accuracy and efficiency in osteosarcoma classification.

  13. Best response game of traffic on road network of non-signalized intersections

    NASA Astrophysics Data System (ADS)

    Yao, Wang; Jia, Ning; Zhong, Shiquan; Li, Liying

    2018-01-01

    This paper studies the traffic flow in a grid road network with non-signalized intersections. The nature of the drivers in the network is simulated such that they play an iterative snowdrift game with other drivers. A cellular automata model is applied to study the characteristics of the traffic flow and the evolution of the behaviour of the drivers during the game. The drivers use best-response as their strategy to update rules. Three major findings are revealed. First, the cooperation rate in simulation experiences staircase-shaped drop as cost to benefit ratio r increases, and cooperation rate can be derived analytically as a function of cost to benefit ratio r. Second, we find that higher cooperation rate corresponds to higher average speed, lower density and higher flow. This reveals that defectors deteriorate the efficiency of traffic on non-signalized intersections. Third, the system experiences more randomness when the density is low because the drivers will not have much opportunity to update strategy when the density is low. These findings help to show how the strategy of drivers in a traffic network evolves and how their interactions influence the overall performance of the traffic system.

  14. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

    DOE PAGES

    Xia, Jing; Rocke, David M.; Perry, George; ...

    2014-01-01

    In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

  15. Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes.

    PubMed

    Fan, Wufeng; Zhou, Yuhan; Li, Hao

    2017-01-01

    In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM) based on pathway interaction network (PIN) which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA) was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs), and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways) with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

  16. CardioNet: a human metabolic network suited for the study of cardiomyocyte metabolism.

    PubMed

    Karlstädt, Anja; Fliegner, Daniela; Kararigas, Georgios; Ruderisch, Hugo Sanchez; Regitz-Zagrosek, Vera; Holzhütter, Hermann-Georg

    2012-08-29

    Availability of oxygen and nutrients in the coronary circulation is a crucial determinant of cardiac performance. Nutrient composition of coronary blood may significantly vary in specific physiological and pathological conditions, for example, administration of special diets, long-term starvation, physical exercise or diabetes. Quantitative analysis of cardiac metabolism from a systems biology perspective may help to a better understanding of the relationship between nutrient supply and efficiency of metabolic processes required for an adequate cardiac output. Here we present CardioNet, the first large-scale reconstruction of the metabolic network of the human cardiomyocyte comprising 1793 metabolic reactions, including 560 transport processes in six compartments. We use flux-balance analysis to demonstrate the capability of the network to accomplish a set of 368 metabolic functions required for maintaining the structural and functional integrity of the cell. Taking the maintenance of ATP, biosynthesis of ceramide, cardiolipin and further important phospholipids as examples, we analyse how a changed supply of glucose, lactate, fatty acids and ketone bodies may influence the efficiency of these essential processes. CardioNet is a functionally validated metabolic network of the human cardiomyocyte that enables theorectical studies of cellular metabolic processes crucial for the accomplishment of an adequate cardiac output.

  17. 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…

  18. Computational Framework for Analysis of Prey–Prey Associations in Interaction Proteomics Identifies Novel Human Protein–Protein Interactions and Networks

    PubMed Central

    Saha, Sudipto; Dazard, Jean-Eudes; Xu, Hua; Ewing, Rob M.

    2013-01-01

    Large-scale protein–protein interaction data sets have been generated for several species including yeast and human and have enabled the identification, quantification, and prediction of cellular molecular networks. Affinity purification-mass spectrometry (AP-MS) is the preeminent methodology for large-scale analysis of protein complexes, performed by immunopurifying a specific “bait” protein and its associated “prey” proteins. The analysis and interpretation of AP-MS data sets is, however, not straightforward. In addition, although yeast AP-MS data sets are relatively comprehensive, current human AP-MS data sets only sparsely cover the human interactome. Here we develop a framework for analysis of AP-MS data sets that addresses the issues of noise, missing data, and sparsity of coverage in the context of a current, real world human AP-MS data set. Our goal is to extend and increase the density of the known human interactome by integrating bait–prey and cocomplexed preys (prey–prey associations) into networks. Our framework incorporates a score for each identified protein, as well as elements of signal processing to improve the confidence of identified protein–protein interactions. We identify many protein networks enriched in known biological processes and functions. In addition, we show that integrated bait–prey and prey–prey interactions can be used to refine network topology and extend known protein networks. PMID:22845868

  19. Protein Network Signatures Associated with Exogenous Biofuels Treatments in Cyanobacterium Synechocystis sp. PCC 6803

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pei, Guangsheng; Chen, Lei; Wang, Jiangxin

    2014-11-03

    Although recognized as a promising microbial cell factory for producing biofuels, current productivity in cyanobacterial systems is low. To make the processes economically feasible, one of the hurdles, which need to be overcome is the low tolerance of hosts to toxic biofuels. Meanwhile, little information is available regarding the cellular responses to biofuels stress in cyanobacteria, which makes it challenging for tolerance engineering. Using large proteomic datasets of Synechocystis under various biofuels stress and environmental perturbation, a protein co-expression network was first constructed and then combined with the experimentally determined protein–protein interaction network. Proteins with statistically higher topological overlap inmore » the integrated network were identified as common responsive proteins to both biofuels stress and environmental perturbations. In addition, a weighted gene co-expression network analysis was performed to distinguish unique responses to biofuels from those to environmental perturbations and to uncover metabolic modules and proteins uniquely associated with biofuels stress. The results showed that biofuel-specific proteins and modules were enriched in several functional categories, including photosynthesis, carbon fixation, and amino acid metabolism, which may represent potential key signatures for biofuels stress responses in Synechocystis. Network-based analysis allowed determination of the responses specifically related to biofuels stress, and the results constituted an important knowledge foundation for tolerance engineering against biofuels in Synechocystis.« less

