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Sample records for boolean biological regulatory

  1. Boolean Networks in Inference and Dynamic Modeling of Biological Systems at the Molecular and Physiological Level

    Science.gov (United States)

    Thakar, Juilee; Albert, Réka

    The following sections are included: * Introduction * Boolean Network Concepts and History * Extensions of the Classical Boolean Framework * Boolean Inference Methods and Examples in Biology * Dynamic Boolean Models: Examples in Plant Biology, Developmental Biology and Immunology * Conclusions * References

  2. A parallel attractor-finding algorithm based on Boolean satisfiability for genetic regulatory networks.

    Science.gov (United States)

    Guo, Wensheng; Yang, Guowu; Wu, Wei; He, Lei; Sun, Mingyu

    2014-01-01

    In biological systems, the dynamic analysis method has gained increasing attention in the past decade. The Boolean network is the most common model of a genetic regulatory network. The interactions of activation and inhibition in the genetic regulatory network are modeled as a set of functions of the Boolean network, while the state transitions in the Boolean network reflect the dynamic property of a genetic regulatory network. A difficult problem for state transition analysis is the finding of attractors. In this paper, we modeled the genetic regulatory network as a Boolean network and proposed a solving algorithm to tackle the attractor finding problem. In the proposed algorithm, we partitioned the Boolean network into several blocks consisting of the strongly connected components according to their gradients, and defined the connection between blocks as decision node. Based on the solutions calculated on the decision nodes and using a satisfiability solving algorithm, we identified the attractors in the state transition graph of each block. The proposed algorithm is benchmarked on a variety of genetic regulatory networks. Compared with existing algorithms, it achieved similar performance on small test cases, and outperformed it on larger and more complex ones, which happens to be the trend of the modern genetic regulatory network. Furthermore, while the existing satisfiability-based algorithms cannot be parallelized due to their inherent algorithm design, the proposed algorithm exhibits a good scalability on parallel computing architectures.

  3. Boolean modeling in systems biology: an overview of methodology and applications

    International Nuclear Information System (INIS)

    Wang, Rui-Sheng; Albert, Réka; Saadatpour, Assieh

    2012-01-01

    Mathematical modeling of biological processes provides deep insights into complex cellular systems. While quantitative and continuous models such as differential equations have been widely used, their use is obstructed in systems wherein the knowledge of mechanistic details and kinetic parameters is scarce. On the other hand, a wealth of molecular level qualitative data on individual components and interactions can be obtained from the experimental literature and high-throughput technologies, making qualitative approaches such as Boolean network modeling extremely useful. In this paper, we build on our research to provide a methodology overview of Boolean modeling in systems biology, including Boolean dynamic modeling of cellular networks, attractor analysis of Boolean dynamic models, as well as inferring biological regulatory mechanisms from high-throughput data using Boolean models. We finally demonstrate how Boolean models can be applied to perform the structural analysis of cellular networks. This overview aims to acquaint life science researchers with the basic steps of Boolean modeling and its applications in several areas of systems biology. (paper)

  4. Polynomial-Time Algorithm for Controllability Test of a Class of Boolean Biological Networks

    Directory of Open Access Journals (Sweden)

    Koichi Kobayashi

    2010-01-01

    Full Text Available In recent years, Boolean-network-model-based approaches to dynamical analysis of complex biological networks such as gene regulatory networks have been extensively studied. One of the fundamental problems in control theory of such networks is the problem of determining whether a given substance quantity can be arbitrarily controlled by operating the other substance quantities, which we call the controllability problem. This paper proposes a polynomial-time algorithm for solving this problem. Although the algorithm is based on a sufficient condition for controllability, it is easily computable for a wider class of large-scale biological networks compared with the existing approaches. A key to this success in our approach is to give up computing Boolean operations in a rigorous way and to exploit an adjacency matrix of a directed graph induced by a Boolean network. By applying the proposed approach to a neurotransmitter signaling pathway, it is shown that it is effective.

  5. Controllability and observability of Boolean networks arising from biology

    Science.gov (United States)

    Li, Rui; Yang, Meng; Chu, Tianguang

    2015-02-01

    Boolean networks are currently receiving considerable attention as a computational scheme for system level analysis and modeling of biological systems. Studying control-related problems in Boolean networks may reveal new insights into the intrinsic control in complex biological systems and enable us to develop strategies for manipulating biological systems using exogenous inputs. This paper considers controllability and observability of Boolean biological networks. We propose a new approach, which draws from the rich theory of symbolic computation, to solve the problems. Consequently, simple necessary and sufficient conditions for reachability, controllability, and observability are obtained, and algorithmic tests for controllability and observability which are based on the Gröbner basis method are presented. As practical applications, we apply the proposed approach to several different biological systems, namely, the mammalian cell-cycle network, the T-cell activation network, the large granular lymphocyte survival signaling network, and the Drosophila segment polarity network, gaining novel insights into the control and/or monitoring of the specific biological systems.

  6. Boolean Models of Biological Processes Explain Cascade-Like Behavior

    Science.gov (United States)

    Chen, Hao; Wang, Guanyu; Simha, Rahul; Du, Chenghang; Zeng, Chen

    2016-01-01

    Biological networks play a key role in determining biological function and therefore, an understanding of their structure and dynamics is of central interest in systems biology. In Boolean models of such networks, the status of each molecule is either “on” or “off” and along with the molecules interact with each other, their individual status changes from “on” to “off” or vice-versa and the system of molecules in the network collectively go through a sequence of changes in state. This sequence of changes is termed a biological process. In this paper, we examine the common perception that events in biomolecular networks occur sequentially, in a cascade-like manner, and ask whether this is likely to be an inherent property. In further investigations of the budding and fission yeast cell-cycle, we identify two generic dynamical rules. A Boolean system that complies with these rules will automatically have a certain robustness. By considering the biological requirements in robustness and designability, we show that those Boolean dynamical systems, compared to an arbitrary dynamical system, statistically present the characteristics of cascadeness and sequentiality, as observed in the budding and fission yeast cell- cycle. These results suggest that cascade-like behavior might be an intrinsic property of biological processes. PMID:26821940

  7. Exploring candidate biological functions by Boolean Function Networks for Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Maria Simak

    Full Text Available The great amount of gene expression data has brought a big challenge for the discovery of Gene Regulatory Network (GRN. For network reconstruction and the investigation of regulatory relations, it is desirable to ensure directness of links between genes on a map, infer their directionality and explore candidate biological functions from high-throughput transcriptomic data. To address these problems, we introduce a Boolean Function Network (BFN model based on techniques of hidden Markov model (HMM, likelihood ratio test and Boolean logic functions. BFN consists of two consecutive tests to establish links between pairs of genes and check their directness. We evaluate the performance of BFN through the application to S. cerevisiae time course data. BFN produces regulatory relations which show consistency with succession of cell cycle phases. Furthermore, it also improves sensitivity and specificity when compared with alternative methods of genetic network reverse engineering. Moreover, we demonstrate that BFN can provide proper resolution for GO enrichment of gene sets. Finally, the Boolean functions discovered by BFN can provide useful insights for the identification of control mechanisms of regulatory processes, which is the special advantage of the proposed approach. In combination with low computational complexity, BFN can serve as an efficient screening tool to reconstruct genes relations on the whole genome level. In addition, the BFN approach is also feasible to a wide range of time course datasets.

  8. Stochastic Boolean networks: An efficient approach to modeling gene regulatory networks

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    Liang Jinghang

    2012-08-01

    network inferred from a T cell immune response dataset. An SBN can also implement the function of an asynchronous PBN and is potentially useful in a hybrid approach in combination with a continuous or single-molecule level stochastic model. Conclusions Stochastic Boolean networks (SBNs are proposed as an efficient approach to modelling gene regulatory networks (GRNs. The SBN approach is able to recover biologically-proven regulatory behaviours, such as the oscillatory dynamics of the p53-Mdm2 network and the dynamic attractors in a T cell immune response network. The proposed approach can further predict the network dynamics when the genes are under perturbation, thus providing biologically meaningful insights for a better understanding of the dynamics of GRNs. The algorithms and methods described in this paper have been implemented in Matlab packages, which are attached as Additional files.

  9. Structures and Boolean Dynamics in Gene Regulatory Networks

    Science.gov (United States)

    Szedlak, Anthony

    This dissertation discusses the topological and dynamical properties of GRNs in cancer, and is divided into four main chapters. First, the basic tools of modern complex network theory are introduced. These traditional tools as well as those developed by myself (set efficiency, interset efficiency, and nested communities) are crucial for understanding the intricate topological properties of GRNs, and later chapters recall these concepts. Second, the biology of gene regulation is discussed, and a method for disease-specific GRN reconstruction developed by our collaboration is presented. This complements the traditional exhaustive experimental approach of building GRNs edge-by-edge by quickly inferring the existence of as of yet undiscovered edges using correlations across sets of gene expression data. This method also provides insight into the distribution of common mutations across GRNs. Third, I demonstrate that the structures present in these reconstructed networks are strongly related to the evolutionary histories of their constituent genes. Investigation of how the forces of evolution shaped the topology of GRNs in multicellular organisms by growing outward from a core of ancient, conserved genes can shed light upon the ''reverse evolution'' of normal cells into unicellular-like cancer states. Next, I simulate the dynamics of the GRNs of cancer cells using the Hopfield model, an infinite range spin-glass model designed with the ability to encode Boolean data as attractor states. This attractor-driven approach facilitates the integration of gene expression data into predictive mathematical models. Perturbations representing therapeutic interventions are applied to sets of genes, and the resulting deviations from their attractor states are recorded, suggesting new potential drug targets for experimentation. Finally, I extend the Hopfield model to modular networks, cyclic attractors, and complex attractors, and apply these concepts to simulations of the cell cycle

  10. On the underlying assumptions of threshold Boolean networks as a model for genetic regulatory network behavior.

    Science.gov (United States)

    Tran, Van; McCall, Matthew N; McMurray, Helene R; Almudevar, Anthony

    2013-01-01

    Boolean networks (BoN) are relatively simple and interpretable models of gene regulatory networks. Specifying these models with fewer parameters while retaining their ability to describe complex regulatory relationships is an ongoing methodological challenge. Additionally, extending these models to incorporate variable gene decay rates, asynchronous gene response, and synergistic regulation while maintaining their Markovian nature increases the applicability of these models to genetic regulatory networks (GRN). We explore a previously-proposed class of BoNs characterized by linear threshold functions, which we refer to as threshold Boolean networks (TBN). Compared to traditional BoNs with unconstrained transition functions, these models require far fewer parameters and offer a more direct interpretation. However, the functional form of a TBN does result in a reduction in the regulatory relationships which can be modeled. We show that TBNs can be readily extended to permit self-degradation, with explicitly modeled degradation rates. We note that the introduction of variable degradation compromises the Markovian property fundamental to BoN models but show that a simple state augmentation procedure restores their Markovian nature. Next, we study the effect of assumptions regarding self-degradation on the set of possible steady states. Our findings are captured in two theorems relating self-degradation and regulatory feedback to the steady state behavior of a TBN. Finally, we explore assumptions of synchronous gene response and asynergistic regulation and show that TBNs can be easily extended to relax these assumptions. Applying our methods to the budding yeast cell-cycle network revealed that although the network is complex, its steady state is simplified by the presence of self-degradation and lack of purely positive regulatory cycles.

  11. Continuous time boolean modeling for biological signaling: application of Gillespie algorithm

    Directory of Open Access Journals (Sweden)

    Stoll Gautier

    2012-08-01

    Full Text Available Abstract Mathematical modeling is used as a Systems Biology tool to answer biological questions, and more precisely, to validate a network that describes biological observations and predict the effect of perturbations. This article presents an algorithm for modeling biological networks in a discrete framework with continuous time. Background There exist two major types of mathematical modeling approaches: (1 quantitative modeling, representing various chemical species concentrations by real numbers, mainly based on differential equations and chemical kinetics formalism; (2 and qualitative modeling, representing chemical species concentrations or activities by a finite set of discrete values. Both approaches answer particular (and often different biological questions. Qualitative modeling approach permits a simple and less detailed description of the biological systems, efficiently describes stable state identification but remains inconvenient in describing the transient kinetics leading to these states. In this context, time is represented by discrete steps. Quantitative modeling, on the other hand, can describe more accurately the dynamical behavior of biological processes as it follows the evolution of concentration or activities of chemical species as a function of time, but requires an important amount of information on the parameters difficult to find in the literature. Results Here, we propose a modeling framework based on a qualitative approach that is intrinsically continuous in time. The algorithm presented in this article fills the gap between qualitative and quantitative modeling. It is based on continuous time Markov process applied on a Boolean state space. In order to describe the temporal evolution of the biological process we wish to model, we explicitly specify the transition rates for each node. For that purpose, we built a language that can be seen as a generalization of Boolean equations. Mathematically, this approach can be

  12. Steady-State Analysis of Genetic Regulatory Networks Modelled by Probabilistic Boolean Networks

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    Wei Zhang

    2006-04-01

    Full Text Available Probabilistic Boolean networks (PBNs have recently been introduced as a promising class of models of genetic regulatory networks. The dynamic behaviour of PBNs can be analysed in the context of Markov chains. A key goal is the determination of the steady-state (long-run behaviour of a PBN by analysing the corresponding Markov chain. This allows one to compute the long-term influence of a gene on another gene or determine the long-term joint probabilistic behaviour of a few selected genes. Because matrix-based methods quickly become prohibitive for large sizes of networks, we propose the use of Monte Carlo methods. However, the rate of convergence to the stationary distribution becomes a central issue. We discuss several approaches for determining the number of iterations necessary to achieve convergence of the Markov chain corresponding to a PBN. Using a recently introduced method based on the theory of two-state Markov chains, we illustrate the approach on a sub-network designed from human glioma gene expression data and determine the joint steadystate probabilities for several groups of genes.

  13. Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord.

    KAUST Repository

    Lovrics, Anna

    2014-11-14

    We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.

  14. Optimization-Based Approaches to Control of Probabilistic Boolean Networks

    Directory of Open Access Journals (Sweden)

    Koichi Kobayashi

    2017-02-01

    Full Text Available Control of gene regulatory networks is one of the fundamental topics in systems biology. In the last decade, control theory of Boolean networks (BNs, which is well known as a model of gene regulatory networks, has been widely studied. In this review paper, our previously proposed methods on optimal control of probabilistic Boolean networks (PBNs are introduced. First, the outline of PBNs is explained. Next, an optimal control method using polynomial optimization is explained. The finite-time optimal control problem is reduced to a polynomial optimization problem. Furthermore, another finite-time optimal control problem, which can be reduced to an integer programming problem, is also explained.

  15. Comparison of Control Approaches in Genetic Regulatory Networks by Using Stochastic Master Equation Models, Probabilistic Boolean Network Models and Differential Equation Models and Estimated Error Analyzes

    Science.gov (United States)

    Caglar, Mehmet Umut; Pal, Ranadip

    2011-03-01

    Central dogma of molecular biology states that ``information cannot be transferred back from protein to either protein or nucleic acid''. However, this assumption is not exactly correct in most of the cases. There are a lot of feedback loops and interactions between different levels of systems. These types of interactions are hard to analyze due to the lack of cell level data and probabilistic - nonlinear nature of interactions. Several models widely used to analyze and simulate these types of nonlinear interactions. Stochastic Master Equation (SME) models give probabilistic nature of the interactions in a detailed manner, with a high calculation cost. On the other hand Probabilistic Boolean Network (PBN) models give a coarse scale picture of the stochastic processes, with a less calculation cost. Differential Equation (DE) models give the time evolution of mean values of processes in a highly cost effective way. The understanding of the relations between the predictions of these models is important to understand the reliability of the simulations of genetic regulatory networks. In this work the success of the mapping between SME, PBN and DE models is analyzed and the accuracy and affectivity of the control policies generated by using PBN and DE models is compared.

  16. Boolean algebra

    CERN Document Server

    Goodstein, R L

    2007-01-01

    This elementary treatment by a distinguished mathematician employs Boolean algebra as a simple medium for introducing important concepts of modern algebra. Numerous examples appear throughout the text, plus full solutions.

  17. Continuous time Boolean modeling for biological signaling: application of Gillespie algorithm.

    OpenAIRE

    Stoll, Gautier; Viara, Eric; Barillot, Emmanuel; Calzone, Laurence

    2012-01-01

    Abstract Mathematical modeling is used as a Systems Biology tool to answer biological questions, and more precisely, to validate a network that describes biological observations and predict the effect of perturbations. This article presents an algorithm for modeling biological networks in a discrete framework with continuous time. Background There exist two major types of mathematical modeling approaches: (1) quantitative modeling, representing various chemical species concentrations by real...

  18. Reliable dynamics in Boolean and continuous networks

    International Nuclear Information System (INIS)

    Ackermann, Eva; Drossel, Barbara; Peixoto, Tiago P

    2012-01-01

    We investigate the dynamical behavior of a model of robust gene regulatory networks which possess ‘entirely reliable’ trajectories. In a Boolean representation, these trajectories are characterized by being insensitive to the order in which the nodes are updated, i.e. they always go through the same sequence of states. The Boolean model for gene activity is compared with a continuous description in terms of differential equations for the concentrations of mRNA and proteins. We found that entirely reliable Boolean trajectories can be reproduced perfectly in the continuous model when realistic Hill coefficients are used. We investigate to what extent this high correspondence between Boolean and continuous trajectories depends on the extent of reliability of the Boolean trajectories, and we identify simple criteria that enable the faithful reproduction of the Boolean dynamics in the continuous description. (paper)

  19. Dynamic Network-Based Epistasis Analysis: Boolean Examples

    Science.gov (United States)

    Azpeitia, Eugenio; Benítez, Mariana; Padilla-Longoria, Pablo; Espinosa-Soto, Carlos; Alvarez-Buylla, Elena R.

    2011-01-01

    In this article we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the inference of gene regulatory networks. Here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson, epistasis is defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus (herein, classical epistasis). Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct inference of gene interaction topologies is hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our article complements previous accounts, not only by focusing on the implications of the hierarchical and

  20. Regulatory Biology: Depressed Metabolic States

    Science.gov (United States)

    Holton, E. M. (Editor)

    1973-01-01

    Exobiological aspects of depressed metabolism and thermoregulation are discussed for subsequent development of biological space flight experiments. Included is a brief description of differential hypothermia in cancer chemotherapy.

  1. Boolean reasoning the logic of boolean equations

    CERN Document Server

    Brown, Frank Markham

    2012-01-01

    A systematic treatment of Boolean reasoning, this concise, newly revised edition combines the works of early logicians with recent investigations, including previously unpublished research results. Brown begins with an overview of elementary mathematical concepts and outlines the theory of Boolean algebras. Two concluding chapters deal with applications. 1990 edition.

  2. Free Boolean Topological Groups

    Directory of Open Access Journals (Sweden)

    Ol’ga Sipacheva

    2015-11-01

    Full Text Available Known and new results on free Boolean topological groups are collected. An account of the properties that these groups share with free or free Abelian topological groups and properties specific to free Boolean groups is given. Special emphasis is placed on the application of set-theoretic methods to the study of Boolean topological groups.

  3. Boolean algebra essentials

    CERN Document Server

    Solomon, Alan D

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Boolean Algebra includes set theory, sentential calculus, fundamental ideas of Boolean algebras, lattices, rings and Boolean algebras, the structure of a Boolean algebra, and Boolean

  4. Dynamic network-based epistasis analysis: Boolean examples

    Directory of Open Access Journals (Sweden)

    Eugenio eAzpeitia

    2011-12-01

    Full Text Available In this review we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the topologies of gene interactions infered. This has been acknowledged in several previous papers and reviews, but here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson (herein, classical epistasis, defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus. Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct gene interaction topologies are hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our review complements previous accounts, not

  5. The spruce budworm and forest: a qualitative comparison of ODE and Boolean models

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    Raina Robeva

    2016-01-01

    Full Text Available Boolean and polynomial models of biological systems have emerged recently as viable companions to differential equations models. It is not immediately clear however whether such models are capable of capturing the multi-stable behaviour of certain biological systems: this behaviour is often sensitive to changes in the values of the model parameters, while Boolean and polynomial models are qualitative in nature. In the past few years, Boolean models of gene regulatory systems have been shown to capture multi-stability at the molecular level, confirming that such models can be used to obtain information about the system’s qualitative dynamics when precise information regarding its parameters may not be available. In this paper, we examine Boolean approximations of a classical ODE model of budworm outbreaks in a forest and show that these models exhibit a qualitative behaviour consistent with that derived from the ODE models. In particular, we demonstrate that these models can capture the bistable nature of insect population outbreaks, thus showing that Boolean models can be successfully utilized beyond the molecular level.

  6. Boolean integral calculus

    Science.gov (United States)

    Tucker, Jerry H.; Tapia, Moiez A.; Bennett, A. Wayne

    1988-01-01

    The concept of Boolean integration is developed, and different Boolean integral operators are introduced. Given the changes in a desired function in terms of the changes in its arguments, the ways of 'integrating' (i.e. realizing) such a function, if it exists, are presented. The necessary and sufficient conditions for integrating, in different senses, the expression specifying the changes are obtained. Boolean calculus has applications in the design of logic circuits and in fault analysis.

  7. Properties of Boolean orthoposets

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    Tkadlec, Josef

    1993-10-01

    A Boolean orthoposet is the orthoposet P fulfilling the following condition: If a, b ∈ P and a ∧ b = 0, then a ⊥ b. This condition seems to be a sound generalization of distributivity in orthoposets. Also, the class of (orthomodular) Boolean orthoposets may play an interesting role in quantum logic theory. This class is wide enough and, on the other hand, enjoys some properties of Boolean algebras. In this paper we summarize results on Boolean orthoposets involving distributivity, set representation, properties of the state space, existence of Jauch-Piron states, and results concerning orthocompleteness and completion.

  8. An Efficient Algorithm for Computing Attractors of Synchronous And Asynchronous Boolean Networks

    Science.gov (United States)

    Zheng, Desheng; Yang, Guowu; Li, Xiaoyu; Wang, Zhicai; Liu, Feng; He, Lei

    2013-01-01

    Biological networks, such as genetic regulatory networks, often contain positive and negative feedback loops that settle down to dynamically stable patterns. Identifying these patterns, the so-called attractors, can provide important insights for biologists to understand the molecular mechanisms underlying many coordinated cellular processes such as cellular division, differentiation, and homeostasis. Both synchronous and asynchronous Boolean networks have been used to simulate genetic regulatory networks and identify their attractors. The common methods of computing attractors are that start with a randomly selected initial state and finish with exhaustive search of the state space of a network. However, the time complexity of these methods grows exponentially with respect to the number and length of attractors. Here, we build two algorithms to achieve the computation of attractors in synchronous and asynchronous Boolean networks. For the synchronous scenario, combing with iterative methods and reduced order binary decision diagrams (ROBDD), we propose an improved algorithm to compute attractors. For another algorithm, the attractors of synchronous Boolean networks are utilized in asynchronous Boolean translation functions to derive attractors of asynchronous scenario. The proposed algorithms are implemented in a procedure called geneFAtt. Compared to existing tools such as genYsis, geneFAtt is significantly faster in computing attractors for empirical experimental systems. Availability The software package is available at https://sites.google.com/site/desheng619/download. PMID:23585840

  9. Optimal stabilization of Boolean networks through collective influence

    Science.gov (United States)

    Wang, Jiannan; Pei, Sen; Wei, Wei; Feng, Xiangnan; Zheng, Zhiming

    2018-03-01

    Boolean networks have attracted much attention due to their wide applications in describing dynamics of biological systems. During past decades, much effort has been invested in unveiling how network structure and update rules affect the stability of Boolean networks. In this paper, we aim to identify and control a minimal set of influential nodes that is capable of stabilizing an unstable Boolean network. For locally treelike Boolean networks with biased truth tables, we propose a greedy algorithm to identify influential nodes in Boolean networks by minimizing the largest eigenvalue of a modified nonbacktracking matrix. We test the performance of the proposed collective influence algorithm on four different networks. Results show that the collective influence algorithm can stabilize each network with a smaller set of nodes compared with other heuristic algorithms. Our work provides a new insight into the mechanism that determines the stability of Boolean networks, which may find applications in identifying virulence genes that lead to serious diseases.

  10. Digital clocks: simple Boolean models can quantitatively describe circadian systems.

    Science.gov (United States)

    Akman, Ozgur E; Watterson, Steven; Parton, Andrew; Binns, Nigel; Millar, Andrew J; Ghazal, Peter

    2012-09-07

    The gene networks that comprise the circadian clock modulate biological function across a range of scales, from gene expression to performance and adaptive behaviour. The clock functions by generating endogenous rhythms that can be entrained to the external 24-h day-night cycle, enabling organisms to optimally time biochemical processes relative to dawn and dusk. In recent years, computational models based on differential equations have become useful tools for dissecting and quantifying the complex regulatory relationships underlying the clock's oscillatory dynamics. However, optimizing the large parameter sets characteristic of these models places intense demands on both computational and experimental resources, limiting the scope of in silico studies. Here, we develop an approach based on Boolean logic that dramatically reduces the parametrization, making the state and parameter spaces finite and tractable. We introduce efficient methods for fitting Boolean models to molecular data, successfully demonstrating their application to synthetic time courses generated by a number of established clock models, as well as experimental expression levels measured using luciferase imaging. Our results indicate that despite their relative simplicity, logic models can (i) simulate circadian oscillations with the correct, experimentally observed phase relationships among genes and (ii) flexibly entrain to light stimuli, reproducing the complex responses to variations in daylength generated by more detailed differential equation formulations. Our work also demonstrates that logic models have sufficient predictive power to identify optimal regulatory structures from experimental data. By presenting the first Boolean models of circadian circuits together with general techniques for their optimization, we hope to establish a new framework for the systematic modelling of more complex clocks, as well as other circuits with different qualitative dynamics. In particular, we anticipate

  11. Digital clocks: simple Boolean models can quantitatively describe circadian systems

    Science.gov (United States)

    Akman, Ozgur E.; Watterson, Steven; Parton, Andrew; Binns, Nigel; Millar, Andrew J.; Ghazal, Peter

    2012-01-01

    The gene networks that comprise the circadian clock modulate biological function across a range of scales, from gene expression to performance and adaptive behaviour. The clock functions by generating endogenous rhythms that can be entrained to the external 24-h day–night cycle, enabling organisms to optimally time biochemical processes relative to dawn and dusk. In recent years, computational models based on differential equations have become useful tools for dissecting and quantifying the complex regulatory relationships underlying the clock's oscillatory dynamics. However, optimizing the large parameter sets characteristic of these models places intense demands on both computational and experimental resources, limiting the scope of in silico studies. Here, we develop an approach based on Boolean logic that dramatically reduces the parametrization, making the state and parameter spaces finite and tractable. We introduce efficient methods for fitting Boolean models to molecular data, successfully demonstrating their application to synthetic time courses generated by a number of established clock models, as well as experimental expression levels measured using luciferase imaging. Our results indicate that despite their relative simplicity, logic models can (i) simulate circadian oscillations with the correct, experimentally observed phase relationships among genes and (ii) flexibly entrain to light stimuli, reproducing the complex responses to variations in daylength generated by more detailed differential equation formulations. Our work also demonstrates that logic models have sufficient predictive power to identify optimal regulatory structures from experimental data. By presenting the first Boolean models of circadian circuits together with general techniques for their optimization, we hope to establish a new framework for the systematic modelling of more complex clocks, as well as other circuits with different qualitative dynamics. In particular, we

  12. Boolean models of biosurfactants production in Pseudomonas fluorescens.

    Directory of Open Access Journals (Sweden)

    Adrien Richard

    Full Text Available Cyclolipopeptides (CLPs are biosurfactants produced by numerous Pseudomonas fluorescens strains. CLP production is known to be regulated at least by the GacA/GacS two-component pathway, but the full regulatory network is yet largely unknown. In the clinical strain MFN1032, CLP production is abolished by a mutation in the phospholipase C gene (plcC and not restored by plcC complementation. Their production is also subject to phenotypic variation. We used a modelling approach with Boolean networks, which takes into account all these observations concerning CLP production without any assumption on the topology of the considered network. Intensive computation yielded numerous models that satisfy these properties. All models minimizing the number of components point to a bistability in CLP production, which requires the presence of a yet unknown key self-inducible regulator. Furthermore, all suggest that a set of yet unexplained phenotypic variants might also be due to this epigenetic switch. The simplest of these Boolean networks was used to propose a biological regulatory network for CLP production. This modelling approach has allowed a possible regulation to be unravelled and an unusual behaviour of CLP production in P. fluorescens to be explained.

  13. Attractor Transformation by Impulsive Control in Boolean Control Network

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    Bo Gao

    2013-01-01

    Full Text Available Boolean control networks have recently been attracting considerable interests as computational models for genetic regulatory networks. In this paper, we present an approach of impulsive control for attractor transitions in Boolean control networks based on the recent developed matrix semitensor product theory. The reachability of attractors is estimated, and the controller is also obtained. The general derivation proposed here is exemplified with a kind of gene model, which is the protein-nucleic acid interactions network, on numerical simulations.

  14. Algebraic partial Boolean algebras

    CERN Document Server

    Smith, D

    2003-01-01

    Partial Boolean algebras, first studied by Kochen and Specker in the 1960s, provide the structure for Bell-Kochen-Specker theorems which deny the existence of non-contextual hidden variable theories. In this paper, we study partial Boolean algebras which are 'algebraic' in the sense that their elements have coordinates in an algebraic number field. Several of these algebras have been discussed recently in a debate on the validity of Bell-Kochen-Specker theorems in the context of finite precision measurements. The main result of this paper is that every algebraic finitely-generated partial Boolean algebra B(T) is finite when the underlying space H is three-dimensional, answering a question of Kochen and showing that Conway and Kochen's infinite algebraic partial Boolean algebra has minimum dimension. This result contrasts the existence of an infinite (non-algebraic) B(T) generated by eight elements in an abstract orthomodular lattice of height 3. We then initiate a study of higher-dimensional algebraic partial...

  15. Algebraic partial Boolean algebras

    Science.gov (United States)

    Smith, Derek

    2003-04-01

    Partial Boolean algebras, first studied by Kochen and Specker in the 1960s, provide the structure for Bell-Kochen-Specker theorems which deny the existence of non-contextual hidden variable theories. In this paper, we study partial Boolean algebras which are 'algebraic' in the sense that their elements have coordinates in an algebraic number field. Several of these algebras have been discussed recently in a debate on the validity of Bell-Kochen-Specker theorems in the context of finite precision measurements. The main result of this paper is that every algebraic finitely-generated partial Boolean algebra B(T) is finite when the underlying space Script H is three-dimensional, answering a question of Kochen and showing that Conway and Kochen's infinite algebraic partial Boolean algebra has minimum dimension. This result contrasts the existence of an infinite (non-algebraic) B(T) generated by eight elements in an abstract orthomodular lattice of height 3. We then initiate a study of higher-dimensional algebraic partial Boolean algebras. First, we describe a restriction on the determinants of the elements of B(T) that are generated by a given set T. We then show that when the generating set T consists of the rays spanning the minimal vectors in a real irreducible root lattice, B(T) is infinite just if that root lattice has an A5 sublattice. Finally, we characterize the rays of B(T) when T consists of the rays spanning the minimal vectors of the root lattice E8.

  16. Algebraic partial Boolean algebras

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Derek [Math Department, Lafayette College, Easton, PA 18042 (United States)

    2003-04-04

    Partial Boolean algebras, first studied by Kochen and Specker in the 1960s, provide the structure for Bell-Kochen-Specker theorems which deny the existence of non-contextual hidden variable theories. In this paper, we study partial Boolean algebras which are 'algebraic' in the sense that their elements have coordinates in an algebraic number field. Several of these algebras have been discussed recently in a debate on the validity of Bell-Kochen-Specker theorems in the context of finite precision measurements. The main result of this paper is that every algebraic finitely-generated partial Boolean algebra B(T) is finite when the underlying space H is three-dimensional, answering a question of Kochen and showing that Conway and Kochen's infinite algebraic partial Boolean algebra has minimum dimension. This result contrasts the existence of an infinite (non-algebraic) B(T) generated by eight elements in an abstract orthomodular lattice of height 3. We then initiate a study of higher-dimensional algebraic partial Boolean algebras. First, we describe a restriction on the determinants of the elements of B(T) that are generated by a given set T. We then show that when the generating set T consists of the rays spanning the minimal vectors in a real irreducible root lattice, B(T) is infinite just if that root lattice has an A{sub 5} sublattice. Finally, we characterize the rays of B(T) when T consists of the rays spanning the minimal vectors of the root lattice E{sub 8}.

  17. Regulatory Evolution and Theoretical Arguments in Evolutionary Biology

    Science.gov (United States)

    Ioannidis, Stavros

    2013-01-01

    The "cis"-regulatory hypothesis is one of the most important claims of evolutionary developmental biology. In this paper I examine the theoretical argument for "cis"-regulatory evolution and its role within evolutionary theorizing. I show that, although the argument has some weaknesses, it acts as a useful example for the importance of current…

  18. A full bayesian approach for boolean genetic network inference.

    Directory of Open Access Journals (Sweden)

    Shengtong Han

    Full Text Available Boolean networks are a simple but efficient model for describing gene regulatory systems. A number of algorithms have been proposed to infer Boolean networks. However, these methods do not take full consideration of the effects of noise and model uncertainty. In this paper, we propose a full Bayesian approach to infer Boolean genetic networks. Markov chain Monte Carlo algorithms are used to obtain the posterior samples of both the network structure and the related parameters. In addition to regular link addition and removal moves, which can guarantee the irreducibility of the Markov chain for traversing the whole network space, carefully constructed mixture proposals are used to improve the Markov chain Monte Carlo convergence. Both simulations and a real application on cell-cycle data show that our method is more powerful than existing methods for the inference of both the topology and logic relations of the Boolean network from observed data.

  19. Social insect colony as a biological regulatory system: modelling information flow in dominance networks.

    Science.gov (United States)

    Nandi, Anjan K; Sumana, Annagiri; Bhattacharya, Kunal

    2014-12-06

    Social insects provide an excellent platform to investigate flow of information in regulatory systems since their successful social organization is essentially achieved by effective information transfer through complex connectivity patterns among the colony members. Network representation of such behavioural interactions offers a powerful tool for structural as well as dynamical analysis of the underlying regulatory systems. In this paper, we focus on the dominance interaction networks in the tropical social wasp Ropalidia marginata-a species where behavioural observations indicate that such interactions are principally responsible for the transfer of information between individuals about their colony needs, resulting in a regulation of their own activities. Our research reveals that the dominance networks of R. marginata are structurally similar to a class of naturally evolved information processing networks, a fact confirmed also by the predominance of a specific substructure-the 'feed-forward loop'-a key functional component in many other information transfer networks. The dynamical analysis through Boolean modelling confirms that the networks are sufficiently stable under small fluctuations and yet capable of more efficient information transfer compared to their randomized counterparts. Our results suggest the involvement of a common structural design principle in different biological regulatory systems and a possible similarity with respect to the effect of selection on the organization levels of such systems. The findings are also consistent with the hypothesis that dominance behaviour has been shaped by natural selection to co-opt the information transfer process in such social insect species, in addition to its primal function of mediation of reproductive competition in the colony. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  20. Adapted Boolean network models for extracellular matrix formation

    Directory of Open Access Journals (Sweden)

    Wollbold Johannes

    2009-07-01

    Full Text Available Abstract Background Due to the rapid data accumulation on pathogenesis and progression of chronic inflammation, there is an increasing demand for approaches to analyse the underlying regulatory networks. For example, rheumatoid arthritis (RA is a chronic inflammatory disease, characterised by joint destruction and perpetuated by activated synovial fibroblasts (SFB. These abnormally express and/or secrete pro-inflammatory cytokines, collagens causing joint fibrosis, or tissue-degrading enzymes resulting in destruction of the extra-cellular matrix (ECM. We applied three methods to analyse ECM regulation: data discretisation to filter out noise and to reduce complexity, Boolean network construction to implement logic relationships, and formal concept analysis (FCA for the formation of minimal, but complete rule sets from the data. Results First, we extracted literature information to develop an interaction network containing 18 genes representing ECM formation and destruction. Subsequently, we constructed an asynchronous Boolean network with biologically plausible time intervals for mRNA and protein production, secretion, and inactivation. Experimental gene expression data was obtained from SFB stimulated by TGFβ1 or by TNFα and discretised thereafter. The Boolean functions of the initial network were improved iteratively by the comparison of the simulation runs to the experimental data and by exploitation of expert knowledge. This resulted in adapted networks for both cytokine stimulation conditions. The simulations were further analysed by the attribute exploration algorithm of FCA, integrating the observed time series in a fine-tuned and automated manner. The resulting temporal rules yielded new contributions to controversially discussed aspects of fibroblast biology (e.g., considerable expression of TNF and MMP9 by fibroblasts stimulation and corroborated previously known facts (e.g., co-expression of collagens and MMPs after TNF

  1. Approximate Reasoning with Fuzzy Booleans

    NARCIS (Netherlands)

    van den Broek, P.M.; Noppen, J.A.R.

    This paper introduces, in analogy to the concept of fuzzy numbers, the concept of fuzzy booleans, and examines approximate reasoning with the compositional rule of inference using fuzzy booleans. It is shown that each set of fuzzy rules is equivalent to a set of fuzzy rules with singleton crisp

  2. Geometric Operators on Boolean Functions

    DEFF Research Database (Denmark)

    Frisvad, Jeppe Revall; Falster, Peter

    In truth-functional propositional logic, any propositional formula represents a Boolean function (according to some valuation of the formula). We describe operators based on Decartes' concept of constructing coordinate systems, for translation of a propositional formula to the image of a Boolean...... function. With this image of a Boolean function corresponding to a propositional formula, we prove that the orthogonal projection operator leads to a theorem describing all rules of inference in propositional reasoning. In other words, we can capture all kinds of inference in propositional logic by means...... of a few geometric operators working on the images of Boolean functions. The operators we describe, arise from the niche area of array-based logic and have previously been tightly bound to an array-based representation of Boolean functions. We redefine the operators in an abstract form to make them...

  3. Cryptographic Boolean functions and applications

    CERN Document Server

    Cusick, Thomas W

    2009-01-01

    Boolean functions are the building blocks of symmetric cryptographic systems. Symmetrical cryptographic algorithms are fundamental tools in the design of all types of digital security systems (i.e. communications, financial and e-commerce).Cryptographic Boolean Functions and Applications is a concise reference that shows how Boolean functions are used in cryptography. Currently, practitioners who need to apply Boolean functions in the design of cryptographic algorithms and protocols need to patch together needed information from a variety of resources (books, journal articles and other sources). This book compiles the key essential information in one easy to use, step-by-step reference. Beginning with the basics of the necessary theory the book goes on to examine more technical topics, some of which are at the frontier of current research.-Serves as a complete resource for the successful design or implementation of cryptographic algorithms or protocols using Boolean functions -Provides engineers and scient...

  4. The stability of Boolean network with transmission sensitivity

    Science.gov (United States)

    Wang, Jiannan; Guo, Binghui; Wei, Wei; Mi, Zhilong; Yin, Ziqiao; Zheng, Zhiming

    2017-09-01

    Boolean network has been widely used in modeling biological systems and one of the key problems is its stability in response to small perturbations. Based on the hypothesis that the states of all nodes are homogenously updated, great progress has been made in previous works. In real biological networks, however, the updates of genes typically show much heterogeneity. To address such conditions, we introduce transmission sensitivity into Boolean network model. By the method of semi-annealed approximation, we illustrate that in a homogenous network, the critical condition of stability has no connection with its transmission sensitivity. As for heterogeneous networks, it reveals that correlations between network topology and transmission sensitivity can have profound effects on the its stability. This result shows a new mechanism that affects the stability of Boolean network, which could be used to control the dynamics in real biological systems.

  5. Development of Boolean calculus and its application

    Science.gov (United States)

    Tapia, M. A.

    1979-01-01

    Formal procedures for synthesis of asynchronous sequential system using commercially available edge-sensitive flip-flops are developed. Boolean differential is defined. The exact number of compatible integrals of a Boolean differential were calculated.

  6. Bistability and Asynchrony in a Boolean Model of the L-arabinose Operon in Escherichia coli.

    Science.gov (United States)

    Jenkins, Andy; Macauley, Matthew

    2017-08-01

    The lactose operon in Escherichia coli was the first known gene regulatory network, and it is frequently used as a prototype for new modeling paradigms. Historically, many of these modeling frameworks use differential equations. More recently, Stigler and Veliz-Cuba proposed a Boolean model that captures the bistability of the system and all of the biological steady states. In this paper, we model the well-known arabinose operon in E. coli with a Boolean network. This has several complex features not found in the lac operon, such as a protein that is both an activator and repressor, a DNA looping mechanism for gene repression, and the lack of inducer exclusion by glucose. For 11 out of 12 choices of initial conditions, we use computational algebra and Sage to verify that the state space contains a single fixed point that correctly matches the biology. The final initial condition, medium levels of arabinose and no glucose, successfully predicts the system's bistability. Finally, we compare the state space under synchronous and asynchronous update and see that the former has several artificial cycles that go away under a general asynchronous update.

  7. Boolean-Valued Belief Functions

    Czech Academy of Sciences Publication Activity Database

    Kramosil, Ivan

    2002-01-01

    Roč. 31, č. 2 (2002), s. 153-181 ISSN 0308-1079 R&D Projects: GA AV ČR IAA1030803 Institutional research plan: AV0Z1030915 Keywords : Dempster-Schafer theory * Boolean algebra Subject RIV: BA - General Mathematics Impact factor: 0.241, year: 2002

  8. Modular Decomposition of Boolean Functions

    NARCIS (Netherlands)

    J.C. Bioch (Cor)

    2002-01-01

    textabstractModular decomposition is a thoroughly investigated topic in many areas such as switching theory, reliability theory, game theory and graph theory. Most appli- cations can be formulated in the framework of Boolean functions. In this paper we give a uni_ed treatment of modular

  9. Learning restricted Boolean network model by time-series data.

    Science.gov (United States)

    Ouyang, Hongjia; Fang, Jie; Shen, Liangzhong; Dougherty, Edward R; Liu, Wenbin

    2014-01-01

    Restricted Boolean networks are simplified Boolean networks that are required for either negative or positive regulations between genes. Higa et al. (BMC Proc 5:S5, 2011) proposed a three-rule algorithm to infer a restricted Boolean network from time-series data. However, the algorithm suffers from a major drawback, namely, it is very sensitive to noise. In this paper, we systematically analyze the regulatory relationships between genes based on the state switch of the target gene and propose an algorithm with which restricted Boolean networks may be inferred from time-series data. We compare the proposed algorithm with the three-rule algorithm and the best-fit algorithm based on both synthetic networks and a well-studied budding yeast cell cycle network. The performance of the algorithms is evaluated by three distance metrics: the normalized-edge Hamming distance [Formula: see text], the normalized Hamming distance of state transition [Formula: see text], and the steady-state distribution distance μ (ssd). Results show that the proposed algorithm outperforms the others according to both [Formula: see text] and [Formula: see text], whereas its performance according to μ (ssd) is intermediate between best-fit and the three-rule algorithms. Thus, our new algorithm is more appropriate for inferring interactions between genes from time-series data.