  20. Modeling of Receptor Tyrosine Kinase Signaling: Computational and Experimental Protocols.

    PubMed

    Fey, Dirk; Aksamitiene, Edita; Kiyatkin, Anatoly; Kholodenko, Boris N

    2017-01-01

    The advent of systems biology has convincingly demonstrated that the integration of experiments and dynamic modelling is a powerful approach to understand the cellular network biology. Here we present experimental and computational protocols that are necessary for applying this integrative approach to the quantitative studies of receptor tyrosine kinase (RTK) signaling networks. Signaling by RTKs controls multiple cellular processes, including the regulation of cell survival, motility, proliferation, differentiation, glucose metabolism, and apoptosis. We describe methods of model building and training on experimentally obtained quantitative datasets, as well as experimental methods of obtaining quantitative dose-response and temporal dependencies of protein phosphorylation and activities. The presented methods make possible (1) both the fine-grained modeling of complex signaling dynamics and identification of salient, course-grained network structures (such as feedback loops) that bring about intricate dynamics, and (2) experimental validation of dynamic models.

  1. Extracellular matrix structure.

    PubMed

    Theocharis, Achilleas D; Skandalis, Spyros S; Gialeli, Chrysostomi; Karamanos, Nikos K

    2016-02-01

    Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.

    PubMed

    Vallat, Laurent; Kemper, Corey A; Jung, Nicolas; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Meyer, Nicolas; Pocheville, Arnaud; Fisher, John W; Gribben, John G; Bahram, Seiamak

    2013-01-08

    Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.

  3. LEOPACK The integrated services communications system based on LEO satellites

    NASA Astrophysics Data System (ADS)

    Negoda, A.; Bunin, S.; Bushuev, E.; Dranovsky, V.

    LEOPACK is yet another LEO satellite project which provides global integrated services for 'business' communications. It utilizes packet rather then circuit switching in both terrestrial and satellite chains as well as cellular approach for frequencies use. Original multiple access protocols and decentralized network control make it possible to organize regionally or logically independent and world-wide networks. Relatively small number of satellites (28) provides virtually global network coverage.

  4. Network approach to patterns in stratocumulus clouds

    NASA Astrophysics Data System (ADS)

    Glassmeier, Franziska; Feingold, Graham

    2017-10-01

    Stratocumulus clouds (Sc) have a significant impact on the amount of sunlight reflected back to space, with important implications for Earth’s climate. Representing Sc and their radiative impact is one of the largest challenges for global climate models. Sc fields self-organize into cellular patterns and thus lend themselves to analysis and quantification in terms of natural cellular networks. Based on large-eddy simulations of Sc fields, we present a first analysis of the geometric structure and self-organization of Sc patterns from this network perspective. Our network analysis shows that the Sc pattern is scale-invariant as a consequence of entropy maximization that is known as Lewis’s Law (scaling parameter: 0.16) and is largely independent of the Sc regime (cloud-free vs. cloudy cell centers). Cells are, on average, hexagonal with a neighbor number variance of about 2, and larger cells tend to be surrounded by smaller cells, as described by an Aboav-Weaire parameter of 0.9. The network structure is neither completely random nor characteristic of natural convection. Instead, it emerges from Sc-specific versions of cell division and cell merging that are shaped by cell expansion. This is shown with a heuristic model of network dynamics that incorporates our physical understanding of cloud processes.

  5. Networking Omic Data to Envisage Systems Biological Regulation.

    PubMed

    Kalapanulak, Saowalak; Saithong, Treenut; Thammarongtham, Chinae

    To understand how biological processes work, it is necessary to explore the systematic regulation governing the behaviour of the processes. Not only driving the normal behavior of organisms, the systematic regulation evidently underlies the temporal responses to surrounding environments (dynamics) and long-term phenotypic adaptation (evolution). The systematic regulation is, in effect, formulated from the regulatory components which collaboratively work together as a network. In the drive to decipher such a code of lives, a spectrum of technologies has continuously been developed in the post-genomic era. With current advances, high-throughput sequencing technologies are tremendously powerful for facilitating genomics and systems biology studies in the attempt to understand system regulation inside the cells. The ability to explore relevant regulatory components which infer transcriptional and signaling regulation, driving core cellular processes, is thus enhanced. This chapter reviews high-throughput sequencing technologies, including second and third generation sequencing technologies, which support the investigation of genomics and transcriptomics data. Utilization of this high-throughput data to form the virtual network of systems regulation is explained, particularly transcriptional regulatory networks. Analysis of the resulting regulatory networks could lead to an understanding of cellular systems regulation at the mechanistic and dynamics levels. The great contribution of the biological networking approach to envisage systems regulation is finally demonstrated by a broad range of examples.

  6. 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

  7. Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach

    PubMed Central

    Ye, Yusen; Gao, Lin; Zhang, Shihua

    2017-01-01

    Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions. PMID:29033978

  8. Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach.

    PubMed

    Ye, Yusen; Gao, Lin; Zhang, Shihua

    2017-01-01

    Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions.

  9. Cutting the wires: modularization of cellular networks for experimental design.

    PubMed

    Lang, Moritz; Summers, Sean; Stelling, Jörg

    2014-01-07

    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. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  10. Network approach to patterns in stratocumulus clouds.

    PubMed

    Glassmeier, Franziska; Feingold, Graham

    2017-10-03

    Stratocumulus clouds (Sc) have a significant impact on the amount of sunlight reflected back to space, with important implications for Earth's climate. Representing Sc and their radiative impact is one of the largest challenges for global climate models. Sc fields self-organize into cellular patterns and thus lend themselves to analysis and quantification in terms of natural cellular networks. Based on large-eddy simulations of Sc fields, we present a first analysis of the geometric structure and self-organization of Sc patterns from this network perspective. Our network analysis shows that the Sc pattern is scale-invariant as a consequence of entropy maximization that is known as Lewis's Law (scaling parameter: 0.16) and is largely independent of the Sc regime (cloud-free vs. cloudy cell centers). Cells are, on average, hexagonal with a neighbor number variance of about 2, and larger cells tend to be surrounded by smaller cells, as described by an Aboav-Weaire parameter of 0.9. The network structure is neither completely random nor characteristic of natural convection. Instead, it emerges from Sc-specific versions of cell division and cell merging that are shaped by cell expansion. This is shown with a heuristic model of network dynamics that incorporates our physical understanding of cloud processes.

  11. A systems biology approach to study systemic inflammation.

    PubMed

    Chen, Bor-Sen; Wu, Chia-Chou

    2014-01-01

    Systemic inflammation needs a precise control on the sequence and magnitude of occurring events. The high throughput data on the host-pathogen interactions gives us an opportunity to have a glimpse on the systemic inflammation. In this article, a dynamic Candida albicans-zebrafish interactive infectious network is built as an example to demonstrate how systems biology approach can be used to study systematic inflammation. In particular, based on microarray data of C. albicans and zebrafish during infection, the hyphal growth, zebrafish, and host-pathogen intercellular PPI networks were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host. The signaling pathways for morphogenesis and hyphal growth of C. albicans were 2 significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins to gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. This integrated network consisting of intercellular invasion and cellular defense processes during infection can improve medical therapies and facilitate development of new antifungal drugs.

  12. Network approach to patterns in stratocumulus clouds

    PubMed Central

    Feingold, Graham

    2017-01-01

    Stratocumulus clouds (Sc) have a significant impact on the amount of sunlight reflected back to space, with important implications for Earth’s climate. Representing Sc and their radiative impact is one of the largest challenges for global climate models. Sc fields self-organize into cellular patterns and thus lend themselves to analysis and quantification in terms of natural cellular networks. Based on large-eddy simulations of Sc fields, we present a first analysis of the geometric structure and self-organization of Sc patterns from this network perspective. Our network analysis shows that the Sc pattern is scale-invariant as a consequence of entropy maximization that is known as Lewis’s Law (scaling parameter: 0.16) and is largely independent of the Sc regime (cloud-free vs. cloudy cell centers). Cells are, on average, hexagonal with a neighbor number variance of about 2, and larger cells tend to be surrounded by smaller cells, as described by an Aboav–Weaire parameter of 0.9. The network structure is neither completely random nor characteristic of natural convection. Instead, it emerges from Sc-specific versions of cell division and cell merging that are shaped by cell expansion. This is shown with a heuristic model of network dynamics that incorporates our physical understanding of cloud processes. PMID:28904097

  13. 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

  14. Barreloid Borders and Neuronal Activity Shape Panglial Gap Junction-Coupled Networks in the Mouse Thalamus.

    PubMed

    Claus, Lena; Philippot, Camille; Griemsmann, Stephanie; Timmermann, Aline; Jabs, Ronald; Henneberger, Christian; Kettenmann, Helmut; Steinhäuser, Christian

    2018-01-01

    The ventral posterior nucleus of the thalamus plays an important role in somatosensory information processing. It contains elongated cellular domains called barreloids, which are the structural basis for the somatotopic organization of vibrissae representation. So far, the organization of glial networks in these barreloid structures and its modulation by neuronal activity has not been studied. We have developed a method to visualize thalamic barreloid fields in acute slices. Combining electrophysiology, immunohistochemistry, and electroporation in transgenic mice with cell type-specific fluorescence labeling, we provide the first structure-function analyses of barreloidal glial gap junction networks. We observed coupled networks, which comprised both astrocytes and oligodendrocytes. The spread of tracers or a fluorescent glucose derivative through these networks was dependent on neuronal activity and limited by the barreloid borders, which were formed by uncoupled or weakly coupled oligodendrocytes. Neuronal somata were distributed homogeneously across barreloid fields with their processes running in parallel to the barreloid borders. Many astrocytes and oligodendrocytes were not part of the panglial networks. Thus, oligodendrocytes are the cellular elements limiting the communicating panglial network to a single barreloid, which might be important to ensure proper metabolic support to active neurons located within a particular vibrissae signaling pathway. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Gene Expression Network Reconstruction by Convex Feature Selection when Incorporating Genetic Perturbations