  10. A novel mutual information-based Boolean network inference method from time-series gene expression data.

    Directory of Open Access Journals (Sweden)

    Shohag Barman

    Full Text Available Inferring a gene regulatory network from time-series gene expression data in systems biology is a challenging problem. Many methods have been suggested, most of which have a scalability limitation due to the combinatorial cost of searching a regulatory set of genes. In addition, they have focused on the accurate inference of a network structure only. Therefore, there is a pressing need to develop a network inference method to search regulatory genes efficiently and to predict the network dynamics accurately.In this study, we employed a Boolean network model with a restricted update rule scheme to capture coarse-grained dynamics, and propose a novel mutual information-based Boolean network inference (MIBNI method. Given time-series gene expression data as an input, the method first identifies a set of initial regulatory genes using mutual information-based feature selection, and then improves the dynamics prediction accuracy by iteratively swapping a pair of genes between sets of the selected regulatory genes and the other genes. Through extensive simulations with artificial datasets, MIBNI showed consistently better performance than six well-known existing methods, REVEAL, Best-Fit, RelNet, CST, CLR, and BIBN in terms of both structural and dynamics prediction accuracy. We further tested the proposed method with two real gene expression datasets for an Escherichia coli gene regulatory network and a fission yeast cell cycle network, and also observed better results using MIBNI compared to the six other methods.Taken together, MIBNI is a promising tool for predicting both the structure and the dynamics of a gene regulatory network.

  11. Boolean gates on actin filaments

    Energy Technology Data Exchange (ETDEWEB)

    Siccardi, Stefano, E-mail: ssiccardi@2ssas.it [The Unconventional Computing Centre, University of the West of England, Bristol (United Kingdom); Tuszynski, Jack A., E-mail: jackt@ualberta.ca [Department of Oncology, University of Alberta, Edmonton, Alberta (Canada); Adamatzky, Andrew, E-mail: andrew.adamatzky@uwe.ac.uk [The Unconventional Computing Centre, University of the West of England, Bristol (United Kingdom)

    2016-01-08

    Actin is a globular protein which forms long polar filaments in the eukaryotic cytoskeleton. Actin networks play a key role in cell mechanics and cell motility. They have also been implicated in information transmission and processing, memory and learning in neuronal cells. The actin filaments have been shown to support propagation of voltage pulses. Here we apply a coupled nonlinear transmission line model of actin filaments to study interactions between voltage pulses. To represent digital information we assign a logical TRUTH value to the presence of a voltage pulse in a given location of the actin filament, and FALSE to the pulse's absence, so that information flows along the filament with pulse transmission. When two pulses, representing Boolean values of input variables, interact, then they can facilitate or inhibit further propagation of each other. We explore this phenomenon to construct Boolean logical gates and a one-bit half-adder with interacting voltage pulses. We discuss implications of these findings on cellular process and technological applications. - Highlights: • We simulate interaction between voltage pulses using on actin filaments. • We use a coupled nonlinear transmission line model. • We design Boolean logical gates via interactions between the voltage pulses. • We construct one-bit half-adder with interacting voltage pulses.

  12. Super-transient scaling in time-delay autonomous Boolean network motifs

    Energy Technology Data Exchange (ETDEWEB)

    D' Huys, Otti, E-mail: otti.dhuys@phy.duke.edu; Haynes, Nicholas D. [Department of Physics, Duke University, Durham, North Carolina 27708 (United States); Lohmann, Johannes [Department of Physics, Duke University, Durham, North Carolina 27708 (United States); Institut für Theoretische Physik, Technische Universität Berlin, Hardenbergstraße 36, 10623 Berlin (Germany); Gauthier, Daniel J. [Department of Physics, Duke University, Durham, North Carolina 27708 (United States); Department of Physics, The Ohio State University, Columbus, Ohio 43210 (United States)

    2016-09-15

    Autonomous Boolean networks are commonly used to model the dynamics of gene regulatory networks and allow for the prediction of stable dynamical attractors. However, most models do not account for time delays along the network links and noise, which are crucial features of real biological systems. Concentrating on two paradigmatic motifs, the toggle switch and the repressilator, we develop an experimental testbed that explicitly includes both inter-node time delays and noise using digital logic elements on field-programmable gate arrays. We observe transients that last millions to billions of characteristic time scales and scale exponentially with the amount of time delays between nodes, a phenomenon known as super-transient scaling. We develop a hybrid model that includes time delays along network links and allows for stochastic variation in the delays. Using this model, we explain the observed super-transient scaling of both motifs and recreate the experimentally measured transient distributions.

  13. Quantum algorithms for testing Boolean functions

    Directory of Open Access Journals (Sweden)

    Erika Andersson

    2010-06-01

    Full Text Available We discuss quantum algorithms, based on the Bernstein-Vazirani algorithm, for finding which variables a Boolean function depends on. There are 2^n possible linear Boolean functions of n variables; given a linear Boolean function, the Bernstein-Vazirani quantum algorithm can deterministically identify which one of these Boolean functions we are given using just one single function query. The same quantum algorithm can also be used to learn which input variables other types of Boolean functions depend on, with a success probability that depends on the form of the Boolean function that is tested, but does not depend on the total number of input variables. We also outline a procedure to futher amplify the success probability, based on another quantum algorithm, the Grover search.

  14. Theory reduction and non-Boolean theories.

    Science.gov (United States)

    Primas, H

    1977-07-19

    It is suggested that biological theories should be embedded into the family of non-Boolean theories based on an orthomodular propositional calculus. The structure of universal theories that include quantal phenomena is investigated and it is shown that their subtheories form a directed set which cannot be totally orders. A precise definition of theory reduction is given; it turns out that hierarchically different descriptive levels are not related by a homomorphic map. A subtheory that is reducible to a more general theory can be associated with the emergence of novel concepts and is in general subject to a wider empirical clissification scheme than the reducing theory. The implications of these results for reductionism, holism, emergence, and their conceptual unification are discussed.

  15. Griffin: A Tool for Symbolic Inference of Synchronous Boolean Molecular Networks

    Science.gov (United States)

    Muñoz, Stalin; Carrillo, Miguel; Azpeitia, Eugenio; Rosenblueth, David A.

    2018-01-01

    Boolean networks are important models of biochemical systems, located at the high end of the abstraction spectrum. A number of Boolean gene networks have been inferred following essentially the same method. Such a method first considers experimental data for a typically underdetermined “regulation” graph. Next, Boolean networks are inferred by using biological constraints to narrow the search space, such as a desired set of (fixed-point or cyclic) attractors. We describe Griffin, a computer tool enhancing this method. Griffin incorporates a number of well-established algorithms, such as Dubrova and Teslenko's algorithm for finding attractors in synchronous Boolean networks. In addition, a formal definition of regulation allows Griffin to employ “symbolic” techniques, able to represent both large sets of network states and Boolean constraints. We observe that when the set of attractors is required to be an exact set, prohibiting additional attractors, a naive Boolean coding of this constraint may be unfeasible. Such cases may be intractable even with symbolic methods, as the number of Boolean constraints may be astronomically large. To overcome this problem, we employ an Artificial Intelligence technique known as “clause learning” considerably increasing Griffin's scalability. Without clause learning only toy examples prohibiting additional attractors are solvable: only one out of seven queries reported here is answered. With clause learning, by contrast, all seven queries are answered. We illustrate Griffin with three case studies drawn from the Arabidopsis thaliana literature. Griffin is available at: http://turing.iimas.unam.mx/griffin. PMID:29559993

  16. Testing Properties of Boolean Functions

    Science.gov (United States)

    2012-01-01

    The JUNTATEST algorithm is based on two simple but powerful ideas. The first idea, initially presented by Fischer et al. [52], is that there is a very...Computer and System Sciences, 61(3):428 – 456, 2000. 12 [75] Subhash Khot. On the power of unique 2-prover 1-round games. In Proc. 34th ACM Symposium on...Sharpness of KKL on Schreier graphs, 2009. Manuscript. 6.4 [84] Michal Parnas, Dana Ron, and Alex Samorodnitsky. Testing basic boolean formu- lae . SIAM J

  17. Version Spaces and Generalized Monotone Boolean Functions

    NARCIS (Netherlands)

    J.C. Bioch (Cor); T. Ibaraki

    2002-01-01

    textabstractWe consider generalized monotone functions f: X --> {0,1} defined for an arbitrary binary relation <= on X by the property x <= y implies f(x) <= f(y). These include the standard monotone (or positive) Boolean functions, regular Boolean functions and other interesting functions as

  18. A SAT-based algorithm for finding attractors in synchronous Boolean networks.

    Science.gov (United States)

    Dubrova, Elena; Teslenko, Maxim

    2011-01-01

    This paper addresses the problem of finding attractors in synchronous Boolean networks. The existing Boolean decision diagram-based algorithms have limited capacity due to the excessive memory requirements of decision diagrams. The simulation-based algorithms can be applied to larger networks, however, they are incomplete. We present an algorithm, which uses a SAT-based bounded model checking to find all attractors in a Boolean network. The efficiency of the presented algorithm is evaluated by analyzing seven networks models of real biological processes, as well as 150,000 randomly generated Boolean networks of sizes between 100 and 7,000. The results show that our approach has a potential to handle an order of magnitude larger models than currently possible.

  19. A novel generalized design methodology and realization of Boolean operations using DNA.

    Science.gov (United States)

    Zoraida, B S E; Arock, Michael; Ronald, B S M; Ponalagusamy, R

    2009-09-01

    The biological deoxyribonucleic acid (DNA) strand has been increasingly seen as a promising computing unit. A new algorithm is formulated in this paper to design any DNA Boolean operator with molecular beacons (MBs) as its input. Boolean operators realized using the proposed design methodology is presented. The developed operators adopt a uniform representation for logical 0 and 1 for any Boolean operator. The Boolean operators designed in this work employ only a hybridization operation at each stage. Further, this paper for the first time brings out the realization of a binary adder and subtractor using molecular beacons. Simulation results of the DNA-based binary adder and subtractor are given to validate the design.

  20. Boolean gates on actin filaments

    Science.gov (United States)

    Siccardi, Stefano; Tuszynski, Jack A.; Adamatzky, Andrew

    2016-01-01

    Actin is a globular protein which forms long polar filaments in the eukaryotic cytoskeleton. Actin networks play a key role in cell mechanics and cell motility. They have also been implicated in information transmission and processing, memory and learning in neuronal cells. The actin filaments have been shown to support propagation of voltage pulses. Here we apply a coupled nonlinear transmission line model of actin filaments to study interactions between voltage pulses. To represent digital information we assign a logical TRUTH value to the presence of a voltage pulse in a given location of the actin filament, and FALSE to the pulse's absence, so that information flows along the filament with pulse transmission. When two pulses, representing Boolean values of input variables, interact, then they can facilitate or inhibit further propagation of each other. We explore this phenomenon to construct Boolean logical gates and a one-bit half-adder with interacting voltage pulses. We discuss implications of these findings on cellular process and technological applications.

  1. Boolean Dependence Logic and Partially-Ordered Connectives

    OpenAIRE

    Ebbing, Johannes; Hella, Lauri; Lohmann, Peter; Virtema, Jonni

    2014-01-01

    We introduce a new variant of dependence logic called Boolean dependence logic. In Boolean dependence logic dependence atoms are of the type =(x_1,...,x_n,\\alpha), where \\alpha is a Boolean variable. Intuitively, with Boolean dependence atoms one can express quantification of relations, while standard dependence atoms express quantification over functions. We compare the expressive power of Boolean dependence logic to dependence logic and first-order logic enriched by partially-ordered connec...

  2. Random networks of Boolean cellular automata

    International Nuclear Information System (INIS)

    Miranda, Enrique

    1990-01-01

    Some recent results about random networks of Boolean automata -the Kauffman model- are reviewed. The structure of configuration space is explored. Ultrametricity between cycles is analyzed and the effects of noise in the dynamics are studied. (Author)

  3. MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems.

    Science.gov (United States)

    Herranz, Héctor; Cohen, Stephen M

    2010-07-01

    Biological systems are continuously challenged by an environment that is variable. Yet, a key feature of developmental and physiological processes is their remarkable stability. This review considers how microRNAs contribute to gene regulatory networks that confer robustness.

  4. Forced synchronization of autonomous dynamical Boolean networks

    International Nuclear Information System (INIS)

    Rivera-Durón, R. R.; Campos-Cantón, E.; Campos-Cantón, I.; Gauthier, Daniel J.

    2015-01-01

    We present the design of an autonomous time-delay Boolean network realized with readily available electronic components. Through simulations and experiments that account for the detailed nonlinear response of each circuit element, we demonstrate that a network with five Boolean nodes displays complex behavior. Furthermore, we show that the dynamics of two identical networks display near-instantaneous synchronization to a periodic state when forced by a common periodic Boolean signal. A theoretical analysis of the network reveals the conditions under which complex behavior is expected in an individual network and the occurrence of synchronization in the forced networks. This research will enable future experiments on autonomous time-delay networks using readily available electronic components with dynamics on a slow enough time-scale so that inexpensive data collection systems can faithfully record the dynamics

  5. Forced synchronization of autonomous dynamical Boolean networks

    Energy Technology Data Exchange (ETDEWEB)

    Rivera-Durón, R. R., E-mail: roberto.rivera@ipicyt.edu.mx; Campos-Cantón, E., E-mail: eric.campos@ipicyt.edu.mx [División de Matemáticas Aplicadas, Instituto Potosino de Investigación Científica y Tecnológica A. C., Camino a la Presa San José 2055, Col. Lomas 4 Sección, C.P. 78216, San Luis Potosí, S.L.P. (Mexico); Campos-Cantón, I. [Facultad de Ciencias, Universidad Autónoma de San Luis Potosí, Álvaro Obregón 64, C.P. 78000, San Luis Potosí, S.L.P. (Mexico); Gauthier, Daniel J. [Department of Physics and Center for Nonlinear and Complex Systems, Duke University, Box 90305, Durham, North Carolina 27708 (United States)

    2015-08-15

    We present the design of an autonomous time-delay Boolean network realized with readily available electronic components. Through simulations and experiments that account for the detailed nonlinear response of each circuit element, we demonstrate that a network with five Boolean nodes displays complex behavior. Furthermore, we show that the dynamics of two identical networks display near-instantaneous synchronization to a periodic state when forced by a common periodic Boolean signal. A theoretical analysis of the network reveals the conditions under which complex behavior is expected in an individual network and the occurrence of synchronization in the forced networks. This research will enable future experiments on autonomous time-delay networks using readily available electronic components with dynamics on a slow enough time-scale so that inexpensive data collection systems can faithfully record the dynamics.

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

    Science.gov (United States)

    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...

  7. A New Calculation for Boolean Derivative Using Cheng Product

    Directory of Open Access Journals (Sweden)

    Hao Chen

    2012-01-01

    Full Text Available The matrix expression and relationships among several definitions of Boolean derivatives are given by using the Cheng product. We introduce several definitions of Boolean derivatives. By using the Cheng product, the matrix expressions of Boolean derivative are given, respectively. Furthermore, the relationships among different definitions are presented. The logical calculation is converted into matrix product. This helps to extend the application of Boolean derivative. At last, an example is given to illustrate the main results.

  8. The Permeability of Boolean Sets of Cylinders

    Directory of Open Access Journals (Sweden)

    Willot F.

    2016-07-01

    Full Text Available Numerical and analytical results on the permeability of Boolean models of randomly-oriented cylinders with circular cross-section are reported. The present work investigates cylinders of prolate (highly-elongated and oblate (nearly flat types. The fluid flows either inside or outside of the cylinders. The Stokes flow is solved using full-fields Fourier-based computations on 3D binarized microstructures. The permeability is given for varying volume fractions of pores. A new upper-bound is derived for the permeability of the Boolean model of oblate cylinders. The behavior of the permeability in the dilute limit is discussed.

  9. Information theory in systems biology. Part I: Gene regulatory and metabolic networks.

    Science.gov (United States)

    Mousavian, Zaynab; Kavousi, Kaveh; Masoudi-Nejad, Ali

    2016-03-01

    "A Mathematical Theory of Communication", was published in 1948 by Claude Shannon to establish a framework that is now known as information theory. In recent decades, information theory has gained much attention in the area of systems biology. The aim of this paper is to provide a systematic review of those contributions that have applied information theory in inferring or understanding of biological systems. Based on the type of system components and the interactions between them, we classify the biological systems into 4 main classes: gene regulatory, metabolic, protein-protein interaction and signaling networks. In the first part of this review, we attempt to introduce most of the existing studies on two types of biological networks, including gene regulatory and metabolic networks, which are founded on the concepts of information theory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Evolutionary Algorithms for Boolean Queries Optimization

    Czech Academy of Sciences Publication Activity Database

    Húsek, Dušan; Snášel, Václav; Neruda, Roman; Owais, S.S.J.; Krömer, P.

    2006-01-01

    Roč. 3, č. 1 (2006), s. 15-20 ISSN 1790-0832 R&D Projects: GA AV ČR 1ET100300414 Institutional research plan: CEZ:AV0Z10300504 Keywords : evolutionary algorithms * genetic algorithms * information retrieval * Boolean query Subject RIV: BA - General Mathematics

  11. Boolean Queries Optimization by Genetic Algorithms

    Czech Academy of Sciences Publication Activity Database

    Húsek, Dušan; Owais, S.S.J.; Krömer, P.; Snášel, Václav

    2005-01-01

    Roč. 15, - (2005), s. 395-409 ISSN 1210-0552 R&D Projects: GA AV ČR 1ET100300414 Institutional research plan: CEZ:AV0Z10300504 Keywords : evolutionary algorithms * genetic algorithms * genetic programming * information retrieval * Boolean query Subject RIV: BB - Applied Statistics, Operational Research

  12. Inference of a Probabilistic Boolean Network from a Single Observed Temporal Sequence

    Directory of Open Access Journals (Sweden)

    Le Yu

    2007-05-01

    Full Text Available The inference of gene regulatory networks is a key issue for genomic signal processing. This paper addresses the inference of probabilistic Boolean networks (PBNs from observed temporal sequences of network states. Since a PBN is composed of a finite number of Boolean networks, a basic observation is that the characteristics of a single Boolean network without perturbation may be determined by its pairwise transitions. Because the network function is fixed and there are no perturbations, a given state will always be followed by a unique state at the succeeding time point. Thus, a transition counting matrix compiled over a data sequence will be sparse and contain only one entry per line. If the network also has perturbations, with small perturbation probability, then the transition counting matrix would have some insignificant nonzero entries replacing some (or all of the zeros. If a data sequence is sufficiently long to adequately populate the matrix, then determination of the functions and inputs underlying the model is straightforward. The difficulty comes when the transition counting matrix consists of data derived from more than one Boolean network. We address the PBN inference procedure in several steps: (1 separate the data sequence into “pure” subsequences corresponding to constituent Boolean networks; (2 given a subsequence, infer a Boolean network; and (3 infer the probabilities of perturbation, the probability of there being a switch between constituent Boolean networks, and the selection probabilities governing which network is to be selected given a switch. Capturing the full dynamic behavior of probabilistic Boolean networks, be they binary or multivalued, will require the use of temporal data, and a great deal of it. This should not be surprising given the complexity of the model and the number of parameters, both transitional and static, that must be estimated. In addition to providing an inference algorithm

  13. Inference of a Probabilistic Boolean Network from a Single Observed Temporal Sequence

    Directory of Open Access Journals (Sweden)

    Xiao Yufei

    2007-01-01

    Full Text Available The inference of gene regulatory networks is a key issue for genomic signal processing. This paper addresses the inference of probabilistic Boolean networks (PBNs from observed temporal sequences of network states. Since a PBN is composed of a finite number of Boolean networks, a basic observation is that the characteristics of a single Boolean network without perturbation may be determined by its pairwise transitions. Because the network function is fixed and there are no perturbations, a given state will always be followed by a unique state at the succeeding time point. Thus, a transition counting matrix compiled over a data sequence will be sparse and contain only one entry per line. If the network also has perturbations, with small perturbation probability, then the transition counting matrix would have some insignificant nonzero entries replacing some (or all of the zeros. If a data sequence is sufficiently long to adequately populate the matrix, then determination of the functions and inputs underlying the model is straightforward. The difficulty comes when the transition counting matrix consists of data derived from more than one Boolean network. We address the PBN inference procedure in several steps: (1 separate the data sequence into "pure" subsequences corresponding to constituent Boolean networks; (2 given a subsequence, infer a Boolean network; and (3 infer the probabilities of perturbation, the probability of there being a switch between constituent Boolean networks, and the selection probabilities governing which network is to be selected given a switch. Capturing the full dynamic behavior of probabilistic Boolean networks, be they binary or multivalued, will require the use of temporal data, and a great deal of it. This should not be surprising given the complexity of the model and the number of parameters, both transitional and static, that must be estimated. In addition to providing an inference algorithm, this paper

  14. Automatic compilation from high-level biologically-oriented programming language to genetic regulatory networks.

    Science.gov (United States)

    Beal, Jacob; Lu, Ting; Weiss, Ron

    2011-01-01

    The field of synthetic biology promises to revolutionize our ability to engineer biological systems, providing important benefits for a variety of applications. Recent advances in DNA synthesis and automated DNA assembly technologies suggest that it is now possible to construct synthetic systems of significant complexity. However, while a variety of novel genetic devices and small engineered gene networks have been successfully demonstrated, the regulatory complexity of synthetic systems that have been reported recently has somewhat plateaued due to a variety of factors, including the complexity of biology itself and the lag in our ability to design and optimize sophisticated biological circuitry. To address the gap between DNA synthesis and circuit design capabilities, we present a platform that enables synthetic biologists to express desired behavior using a convenient high-level biologically-oriented programming language, Proto. The high level specification is compiled, using a regulatory motif based mechanism, to a gene network, optimized, and then converted to a computational simulation for numerical verification. Through several example programs we illustrate the automated process of biological system design with our platform, and show that our compiler optimizations can yield significant reductions in the number of genes (~ 50%) and latency of the optimized engineered gene networks. Our platform provides a convenient and accessible tool for the automated design of sophisticated synthetic biological systems, bridging an important gap between DNA synthesis and circuit design capabilities. Our platform is user-friendly and features biologically relevant compiler optimizations, providing an important foundation for the development of sophisticated biological systems.

  15. Low doses of ionizing radiation: Biological effects and regulatory control. Contributed papers

    International Nuclear Information System (INIS)

    1997-11-01

    The International Atomic Energy Agency and the World Health Organization, in cooperation with the United Nations Scientific Committee on the Effects of Atomic Radiation, organized an international conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, held in seville, Spain, from 17 to 21 November 1997. This technical document contains concise papers submitted to the conference

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

    Directory of Open Access Journals (Sweden)

    Shah Imran

    2011-07-01

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

  17. An efficient algorithm to identify the optimal one-bit perturbation based on the basin-of-state size of Boolean networks.

    Science.gov (United States)

    Hu, Mingxiao; Shen, Liangzhong; Zan, Xiangzhen; Shang, Xuequn; Liu, Wenbin

    2016-05-19

    Boolean networks are widely used to model gene regulatory networks and to design therapeutic intervention strategies to affect the long-term behavior of systems. In this paper, we investigate the less-studied one-bit perturbation, which falls under the category of structural intervention. Previous works focused on finding the optimal one-bit perturbation to maximally alter the steady-state distribution (SSD) of undesirable states through matrix perturbation theory. However, the application of the SSD is limited to Boolean networks with about ten genes. In 2007, Xiao et al. proposed to search the optimal one-bit perturbation by altering the sizes of the basin of attractions (BOAs). However, their algorithm requires close observation of the state-transition diagram. In this paper, we propose an algorithm that efficiently determines the BOA size after a perturbation. Our idea is that, if we construct the basin of states for all states, then the size of the BOA of perturbed networks can be obtained just by updating the paths of the states whose transitions have been affected. Results from both synthetic and real biological networks show that the proposed algorithm performs better than the exhaustive SSD-based algorithm and can be applied to networks with about 25 genes.

  18. Boolean representations of simplicial complexes and matroids

    CERN Document Server

    Rhodes, John

    2015-01-01

    This self-contained monograph explores a new theory centered around boolean representations of simplicial complexes leading to a new class of complexes featuring matroids as central to the theory. The book illustrates these new tools to study the classical theory of matroids as well as their important geometric connections. Moreover, many geometric and topological features of the theory of matroids find their counterparts in this extended context.   Graduate students and researchers working in the areas of combinatorics, geometry, topology, algebra and lattice theory will find this monograph appealing due to the wide range of new problems raised by the theory. Combinatorialists will find this extension of the theory of matroids useful as it opens new lines of research within and beyond matroids. The geometric features and geometric/topological applications will appeal to geometers. Topologists who desire to perform algebraic topology computations will appreciate the algorithmic potential of boolean represent...

  19. Totally optimal decision trees for Boolean functions

    KAUST Repository

    Chikalov, Igor

    2016-07-28

    We study decision trees which are totally optimal relative to different sets of complexity parameters for Boolean functions. A totally optimal tree is an optimal tree relative to each parameter from the set simultaneously. We consider the parameters characterizing both time (in the worst- and average-case) and space complexity of decision trees, i.e., depth, total path length (average depth), and number of nodes. We have created tools based on extensions of dynamic programming to study totally optimal trees. These tools are applicable to both exact and approximate decision trees, and allow us to make multi-stage optimization of decision trees relative to different parameters and to count the number of optimal trees. Based on the experimental results we have formulated the following hypotheses (and subsequently proved): for almost all Boolean functions there exist totally optimal decision trees (i) relative to the depth and number of nodes, and (ii) relative to the depth and average depth.

  20. Quotients of Boolean algebras and regular subalgebras

    Czech Academy of Sciences Publication Activity Database

    Balcar, Bohuslav; Pazák, Tomáš

    2010-01-01

    Roč. 49, č. 3 (2010), s. 329-342 ISSN 1432-0665 R&D Projects: GA AV ČR IAA100190509; GA MŠk MEB060909 Institutional research plan: CEZ:AV0Z10190503; CEZ:AV0Z10750506 Keywords : Boolean algebra * sequential topology * ZFC extension * ideal Subject RIV: BA - General Mathematics Impact factor: 0.414, year: 2010 http://link.springer.com/article/10.1007%2Fs00153-010-0174-y

  1. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

    NARCIS (Netherlands)

    He, F.; Murabito, E.; Westerhoff, H.V.

    2016-01-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out throughin silicotheoretical studies with the aim to guide and complement furtherin vitroandin vivoexperimental

  2. Automatic compilation from high-level biologically-oriented programming language to genetic regulatory networks.

    Directory of Open Access Journals (Sweden)

    Jacob Beal

    Full Text Available The field of synthetic biology promises to revolutionize our ability to engineer biological systems, providing important benefits for a variety of applications. Recent advances in DNA synthesis and automated DNA assembly technologies suggest that it is now possible to construct synthetic systems of significant complexity. However, while a variety of novel genetic devices and small engineered gene networks have been successfully demonstrated, the regulatory complexity of synthetic systems that have been reported recently has somewhat plateaued due to a variety of factors, including the complexity of biology itself and the lag in our ability to design and optimize sophisticated biological circuitry.To address the gap between DNA synthesis and circuit design capabilities, we present a platform that enables synthetic biologists to express desired behavior using a convenient high-level biologically-oriented programming language, Proto. The high level specification is compiled, using a regulatory motif based mechanism, to a gene network, optimized, and then converted to a computational simulation for numerical verification. Through several example programs we illustrate the automated process of biological system design with our platform, and show that our compiler optimizations can yield significant reductions in the number of genes (~ 50% and latency of the optimized engineered gene networks.Our platform provides a convenient and accessible tool for the automated design of sophisticated synthetic biological systems, bridging an important gap between DNA synthesis and circuit design capabilities. Our platform is user-friendly and features biologically relevant compiler optimizations, providing an important foundation for the development of sophisticated biological systems.

  3. Unlimited multistability and Boolean logic in microbial signalling

    DEFF Research Database (Denmark)

    Kothamachu, Varun B; Feliu, Elisenda; Cardelli, Luca

    2015-01-01

    reactions. We develop a mathematical framework for analysing microbial systems with multi-domain HK receptors known as hybrid and unorthodox HKs. We show that these systems embed a simple core network that exhibits multistability, thereby unveiling a novel biochemical mechanism for multistability. We...... further prove that sharing of downstream components allows a system with n multi-domain hybrid HKs to attain 3n steady states. We find that such systems, when sensing distinct signals, can readily implement Boolean logic functions on these signals. Using two experimentally studied examples of two......-component systems implementing hybrid HKs, we show that bistability and implementation of logic functions are possible under biologically feasible reaction rates. Furthermore, we show that all sequenced microbial genomes contain significant numbers of hybrid and unorthodox HKs, and some genomes have a larger...

  4. A Systems’ Biology Approach to Study MicroRNA-Mediated Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Xin Lai

    2013-01-01

    Full Text Available MicroRNAs (miRNAs are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. Such an approach is characterized by an iterative process, including biological data acquisition and integration, network construction, mathematical modeling and experimental validation. To demonstrate the application of this approach, we adopt it to investigate mechanisms of collective repression on p21 by multiple miRNAs. We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. Based on the network structure, a detailed mechanistic model is established and its parameter values are determined using data. Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts.

  5. Boolean Differentiation Equations Applicable in Reconfigurable Computational Medium

    Directory of Open Access Journals (Sweden)

    Shidlovskiy Stanislav

    2016-01-01

    Full Text Available High performance computing environment synthesis with parallel architecture reconstructing throughout the process itself is described. Synthesized computational medium involving Boolean differential equation calculations so as to function in real-time image processing. Automaton imaging was illustrated involving the rearrangement of every processing medium element to calculate the partial differentials of n-th order in respect to Boolean function variables. The method of obtaining setting codes for each element was also described. An example in calculating 2nd -order Boolean derivative to two differentials in respect to Boolean functions, depending on three arguments within the reconstructible computational medium of 8×8 processing elements was given.

  6. The Number of Monotone and Self-Dual Boolean Functions

    Directory of Open Access Journals (Sweden)

    Haviarova L.

    2014-12-01

    Full Text Available In the present paper we study properties of pre-complete class of Boolean functions - monotone Boolean functions. We discuss interval graph, the abbreviated d.n.f., a minimal d.n.f. and a shortest d.n.f. of this function. Then we present a d.n.f. with the highest number of conjunctionsand we determinate the exact number of them. We count the number of monotone Boolean functions with some special properties. In the end we estimate the number of Boolean functionthat are monotone and self-dual at the same time.

  7. Large Sets in Boolean and Non-Boolean Groups and Topology

    Directory of Open Access Journals (Sweden)

    Ol’ga V. Sipacheva

    2017-10-01

    Full Text Available Various notions of large sets in groups, including the classical notions of thick, syndetic, and piecewise syndetic sets and the new notion of vast sets in groups, are studied with emphasis on the interplay between such sets in Boolean groups. Natural topologies closely related to vast sets are considered; as a byproduct, interesting relations between vast sets and ultrafilters are revealed.

  8. Regulatory administrative databases in FDA's Center for Biologics Evaluation and Research: convergence toward a unified database.

    Science.gov (United States)

    Smith, Jeffrey K

    2013-04-01

    Regulatory administrative database systems within the Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) are essential to supporting its core mission, as a regulatory agency. Such systems are used within FDA to manage information and processes surrounding the processing, review, and tracking of investigational and marketed product submissions. This is an area of increasing interest in the pharmaceutical industry and has been a topic at trade association conferences (Buckley 2012). Such databases in CBER are complex, not for the type or relevance of the data to any particular scientific discipline but because of the variety of regulatory submission types and processes the systems support using the data. Commonalities among different data domains of CBER's regulatory administrative databases are discussed. These commonalities have evolved enough to constitute real database convergence and provide a valuable asset for business process intelligence. Balancing review workload across staff, exploring areas of risk in review capacity, process improvement, and presenting a clear and comprehensive landscape of review obligations are just some of the opportunities of such intelligence. This convergence has been occurring in the presence of usual forces that tend to drive information technology (IT) systems development toward separate stovepipes and data silos. CBER has achieved a significant level of convergence through a gradual process, using a clear goal, agreed upon development practices, and transparency of database objects, rather than through a single, discrete project or IT vendor solution. This approach offers a path forward for FDA systems toward a unified database.

  9. A complexity theory based on Boolean algebra

    DEFF Research Database (Denmark)

    Skyum, Sven; Valiant, Leslie

    1985-01-01

    A projection of a Boolean function is a function obtained by substituting for each of its variables a variable, the negation of a variable, or a constant. Reducibilities among computational problems under this relation of projection are considered. It is shown that much of what is of everyday rel...... relevance in Turing-machine-based complexity theory can be replicated easily and naturally in this elementary framework. Finer distinctions about the computational relationships among natural problems can be made than in previous formulations and some negative results are proved....

  10. The Boolean algebra and central Galois algebras

    Directory of Open Access Journals (Sweden)

    George Szeto

    2001-01-01

    Full Text Available Let B be a Galois algebra with Galois group G, Jg={b∈B∣bx=g(xb   for all   x∈B} for g∈G, and BJg=Beg for a central idempotent eg. Then a relation is given between the set of elements in the Boolean algebra (Ba,≤ generated by {0,eg∣g∈G} and a set of subgroups of G, and a central Galois algebra Be with a Galois subgroup of G is characterized for an e∈Ba.

  11. Boolean Factor Analysis by Attractor Neural Network

    Czech Academy of Sciences Publication Activity Database

    Frolov, A. A.; Húsek, Dušan; Muraviev, I. P.; Polyakov, P.Y.

    2007-01-01

    Roč. 18, č. 3 (2007), s. 698-707 ISSN 1045-9227 R&D Projects: GA AV ČR 1ET100300419; GA ČR GA201/05/0079 Institutional research plan: CEZ:AV0Z10300504 Keywords : recurrent neural network * Hopfield-like neural network * associative memory * unsupervised learning * neural network architecture * neural network application * statistics * Boolean factor analysis * dimensionality reduction * features clustering * concepts search * information retrieval Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.769, year: 2007

  12. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    Science.gov (United States)

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

  13. Efficient Instantiation of Parameterised Boolean Equation Systems to Parity Games

    NARCIS (Netherlands)

    Kant, Gijs; van de Pol, Jan Cornelis; Wijs, A.J.; Bošnački, D.; Edelkamp, S.

    Parameterised Boolean Equation Systems (PBESs) are sequences of Boolean fixed point equations with data variables, used for, e.g., verification of modal μ-calculus formulae for process algebraic specifications with data. Solving a PBES is usually done by instantiation to a Parity Game and then

  14. Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Sarah R. [J. Craig Venter Inst., Rockville, MD (United States); Rodemeyer, Michael [Univ. of Virginia, Charlottesville, VA (United States); Garfinkel, Michele S. [EMBO, Heidelberg (Germany); Friedman, Robert M. [J. Craig Venter Inst., Rockville, MD (United States)

    2014-05-01

    Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options Sarah R. Carter, Ph.D., J. Craig Venter Institute; Michael Rodemeyer, J.D., University of Virginia; Michele S. Garfinkel, Ph.D., EMBO; Robert M. Friedman, Ph.D., J. Craig Venter Institute In recent years, a range of genetic engineering techniques referred to as “synthetic biology” has significantly expanded the tool kit available to scientists and engineers, providing them with far greater capabilities to engineer organisms than previous techniques allowed. The field of synthetic biology includes the relatively new ability to synthesize long pieces of DNA from chemicals, as well as improved methods for genetic manipulation and design of genetic pathways to achieve more precise control of biological systems. These advances will help usher in a new generation of genetically engineered microbes, plants, and animals. The JCVI Policy Center team, along with researchers at the University of Virginia and EMBO, examined how well the current U.S. regulatory system for genetically engineered products will handle the near-term introduction of organisms engineered using synthetic biology. In particular, the focus was on those organisms intended to be used or grown directly in the environment, outside of a contained facility. The study concludes that the U.S. regulatory agencies have adequate legal authority to address most, but not all, potential environmental, health and safety concerns posed by these organisms. Such near-term products are likely to represent incremental changes rather than a marked departure from previous genetically engineered organisms. However, the study also identified two key challenges for the regulatory system, which are detailed in the report. First, USDA’s authority over genetically engineered plants depends on the use of an older engineering technique that is no longer necessary for many applications. The shift to synthetic biology and other newer genetic

  15. An adaptable Boolean net trainable to control a computing robot

    International Nuclear Information System (INIS)

    Lauria, F. E.; Prevete, R.; Milo, M.; Visco, S.

    1999-01-01

    We discuss a method to implement in a Boolean neural network a Hebbian rule so to obtain an adaptable universal control system. We start by presenting both the Boolean neural net and the Hebbian rule we have considered. Then we discuss, first, the problems arising when the latter is naively implemented in a Boolean neural net, second, the method consenting us to overcome them and the ensuing adaptable Boolean neural net paradigm. Next, we present the adaptable Boolean neural net as an intelligent control system, actually controlling a writing robot, and discuss how to train it in the execution of the elementary arithmetic operations on operands represented by numerals with an arbitrary number of digits

  16. Boolean orthoposets and two-valued states on them

    Science.gov (United States)

    Tkadlec, Josef

    1992-06-01

    A Boolean orthoposet (see e.g. [2]) is the orthoposet P fulfilling the following condition: If a, b ∈ P and a ∧ b = 0 then a⊥ b. This condition seems to be a sound generalization of distributivity in orthoposets (see e.g. [8]). Also, the class of (orthomodular) Boolean orthoposets may play an interesting role in quantum logic theory. This class is wide enough (see [4,3]) and on the other hand, enjoys some properties of Boolean algebras [4,8,5]. In quantum logic theory an important role is played by so-called Jauch-Piron states [1,6,7]. In this paper we clarify the connection between Boolean orthoposets and orthoposets with "enough" two-valued Jauch-Piron states. Further, we obtain a characterization of Boolean orthoposets in terms of two-valued states.

  17. Reverse engineering Boolean networks: from Bernoulli mixture models to rule based systems.

    Directory of Open Access Journals (Sweden)

    Mehreen Saeed

    Full Text Available A Boolean network is a graphical model for representing and analyzing the behavior of gene regulatory networks (GRN. In this context, the accurate and efficient reconstruction of a Boolean network is essential for understanding the gene regulation mechanism and the complex relations that exist therein. In this paper we introduce an elegant and efficient algorithm for the reverse engineering of Boolean networks from a time series of multivariate binary data corresponding to gene expression data. We call our method ReBMM, i.e., reverse engineering based on Bernoulli mixture models. The time complexity of most of the existing reverse engineering techniques is quite high and depends upon the indegree of a node in the network. Due to the high complexity of these methods, they can only be applied to sparsely connected networks of small sizes. ReBMM has a time complexity factor, which is independent of the indegree of a node and is quadratic in the number of nodes in the network, a big improvement over other techniques and yet there is little or no compromise in accuracy. We have tested ReBMM on a number of artificial datasets along with simulated data derived from a plant signaling network. We also used this method to reconstruct a network from real experimental observations of microarray data of the yeast cell cycle. Our method provides a natural framework for generating rules from a probabilistic model. It is simple, intuitive and illustrates excellent empirical results.

  18. Epidemiologic studies of occupational pesticide exposure and cancer: regulatory risk assessments and biologic plausibility.

    Science.gov (United States)

    Acquavella, John; Doe, John; Tomenson, John; Chester, Graham; Cowell, John; Bloemen, Louis

    2003-01-01

    Epidemiologic studies frequently show associations between self-reported use of specific pesticides and human cancers. These findings have engendered debate largely on methodologic grounds. However, biologic plausibility is a more fundamental issue that has received only superficial attention. The purpose of this commentary is to review briefly the toxicology and exposure data that are developed as part of the pesticide regulatory process and to discuss the applicability of this data to epidemiologic research. The authors also provide a generic example of how worker pesticide exposures might be estimated and compared to relevant toxicologic dose levels. This example provides guidance for better characterization of exposure and for consideration of biologic plausibility in epidemiologic studies of pesticides.

  19. Evolutionary Algorithms for Boolean Functions in Diverse Domains of Cryptography.

    Science.gov (United States)

    Picek, Stjepan; Carlet, Claude; Guilley, Sylvain; Miller, Julian F; Jakobovic, Domagoj

    2016-01-01

    The role of Boolean functions is prominent in several areas including cryptography, sequences, and coding theory. Therefore, various methods for the construction of Boolean functions with desired properties are of direct interest. New motivations on the role of Boolean functions in cryptography with attendant new properties have emerged over the years. There are still many combinations of design criteria left unexplored and in this matter evolutionary computation can play a distinct role. This article concentrates on two scenarios for the use of Boolean functions in cryptography. The first uses Boolean functions as the source of the nonlinearity in filter and combiner generators. Although relatively well explored using evolutionary algorithms, it still presents an interesting goal in terms of the practical sizes of Boolean functions. The second scenario appeared rather recently where the objective is to find Boolean functions that have various orders of the correlation immunity and minimal Hamming weight. In both these scenarios we see that evolutionary algorithms are able to find high-quality solutions where genetic programming performs the best.

  20. Intervention in Context-Sensitive Probabilistic Boolean Networks Revisited

    Directory of Open Access Journals (Sweden)

    Faryabi Babak

    2009-01-01

    Full Text Available An approximate representation for the state space of a context-sensitive probabilistic Boolean network has previously been proposed and utilized to devise therapeutic intervention strategies. Whereas the full state of a context-sensitive probabilistic Boolean network is specified by an ordered pair composed of a network context and a gene-activity profile, this approximate representation collapses the state space onto the gene-activity profiles alone. This reduction yields an approximate transition probability matrix, absent of context, for the Markov chain associated with the context-sensitive probabilistic Boolean network. As with many approximation methods, a price must be paid for using a reduced model representation, namely, some loss of optimality relative to using the full state space. This paper examines the effects on intervention performance caused by the reduction with respect to various values of the model parameters. This task is performed using a new derivation for the transition probability matrix of the context-sensitive probabilistic Boolean network. This expression of transition probability distributions is in concert with the original definition of context-sensitive probabilistic Boolean network. The performance of optimal and approximate therapeutic strategies is compared for both synthetic networks and a real case study. It is observed that the approximate representation describes the dynamics of the context-sensitive probabilistic Boolean network through the instantaneously random probabilistic Boolean network with similar parameters.

  1. Boolean networks with robust and reliable trajectories

    International Nuclear Information System (INIS)

    Schmal, Christoph; Peixoto, Tiago P; Drossel, Barbara

    2010-01-01

    We construct and investigate Boolean networks that follow a given reliable trajectory in state space, which is insensitive to fluctuations in the updating schedule and which is also robust against noise. Robustness is quantified as the probability that the dynamics return to the reliable trajectory after a perturbation of the state of a single node. In order to achieve high robustness, we navigate through the space of possible update functions by using an evolutionary algorithm. We constrain the networks to those having the minimum number of connections required to obtain the reliable trajectory. Surprisingly, we find that robustness always reaches values close to 100% during the evolutionary optimization process. The set of update functions can be evolved such that it differs only slightly from that of networks that were not optimized with respect to robustness. The state space of the optimized networks is dominated by the basin of attraction of the reliable trajectory.

  2. The Boolean algebra of Galois algebras

    Directory of Open Access Journals (Sweden)

    Lianyong Xue

    2003-02-01

    Full Text Available Let B be a Galois algebra with Galois group G, Jg={b∈B|bx=g(xb for all x∈B} for each g∈G, and BJg=Beg for a central idempotent eg, Ba the Boolean algebra generated by {0,eg|g∈G}, e a nonzero element in Ba, and He={g∈G|eeg=e}. Then, a monomial e is characterized, and the Galois extension Be, generated by e with Galois group He, is investigated.

  3. Multipath Detection Using Boolean Satisfiability Techniques

    Directory of Open Access Journals (Sweden)

    Fadi A. Aloul

    2011-01-01

    Full Text Available A new technique for multipath detection in wideband mobile radio systems is presented. The proposed scheme is based on an intelligent search algorithm using Boolean Satisfiability (SAT techniques to search through the uncertainty region of the multipath delays. The SAT-based scheme utilizes the known structure of the transmitted wideband signal, for example, pseudo-random (PN code, to effectively search through the entire space by eliminating subspaces that do not contain a possible solution. The paper presents a framework for modeling the multipath detection problem as a SAT application. It also provides simulation results that demonstrate the effectiveness of the proposed scheme in detecting the multipath components in frequency-selective Rayleigh fading channels.

  4. Representing Boolean Functions by Decision Trees

    KAUST Repository

    Chikalov, Igor

    2011-01-01

    A Boolean or discrete function can be represented by a decision tree. A compact form of decision tree named binary decision diagram or branching program is widely known in logic design [2, 40]. This representation is equivalent to other forms, and in some cases it is more compact than values table or even the formula [44]. Representing a function in the form of decision tree allows applying graph algorithms for various transformations [10]. Decision trees and branching programs are used for effective hardware [15] and software [5] implementation of functions. For the implementation to be effective, the function representation should have minimal time and space complexity. The average depth of decision tree characterizes the expected computing time, and the number of nodes in branching program characterizes the number of functional elements required for implementation. Often these two criteria are incompatible, i.e. there is no solution that is optimal on both time and space complexity. © Springer-Verlag Berlin Heidelberg 2011.

  5. Equivalence Checking of Combinational Circuits using Boolean Expression Diagrams

    DEFF Research Database (Denmark)

    Hulgaard, Henrik; Williams, Poul Frederick; Andersen, Henrik Reif

    1999-01-01

    The combinational logic-level equivalence problem is to determine whether two given combinational circuits implement the same Boolean function. This problem arises in a number of CAD applications, for example when checking the correctness of incremental design changes (performed either manually...... or by a design automation tool).This paper introduces a data structure called Boolean Expression Diagrams (BEDs) and two algorithms for transforming a BED into a Reduced Ordered Binary Decision Diagram (OBDD). BEDs are capable of representing any Boolean circuit in linear space and can exploit structural...

  6. Complementing ODE-Based System Analysis Using Boolean Networks Derived from an Euler-Like Transformation.

    Science.gov (United States)

    Stötzel, Claudia; Röblitz, Susanna; Siebert, Heike

    2015-01-01

    In this paper, we present a systematic transition scheme for a large class of ordinary differential equations (ODEs) into Boolean networks. Our transition scheme can be applied to any system of ODEs whose right hand sides can be written as sums and products of monotone functions. It performs an Euler-like step which uses the signs of the right hand sides to obtain the Boolean update functions for every variable of the corresponding discrete model. The discrete model can, on one hand, be considered as another representation of the biological system or, alternatively, it can be used to further the analysis of the original ODE model. Since the generic transformation method does not guarantee any property conservation, a subsequent validation step is required. Depending on the purpose of the model this step can be based on experimental data or ODE simulations and characteristics. Analysis of the resulting Boolean model, both on its own and in comparison with the ODE model, then allows to investigate system properties not accessible in a purely continuous setting. The method is exemplarily applied to a previously published model of the bovine estrous cycle, which leads to new insights regarding the regulation among the components, and also indicates strongly that the system is tailored to generate stable oscillations.

  7. Using Common Table Expressions to Build a Scalable Boolean Query Generator for Clinical Data Warehouses

    Science.gov (United States)

    Harris, Daniel R.; Henderson, Darren W.; Kavuluru, Ramakanth; Stromberg, Arnold J.; Johnson, Todd R.

    2015-01-01

    We present a custom, Boolean query generator utilizing common-table expressions (CTEs) that is capable of scaling with big datasets. The generator maps user-defined Boolean queries, such as those interactively created in clinical-research and general-purpose healthcare tools, into SQL. We demonstrate the effectiveness of this generator by integrating our work into the Informatics for Integrating Biology and the Bedside (i2b2) query tool and show that it is capable of scaling. Our custom generator replaces and outperforms the default query generator found within the Clinical Research Chart (CRC) cell of i2b2. In our experiments, sixteen different types of i2b2 queries were identified by varying four constraints: date, frequency, exclusion criteria, and whether selected concepts occurred in the same encounter. We generated non-trivial, random Boolean queries based on these 16 types; the corresponding SQL queries produced by both generators were compared by execution times. The CTE-based solution significantly outperformed the default query generator and provided a much more consistent response time across all query types (M=2.03, SD=6.64 vs. M=75.82, SD=238.88 seconds). Without costly hardware upgrades, we provide a scalable solution based on CTEs with very promising empirical results centered on performance gains. The evaluation methodology used for this provides a means of profiling clinical data warehouse performance. PMID:25192572

  8. PARAMETER ESTIMATION IN NON-HOMOGENEOUS BOOLEAN MODELS: AN APPLICATION TO PLANT DEFENSE RESPONSE

    Directory of Open Access Journals (Sweden)

    Maria Angeles Gallego

    2014-11-01

    Full Text Available Many medical and biological problems require to extract information from microscopical images. Boolean models have been extensively used to analyze binary images of random clumps in many scientific fields. In this paper, a particular type of Boolean model with an underlying non-stationary point process is considered. The intensity of the underlying point process is formulated as a fixed function of the distance to a region of interest. A method to estimate the parameters of this Boolean model is introduced, and its performance is checked in two different settings. Firstly, a comparative study with other existent methods is done using simulated data. Secondly, the method is applied to analyze the longleaf data set, which is a very popular data set in the context of point processes included in the R package spatstat. Obtained results show that the new method provides as accurate estimates as those obtained with more complex methods developed for the general case. Finally, to illustrate the application of this model and this method, a particular type of phytopathological images are analyzed. These images show callose depositions in leaves of Arabidopsis plants. The analysis of callose depositions, is very popular in the phytopathological literature to quantify activity of plant immunity.

  9. Using synthetic biology to distinguish and overcome regulatory and functional barriers related to nitrogen fixation.

    Directory of Open Access Journals (Sweden)

    Xia Wang

    Full Text Available Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

  10. Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer

    Directory of Open Access Journals (Sweden)

    Samra Khalid

    2016-10-01

    Full Text Available Background Breast cancer (BC is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s. It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α associated Biological Regulatory Network (BRN for a small part of complex events that leads to BC metastasis. Methods A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN to analyze the logical parameters of the involved entities. Results In-silico based discrete and continuous modeling of ER-α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER-α, IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. Conclusion The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER-α, IGF-1R and EGFR for wet lab experiments as well as provided valuable insights in the treatment of cancers

  11. Synchronization in an array of coupled Boolean networks

    International Nuclear Information System (INIS)

    Li, Rui; Chu, Tianguang

    2012-01-01

    This Letter presents an analytical study of synchronization in an array of coupled deterministic Boolean networks. A necessary and sufficient criterion for synchronization is established based on algebraic representations of logical dynamics in terms of the semi-tensor product of matrices. Some basic properties of a synchronized array of Boolean networks are then derived for the existence of transient states and the upper bound of the number of fixed points. Particularly, an interesting consequence indicates that a “large” mismatch between two coupled Boolean networks in the array may result in loss of synchrony in the entire system. Examples, including the Boolean model of coupled oscillations in the cell cycle, are given to illustrate the present results. -- Highlights: ► We analytically study synchronization in an array of coupled Boolean networks. ► The study is based on the algebraic representations of logical dynamics. ► A necessary and sufficient algebraic criterion for synchronization is established. ► It reveals some basic properties of a synchronized array of Boolean networks. ► A large mismatch between two coupled networks may result in the loss of synchrony.

  12. Boolean network model of the Pseudomonas aeruginosa quorum sensing circuits.

    Science.gov (United States)

    Dallidis, Stylianos E; Karafyllidis, Ioannis G

    2014-09-01

    To coordinate their behavior and virulence and to synchronize attacks against their hosts, bacteria communicate by continuously producing signaling molecules (called autoinducers) and continuously monitoring the concentration of these molecules. This communication is controlled by biological circuits called quorum sensing (QS) circuits. Recently QS circuits and have been recognized as an alternative target for controlling bacterial virulence and infections without the use of antibiotics. Pseudomonas aeruginosa is a Gram-negative bacterium that infects insects, plants, animals and humans and can cause acute infections. This bacterium has three interconnected QS circuits that form a very complex and versatile QS system, the operation of which is still under investigation. Here we use Boolean networks to model the complete QS system of Pseudomonas aeruginosa and we simulate and analyze its operation in both synchronous and asynchronous modes. The state space of the QS system is constructed and it turned out to be very large, hierarchical, modular and scale-free. Furthermore, we developed a simulation tool that can simulate gene knock-outs and study their effect on the regulons controlled by the three QS circuits. The model and tools we developed will give to life scientists a deeper insight to this complex QS system.

  13. Regulatory and information support for evaluation of biological productivity of Ukrainian forests and climate change

    Science.gov (United States)

    Lakyda, Petro; Vasylyshyn, Roman; Lakyda, Ivan

    2013-04-01

    Stabilization and preservation of the planet's climate system today is regarded as one of the most important global political-economic, environmental and social problems of mankind. Rising concentration of carbon dioxide in the planet's atmosphere due to anthropogenic impact is the main reason leading to global climate change. Due to the above mentioned, social demands on forests are changing their biosphere role and function of natural sink of greenhouse gases becomes top priority. It is known that one of the most essential components of biological productivity of forests is their live biomass. Absorption, long-term sequestration of carbon and generation of oxygen are secured by its components. System research of its parametric structure and development of regulatory and reference information for assessment of aboveground live biomass components of trees and stands of the main forest-forming tree species in Ukraine began over twenty-five years ago at the department of forest mensuration and forest inventory of National University of Life and Environmental Sciences of Ukraine, involving staff from other research institutions. Today, regulatory and reference materials for evaluation of parametric structure of live biomass are developed for trees of the following major forest-forming tree species of Ukraine: Scots pine of natural and artificial origin, Crimean pine, Norway spruce, silver fir, pedunculate oak, European beech, hornbeam, ash, common birch, aspen and black alder (P.I. Lakyda et al., 2011). An ongoing process on development of similar regulatory and reference materials for forest stands of the abovementioned forest-forming tree species of Ukraine is secured by scientists of departments of forest management, and forest mensuration and forest inventory. The total experimental research base is 609 temporary sample plots, where 4880 model trees were processed, including 3195 model trees with estimates of live biomass components. Laboratory studies conducted

  14. Highly sensitive quantification of key regulatory oxysterols in biological samples by LC-ESI-MS/MS.

    Science.gov (United States)

    Honda, Akira; Yamashita, Kouwa; Hara, Takashi; Ikegami, Tadashi; Miyazaki, Teruo; Shirai, Mutsumi; Xu, Guorong; Numazawa, Mitsuteru; Matsuzaki, Yasushi

    2009-02-01

    We describe a highly sensitive and specific method for the quantification of key regulatory oxysterols in biological samples. This method is based upon a stable isotope dilution technique by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After alkaline hydrolysis of human serum (5 microl) or rat liver microsomes (1 mg protein), oxysterols were extracted, derivatized into picolinyl esters, and analyzed by LC-MS/MS using the electrospray ionization mode. The detection limits of the picolinyl esters of 4beta-hydroxycholesterol, 7alpha-hydroxycholesterol, 22R-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, and 24S,25-epoxycholesterol were 2-10 fg (5-25 amol) on-column (signal-to-noise ratio = 3). Reproducibilities and recoveries of these oxysterols were validated according to one-way layout and polynomial equation, respectively. The variances between sample preparations and between measurements by this method were calculated to be 1.8% to 12.7% and 2.9% to 11.9%, respectively. The recovery experiments were performed using rat liver microsomes spiked with 0.05 ng to 12 ng of oxysterols, and recoveries of the oxysterols ranged from 86.7% to 107.3%, with a mean recovery of 100.6%. This method provides reproducible and reliable results for the quantification of oxysterols in small amounts of biological samples.

  15. PROTECTING ECOSYSTEMS BY WAY OF BIOLOGICAL CONTROL: CURSORY REFLECTIONS ON THE MAIN REGULATORY INSTRUMENTS FOR BIOLOGICAL CONTROL AGENTS, PRESENT AND FUTURE

    Directory of Open Access Journals (Sweden)

    R Alberts

    2013-06-01

    Full Text Available Although there are numerous threats to ecosystems and the resultant ecosystem services, alien and invasive plants (AIP have been identified as being one of the major causes of ecosystem destruction. In addressing the threat of alien and invasive plants through the use of various mechanisms, the regulatory framework imposed by legislation is key in ensuring that that controlling AIPs does in fact not do more harm than good. One such control mechanism, which has the potential to do wonders or wreak havoc if not adroitly implemented, is that of using biological control agents. This contribution provides a brief overview on the three main regulatory instruments used to control biological control agents in South Africa, namely the Conservation of Agricultural Resources Act 43 of 1983, the Agricultural Pests Act 36 of 1983 and the National Environmental Management: Biodiversity Act 10 of 2004. It also considers possible future developments on the regulation of biological control agents.

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

    Directory of Open Access Journals (Sweden)

    Natalie Berestovsky

    Full Text Available 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

  17. Unlimited multistability and Boolean logic in microbial signalling.

    Science.gov (United States)

    Kothamachu, Varun B; Feliu, Elisenda; Cardelli, Luca; Soyer, Orkun S

    2015-07-06

    The ability to map environmental signals onto distinct internal physiological states or programmes is critical for single-celled microbes. A crucial systems dynamics feature underpinning such ability is multistability. While unlimited multistability is known to arise from multi-site phosphorylation seen in the signalling networks of eukaryotic cells, a similarly universal mechanism has not been identified in microbial signalling systems. These systems are generally known as two-component systems comprising histidine kinase (HK) receptors and response regulator proteins engaging in phosphotransfer reactions. We develop a mathematical framework for analysing microbial systems with multi-domain HK receptors known as hybrid and unorthodox HKs. We show that these systems embed a simple core network that exhibits multistability, thereby unveiling a novel biochemical mechanism for multistability. We further prove that sharing of downstream components allows a system with n multi-domain hybrid HKs to attain 3n steady states. We find that such systems, when sensing distinct signals, can readily implement Boolean logic functions on these signals. Using two experimentally studied examples of two-component systems implementing hybrid HKs, we show that bistability and implementation of logic functions are possible under biologically feasible reaction rates. Furthermore, we show that all sequenced microbial genomes contain significant numbers of hybrid and unorthodox HKs, and some genomes have a larger fraction of these proteins compared with regular HKs. Microbial cells are thus theoretically unbounded in mapping distinct environmental signals onto distinct physiological states and perform complex computations on them. These findings facilitate the understanding of natural two-component systems and allow their engineering through synthetic biology.

  18. Harnessing Advances in T Regulatory Cell Biology for Cellular Therapy in Transplantation.

    Science.gov (United States)

    Lam, Avery J; Hoeppli, Romy E; Levings, Megan K

    2017-10-01

    Cellular therapy with CD4FOXP3 T regulatory (Treg) cells is a promising strategy to induce tolerance after solid-organ transplantation or prevent graft-versus-host disease after transfer of hematopoietic stem cells. Treg cells currently used in clinical trials are either polyclonal, donor- or antigen-specific. Aside from variations in isolation and expansion protocols, however, most therapeutic Treg cell-based products are much alike. Ongoing basic science work has provided considerable new insight into multiple facets of Treg cell biology, including their stability, homing, and functional specialization; integrating these basic science discoveries with clinical efforts will support the development of next-generation therapeutic Treg cells with enhanced efficacy. In this review, we summarize recent advances in knowledge of how Treg cells home to lymphoid and peripheral tissues, and control antibody production and tissue repair. We also discuss newly appreciated pathways that modulate context-specific Treg cell function and stability. Strategies to improve and tailor Treg cells for cell therapy to induce transplantation tolerance are highlighted.

  19. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

    Directory of Open Access Journals (Sweden)

    Dimitrios Mougiakakos

    2011-03-01

    Full Text Available Regulatory T cells (Tregs were initially described as "suppressive" lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

  20. An Efficient Steady-State Analysis Method for Large Boolean Networks with High Maximum Node Connectivity.

    Science.gov (United States)

    Hong, Changki; Hwang, Jeewon; Cho, Kwang-Hyun; Shin, Insik

    2015-01-01

    Boolean networks have been widely used to model biological processes lacking detailed kinetic information. Despite their simplicity, Boolean network dynamics can still capture some important features of biological systems such as stable cell phenotypes represented by steady states. For small models, steady states can be determined through exhaustive enumeration of all state transitions. As the number of nodes increases, however, the state space grows exponentially thus making it difficult to find steady states. Over the last several decades, many studies have addressed how to handle such a state space explosion. Recently, increasing attention has been paid to a satisfiability solving algorithm due to its potential scalability to handle large networks. Meanwhile, there still lies a problem in the case of large models with high maximum node connectivity where the satisfiability solving algorithm is known to be computationally intractable. To address the problem, this paper presents a new partitioning-based method that breaks down a given network into smaller subnetworks. Steady states of each subnetworks are identified by independently applying the satisfiability solving algorithm. Then, they are combined to construct the steady states of the overall network. To efficiently apply the satisfiability solving algorithm to each subnetwork, it is crucial to find the best partition of the network. In this paper, we propose a method that divides each subnetwork to be smallest in size and lowest in maximum node connectivity. This minimizes the total cost of finding all steady states in entire subnetworks. The proposed algorithm is compared with others for steady states identification through a number of simulations on both published small models and randomly generated large models with differing maximum node connectivities. The simulation results show that our method can scale up to several hundreds of nodes even for Boolean networks with high maximum node connectivity. The

  1. A comparison of hypertext and Boolean access to biomedical information.

    Science.gov (United States)

    Friedman, C P; Wildemuth, B M; Muriuki, M; Gant, S P; Downs, S M; Twarog, R G; de Bliek, R

    1996-01-01

    This study explored which of two modes of access to a biomedical database better supported problem solving in bacteriology. Boolean access, which allowed subjects to frame their queries as combinations of keywords, was compared to hypertext access, which allowed subjects to navigate from one database node to another. The accessible biomedical data were identical across systems. Data were collected from 42 first year medical students, each randomized to the Boolean or hypertext system, before and after their bacteriology course. Subjects worked eight clinical case problems, first using only their personal knowledge and, subsequently, with aid from the database. Database retrievals enabled students to answer questions they could not answer based on personal knowledge only. This effect was greater when personal knowledge of bacteriology was lower. The results also suggest that hypertext was superior to Boolean access in helping subjects identify possible infectious agents in these clinical case problems.

  2. Sieve-based relation extraction of gene regulatory networks from biological literature.

    Science.gov (United States)

    Žitnik, Slavko; Žitnik, Marinka; Zupan, Blaž; Bajec, Marko

    2015-01-01

    Relation extraction is an essential procedure in literature mining. It focuses on extracting semantic relations between parts of text, called mentions. Biomedical literature includes an enormous amount of textual descriptions of biological entities, their interactions and results of related experiments. To extract them in an explicit, computer readable format, these relations were at first extracted manually from databases. Manual curation was later replaced with automatic or semi-automatic tools with natural language processing capabilities. The current challenge is the development of information extraction procedures that can directly infer more complex relational structures, such as gene regulatory networks. We develop a computational approach for extraction of gene regulatory networks from textual data. Our method is designed as a sieve-based system and uses linear-chain conditional random fields and rules for relation extraction. With this method we successfully extracted the sporulation gene regulation network in the bacterium Bacillus subtilis for the information extraction challenge at the BioNLP 2013 conference. To enable extraction of distant relations using first-order models, we transform the data into skip-mention sequences. We infer multiple models, each of which is able to extract different relationship types. Following the shared task, we conducted additional analysis using different system settings that resulted in reducing the reconstruction error of bacterial sporulation network from 0.73 to 0.68, measured as the slot error rate between the predicted and the reference network. We observe that all relation extraction sieves contribute to the predictive performance of the proposed approach. Also, features constructed by considering mention words and their prefixes and suffixes are the most important features for higher accuracy of extraction. Analysis of distances between different mention types in the text shows that our choice of transforming

  3. Refinement monoids, equidecomposability types, and boolean inverse semigroups

    CERN Document Server

    Wehrung, Friedrich

    2017-01-01

    Adopting a new universal algebraic approach, this book explores and consolidates the link between Tarski's classical theory of equidecomposability types monoids, abstract measure theory (in the spirit of Hans Dobbertin's work on monoid-valued measures on Boolean algebras) and the nonstable K-theory of rings. This is done via the study of a monoid invariant, defined on Boolean inverse semigroups, called the type monoid. The new techniques contrast with the currently available topological approaches. Many positive results, but also many counterexamples, are provided.

  4. Equivalence Checking of Combinational Circuits using Boolean Expression Diagrams

    DEFF Research Database (Denmark)

    Hulgaard, Henrik; Williams, Poul Frederick; Andersen, Henrik Reif

    1999-01-01

    or by a design automation tool).This paper introduces a data structure called Boolean Expression Diagrams (BEDs) and two algorithms for transforming a BED into a Reduced Ordered Binary Decision Diagram (OBDD). BEDs are capable of representing any Boolean circuit in linear space and can exploit structural...... similarities between the two circuits that are compared. These properties make BEDs suitable for verifying the equivalence of combinational circuits. BEDs can be seen as an intermediate representation between circuits (which are compact) and OBDDs (which are canonical).Based on a large number of combinational...

  5. A Boolean Approach to Airline Business Model Innovation

    DEFF Research Database (Denmark)

    Hvass, Kristian Anders

    Research in business model innovation has identified its significance in creating a sustainable competitive advantage for a firm, yet there are few empirical studies identifying which combination of business model activities lead to success and therefore deserve innovative attention. This study...... analyzes the business models of North America low-cost carriers from 2001 to 2010 using a Boolean minimization algorithm to identify which combinations of business model activities lead to operational profitability. The research aim is threefold: complement airline literature in the realm of business model...... innovation, introduce Boolean minimization methods to the field, and propose alternative business model activities to North American carriers striving for positive operating results....

  6. On Kolmogorov's superpositions and Boolean functions

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.

    1998-12-31

    The paper overviews results dealing with the approximation capabilities of neural networks, as well as bounds on the size of threshold gate circuits. Based on an explicit numerical (i.e., constructive) algorithm for Kolmogorov's superpositions they will show that for obtaining minimum size neutral networks for implementing any Boolean function, the activation function of the neurons is the identity function. Because classical AND-OR implementations, as well as threshold gate implementations require exponential size (in the worst case), it will follow that size-optimal solutions for implementing arbitrary Boolean functions require analog circuitry. Conclusions and several comments on the required precision are ending the paper.

  7. Constant-Overhead Secure Computation of Boolean Circuits using Preprocessing

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Zakarias, Sarah Nouhad Haddad

    We present a protocol for securely computing a Boolean circuit $C$ in presence of a dishonest and malicious majority. The protocol is unconditionally secure, assuming access to a preprocessing functionality that is not given the inputs to compute on. For a large number of players the work done by...... with an additional multiplication property. We also show a new algorithm for verifying the product of Boolean matrices in quadratic time with exponentially small error probability, where previous methods would only give a constant error....

  8. A systems biology model of the regulatory network in Populus leaves reveals interacting regulators and conserved regulation

    Directory of Open Access Journals (Sweden)

    Hvidsten Torgeir R

    2011-01-01

    Full Text Available Abstract Background Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods are now also being applied to organisms such as Populus, a woody perennial tree, in order to understand the specific characteristics of these species. Results We present a systems biology model of the regulatory network of Populus leaves. The network is reverse-engineered from promoter information and expression profiles of leaf-specific genes measured over a large set of conditions related to stress and developmental. The network model incorporates interactions between regulators, such as synergistic and competitive relationships, by evaluating increasingly more complex regulatory mechanisms, and is therefore able to identify new regulators of leaf development not found by traditional genomics methods based on pair-wise expression similarity. The approach is shown to explain available gene function information and to provide robust prediction of expression levels in new data. We also use the predictive capability of the model to identify condition-specific regulation as well as conserved regulation between Populus and Arabidopsis. Conclusions We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions

  9. Identification and Characterization of 5′ Untranslated Regions (5′UTRs in Zymomonas mobilis as Regulatory Biological Parts

    Directory of Open Access Journals (Sweden)

    Seung Hee Cho

    2017-12-01

    Full Text Available Regulatory RNA regions within a transcript, particularly in the 5′ untranslated region (5′UTR, have been shown in a variety of organisms to control the expression levels of these mRNAs in response to various metabolites or environmental conditions. Considering the unique tolerance of Zymomonas mobilis to ethanol and the growing interest in engineering microbial strains with enhanced tolerance to industrial inhibitors, we searched natural cis-regulatory regions in this microorganism using transcriptomic data and bioinformatics analysis. Potential regulatory 5′UTRs were identified and filtered based on length, gene function, relative gene counts, and conservation in other organisms. An in vivo fluorescence-based screening system was developed to confirm the responsiveness of 36 5′UTR candidates to ethanol, acetate, and xylose stresses. UTR_ZMO0347 (5′UTR of gene ZMO0347 encoding the RNA binding protein Hfq was found to down-regulate downstream gene expression under ethanol stress. Genomic deletion of UTR_ZMO0347 led to a general decrease of hfq expression at the transcript level and increased sensitivity for observed changes in Hfq expression at the protein level. The role of UTR_ZMO0347 and other 5′UTRs gives us insight into the regulatory network of Z. mobilis in response to stress and unlocks new strategies for engineering robust industrial strains as well as for harvesting novel responsive regulatory biological parts for controllable gene expression platforms in this organism.

  10. Document Ranking in E-Extended Boolean Logic

    Czech Academy of Sciences Publication Activity Database

    Holub, M.; Húsek, Dušan; Pokorný, J.

    1996-01-01

    Roč. 4, č. 7 (1996), s. 3-17 ISSN 1310-0513. [Annual Colloquium on IR Research /19./. Aberdeen, 08.04.1997-09.04.1997] R&D Projects: GA ČR GA102/94/0728 Keywords : information retrieval * document ranking * extended Boolean logic

  11. On the Road to Genetic Boolean Matrix Factorization

    Czech Academy of Sciences Publication Activity Database

    Snášel, V.; Platoš, J.; Krömer, P.; Húsek, Dušan; Frolov, A.

    2007-01-01

    Roč. 17, č. 6 (2007), s. 675-688 ISSN 1210-0552 Institutional research plan: CEZ:AV0Z10300504 Keywords : data mining * genetic algorithms * Boolean factorization * binary data * machine learning * feature extraction Subject RIV: IN - Informatics, Computer Science Impact factor: 0.280, year: 2007

  12. Free Boolean algebras over unions of two well orderings

    Czech Academy of Sciences Publication Activity Database

    Bonnet, R.; Faouzi, L.; Kubiś, Wieslaw

    2009-01-01

    Roč. 156, č. 7 (2009), s. 1177-1185 ISSN 0166-8641 Institutional research plan: CEZ:AV0Z10190503 Keywords : Well quasi orderings * Poset algebras * Superatomic Boolean algebras * Compact distributive lattices Subject RIV: BA - General Mathematics Impact factor: 0.441, year: 2009

  13. Complexity of Identification and Dualization of Positive Boolean Functions

    NARCIS (Netherlands)

    J.C. Bioch (Cor); T. Ibaraki

    1995-01-01

    textabstractWe consider in this paper the problem of identifying min T(f{hook}) and max F(f{hook}) of a positive (i.e., monotone) Boolean function f{hook}, by using membership queries only, where min T(f{hook}) (max F(f{hook})) denotes the set of minimal true vectors (maximal false vectors) of

  14. Development of Boolean calculus and its applications. [digital systems design

    Science.gov (United States)

    Tapia, M. A.

    1980-01-01

    The development of Boolean calculus for its application to developing digital system design methodologies that would reduce system complexity, size, cost, speed, power requirements, etc., is discussed. Synthesis procedures for logic circuits are examined particularly asynchronous circuits using clock triggered flip flops.

  15. Integer programming-based method for observability of singleton attractors in Boolean networks.

    Science.gov (United States)

    Cheng, Xiaoqing; Qiu, Yushan; Hou, Wenpin; Ching, Wai-Ki

    2017-02-01

    Boolean network (BN) is a popular mathematical model for revealing the behaviour of a genetic regulatory network. Furthermore, observability, an important network feature, plays a significant role in understanding the underlying network. Several studies have been done on analysis of observability of BNs and complex networks. However, the observability of attractor cycles, which can serve as biomarker detection, has not yet been addressed in the literature. This is an important, interesting and challenging problem that deserves a detailed study. In this study, a novel problem was first proposed on attractor observability in BNs. Identification of the minimum set of consecutive nodes can be used to discriminate different attractors. Furthermore, it can serve as a biomarker for different disease types (represented as different attractor cycles). Then a novel integer programming method was developed to identify the desired set of nodes. The proposed approach is demonstrated and verified by numerical examples. The computational results further illustrates that the proposed model is effective and efficient.

  16. Mammalian synthetic biology: emerging medical applications

    Science.gov (United States)

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M.; Krams, Rob

    2015-01-01

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. PMID:25808341

  17. Validation of an entirely in vitro approach for rapid prototyping of DNA regulatory elements for synthetic biology

    Science.gov (United States)

    Chappell, James; Jensen, Kirsten; Freemont, Paul S.

    2013-01-01

    A bottleneck in our capacity to rationally and predictably engineer biological systems is the limited number of well-characterized genetic elements from which to build. Current characterization methods are tied to measurements in living systems, the transformation and culturing of which are inherently time-consuming. To address this, we have validated a completely in vitro approach for the characterization of DNA regulatory elements using Escherichia coli extract cell-free systems. Importantly, we demonstrate that characterization in cell-free systems correlates and is reflective of performance in vivo for the most frequently used DNA regulatory elements. Moreover, we devise a rapid and completely in vitro method to generate DNA templates for cell-free systems, bypassing the need for DNA template generation and amplification from living cells. This in vitro approach is significantly quicker than current characterization methods and is amenable to high-throughput techniques, providing a valuable tool for rapidly prototyping libraries of DNA regulatory elements for synthetic biology. PMID:23371936

  18. Low doses of ionizing radiation: Biological effects and regulatory control. Invited papers and discussions. Proceedings of an international conference

    International Nuclear Information System (INIS)

    1998-01-01

    The levels and biological effects resulting from exposure to ionizing radiation are continuously reviewed by the United Nations Committee on the Effects of Atomic Radiation (UNSCEAR). Since its creation in 1928, the International Commission on Radiological Protection (ICRP) has issued recommendations on protection against ionizing radiation. The UNSCEAR estimates and the ICRP recommendations have served as the basis for national and international safety standards on radiation safety, including those developed by the International Atomic Energy Agency (IAEA) and the World Health Organization (WHO). Concerning health effects of low doses of ionizing radiation, the international standards are based on the plausible assumption that, above the unavoidable background radiation dose, the probability of effects increases linearly with dose, i.e. on a 'linear, no threshold' (LNT) assumption. However, in recent years the biological estimates of health effects of low doses of ionizing radiation and the regulatory approach to the control of low level radiation exposure have been much debated. To foster information exchange on the relevant issues, an International Conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, jointly sponsored by the IAEA and WHO in co-operation with UNSCEAR, was held from 17-21 November 1997 at Seville, Spain. These Proceedings contain the invited special reports, keynote papers, summaries of discussions, session summaries and addresses presented at the opening and closing of the Conference

  19. Compensatory interactions to stabilize multiple steady states or mitigate the effects of multiple deregulations in biological networks

    Science.gov (United States)

    Yang, Gang; Campbell, Colin; Albert, RéKa

    Complex diseases can be modeled as damage to intra-cellular networks that results in abnormal cell behaviors. Network-based dynamic models such as Boolean models have been employed to model a variety of biological systems including those corresponding to disease. Previous work designed compensatory interactions to stabilize an attractor of a Boolean network after single node damage. We generalize this method to a multi-node damage scenario and to the simultaneous stabilization of multiple steady state attractors. We presents three key results. First, we use analytical and computational methods to study how network structure and regulatory logic affect the resilience of the network's steady states to single node perturbation. Second, we present an algorithm to design compensatory interventions to stabilize a steady state of the network after double node damage and evaluate it on random Boolean networks and two intra-cellular network models relevant to cancer. Third, we apply the algorithm on stabilizing two steady states simultaneously after a single node damage and discuss the emerging situations and their corresponding frequencies. We also apply the algorithm to the biological examples.

  20. Noisy random Boolean formulae: a statistical physics perspective.

    Science.gov (United States)

    Mozeika, Alexander; Saad, David; Raymond, Jack

    2010-10-01

    Properties of computing Boolean circuits composed of noisy logical gates are studied using the statistical physics methodology. A formula-growth model that gives rise to random Boolean functions is mapped onto a spin system, which facilitates the study of their typical behavior in the presence of noise. Bounds on their performance, derived in the information theory literature for specific gates, are straightforwardly retrieved, generalized and identified as the corresponding macroscopic phase transitions. The framework is employed for deriving results on error-rates at various function-depths and function sensitivity, and their dependence on the gate-type and noise model used. These are difficult to obtain via the traditional methods used in this field.

  1. High Quality Test Pattern Generation and Boolean Satisfiability

    CERN Document Server

    Eggersglüß, Stephan

    2012-01-01

    This book provides an overview of automatic test pattern generation (ATPG) and introduces novel techniques to complement classical ATPG, based on Boolean Satisfiability (SAT).  A fast and highly fault efficient SAT-based ATPG framework is presented which is also able to generate high-quality delay tests such as robust path delay tests, as well as tests with long propagation paths to detect small delay defects. The aim of the techniques and methodologies presented in this book is to improve SAT-based ATPG, in order to make it applicable in industrial practice. Readers will learn to improve the performance and robustness of the overall test generation process, so that the ATPG algorithm reliably will generate test patterns for most targeted faults in acceptable run time to meet the high fault coverage demands of industry. The techniques and improvements presented in this book provide the following advantages: Provides a comprehensive introduction to test generation and Boolean Satisfiability (SAT); Describes a...

  2. Mapping knowledge to boolean dynamic systems in Bateson's epistemology.

    Science.gov (United States)

    Malloy, Thomas E; Jensen, Gary C; Song, Timothy

    2005-01-01

    Gregory Bateson (1972, 1979) established an epistemology that integrates mind and nature as a necessary unity, a unity in which learning and evolution share fundamental principles and in which criteria for mental process are explicitly specified. E42 is a suite of freely available Java applets that constitute an online research lab for creating and interacting with simulations of the Boolean systems developed by Kauffman (1993) in his study of evolution where he proposed that self-organization and natural selection are co-principles "weaving the tapestry of life." This paper maps Boolean systems, developed in the study of evolution, onto Bateson's epistemology in general and onto his criteria of mental process in particular.

  3. Boolean Functions with a Simple Certificate for CNF Complexity

    Czech Academy of Sciences Publication Activity Database

    Čepek, O.; Kučera, P.; Savický, Petr

    2012-01-01

    Roč. 160, 4-5 (2012), s. 365-382 ISSN 0166-218X R&D Projects: GA MŠk(CZ) 1M0545 Grant - others:GA ČR(CZ) GP201/07/P168; GA ČR(CZ) GAP202/10/1188 Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean functions * CNF representations Subject RIV: BA - General Mathematics Impact factor: 0.718, year: 2012

  4. Elements of Boolean-Valued Dempster-Shafer Theory

    Czech Academy of Sciences Publication Activity Database

    Kramosil, Ivan

    2000-01-01

    Roč. 10, č. 5 (2000), s. 825-835 ISSN 1210-0552. [SOFSEM 2000 Workshop on Soft Computing. Milovy, 27.11.2000-28.11.2000] R&D Projects: GA ČR GA201/00/1489 Institutional research plan: AV0Z1030915 Keywords : Boolean algebra * belief function * Dempster-Shafer theory * Dempster combination rule * nonspecifity degree Subject RIV: BA - General Mathematics

  5. SETS, Boolean Manipulation for Network Analysis and Fault Tree Analysis

    International Nuclear Information System (INIS)

    Worrell, R.B.

    1985-01-01

    Description of problem or function - SETS is used for symbolic manipulation of set (or Boolean) equations, particularly the reduction of set equations by the application of set identities. It is a flexible and efficient tool for performing probabilistic risk analysis (PRA), vital area analysis, and common cause analysis. The equation manipulation capabilities of SETS can also be used to analyze non-coherent fault trees and determine prime implicants of Boolean functions, to verify circuit design implementation, to determine minimum cost fire protection requirements for nuclear reactor plants, to obtain solutions to combinatorial optimization problems with Boolean constraints, and to determine the susceptibility of a facility to unauthorized access through nullification of sensors in its protection system. 4. Method of solution - The SETS program is used to read, interpret, and execute the statements of a SETS user program which is an algorithm that specifies the particular manipulations to be performed and the order in which they are to occur. 5. Restrictions on the complexity of the problem - Any properly formed set equation involving the set operations of union, intersection, and complement is acceptable for processing by the SETS program. Restrictions on the size of a set equation that can be processed are not absolute but rather are related to the number of terms in the disjunctive normal form of the equation, the number of literals in the equation, etc. Nevertheless, set equations involving thousands and even hundreds of thousands of terms can be processed successfully

  6. Approximating Attractors of Boolean Networks by Iterative CTL Model Checking.

    Science.gov (United States)

    Klarner, Hannes; Siebert, Heike

    2015-01-01

    This paper introduces the notion of approximating asynchronous attractors of Boolean networks by minimal trap spaces. We define three criteria for determining the quality of an approximation: "faithfulness" which requires that the oscillating variables of all attractors in a trap space correspond to their dimensions, "univocality" which requires that there is a unique attractor in each trap space, and "completeness" which requires that there are no attractors outside of a given set of trap spaces. Each is a reachability property for which we give equivalent model checking queries. Whereas faithfulness and univocality can be decided by model checking the corresponding subnetworks, the naive query for completeness must be evaluated on the full state space. Our main result is an alternative approach which is based on the iterative refinement of an initially poor approximation. The algorithm detects so-called autonomous sets in the interaction graph, variables that contain all their regulators, and considers their intersection and extension in order to perform model checking on the smallest possible state spaces. A benchmark, in which we apply the algorithm to 18 published Boolean networks, is given. In each case, the minimal trap spaces are faithful, univocal, and complete, which suggests that they are in general good approximations for the asymptotics of Boolean networks.

  7. Boolean models can explain bistability in the lac operon.

    Science.gov (United States)

    Veliz-Cuba, Alan; Stigler, Brandilyn

    2011-06-01

    The lac operon in Escherichia coli has been studied extensively and is one of the earliest gene systems found to undergo both positive and negative control. The lac operon is known to exhibit bistability, in the sense that the operon is either induced or uninduced. Many dynamical models have been proposed to capture this phenomenon. While most are based on complex mathematical formulations, it has been suggested that for other gene systems network topology is sufficient to produce the desired dynamical behavior. We present a Boolean network as a discrete model for the lac operon. Our model includes the two main glucose control mechanisms of catabolite repression and inducer exclusion. We show that this Boolean model is capable of predicting the ON and OFF steady states and bistability. Further, we present a reduced model which shows that lac mRNA and lactose form the core of the lac operon, and that this reduced model exhibits the same dynamics. This work suggests that the key to model qualitative dynamics of gene systems is the topology of the network and Boolean models are well suited for this purpose.

  8. Approximating attractors of Boolean networks by iterative CTL model checking

    Directory of Open Access Journals (Sweden)

    Hannes eKlarner

    2015-09-01

    Full Text Available This paper introduces the notion of approximating asynchronous attractors of Boolean networks by minimal trap spaces. We define three criteria for determining the quality of an approximation: faithfulness which requires that the oscillating variables of all attractors in a trapspace correspond to their dimensions, univocality which requires that there is a unique attractor in each trap space and completeness which requires that there are no attractors outside of a given set of trap spaces. Each is a reachability property for which we give equivalent model checking queries. Whereas faithfulness and univocality can be decided by model checking the corresponding subnetworks, the naive query for completeness must be evaluated on the full state space. Our main result is an alternative approach which is based on the iterative refinement of an initially poor approximation. The algorithm detects so-called autonomous sets in the interaction graph, variables that contain all their regulators, and considers their intersection and extension in order to perform model checking on the smallest possible state spaces. A benchmark, in which we apply the algorithm to 18 published Boolean networks, is given. In each case, the minimal trap spaces are faithful, univocal and complete which suggests that they are in general good approximations for the asymptotics of Boolean networks.