    PubMed Central

    Logsdon, Benjamin A.; Mezey, Jason

    2010-01-01

    Cellular gene expression measurements contain regulatory information that can be used to discover novel network relationships. Here, we present a new algorithm for network reconstruction powered by the adaptive lasso, a theoretically and empirically well-behaved method for selecting the regulatory features of a network. Any algorithms designed for network discovery that make use of directed probabilistic graphs require perturbations, produced by either experiments or naturally occurring genetic variation, to successfully infer unique regulatory relationships from gene expression data. Our approach makes use of appropriately selected cis-expression Quantitative Trait Loci (cis-eQTL), which provide a sufficient set of independent perturbations for maximum network resolution. We compare the performance of our network reconstruction algorithm to four other approaches: the PC-algorithm, QTLnet, the QDG algorithm, and the NEO algorithm, all of which have been used to reconstruct directed networks among phenotypes leveraging QTL. We show that the adaptive lasso can outperform these algorithms for networks of ten genes and ten cis-eQTL, and is competitive with the QDG algorithm for networks with thirty genes and thirty cis-eQTL, with rich topologies and hundreds of samples. Using this novel approach, we identify unique sets of directed relationships in Saccharomyces cerevisiae when analyzing genome-wide gene expression data for an intercross between a wild strain and a lab strain. We recover novel putative network relationships between a tyrosine biosynthesis gene (TYR1), and genes involved in endocytosis (RCY1), the spindle checkpoint (BUB2), sulfonate catabolism (JLP1), and cell-cell communication (PRM7). Our algorithm provides a synthesis of feature selection methods and graphical model theory that has the potential to reveal new directed regulatory relationships from the analysis of population level genetic and gene expression data. PMID:21152011

  16. Unique and shared roles of the posterior parietal and dorsolateral prefrontal cortex in cognitive functions

    PubMed Central

    Katsuki, Fumi; Constantinidis, Christos

    2012-01-01

    The dorsolateral prefrontal cortex (PFC) and posterior parietal cortex (PPC) are two parts of a broader brain network involved in the control of cognitive functions such as working-memory, spatial attention, and decision-making. The two areas share many functional properties and exhibit similar patterns of activation during the execution of mental operations. However, neurophysiological experiments in non-human primates have also documented subtle differences, revealing functional specialization within the fronto-parietal network. These differences include the ability of the PFC to influence memory performance, attention allocation, and motor responses to a greater extent, and to resist interference by distracting stimuli. In recent years, distinct cellular and anatomical differences have been identified, offering insights into how functional specialization is achieved. This article reviews the common functions and functional differences between the PFC and PPC, and their underlying mechanisms. PMID:22563310

  17. Multiscale simulations of anisotropic particles combining molecular dynamics and Green's function reaction dynamics

    NASA Astrophysics Data System (ADS)

    Vijaykumar, Adithya; Ouldridge, Thomas E.; ten Wolde, Pieter Rein; Bolhuis, Peter G.

    2017-03-01

    The modeling of complex reaction-diffusion processes in, for instance, cellular biochemical networks or self-assembling soft matter can be tremendously sped up by employing a multiscale algorithm which combines the mesoscopic Green's Function Reaction Dynamics (GFRD) method with explicit stochastic Brownian, Langevin, or deterministic molecular dynamics to treat reactants at the microscopic scale [A. Vijaykumar, P. G. Bolhuis, and P. R. ten Wolde, J. Chem. Phys. 143, 214102 (2015)]. Here we extend this multiscale MD-GFRD approach to include the orientational dynamics that is crucial to describe the anisotropic interactions often prevalent in biomolecular systems. We present the novel algorithm focusing on Brownian dynamics only, although the methodology is generic. We illustrate the novel algorithm using a simple patchy particle model. After validation of the algorithm, we discuss its performance. The rotational Brownian dynamics MD-GFRD multiscale method will open up the possibility for large scale simulations of protein signalling networks.

  18. Mapping Cellular Polarity Networks Using Mass Spectrometry-based Strategies.

    PubMed

    Daulat, Avais M; Puvirajesinghe, Tania M; Camoin, Luc; Borg, Jean-Paul

    2018-05-18

    Cell polarity is a vital biological process involved in the building, maintenance and normal functioning of tissues in invertebrates and vertebrates. Unsurprisingly, molecular defects affecting polarity organization and functions have a strong impact on tissue homeostasis, embryonic development and adult life, and may directly or indirectly lead to diseases. Genetic studies have demonstrated the causative effect of several polarity genes in diseases; however, much remains to be clarified before a comprehensive view of the molecular organization and regulation of the protein networks associated with polarity proteins is obtained. This challenge can be approached head-on using proteomics to identify protein complexes involved in cell polarity and their modifications in a spatio-temporal manner. We review the fundamental basics of mass spectrometry techniques and provide an in-depth analysis of how mass spectrometry has been instrumental in understanding the complex and dynamic nature of some cell polarity networks at the tissue (apico-basal and planar cell polarities) and cellular (cell migration, ciliogenesis) levels, with the fine dissection of the interconnections between prototypic cell polarity proteins and signal transduction cascades in normal and pathological situations. This review primarily focuses on epithelial structures which are the fundamental building blocks for most metazoan tissues, used as the archetypal model to study cellular polarity. This field offers broad perspectives thanks to the ever-increasing sensitivity of mass spectrometry and its use in combination with recently developed molecular strategies able to probe in situ proteomic networks. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. SMAC: A soft MAC to reduce control overhead and latency in CDMA-based AMI networks

    DOE PAGES

    Garlapati, Shravan; Kuruganti, Teja; Buehrer, Michael R.; ...