  9. Binary higher order neural networks for realizing Boolean functions.

    Science.gov (United States)

    Zhang, Chao; Yang, Jie; Wu, Wei

    2011-05-01

    In order to more efficiently realize Boolean functions by using neural networks, we propose a binary product-unit neural network (BPUNN) and a binary π-ς neural network (BPSNN). The network weights can be determined by one-step training. It is shown that the addition " σ," the multiplication " π," and two kinds of special weighting operations in BPUNN and BPSNN can implement the logical operators " ∨," " ∧," and " ¬" on Boolean algebra 〈Z(2),∨,∧,¬,0,1〉 (Z(2)={0,1}), respectively. The proposed two neural networks enjoy the following advantages over the existing networks: 1) for a complete truth table of N variables with both truth and false assignments, the corresponding Boolean function can be realized by accordingly choosing a BPUNN or a BPSNN such that at most 2(N-1) hidden nodes are needed, while O(2(N)), precisely 2(N) or at most 2(N), hidden nodes are needed by existing networks; 2) a new network BPUPS based on a collaboration of BPUNN and BPSNN can be defined to deal with incomplete truth tables, while the existing networks can only deal with complete truth tables; and 3) the values of the weights are all simply -1 or 1, while the weights of all the existing networks are real numbers. Supporting numerical experiments are provided as well. Finally, we present the risk bounds of BPUNN, BPSNN, and BPUPS, and then analyze their probably approximately correct learnability.

  10. FDA regulatory affairs: a guide for prescription drugs, medical devices, and biologics

    National Research Council Canada - National Science Library

    Mantus, David; Pisano, Douglas J

    2008-01-01

    ...: A Guide for Prescription Drugs, Medical Devices, and Biologics, Second Edition are covered in a straightforward format. It is a compilation and commentary of selected laws and regulations pertaining to the development and approval of drugs, biologics, and medical devices in the United States. It is not intended to take the place of an actual r...

  11. METHODOLOGICAL APPROACHES AND CLINICAL RESEARCH METHODS AND REGULATORY ADAPTATION PROCESSES IN A BIOLOGICAL SYSTEM «PREGNANT WOMAN»

    Directory of Open Access Journals (Sweden)

    Галина Александровна Ушакова

    2016-11-01

    Full Text Available Regulatory and adaptation processes are needed for the physiological development of the «pregnant woman» biological system («gravida». Methodologically biological system «gravid» considered as a cybernetic system in which there are «inputs» and «outputs» forward and backward linkages, implemented processes and information management. One of the universal methods of communication are oscillatory processes. The system «gravida» hemodynamic fluctuations are cardiac activity and the mother of the fetus. Information is exchanged through the placenta by changing the heart rate variability of mother and fetus. The first time the definition of gravidarnogo homeostasis homeokinesis, homeorhesis, homeoclasis.

  12. Regulatory inhibition of biological tissue mineralization by calcium phosphate through post-nucleation shielding by fetuin-A

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Joshua C., E-mail: joshchang@ucla.edu [Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA and Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio 43210 (United States); Miura, Robert M., E-mail: miura@njit.edu [Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, New Jersey 07102 (United States)

    2016-04-21

    In vertebrates, insufficient availability of calcium and inorganic phosphate ions in extracellular fluids leads to loss of bone density and neuronal hyper-excitability. To counteract this problem, calcium ions are usually present at high concentrations throughout bodily fluids—at concentrations exceeding the saturation point. This condition leads to the opposite situation where unwanted mineral sedimentation may occur. Remarkably, ectopic or out-of-place sedimentation into soft tissues is rare, in spite of the thermodynamic driving factors. This fortunate fact is due to the presence of auto-regulatory proteins that are found in abundance in bodily fluids. Yet, many important inflammatory disorders such as atherosclerosis and osteoarthritis are associated with this undesired calcification. Hence, it is important to gain an understanding of the regulatory process and the conditions under which it can go awry. In this manuscript, we extend mean-field continuum classical nucleation theory of the growth of clusters to encompass surface shielding. We use this formulation to study the regulation of sedimentation of calcium phosphate salts in biological tissues through the mechanism of post-nuclear shielding of nascent mineral particles by binding proteins. We develop a mathematical description of this phenomenon using a countable system of hyperbolic partial differential equations. A critical concentration of regulatory protein is identified as a function of the physical parameters that describe the system.

  13. Regulatory inhibition of biological tissue mineralization by calcium phosphate through post-nucleation shielding by fetuin-A

    Science.gov (United States)

    Chang, Joshua C.; Miura, Robert M.

    2016-04-01

    In vertebrates, insufficient availability of calcium and inorganic phosphate ions in extracellular fluids leads to loss of bone density and neuronal hyper-excitability. To counteract this problem, calcium ions are usually present at high concentrations throughout bodily fluids—at concentrations exceeding the saturation point. This condition leads to the opposite situation where unwanted mineral sedimentation may occur. Remarkably, ectopic or out-of-place sedimentation into soft tissues is rare, in spite of the thermodynamic driving factors. This fortunate fact is due to the presence of auto-regulatory proteins that are found in abundance in bodily fluids. Yet, many important inflammatory disorders such as atherosclerosis and osteoarthritis are associated with this undesired calcification. Hence, it is important to gain an understanding of the regulatory process and the conditions under which it can go awry. In this manuscript, we extend mean-field continuum classical nucleation theory of the growth of clusters to encompass surface shielding. We use this formulation to study the regulation of sedimentation of calcium phosphate salts in biological tissues through the mechanism of post-nuclear shielding of nascent mineral particles by binding proteins. We develop a mathematical description of this phenomenon using a countable system of hyperbolic partial differential equations. A critical concentration of regulatory protein is identified as a function of the physical parameters that describe the system.

  14. On the Computation of Comprehensive Boolean Gröbner Bases

    Science.gov (United States)

    Inoue, Shutaro

    We show that a comprehensive Boolean Gröbner basis of an ideal I in a Boolean polynomial ring B (bar A,bar X) with main variables bar X and parameters bar A can be obtained by simply computing a usual Boolean Gröbner basis of I regarding both bar X and bar A as variables with a certain block term order such that bar X ≫ bar A. The result together with a fact that a finite Boolean ring is isomorphic to a direct product of the Galois field mathbb{GF}_2 enables us to compute a comprehensive Boolean Gröbner basis by only computing corresponding Gröbner bases in a polynomial ring over mathbb{GF}_2. Our implementation in a computer algebra system Risa/Asir shows that our method is extremely efficient comparing with existing computation algorithms of comprehensive Boolean Gröbner bases.

  15. A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining

    Directory of Open Access Journals (Sweden)

    Lan Chung-Yu

    2008-09-01

    Full Text Available Abstract Background Inflammation is a hallmark of many human diseases. Elucidating the mechanisms underlying systemic inflammation has long been an important topic in basic and clinical research. When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease. However, it is difficult to recognize and evaluate relevant biological processes from the huge quantities of experimental data. It is hence appealing to find an algorithm which can generate a gene regulatory network of systemic inflammation from high-throughput genomic studies of human diseases. Such network will be essential for us to extract valuable information from the complex and chaotic network under diseased conditions. Results In this study, we construct a gene regulatory network of inflammation using data extracted from the Ensembl and JASPAR databases. We also integrate and apply a number of systematic algorithms like cross correlation threshold, maximum likelihood estimation method and Akaike Information Criterion (AIC on time-lapsed microarray data to refine the genome-wide transcriptional regulatory network in response to bacterial endotoxins in the context of dynamic activated genes, which are regulated by transcription factors (TFs such as NF-κB. This systematic approach is used to investigate the stochastic interaction represented by the dynamic leukocyte gene expression profiles of human subject exposed to an inflammatory stimulus (bacterial endotoxin. Based on the kinetic parameters of the dynamic gene regulatory network, we identify important properties (such as susceptibility to infection of the immune system, which may be useful for translational research. Finally, robustness of the inflammatory gene network is also inferred by analyzing the hubs and "weak ties" structures of the gene network

  16. From cell biology to immunology: Controlling metastatic progression of cancer via microRNA regulatory networks.

    Science.gov (United States)

    Park, Jae Hyon; Theodoratou, Evropi; Calin, George A; Shin, Jae Il

    2016-01-01

    Recently, the study of microRNAs has expanded our knowledge of the fundamental processes of cancer biology and the underlying mechanisms behind tumor metastasis. Extensive research in the fields of microRNA and its novel mechanisms of actions against various cancers has more recently led to the trial of a first cancer-targeted microRNA drug, MRX34. Yet, these microRNAs are mostly being studied and clinically trialed solely based on the understanding of their cell biologic effects, thus, neglecting the important immunologic effects that are sometimes opposite of the cell biologic effects. Here, we summarize both the cell biologic and immunologic effects of various microRNAs and discuss the importance of considering both effects before using them in clinical settings. We stress the importance of understanding the miRNA's effect on cancer metastasis from a "systems" perspective before developing a miRNA-targeted therapeutic in treating cancer metastasis.

  17. The mathematics of a quantum Hamiltonian computing half adder Boolean logic gate.

    Science.gov (United States)

    Dridi, G; Julien, R; Hliwa, M; Joachim, C

    2015-08-28

    The mathematics behind the quantum Hamiltonian computing (QHC) approach of designing Boolean logic gates with a quantum system are given. Using the quantum eigenvalue repulsion effect, the QHC AND, NAND, OR, NOR, XOR, and NXOR Hamiltonian Boolean matrices are constructed. This is applied to the construction of a QHC half adder Hamiltonian matrix requiring only six quantum states to fullfil a half Boolean logical truth table. The QHC design rules open a nano-architectronic way of constructing Boolean logic gates inside a single molecule or atom by atom at the surface of a passivated semi-conductor.

  18. Regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

  19. An Association Rule Mining Algorithm Based on a Boolean Matrix

    Directory of Open Access Journals (Sweden)

    Hanbing Liu

    2007-09-01

    Full Text Available Association rule mining is a very important research topic in the field of data mining. Discovering frequent itemsets is the key process in association rule mining. Traditional association rule algorithms adopt an iterative method to discovery, which requires very large calculations and a complicated transaction process. Because of this, a new association rule algorithm called ABBM is proposed in this paper. This new algorithm adopts a Boolean vector "relational calculus" method to discovering frequent itemsets. Experimental results show that this algorithm can quickly discover frequent itemsets and effectively mine potential association rules.

  20. A Construction of Boolean Functions with Good Cryptographic Properties

    Science.gov (United States)

    2014-01-01

    over Fn2 defined by Wf (u) = ∑ x∈Fn2 (−1)f(x)+u·x, where u ∈ Fn2 and u · x is an inner product , for instance, u · x = u1x1 + u2x3 + · · · + unxn, where u...later on for all these classes. We mention also the paper of Pasalic [27], which introduces the notion of high degree product (HDP) to mea- sure the...2008, LNCS 5350, Springer–Verlag, 2008, pp. 425–440. [10] C. Carlet and K. Feng, “An Infinite Class of Balanced Vectorial Boolean Functions with Optimum

  1. A Boolean Approach to Airline Business Model Innovation

    DEFF Research Database (Denmark)

    Hvass, Kristian Anders

    Research in business model innovation has identified its significance in creating a sustainable competitive advantage for a firm, yet there are few empirical studies identifying which combination of business model activities lead to success and therefore deserve innovative attention. This study...... analyzes the business models of North America low-cost carriers from 2001 to 2010 using a Boolean minimization algorithm to identify which combinations of business model activities lead to operational profitability. The research aim is threefold: complement airline literature in the realm of business model...

  2. Bebop to the Boolean boogie an unconventional guide to electronics

    CERN Document Server

    Maxfield, Clive

    2003-01-01

    From reviews of the first edition:""If you want to be reminded of the joy of electronics, take a look at Clive (Max) Maxfield's book Bebop to the Boolean Boogie.""--Computer Design ""Lives up to its title as a useful and entertaining technical guide....well-suited for students, technical writers, technicians, and sales and marketing people.""--Electronic Design""Writing a book like this one takes audacity! ... Maxfield writes lucidly on a variety of complex topics without 'writing down' to his audience."" --EDN""A highly readable, well-illustrated guided tour

  3. Two Expectation-Maximization Algorithms for Boolean Factor Analysis

    Czech Academy of Sciences Publication Activity Database

    Frolov, A. A.; Húsek, Dušan; Polyakov, P.Y.

    2014-01-01

    Roč. 130, 23 April (2014), s. 83-97 ISSN 0925-2312 R&D Projects: GA ČR GAP202/10/0262 Grant - others:GA MŠk(CZ) ED1.1.00/02.0070; GA MŠk(CZ) EE.2.3.20.0073 Program:ED Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean Factor analysis * Binary Matrix factorization * Neural networks * Binary data model * Dimension reduction * Bars problem Subject RIV: IN - Informatics, Computer Science Impact factor: 2.083, year: 2014

  4. Complexity classifications for different equivalence and audit problems for Boolean circuits

    OpenAIRE

    Böhler, Elmar; Creignou, Nadia; Galota, Matthias; Reith, Steffen; Schnoor, Henning; Vollmer, Heribert

    2010-01-01

    We study Boolean circuits as a representation of Boolean functions and conskier different equivalence, audit, and enumeration problems. For a number of restricted sets of gate types (bases) we obtain efficient algorithms, while for all other gate types we show these problems are at least NP-hard.

  5. The Importance of the mTOR Regulatory Network in Chondrocyte Biology and Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Elena V. Tchetina

    2014-07-01

    Full Text Available Osteoarthritis (OA is a chronic disorder associated mainly with pain, limited range of motion, stiffness, joint inflammation, and articular cartilage (AC destruction. Recent studies demonstrated the involvement of chondrocyte differentiation (hypertrophy as one of the mechanisms of cartilage degradation in OA. This indicates the involvement of profound alterations in chondrocyte metabolism in the course of cartilage resorption orchestrated by principal changes in the regulation of cellular function. Mammalian target of rapamycin (mTOR controls critical cellular processes such as growth, proliferation, and protein synthesis, and integrates extracellular signals from growth factors and hormones with amino acid availability and intracellular energy status. The importance of mTOR activity during AC destruction in OA is supported by considerable alterations in the mTOR regulatory network, involving multiple intracellular (availability of growth factors, adenosine triphosphate [ATP], and oxygen as well as autophagy and extracellular (glucose, amino acid, lipid, and hexosamine signals. Moreover, variable mTOR gene expression in the peripheral blood of OA patients is associated with increases in pain or synovitis, and indicates a profound metabolic dissimilarity among patients that might require differential approaches to treatment. These issues are discussed in the present review article.

  6. Dynamic regulatory on/off minimization for biological systems under internal temporal perturbations

    Directory of Open Access Journals (Sweden)

    Kleessen Sabrina

    2012-03-01

    Full Text Available Abstract Background Flux balance analysis (FBA together with its extension, dynamic FBA, have proven instrumental for analyzing the robustness and dynamics of metabolic networks by employing only the stoichiometry of the included reactions coupled with adequately chosen objective function. In addition, under the assumption of minimization of metabolic adjustment, dynamic FBA has recently been employed to analyze the transition between metabolic states. Results Here, we propose a suite of novel methods for analyzing the dynamics of (internally perturbed metabolic networks and for quantifying their robustness with limited knowledge of kinetic parameters. Following the biochemically meaningful premise that metabolite concentrations exhibit smooth temporal changes, the proposed methods rely on minimizing the significant fluctuations of metabolic profiles to predict the time-resolved metabolic state, characterized by both fluxes and concentrations. By conducting a comparative analysis with a kinetic model of the Calvin-Benson cycle and a model of plant carbohydrate metabolism, we demonstrate that the principle of regulatory on/off minimization coupled with dynamic FBA can accurately predict the changes in metabolic states. Conclusions Our methods outperform the existing dynamic FBA-based modeling alternatives, and could help in revealing the mechanisms for maintaining robustness of dynamic processes in metabolic networks over time.

  7. Regulatory-Science: Biphasic Cancer Models or the LNT—Not Just a Matter of Biology!

    Science.gov (United States)

    Ricci, Paolo F.; Sammis, Ian R.

    2012-01-01

    There is no doubt that prudence and risk aversion must guide public decisions when the associated adverse outcomes are either serious or irreversible. With any carcinogen, the levels of risk and needed protection before and after an event occurs, are determined by dose-response models. Regulatory law should not crowd out the actual beneficial effects from low dose exposures—when demonstrable—that are inevitably lost when it adopts the linear non-threshold (LNT) as its causal model. Because regulating exposures requires planning and developing protective measures for future acute and chronic exposures, public management decisions should be based on minimizing costs and harmful exposures. We address the direct and indirect effects of causation when the danger consists of exposure to very low levels of carcinogens and toxicants. The societal consequences of a policy can be deleterious when that policy is based on a risk assumed by the LNT, in cases where low exposures are actually beneficial. Our work develops the science and the law of causal risk modeling: both are interwoven. We suggest how their relevant characteristics differ, but do not attempt to keep them separated; as we demonstrate, this union, however unsatisfactory, cannot be severed. PMID:22740778

  8. Regulatory-Science: Biphasic Cancer Models or the LNT-Not Just a Matter of Biology!

    Science.gov (United States)

    Ricci, Paolo F; Sammis, Ian R

    2012-01-01

    There is no doubt that prudence and risk aversion must guide public decisions when the associated adverse outcomes are either serious or irreversible. With any carcinogen, the levels of risk and needed protection before and after an event occurs, are determined by dose-response models. Regulatory law should not crowd out the actual beneficial effects from low dose exposures-when demonstrable-that are inevitably lost when it adopts the linear non-threshold (LNT) as its causal model. Because regulating exposures requires planning and developing protective measures for future acute and chronic exposures, public management decisions should be based on minimizing costs and harmful exposures. We address the direct and indirect effects of causation when the danger consists of exposure to very low levels of carcinogens and toxicants. The societal consequences of a policy can be deleterious when that policy is based on a risk assumed by the LNT, in cases where low exposures are actually beneficial. Our work develops the science and the law of causal risk modeling: both are interwoven. We suggest how their relevant characteristics differ, but do not attempt to keep them separated; as we demonstrate, this union, however unsatisfactory, cannot be severed.

  9. Proposed method to construct Boolean functions with maximum possible annihilator immunity

    Science.gov (United States)

    Goyal, Rajni; Panigrahi, Anupama; Bansal, Rohit

    2017-07-01

    Nonlinearity and Algebraic(annihilator) immunity are two core properties of a Boolean function because optimum values of Annihilator Immunity and nonlinearity are required to resist fast algebraic attack and differential cryptanalysis respectively. For a secure cypher system, Boolean function(S-Boxes) should resist maximum number of attacks. It is possible if a Boolean function has optimal trade-off among its properties. Before constructing Boolean functions, we fixed the criteria of our constructions based on its properties. In present work, our construction is based on annihilator immunity and nonlinearity. While keeping above facts in mind,, we have developed a multi-objective evolutionary approach based on NSGA-II and got the optimum value of annihilator immunity with good bound of nonlinearity. We have constructed balanced Boolean functions having the best trade-off among balancedness, Annihilator immunity and nonlinearity for 5, 6 and 7 variables by the proposed method.

  10. Chemical Visualization of Boolean Functions: A Simple Chemical Computer

    Science.gov (United States)

    Blittersdorf, R.; Müller, J.; Schneider, F. W.

    1995-08-01

    We present a chemical realization of the Boolean functions AND, OR, NAND, and NOR with a neutralization reaction carried out in three coupled continuous flow stirred tank reactors (CSTR). Two of these CSTR's are used as input reactors, the third reactor marks the output. The chemical reaction is the neutralization of hydrochloric acid (HCl) with sodium hydroxide (NaOH) in the presence of phenolphtalein as an indicator, which is red in alkaline solutions and colorless in acidic solutions representing the two binary states 1 and 0, respectively. The time required for a "chemical computation" is determined by the flow rate of reactant solutions into the reactors since the neutralization reaction itself is very fast. While the acid flow to all reactors is equal and constant, the flow rate of NaOH solution controls the states of the input reactors. The connectivities between the input and output reactors determine the flow rate of NaOH solution into the output reactor, according to the chosen Boolean function. Thus the state of the output reactor depends on the states of the input reactors.

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

    Science.gov (United States)

    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.

  12. Synchronization Analysis of Master-Slave Probabilistic Boolean Networks.

    Science.gov (United States)

    Lu, Jianquan; Zhong, Jie; Li, Lulu; Ho, Daniel W C; Cao, Jinde

    2015-08-28

    In this paper, we analyze the synchronization problem of master-slave probabilistic Boolean networks (PBNs). The master Boolean network (BN) is a deterministic BN, while the slave BN is determined by a series of possible logical functions with certain probability at each discrete time point. In this paper, we firstly define the synchronization of master-slave PBNs with probability one, and then we investigate synchronization with probability one. By resorting to new approach called semi-tensor product (STP), the master-slave PBNs are expressed in equivalent algebraic forms. Based on the algebraic form, some necessary and sufficient criteria are derived to guarantee synchronization with probability one. Further, we study the synchronization of master-slave PBNs in probability. Synchronization in probability implies that for any initial states, the master BN can be synchronized by the slave BN with certain probability, while synchronization with probability one implies that master BN can be synchronized by the slave BN with probability one. Based on the equivalent algebraic form, some efficient conditions are derived to guarantee synchronization in probability. Finally, several numerical examples are presented to show the effectiveness of the main results.

  13. Efficient Instantiation of Parameterised Boolean Equation Systems to Parity Games

    Directory of Open Access Journals (Sweden)

    Gijs Kant

    2012-10-01

    Full Text Available Parameterised Boolean Equation Systems (PBESs are sequences of Boolean fixed point equations with data variables, used for, e.g., verification of modal mu-calculus formulae for process algebraic specifications with data. Solving a PBES is usually done by instantiation to a Parity Game and then solving the game. Practical game solvers exist, but the instantiation step is the bottleneck. We enhance the instantiation in two steps. First, we transform the PBES to a Parameterised Parity Game (PPG, a PBES with each equation either conjunctive or disjunctive. Then we use LTSmin, that offers transition caching, efficient storage of states and both distributed and symbolic state space generation, for generating the game graph. To that end we define a language module for LTSmin, consisting of an encoding of variables with parameters into state vectors, a grouped transition relation and a dependency matrix to indicate the dependencies between parts of the state vector and transition groups. Benchmarks on some large case studies, show that the method speeds up the instantiation significantly and decreases memory usage drastically.

  14. Physical, biologic, and phenotypic properties of natural regulatory cells in murine bone marrow

    International Nuclear Information System (INIS)

    Dorshkind, K.; Rosse, C.

    1982-01-01

    A lymphocyte-enriched fraction of murine bone marrow (BML) contains natural regulatory cells (NRC) that can inhibit, on a dose-dependent basis, proliferative and cytotoxic responses to alloantigens in a mixed lymphocyte culture. The objective of this study was to investigate the characteristics of the cells responsible for this phenomenon in CBA mice. Maximal suppression was obtained with BML cells themselves rather than cell products. Light-scatter analysis of NRC on the fluorescence-activated cell sorter demonstrated them to be larger than small lymphocytes, and their sedimentation in discontinuous Percoll gradients showed the cells to be of heterogeneous density. This heterogeneity is further reflected by the fact that both plastic adherent and nonadherent BML are suppressive. NRC must be viable in order to mediate suppression; they are cortisone-resistant and are not affected by doses of gamma irradiation up to 1,000 R. NRC are not T or B lymphocytes or Ia-bearing macrophages. The involvement of mature granulocytes and macrophages in natural suppression is unlikely in that NRC do not bear Fc receptors. Elimination of cells from BML with the natural killer (NK) surface marker Asialo GM1 does not abrogate suppression. NRC are capable of mediating suppression across major and minor histocompatibility complex barriers. While lymphoid cells are prominent in BML, the contamination of this marrow fraction with immature granulocytes and monocytes makes a morphologic identification of NRC difficult. These characteristics are most consistent with NRC begin immature marrow cells of undetermined lineage. The relationship of NRC to naturally occurring marrow suppressor cells described in other systems is not yet clear and awaits experimental clarification

  15. Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.

    Science.gov (United States)

    Ravichandran, Srikanth; Del Sol, Antonio

    2017-02-01

    Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell-based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  16. Milk Leptin Surge and Biological Rhythms of Leptin and Other Regulatory Proteins in Breastmilk.

    Science.gov (United States)

    Nozhenko, Yuriy; Asnani-Kishnani, Madhu; Rodríguez, Ana M; Palou, Andreu

    2015-01-01

    A significant number of chronic diseases are linked to perinatal nutrition, and prevention may be associated to naturally occurring components of breast milk. One key hormone in breast milk is leptin, related with the protection from obesity in the adulthood, thus knowing its changes through the day or lactation is crucial. We aimed to investigate the daily rhythms in the milk levels of leptin, together with other two related hormones, ghrelin and adiponectin, during lactation (days 5, 10 and 15) in rat dams, and the relation with morphometric parameters (dams and pups). Summarizing the main results, the existence of biological rhythms, but not daily and maybe circasemidian, was confirmed for the three hormones at the earliest period of lactation. The correlations performed generally showed a possible dependence of milk hormone levels on plasma levels at the early phase of lactation, while with the progression of lactation this dependence may fade and the hormone levels are suggested to be more dependent on mammary gland production/maturation. There was also a correlation between milk leptin and adiponectin levels, especially in the first half of lactation, suggesting a possible parallel regulation. Interestingly, we describe a milk leptin surge around the mid of lactation (at day 10) which may be related with pup's growth (males and females) and with the well-known (in the literature) plasma leptin surge in pups. All this knowledge may be crucial for future applications in the development of formula milk and in relation with the role of leptin surge during lactation.

  17. Structured Development and Promotion of a Research Field: Hormesis in Biology, Toxicology, and Environmental Regulatory Science.

    Science.gov (United States)

    Mushak, Paul; Elliott, Kevin C

    2015-12-01

    The ability of powerful and well-funded interest groups to steer scientific research in ways that advance their goals has become a significant social concern. This steering ability is increasingly being recognized in the peer-reviewed scientific literature and in findings of deliberative scientific bodies. This paper provides a case study that illustrates some of the major strategies that can be used to structure and advance a controversial research field. It focuses on hormesis, described as a type of dose-response relationship in toxicology and biology showing low-dose stimulation but high-dose inhibition, or the reverse. Hormesis proponents tout its significance, arguing that substances toxic at high doses and beneficial at lower doses should be regulated less stringently. We identify five strategies employed by hormesis proponents to foster its acceptance: (1) creating institutions focused on supporting hormesis; (2) developing terminology, study designs, and data interpretations that cast it in a favorable light; (3) using bibliometric techniques and surveys to attract attention; (4) aggressively advocating for the phenomenon and challenging critics; and (5) working with outside interest groups to apply the hormesis phenomenon in the economic and political spheres. We also suggest a number of oversight strategies that can be implemented to help promote credible and socially responsible research in cases like this one.

  18. Genomics and medicine: an anticipation. From Boolean Mendelian genetics to multifactorial molecular medicine.

    Science.gov (United States)

    Kaplan, J C; Junien, C

    2000-12-01

    The major impact of the completion of the human genome sequence will be the understanding of diseases, with deduced therapy. In the field of genetic disorders, we will complete the catalogue of monogenic diseases, also called Mendelian diseases because they obey the Boolean logic of Mendel's laws. The major challenge now is to decipher the polygenic and multifactorial etiology of common diseases, such as cancer, cardio-vascular, nutritional, allergic, auto-immune and degenerative diseases. In fact, every gene, when mutated, is a potential disease gene, and we end up with the new concept of 'reverse medicine'; i.e., deriving new diseases or pathogenic pathways from the knowledge of the structure and function of every gene. By going from sequence to function (functional genomics and proteomics) we will gain insight into basic mechanisms of major functions such as cell proliferation, differentiation and development, which are perturbed in many pathological processes. By learning the meaning of some non-coding and of regulatory sequences our understanding will gain in complexity, generating a molecular and supramolecular integrated physiology, helping to build a molecular patho-physiology of the different syndromes. Besides those cognitive advances, there are also other issues at stake, such as: progress in diagnostic and prediction (predictive medicine); progress in therapy (pharmacogenomics and gene-based therapy); ethical issues; impact on business.

  19. Milk Leptin Surge and Biological Rhythms of Leptin and Other Regulatory Proteins in Breastmilk.

    Directory of Open Access Journals (Sweden)

    Yuriy Nozhenko

    Full Text Available A significant number of chronic diseases are linked to perinatal nutrition, and prevention may be associated to naturally occurring components of breast milk. One key hormone in breast milk is leptin, related with the protection from obesity in the adulthood, thus knowing its changes through the day or lactation is crucial. We aimed to investigate the daily rhythms in the milk levels of leptin, together with other two related hormones, ghrelin and adiponectin, during lactation (days 5, 10 and 15 in rat dams, and the relation with morphometric parameters (dams and pups. Summarizing the main results, the existence of biological rhythms, but not daily and maybe circasemidian, was confirmed for the three hormones at the earliest period of lactation. The correlations performed generally showed a possible dependence of milk hormone levels on plasma levels at the early phase of lactation, while with the progression of lactation this dependence may fade and the hormone levels are suggested to be more dependent on mammary gland production/maturation. There was also a correlation between milk leptin and adiponectin levels, especially in the first half of lactation, suggesting a possible parallel regulation. Interestingly, we describe a milk leptin surge around the mid of lactation (at day 10 which may be related with pup's growth (males and females and with the well-known (in the literature plasma leptin surge in pups. All this knowledge may be crucial for future applications in the development of formula milk and in relation with the role of leptin surge during lactation.

  20. Reconfigurable Boolean logic using magnetic single-electron transistors.

    Directory of Open Access Journals (Sweden)

    M Fernando Gonzalez-Zalba

    Full Text Available We propose a novel hybrid single-electron device for reprogrammable low-power logic operations, the magnetic single-electron transistor (MSET. The device consists of an aluminium single-electron transistor with a GaMnAs magnetic back-gate. Changing between different logic gate functions is realized by reorienting the magnetic moments of the magnetic layer, which induces a voltage shift on the Coulomb blockade oscillations of the MSET. We show that we can arbitrarily reprogram the function of the device from an n-type SET for in-plane magnetization of the GaMnAs layer to p-type SET for out-of-plane magnetization orientation. Moreover, we demonstrate a set of reprogrammable Boolean gates and its logical complement at the single device level. Finally, we propose two sets of reconfigurable binary gates using combinations of two MSETs in a pull-down network.

  1. Reconfigurable Boolean Logic Using Magnetic Single-Electron Transistors

    Science.gov (United States)

    Gonzalez-Zalba, M. Fernando; Ciccarelli, Chiara; Zarbo, Liviu P.; Irvine, Andrew C.; Campion, Richard C.; Gallagher, Bryan L.; Jungwirth, Tomas; Ferguson, Andrew J.; Wunderlich, Joerg

    2015-01-01

    We propose a novel hybrid single-electron device for reprogrammable low-power logic operations, the magnetic single-electron transistor (MSET). The device consists of an aluminium single-electron transistor with a GaMnAs magnetic back-gate. Changing between different logic gate functions is realized by reorienting the magnetic moments of the magnetic layer, which induces a voltage shift on the Coulomb blockade oscillations of the MSET. We show that we can arbitrarily reprogram the function of the device from an n-type SET for in-plane magnetization of the GaMnAs layer to p-type SET for out-of-plane magnetization orientation. Moreover, we demonstrate a set of reprogrammable Boolean gates and its logical complement at the single device level. Finally, we propose two sets of reconfigurable binary gates using combinations of two MSETs in a pull-down network. PMID:25923789

  2. Identification of Boolean Networks Using Premined Network Topology Information.

    Science.gov (United States)

    Zhang, Xiaohua; Han, Huaxiang; Zhang, Weidong

    2017-02-01

    This brief aims to reduce the data requirement for the identification of Boolean networks (BNs) by using the premined network topology information. First, a matching table is created and used for sifting the true from the false dependences among the nodes in the BNs. Then, a dynamic extension to matching table is developed to enable the dynamic locating of matching pairs to start as soon as possible. Next, based on the pseudocommutative property of the semitensor product, a position-transform mining is carried out to further improve data utilization. Combining the above, the topology of the BNs can be premined for the subsequent identification. Examples are given to illustrate the efficiency of reducing the data requirement. Some excellent features, such as the online and parallel processing ability, are also demonstrated.

  3. ZKBoo: Faster Zero-Knowledge for Boolean Circuits

    DEFF Research Database (Denmark)

    Giacomelli, Irene; Madsen, Jesper; Orlandi, Claudio

    2016-01-01

    variants of IKOS, which highlights their pros and cons for practically rele- vant soundness parameters; ◦ A generalization and simplification of their approach, which leads to faster Σ-protocols (that can be made non-interactive using the Fiat-Shamir heuristic) for state- ments of the form “I know x...... such that y = φ (x)” (where φ is a circuit and y a public value); ◦ A case study, where we provide explicit protocols, implementations and benchmarking of zero-knowledge protocols for the SHA-1 and SHA-256 circuits.......In this paper we describe ZKBoo, a proposal for practically efficient zero-knowledge arguments especially tailored for Boolean circuits and report on a proof-of- concept implementation. As an highlight, we can generate (resp. verify) a non-interactive proof for the SHA-1 circuit in approximately 13...

  4. Algebraic characteristics and satisfiability threshold of random Boolean equations

    Science.gov (United States)

    Guo, Binghui; Wei, Wei; Sun, Yifan; Zheng, Zhiming

    2010-03-01

    The satisfiability of a class of random Boolean equations named massive algebraic system septated to linear and nonlinear subproblems is studied in this paper. On one hand, the correlation between the magnetization of generators and the clustering of solutions of the linear subproblem is investigated by analyzing the Gaussian elimination process. On the other hand, the characteristics of maximal elements of solutions of the nonlinear subproblem are studied by introducing the partial order among solutions. Based on the algebraic characteristics of these two subproblems, the upper and lower bounds of satisfiability threshold of massive algebraic system are obtained by unit-clause propagation and leaf-removal process, and coincide as the ratio of nonlinear equations q>0.739 in which analytical values of the satisfiability threshold can be derived. Furthermore, a complete algorithm with heuristic decimation is proposed to observe the approximation of the satisfiability threshold, which performs more efficiently than the classical ones.

  5. Boolean Algebra Application in Analysis of Flight Accidents

    Directory of Open Access Journals (Sweden)

    Casandra Venera BALAN

    2015-12-01

    Full Text Available Fault tree analysis is a deductive approach for resolving an undesired event into its causes, identifying the causes of a failure and providing a framework for a qualitative and quantitative evaluation of the top event. An alternative approach to fault tree analysis methods calculus goes to logical expressions and it is based on a graphical representation of the data structure for a logic - based binary decision diagram representation. In this analysis, such sites will be reduced to a minimal size and arranged in the sense that the variables appear in the same order in each path. An event can be defined as a statement that can be true or false. Therefore, Boolean algebra rules allow restructuring of a Fault Tree into one equivalent to it, but simpler.

  6. Logical Attractors: a Boolean Approach to the Dynamics of Psychosis

    Science.gov (United States)

    Kupper, Z.; Hoffmann, H.

    A Boolean modeling approach to attractors in the dynamics of psychosis is presented: Kinetic Logic, originating from R. Thomas, describes systems on an intermediate level between a purely verbal, qualitative description and a description using nonlinear differential equations. With this method we may model impact, feedback and temporal evolution, as well as analyze the resulting attractors. In our previous research the method has been applied to general and more specific questions in the dynamics of psychotic disorders. In this paper a model is introduced that describes different dynamical patterns of chronic psychosis in the context of vocational rehabilitation. It also shows to be useful in formulating and exploring possible treatment strategies. Finally, some of the limitations and benefits of Kinetic Logic as a modeling tool for psychology and psychiatry are discussed.

  7. Bio-logic builder: a non-technical tool for building dynamical, qualitative models.

    Science.gov (United States)

    Helikar, Tomáš; Kowal, Bryan; Madrahimov, Alex; Shrestha, Manish; Pedersen, Jay; Limbu, Kahani; Thapa, Ishwor; Rowley, Thaine; Satalkar, Rahul; Kochi, Naomi; Konvalina, John; Rogers, Jim A

    2012-01-01

    Computational modeling of biological processes is a promising tool in biomedical research. While a large part of its potential lies in the ability to integrate it with laboratory research, modeling currently generally requires a high degree of training in mathematics and/or computer science. To help address this issue, we have developed a web-based tool, Bio-Logic Builder, that enables laboratory scientists to define mathematical representations (based on a discrete formalism) of biological regulatory mechanisms in a modular and non-technical fashion. As part of the user interface, generalized "bio-logic" modules have been defined to provide users with the building blocks for many biological processes. To build/modify computational models, experimentalists provide purely qualitative information about a particular regulatory mechanisms as is generally found in the laboratory. The Bio-Logic Builder subsequently converts the provided information into a mathematical representation described with Boolean expressions/rules. We used this tool to build a number of dynamical models, including a 130-protein large-scale model of signal transduction with over 800 interactions, influenza A replication cycle with 127 species and 200+ interactions, and mammalian and budding yeast cell cycles. We also show that any and all qualitative regulatory mechanisms can be built using this tool.

  8. Collaborative international research: ethical and regulatory issues pertaining to human biological materials at a South African institutional research ethics committee.

    Science.gov (United States)

    Sathar, Aslam; Dhai, Amaboo; van der Linde, Stephan

    2014-12-01

    Human Biological Materials (HBMs) are an invaluable resource in biomedical research. To determine if researchers and a Research Ethics Committee (REC) at a South African institution addressed ethical issues pertaining to HBMs in collaborative research with developed countries. Ethically approved retrospective cross-sectional descriptive audit. Of the 1305 protocols audited, 151 (11.57%) fulfilled the study's inclusion criteria. Compared to other developed countries, a majority of sponsors (90) were from the USA (p = 0.0001). The principle investigators (PIs) in all 151 protocols informed the REC of their intent to store HBMs. Only 132 protocols informed research participants (P research participants, 116 protocols (76.8%) solicited broad consent compared to specific consent (32; 21.2%) [p research participants (67) that HBMs would be exported (p = 0.011). Export permits (EPs) and Material Transfer Agreements (MTAs) were not available in 109 and 143 protocols, respectively. Researchers and the REC did not adequately address the inter-related ethical and regulatory issues pertaining to HBMs. There was a lack of congruence between the ethical guidelines of developed countries and their actions which are central to the access to HBMs in collaborative research. HBMs may be leaving South Africa without EPs and MTAs during the process of international collaborative research. © 2013 John Wiley & Sons Ltd.

  9. Interchangeability of biosimilar and biological reference product: updated regulatory positions and pre- and post-marketing evidence.

    Science.gov (United States)

    Trifirò, Gianluca; Marcianò, Ilaria; Ingrasciotta, Ylenia

    2018-03-01

    Since 2006, biosimilars have been available in several countries worldwide, thus allowing for potential savings in pharmaceutical expenditure. However, there have been numerous debates about the interchangeability of biosimilars and reference products based on concerns of immunogenicity by switching between biological products, which may cause lack of effect and toxicity. Areas covered: The authors provide the reader with an overview of the different positions of regulatory authorities on the interchangeability and automatic substitution of biosimilars and reference products. Presently, the FDA allows automatic substitution without prescriber intervention if the biosimilar is interchangeable with reference products, while the European Medicines Agency delegate to each single EU member state. Expert opinion: Different approaches in defining interchangeability and automatic substitution call for harmonization to increase confidence of healthcare professionals and patients about the clinical impact of switching. Networks of electronic healthcare records and administrative databases, potentially linkable to clinical charts and registries may rapidly assess frequency and benefit-risk profile of different switching patterns in routine care at different levels, thus integrating and strengthening pre-marketing evidence.

  10. Systems Biology Approach to the Dissection of the Complexity of Regulatory Networks in the S. scrofa Cardiocirculatory System

    Directory of Open Access Journals (Sweden)

    Paolo Martini

    2013-11-01

    Full Text Available Genome-wide experiments are routinely used to increase the understanding of the biological processes involved in the development and maintenance of a variety of pathologies. Although the technical feasibility of this type of experiment has improved in recent years, data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. Here, we review strategies used in the gene set approach, and using datasets for the pig cardiocirculatory system as a case study, we demonstrate how the use of a combination of these strategies can enhance the interpretation of results. Gene set analyses are able to distinguish vessels from the heart and arteries from veins in a manner that is consistent with the different cellular composition of smooth muscle cells. By integrating microRNA elements in the regulatory circuits identified, we find that vessel specificity is maintained through specific miRNAs, such as miR-133a and miR-143, which show anti-correlated expression with their mRNA targets.

  11. Boolean and advanced searching for EDGAR data on www.sec.gov

    Data.gov (United States)

    Securities and Exchange Commission — This search allows users to enter complex boolean queries to access all but the most recent day's EDGAR filings on www.sec.gov. Filings are from 1994 to present.

  12. Sensitivity analysis of efficient solution in vector MINMAX boolean programming problem

    Directory of Open Access Journals (Sweden)

    Vladimir A. Emelichev

    2002-11-01

    Full Text Available We consider a multiple criterion Boolean programming problem with MINMAX partial criteria. The extreme level of independent perturbations of partial criteria parameters such that efficient (Pareto optimal solution preserves optimality was obtained.

  13. Constructivizability of the Boolean algebra B(ω) with a distinguished automorphism

    Czech Academy of Sciences Publication Activity Database

    Bazhenov, N. A.; Tukhbatullina, Regina

    2012-01-01

    Roč. 51, č. 5 (2012), s. 384-403 ISSN 0002-5232 Institutional support: PRVOUK-P23 Keywords : Boolean algebra * constructivizability * degree spectra of structures Subject RIV: AH - Economics Impact factor: 0.493, year: 2012

  14. Totally Optimal Decision Trees for Monotone Boolean Functions with at Most Five Variables

    KAUST Repository

    Chikalov, Igor

    2013-01-01

    In this paper, we present the empirical results for relationships between time (depth) and space (number of nodes) complexity of decision trees computing monotone Boolean functions, with at most five variables. We use Dagger (a tool for optimization of decision trees and decision rules) to conduct experiments. We show that, for each monotone Boolean function with at most five variables, there exists a totally optimal decision tree which is optimal with respect to both depth and number of nodes.

  15. Interpolation of the discrete logarithm in a finite field of characteristic two by Boolean functions

    DEFF Research Database (Denmark)

    Brandstaetter, Nina; Lange, Tanja; Winterhof, Arne

    2005-01-01

    We obtain bounds on degree, weight, and the maximal Fourier coefficient of Boolean functions interpolating the discrete logarithm in finite fields of characteristic two. These bounds complement earlier results for finite fields of odd characteristic.......We obtain bounds on degree, weight, and the maximal Fourier coefficient of Boolean functions interpolating the discrete logarithm in finite fields of characteristic two. These bounds complement earlier results for finite fields of odd characteristic....

  16. Correlation Immunity, Avalanche Features, and Other Cryptographic Properties of Generalized Boolean Functions

    Science.gov (United States)

    2017-09-01

    duties due to Sailors, across the globe, who stand the watch. As Winston Churchill once said, “we sleep safely at night because rough men stand ready...Chapter 2 contains definitions and preliminary generalized Boolean function material. This is followed by Chapters 3–5, which contain the bulk of the...Generalized Boolean Functions Sic Parvis Magna Sir Francis DrakeA In this chapter we begin by covering some basic definitions and properties which we will make

  17. An Attractor-Based Complexity Measurement for Boolean Recurrent Neural Networks

    Science.gov (United States)

    Cabessa, Jérémie; Villa, Alessandro E. P.

    2014-01-01

    We provide a novel refined attractor-based complexity measurement for Boolean recurrent neural networks that represents an assessment of their computational power in terms of the significance of their attractor dynamics. This complexity measurement is achieved by first proving a computational equivalence between Boolean recurrent neural networks and some specific class of -automata, and then translating the most refined classification of -automata to the Boolean neural network context. As a result, a hierarchical classification of Boolean neural networks based on their attractive dynamics is obtained, thus providing a novel refined attractor-based complexity measurement for Boolean recurrent neural networks. These results provide new theoretical insights to the computational and dynamical capabilities of neural networks according to their attractive potentialities. An application of our findings is illustrated by the analysis of the dynamics of a simplified model of the basal ganglia-thalamocortical network simulated by a Boolean recurrent neural network. This example shows the significance of measuring network complexity, and how our results bear new founding elements for the understanding of the complexity of real brain circuits. PMID:24727866

  18. Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity.

    Science.gov (United States)

    Tong, Jiefei; Elowe, Sabine; Nash, Piers; Pawson, Tony

    2003-02-21

    Signaling by the Eph family of receptor tyrosine kinases (RTKs) is complex, because they can interact with a variety of intracellular targets, and can potentially induce distinct responses in different cell types. In NG108 neuronal cells, activated EphB2 recruits p120RasGAP, in a fashion that is associated with down-regulation of the Ras-Erk mitogen-activated kinase (MAPK) pathway and neurite retraction. To pursue the role of the Ras-MAPK pathway in EphB2-mediated growth cone collapse, and to explore the biochemical and biological functions of Eph receptors, we sought to re-engineer the signaling properties of EphB2 by manipulating its regulatory motifs and SH2 binding sites. An EphB2 mutant that retained juxtamembrane (JM) RasGAP binding sites but incorporated a Grb2 binding motif at an alternate RasGAP binding site within the kinase domain had little effect on basal Erk MAPK activation. In contrast, elimination of all RasGAP binding sites, accompanied by the addition of a Grb2 binding site within the kinase domain, led to an increase in phospho-Erk levels in NG108 cells following ephrin-B1 stimulation. Functional assays indicated a correlation between neurite retraction and the ability of the EphB2 mutants to down-regulate Ras-Erk MAPK signaling. These data suggest that EphB2 can be designed to repress, stabilize, or activate the Ras-Erk MAPK pathway by the manipulation of RasGAP and Grb2 SH2 domain binding sites and support the notion that Erk MAPK regulation plays a significant role in axon guidance. The behavior of EphB2 variants with mutations in the JM region and kinase domains suggests an intricate pattern of regulation and target recognition by Eph receptors.

  19. A canonical correlation analysis-based dynamic bayesian network prior to infer gene regulatory networks from multiple types of biological data.

    Science.gov (United States)

    Baur, Brittany; Bozdag, Serdar

    2015-04-01

    One of the challenging and important computational problems in systems biology is to infer gene regulatory networks (GRNs) of biological systems. Several methods that exploit gene expression data have been developed to tackle this problem. In this study, we propose the use of copy number and DNA methylation data to infer GRNs. We developed an algorithm that scores regulatory interactions between genes based on canonical correlation analysis. In this algorithm, copy number or DNA methylation variables are treated as potential regulator variables, and expression variables are treated as potential target variables. We first validated that the canonical correlation analysis method is able to infer true interactions in high accuracy. We showed that the use of DNA methylation or copy number datasets leads to improved inference over steady-state expression. Our results also showed that epigenetic and structural information could be used to infer directionality of regulatory interactions. Additional improvements in GRN inference can be gleaned from incorporating the result in an informative prior in a dynamic Bayesian algorithm. This is the first study that incorporates copy number and DNA methylation into an informative prior in dynamic Bayesian framework. By closely examining top-scoring interactions with different sources of epigenetic or structural information, we also identified potential novel regulatory interactions.

  20. Damage Spreading in Spatial and Small-world Random Boolean Networks

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Qiming [Fermilab; Teuscher, Christof [Portland State U.

    2014-02-18

    The study of the response of complex dynamical social, biological, or technological networks to external perturbations has numerous applications. Random Boolean Networks (RBNs) are commonly used a simple generic model for certain dynamics of complex systems. Traditionally, RBNs are interconnected randomly and without considering any spatial extension and arrangement of the links and nodes. However, most real-world networks are spatially extended and arranged with regular, power-law, small-world, or other non-random connections. Here we explore the RBN network topology between extreme local connections, random small-world, and pure random networks, and study the damage spreading with small perturbations. We find that spatially local connections change the scaling of the relevant component at very low connectivities ($\\bar{K} \\ll 1$) and that the critical connectivity of stability $K_s$ changes compared to random networks. At higher $\\bar{K}$, this scaling remains unchanged. We also show that the relevant component of spatially local networks scales with a power-law as the system size N increases, but with a different exponent for local and small-world networks. The scaling behaviors are obtained by finite-size scaling. We further investigate the wiring cost of the networks. From an engineering perspective, our new findings provide the key design trade-offs between damage spreading (robustness), the network's wiring cost, and the network's communication characteristics.

  1. Regulatory and biosafety issues in relation to transgenic animals in food and agriculture, feeds containing genetically modified organisms (GMO) and veterinary biologics

    International Nuclear Information System (INIS)

    Kochhar, H.P.S.; Gifford, G.A.; Kahn, S.

    2005-01-01

    Development of an effective regulatory system for genetically engineered animals and their products has been the subject of increasing discussion among researchers, industry and policy developers, as well as the public. Since transgenesis and cloning are relatively new scientific techniques, transgenic animals are new organisms for which there is limited information. The issues associated with the regulation and biosafety of transgenic animals pertain to environmental impact, human food safety, animal health and welfare, trade and ethics. To regulate this new and powerful technology predicated on limited background information is a challenge not only for the regulators, but also for the developers of such animals, who strive to prove that the animals are safe and merit bio-equivalency to their conventional counterparts. In principle, an effective regulatory sieve should permit safe products while forming a formidable barrier for those assessed of posing an unacceptable risk. Adoption of transgenic technology for use in agriculture will depend upon various factors that range from perceived benefits for humans and animals, to safe propagation, animal welfare considerations and integrity of species, as well as effects on bio-diversity. A regulatory framework designed to address the concerns connected with the environmental release of transgenic animals needs to also take into account the ability of genetically modified animals to survive and compete with conventional populations. Regulatory initiatives for biotechnology-derived animals and their products should ensure high standards for human and animal health; a sound scientific basis for evaluation; transparency and public involvement; and maintenance of genetic diversity. Feeds obtained by use of biotechnology have to be evaluated for animal and human safety by using parameters that define their molecular characterization, nutritional qualities and toxicological aspects, while veterinary biologics derived from

  2. Graphene-based non-Boolean logic circuits

    Science.gov (United States)

    Liu, Guanxiong; Ahsan, Sonia; Khitun, Alexander G.; Lake, Roger K.; Balandin, Alexander A.

    2013-10-01

    Graphene revealed a number of unique properties beneficial for electronics. However, graphene does not have an energy band-gap, which presents a serious hurdle for its applications in digital logic gates. The efforts to induce a band-gap in graphene via quantum confinement or surface functionalization have not resulted in a breakthrough. Here we show that the negative differential resistance experimentally observed in graphene field-effect transistors of "conventional" design allows for construction of viable non-Boolean computational architectures with the gapless graphene. The negative differential resistance—observed under certain biasing schemes—is an intrinsic property of graphene, resulting from its symmetric band structure. Our atomistic modeling shows that the negative differential resistance appears not only in the drift-diffusion regime but also in the ballistic regime at the nanometer-scale—although the physics changes. The obtained results present a conceptual change in graphene research and indicate an alternative route for graphene's applications in information processing.

  3. An algebra-based method for inferring gene regulatory networks.

    Science.gov (United States)

    Vera-Licona, Paola; Jarrah, Abdul; Garcia-Puente, Luis David; McGee, John; Laubenbacher, Reinhard

    2014-03-26

    The inference of gene regulatory networks (GRNs) from experimental observations is at the heart of systems biology. This includes the inference of both the network topology and its dynamics. While there are many algorithms available to infer the network topology from experimental data, less emphasis has been placed on methods that infer network dynamics. Furthermore, since the network inference problem is typically underdetermined, it is essential to have the option of incorporating into the inference process, prior knowledge about the network, along with an effective description of the search space of dynamic models. Finally, it is also important to have an understanding of how a given inference method is affected by experimental and other noise in the data used. This paper contains a novel inference algorithm using the algebraic framework of Boolean polynomial dynamical systems (BPDS), meeting all these requirements. The algorithm takes as input time series data, including those from network perturbations, such as knock-out mutant strains and RNAi experiments. It allows for the incorporation of prior biological knowledge while being robust to significant levels of noise in the data used for inference. It uses an evolutionary algorithm for local optimization with an encoding of the mathematical models as BPDS. The BPDS framework allows an effective representation of the search space for algebraic dynamic models that improves computational performance. The algorithm is validated with both simulated and experimental microarray expression profile data. Robustness to noise is tested using a published mathematical model of the segment polarity gene network in Drosophila melanogaster. Benchmarking of the algorithm is done by comparison with a spectrum of state-of-the-art network inference methods on data from the synthetic IRMA network to demonstrate that our method has good precision and recall for the network reconstruction task, while also predicting several of the

  4. TESTING HISTOLOGICAL IMAGES OF MAMMARY TISSUES ON COMPATIBILITY WITH THE BOOLEAN MODEL OF RANDOM SETS

    Directory of Open Access Journals (Sweden)

    Tomáš Mrkvička

    2011-03-01

    Full Text Available Methods for testing the Boolean model assumption from binary images are briefly reviewed. Two hundred binary images of mammary cancer tissue and 200 images of mastopathic tissue were tested individually on the Boolean model assumption. In a previous paper, it had been found that a Monte Carlo method based on the approximation of the envelopes by a multi-normal distribution with the normalized intrinsic volume densities of parallel sets as a summary statistics had the highest power for this purpose. Hence, this method was used here as its first application to real biomedical data. It was found that mastopathic tissue deviates from the Boolean model significantly more strongly than mammary cancer tissue does.

  5. Mechanical system reliability analysis using a combination of graph theory and Boolean function

    International Nuclear Information System (INIS)

    Tang, J.

    2001-01-01

    A new method based on graph theory and Boolean function for assessing reliability of mechanical systems is proposed. The procedure for this approach consists of two parts. By using the graph theory, the formula for the reliability of a mechanical system that considers the interrelations of subsystems or components is generated. Use of the Boolean function to examine the failure interactions of two particular elements of the system, followed with demonstrations of how to incorporate such failure dependencies into the analysis of larger systems, a constructive algorithm for quantifying the genuine interconnections between the subsystems or components is provided. The combination of graph theory and Boolean function provides an effective way to evaluate the reliability of a large, complex mechanical system. A numerical example demonstrates that this method an effective approaches in system reliability analysis

  6. Coded diffraction system in X-ray crystallography using a boolean phase coded aperture approximation

    Science.gov (United States)

    Pinilla, Samuel; Poveda, Juan; Arguello, Henry

    2018-03-01

    Phase retrieval is a problem present in many applications such as optics, astronomical imaging, computational biology and X-ray crystallography. Recent work has shown that the phase can be better recovered when the acquisition architecture includes a coded aperture, which modulates the signal before diffraction, such that the underlying signal is recovered from coded diffraction patterns. Moreover, this type of modulation effect, before the diffraction operation, can be obtained using a phase coded aperture, just after the sample under study. However, a practical implementation of a phase coded aperture in an X-ray application is not feasible, because it is computationally modeled as a matrix with complex entries which requires changing the phase of the diffracted beams. In fact, changing the phase implies finding a material that allows to deviate the direction of an X-ray beam, which can considerably increase the implementation costs. Hence, this paper describes a low cost coded X-ray diffraction system based on block-unblock coded apertures that enables phase reconstruction. The proposed system approximates the phase coded aperture with a block-unblock coded aperture by using the detour-phase method. Moreover, the SAXS/WAXS X-ray crystallography software was used to simulate the diffraction patterns of a real crystal structure called Rhombic Dodecahedron. Additionally, several simulations were carried out to analyze the performance of block-unblock approximations in recovering the phase, using the simulated diffraction patterns. Furthermore, the quality of the reconstructions was measured in terms of the Peak Signal to Noise Ratio (PSNR). Results show that the performance of the block-unblock phase coded apertures approximation decreases at most 12.5% compared with the phase coded apertures. Moreover, the quality of the reconstructions using the boolean approximations is up to 2.5 dB of PSNR less with respect to the phase coded aperture reconstructions.

  7. Ordinary differential equations and Boolean networks in application to modelling of 6-mercaptopurine metabolism.

    Science.gov (United States)

    Lavrova, Anastasia I; Postnikov, Eugene B; Zyubin, Andrey Yu; Babak, Svetlana V

    2017-04-01

    We consider two approaches to modelling the cell metabolism of 6-mercaptopurine, one of the important chemotherapy drugs used for treating acute lymphocytic leukaemia: kinetic ordinary differential equations, and Boolean networks supplied with one controlling node, which takes continual values. We analyse their interplay with respect to taking into account ATP concentration as a key parameter of switching between different pathways. It is shown that the Boolean networks, which allow avoiding the complexity of general kinetic modelling, preserve the possibility of reproducing the principal switching mechanism.

  8. Improving the quantum cost of reversible Boolean functions using reorder algorithm

    Science.gov (United States)

    Ahmed, Taghreed; Younes, Ahmed; Elsayed, Ashraf

    2018-05-01

    This paper introduces a novel algorithm to synthesize a low-cost reversible circuits for any Boolean function with n inputs represented as a Positive Polarity Reed-Muller expansion. The proposed algorithm applies a predefined rules to reorder the terms in the function to minimize the multi-calculation of common parts of the Boolean function to decrease the quantum cost of the reversible circuit. The paper achieves a decrease in the quantum cost and/or the circuit length, on average, when compared with relevant work in the literature.

  9. Boolean Matching Filters Based on Row and Column Weights of Reed–Muller Polarity Coefficient Matrix

    Directory of Open Access Journals (Sweden)

    Chip-Hong Chang

    2002-01-01

    Full Text Available In this article, we have shown, by means of the EXOR Ternary Decision Diagram that the number of literals and product terms of the Fixed Polarity Reed–Muller (FPRM expansions can be used to fully classify all Boolean functions in NP equivalent class and NPN equivalent class, respectively. Efficient graph based algorithms to compute the complete weight vectors have been presented. The proof and computation method has led to the derivation of a set of characteristic signatures that has low probability of aliasing when used as the Boolean matching filters in library mapping.

  10. Fitting Boolean networks from steady state perturbation data.

    Science.gov (United States)

    Almudevar, Anthony; McCall, Matthew N; McMurray, Helene; Land, Hartmut

    2011-10-05

    Gene perturbation experiments are commonly used for the reconstruction of gene regulatory networks. Typical experimental methodology imposes persistent changes on the network. The resulting data must therefore be interpreted as a steady state from an altered gene regulatory network, rather than a direct observation of the original network. In this article an implicit modeling methodology is proposed in which the unperturbed network of interest is scored by first modeling the persistent perturbation, then predicting the steady state, which may then be compared to the observed data. This results in a many-to-one inverse problem, so a computational Bayesian approach is used to assess model uncertainty. The methodology is first demonstrated on a number of synthetic networks. It is shown that the Bayesian approach correctly assigns high posterior probability to the network structure and steady state behavior. Further, it is demonstrated that where uncertainty of model features is indicated, the uncertainty may be accurately resolved with further perturbation experiments. The methodology is then applied to the modeling of a gene regulatory network using perturbation data from nine genes which have been shown to respond synergistically to known oncogenic mutations. A hypothetical model emerges which conforms to reported regulatory properties of these genes. Furthermore, the Bayesian methodology is shown to be consistent in the sense that multiple randomized applications of the fitting algorithm converge to an approximately common posterior density on the space of models. Such consistency is generally not feasible for algorithms which report only single models. We conclude that fully Bayesian methods, coupled with models which accurately account for experimental constraints, are a suitable tool for the inference of gene regulatory networks, in terms of accuracy, estimation of model uncertainty, and experimental design.

  11. A Boolean Consistent Fuzzy Inference System for Diagnosing Diseases and Its Application for Determining Peritonitis Likelihood

    Directory of Open Access Journals (Sweden)

    Ivana Dragović

    2015-01-01

    Full Text Available Fuzzy inference systems (FIS enable automated assessment and reasoning in a logically consistent manner akin to the way in which humans reason. However, since no conventional fuzzy set theory is in the Boolean frame, it is proposed that Boolean consistent fuzzy logic should be used in the evaluation of rules. The main distinction of this approach is that it requires the execution of a set of structural transformations before the actual values can be introduced, which can, in certain cases, lead to different results. While a Boolean consistent FIS could be used for establishing the diagnostic criteria for any given disease, in this paper it is applied for determining the likelihood of peritonitis, as the leading complication of peritoneal dialysis (PD. Given that patients could be located far away from healthcare institutions (as peritoneal dialysis is a form of home dialysis the proposed Boolean consistent FIS would enable patients to easily estimate the likelihood of them having peritonitis (where a high likelihood would suggest that prompt treatment is indicated, when medical experts are not close at hand.

  12. Complete ccc Boolean algebras, the order sequential topology, and a problem of von Neumann

    Czech Academy of Sciences Publication Activity Database

    Balcar, Bohuslav; Jech, Thomas; Pazák, Tomáš

    2005-01-01

    Roč. 37, č. 6 (2005), s. 885-898 ISSN 0024-6093 Institutional research plan: CEZ:AV0Z10750506; CEZ:AV0Z10190503 Keywords : Boolean algebras * Maharam submeasure * weak distributivity * independent reals Subject RIV: BA - General Mathematics Impact factor: 0.477, year: 2005

  13. Characterization of Boolean Algebras in Terms of Certain States of Jauch-Piron Type

    Science.gov (United States)

    Matoušek, Milan; Pták, Pavel

    2015-12-01

    Suppose that L is an orthomodular lattice (a quantum logic). We show that L is Boolean exactly if L possesses a strongly unital set of weakly Jauch-Piron states, or if L possesses a unital set of weakly positive states. We also discuss some general properties of Jauch-Piron-like states.

  14. Yes/No/Maybe: A Boolean attempt at feedback | Louw | Journal for ...

    African Journals Online (AJOL)

    This paper describes an experiment in which Boolean feedback (a kind of checklist) was used to provide feedback on the paragraph structures of first year students in an Academic Literacy course. We begin by introducing the major problems with feedback on L2 writing and establishing why a focus on paragraph structures ...

  15. The Concept of the "Imploded Boolean Search": A Case Study with Undergraduate Chemistry Students

    Science.gov (United States)

    Tomaszewski, Robert

    2016-01-01

    Critical thinking and analytical problem-solving skills in research involves using different search strategies. A proposed concept for an "Imploded Boolean Search" combines three unique identifiable field types to perform a search: keyword(s), numerical value(s), and a chemical structure or reaction. The object of this type of search is…

  16. GBL-2D Version 1.0: a 2D geometry boolean library.

    Energy Technology Data Exchange (ETDEWEB)

    McBride, Cory L. (Elemental Technologies, American Fort, UT); Schmidt, Rodney Cannon; Yarberry, Victor R.; Meyers, Ray J. (Elemental Technologies, American Fort, UT)

    2006-11-01

    This report describes version 1.0 of GBL-2D, a geometric Boolean library for 2D objects. The library is written in C++ and consists of a set of classes and routines. The classes primarily represent geometric data and relationships. Classes are provided for 2D points, lines, arcs, edge uses, loops, surfaces and mask sets. The routines contain algorithms for geometric Boolean operations and utility functions. Routines are provided that incorporate the Boolean operations: Union(OR), XOR, Intersection and Difference. A variety of additional analytical geometry routines and routines for importing and exporting the data in various file formats are also provided. The GBL-2D library was originally developed as a geometric modeling engine for use with a separate software tool, called SummitView [1], that manipulates the 2D mask sets created by designers of Micro-Electro-Mechanical Systems (MEMS). However, many other practical applications for this type of software can be envisioned because the need to perform 2D Boolean operations can arise in many contexts.

  17. Computable categoricity of the Boolean algebra B(omega) with a distinguished automorphism

    Czech Academy of Sciences Publication Activity Database

    Bazhenov, N. A.; Tukhbatullina, Regina

    2013-01-01

    Roč. 52, č. 2 (2013), s. 89-97 ISSN 0002-5232 Institutional support: PRVOUK-P23 Keywords : Boolean algebra with distinguished automorphism * computable categoricity * categoricity spectrum Subject RIV: BA - General Mathematics Impact factor: 0.488, year: 2013

  18. Analysis and control of Boolean networks a semi-tensor product approach

    CERN Document Server

    Cheng, Daizhan; Li, Zhiqiang

    2010-01-01

    This book presents a new approach to the investigation of Boolean control networks, using the semi-tensor product (STP), which can express a logical function as a conventional discrete-time linear system. This makes it possible to analyze basic control problems.

  19. Comparison of Detection and Classification Algorithms Using Boolean and Fuzzy Techniques

    Directory of Open Access Journals (Sweden)

    Rahul Dixit

    2012-01-01

    Full Text Available Modern military ranging, tracking, and classification systems are capable of generating large quantities of data. Conventional “brute-force” computational techniques, even with Moore’s law for processors, present a prohibitive computational challenge, and often, the system either fails to “lock onto” a target of interest within the available duty cycle, or the data stream is simply discarded because the system runs out of processing power or time. In searching for high-fidelity convergence, researchers have experimented with various reduction techniques, often using logic diagrams to make inferences from related signal data. Conventional Boolean and fuzzy logic systems generate a very large number of rules, which often are difficult to handle due to limitations in the processors. Published research has shown that reasonable approximations of the target are preferred over incomplete computations. This paper gives a figure of merit for comparing various logic analysis methods and presents results for a hypothetical target classification scenario. Novel multiquantization Boolean approaches also reduce the complexity of these multivariate analyses, making it possible to better use the available data to approximate target classification. This paper shows how such preprocessing can reasonably preserve result confidence and compares the results between Boolean, multi-quantization Boolean, and fuzzy techniques.

  20. Evolutionary approaches for the reverse-engineering of gene regulatory networks: A study on a biologically realistic dataset

    Directory of Open Access Journals (Sweden)

    Gidrol Xavier

    2008-02-01

    Full Text Available Abstract Background Inferring gene regulatory networks from data requires the development of algorithms devoted to structure extraction. When only static data are available, gene interactions may be modelled by a Bayesian Network (BN that represents the presence of direct interactions from regulators to regulees by conditional probability distributions. We used enhanced evolutionary algorithms to stochastically evolve a set of candidate BN structures and found the model that best fits data without prior knowledge. Results We proposed various evolutionary strategies suitable for the task and tested our choices using simulated data drawn from a given bio-realistic network of 35 nodes, the so-called insulin network, which has been used in the literature for benchmarking. We assessed the inferred models against this reference to obtain statistical performance results. We then compared performances of evolutionary algorithms using two kinds of recombination operators that operate at different scales in the graphs. We introduced a niching strategy that reinforces diversity through the population and avoided trapping of the algorithm in one local minimum in the early steps of learning. We show the limited effect of the mutation operator when niching is applied. Finally, we compared our best evolutionary approach with various well known learning algorithms (MCMC, K2, greedy search, TPDA, MMHC devoted to BN structure learning. Conclusion We studied the behaviour of an evolutionary approach enhanced by niching for the learning of gene regulatory networks with BN. We show that this approach outperforms classical structure learning methods in elucidating the original model. These results were obtained for the learning of a bio-realistic network and, more importantly, on various small datasets. This is a suitable approach for learning transcriptional regulatory networks from real datasets without prior knowledge.

  1. Biology

    Indian Academy of Sciences (India)

    I am particularly happy that the Academy is bringing out this document by Professor M S. Valiathan on Ayurvedic Biology. It is an effort to place before the scientific community, especially that of India, the unique scientific opportunities that arise out of viewing Ayurveda from the perspective of contemporary science, its tools ...

  2. A systems biology approach identified different regulatory networks targeted by KSHV miR-K12-11 in B cells and endothelial cells.

    Science.gov (United States)

    Yang, Yajie; Boss, Isaac W; McIntyre, Lauren M; Renne, Rolf

    2014-08-08

    Kaposi's sarcoma associated herpes virus (KSHV) is associated with tumors of endothelial and lymphoid origin. During latent infection, KSHV expresses miR-K12-11, an ortholog of the human tumor gene hsa-miR-155. Both gene products are microRNAs (miRNAs), which are important post-transcriptional regulators that contribute to tissue specific gene expression. Advances in target identification technologies and molecular interaction databases have allowed a systems biology approach to unravel the gene regulatory networks (GRNs) triggered by miR-K12-11 in endothelial and lymphoid cells. Understanding the tissue specific function of miR-K12-11 will help to elucidate underlying mechanisms of KSHV pathogenesis. Ectopic expression of miR-K12-11 differentially affected gene expression in BJAB cells of lymphoid origin and TIVE cells of endothelial origin. Direct miRNA targeting accounted for a small fraction of the observed transcriptome changes: only 29 genes were identified as putative direct targets of miR-K12-11 in both cell types. However, a number of commonly affected biological pathways, such as carbohydrate metabolism and interferon response related signaling, were revealed by gene ontology analysis. Integration of transcriptome profiling, bioinformatic algorithms, and databases of protein-protein interactome from the ENCODE project identified different nodes of GRNs utilized by miR-K12-11 in a tissue-specific fashion. These effector genes, including cancer associated transcription factors and signaling proteins, amplified the regulatory potential of a single miRNA, from a small set of putative direct targets to a larger set of genes. This is the first comparative analysis of miRNA-K12-11's effects in endothelial and B cells, from tissues infected with KSHV in vivo. MiR-K12-11 was able to broadly modulate gene expression in both cell types. Using a systems biology approach, we inferred that miR-K12-11 establishes its GRN by both repressing master TFs and influencing

  3. HlMyb3, a putative regulatory factor in hop (Humulus lupulus L.), shows diverse biological effects in heterologous transgenotes

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Jaroslav; Kocábek, Tomáš; Patzak, J.; Škopek, Josef; Maloukh, L.; Heyerick, A.; Füssy, Z.; Roldán-Ruiz, I.; De Keukeleire, D.

    2007-01-01

    Roč. 55, č. 19 (2007), s. 7767-7776 ISSN 0021-8561 R&D Projects: GA ČR GA521/03/0072; GA MŠk ME 940 Institutional research plan: CEZ:AV0Z50510513 Keywords : cDNA library * Humulus lupulus L. Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.532, year: 2007

  4. Synthetic biology between challenges and risks: suggestions for a model of governance and a regulatory framework, based on fundamental rights.

    Science.gov (United States)

    Colussi, Ilaria Anna

    2013-01-01

    This paper deals with the emerging synthetic biology, its challenges and risks, and tries to design a model for the governance and regulation of the field. The model is called of "prudent vigilance" (inspired by the report about synthetic biology, drafted by the U.S. Presidential Commission on Bioethics, 2010), and it entails (a) an ongoing and periodically revised process of assessment and management of all the risks and concerns, and (b) the adoption of policies - taken through "hard law" and "soft law" sources - that are based on the principle of proportionality (among benefits and risks), on a reasonable balancing between different interests and rights at stake, and are oriented by a constitutional frame, which is represented by the protection of fundamental human rights emerging in the field of synthetic biology (right to life, right to health, dignity, freedom of scientific research, right to environment). After the theoretical explanation of the model, its operability is "checked", by considering its application with reference to only one specific risk brought up by synthetic biology - biosecurity risk, i.e. the risk of bioterrorism.

  5. Matrix formalism to describe functional states of transcriptional regulatory systems.

    Directory of Open Access Journals (Sweden)

    Erwin P Gianchandani

    2006-08-01

    Full Text Available Complex regulatory networks control the transcription state of a genome. These transcriptional regulatory networks (TRNs have been mathematically described using a Boolean formalism, in which the state of a gene is represented as either transcribed or not transcribed in response to regulatory signals. The Boolean formalism results in a series of regulatory rules for the individual genes of a TRN that in turn can be used to link environmental cues to the transcription state of a genome, thereby forming a complete transcriptional regulatory system (TRS. Herein, we develop a formalism that represents such a set of regulatory rules in a matrix form. Matrix formalism allows for the systemic characterization of the properties of a TRS and facilitates the computation of the transcriptional state of the genome under any given set of environmental conditions. Additionally, it provides a means to incorporate mechanistic detail of a TRS as it becomes available. In this study, the regulatory network matrix, R, for a prototypic TRS is characterized and the fundamental subspaces of this matrix are described. We illustrate how the matrix representation of a TRS coupled with its environment (R* allows for a sampling of all possible expression states of a given network, and furthermore, how the fundamental subspaces of the matrix provide a way to study key TRS features and may assist in experimental design.

  6. [Life as regulatory activity and self-realization: debate surrounding the concept of biological regulation in Goldstein and Canguilhem].

    Science.gov (United States)

    Ostachuk, Agustín

    2015-12-01

    The influence of Kurt Goldstein on the thinking of Georges Canguilhem extended throughout his entire work. This paper seeks to examine this relationship in order to conduct a study of the norm as a nexus or connection between the concept and life. Consequently, this work will be a reflection on the approach to life as a regulatory activity and self-realization. For this, it will be necessary to redefine the concepts of health and disease, and make a crossover between the two. At the end of this trajectory, it will be found that these concepts can explain the identity between the concept and life, which leads to the unexpected conclusion that the cure is ultimately self-healing.

  7. Regulatory dynamics of network architecture and function in tristable genetic circuit of Leishmania: a mathematical biology approach.

    Science.gov (United States)

    Mandlik, Vineetha; Gurav, Mayuri; Singh, Shailza

    2015-01-01

    The emerging field of synthetic biology has led to the design of tailor-made synthetic circuits for several therapeutic applications. Biological networks can be reprogramed by designing synthetic circuits that modulate the expression of target proteins. IPCS (inositol phosphorylceramide synthase) has been an attractive target in the sphingolipid metabolism of the parasite Leishmania. In this study, we have constructed a tristable circuit for the IPCS protein. The circuit has been validated and its long-term behavior has been assessed. The robustness and evolvability of the circuit has been estimated using evolutionary algorithms. The tristable synthetic circuit has been specifically designed to improve the rate of production of phosphatidylcholine: ceramide cholinephosphotransferase 4 (SLS4 protein). Site-specific delivery of the circuit into the parasite-infected macrophages could serve as a possible therapeutic intervention of the infectious disease 'Leishmaniasis'.

  8. The Biology of Autoimmune Response in the Scurfy Mice that Lack the CD4+Foxp3+ Regulatory T-Cells.

    Science.gov (United States)

    Ju, Shyr-Te; Sharma, Rahul; Gaskin, Felicia; Kung, John T; Fu, Shu Man

    2012-04-04

    Due to a mutation in the Foxp3 transcription factor, Scurfy mice lack regulatory T-cells that maintain self-tolerance of the immune system. They develop multi-organ inflammation (MOI) and die around four weeks old. The affected organs are skin, tail, lungs and liver. In humans, endocrine and gastrointestinal inflammation are also observed, hence the disease is termed IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome. The three week period of fatal MOI offers a useful autoimmune model in which the controls by genetics, T-cell subsets, cytokines, and effector mechanisms could be efficiently investigated. In this report, we will review published work, summarize our recent studies of Scurfy double mutants lacking specific autoimmune-related genes, discuss the cellular and cytokine controls by these genes on MOI, the organ-specificities of the MOI controlled by environments, and the effector mechanisms regulated by specific Th cytokines, including several newly identified control mechanisms for organ-specific autoimmune response.

  9. A GA-P algorithm to automatically formulate extended Boolean queries for a fuzzy information retrieval system

    OpenAIRE

    Cordón García, Oscar; Moya Anegón, Félix de; Zarco Fernández, Carmen

    2000-01-01

    [ES] Although the fuzzy retrieval model constitutes a powerful extension of the boolean one, being able to deal with the imprecision and subjectivity existing in the Information Retrieval process, users are not usually able to express their query requirements in the form of an extended boolean query including weights. To solve this problem, different tools to assist the user in the query formulation have been proposed. In this paper, the genetic algorithm-programming technique is considered t...

  10. A system biology approach to identify regulatory pathways underlying the neuroendocrine control of female puberty in rats and nonhuman primates.

    Science.gov (United States)

    Lomniczi, Alejandro; Wright, Hollis; Castellano, Juan Manuel; Sonmez, Kemal; Ojeda, Sergio R

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Puberty is a major developmental milestone controlled by the interaction of genetic factors and environmental cues of mostly metabolic and circadian nature. An increased pulsatile release of the decapeptide gonadotropin releasing hormone (GnRH) from hypothalamic neurosecretory neurons is required for both the initiation and progression of the pubertal process. This increase is brought about by coordinated changes that occur in neuronal and glial networks associated with GnRH neurons. These changes ultimately result in increased neuronal and glial stimulatory inputs to the GnRH neuronal network and a reduction of transsynaptic inhibitory influences. While some of the major players controlling pubertal GnRH secretion have been identified using gene-centric approaches, much less is known about the system-wide control of the overall process. Because the pubertal activation of GnRH release involves a diversity of cellular phenotypes, and a myriad of intracellular and cell-to-cell signaling molecules, it appears that the overall process is controlled by a highly coordinated and interactive regulatory system involving hundreds, if not thousands, of gene products. In this article we will discuss emerging evidence suggesting that these genes are arranged as functionally connected networks organized, both internally and across sub-networks, in a hierarchical fashion. According to this concept, the core of these networks is composed of transcriptional regulators that, by directing expression of downstream subordinate genes, provide both stability and coordination to the cellular networks involved in initiating the pubertal process. The integrative response of these gene networks to external inputs is postulated to be coordinated by epigenetic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. CIRCUIT IMPLEMENTATION OF VHDL-DESCRIPTIONS OF SYSTEMS OF PARTIAL BOOLEAN FUNCTIONS

    Directory of Open Access Journals (Sweden)

    P. N. Bibilo

    2016-01-01

    Full Text Available Method for description of incompletely specified (partial Boolean functions in VHDL is proposed. Examples of synthesized VHDL models of partial Boolean functions are presented; and the results of experiments on circuit implementation of VHDL descriptions of systems of partial functions. The realizability of original partial functions in logical circuits was verified by formal verification. The results of the experiments show that the preliminary minimization in DNF class and in the class of BDD representations for pseudo-random systems of completely specified functions does not improve practically (and in the case of BDD sometimes worsens the results of the subsequent synthesis in the basis of FPGA unlike the significant efficiency of these procedures for the synthesis of benchmark circuits taken from the practice of the design.

  12. Hypercontractive inequality for pseudo-Boolean functions of bounded Fourier width

    DEFF Research Database (Denmark)

    Gutin, Gregory; Yeo, Anders

    2012-01-01

    A function f: -1,1n→R is called pseudo-Boolean. It is well-known that each pseudo-Boolean function f can be written as f(x)=∑ I∈Ff̂(I) χI(x), where F⊆I:I⊆[n], [n]=1,2,...,n, χI(x)= ∏ i∈I xi and f̂(I) are non-zero reals. The degree of f is max|I|:I∈F and the width of f is the minimum integer ρ suc...... for each q>papplications, we prove a stronger inequality: || f||4≤( 2ρ+1)14|| f||2....

  13. Complete CCC Boolean Algebras, the order Sequential Topology, and a Problem of von Neumann

    Czech Academy of Sciences Publication Activity Database

    Balcar, Bohuslav; Jech, Thomas; Pazák, Tomáš

    2005-01-01

    Roč. 37, č. 6 (2005), s. 885-898 ISSN 0024-6093 R&D Projects: GA ČR(CZ) GA201/02/0857; GA ČR(CZ) GA201/03/0933 Institutional research plan: CEZ:AV0Z10190503 Keywords : Boolean algebra * Maharam submeasure * weak distributivity Subject RIV: BA - General Mathematics Impact factor: 0.477, year: 2005

  14. Rates of Minimization of Error Functionals over Boolean Variable-Basis Functions

    Czech Academy of Sciences Publication Activity Database

    Kainen, P.C.; Kůrková, Věra; Sanguineti, M.

    2005-01-01

    Roč. 4, č. 4 (2005), s. 355-368 ISSN 1570-1166 R&D Projects: GA ČR GA201/02/0428; GA ČR GA201/05/0557 Grant - others:Area MC 6(EU) Project 22 Institutional research plan: CEZ:AV0Z10300504 Keywords : high-dimensional optimization * minimizing sequences * Boolean decision functions * decision tree Subject RIV: BA - General Mathematics

  15. Recurrent Neural Network Based Boolean Factor Analysis and its Application to Word Clustering

    Czech Academy of Sciences Publication Activity Database

    Frolov, A. A.; Húsek, Dušan; Polyakov, P.Y.

    2009-01-01

    Roč. 20, č. 7 (2009), s. 1073-1086 ISSN 1045-9227 R&D Projects: GA MŠk(CZ) 1M0567 Institutional research plan: CEZ:AV0Z10300504 Keywords : recurrent neural network * Hopfield-like neural network * associative memory * unsupervised learning * neural network architecture * neural network application * statistics * Boolean factor analysis * concepts search * information retrieval Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.889, year: 2009

  16. Comparison of Seven Methods for Boolean Factor Analysis and Their Evaluation by Information Gain

    Czech Academy of Sciences Publication Activity Database

    Frolov, A.; Húsek, Dušan; Polyakov, P.Y.

    2016-01-01

    Roč. 27, č. 3 (2016), s. 538-550 ISSN 2162-237X R&D Projects: GA MŠk ED1.1.00/02.0070 Institutional support: RVO:67985807 Keywords : associative memory * bars problem (BP) * Boolean factor analysis (BFA) * data mining * dimension reduction * Hebbian learning rule * information gain * likelihood maximization (LM) * neural network application * recurrent neural network * statistics Subject RIV: IN - Informatics, Computer Science Impact factor: 6.108, year: 2016

  17. Representations and Rates of Approximation of Real-Valued Boolean Functions by Neural Networks

    Czech Academy of Sciences Publication Activity Database

    Kůrková, Věra; Savický, Petr; Hlaváčková, Kateřina

    1998-01-01

    Roč. 11, č. 4 (1998), s. 651-659 ISSN 0893-6080 R&D Projects: GA AV ČR IAA2030602; GA AV ČR IAA2075606; GA ČR GA201/95/0976 Keywords : real-valued Boolean function * percepron network * rate of approximation * variation with respect to half-spaces * decision tree * Hadamard communication matrix Subject RIV: BA - General Mathematics Impact factor: 1.017, year: 1998

  18. Completely positive matrices over Boolean algebras and their CP-rank

    Directory of Open Access Journals (Sweden)

    Mohindru Preeti

    2015-04-01

    Full Text Available Drew, Johnson and Loewy conjectured that for n ≥ 4, the CP-rank of every n × n completely positive real matrix is at most [n2/4]. In this paper, we prove this conjecture for n × n completely positive matrices over Boolean algebras (finite or infinite. In addition,we formulate various CP-rank inequalities of completely positive matrices over special semirings using semiring homomorphisms.

  19. Examination of the regulatory frameworks applicable to biologic drugs (including stem cells and their progeny) in Europe, the U.S., and Australia: part I--a method of manual documentary analysis.

    Science.gov (United States)

    Ilic, Nina; Savic, Snezana; Siegel, Evan; Atkinson, Kerry; Tasic, Ljiljana

    2012-12-01

    Recent development of a wide range of regulatory standards applicable to production and use of tissues, cells, and other biologics (or biologicals), as advanced therapies, indicates considerable interest in the regulation of these products. The objective of this study was to analyze and compare high-tier documents within the Australian, European, and U.S. biologic drug regulatory environments using qualitative methodology. Cohort 1 of the selected 18 high-tier regulatory documents from the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and the Therapeutic Goods Administration (TGA) regulatory frameworks were subject to a manual documentary analysis. These documents were consistent with the legal requirements for manufacturing and use of biologic drugs in humans and fall into six different categories. Manual analysis included a terminology search. The occurrence, frequency, and interchangeable use of different terms and phrases were recorded in the manual documentary analysis. Despite obvious differences, manual documentary analysis revealed certain consistency in use of terminology across analyzed frameworks. Phrase search frequencies have shown less uniformity than the search of terms. Overall, the EMA framework's documents referred to "medicinal products" and "marketing authorization(s)," the FDA documents discussed "drug(s)" or "biologic(s)," and the TGA documents referred to "biological(s)." Although high-tier documents often use different terminology they share concepts and themes. Documents originating from the same source have more conjunction in their terminology although they belong to different frameworks (i.e., Good Clinical Practice requirements based on the Declaration of Helsinki, 1964). Automated (software-based) documentary analysis should be obtained for the conceptual and relational analysis.

  20. PATHLOGIC-S: a scalable Boolean framework for modelling cellular signalling.

    Directory of Open Access Journals (Sweden)

    Liam G Fearnley

    Full Text Available Curated databases of signal transduction have grown to describe several thousand reactions, and efficient use of these data requires the development of modelling tools to elucidate and explore system properties. We present PATHLOGIC-S, a Boolean specification for a signalling model, with its associated GPL-licensed implementation using integer programming techniques. The PATHLOGIC-S specification has been designed to function on current desktop workstations, and is capable of providing analyses on some of the largest currently available datasets through use of Boolean modelling techniques to generate predictions of stable and semi-stable network states from data in community file formats. PATHLOGIC-S also addresses major problems associated with the presence and modelling of inhibition in Boolean systems, and reduces logical incoherence due to common inhibitory mechanisms in signalling systems. We apply this approach to signal transduction networks including Reactome and two pathways from the Panther Pathways database, and present the results of computations on each along with a discussion of execution time. A software implementation of the framework and model is freely available under a GPL license.

  1. Integer programming-based method for designing synthetic metabolic networks by Minimum Reaction Insertion in a Boolean model.