    2015-10-26

    The utilization of state-of-the-art 3G cellular CDMA technologies in a utility owned AMI network results in a large amount of control traffic relative to data traffic, increases the average packet delay and hence are not an appropriate choice for smart grid distribution applications. Like the CDG, we consider a utility owned cellular like CDMA network for smart grid distribution applications and classify the distribution smart grid data as scheduled data and random data. Also, we propose SMAC protocol, which changes its mode of operation based on the type of the data being collected to reduce the data collection latency andmore » control overhead when compared to 3G cellular CDMA2000 MAC. The reduction in the data collection latency and control overhead aids in increasing the number of smart meters served by a base station within the periodic data collection interval, which further reduces the number of base stations needed by a utility or reduces the bandwidth needed to collect data from all the smart meters. The reduction in the number of base stations and/or the reduction in the data transmission bandwidth reduces the CAPital EXpenditure (CAPEX) and OPerational EXpenditure (OPEX) of the AMI network. Finally, the proposed SMAC protocol is analyzed using markov chain, analytical expressions for average throughput and average packet delay are derived, and simulation results are also provided to verify the analysis.« less

  20. Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Skinner, F. K.; Department of Medicine; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease.more » Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.« less

  1. Impulsive effect on global exponential stability of BAM fuzzy cellular neural networks with time-varying delays

    NASA Astrophysics Data System (ADS)

    Li, Kelin

    2010-02-01

    In this article, a class of impulsive bidirectional associative memory (BAM) fuzzy cellular neural networks (FCNNs) with time-varying delays is formulated and investigated. By employing delay differential inequality and M-matrix theory, some sufficient conditions ensuring the existence, uniqueness and global exponential stability of equilibrium point for impulsive BAM FCNNs with time-varying delays are obtained. In particular, a precise estimate of the exponential convergence rate is also provided, which depends on system parameters and impulsive perturbation intention. It is believed that these results are significant and useful for the design and applications of BAM FCNNs. An example is given to show the effectiveness of the results obtained here.

  2. Combination therapeutics in complex diseases.

    PubMed

    He, Bing; Lu, Cheng; Zheng, Guang; He, Xiaojuan; Wang, Maolin; Chen, Gao; Zhang, Ge; Lu, Aiping

    2016-12-01

    The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  3. Quantitative interactome reveals that porcine reproductive and respiratory syndrome virus nonstructural protein 2 forms a complex with viral nucleocapsid protein and cellular vimentin.

    PubMed

    Song, Tao; Fang, Liurong; Wang, Dang; Zhang, Ruoxi; Zeng, Songlin; An, Kang; Chen, Huanchun; Xiao, Shaobo

    2016-06-16

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has heavily impacted the global swine industry. The PRRSV nonstructural protein 2 (nsp2) plays crucial roles in viral replication and host immune regulation, most likely by interacting with viral or cellular proteins that have not yet been identified. In this study, a quantitative interactome approach based on immunoprecipitation and stable isotope labeling with amino acids in cell culture (SILAC) was performed to identify nsp2-interacting proteins in PRRSV-infected cells with an nsp2-specific monoclonal antibody. Nine viral proteins and 62 cellular proteins were identified as potential nsp2-interacting partners. Our data demonstrate that the PRRSV nsp1α, nsp1β, and nucleocapsid proteins all interact directly with nsp2. Nsp2-interacting cellular proteins were classified into different functional groups and an interactome network of nsp2 was generated. Interestingly, cellular vimentin, a known receptor for PRRSV, forms a complex with nsp2 by using viral nucleocapsid protein as an intermediate. Taken together, the nsp2 interactome under the condition of virus infection clarifies a role of nsp2 in PRRSV replication and immune evasion. Viral proteins must interact with other virus-encoded proteins and/or host cellular proteins to function, and interactome analysis is an ideal approach for identifying such interacting proteins. In this study, we used the quantitative interactome methodology to identify the viral and cellular proteins that potentially interact with the nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) under virus infection conditions, thus providing a rich source of potential viral and cellular interaction partners for PRRSV nsp2. Based on the interactome data, we further demonstrated that PRRSV nsp2 and nucleocapsid protein together with cellular vimentin, form a complex that may be essential for viral attachment and replication, which partly explains the role of nsp2 in PRRSV replication and immune evasion. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Demonstration of novel, secure, real-time, portable ultrasound transmission from an austere international location.

    PubMed

    Ogedegbe, Chinwe; Morchel, Herman; Hazelwood, Vikki; Hassler, Cynthia; Feldman, Joseph

    2012-01-01

    There is not sufficient access to medical care or medical expertise in many parts of the world. An innovative telemedicine system has been developed to provide expert medical guidance to field caregivers [who have less medical expertise but can reach the patient population in need]. Real-time ultrasound video images have been securely transmitted from the Dominican Republic to Hackensack University Medical Center, Hackensack NJ (HackensackUMC), while the expert physician at HackensackUMC maintained direct voice communication with the field caregiver. Utilizing a portable ultrasound machine (Sonosite) integrated with portable broadcasting device (LiveU), extended Focused Assessment Sonography in Trauma (e-FAST) examinations were performed on healthy volunteers and transmitted via the local cellular network. Additionally, two e-FAST examinations were conducted from a remote location without cellular coverage and transmitted via broad ground area network (BGAN) satellites. The demonstration took the technology "out of the lab" and into a real life, austere environment. The conditions of the Dominican Republic ultrasound mission provided experience on how to manage and utilize this innovative technology in areas where reliable communications and medical coverage are not readily available. The resilient transmission capabilities coupled with the security features deem this portable Telesonography (TS) equipment highly useful in the telemedicine forefront by offering healthcare in underdeveloped areas as well as potentially enhancing throughput in disaster situations.