    Science.gov (United States)

    Lu, Wei; Tamura, Takeyuki; Song, Jiangning; Akutsu, Tatsuya

    2014-01-01

    In this paper, we consider the Minimum Reaction Insertion (MRI) problem for finding the minimum number of additional reactions from a reference metabolic network to a host metabolic network so that a target compound becomes producible in the revised host metabolic network in a Boolean model. Although a similar problem for larger networks is solvable in a flux balance analysis (FBA)-based model, the solution of the FBA-based model tends to include more reactions than that of the Boolean model. However, solving MRI using the Boolean model is computationally more expensive than using the FBA-based model since the Boolean model needs more integer variables. Therefore, in this study, to solve MRI for larger networks in the Boolean model, we have developed an efficient Integer Programming formalization method in which the number of integer variables is reduced by the notion of feedback vertex set and minimal valid assignment. As a result of computer experiments conducted using the data of metabolic networks of E. coli and reference networks downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we have found that the developed method can appropriately solve MRI in the Boolean model and is applicable to large scale-networks for which an exhaustive search does not work. We have also compared the developed method with the existing connectivity-based methods and FBA-based methods, and show the difference between the solutions of our method and the existing methods. A theoretical analysis of MRI is also conducted, and the NP-completeness of MRI is proved in the Boolean model. Our developed software is available at "http://sunflower.kuicr.kyoto-u.ac.jp/~rogi/minRect/minRect.html."

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

    Directory of Open Access Journals (Sweden)

    Saurabh Vashishtha

    Full Text Available 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.

  3. Model checking optimal finite-horizon control for probabilistic gene regulatory networks.

    Science.gov (United States)

    Wei, Ou; Guo, Zonghao; Niu, Yun; Liao, Wenyuan

    2017-12-14

    Probabilistic Boolean networks (PBNs) have been proposed for analyzing external control in gene regulatory networks with incorporation of uncertainty. A context-sensitive PBN with perturbation (CS-PBNp), extending a PBN with context-sensitivity to reflect the inherent biological stability and random perturbations to express the impact of external stimuli, is considered to be more suitable for modeling small biological systems intervened by conditions from the outside. In this paper, we apply probabilistic model checking, a formal verification technique, to optimal control for a CS-PBNp that minimizes the expected cost over a finite control horizon. We first describe a procedure of modeling a CS-PBNp using the language provided by a widely used probabilistic model checker PRISM. We then analyze the reward-based temporal properties and the computation in probabilistic model checking; based on the analysis, we provide a method to formulate the optimal control problem as minimum reachability reward properties. Furthermore, we incorporate control and state cost information into the PRISM code of a CS-PBNp such that automated model checking a minimum reachability reward property on the code gives the solution to the optimal control problem. We conduct experiments on two examples, an apoptosis network and a WNT5A network. Preliminary experiment results show the feasibility and effectiveness of our approach. The approach based on probabilistic model checking for optimal control avoids explicit computation of large-size state transition relations associated with PBNs. It enables a natural depiction of the dynamics of gene regulatory networks, and provides a canonical form to formulate optimal control problems using temporal properties that can be automated solved by leveraging the analysis power of underlying model checking engines. This work will be helpful for further utilization of the advances in formal verification techniques in system biology.

  4. Regulatory effect of evodiamine on the malignant biological behaviors and Wnt/β-catenin signaling pathway of colorectal cancer cell lines HT29

    Directory of Open Access Journals (Sweden)

    Yuan-Hui Wang

    2016-04-01

    Full Text Available Objective: To study the regulatory effect of evodiamine on the malignant biological behaviors and Wnt/β-catenin signaling pathway of colorectal cancer cell lines HT29. Methods: Colorectal cancer cell lines HT29 were cultured and divided into blank control group and evodiamine group, and after different treatment, cell viability, proportion of different cell cycle as well as the contents of VEGFA, VEGFB, VEGFC, MMP3, MMP14, Wnt and β-catenin were detected. Results: (1 Cell viability: MTT value of evodiamine group was significantly lower than that of blank control group; (2 Cell cycle: proportion of both S phase and G2/M phase of evodiamine group were lower than those of blank control group, and proportion of G0/ G1 phase was higher than that of blank control group; (3 VEGF and MMP contents: VEGFA, VEGFB, VEGFC, MMP3 and MMP14 contents of evodiamine group were lower than those of blank control group; (4 Wnt/β-catenin signaling pathway: Wnt and β-catenin contents of evodiamine group were lower than those of blank control group. Conclusion: Evodiamine can inhibit the proliferation of colorectal cancer cell lines HT29 and down-regulate the expression of VEGF and MMP, and the effect may be achieved by inhibiting the activation of Wnt/β-catenin signaling pathway.

  5. Variances as order parameter and complexity measure for random Boolean networks

    International Nuclear Information System (INIS)

    Luque, Bartolo; Ballesteros, Fernando J; Fernandez, Manuel

    2005-01-01

    Several order parameters have been considered to predict and characterize the transition between ordered and disordered phases in random Boolean networks, such as the Hamming distance between replicas or the stable core, which have been successfully used. In this work, we propose a natural and clear new order parameter: the temporal variance. We compute its value analytically and compare it with the results of numerical experiments. Finally, we propose a complexity measure based on the compromise between temporal and spatial variances. This new order parameter and its related complexity measure can be easily applied to other complex systems

  6. A quantum speedup in machine learning: finding an N-bit Boolean function for a classification

    International Nuclear Information System (INIS)

    Yoo, Seokwon; Lee, Jinhyoung; Bang, Jeongho; Lee, Changhyoup

    2014-01-01

    We compare quantum and classical machines designed for learning an N-bit Boolean function in order to address how a quantum system improves the machine learning behavior. The machines of the two types consist of the same number of operations and control parameters, but only the quantum machines utilize the quantum coherence naturally induced by unitary operators. We show that quantum superposition enables quantum learning that is faster than classical learning by expanding the approximate solution regions, i.e., the acceptable regions. This is also demonstrated by means of numerical simulations with a standard feedback model, namely random search, and a practical model, namely differential evolution. (paper)

  7. A new separation algorithm for the Boolean quadric and cut polytopes

    DEFF Research Database (Denmark)

    Sørensen, Michael Malmros; Letchford, Adam N.

    2014-01-01

    present a new algorithm, which separates over a class of valid inequalities that includes all odd bicycle wheel inequalities and (2p+1,2)(2p+1,2)-circulant inequalities. It exploits, in a non-trivial way, three known results in the literature: one on the separation of View the MathML source{0,12}-cuts......A separation algorithm is a procedure for generating cutting planes. Up to now, only a few polynomial-time separation algorithms were known for the Boolean quadric and cut polytopes. These polytopes arise in connection with zero–one quadratic programming and the max-cut problem, respectively. We...

  8. Approximating the Influence of a monotone Boolean function in O(\\sqrt{n}) query complexity

    OpenAIRE

    Ron, Dana; Rubinfeld, Ronitt; Safra, Muli; Weinstein, Omri

    2011-01-01

    The {\\em Total Influence} ({\\em Average Sensitivity) of a discrete function is one of its fundamental measures. We study the problem of approximating the total influence of a monotone Boolean function \\ifnum\\plusminus=1 $f: \\{\\pm1\\}^n \\longrightarrow \\{\\pm1\\}$, \\else $f: \\bitset^n \\to \\bitset$, \\fi which we denote by $I[f]$. We present a randomized algorithm that approximates the influence of such functions to within a multiplicative factor of $(1\\pm \\eps)$ by performing $O(\\frac{\\sqrt{n}\\log...

  9. Efficient Multi-Valued Bounded Model Checking for LTL over Quasi-Boolean Algebras

    OpenAIRE

    Andrade, Jefferson O.; Kameyama, Yukiyoshi

    2012-01-01

    Multi-valued Model Checking extends classical, two-valued model checking to multi-valued logic such as Quasi-Boolean logic. The added expressivity is useful in dealing with such concepts as incompleteness and uncertainty in target systems, while it comes with the cost of time and space. Chechik and others proposed an efficient reduction from multi-valued model checking problems to two-valued ones, but to the authors' knowledge, no study was done for multi-valued bounded model checking. In thi...

  10. Assessment of Electronic Circuits Reliability Using Boolean Truth Table Modeling Method

    International Nuclear Information System (INIS)

    EI-Shanshoury, A.I.

    2011-01-01

    This paper explores the use of Boolean Truth Table modeling Method (BTTM) in the analysis of qualitative data. It is widely used in certain fields especially in the fields of electrical and electronic engineering. Our work focuses on the evaluation of power supply circuit reliability using (BTTM) which involves systematic attempts to falsify and identify hypotheses on the basis of truth tables constructed from qualitative data. Reliability parameters such as the system's failure rates for the power supply case study are estimated. All possible state combinations (operating and failed states) of the major components in the circuit were listed and their effects on overall system were studied

  11. Qubits and quantum Hamiltonian computing performances for operating a digital Boolean 1/2-adder

    Science.gov (United States)

    Dridi, Ghassen; Faizy Namarvar, Omid; Joachim, Christian

    2018-04-01

    Quantum Boolean (1 + 1) digits 1/2-adders are designed with 3 qubits for the quantum computing (Qubits) and 4 quantum states for the quantum Hamiltonian computing (QHC) approaches. Detailed analytical solutions are provided to analyse the time operation of those different 1/2-adder gates. QHC is more robust to noise than Qubits and requires about the same amount of energy for running its 1/2-adder logical operations. QHC is faster in time than Qubits but its logical output measurement takes longer.

  12. Construction of a fuzzy and all Boolean logic gates based on DNA

    DEFF Research Database (Denmark)

    M. Zadegan, Reza; Jepsen, Mette D E; Hildebrandt, Lasse

    2015-01-01

    to the operation of the six Boolean logic gates AND, NAND, OR, NOR, XOR, and XNOR. The logic gate complex is shown to work also when implemented in a three-dimensional DNA origami box structure, where it controlled the position of the lid in a closed or open position. Implementation of multiple microRNA sensitive...... DNA locks on one DNA origami box structure enabled fuzzy logical operation that allows biosensing of complex molecular signals. Integrating logic gates with DNA origami systems opens a vast avenue to applications in the fields of nanomedicine for diagnostics and therapeutics....

  13. Variances as order parameter and complexity measure for random Boolean networks

    Energy Technology Data Exchange (ETDEWEB)

    Luque, Bartolo [Departamento de Matematica Aplicada y EstadIstica, Escuela Superior de Ingenieros Aeronauticos, Universidad Politecnica de Madrid, Plaza Cardenal Cisneros 3, Madrid 28040 (Spain); Ballesteros, Fernando J [Observatori Astronomic, Universitat de Valencia, Ed. Instituts d' Investigacio, Pol. La Coma s/n, E-46980 Paterna, Valencia (Spain); Fernandez, Manuel [Departamento de Matematica Aplicada y EstadIstica, Escuela Superior de Ingenieros Aeronauticos, Universidad Politecnica de Madrid, Plaza Cardenal Cisneros 3, Madrid 28040 (Spain)

    2005-02-04

    Several order parameters have been considered to predict and characterize the transition between ordered and disordered phases in random Boolean networks, such as the Hamming distance between replicas or the stable core, which have been successfully used. In this work, we propose a natural and clear new order parameter: the temporal variance. We compute its value analytically and compare it with the results of numerical experiments. Finally, we propose a complexity measure based on the compromise between temporal and spatial variances. This new order parameter and its related complexity measure can be easily applied to other complex systems.

  14. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  15. On a coverage process ranging from the Boolean model to the Poisson–Voronoi tessellation with applications to wireless communications

    OpenAIRE

    Baccelli, François; Błaszczyszyn, Bartłomiej

    2001-01-01

    Projet MCR; We define and analyze a random coverage process of the $d$-dimensional Euclidian space which allows one to describe a continuous spectrum that ranges from the Boolean model to the Poisson-Voronoi tessellation to the Johnson-Mehl model. Like for the Boolean model, the minimal stochastic setting consists of a Poisson point process on this Euclidian space and a sequence of real valued random variables considered as marks of this point process. In this coverage process, the cell attac...

  16. Finding optimal control policy in probabilistic Boolean Networks with hard constraints by using integer programming and dynamic programming.

    Science.gov (United States)

    Chen, Xi; Akutsu, Tatsuya; Tamura, Takeyuki; Ching, Wai-Ki

    2013-01-01

    Boolean Networks (BNs) and Probabilistic Boolean Networks (PBNs) are studied in this paper from the viewpoint of control problems. For BN CONTROL, by applying external control, we propose to derive the network to the desired state within a few time steps. For PBN CONTROL, we propose to find a control sequence such that the network will terminate in the desired state with a maximum probability. Also, we propose to minimise the maximum cost of the terminal state to which the network will enter. We also present a hardness result suggesting that PBN CONTROL is harder than BN CONTROL.

  17. An Extension of Proof Graphs for Disjunctive Parameterised Boolean Equation Systems

    Directory of Open Access Journals (Sweden)

    Yutaro Nagae

    2017-01-01

    Full Text Available A parameterised Boolean equation system (PBES is a set of equations that defines sets as the least and/or greatest fixed-points that satisfy the equations. This system is regarded as a declarative program defining functions that take a datum and returns a Boolean value. The membership problem of PBESs is a problem to decide whether a given element is in the defined set or not, which corresponds to an execution of the program. This paper introduces reduced proof graphs, and studies a technique to solve the membership problem of PBESs, which is undecidable in general, by transforming it into a reduced proof graph. A vertex X(v in a proof graph represents that the data v is in the set X, if the graph satisfies conditions induced from a given PBES. Proof graphs are, however, infinite in general. Thus we introduce vertices each of which stands for a set of vertices of the original ones, which possibly results in a finite graph. For a subclass of disjunctive PBESs, we clarify some conditions which reduced proof graphs should satisfy. We also show some examples having no finite proof graph except for reduced one. We further propose a reduced dependency space, which contains reduced proof graphs as sub-graphs if a proof graph exists. We provide a procedure to construct finite reduced dependency spaces, and show the soundness and completeness of the procedure.

  18. Boolean network model for cancer pathways: predicting carcinogenesis and targeted therapy outcomes.

    Directory of Open Access Journals (Sweden)

    Herman F Fumiã

    Full Text Available A Boolean dynamical system integrating the main signaling pathways involved in cancer is constructed based on the currently known protein-protein interaction network. This system exhibits stationary protein activation patterns--attractors--dependent on the cell's microenvironment. These dynamical attractors were determined through simulations and their stabilities against mutations were tested. In a higher hierarchical level, it was possible to group the network attractors into distinct cell phenotypes and determine driver mutations that promote phenotypic transitions. We find that driver nodes are not necessarily central in the network topology, but at least they are direct regulators of central components towards which converge or through which crosstalk distinct cancer signaling pathways. The predicted drivers are in agreement with those pointed out by diverse census of cancer genes recently performed for several human cancers. Furthermore, our results demonstrate that cell phenotypes can evolve towards full malignancy through distinct sequences of accumulated mutations. In particular, the network model supports routes of carcinogenesis known for some tumor types. Finally, the Boolean network model is employed to evaluate the outcome of molecularly targeted cancer therapies. The major find is that monotherapies were additive in their effects and that the association of targeted drugs is necessary for cancer eradication.

  19. Robust Template Decomposition without Weight Restriction for Cellular Neural Networks Implementing Arbitrary Boolean Functions Using Support Vector Classifiers

    Directory of Open Access Journals (Sweden)

    Yih-Lon Lin

    2013-01-01

    Full Text Available If the given Boolean function is linearly separable, a robust uncoupled cellular neural network can be designed as a maximal margin classifier. On the other hand, if the given Boolean function is linearly separable but has a small geometric margin or it is not linearly separable, a popular approach is to find a sequence of robust uncoupled cellular neural networks implementing the given Boolean function. In the past research works using this approach, the control template parameters and thresholds are restricted to assume only a given finite set of integers, and this is certainly unnecessary for the template design. In this study, we try to remove this restriction. Minterm- and maxterm-based decomposition algorithms utilizing the soft margin and maximal margin support vector classifiers are proposed to design a sequence of robust templates implementing an arbitrary Boolean function. Several illustrative examples are simulated to demonstrate the efficiency of the proposed method by comparing our results with those produced by other decomposition methods with restricted weights.

  20. Effects of exogenous IL-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T cells.

    Science.gov (United States)

    Chen, Yu-Hua; Zhou, Bi-Yun; Wu, Guo-Cai; Liao, De-Quan; Li, Jing; Liang, Si-Si; Wu, Xian-Jin; Xu, Jun-Fa; Chen, Yong-Hua; Di, Xiao-Qing; Lin, Qiong-Yan

    2018-02-14

    This study aims to investigate the effects of exogenous interleukin (IL)-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T (Treg) cells. After isolating the CD4+ CD25+ Treg cells from the peripheral blood, flow cytometry was used to detect the purity of the Treg cells. A549 cells were divided into blank (no transfection), empty plasmid (transfection with pIRES2-EGFP empty plasmid) or IL-37 group (transfection with pIRES2-EGFP-IL-37 plasmid). RT-PCR was used to detect mRNA expression of IL-37 and ELISA to determine IL-37 and MMP-9 expressions. Western blotting was applied to detect the protein expressions of PCNA, Ki-67, Cyclin D1, CDK4, cleaved caspase-3 and cleaved caspase-9. MTT assay, flow cytometry, scratch test and transwell assay were performed to detect cell proliferation, cycle, apoptosis, migration and invasion. Effect of exogenous IL-37 on the chemotaxis of Treg cells was measured through transwell assay. Xenograft models in nude mice were eastablished to detect the impact of IL-37 on A549 cells. The IL-37 group had a higher IL-37 expression, cell apoptosis in the early stage and percentage of cells in the G0/G1 phase than the blank and empty plasmid groups. The IL-37 group had a lower MMP-9 expression, optical density (OD), percentage of cells in the S and G2/M phases, migration, invasion and chemotaxis of CD4+CD25+ Foxp3+ Treg cells. The xenograft volume and weight of nude mice in the IL-37 group were lower than those in the blank and empty plasmid groups. Compared with the blank and empty plasmid groups, the IL-37 group had significantly reduced expression of PCNA, Ki-67, Cyclin D1 and CDK4 but elevated expression of cleaved caspase-3 and cleaved caspase-9. Therefore, exogenous IL-37 inhibits the proliferation, migration and invasion of human lung adenocarcinoma A549 cells as well as the chemotaxis of Treg cells while promoting the apoptosis of A549 cells.

  1. Cross-regulatory network in Pseudomonas aeruginosa biofilm genes and TiO2anatase induced molecular perturbations in key proteins unraveled by a systems biology approach.

    Science.gov (United States)

    Anupama, Rani; Sajitha Lulu, S; Mukherjee, Amitava; Babu, Subramanian

    2018-03-20

    A systems biology approach was used to study all the biofilm related genes of P. aeruginosa PAO1, and the interaction of titanium dioxide (TiO 2 ) anatase with biofilm related proteins. Among the 71 genes, the interactions of all the nodal pairs were extracted by STRING 10.5 database. The inter-relationship among these genes was predicted by constructing complete PPI network and visualized in Cytoscape v 3.4.0. Total number of nodes of the network was found to be 335 and edges were 795. The network was further investigated for its clusters and the best cluster was further analyzed for the hub proteins which significantly contribute in cross-regulation of the biofilm related process. The hub proteins were identified based on four topological parameters of degree, closeness, betweeness and radiality. Four major hub proteins of P. aeruginosa PAO1 were identified to be algD, gacS, rpoS and rpoN which were common in all the hubs. Further, we have also elucidated the probable mechanism of TiO 2 interaction with P. aeruginosa PAO1 at molecular level. Using STITCH server, the major target gene of TiO 2 was identified as katA which also appeared commonly in our main dataset and this gene has been focused for the further study because of its unique common appearance in gene-gene network as well as gene-anatase network. The direct interacting partners of katA were found to be dnaK, hfq, rpoS and rpoA. Based on these findings and available gene regulatory information, probable TiO 2 interacting cascade has been represented. This in silico study of P. aeruginosa PAO1 biofilm genes and the interaction of protein products with TiO 2 might be significant to understand the perspective pathogenic resistance as well as the toxicity research pertaining to nanoparticles. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. On the solution of nonconvex cardinality Boolean quadratic programming problems: a computational study

    KAUST Repository

    Lima, Ricardo

    2016-06-16

    This paper addresses the solution of a cardinality Boolean quadratic programming problem using three different approaches. The first transforms the original problem into six mixed-integer linear programming (MILP) formulations. The second approach takes one of the MILP formulations and relies on the specific features of an MILP solver, namely using starting incumbents, polishing, and callbacks. The last involves the direct solution of the original problem by solvers that can accomodate the nonlinear combinatorial problem. Particular emphasis is placed on the definition of the MILP reformulations and their comparison with the other approaches. The results indicate that the data of the problem has a strong influence on the performance of the different approaches, and that there are clear-cut approaches that are better for some instances of the data. A detailed analysis of the results is made to identify the most effective approaches for specific instances of the data. © 2016 Springer Science+Business Media New York

  3. Dynamics of random Boolean networks under fully asynchronous stochastic update based on linear representation.

    Directory of Open Access Journals (Sweden)

    Chao Luo

    Full Text Available A novel algebraic approach is proposed to study dynamics of asynchronous random Boolean networks where a random number of nodes can be updated at each time step (ARBNs. In this article, the logical equations of ARBNs are converted into the discrete-time linear representation and dynamical behaviors of systems are investigated. We provide a general formula of network transition matrices of ARBNs as well as a necessary and sufficient algebraic criterion to determine whether a group of given states compose an attractor of length[Formula: see text] in ARBNs. Consequently, algorithms are achieved to find all of the attractors and basins in ARBNs. Examples are showed to demonstrate the feasibility of the proposed scheme.

  4. The universal magnetic tunnel junction logic gates representing 16 binary Boolean logic operations

    Science.gov (United States)

    Lee, Junwoo; Suh, Dong Ik; Park, Wanjun

    2015-05-01

    The novel devices are expected to shift the paradigm of a logic operation by their own nature, replacing the conventional devices. In this study, the nature of our fabricated magnetic tunnel junction (MTJ) that responds to the two external inputs, magnetic field and voltage bias, demonstrated seven basic logic operations. The seven operations were obtained by the electric-field-assisted switching characteristics, where the surface magnetoelectric effect occurs due to a sufficiently thin free layer. The MTJ was transformed as a universal logic gate combined with three supplementary circuits: A multiplexer (MUX), a Wheatstone bridge, and a comparator. With these circuits, the universal logic gates demonstrated 16 binary Boolean logic operations in one logic stage. A possible further approach is parallel computations through a complimentary of MUX and comparator, capable of driving multiple logic gates. A reconfigurable property can also be realized when different logic operations are produced from different level of voltages applying to the same configuration of the logic gate.

  5. Ones and zeros understanding Boolean algebra digital circuits and the logic of sets

    CERN Document Server

    Gregg, John

    1998-01-01

    "Ones and Zeros explains, in lay terms, Boolean algebra, the suprisingly simple system of mathematical logic used in digital computer circuitry. Ones and Zeros follows the development of this logic system from its origins in Victorian England to its rediscovery in this century as the foundation of all modern computing machinery. Readers will learn about the interesting history of the development of symbolic logic in particular, and the often misunderstood process of mathematical invention and scientific discovery, in general. Ones and Zeros also features practical exercises with answers, real-world examples of digital circuit design, and a reading list." "Ones and Zeros will be of particular interest to software engineers who want to gain a comprehensive understanding of computer hardware." "Outstanding features include: a history of mathematical logic, an explanation of the logic of digital circuits, and hands-on exercises and examples."--Jacket.

  6. Order-to-chaos transition in the hardness of random Boolean satisfiability problems

    Science.gov (United States)

    Varga, Melinda; Sumi, Róbert; Toroczkai, Zoltán; Ercsey-Ravasz, Mária

    2016-05-01

    Transient chaos is a ubiquitous phenomenon characterizing the dynamics of phase-space trajectories evolving towards a steady-state attractor in physical systems as diverse as fluids, chemical reactions, and condensed matter systems. Here we show that transient chaos also appears in the dynamics of certain efficient algorithms searching for solutions of constraint satisfaction problems that include scheduling, circuit design, routing, database problems, and even Sudoku. In particular, we present a study of the emergence of hardness in Boolean satisfiability (k -SAT), a canonical class of constraint satisfaction problems, by using an analog deterministic algorithm based on a system of ordinary differential equations. Problem hardness is defined through the escape rate κ , an invariant measure of transient chaos of the dynamical system corresponding to the analog algorithm, and it expresses the rate at which the trajectory approaches a solution. We show that for a given density of constraints and fixed number of Boolean variables N , the hardness of formulas in random k -SAT ensembles has a wide variation, approximable by a lognormal distribution. We also show that when increasing the density of constraints α , hardness appears through a second-order phase transition at αχ in the random 3-SAT ensemble where dynamical trajectories become transiently chaotic. A similar behavior is found in 4-SAT as well, however, such a transition does not occur for 2-SAT. This behavior also implies a novel type of transient chaos in which the escape rate has an exponential-algebraic dependence on the critical parameter κ ˜NB |α - αχ|1-γ with 0 <γ <1 . We demonstrate that the transition is generated by the appearance of metastable basins in the solution space as the density of constraints α is increased.

  7. Recurrent-neural-network-based Boolean factor analysis and its application to word clustering.

    Science.gov (United States)

    Frolov, Alexander A; Husek, Dusan; Polyakov, Pavel Yu

    2009-07-01

    The objective of this paper is to introduce a neural-network-based algorithm for word clustering as an extension of the neural-network-based Boolean factor analysis algorithm (Frolov , 2007). It is shown that this extended algorithm supports even the more complex model of signals that are supposed to be related to textual documents. It is hypothesized that every topic in textual data is characterized by a set of words which coherently appear in documents dedicated to a given topic. The appearance of each word in a document is coded by the activity of a particular neuron. In accordance with the Hebbian learning rule implemented in the network, sets of coherently appearing words (treated as factors) create tightly connected groups of neurons, hence, revealing them as attractors of the network dynamics. The found factors are eliminated from the network memory by the Hebbian unlearning rule facilitating the search of other factors. Topics related to the found sets of words can be identified based on the words' semantics. To make the method complete, a special technique based on a Bayesian procedure has been developed for the following purposes: first, to provide a complete description of factors in terms of component probability, and second, to enhance the accuracy of classification of signals to determine whether it contains the factor. Since it is assumed that every word may possibly contribute to several topics, the proposed method might be related to the method of fuzzy clustering. In this paper, we show that the results of Boolean factor analysis and fuzzy clustering are not contradictory, but complementary. To demonstrate the capabilities of this attempt, the method is applied to two types of textual data on neural networks in two different languages. The obtained topics and corresponding words are at a good level of agreement despite the fact that identical topics in Russian and English conferences contain different sets of keywords.

  8. Prediction of regulatory elements

    DEFF Research Database (Denmark)

    Sandelin, Albin

    2008-01-01

    Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet-lab...

  9. APPLICATION OF THE OVERLAY WEIGHTED MODEL AND BOOLEAN LOGIC TO DETERMINE THE BEST LOCATIONS FOR ARTIFICIAL RECHARGE OF GROUNDWATER

    Directory of Open Access Journals (Sweden)

    Max Billib

    2011-12-01

    Full Text Available With population increase, lack of conventional fresh water resources and uncertainties due to climate change, there is growing interest in the arid and semi-arid areas to increase groundwater recharge with recycled water. Finding the best locations for artificial recharge of groundwater in such areas is one of the most crucial design steps to guarantee the long life and the sustainability of these projects. This study presents two ways to go about performing analysis; creating a suitability map to find out the suitability of every location on the map and another way is querying the created data sets to obtain a Boolean result of true or false map. These techniques have been applied on Sadat Industrial City which is located in a semi arid area in the western desert fringes of The Nile delta in the north west of Egypt. Thematic layers for number of parameters were prepared from some maps and satellite images and they have been classified, weighted and integrated in ArcGIS environment. By the means of the overlay weighted model in ArcGIS a suitability map which is classified into number of priority zones was obtained and it could be compared with the obtained true-false map of Boolean logic. Both methods suggested mostly the northern parts of the city for groundwater recharge; however the weighted model could give more accurate suitability map while Boolean logic suggested wider ranges of areas. This study recommends Boolean logic as a first estimator for locating the best locations as it is easier and not time consuming, while the overlay weighted model for more accurate results.

  10. APPLICATION OF THE OVERLAY WEIGHTED MODEL AND BOOLEAN LOGIC TO DETERMINE THE BEST LOCATIONS FOR ARTIFICIAL RECHARGE OF GROUNDWATER

    Directory of Open Access Journals (Sweden)

    Peter H.S. Riad

    2011-01-01

    Full Text Available With population increase, lack of conventional fresh water resources and uncertainties due to climate change, there is growing interest in the arid and semi-arid areas to increase groundwater recharge with recycled water. Finding the best locations for artificial recharge of groundwater in such areas is one of the most crucial design steps to guarantee the long life and the sustainability of these projects. This study presents two ways to go about performing analysis; creating a suitability map to find out the suitability of every location on the map and another way is querying the created data sets to obtain a Boolean result of true or false map. These techniques have been applied on Sadat Industrial City which is located in a semi arid area in the western desert fringes of The Nile delta in the north west of Egypt. Thematic layers for number of parameters were prepared from some maps and satellite images and they have been classified, weighted and integrated in ArcGIS environment. By the means of the overlay weighted model in ArcGIS a suitability map which is classified into number of priority zones was obtained and it could be compared with the obtained true-false map of Boolean logic. Both methods suggested mostly the northern parts of the city for groundwater recharge; however the weighted model could give more accurate suitability map while Boolean logic suggested wider ranges of areas. This study recommends Boolean logic as a first estimator for locating the best locations as it is easier and not time consuming, while the overlay weighted model for more accurate results.

  11. Origin and Elimination of Two Global Spurious Attractors in Hopfield-Like Neural Network Performing Boolean Factor Analysis

    Czech Academy of Sciences Publication Activity Database

    Frolov, A. A.; Húsek, Dušan; Muraviev, I. P.; Polyakov, P.Y.

    2010-01-01

    Roč. 73, č. 7-9 (2010), s. 1394-1404 ISSN 0925-2312 R&D Projects: GA ČR GA205/09/1079; GA MŠk(CZ) 1M0567 Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean factor analysis * Hopfield neural Network * unsupervised learning * dimension reduction * data mining Subject RIV: IN - Informatics, Computer Science Impact factor: 1.429, year: 2010

  12. Realisation of all 16 Boolean logic functions in a single magnetoresistance memory cell

    Science.gov (United States)

    Gao, Shuang; Yang, Guang; Cui, Bin; Wang, Shouguo; Zeng, Fei; Song, Cheng; Pan, Feng

    2016-06-01

    Stateful logic circuits based on next-generation nonvolatile memories, such as magnetoresistance random access memory (MRAM), promise to break the long-standing von Neumann bottleneck in state-of-the-art data processing devices. For the successful commercialisation of stateful logic circuits, a critical step is realizing the best use of a single memory cell to perform logic functions. In this work, we propose a method for implementing all 16 Boolean logic functions in a single MRAM cell, namely a magnetoresistance (MR) unit. Based on our experimental results, we conclude that this method is applicable to any MR unit with a double-hump-like hysteresis loop, especially pseudo-spin-valve magnetic tunnel junctions with a high MR ratio. Moreover, after simply reversing the correspondence between voltage signals and output logic values, this method could also be applicable to any MR unit with a double-pit-like hysteresis loop. These results may provide a helpful solution for the final commercialisation of MRAM-based stateful logic circuits in the near future.Stateful logic circuits based on next-generation nonvolatile memories, such as magnetoresistance random access memory (MRAM), promise to break the long-standing von Neumann bottleneck in state-of-the-art data processing devices. For the successful commercialisation of stateful logic circuits, a critical step is realizing the best use of a single memory cell to perform logic functions. In this work, we propose a method for implementing all 16 Boolean logic functions in a single MRAM cell, namely a magnetoresistance (MR) unit. Based on our experimental results, we conclude that this method is applicable to any MR unit with a double-hump-like hysteresis loop, especially pseudo-spin-valve magnetic tunnel junctions with a high MR ratio. Moreover, after simply reversing the correspondence between voltage signals and output logic values, this method could also be applicable to any MR unit with a double-pit-like hysteresis

  13. Boolean modeling of neural systems with point-process inputs and outputs. Part I: theory and simulations.

    Science.gov (United States)

    Marmarelis, Vasilis Z; Zanos, Theodoros P; Berger, Theodore W

    2009-08-01

    This paper presents a new modeling approach for neural systems with point-process (spike) inputs and outputs that utilizes Boolean operators (i.e. modulo 2 multiplication and addition that correspond to the logical AND and OR operations respectively, as well as the AND_NOT logical operation representing inhibitory effects). The form of the employed mathematical models is akin to a "Boolean-Volterra" model that contains the product terms of all relevant input lags in a hierarchical order, where terms of order higher than first represent nonlinear interactions among the various lagged values of each input point-process or among lagged values of various inputs (if multiple inputs exist) as they reflect on the output. The coefficients of this Boolean-Volterra model are also binary variables that indicate the presence or absence of the respective term in each specific model/system. Simulations are used to explore the properties of such models and the feasibility of their accurate estimation from short data-records in the presence of noise (i.e. spurious spikes). The results demonstrate the feasibility of obtaining reliable estimates of such models, with excitatory and inhibitory terms, in the presence of considerable noise (spurious spikes) in the outputs and/or the inputs in a computationally efficient manner. A pilot application of this approach to an actual neural system is presented in the companion paper (Part II).

  14. A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology.

    Science.gov (United States)

    Chen, Bor-Sen; Lin, Ying-Po

    2013-01-01

    Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view.

  15. An Improvement to a Multi-Client Searchable Encryption Scheme for Boolean Queries.

    Science.gov (United States)

    Jiang, Han; Li, Xue; Xu, Qiuliang

    2016-12-01

    The migration of e-health systems to the cloud computing brings huge benefits, as same as some security risks. Searchable Encryption(SE) is a cryptography encryption scheme that can protect the confidentiality of data and utilize the encrypted data at the same time. The SE scheme proposed by Cash et al. in Crypto2013 and its follow-up work in CCS2013 are most practical SE Scheme that support Boolean queries at present. In their scheme, the data user has to generate the search tokens by the counter number one by one and interact with server repeatedly, until he meets the correct one, or goes through plenty of tokens to illustrate that there is no search result. In this paper, we make an improvement to their scheme. We allow server to send back some information and help the user to generate exact search token in the search phase. In our scheme, there are only two round interaction between server and user, and the search token has [Formula: see text] elements, where n is the keywords number in query expression, and [Formula: see text] is the minimum documents number that contains one of keyword in query expression, and the computation cost of server is [Formula: see text] modular exponentiation operation.

  16. Prescribed burning impact on forest soil properties--a Fuzzy Boolean Nets approach.

    Science.gov (United States)

    Castro, Ana C Meira; Paulo Carvalho, Joao; Ribeiro, S

    2011-02-01

    The Portuguese northern forests are often and severely affected by wildfires during the Summer season. These occurrences significantly affect and negatively impact all ecosystems, namely soil, fauna and flora. In order to reduce the occurrences of natural wildfires, some measures to control the availability of fuel mass are regularly implemented. Those preventive actions concern mainly prescribed burnings and vegetation pruning. This work reports on the impact of a prescribed burning on several forest soil properties, namely pH, soil moisture, organic matter content and iron content, by monitoring the soil self-recovery capabilities during a one year span. The experiments were carried out in soil cover over a natural site of Andaluzitic schist, in Gramelas, Caminha, Portugal, which was kept intact from prescribed burnings during a period of four years. Soil samples were collected from five plots at three different layers (0-3, 3-6 and 6-18) 1 day before prescribed fire and at regular intervals after the prescribed fire. This paper presents an approach where Fuzzy Boolean Nets (FBN) and Fuzzy reasoning are used to extract qualitative knowledge regarding the effect of prescribed fire burning on soil properties. FBN were chosen due to the scarcity on available quantitative data. The results showed that soil properties were affected by prescribed burning practice and were unable to recover their initial values after one year. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Efficient Multi-Valued Bounded Model Checking for LTL over Quasi-Boolean Algebras

    Science.gov (United States)

    Andrade, Jefferson O.; Kameyama, Yukiyoshi

    Multi-valued Model Checking extends classical, two-valued model checking to multi-valued logic such as Quasi-Boolean logic. The added expressivity is useful in dealing with such concepts as incompleteness and uncertainty in target systems, while it comes with the cost of time and space. Chechik and others proposed an efficient reduction from multi-valued model checking problems to two-valued ones, but to the authors' knowledge, no study was done for multi-valued bounded model checking. In this paper, we propose a novel, efficient algorithm for multi-valued bounded model checking. A notable feature of our algorithm is that it is not based on reduction of multi-values into two-values; instead, it generates a single formula which represents multi-valuedness by a suitable encoding, and asks a standard SAT solver to check its satisfiability. Our experimental results show a significant improvement in the number of variables and clauses and also in execution time compared with the reduction-based one.

  18. Runtime analysis of the (mu+1) EA on simple Pseudo-Boolean functions.

    Science.gov (United States)

    Witt, Carsten

    2006-01-01

    Although Evolutionary Algorithms (EAs) have been successfully applied to optimization in discrete search spaces, theoretical developments remain weak, in particular for population-based EAs. This paper presents a first rigorous analysis of the (mu+1) EA on pseudo-Boolean functions. Using three well-known example functions from the analysis of the (1+1) EA, we derive bounds on the expected runtime and success probability. For two of these functions, upper and lower bounds on the expected runtime are tight, and on all three functions, the (mu+1) EA is never more efficient than the (1+1) EA. Moreover, all lower bounds grow with mu. On a more complicated function, however, a small increase of mu probably decreases the expected runtime drastically. This paper develops a new proof technique that bounds the runtime of the (mu+1) EA. It investigates the stochastic process for creating family trees of individuals; the depth of these trees is bounded. Thereby, the progress of the population towards the optimum is captured. This new technique is general enough to be applied to other population-based EAs.

  19. On control of singleton attractors in multiple Boolean networks: integer programming-based method.

    Science.gov (United States)

    Qiu, Yushan; Tamura, Takeyuki; Ching, Wai-Ki; Akutsu, Tatsuya

    2014-01-01

    Boolean network (BN) is a mathematical model for genetic network and control of genetic networks has become an important issue owing to their potential application in the field of drug discovery and treatment of intractable diseases. Early researches have focused primarily on the analysis of attractor control for a randomly generated BN. However, one may also consider how anti-cancer drugs act in both normal and cancer cells. Thus, the development of controls for multiple BNs is an important and interesting challenge. In this article, we formulate three novel problems about attractor control for two BNs (i.e., normal cell and cancer cell). The first is about finding a control that can significantly damage cancer cells but has a limited damage to normal cells. The second is about finding a control for normal cells with a guaranteed damaging effect on cancer cells. Finally, we formulate a definition for finding a control for cancer cells with limited damaging effect on normal cells. We propose integer programming-based methods for solving these problems in a unified manner, and we conduct computational experiments to illustrate the efficiency and the effectiveness of our method for our multiple-BN control problems. We present three novel control problems for multiple BNs that are realistic control models for gene regulation networks and adopt an integer programming approach to address these problems. Experimental results indicate that our proposed method is useful and effective for moderate size BNs.

  20. The boolean algebra with restricted variables as a tool for fault tree modularization

    International Nuclear Information System (INIS)

    Caldarola, L.; Wickenhaeuser, A.

    1981-08-01

    The number of minimal cut sets (m.c.s.) of very complex and highly interconnected fault trees can become extremely large (e.g. more than 10 7 ). In this case the usual analytical approach of dissecting the fault tree TOP variable into m.c.s. is not only computationally prohibitively expensive, but also meaningless because it does not offer any synthetic overview of system behavior. The method proposed in this paper overcomes the deficiencies of the analytical method. It is shown that, by applying boolean algebra with restricted variables (b.a.w.r.v.), the concept of fault tree modularization can be straightforwardly extended from a single gate to a set of gates. Thus, large fault trees are divided into smaller fault trees (modules), which are connected to each other according to a simple scheme. This scheme is represented by a block diagram in which each block is a module. The modules are analyzed separately by the m.c.s. method, and the results are combined according of the TOP event. The method allows the calculation of very large fault trees in a short time and offers a synthetic overview of systems behavior through the block diagram. Numerical examples are also included. Calculations have been carried out by using the computer code MUSTAMO, which is based on the theory developed in this paper. (orig.) [de

  1. Construction of a fuzzy and Boolean logic gates based on DNA.

    Science.gov (United States)

    Zadegan, Reza M; Jepsen, Mette D E; Hildebrandt, Lasse L; Birkedal, Victoria; Kjems, Jørgen

    2015-04-17

    Logic gates are devices that can perform logical operations by transforming a set of inputs into a predictable single detectable output. The hybridization properties, structure, and function of nucleic acids can be used to make DNA-based logic gates. These devices are important modules in molecular computing and biosensing. The ideal logic gate system should provide a wide selection of logical operations, and be integrable in multiple copies into more complex structures. Here we show the successful construction of a small DNA-based logic gate complex that produces fluorescent outputs corresponding to the operation of the six Boolean logic gates AND, NAND, OR, NOR, XOR, and XNOR. The logic gate complex is shown to work also when implemented in a three-dimensional DNA origami box structure, where it controlled the position of the lid in a closed or open position. Implementation of multiple microRNA sensitive DNA locks on one DNA origami box structure enabled fuzzy logical operation that allows biosensing of complex molecular signals. Integrating logic gates with DNA origami systems opens a vast avenue to applications in the fields of nanomedicine for diagnostics and therapeutics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A High-Level Petri Net Framework for Genetic Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Banks Richard

    2007-12-01

    Full Text Available To understand the function of genetic regulatory networks in the development of cellular systems, we must not only realise the individual network entities, but also the manner by which they interact. Multi-valued networks are a promising qualitative approach for modelling such genetic regulatory networks, however, at present they have limited formal analysis techniques and tools. We present a flexible formal framework for modelling and analysing multi-valued genetic regulatory networks using high-level Petri nets and logic minimization techniques. We demonstrate our approach with a detailed case study in which part of the genetic regulatory network responsible for the carbon starvation stress response in Escherichia coli is modelled and analysed. We then compare and contrast this multivalued model to a corresponding Boolean model and consider their formal relationship.

  3. [Regulatory science researches of nanomedicines].

    Science.gov (United States)

    Sakai-Kato, Kumiko; Goda, Yukihiro

    2014-01-01

    Recently, the development of nanomedicines is progressing. These are designed to ensure high stability and to optimize the pharmacokinetics in vivo. The polymeric micelles and lipid nanoparticles are typical such examples. Because the unique size-specific interaction with biological systems or biodistribution may have significant impacts on the efficacy and safety of nanomedicines, regulatory science researches of nanomedicines are required. In this review, the authors introduce our initiatives of the regulatory science researches of nanomedicines.

  4. Concept locator: a client-server application for retrieval of UMLS metathesaurus concepts through complex boolean query.

    Science.gov (United States)

    Nadkarni, P M

    1997-08-01

    Concept Locator (CL) is a client-server application that accesses a Sybase relational database server containing a subset of the UMLS Metathesaurus for the purpose of retrieval of concepts corresponding to one or more query expressions supplied to it. CL's query grammar permits complex Boolean expressions, wildcard patterns, and parenthesized (nested) subexpressions. CL translates the query expressions supplied to it into one or more SQL statements that actually perform the retrieval. The generated SQL is optimized by the client to take advantage of the strengths of the server's query optimizer, and sidesteps its weaknesses, so that execution is reasonably efficient.

  5. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

    , legal and cultural, on a global scale. Against this background, this special issue sets out to explore the multifaceted meaning, potential and impact as well as the social praxis of regulatory governance. Under the notions rules, resistance and responsibility the special issue pins out three overall......Regulatory governance frameworks have become essential building blocks of world society. From supply chains to the regimes surrounding international organizations, extensive governance frameworks have emerged which structure and channel a variety of social exchanges, including economic, political...

  6. pcaGoPromoter--an R package for biological and regulatory interpretation of principal components in genome-wide gene expression data.

    Directory of Open Access Journals (Sweden)

    Morten Hansen

    Full Text Available Analyzing data obtained from genome-wide gene expression experiments is challenging due to the quantity of variables, the need for multivariate analyses, and the demands of managing large amounts of data. Here we present the R package pcaGoPromoter, which facilitates the interpretation of genome-wide expression data and overcomes the aforementioned problems. In the first step, principal component analysis (PCA is applied to survey any differences between experiments and possible groupings. The next step is the interpretation of the principal components with respect to both biological function and regulation by predicted transcription factor binding sites. The robustness of the results is evaluated using cross-validation, and illustrative plots of PCA scores and gene ontology terms are available. pcaGoPromoter works with any platform that uses gene symbols or Entrez IDs as probe identifiers. In addition, support for several popular Affymetrix GeneChip platforms is provided. To illustrate the features of the pcaGoPromoter package a serum stimulation experiment was performed and the genome-wide gene expression in the resulting samples was profiled using the Affymetrix Human Genome U133 Plus 2.0 chip. Array data were analyzed using pcaGoPromoter package tools, resulting in a clear separation of the experiments into three groups: controls, serum only and serum with inhibitor. Functional annotation of the axes in the PCA score plot showed the expected serum-promoted biological processes, e.g., cell cycle progression and the predicted involvement of expected transcription factors, including E2F. In addition, unexpected results, e.g., cholesterol synthesis in serum-depleted cells and NF-κB activation in inhibitor treated cells, were noted. In summary, the pcaGoPromoter R package provides a collection of tools for analyzing gene expression data. These tools give an overview of the input data via PCA, functional interpretation by gene ontology terms

  7. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    , legal documents, technological devices, organizational structures, and work practices aimed at minimizing risk. I use this term to reorient the analytical attention with respect to safety regulation. Instead of evaluating whether safety is achieved, the point is to explore the types of “safety” produced...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  8. pcaGoPromoter--an R package for biological and regulatory interpretation of principal components in genome-wide gene expression data

    DEFF Research Database (Denmark)

    Hansen, Morten; Gerds, Thomas Alexander; Nielsen, Ole Haagen

    2012-01-01

    Analyzing data obtained from genome-wide gene expression experiments is challenging due to the quantity of variables, the need for multivariate analyses, and the demands of managing large amounts of data. Here we present the R package pcaGoPromoter, which facilitates the interpretation of genome......-wide expression data and overcomes the aforementioned problems. In the first step, principal component analysis (PCA) is applied to survey any differences between experiments and possible groupings. The next step is the interpretation of the principal components with respect to both biological function...... and regulation by predicted transcription factor binding sites. The robustness of the results is evaluated using cross-validation, and illustrative plots of PCA scores and gene ontology terms are available. pcaGoPromoter works with any platform that uses gene symbols or Entrez IDs as probe identifiers...

  9. The p85α regulatory subunit of PI3K mediates cAMP-PKA and retinoic acid biological effects on MCF7 cell growth and migration.

    Science.gov (United States)

    Donini, Caterina F; Di Zazzo, Erika; Zuchegna, Candida; Di Domenico, Marina; D'Inzeo, Sonia; Nicolussi, Arianna; Avvedimento, Enrico V; Coppa, Anna; Porcellini, Antonio

    2012-05-01

    Phosphoinositide-3-OH kinase (PI3K) signalling regulates various cellular processes, including cell survival, growth, proliferation and motility, and is among the most frequently mutated pathways in cancer. Although the involvement of p85αPI3K SH2 domain in signal transduction has been extensively studied, the function of the SH3 domain at the N-terminus remains elusive. A serine (at codon 83) adjacent to the N-terminal SH3 domain in the PI3K regulatory subunit p85αPI3K that is phosphorylated by protein kinase A (PKA) in vivo and in vitro has been identified. Virtually all receptors binding p85αPI3K can cooperate with cAMP-PKA signals via phosphorylation of p85αPI3KSer83. To analyse the role of p85αPI3KSer83 in retinoic acid (RA) and cAMP signalling, in MCF7 cells, we used p85αPI3K mutated forms, in which Ser83 has been substituted with alanine (p85A) to prevent phosphorylation or with aspartic acid (p85D) to mimic the phosphorylated residue. We demonstrated that p85αPI3KSer83 is crucial for the synergistic enhancement of RARα/p85αPI3K binding induced by cAMP/RA co-treatment in MCF7 cells. Growth curves, colorimetric MTT assay and cell cycle analysis demonstrated that phosphorylation of p85αPI3KSer83 plays an important role in the control of MCF7 cell proliferation and in RA-induced inhibition of proliferation. Wound healing and transwell experiments demonstrated that p85αPI3KSer83 was also essential both for the control of migratory behaviour and for the reduction of motility induced by RA. This study points to p85αPI3KSer83 as the physical link between different pathways (cAMP-PKA, RA and FAK), and as an important regulator of MCF7 cell proliferation and migration.

  10. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    Directory of Open Access Journals (Sweden)

    Joana P Gonçalves

    Full Text Available Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1 apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2 ignore local patterns, abundant in most interesting cases of transcriptional activity; (3 neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4 limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots. Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in

  11. Access and Benefit Sharing under the Convention on Biological Diversity and Its Protocol: What Can Some Numbers Tell Us about the Effectiveness of the Regulatory Regime?

    Directory of Open Access Journals (Sweden)

    Nicolas Pauchard

    2017-02-01

    Full Text Available The Convention on Biological Diversity (CBD, adopted in 1992 and entered into force at the end of 1993, established a global regime on access to genetic resources (GR and sharing of benefits arising from their utilization (Access and Benefit Sharing (ABS regime. Its protocol—the Nagoya Protocol (NP—which entered into force 21 years later in 2014, clears up some terminological ambiguities of the Convention, clarifies and develops several procedural and instrumental elements of the regime, and obliges States Parties to implement some of its provisions, including the core instrument of the regime: the bilateral ABS agreement between users and providers of GR, that became a condition for obtaining access to the resource. However, scholars who analyzed the ABS regime as well as its official bodies find, and sometimes deplore, the small number of ABS agreements concluded so far, under the CBD as under the NP. This paper has two objectives: First, to assess the effectiveness of the ABS regime implemented by the CBD and the NP on the basis of its central instrument: the ABS agreements concluded between users and providers of GR. The aim is to accurately document the number of ABS agreements concluded since the entry into force of the regime. To our knowledge, such a counting that is neither piecemeal nor has an estimate yet been produced. To do so, I combine several sources, including first hand data collected from the official information agencies—the National Focal Points (NFP—of each of the States Parties to the NP. Second, I provide a critical summary of the existing explanations of the low number of ABS agreements concluded and I evaluate the corresponding causal mechanisms, relying on the results I obtained regarding the number of permits and agreements.

  12. A universal algorithm for genome-wide in silicio identification of biologically significant gene promoter putative cis-regulatory-elements; identification of new elements for reactive oxygen species and sucrose signaling in Arabidopsis.

    Science.gov (United States)

    Geisler, Matt; Kleczkowski, Leszek A; Karpinski, Stanislaw

    2006-02-01

    Short motifs of many cis-regulatory elements (CREs) can be found in the promoters of most Arabidopsis genes, and this raises the question of how their presence can confer specific regulation. We developed a universal algorithm to test the biological significance of CREs by first identifying every Arabidopsis gene with a CRE and then statistically correlating the presence or absence of the element with the gene expression profile on multiple DNA microarrays. This algorithm was successfully verified for previously characterized abscisic acid, ethylene, sucrose and drought responsive CREs in Arabidopsis, showing that the presence of these elements indeed correlates with treatment-specific gene induction. Later, we used standard motif sampling methods to identify 128 putative motifs induced by excess light, reactive oxygen species and sucrose. Our algorithm was able to filter 20 out of 128 novel CREs which significantly correlated with gene induction by either heat, reactive oxygen species and/or sucrose. The position, orientation and sequence specificity of CREs was tested in silicio by analyzing the expression of genes with naturally occurring sequence variations. In three novel CREs the forward orientation correlated with sucrose induction and the reverse orientation with sucrose suppression. The functionality of the predicted novel CREs was experimentally confirmed using Arabidopsis cell-suspension cultures transformed with short promoter fragments or artificial promoters fused with the GUS reporter gene. Our genome-wide analysis opens up new possibilities for in silicio verification of the biological significance of newly discovered CREs, and allows for subsequent selection of such CREs for experimental studies.

  13. Comparison of Boolean analysis and standard phylogenetic methods using artificially evolved and natural mt-tRNA sequences from great apes.

    Science.gov (United States)

    Ari, Eszter; Ittzés, Péter; Podani, János; Thi, Quynh Chi Le; Jakó, Eena

    2012-04-01

    Boolean analysis (or BOOL-AN; Jakó et al., 2009. BOOL-AN: A method for comparative sequence analysis and phylogenetic reconstruction. Mol. Phylogenet. Evol. 52, 887-97.), a recently developed method for sequence comparison uses the Iterative Canonical Form of Boolean functions. It considers sequence information in a way entirely different from standard phylogenetic methods (i.e. Maximum Parsimony, Maximum-Likelihood, Neighbor-Joining, and Bayesian analysis). The performance and reliability of Boolean analysis were tested and compared with the standard phylogenetic methods, using artificially evolved - simulated - nucleotide sequences and the 22 mitochondrial tRNA genes of the great apes. At the outset, we assumed that the phylogeny of Hominidae is generally well established, and the guide tree of artificial sequence evolution can also be used as a benchmark. These offer a possibility to compare and test the performance of different phylogenetic methods. Trees were reconstructed by each method from 2500 simulated sequences and 22 mitochondrial tRNA sequences. We also introduced a special re-sampling method for Boolean analysis on permuted sequence sites, the P-BOOL-AN procedure. Considering the reliability values (branch support values of consensus trees and Robinson-Foulds distances) we used for simulated sequence trees produced by different phylogenetic methods, BOOL-AN appeared as the most reliable method. Although the mitochondrial tRNA sequences of great apes are relatively short (59-75 bases long) and the ratio of their constant characters is about 75%, BOOL-AN, P-BOOL-AN and the Bayesian approach produced the same tree-topology as the established phylogeny, while the outcomes of Maximum Parsimony, Maximum-Likelihood and Neighbor-Joining methods were equivocal. We conclude that Boolean analysis is a promising alternative to existing methods of sequence comparison for phylogenetic reconstruction and congruence analysis. Copyright © 2012 Elsevier Inc. All

  14. INCLUSION RATIO BASED ESTIMATOR FOR THE MEAN LENGTH OF THE BOOLEAN LINE SEGMENT MODEL WITH AN APPLICATION TO NANOCRYSTALLINE CELLULOSE

    Directory of Open Access Journals (Sweden)

    Mikko Niilo-Rämä

    2014-06-01

    Full Text Available A novel estimator for estimating the mean length of fibres is proposed for censored data observed in square shaped windows. Instead of observing the fibre lengths, we observe the ratio between the intensity estimates of minus-sampling and plus-sampling. It is well-known that both intensity estimators are biased. In the current work, we derive the ratio of these biases as a function of the mean length assuming a Boolean line segment model with exponentially distributed lengths and uniformly distributed directions. Having the observed ratio of the intensity estimators, the inverse of the derived function is suggested as a new estimator for the mean length. For this estimator, an approximation of its variance is derived. The accuracies of the approximations are evaluated by means of simulation experiments. The novel method is compared to other methods and applied to real-world industrial data from nanocellulose crystalline.

  15. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  16. Discovery of regulatory elements is improved by a discriminatory approach

    DEFF Research Database (Denmark)

    Valen, Eivind; Sandelin, Albin; Winther, Ole

    2009-01-01

    A major goal in post-genome biology is the complete mapping of the gene regulatory networks for every organism. Identification of regulatory elements is a prerequisite for realizing this ambitious goal. A common problem is finding regulatory patterns in promoters of a group of co-expressed genes,...

  17. What's the Regulatory Value of a Target Product Profile?

    Science.gov (United States)

    Breder, Christopher D; Du, Wenny; Tyndall, Adria

    2017-07-01

    Target product profiles (TPPs) are used as a regulatory tool for dialog on clinical development or manufacturing plans. Drugs and biologics approved by the FDA that mention TPPs are associated with more efficient regulatory review times, perhaps as a result of increased planning or because the TPP promotes well-organized regulatory dialog. Published by Elsevier Ltd.

  18. Synthetic biological networks

    International Nuclear Information System (INIS)

    Archer, Eric; Süel, Gürol M

    2013-01-01

    Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

  19. Robustness Analysis of Gene Regulatory Networks

    Science.gov (United States)

    Kadelka, Claus T.

    Cells generally manage to maintain stable phenotypes in the face of widely varying environmental conditions. This fact is particularly surprising since the key step of gene expression is fundamentally a stochastic process. Many hypotheses have been suggested to explain this robustness. First, the special topology of gene regulatory networks (GRNs) seems to be an important factor as they possess feedforward loops and certain other topological features much more frequently than expected. Second, genes often regulate each other in a canalizing fashion: there exists a dominance order amidst the regulators of a gene, which in silico leads to very robust phenotypes. Lastly, an entirely novel gene regulatory mechanism, discovered and studied during the last two decades, which is believed to play an important role in cancer, is shedding some light on how canalization may in fact take place as part of a cell's gene regulatory program. Short segments of single-stranded RNA, so-called microRNAs, which are embedded in several different types of feedforward loops, help smooth out noise and generate canalizing effects in gene regulation by overriding the effect of certain genes on others. Boolean networks and their multi-state extensions have been successfully used to model GRNs for many years. In this dissertation, GRNs are represented in the time- and state-discrete framework of Stochastic Discrete Dynamical Systems (SDDS), which captures the cell-inherent stochasticity. Each gene has finitely many different concentration levels and its concentration at the next time step is determined by a gene-specific update rule that depends on the current concentration of the gene's regulators. The update rules in published gene regulatory networks are often nested canalizing functions. In Chapter 2, this class of functions is introduced, generalized and analyzed with respect to its potential to confer robustness. Chapter 3 describes a simulation study, which supports the hypothesis that

  20. Regulatory Anatomy

    OpenAIRE

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term ?safety logics? to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, legal documents, technological devices, organizational structures, and work practices aimed at minimizing risk. I use this term to reorient the analytical attention with respect to safety regulation. In...

  1. Regulatory considerations for biosimilars

    Directory of Open Access Journals (Sweden)

    Ranjani Nellore

    2010-01-01

    Full Text Available Currently there is considerable interest in the legislative debate around generic biological drugs or "biosimilars" in the EU and US due to the large, lucrative market that it offers to the industry. While some countries have issued a few regulatory guidelines as well as product specific requirements, there is no general consensus as to a single, simple mechanism similar to the bioequivalence determination that leads to approval of generic small molecules all over the world. The inherent complex nature of the molecules, along with complicated manufacturing and analytical techniques to characterize them make it difficult to rely on a single human pharmacokinetic study for assurance of safety and efficacy. In general, the concept of comparability has been used for evaluation of the currently approved "similar" biological where a step by step assessment on the quality, preclinical and clinical aspects is made. In India, the focus is primarily on the availability and affordability of life-saving drugs. In this context every product needs to be evaluated on its own merit irrespective of the innovator brand. The formation of the National Biotechnology Regulatory Authority may provide a step in the right direction for regulation of these complex molecules. However, in order to have an efficient machinery for initial approval and ongoing oversight with a country-specific focus, cooperation with international authorities for granting approvals and continuous risk-benefit review is essential. Several steps are still needed for India to be perceived as a country that leads the world in providing quality biological products.

  2. Modular genetic regulatory networks increase organization during pattern formation.

    Science.gov (United States)

    Mohamadlou, Hamid; Podgorski, Gregory J; Flann, Nicholas S

    2016-08-01

    Studies have shown that genetic regulatory networks (GRNs) consist of modules that are densely connected subnetworks that function quasi-autonomously. Modules may be recognized motifs that comprise of two or three genes with particular regulatory functions and connectivity or be purely structural and identified through connection density. It is unclear what evolutionary and developmental advantages modular structure and in particular motifs provide that have led to this enrichment. This study seeks to understand how modules within developmental GRNs influence the complexity of multicellular patterns that emerge from the dynamics of the regulatory networks. We apply an algorithmic complexity to measure the organization of the patterns. A computational study was performed by creating Boolean intracellular networks within a simulated epithelial field of embryonic cells, where each cell contains the same network and communicates with adjacent cells using contact-mediated signaling. Intracellular networks with random connectivity were compared to those with modular connectivity and with motifs. Results show that modularity effects network dynamics and pattern organization significantly. In particular: (1) modular connectivity alone increases complexity in network dynamics and patterns; (2) bistable switch motifs simplify both the pattern and network dynamics; (3) all other motifs with feedback loops increase multicellular pattern complexity while simplifying the network dynamics; (4) negative feedback loops affect the dynamics complexity more significantly than positive feedback loops. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Logical knowledge representation of regulatory relations in biomedical pathways

    DEFF Research Database (Denmark)

    Zambach, Sine; Hansen, Jens Ulrik

    2010-01-01

    Knowledge on regulatory relations, in for example regulatory pathways in biology, is used widely in experiment design by biomedical researchers and in systems biology. The knowledge has typically either been represented through simple graphs or through very expressive differential equation simula...

  4. Biosimilars: State of Clinical and Regulatory Science.

    Science.gov (United States)

    Klein, Agnes Victoria; Wang, Jian; Feagan, Brian G; Omoto, Mark

    2017-01-01

    On May 12, 2017, various issues and challenges associated with biologics were discussed during a session of the annual joint conference of Canadian Society for Pharmaceutical Sciences and Canadian Chapter of Controlled Release Society at Hyatt Regency Hotel, Montréal, QC, Canada.  An update on the Canadian regulatory guidelines for biosimilars was given, followed by viewpoints expressed by regulatory, academic and industry scientists.  Topics of discussion included: reference biologic drug, clinical considerations, immunogenicity, extrapolation and clarification of terminology, product monograph, international collaboration, switching and interchangeability, naming conventions, clinical and non-clinical evaluation, authorization of indications, statistical equivalence, the nor-switch study and biologics marketplace.

  5. Generalized Boolean logic Driven Markov Processes: A powerful modeling framework for Model-Based Safety Analysis of dynamic repairable and reconfigurable systems

    International Nuclear Information System (INIS)

    Piriou, Pierre-Yves; Faure, Jean-Marc; Lesage, Jean-Jacques

    2017-01-01

    This paper presents a modeling framework that permits to describe in an integrated manner the structure of the critical system to analyze, by using an enriched fault tree, the dysfunctional behavior of its components, by means of Markov processes, and the reconfiguration strategies that have been planned to ensure safety and availability, with Moore machines. This framework has been developed from BDMP (Boolean logic Driven Markov Processes), a previous framework for dynamic repairable systems. First, the contribution is motivated by pinpointing the limitations of BDMP to model complex reconfiguration strategies and the failures of the control of these strategies. The syntax and semantics of GBDMP (Generalized Boolean logic Driven Markov Processes) are then formally defined; in particular, an algorithm to analyze the dynamic behavior of a GBDMP model is developed. The modeling capabilities of this framework are illustrated on three representative examples. Last, qualitative and quantitative analysis of GDBMP models highlight the benefits of the approach.

  6. Systems Biology of Metabolism.

    Science.gov (United States)

    Nielsen, Jens

    2017-06-20

    Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are described, and two different types of mathematical models used for studying metabolism are discussed: kinetic models and genome-scale metabolic models. The use of different omics technologies, including transcriptomics, proteomics, metabolomics, and fluxomics, for studying metabolism is presented. Finally, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed.

  7. Algorithm for finding partitionings of hard variants of boolean satisfiability problem with application to inversion of some cryptographic functions.

    Science.gov (United States)

    Semenov, Alexander; Zaikin, Oleg

    2016-01-01

    In this paper we propose an approach for constructing partitionings of hard variants of the Boolean satisfiability problem (SAT). Such partitionings can be used for solving corresponding SAT instances in parallel. For the same SAT instance one can construct different partitionings, each of them is a set of simplified versions of the original SAT instance. The effectiveness of an arbitrary partitioning is determined by the total time of solving of all SAT instances from it. We suggest the approach, based on the Monte Carlo method, for estimating time of processing of an arbitrary partitioning. With each partitioning we associate a point in the special finite search space. The estimation of effectiveness of the particular partitioning is the value of predictive function in the corresponding point of this space. The problem of search for an effective partitioning can be formulated as a problem of optimization of the predictive function. We use metaheuristic algorithms (simulated annealing and tabu search) to move from point to point in the search space. In our computational experiments we found partitionings for SAT instances encoding problems of inversion of some cryptographic functions. Several of these SAT instances with realistic predicted solving time were successfully solved on a computing cluster and in the volunteer computing project SAT@home. The solving time agrees well with estimations obtained by the proposed method.

  8. Adaptive Dynamics of Regulatory Networks: Size Matters

    Directory of Open Access Journals (Sweden)

    Martinetz Thomas

    2009-01-01

    Full Text Available To accomplish adaptability, all living organisms are constructed of regulatory networks on different levels which are capable to differentially respond to a variety of environmental inputs. Structure of regulatory networks determines their phenotypical plasticity, that is, the degree of detail and appropriateness of regulatory replies to environmental or developmental challenges. This regulatory network structure is encoded within the genotype. Our conceptual simulation study investigates how network structure constrains the evolution of networks and their adaptive abilities. The focus is on the structural parameter network size. We show that small regulatory networks adapt fast, but not as good as larger networks in the longer perspective. Selection leads to an optimal network size dependent on heterogeneity of the environment and time pressure of adaptation. Optimal mutation rates are higher for smaller networks. We put special emphasis on discussing our simulation results on the background of functional observations from experimental and evolutionary biology.

  9. Linking network topology to function. Comment on "Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function" by O.C. Martin, A. Krzywicki and M. Zagorski

    Science.gov (United States)

    di Bernardo, Diego

    2016-07-01

    The review by Martin et al. deals with a long standing problem at the interface of complex systems and molecular biology, that is the relationship between the topology of a complex network and its function. In biological terms the problem translates to relating the topology of gene regulatory networks (GRNs) to specific cellular functions. GRNs control the spatial and temporal activity of the genes encoded in the cell's genome by means of specialised proteins called Transcription Factors (TFs). A TF is able to recognise and bind specifically to a sequence (TF biding site) of variable length (order of magnitude of 10) found upstream of the sequence encoding one or more genes (at least in prokaryotes) and thus activating or repressing their transcription. TFs can thus be distinguished in activator and repressor. The picture can become more complex since some classes of TFs can form hetero-dimers consisting of a protein complex whose subunits are the individual TFs. Heterodimers can have completely different binding sites and activity compared to their individual parts. In this review the authors limit their attention to prokaryotes where the complexity of GRNs is somewhat reduced. Moreover they exploit a unique feature of living systems, i.e. evolution, to understand whether function can shape network topology. Indeed, prokaryotes such as bacteria are among the oldest living systems that have become perfectly adapted to their environment over geological scales and thus have reached an evolutionary steady-state where the fitness of the population has reached a plateau. By integrating in silico analysis and comparative evolution, the authors show that indeed function does tend to shape the structure of a GRN, however this trend is not always present and depends on the properties of the network being examined. Interestingly, the trend is more apparent for sparse networks, i.e. where the density of edges is very low. Sparsity is indeed one of the most prominent features

  10. Access and benefit sharing (ABS) under the convention on biological diversity (CBD): implications for microbial biological control

    Science.gov (United States)

    Researchers and implementers of biological control are confronted with a variety of scientific, regulatory and administrative challenges to their biological control programs. One developing challenge will arise from the implementation of provisions of the Convention on Biological Diversity (CBD) co...

  11. Singular Perturbation Analysis and Gene Regulatory Networks with Delay

    Science.gov (United States)

    Shlykova, Irina; Ponosov, Arcady

    2009-09-01

    There are different ways of how to model gene regulatory networks. Differential equations allow for a detailed description of the network's dynamics and provide an explicit model of the gene concentration changes over time. Production and relative degradation rate functions used in such models depend on the vector of steeply sloped threshold functions which characterize the activity of genes. The most popular example of the threshold functions comes from the Boolean network approach, where the threshold functions are given by step functions. The system of differential equations becomes then piecewise linear. The dynamics of this system can be described very easily between the thresholds, but not in the switching domains. For instance this approach fails to analyze stationary points of the system and to define continuous solutions in the switching domains. These problems were studied in [2], [3], but the proposed model did not take into account a time delay in cellular systems. However, analysis of real gene expression data shows a considerable number of time-delayed interactions suggesting that time delay is essential in gene regulation. Therefore, delays may have a great effect on the dynamics of the system presenting one of the critical factors that should be considered in reconstruction of gene regulatory networks. The goal of this work is to apply the singular perturbation analysis to certain systems with delay and to obtain an analog of Tikhonov's theorem, which provides sufficient conditions for constracting the limit system in the delay case.

  12. Inference of gene regulatory networks from time series by Tsallis entropy

    Directory of Open Access Journals (Sweden)

    de Oliveira Evaldo A

    2011-05-01

    Full Text Available Abstract Background The inference of gene regulatory networks (GRNs from large-scale expression profiles is one of the most challenging problems of Systems Biology nowadays. Many techniques and models have been proposed for this task. However, it is not generally possible to recover the original topology with great accuracy, mainly due to the short time series data in face of the high complexity of the networks and the intrinsic noise of the expression measurements. In order to improve the accuracy of GRNs inference methods based on entropy (mutual information, a new criterion function is here proposed. Results In this paper we introduce the use of generalized entropy proposed by Tsallis, for the inference of GRNs from time series expression profiles. The inference process is based on a feature selection approach and the conditional entropy is applied as criterion function. In order to assess the proposed methodology, the algorithm is applied to recover the network topology from temporal expressions generated by an artificial gene network (AGN model as well as from the DREAM challenge. The adopted AGN is based on theoretical models of complex networks and its gene transference function is obtained from random drawing on the set of possible Boolean functions, thus creating its dynamics. On the other hand, DREAM time series data presents variation of network size and its topologies are based on real networks. The dynamics are generated by continuous differential equations with noise and perturbation. By adopting both data sources, it is possible to estimate the average quality of the inference with respect to different network topologies, transfer functions and network sizes. Conclusions A remarkable improvement of accuracy was observed in the experimental results by reducing the number of false connections in the inferred topology by the non-Shannon entropy. The obtained best free parameter of the Tsallis entropy was on average in the range 2.5

  13. Towards Logical Designs In Biology

    Indian Academy of Sciences (India)

    Towards Logical Designs in Biology. Garima Agarwal. General Article Volume 12 Issue 2 February 2007 pp 29-38. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/012/02/0029-0038. Keywords. Synthetic biology; logic gates; regulatory modules; gene circuits. Author Affiliations.

  14. Nonvolatile “AND,” “OR,” and “NOT” Boolean logic gates based on phase-change memory

    International Nuclear Information System (INIS)

    Li, Y.; Zhong, Y. P.; Deng, Y. F.; Zhou, Y. X.; Xu, L.; Miao, X. S.

    2013-01-01

    Electronic devices or circuits that can implement both logic and memory functions are regarded as the building blocks for future massive parallel computing beyond von Neumann architecture. Here we proposed phase-change memory (PCM)-based nonvolatile logic gates capable of AND, OR, and NOT Boolean logic operations verified in SPICE simulations and circuit experiments. The logic operations are parallel computing and results can be stored directly in the states of the logic gates, facilitating the combination of computing and memory in the same circuit. These results are encouraging for ultralow-power and high-speed nonvolatile logic circuit design based on novel memory devices

  15. Psychological state is related to the remission of the Boolean-based definition of patient global assessment in patients with rheumatoid arthritis.

    Science.gov (United States)

    Fusama, Mie; Miura, Yasushi; Yukioka, Kumiko; Kuroiwa, Takanori; Yukioka, Chikako; Inoue, Miyako; Nakanishi, Tae; Murata, Norikazu; Takai, Noriko; Higashi, Kayoko; Kuritani, Taro; Maeda, Keiji; Sano, Hajime; Yukioka, Masao; Nakahara, Hideko

    2015-09-01

    To evaluate whether the psychological state is related to the Boolean-based definition of patient global assessment (PGA) remission in patients with rheumatoid arthritis (RA). Patients with RA who met the criteria of swollen joint count (SJC) ≤ 1, tender joint count (TJC) ≤ 1 and C-reactive protein (CRP) ≤ 1 were divided into two groups, PGA remission group (PGA ≤ 1 cm) and non-remission group (PGA > 1 cm). Anxiety was evaluated utilizing the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), while depression was evaluated with HADS-Depression (HADS-D) and the Center for Epidemiologic Studies Depression Scale (CES-D). Comparison analyses were done between the PGA remission and non-remission groups in HADS-A, HADS-D and CES-D. Seventy-eight patients met the criteria for SJC ≤ 1, TJC ≤ 1 and CRP ≤ 1. There were no significant differences between the PGA remission group (n = 45) and the non-remission group (n = 33) in age, sex, disease duration and Steinbrocker's class and stage. HADS-A, HADS-D and CES-D scores were significantly lower in the PGA remission group. Patients with RA who did not meet the PGA remission criteria despite good disease condition were in a poorer psychological state than those who satisfied the Boolean-based definition of clinical remission. Psychological support might be effective for improvement of PGA, resulting in the attainment of true remission.

  16. Using boolean and fuzzy logic combined with analytic hierarchy process for hazardous waste landfill site selection: A case study from Hormozgan province, Iran

    Directory of Open Access Journals (Sweden)

    Mahdieh Saadat Foomani

    2017-01-01

    Full Text Available Hazardous wastes include numerous kinds of discarded chemicals and other wastes generated from industrial, commercial, and institutional activities. These types of waste present immediate or long-term risks to humans, animals, plants, or the environment and therefore require special handling for safe disposal. Landfills that can accept hazardous wastes are excavated or engineered sites where these special types of waste can be disposed of securely. Since landfills are permanent sites, special attention must be afforded in selecting the location. This paper investigated the use of the Boolean theory and Fuzzy logic in combination with Analytic Hierarchy Process (AHP methods by applying GIS and IDRISI software for the selection of a hazardous waste landfill site in the Iranian province of Hormozgan. The best location was determined via the Fuzzy and the Boolean methodologies. By collating the area selected for the hazardous waste landfill, this study found that Fuzzy logic with an AND operator had the best options for this purpose. In the end, the most suitable area for a hazardous waste landfill was about 1.6 km2 which was obtained by employing Fuzzy in combination with AHP and by using an AND operator. In addition, all the fundamental criteria affecting the landfill location were considered.

  17. Regulatory RNAs in Planarians.

    Science.gov (United States)

    Pawlicka, Kamila; Perrigue, Patrick M; Barciszewski, Jan

    2016-01-01

    The full scope of regulatory RNA evolution and function in epigenetic processes is still not well understood. The development of planarian flatworms to be used as a simple model organism for research has shown a great potential to address gaps in the knowledge in this field of study. The genomes of planarians encode a wide array of regulatory RNAs that function in gene regulation. Here, we review planarians as a suitable model organism for the identification and function of regulatory RNAs.

  18. Comparative analysis of regulatory information and circuits across distant species.

    Science.gov (United States)

    Boyle, Alan P; Araya, Carlos L; Brdlik, Cathleen; Cayting, Philip; Cheng, Chao; Cheng, Yong; Gardner, Kathryn; Hillier, LaDeana W; Janette, Judith; Jiang, Lixia; Kasper, Dionna; Kawli, Trupti; Kheradpour, Pouya; Kundaje, Anshul; Li, Jingyi Jessica; Ma, Lijia; Niu, Wei; Rehm, E Jay; Rozowsky, Joel; Slattery, Matthew; Spokony, Rebecca; Terrell, Robert; Vafeados, Dionne; Wang, Daifeng; Weisdepp, Peter; Wu, Yi-Chieh; Xie, Dan; Yan, Koon-Kiu; Feingold, Elise A; Good, Peter J; Pazin, Michael J; Huang, Haiyan; Bickel, Peter J; Brenner, Steven E; Reinke, Valerie; Waterston, Robert H; Gerstein, Mark; White, Kevin P; Kellis, Manolis; Snyder, Michael

    2014-08-28

    Despite the large evolutionary distances between metazoan species, they can show remarkable commonalities in their biology, and this has helped to establish fly and worm as model organisms for human biology. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. Here we map the genome-wide binding locations of 165 human, 93 worm and 52 fly transcription regulatory factors, generating a total of 1,019 data sets from diverse cell types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regulatory networks are remarkably conserved and that orthologous regulatory factor families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual network connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding of the regulatory underpinnings of model organism biology and how these relate to human biology, development and disease.

  19. Mammalian Synthetic Biology

    OpenAIRE

    Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

    2016-01-01

    The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-pote...

  20. Using of the Boolean Stochastic Generation method to target field investigations: the Mortisa landslide (eastern Italian Alps) case study

    Science.gov (United States)

    Bossi, Giulia; Marcato, Gianluca; Gottardi, Guido; Borgatti, Lisa

    2016-04-01

    When designing the geotechnical model of a landslide the information to define the soil profile within the slope is usually inferred from a small amount of data. This is particularly true for large landslides where the study area is vast and the variability of terrains is high. In this framework, a method allowing the best locations for further field investigation campaigns to be identified would be extremely useful. The Boolean Stochastic Generation method (BoSG), which randomly generates different soil distributions of two definite soil types in both 2D and 3D models, is a newly developed algorithm that can guide in this process. In this work the method has been applied to the Mortisa landslide case study, which is located in the Cortina d'Ampezzo valley (Veneto, Italy), part of the Dolomites UNESCO World Heritage list. The mudslide is 3.5 km long, stretching from 1750 to 1300 m a.s.l., and is located in a highly antrophized area where is damaging some buildings and a national road with its almost continuous movements. In fact, from year 2008, GNSS surveys recorded rates of displacements reaching 1.2 m/year in the most active parts of the landslide; the movements occur on a slip surfaces are located between 20 and 50 m below the surface. From the borecores some wooden samples were extracted allowing to reconstruct the sequence of events that led to the development of the present-day Mortisa slope. Interdigitated layers of gravel in a silty clay matrix originated from subsequent earth and debris flows events since the Lateglacial compose the landslide body, a condition that is particularly apt to be investigated with BoSG. A BoSG run for the Mortisa landslide was performed calculating 1200 soil configurations and using laboratory test parameters for the silty-clay matrix. The results were stacked in a tridimensional matrix in order to calculate the mean and the standard deviation (SD) of displacements for each element of the model mesh. In this way maps of the SD

  1. 3 CFR - Regulatory Review

    Science.gov (United States)

    2010-01-01

    ... Departments and Agencies For well over two decades, the Office of Information and Regulatory Affairs (OIRA) at... opportunities and security. While recognizing the expertise and authority of executive branch departments and... as a means of promoting regulatory goals. The fundamental principles and structures governing...

  2. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-10-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  3. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-08-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  4. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1991-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  5. Nuclear Regulatory legislation

    International Nuclear Information System (INIS)

    1984-06-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 97th Congress, 2nd Session, has been prepared by the Office of the Executive Legal Director, U.S. Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document

  6. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  7. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-01-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  8. TIGER: Toolbox for integrating genome-scale metabolic models, expression data, and transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    Jensen Paul A

    2011-09-01

    Full Text Available Abstract Background Several methods have been developed for analyzing genome-scale models of metabolism and transcriptional regulation. Many of these methods, such as Flux Balance Analysis, use constrained optimization to predict relationships between metabolic flux and the genes that encode and regulate enzyme activity. Recently, mixed integer programming has been used to encode these gene-protein-reaction (GPR relationships into a single optimization problem, but these techniques are often of limited generality and lack a tool for automating the conversion of rules to a coupled regulatory/metabolic model. Results We present TIGER, a Toolbox for Integrating Genome-scale Metabolism, Expression, and Regulation. TIGER converts a series of generalized, Boolean or multilevel rules into a set of mixed integer inequalities. The package also includes implementations of existing algorithms to integrate high-throughput expression data with genome-scale models of metabolism and transcriptional regulation. We demonstrate how TIGER automates the coupling of a genome-scale metabolic model with GPR logic and models of transcriptional regulation, thereby serving as a platform for algorithm development and large-scale metabolic analysis. Additionally, we demonstrate how TIGER's algorithms can be used to identify inconsistencies and improve existing models of transcriptional regulation with examples from the reconstructed transcriptional regulatory network of Saccharomyces cerevisiae. Conclusion The TIGER package provides a consistent platform for algorithm development and extending existing genome-scale metabolic models with regulatory networks and high-throughput data.

  9. An oral administration of a recombinant anti-TNF fusion protein is biologically active in the gut promoting regulatory T cells: Results of a phase I clinical trial using a novel oral anti-TNF alpha-based therapy.

    Science.gov (United States)

    Almon, Einat; Khoury, Tawfik; Drori, Ariel; Gingis-Velitski, Svetlana; Alon, Sari; Chertkoff, Raul; Mushkat, Mordechai; Shaaltiel, Yoseph; Ilan, Yaron

    2017-07-01

    An orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human IgG1 domain. Aim This study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans. Three different doses (2, 8 or 16mg/day) of PRX-106 were orally administered for five consecutive days in 14 healthy volunteered participants. Subjects were followed for safety parameters and for an effect on T lymphocytes subsets and cytokine levels. An oral administration of PRX-106 was safe and well tolerated. The PK study showed that PRX106 is not absorbed. No effect on white blood cells and lymphocytes counts were noted. A dose dependent effect was noted on systemic lymphocytes. The oral administration of all three dosages was associated with an increase in CD4+CD25+ and CD8+CD25+ subset of suppressor lymphocytes. A marked increase in CD4+CD25+FoxP3 regulatory T cells was noted in the 8mg treated group. In addition, NKT regulatory cells, CD3+CD69+ and CD4+CD62 lymphocyte subsets increased with treatment. No changes in serum TNF alpha were observed. An oral administration of the non-absorbable recombinant anti-TNF fusion protein, PRX-106, is safe, not associated with immune suppression, while inducing a favorable anti-inflammatory immune modulation. The PRX-106 may provide a safe orally administered effective anti-TNF alpha-based immune therapy for inflammatory bowel diseases and non-alcoholic steatohepatitis, as well as other autoimmune, TNF-mediated diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology.

    Science.gov (United States)

    Jafari, Mohieddin; Ansari-Pour, Naser; Azimzadeh, Sadegh; Mirzaie, Mehdi

    It is nearly half a century past the age of the introduction of the Central Dogma (CD) of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology.

  11. Release measurements, release from regulatory control and inactive removal of the heavy concrete from the biological shield of the Seibersdorf research reactor; Freimessen, Freigabe und Entsorgung des Barytbetons vom biologischen Schild des Forschungsreaktors Seibersdorf

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, F.; Steger, F.; Djuricic, M.; Metzker, E.; Lechner, C. [Nuclear Engineering Seibersdorf GmbH (NES), Seibersdorf (Austria); Feichtinger, J. [Oesterreichisches Forschungszentrum Seibersdorf GmbH, Vienna (Austria)

    2009-07-01

    The ASTRA reactor in the Research Centre Seibersdorf was switched off finally on 31 July 1999 after 38 years successful operation and thus the decommissioning and dismantling of the reactor was decided. Apart from other system parts the biological shield, made of barite concrete was dismantled. As a dismantling and/or deconstruct method 'a block-by-block' removal was selected and used. Because on the upper parts of the biological shield no activation could be expected, these parts were free-measured only gammaspectrometrically using ISOCS (in-Situ Object Counting system) and disposed. Afterwards the lower, neutronactivated part was removed with the same cut technology as the upper part, mechanically reduced and the reinforcing irons removed. The broken heavy concrete was filled into Standard-200-Liter-barrels, was free-measured by the measuring system RADOS and disposed. Not released parts were taken to the interim storage facility of NES. (orig.)

  12. Small-scale universality and large-scale diversity. Comment on "Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function" by O.C. Martin, A. Krzywicki, and M. Zagorski

    Science.gov (United States)

    Ispolatov, Yaroslav

    2016-07-01

    Martin et al. undertook an arduous task of reviewing vast literature on evolution and functionality of directed biological networks and gene networks in particular. The literature is assessed addressing a question of whether a set of features particular for gene networks is repeatedly recreated among unrelated species driven by selection pressure or has evolved once and is being inherited. To argue for the former mechanism, Martin and colleagues explore the following examples: Scale-free out-degree distribution.

  13. Regulatory guidance document

    International Nuclear Information System (INIS)

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM's evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7

  14. Transcription regulatory networks analysis using CAGE

    KAUST Repository

    Tegnér, Jesper N.

    2009-10-01

    Mapping out cellular networks in general and transcriptional networks in particular has proved to be a bottle-neck hampering our understanding of biological processes. Integrative approaches fusing computational and experimental technologies for decoding transcriptional networks at a high level of resolution is therefore of uttermost importance. Yet, this is challenging since the control of gene expression in eukaryotes is a complex multi-level process influenced by several epigenetic factors and the fine interplay between regulatory proteins and the promoter structure governing the combinatorial regulation of gene expression. In this chapter we review how the CAGE data can be integrated with other measurements such as expression, physical interactions and computational prediction of regulatory motifs, which together can provide a genome-wide picture of eukaryotic transcriptional regulatory networks at a new level of resolution. © 2010 by Pan Stanford Publishing Pte. Ltd. All rights reserved.