  5. Novel method for water vapour monitoring using wireless communication networks measurements

    NASA Astrophysics Data System (ADS)

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

    2009-04-01

    We propose a new technique for monitoring near-surface water vapour, by estimating humidity from data collected through existing wireless communication networks. Water vapour plays a crucial part in a variety of atmospheric processes. As the most influential of greenhouse gases, it absorbs long-wave terrestrial radiation. The water vapour cycle of evaporation and recondensation is a major energy redistributing mechanism transferring heat energy from the Earth's surface to the atmosphere. Additionally, humidity has an important role in weather forecasting as a key variable required for initialization of atmospheric models and hazard warning techniques. However, current methods of monitoring humidity suffer from low spatial resolution, high cost or a lack of precision when measuring near ground levels. Weather conditions and atmospheric phenomena affect the electromagnetic channel, causing attenuations to the radio signals. Thus, wireless communication networks are in effect built-in environmental monitoring facilities. The wireless microwave links, used in these networks, are widely deployed by cellular providers for backhaul communication between base stations, a few tens of meters above ground level. As a result, the proposed method can provide moisture observations at high temporal and spatial resolution. Further, the implementation cost is minimal, since the data used is already collected and saved by the cellular operators. In addition - many of these links are installed in areas where access is difficult such as orographic terrain and complex topography. As such, our method enables measurements in places that have been hard to measure in the past, or have never been measured before. The technique is restricted to weather conditions which include absence of rain, fog or clouds along the propagation path. We present results from real-data measurements taken from microwave links used in a backhaul cellular network that show very good agreement with surface station humidity measurements.

  6. Global functional analyses of cellular responses to pore-forming toxins.

    PubMed

    Kao, Cheng-Yuan; Los, Ferdinand C O; Huffman, Danielle L; Wachi, Shinichiro; Kloft, Nicole; Husmann, Matthias; Karabrahimi, Valbona; Schwartz, Jean-Louis; Bellier, Audrey; Ha, Christine; Sagong, Youn; Fan, Hui; Ghosh, Partho; Hsieh, Mindy; Hsu, Chih-Shen; Chen, Li; Aroian, Raffi V

    2011-03-01

    Here we present the first global functional analysis of cellular responses to pore-forming toxins (PFTs). PFTs are uniquely important bacterial virulence factors, comprising the single largest class of bacterial protein toxins and being important for the pathogenesis in humans of many Gram positive and Gram negative bacteria. Their mode of action is deceptively simple, poking holes in the plasma membrane of cells. The scattered studies to date of PFT-host cell interactions indicate a handful of genes are involved in cellular defenses to PFTs. How many genes are involved in cellular defenses against PFTs and how cellular defenses are coordinated are unknown. To address these questions, we performed the first genome-wide RNA interference (RNAi) screen for genes that, when knocked down, result in hypersensitivity to a PFT. This screen identifies 106 genes (∼0.5% of genome) in seven functional groups that protect Caenorhabditis elegans from PFT attack. Interactome analyses of these 106 genes suggest that two previously identified mitogen-activated protein kinase (MAPK) pathways, one (p38) studied in detail and the other (JNK) not, form a core PFT defense network. Additional microarray, real-time PCR, and functional studies reveal that the JNK MAPK pathway, but not the p38 MAPK pathway, is a key central regulator of PFT-induced transcriptional and functional responses. We find C. elegans activator protein 1 (AP-1; c-jun, c-fos) is a downstream target of the JNK-mediated PFT protection pathway, protects C. elegans against both small-pore and large-pore PFTs and protects human cells against a large-pore PFT. This in vivo RNAi genomic study of PFT responses proves that cellular commitment to PFT defenses is enormous, demonstrates the JNK MAPK pathway as a key regulator of transcriptionally-induced PFT defenses, and identifies AP-1 as the first cellular component broadly important for defense against large- and small-pore PFTs.

  7. Organization of excitable dynamics in hierarchical biological networks.

    PubMed

    Müller-Linow, Mark; Hilgetag, Claus C; Hütt, Marc-Thorsten

    2008-09-26

    This study investigates the contributions of network topology features to the dynamic behavior of hierarchically organized excitable networks. Representatives of different types of hierarchical networks as well as two biological neural networks are explored with a three-state model of node activation for systematically varying levels of random background network stimulation. The results demonstrate that two principal topological aspects of hierarchical networks, node centrality and network modularity, correlate with the network activity patterns at different levels of spontaneous network activation. The approach also shows that the dynamic behavior of the cerebral cortical systems network in the cat is dominated by the network's modular organization, while the activation behavior of the cellular neuronal network of Caenorhabditis elegans is strongly influenced by hub nodes. These findings indicate the interaction of multiple topological features and dynamic states in the function of complex biological networks.

  8. VLSI neuroprocessors

    NASA Technical Reports Server (NTRS)

    Kemeny, Sabrina E.

    1994-01-01

    Electronic and optoelectronic hardware implementations of highly parallel computing architectures address several ill-defined and/or computation-intensive problems not easily solved by conventional computing techniques. The concurrent processing architectures developed are derived from a variety of advanced computing paradigms including neural network models, fuzzy logic, and cellular automata. Hardware implementation technologies range from state-of-the-art digital/analog custom-VLSI to advanced optoelectronic devices such as computer-generated holograms and e-beam fabricated Dammann gratings. JPL's concurrent processing devices group has developed a broad technology base in hardware implementable parallel algorithms, low-power and high-speed VLSI designs and building block VLSI chips, leading to application-specific high-performance embeddable processors. Application areas include high throughput map-data classification using feedforward neural networks, terrain based tactical movement planner using cellular automata, resource optimization (weapon-target assignment) using a multidimensional feedback network with lateral inhibition, and classification of rocks using an inner-product scheme on thematic mapper data. In addition to addressing specific functional needs of DOD and NASA, the JPL-developed concurrent processing device technology is also being customized for a variety of commercial applications (in collaboration with industrial partners), and is being transferred to U.S. industries. This viewgraph p resentation focuses on two application-specific processors which solve the computation intensive tasks of resource allocation (weapon-target assignment) and terrain based tactical movement planning using two extremely different topologies. Resource allocation is implemented as an asynchronous analog competitive assignment architecture inspired by the Hopfield network. Hardware realization leads to a two to four order of magnitude speed-up over conventional techniques and enables multiple assignments, (many to many), not achievable with standard statistical approaches. Tactical movement planning (finding the best path from A to B) is accomplished with a digital two-dimensional concurrent processor array. By exploiting the natural parallel decomposition of the problem in silicon, a four order of magnitude speed-up over optimized software approaches has been demonstrated.

  9. A gene network bioinformatics analysis for pemphigoid autoimmune blistering diseases.

    PubMed

    Barone, Antonio; Toti, Paolo; Giuca, Maria Rita; Derchi, Giacomo; Covani, Ugo

    2015-07-01

    In this theoretical study, a text mining search and clustering analysis of data related to genes potentially involved in human pemphigoid autoimmune blistering diseases (PAIBD) was performed using web tools to create a gene/protein interaction network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was employed to identify a final set of PAIBD-involved genes and to calculate the overall significant interactions among genes: for each gene, the weighted number of links, or WNL, was registered and a clustering procedure was performed using the WNL analysis. Genes were ranked in class (leader, B, C, D and so on, up to orphans). An ontological analysis was performed for the set of 'leader' genes. Using the above-mentioned data network, 115 genes represented the final set; leader genes numbered 7 (intercellular adhesion molecule 1 (ICAM-1), interferon gamma (IFNG), interleukin (IL)-2, IL-4, IL-6, IL-8 and tumour necrosis factor (TNF)), class B genes were 13, whereas the orphans were 24. The ontological analysis attested that the molecular action was focused on extracellular space and cell surface, whereas the activation and regulation of the immunity system was widely involved. Despite the limited knowledge of the present pathologic phenomenon, attested by the presence of 24 genes revealing no protein-protein direct or indirect interactions, the network showed significant pathways gathered in several subgroups: cellular components, molecular functions, biological processes and the pathologic phenomenon obtained from the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database. The molecular basis for PAIBD was summarised and expanded, which will perhaps give researchers promising directions for the identification of new therapeutic targets.

  10. 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, we are currently integrating our approach into open source online tool. In summary, our results demonstrate that CML represent promising environmental observation network, suitable especially for urban rainfall monitoring. The developed approach integrated into an open source online tool can be conveniently used e.g. by local operators or authorities to evaluate the suitability of their region for CML weather monitoring and estimate the credible spatial-resolution of a CML weather monitoring product. Atlas, D. and Ulbrich, C. W. (1977) Path- and Area-Integrated Rainfall Measurement by Microwave Attenuation in the 1-3 cm Band. Journal of Applied Meteorology, 16(12), 1322-1331. Fencl, M., Rieckermann, J., Sýkora, P., Stránský, D., and Bareš, V. (2015) Commercial microwave links instead of rain gauges: fiction or reality? Water Science & Technology, 71(1), 31. Acknowledgements to Czech Science Foundation project No. 14-22978S and Czech Technical University in Prague project No. SGS15/050/OHK1/1T/11.

  11. FunCoup 3.0: database of genome-wide functional coupling networks

    PubMed Central

    Schmitt, Thomas; Ogris, Christoph; Sonnhammer, Erik L. L.

    2014-01-01

    We present an update of the FunCoup database (http://FunCoup.sbc.su.se) of functional couplings, or functional associations, between genes and gene products. Identifying these functional couplings is an important step in the understanding of higher level mechanisms performed by complex cellular processes. FunCoup distinguishes between four classes of couplings: participation in the same signaling cascade, participation in the same metabolic process, co-membership in a protein complex and physical interaction. For each of these four classes, several types of experimental and statistical evidence are combined by Bayesian integration to predict genome-wide functional coupling networks. The FunCoup framework has been completely re-implemented to allow for more frequent future updates. It contains many improvements, such as a regularization procedure to automatically downweight redundant evidences and a novel method to incorporate phylogenetic profile similarity. Several datasets have been updated and new data have been added in FunCoup 3.0. Furthermore, we have developed a new Web site, which provides powerful tools to explore the predicted networks and to retrieve detailed information about the data underlying each prediction. PMID:24185702

  12. Functional Stem Cell Integration into Neural Networks Assessed by Organotypic Slice Cultures.

    PubMed

    Forsberg, David; Thonabulsombat, Charoensri; Jäderstad, Johan; Jäderstad, Linda Maria; Olivius, Petri; Herlenius, Eric

    2017-08-14

    Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional contacts between the implanted cells and the host tissue. Therefore, it is of fundamental interest to establish protocols that allow us to delineate a detailed time course of grafted stem cell survival, migration, differentiation, integration, and functional interaction with the host. One option for in vitro studies is to examine the integration of exogenous stem cells into an existing active neural network in ex vivo organotypic cultures. Organotypic cultures leave the structural integrity essentially intact while still allowing the microenvironment to be carefully controlled. This allows detailed studies over time of cellular responses and cell-cell interactions, which are not readily performed in vivo. This unit describes procedures for using organotypic slice cultures as ex vivo model systems for studying neural stem cell and embryonic stem cell engraftment and communication with CNS host tissue. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  13. Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.

    PubMed

    Pan, Joshua; Meyers, Robin M; Michel, Brittany C; Mashtalir, Nazar; Sizemore, Ann E; Wells, Jonathan N; Cassel, Seth H; Vazquez, Francisca; Weir, Barbara A; Hahn, William C; Marsh, Joseph A; Tsherniak, Aviad; Kadoch, Cigall

    2018-05-23

    Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex. Finally, by integrating functional networks with large protein-protein interaction networks, we discovered novel protein complexes involving recently evolved genes of unknown function. Taken together, these findings demonstrate the utility of genetic perturbation screens alone, and in combination with large-scale biophysical data, to enhance our understanding of mammalian protein complexes in normal and disease states. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Modeling and visualizing cell type switching.

    PubMed

    Ghaffarizadeh, Ahmadreza; Podgorski, Gregory J; Flann, Nicholas S

    2014-01-01

    Understanding cellular differentiation is critical in explaining development and for taming diseases such as cancer. Differentiation is conventionally represented using bifurcating lineage trees. However, these lineage trees cannot readily capture or quantify all the types of transitions now known to occur between cell types, including transdifferentiation or differentiation off standard paths. This work introduces a new analysis and visualization technique that is capable of representing all possible transitions between cell states compactly, quantitatively, and intuitively. This method considers the regulatory network of transcription factors that control cell type determination and then performs an analysis of network dynamics to identify stable expression profiles and the potential cell types that they represent. A visualization tool called CellDiff3D creates an intuitive three-dimensional graph that shows the overall direction and probability of transitions between all pairs of cell types within a lineage. In this study, the influence of gene expression noise and mutational changes during myeloid cell differentiation are presented as a demonstration of the CellDiff3D technique, a new approach to quantify and envision all possible cell state transitions in any lineage network.

  15. FunCoup 3.0: database of genome-wide functional coupling networks.

    PubMed

    Schmitt, Thomas; Ogris, Christoph; Sonnhammer, Erik L L

    2014-01-01

    We present an update of the FunCoup database (http://FunCoup.sbc.su.se) of functional couplings, or functional associations, between genes and gene products. Identifying these functional couplings is an important step in the understanding of higher level mechanisms performed by complex cellular processes. FunCoup distinguishes between four classes of couplings: participation in the same signaling cascade, participation in the same metabolic process, co-membership in a protein complex and physical interaction. For each of these four classes, several types of experimental and statistical evidence are combined by Bayesian integration to predict genome-wide functional coupling networks. The FunCoup framework has been completely re-implemented to allow for more frequent future updates. It contains many improvements, such as a regularization procedure to automatically downweight redundant evidences and a novel method to incorporate phylogenetic profile similarity. Several datasets have been updated and new data have been added in FunCoup 3.0. Furthermore, we have developed a new Web site, which provides powerful tools to explore the predicted networks and to retrieve detailed information about the data underlying each prediction.

  16. Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

    EPA Science Inventory

    Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

  17. Chemical Genetic Screens for TDP-43 Modifiers and ALS Drug Discovery

    DTIC Science & Technology

    2015-03-01

    Blackstone , 2012). Recently, a large network including many of these genes have been identify and this network is highly similar to Parkinson’s, ALS and...10.1186/1750- 1326-8-30 Blackstone , C. (2012). Cellular pathways of hereditary spastic paraplegia. Annu. Rev. Neurosci. 35, 25–47. doi: 10.1146/annurev

  18. 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…

  19. Nodule Detection in a Lung Region that's Segmented with Using Genetic Cellular Neural Networks and 3D Template Matching with Fuzzy Rule Based Thresholding

    PubMed Central

    Osman, Onur; Ucan, Osman N.

    2008-01-01

    Objective The purpose of this study was to develop a new method for automated lung nodule detection in serial section CT images with using the characteristics of the 3D appearance of the nodules that distinguish themselves from the vessels. Materials and Methods Lung nodules were detected in four steps. First, to reduce the number of region of interests (ROIs) and the computation time, the lung regions of the CTs were segmented using Genetic Cellular Neural Networks (G-CNN). Then, for each lung region, ROIs were specified with using the 8 directional search; +1 or -1 values were assigned to each voxel. The 3D ROI image was obtained by combining all the 2-Dimensional (2D) ROI images. A 3D template was created to find the nodule-like structures on the 3D ROI image. Convolution of the 3D ROI image with the proposed template strengthens the shapes that are similar to those of the template and it weakens the other ones. Finally, fuzzy rule based thresholding was applied and the ROI's were found. To test the system's efficiency, we used 16 cases with a total of 425 slices, which were taken from the Lung Image Database Consortium (LIDC) dataset. Results The computer aided diagnosis (CAD) system achieved 100% sensitivity with 13.375 FPs per case when the nodule thickness was greater than or equal to 5.625 mm. Conclusion Our results indicate that the detection performance of our algorithm is satisfactory, and this may well improve the performance of computer-aided detection of lung nodules. PMID:18253070

  20. Ultrasensitive response motifs: basic amplifiers in molecular signalling networks

    PubMed Central

    Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

    2013-01-01

    Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029

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