  15. Managing Regulatory Body Competence

    International Nuclear Information System (INIS)

    2013-01-01

    In 2001, the IAEA published TECDOC 1254, which examined the way in which the recognized functions of a regulatory body for nuclear facilities results in competence needs. Using the systematic approach to training (SAT), TECDOC 1254 provided a framework for regulatory bodies for managing training and developing and their maintaining their competence. It has been successfully used by many regulators. The IAEA has also introduced a methodology and an assessment tool - Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) - which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2009, the IAEA established a steering committee (supported by a bureau) with the mission to advise the IAEA on how it could best assist Member States to develop suitable competence management systems for their regulatory bodies. The committee recommended the development of a safety report on managing staff competence as an integral part of a regulatory body's management system. This Safety Report was developed in response to this request. It supersedes TECDOC 1254, broadens its application to regulatory bodies for all facilities and activities, and builds upon the experience gained through the application of TECDOC 1254 and SARCoN and the feedback received from Member States. This Safety Report applies to the management of adequate competence as needs change, and as such is equally applicable to the needs of States 'embarking' on a nuclear power programme. It also deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an 'embarking' State's regulatory system

  16. The next step in biology: A periodic table?

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    2007-08-06

    Aug 6, 2007 ... At the fundamental level, biological components may be genes, as in regulatory networks, ... protein fold as the fundamental unit. [Dhar P K 2007 The next step in biology: A periodic table?; .... management table' would set boundary conditions to these processes by adding regulatory loops, quantitative.

  17. Mutational robustness of gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Aalt D J van Dijk

    Full Text Available Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive. In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence.

  18. Emotion: The Self-regulatory Sense

    Science.gov (United States)

    2014-01-01

    While emotion is a central component of human health and well-being, traditional approaches to understanding its biological function have been wanting. A dynamic systems model, however, broadly redefines and recasts emotion as a primary sensory system—perhaps the first sensory system to have emerged, serving the ancient autopoietic function of “self-regulation.” Drawing upon molecular biology and revelations from the field of epigenetics, the model suggests that human emotional perceptions provide an ongoing stream of “self-relevant” sensory information concerning optimally adaptive states between the organism and its immediate environment, along with coupled behavioral corrections that honor a universal self-regulatory logic, one still encoded within cellular signaling and immune functions. Exemplified by the fundamental molecular circuitry of sensorimotor control in the E coli bacterium, the model suggests that the hedonic (affective) categories emerge directly from positive and negative feedback processes, their good/bad binary appraisals relating to dual self-regulatory behavioral regimes—evolutionary purposes, through which organisms actively participate in natural selection, and through which humans can interpret optimal or deficit states of balanced being and becoming. The self-regulatory sensory paradigm transcends anthropomorphism, unites divergent theoretical perspectives and isolated bodies of literature, while challenging time-honored assumptions. While suppressive regulatory strategies abound, it suggests that emotions are better understood as regulating us, providing a service crucial to all semantic language, learning systems, evaluative decision-making, and fundamental to optimal physical, mental, and social health. PMID:24808986

  19. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-04-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  20. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-10-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  1. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

    Mathur, Melina; Xiang, Joy S; Smolke, Christina D

    2017-01-02

    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

  2. Intervention in gene regulatory networks via greedy control policies based on long-run behavior

    Directory of Open Access Journals (Sweden)

    Ghaffari Noushin

    2009-06-01

    Full Text Available Abstract Background A salient purpose for studying gene regulatory networks is to derive intervention strategies, the goals being to identify potential drug targets and design gene-based therapeutic intervention. Optimal stochastic control based on the transition probability matrix of the underlying Markov chain has been studied extensively for probabilistic Boolean networks. Optimization is based on minimization of a cost function and a key goal of control is to reduce the steady-state probability mass of undesirable network states. Owing to computational complexity, it is difficult to apply optimal control for large networks. Results In this paper, we propose three new greedy stationary control policies by directly investigating the effects on the network long-run behavior. Similar to the recently proposed mean-first-passage-time (MFPT control policy, these policies do not depend on minimization of a cost function and avoid the computational burden of dynamic programming. They can be used to design stationary control policies that avoid the need for a user-defined cost function because they are based directly on long-run network behavior; they can be used as an alternative to dynamic programming algorithms when the latter are computationally prohibitive; and they can be used to predict the best control gene with reduced computational complexity, even when one is employing dynamic programming to derive the final control policy. We compare the performance of these three greedy control policies and the MFPT policy using randomly generated probabilistic Boolean networks and give a preliminary example for intervening in a mammalian cell cycle network. Conclusion The newly proposed control policies have better performance in general than the MFPT policy and, as indicated by the results on the mammalian cell cycle network, they can potentially serve as future gene therapeutic intervention strategies.

  3. Technical Memory 2010. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2010-01-01

    The technical memory 2010 of the Nuclear Regulatory Authority of Argentine Republic, compile the papers published in the subject on radiation protection and nuclear safety presented in journals, technical reports, congress or meetings of these subjects by the ARN personnel during 2010. In this edition the documents are presented on: environmental protection; safety transport of radioactive materials; regulations; licensing of medical installations; biological radiation effects; therapeutic uses of ionizing radiation and radioprotection of patients; internal dosimetry; radioactive waste management [es

  4. Technical Memory 2011. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2011-01-01

    The technical memory 2011 of the Nuclear Regulatory Authority of Argentine Republic, compile the papers published in the subject on radiation protection and nuclear safety presented in journals, technical reports, congress or meetings of these subjects by the ARN personnel during 2011. In this edition the documents are presented on: environmental protection; safety transport of radioactive materials; regulations; licensing of medical installations; biological radiation effects; therapeutic uses of ionizing radiation and radioprotection of patients; internal dosimetry; radioactive waste management [es

  5. [Circadian rhythms and systems biology].

    Science.gov (United States)

    Goldbeter, Albert; Gérard, Claude; Leloup, Jean-Christophe

    2010-01-01

    Cellular rhythms represent a field of choice for studies in system biology. The examples of circadian rhythms and of the cell cycle show how the experimental and modeling approaches contribute to clarify the conditions in which periodic behavior spontaneously arises in regulatory networks at the cellular level. Circadian rhythms originate from intertwined positive and negative feedback loops controlling the expression of several clock genes. Models can be used to address the dynamical bases of physiological disorders related to dysfunctions of the mammalian circadian clock. The cell cycle is driven by a network of cyclin-dependent kinases (Cdks). Modeled in the form of four modules coupled through multiple regulatory interactions, the Cdk network operates in an oscillatory manner in the presence of sufficient amounts of growth factor. For circadian rhythms and the cell cycle, as for other recently observed cellular rhythms, periodic behavior represents an emergent property of biological systems related to their regulatory structure.

  6. Metabolism of biologics: biotherapeutic proteins.

    Science.gov (United States)

    Hamuro, Lora L; Kishnani, Narendra S

    2012-01-01

    Recombinant therapeutic protein drugs have now been in clinical use for nearly three decades and have advanced considerably in complexity over this time period. Regulatory approvals of some early pioneering protein drugs did not require characterization of metabolism, but more recently regulatory expectations and guidance have appropriately evolved. Sponsors may now be expected to investigate metabolism of newer biologics as the structural complexity of proteins has increased markedly, particularly with the introduction of conjugated and modified proteins. This review discusses the value and need for metabolite characterization of some therapeutic proteins by presenting select examples. Regulatory expectations will undoubtedly evolve further with the development of other novel macromolecular biologic therapeutics based on modified nucleic acids, novel conjugated lipids and polysaccharides.

  7. Fiscal 1998 achievement report on regional consortium research and development project. Regional consortium of venture business fostering type--Creation of key industries (Development of technologies for manufacturing and utilizing various biological regulatory substances using Hokkaido-produced biomasses as materials); 1998 nendo Dosan biomass wo genryo to shita kakushu seitai chosetsu kino busshitsu no seisan riyo gijutsu kaihatsu seika hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    The efforts aim to meet consumers' needs for products that will prevent lifestyle diseases or the like. For this purpose, substances answering the purpose are extracted from Hokkaido-produced agricultural and aquatic biomasses, and prepared for testing. Researches are conducted on how they behave in the enzyme, cell, and biological systems, and active substances are isolated and identified. In relation to the aquatic biomass, a technology is established of extracting and separating DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), taurine, etc., which are multivalent unsaturated fatty acids effective in preventing lifestyle diseases, from the unused parts of the squid. In relation to the agricultural biomass, antimicrobial active substances are extracted and separated from small fruit plants such as the chicory. Long-keeping foods are tentatively produced by the addition of dried powder of the chicory root tuber. In the elucidation of various biological regulatory substances contained in the Hokkaido-produced biomasses, they are tested for their abilities to resist microbes and active oxygen. Furthermore, verification tests are conducted by administering the substances to the senescence-accelerated mouse (SAM). (NEDO)

  8. Constructing biological pathways by a two-step counting approach.

    Directory of Open Access Journals (Sweden)

    Hsiuying Wang

    Full Text Available Networks are widely used in biology to represent the relationships between genes and gene functions. In Boolean biological models, it is mainly assumed that there are two states to represent a gene: on-state and off-state. It is typically assumed that the relationship between two genes can be characterized by two kinds of pairwise relationships: similarity and prerequisite. Many approaches have been proposed in the literature to reconstruct biological relationships. In this article, we propose a two-step method to reconstruct the biological pathway when the binary array data have measurement error. For a pair of genes in a sample, the first step of this approach is to assign counting numbers for every relationship and select the relationship with counting number greater than a threshold. The second step is to calculate the asymptotic p-values for hypotheses of possible relationships and select relationships with a large p-value. This new method has the advantages of easy calculation for the counting numbers and simple closed forms for the p-value. The simulation study and real data example show that the two-step counting method can accurately reconstruct the biological pathway and outperform the existing methods. Compared with the other existing methods, this two-step method can provide a more accurate and efficient alternative approach for reconstructing the biological network.

  9. Systems Biology

    Indian Academy of Sciences (India)

    IAS Admin

    Systems biology seeks to study biological systems as a whole, contrary to the reductionist approach that has dominated biology. Such a view of biological systems emanating from strong foundations of molecular level understanding of the individual components in terms of their form, function and interactions is promising to ...

  10. Echinoderm systems for gene regulatory studies in evolution and development.

    Science.gov (United States)

    Arnone, Maria Ina; Andrikou, Carmen; Annunziata, Rossella

    2016-08-01

    One of the main challenges in Evolutionary Developmental Biology is to understand to which extent developmental changes are driven by regulatory alterations in the genomic sequence. In the recent years, the focus of comparative developmental studies has moved towards a systems biology approach providing a better understanding of the evolution of gene interactions that form the so called Gene Regulatory Networks (GRN). Echinoderms provide a powerful system to reveal regulatory mechanisms and within the past decade, due to the latest technological innovations, a great number of studies have provided valuable information for comparative GRN analyses. In this review we describe recent advances in evolution of GRNs arising from echinoderm systems, focusing on the properties of conserved regulatory kernels, circuit co-option events and GRN topological rearrangements. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Radiation and the regulatory landscape of neo2-Darwinism

    International Nuclear Information System (INIS)

    Rollo, C. David

    2006-01-01

    Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo 2 -Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology

  12. Perceptions of regulatory approaches

    International Nuclear Information System (INIS)

    Halin, Magnus; Leinonen, Ruusaliisa

    2012-01-01

    Ms. Ruusaliisa Leinonen and Mr. Magnus Halin from Fortum gave a joint presentation on industry perceptions of regulatory oversight of LMfS/SC. It was concluded that an open culture of discussion exists between the regulator (STUK) and the licensee, based on the common goal of nuclear safety. An example was provided of on how regulatory interventions helped foster improvements to individual and collective dose rate trends, which had remained static. Regulatory interventions included discussions on the ALARA concept to reinforce the requirement to continuously strive for improvements in safety performance. Safety culture has also been built into regulatory inspections in recent years. Training days have also been organised by the regulatory body to help develop a shared understanding of safety culture between licensee and regulatory personnel. Fortum has also developed their own training for managers and supervisors. Training and ongoing discussion on LMfS/SC safety culture is considered particularly important because both Fortum and the regulatory body are experiencing an influx of new staff due to the demographic profile of their organisations. It was noted that further work is needed to reach a common understanding of safety culture on a practical level (e.g., for a mechanic setting to work), and in relation to the inspection criteria used by the regulator. The challenges associated with companies with a mix of energy types were also discussed. This can make it more difficult to understand responsibilities and decision making processes, including the role of the parent body organisation. It also makes communication more challenging due to increased complexity and a larger number of stakeholders

  13. Mathematical biology modules based on modern molecular biology and modern discrete mathematics.

    Science.gov (United States)

    Robeva, Raina; Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network.

  14. Mathematical Biology Modules Based on Modern Molecular Biology and Modern Discrete Mathematics

    Science.gov (United States)

    Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network. PMID:20810955

  15. Networks in Cell Biology

    Science.gov (United States)

    Buchanan, Mark; Caldarelli, Guido; De Los Rios, Paolo; Rao, Francesco; Vendruscolo, Michele

    2010-05-01

    Introduction; 1. Network views of the cell Paolo De Los Rios and Michele Vendruscolo; 2. Transcriptional regulatory networks Sarath Chandra Janga and M. Madan Babu; 3. Transcription factors and gene regulatory networks Matteo Brilli, Elissa Calistri and Pietro Lió; 4. Experimental methods for protein interaction identification Peter Uetz, Björn Titz, Seesandra V. Rajagopala and Gerard Cagney; 5. Modeling protein interaction networks Francesco Rao; 6. Dynamics and evolution of metabolic networks Daniel Segré; 7. Hierarchical modularity in biological networks: the case of metabolic networks Erzsébet Ravasz Regan; 8. Signalling networks Gian Paolo Rossini; Appendix 1. Complex networks: from local to global properties D. Garlaschelli and G. Caldarelli; Appendix 2. Modelling the local structure of networks D. Garlaschelli and G. Caldarelli; Appendix 3. Higher-order topological properties S. Ahnert, T. Fink and G. Caldarelli; Appendix 4. Elementary mathematical concepts A. Gabrielli and G. Caldarelli; References.

  16. Federal Reserve System Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... [The Regulatory Plan and Unified Agenda of Federal Regulatory and Deregulatory Actions] [Federal Reserve System Semiannual Regulatory Agenda ] Part XXI Federal Reserve System Semiannual Regulatory Agenda... Flexibility Agenda AGENCY: Board of Governors of the Federal Reserve System. ACTION: Semiannual regulatory...

  17. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    Wieland, Patricia; Almeida, Ivan Pedro Salati de

    2011-01-01

    The scientific considerations upon which the nuclear regulations are based provide objective criteria for decisions on nuclear safety matters. However, the decisions that a regulatory agency takes go far beyond granting or not an operating license based on assessment of compliance. It may involve decisions about hiring experts or research, appeals, responses to other government agencies, international agreements, etc.. In all cases, top management of the regulatory agency should hear and decide the best balance between the benefits of regulatory action and undue risks and other associated impacts that may arise, including issues of credibility and reputation. The establishment of a decision framework based on well established principles and criteria ensures performance stability and consistency, preventing individual subjectivity. This article analyzes the challenges to the decision-making by regulatory agencies to ensure coherence and consistency in decisions, even in situations where there is uncertainty, lack of reliable information and even divergence of opinions among experts. The article explores the basic elements for a framework for regulatory decision-making. (author)

  18. Process-driven inference of biological network structure: feasibility, minimality, and multiplicity.

    Directory of Open Access Journals (Sweden)

    Guanyu Wang

    Full Text Available A common problem in molecular biology is to use experimental data, such as microarray data, to infer knowledge about the structure of interactions between important molecules in subsystems of the cell. By approximating the state of each molecule as "on" or "off", it becomes possible to simplify the problem, and exploit the tools of boolean analysis for such inference. Amongst boolean techniques, the process-driven approach has shown promise in being able to identify putative network structures, as well as stability and modularity properties. This paper examines the process-driven approach more formally, and makes four contributions about the computational complexity of the inference problem, under the "dominant inhibition" assumption of molecular interactions. The first is a proof that the feasibility problem (does there exist a network that explains the data? can be solved in polynomial-time. Second, the minimality problem (what is the smallest network that explains the data? is shown to be NP-hard, and therefore unlikely to result in a polynomial-time algorithm. Third, a simple polynomial-time heuristic is shown to produce near-minimal solutions, as demonstrated by simulation. Fourth, the theoretical framework explains how multiplicity (the number of network solutions to realize a given biological process, which can take exponential-time to compute, can instead be accurately estimated by a fast, polynomial-time heuristic.

  19. Nuclear Regulatory Legislation

    International Nuclear Information System (INIS)

    1989-08-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 100th Congress, 2nd Session, has been prepared by the Office of the General Counsel, US Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document. Persons using this document are placed on notice that it may not be used as an authoritative citation in lieu of the primary legislative sources. Furthermore, while every effort has been made to ensure the completeness and accuracy of this material, neither the United States Government, the Nuclear Regulatory Commission, nor any of their employees makes any expressed or implied warranty or assumes liability for the accuracy or completeness of the material presented in this compilation

  20. Regulatory and licensee surveys

    International Nuclear Information System (INIS)

    2009-01-01

    Prior to the workshop two CSNI/WGHOF surveys were distributed. One survey was directed at regulatory bodies and the other was directed at plant licensees. The surveys were: 1 - Regulatory Expectations of Licensees' Arrangements to Ensure Suitable Organisational Structure, Resources and Competencies to Manage Safety (sent to WGHOF regulatory members). The survey requested that the respondents provide a brief overview of the situation related to plant organisations in their country, their regulatory expectations and their formal requirements. The survey addressed three subjects: the demonstration and documentation of organisational structures, resources and competencies, organisational changes, issues for improvement (for both current and new plants). Responses were received from eleven regulatory bodies. 2 - Approaches to Justify Organisational Suitability (sent to selected licensees). The purpose of the survey to was to gain an understanding of how licensees ensure organisational suitability, resources and competencies. This information was used to assist in the development of the issues and subjects that were addressed at the group discussion sessions. Responses were received from over fifteen licensees from nine countries. The survey requested that the licensees provide information on how they ensure effective organisational structures at their plants. The survey grouped the questions into the following four categories: organisational safety functions, resource and competence, decision-making and communication, good examples and improvement needs. The findings from these surveys were used in conjunction with other factors to identify the key issues for the workshop discussion sessions. The responses from these two surveys are discussed briefly in Sections 4 and 5 of this report. More extensive reviews of the regulatory and licensee responses are provided in Appendix 1

  1. Balanced Integrated Regulatory Oversight

    International Nuclear Information System (INIS)

    Borchardt, R.W.

    2010-01-01

    Reactor safety, protecting the public health and safety, and protecting the environment must always be the nuclear regulator's top priorities. Enabling the use of nuclear power for the benefit of society, while protecting the public and the environment requires the regulator to balance many factors. In addition, the regulator is only one part of the overall government that must consider many factors as it carries out its societal responsibilities. Some of the factors that must be balanced and the practical impacts on how the regulator carries out its responsibilities will be addressed. The first International Conference on Effective Regulatory Systems, held in Moscow, Russian Federation, in 2006, focused on safety and security challenges with a goal of improving regulatory effectiveness through cooperation and sharing of information and best practices. The challenge of meeting both safety and security objectives is one example of potentially competing programmes that must be balanced. Other balances that must be evaluated include the benefits of safety improvements compared to the cost of implementation, the use of deterministic and probabilistic approaches, communication openness balanced with the protection of information that could be used for detrimental purposes, and timeliness of regulatory decision making balanced with the need to perform quality work in support of oversight responsibilities. A balanced and integrated approach to regulatory oversight is vital to ensuring that the regulatory body remains effective in its mission to enable the use of nuclear power while protecting the public and the environment. This concept is applicable to nations beginning a nuclear programme as well as established and experienced regulatory bodies. (author)

  2. Biological computation

    CERN Document Server

    Lamm, Ehud

    2011-01-01

    Introduction and Biological BackgroundBiological ComputationThe Influence of Biology on Mathematics-Historical ExamplesBiological IntroductionModels and Simulations Cellular Automata Biological BackgroundThe Game of Life General Definition of Cellular Automata One-Dimensional AutomataExamples of Cellular AutomataComparison with a Continuous Mathematical Model Computational UniversalitySelf-Replication Pseudo Code Evolutionary ComputationEvolutionary Biology and Evolutionary ComputationGenetic AlgorithmsExample ApplicationsAnalysis of the Behavior of Genetic AlgorithmsLamarckian Evolution Genet

  3. US Competitiveness in Synthetic Biology.

    Science.gov (United States)

    Gronvall, Gigi Kwik

    2015-01-01

    Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

  4. Transcriptional regulatory programs underlying barley germination and regulatory functions of Gibberellin and abscisic acid

    Science.gov (United States)

    2011-01-01

    Background Seed germination is a complex multi-stage developmental process, and mainly accomplished through concerted activities of many gene products and biological pathways that are often subjected to strict developmental regulation. Gibberellins (GA) and abscisic acid (ABA) are two key phytohormones regulating seed germination and seedling growth. However, transcriptional regulatory networks underlying seed germination and its associated biological pathways are largely unknown. Results The studies examined transcriptomes of barley representing six distinct and well characterized germination stages and revealed that the transcriptional regulatory program underlying barley germination was composed of early, late, and post-germination phases. Each phase was accompanied with transcriptional up-regulation of distinct biological pathways. Cell wall synthesis and regulatory components including transcription factors, signaling and post-translational modification components were specifically and transiently up-regulated in early germination phase while histone families and many metabolic pathways were up-regulated in late germination phase. Photosynthesis and seed reserve mobilization pathways were up-regulated in post-germination phase. However, stress related pathways and seed storage proteins were suppressed through the entire course of germination. A set of genes were transiently up-regulated within three hours of imbibition, and might play roles in initiating biological pathways involved in seed germination. However, highly abundant transcripts in dry barley and Arabidopsis seeds were significantly conserved. Comparison with transcriptomes of barley aleurone in response to GA and ABA identified three sets of germination responsive genes that were regulated coordinately by GA, antagonistically by ABA, and coordinately by GA but antagonistically by ABA. Major CHO metabolism, cell wall degradation and protein degradation pathways were up-regulated by both GA and seed

  5. Regulatory stability and credibility

    International Nuclear Information System (INIS)

    Lee, B. Jr.

    1988-01-01

    The author discusses programs within the nuclear industry dedicated to enhancing the utilities' role in achieving operational excellence. The activities of the Nuclear Management and Resources Council (NUMARC), INPO, and EPRI are described. NRC regulations are addressed. The author identifies and focuses on the importance of a stable and credible regulatory process for the achievement of operational excellence

  6. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1989-07-01

    This document is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  7. Developing regulatory approaches

    International Nuclear Information System (INIS)

    Axelsson, Lars

    2012-01-01

    Lars Axelsson presented SSM progress on oversight of LMfS/SC since the Chester 1 Workshop in 2007. Current SSM approaches for safety culture oversight include targeted safety management and safety culture inspections, compliance inspections which cover aspects of safety management/safety culture and multi-disciplinary team inspections. Examples of themes for targeted inspections include management of ambiguous operational situations or other weak signals, understanding of and attitudes to Human Performance tools, the Safety Department's role and authority and Leadership for safety. All regulatory activities provide inputs for the SSM yearly safety evaluation of each licensee. A form has been developed to capture safety culture observations from inspections and other interactions with licensees. Analysis will be performed to identify patterns and provide information to support planning of specific Safety Culture activities. Training has been developed for regulatory staff to enhance the quality of regulatory interventions on safety culture. This includes a half-day seminar to provide an overview of safety culture, and a workshop which provides more in-depth discussion on cultural issues and how to capture those during regulatory activities. Future plans include guidance for inspectors, and informal seminars on safety culture with licensees

  8. Comments on regulatory reform

    International Nuclear Information System (INIS)

    Hendrie, J.M.

    1982-01-01

    Nuclear regulatory reform is divided into two parts. The first part contains all those matters for which new legislation is required. The second part concerns all those matters that are within the power of the Commission under existing statutes. Recommendations are presented

  9. OAR Regulatory Reform

    Science.gov (United States)

    The U.S. EPA's Office of Air and Radiation is hosting a public teleconference to solicit input on specific air and radiation actions that should be considered for “repeal, replacement, or modification” to reduce regulatory burden consistent with EO 13777.

  10. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-02-01

    This document is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considered action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  11. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1992-07-01

    This document compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rule making which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  12. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1992-11-01

    This document provides a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  13. Regulatory Challenges for Cartilage Repair Technologies.

    Science.gov (United States)

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

  14. Introduction to Network Analysis in Systems Biology

    OpenAIRE

    Ma’ayan, Avi

    2011-01-01

    This Teaching Resource provides lecture notes, slides, and a problem set for a set of three lectures from a course entitled “Systems Biology: Biomedical Modeling.” The materials are from three separate lectures introducing applications of graph theory and network analysis in systems biology. The first lecture describes different types of intracellular networks, methods for constructing biological networks, and different types of graphs used to represent regulatory intracellular networks. The ...

  15. Synthetic biology and occupational risk.

    Science.gov (United States)

    Howard, John; Murashov, Vladimir; Schulte, Paul

    2017-03-01

    Synthetic biology is an emerging interdisciplinary field of biotechnology that involves applying the principles of engineering and chemical design to biological systems. Biosafety professionals have done an excellent job in addressing research laboratory safety as synthetic biology and gene editing have emerged from the larger field of biotechnology. Despite these efforts, risks posed by synthetic biology are of increasing concern as research procedures scale up to industrial processes in the larger bioeconomy. A greater number and variety of workers will be exposed to commercial synthetic biology risks in the future, including risks to a variety of workers from the use of lentiviral vectors as gene transfer devices. There is a need to review and enhance current protection measures in the field of synthetic biology, whether in experimental laboratories where new advances are being researched, in health care settings where treatments using viral vectors as gene delivery systems are increasingly being used, or in the industrial bioeconomy. Enhanced worker protection measures should include increased injury and illness surveillance of the synthetic biology workforce; proactive risk assessment and management of synthetic biology products; research on the relative effectiveness of extrinsic and intrinsic biocontainment methods; specific safety guidance for synthetic biology industrial processes; determination of appropriate medical mitigation measures for lentiviral vector exposure incidents; and greater awareness and involvement in synthetic biology safety by the general occupational safety and health community as well as by government occupational safety and health research and regulatory agencies.

  16. Digest: Ant workers might use ancient regulatory pathways to divide labor

    Czech Academy of Sciences Publication Activity Database

    Ernst, Ulrich R.

    2017-01-01

    Roč. 71, č. 1 (2017), s. 193-194 ISSN 0014-3820 Institutional support: RVO:61388963 Keywords : regulatory pathways * social insect * ants Subject RIV: EH - Ecology, Behaviour OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 4.201, year: 2016

  17. Functional footprinting of regulatory DNA.

    Science.gov (United States)

    Vierstra, Jeff; Reik, Andreas; Chang, Kai-Hsin; Stehling-Sun, Sandra; Zhou, Yuanyue; Hinkley, Sarah J; Paschon, David E; Zhang, Lei; Psatha, Nikoletta; Bendana, Yuri R; O'Neil, Colleen M; Song, Alexander H; Mich, Andrea K; Liu, Pei-Qi; Lee, Gary; Bauer, Daniel E; Holmes, Michael C; Orkin, Stuart H; Papayannopoulou, Thalia; Stamatoyannopoulos, George; Rebar, Edward J; Gregory, Philip D; Urnov, Fyodor D; Stamatoyannopoulos, John A

    2015-10-01

    Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the contribution of individual sites to regulatory function remains challenging to define. We describe an approach that exploits the error-prone nature of genome editing-induced double-strand break repair to map functional elements within regulatory DNA at nucleotide resolution. We demonstrate the approach on a human erythroid enhancer, revealing single TF recognition sites that gate the majority of downstream regulatory function.

  18. Consistent Regulatory Policy under Uncertainty

    OpenAIRE

    Michael J. Brennan; Eduardo S. Schwartz

    1982-01-01

    This article is concerned with the effects of regulation on the risk and value of the regulated firm in a dynamic context. Current regulatory practice is shown to be logically deficient, since it ignores the effect of regulatory policy on the cost of capital and therefore on the appropriate allowed rate of return. A notion of consistency in regulatory policy is developed, and it is shown how consistent regulatory policies may be implemented once the valuation problem is solved.

  19. Nuclear Regulatory Commission information digest

    Energy Technology Data Exchange (ETDEWEB)

    None,

    1990-03-01

    The Nuclear Regulatory Commission information digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the commission. This is an annual publication for the general use of the NRC Staff and is available to the public. The digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide.

  20. XcisClique: analysis of regulatory bicliques

    Directory of Open Access Journals (Sweden)

    Grene Ruth

    2006-04-01

    Full Text Available Abstract Background Modeling of cis-elements or regulatory motifs in promoter (upstream regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions. Methods XcisClique, the system developed in this work, is a comprehensive infrastructure that associates annotated genome and gene expression data, models known cis-elements as regular expressions, identifies maximal bicliques in a bipartite gene-motif graph; and ranks bicliques based on their computed statistical significance. Significance is a function of the probability of occurrence of those motifs in a biclique (a hypergeometric distribution, and on the new sum of absolute values statistic (SAV that uses Spearman correlations of gene expression vectors. SAV is a statistic well-suited for this purpose as described in the discussion. Results XcisClique identifies new motif and gene combinations that might indicate as yet unidentified involvement of sets of genes in biological functions and processes. It currently supports Arabidopsis thaliana and can be adapted to other organisms, assuming the existence of annotated genomic sequences, suitable gene expression data, and identified regulatory motifs. A subset of Xcis Clique functionalities, including the motif visualization component MotifSee, source code, and supplementary material are available at https://bioinformatics.cs.vt.edu/xcisclique/.

  1. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-07-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter. The rules on which final action has been taken since March 31, 1993 are: Repeal of NRC standards of conduct; Fitness-for-duty requirements for licensees who possess, use, or transport Category I material; Training and qualification of nuclear power plant personnel; Monitoring the effectiveness of maintenance at nuclear power plants; Licensing requirements for land disposal of radioactive wastes; and Licensees' announcements of safeguards inspections

  2. A flexible regulatory framework

    International Nuclear Information System (INIS)

    Silvennoinen, T.

    2000-01-01

    Regulatory reform of the Finnish electricity market meant opening up potentially competitive parts of the electricity sector to competition and eliminating all unnecessary forms of regulation covering generation, wholesale supply, retail supply, and foreign trade in electricity. New types of control and regulatory mechanisms and institutions were set up for those parts of the electricity industry that were excluded from competition, such as network operations. Network activities now have to be licensed, whereas no licence is needed for generation or supply. A new sector-specific regulatory authority was established in 1995 to coincide with the implementation of the Electricity Market Act, known as the Electricity Market Authority. This is responsible for regulating network activities and retail supply to captive customers. The core function of the authority, which employs some 14 people, is to promote the smooth operation of the Finnish electricity market and to oversee the implementation of the Electricity Market Act and its provisions. Its most important duties are linked to overseeing the process by which network companies price their electricity. As price regulation no longer exists, all the companies in the electricity sector set their tariffs independently, even network companies. The job of controlling the pricing of network services is handed by the Electricity Market Authority, following the principles of competition control. Pricing control takes place ex post - after a pricing system has been adopted by a company and concentrates on individual cases and companies. There is no ex ante system of setting or approving prices and tariffs by the regulator. The tariffs and pricing of network services can be evaluated, however, by both the Electricity Market Authority and the Finnish Competition Authority, which have overlapping powers as regards the pricing of network activities. The Finnish regulatory framework can be described as a system of light

  3. Essays in Regulatory Economics

    OpenAIRE

    Guerrero, Santiago

    2011-01-01

    This dissertation consists of three essays. The objective of the essays is to study the impacts of different regulations on the behavior of regulated agents. The first two essays focus on the analysis of non-traditional regulatory policies that complement traditional regulations consisting of inspections and fines for plants that violate regulations. The third essay studies the impacts of the Minimum Legal Drinking Age regulation on alcohol and marijuana consumption. The first essay of this d...

  4. Regulatory aspects of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Kristensen, K.

    1985-01-01

    Regulatory systems in the field of radiopharmaceuticals have two main purposes: efficacy and safety. Efficacy expresses the quality of the diagnostic and therapeutic process for the patient. Safety involves the patient, the staff, and the environment. The world situation regarding regulations for radiopharmaceuticals is reviewed on the basis of a survey in WHO Member States. The main content of such regulations is discussed. The special properties of radiopharmaceuticals compared with ordinary drugs may call for modified regulations. Several countries are preparing such regulations. Close co-operation and good understanding among scientists working in hospital research, industry and regulatory bodies will be of great importance for the fast and safe introduction of new radiopharmaceuticals for the benefit of the patient. Before introducing new legislation in this field, a radiopharmaceutical expert should analyse the situation in the country and the relationship to the existing regulations. It is expected that the most important factor in promoting the fast introduction of new, safe and effective radiopharmaceuticals will be the training of people working within the regulatory bodies. It is foreseen that the IAEA and WHO will have an important role to play by providing expert advice and training in this area. (author)

  5. The changing regulatory environment

    International Nuclear Information System (INIS)

    Caron, G.

    1999-01-01

    The role and value of regulation in the energy sector was discussed, demonstrating how, despite common perception, regulation is an essential part of Canada's strategy to find and develop new opportunities. The future vision of regulation for industry participants was presented with particular focus on issues related to streamlining the regulatory process. As far as pipelines are concerned, regulatory actions are necessary to facilitate capacity increases and to ensure the line's integrity, safety and environmental record. Furthermore, regulation provides economic solutions where market forces cannot provide them, as for example where business has elements of monopoly. It arbitrates interests of landowners, business, consumers, and environmental groups. It looks for ways to ensure conditions under which competition can flourish. It acts as the guardian of citizens' rights in a democratic society by providing citizens with an opportunity to be heard on the building or expansion of pipelines and associated facilities. As citizens become more and more concerned about their property and the land that surrounds them, citizen involvement in decision making about how industry activity affects their quality of life will become correspondingly more important. Regulatory agencies are committed to facilitate this engagement by flexible hearing procedures and by making use of evolving communication and information technology

  6. Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Wiley, H S.

    2006-06-01

    The biology revolution over the last 50 years has been driven by the ascendancy of molecular biology. This was enthusiastically embraced by most biologists because it took us into increasingly familiar territory. It took mysterious processes, such as the replication of genetic material and assigned them parts that could be readily understood by the human mind. When we think of ''molecular machines'' as being the underlying basis of life, we are using a paradigm derived from everyday experience. However, the price that we paid was a relentless drive towards reductionism and the attendant balkanization of biology. Now along comes ''systems biology'' that promises us a solution to the problem of ''knowing more and more about less and less''. Unlike molecular biology, systems biology appears to be taking us into unfamiliar intellectual territory, such as statistics, mathematics and computer modeling. Not surprisingly, systems biology has met with widespread skepticism and resistance. Why do we need systems biology anyway and how does this new area of research promise to change the face of biology in the next couple of decades?

  7. Biological therapeutics

    National Research Council Canada - National Science Library

    Greenstein, Ben; Brook, Daniel A

    2011-01-01

    This introductory textbook covers all the main categories of biological medicines, including vaccines, hormonal preparations, drugs for rheumatoid arthritis and other connective tissue diseases, drugs...

  8. Unblocking Blockbusters: Using Boolean Text-Mining to Optimise Clinical Trial Design and Timeline for Novel Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Richard J. Epstein

    2009-08-01

    Full Text Available Two problems now threaten the future of anticancer drug development: (i the information explosion has made research into new target-specific drugs more duplication-prone, and hence less cost-efficient; and (ii high-throughput genomic technologies have failed to deliver the anticipated early windfall of novel first-in-class drugs. Here it is argued that the resulting crisis of blockbuster drug development may be remedied in part by innovative exploitation of informatic power. Using scenarios relating to oncology, it is shown that rapid data-mining of the scientific literature can refine therapeutic hypotheses and thus reduce empirical reliance on preclinical model development and early-phase clinical trials. Moreover, as personalised medicine evolves, this approach may inform biomarker-guided phase III trial strategies for noncytotoxic (antimetastatic drugs that prolong patient survival without necessarily inducing tumor shrinkage. Though not replacing conventional gold standards, these findings suggest that this computational research approach could reduce costly ‘blue skies’ R&D investment and time to market for new biological drugs, thereby helping to reverse unsustainable drug price inflation.

  9. Unblocking Blockbusters: Using Boolean Text-Mining to Optimise Clinical Trial Design and Timeline for Novel Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Richard J. Epstein

    2009-01-01

    Full Text Available Two problems now threaten the future of anticancer drug development: (i the information explosion has made research into new target-specific drugs more duplication-prone, and hence less cost-efficient; and (ii high-throughput genomic technologies have failed to deliver the anticipated early windfall of novel first-in-class drugs. Here it is argued that the resulting crisis of blockbuster drug development may be remedied in part by innovative exploitation of informatic power. Using scenarios relating to oncology, it is shown that rapid data-mining of the scientific literature can refine therapeutic hypotheses and thus reduce empirical reliance on preclinical model development and early-phase clinical trials. Moreover, as personalised medicine evolves, this approach may inform biomarker-guided phase III trial strategies for noncytotoxic (antimetastatic drugs that prolong patient survival without necessarily inducing tumor shrinkage. Though not replacing conventional gold standards, these findings suggest that this computational research approach could reduce costly ‘blue skies’ R&D investment and time to market for new biological drugs, thereby helping to reverse unsustainable drug price inflation.

  10. 75 FR 21955 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-04-26

    ... Part XXI National Credit Union Administration ###Semiannual Regulatory Agenda### [[Page 21956... Regulatory Agenda AGENCY: National Credit Union Administration (NCUA). ACTION: Semiannual regulatory agenda... included in the Unified Agenda of Federal Regulatory and Deregulatory Actions. DATES: This information is...

  11. Regulatory and clinical considerations for biosimilar oncology drugs

    Science.gov (United States)

    Bennett, Charles L; Chen, Brian; Hermanson, Terhi; Wyatt, Michael D; Schulz, Richard M; Georgantopoulos, Peter; Kessler, Samuel; Raisch, Dennis W; Qureshi, Zaina P; Lu, Z Kevin; Love, Bryan L; Noxon, Virginia; Bobolts, Laura; Armitage, Melissa; Bian, John; Ray, Paul; Ablin, Richard J; Hrushesky, William J; Macdougall, Iain C; Sartor, Oliver; Armitage, James O

    2015-01-01

    Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents—molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs—provide opportunities both to improve healthcare access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns. PMID:25456378

  12. Statistics of optimal information flow in ensembles of regulatory motifs

    Science.gov (United States)

    Crisanti, Andrea; De Martino, Andrea; Fiorentino, Jonathan

    2018-02-01

    Genetic regulatory circuits universally cope with different sources of noise that limit their ability to coordinate input and output signals. In many cases, optimal regulatory performance can be thought to correspond to configurations of variables and parameters that maximize the mutual information between inputs and outputs. Since the mid-2000s, such optima have been well characterized in several biologically relevant cases. Here we use methods of statistical field theory to calculate the statistics of the maximal mutual information (the "capacity") achievable by tuning the input variable only in an ensemble of regulatory motifs, such that a single controller regulates N targets. Assuming (i) sufficiently large N , (ii) quenched random kinetic parameters, and (iii) small noise affecting the input-output channels, we can accurately reproduce numerical simulations both for the mean capacity and for the whole distribution. Our results provide insight into the inherent variability in effectiveness occurring in regulatory systems with heterogeneous kinetic parameters.

  13. Statistics of optimal information flow in ensembles of regulatory motifs.

    Science.gov (United States)

    Crisanti, Andrea; De Martino, Andrea; Fiorentino, Jonathan

    2018-02-01

    Genetic regulatory circuits universally cope with different sources of noise that limit their ability to coordinate input and output signals. In many cases, optimal regulatory performance can be thought to correspond to configurations of variables and parameters that maximize the mutual information between inputs and outputs. Since the mid-2000s, such optima have been well characterized in several biologically relevant cases. Here we use methods of statistical field theory to calculate the statistics of the maximal mutual information (the "capacity") achievable by tuning the input variable only in an ensemble of regulatory motifs, such that a single controller regulates N targets. Assuming (i) sufficiently large N, (ii) quenched random kinetic parameters, and (iii) small noise affecting the input-output channels, we can accurately reproduce numerical simulations both for the mean capacity and for the whole distribution. Our results provide insight into the inherent variability in effectiveness occurring in regulatory systems with heterogeneous kinetic parameters.

  14. Technical Memory 2008. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2011-01-01

    The technical memory 2008 of the Nuclear Regulatory Authority of Argentine Republic, compile the papers published in the subject on radiation protection and nuclear safety, and presented in journals, technical reports, congress or meetings of these specialties by personnel of the mentioned institution during 2008. In this edition the documents are presented on: environmental protection; transport of radioactive materials; regulations; research reactors and nuclear power plants; biological radiation effects; therapeutic uses of ionizing radiation and radioprotection of patients; internal dosimetry; physical dosimetry; knowledge management; radioactive waste management. [es

  15. Regulatory and Radiological Assessment of Co-60 Teletherapy Unit ...

    African Journals Online (AJOL)

    The regulatory and radiological safety of a Radiotherapy Unit has been assessed based on the technical and performance specification given on the GWGP 80 cobalt-60 equipment, the biological shielding effectiveness and the organizational structure for the operation of the facility. The assessment involved the evaluation ...

  16. Inferring Drosophila gap gene regulatory network: A parameter sensitivity and perturbation analysis

    NARCIS (Netherlands)

    Fomekong-Nanfack, Y.; Postma, M.; Kaandorp, J.A.

    2009-01-01

    Background: Inverse modelling of gene regulatory networks (GRNs) capable of simulating continuous spatio-temporal biological processes requires accurate data and a good description of the system. If quantitative relations between genes cannot be extracted from direct measurements, an efficient

  17. Characterization of noncoding regulatory DNA in the human genome.

    Science.gov (United States)

    Elkon, Ran; Agami, Reuven

    2017-08-08

    Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.

  18. Understanding Biological Regulation Through Synthetic Biology.

    Science.gov (United States)

    Bashor, Caleb J; Collins, James J

    2018-03-16

    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. Expected final online publication date for the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  19. Is synthetic biology mechanical biology?

    Science.gov (United States)

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  20. Boolean Logic Tree of Label-Free Dual-Signal Electrochemical Aptasensor System for Biosensing, Three-State Logic Computation, and Keypad Lock Security Operation.

    Science.gov (United States)

    Lu, Jiao Yang; Zhang, Xin Xing; Huang, Wei Tao; Zhu, Qiu Yan; Ding, Xue Zhi; Xia, Li Qiu; Luo, Hong Qun; Li, Nian Bing

    2017-09-19

    The most serious and yet unsolved problems of molecular logic computing consist in how to connect molecular events in complex systems into a usable device with specific functions and how to selectively control branchy logic processes from the cascading logic systems. This report demonstrates that a Boolean logic tree is utilized to organize and connect "plug and play" chemical events DNA, nanomaterials, organic dye, biomolecule, and denaturant for developing the dual-signal electrochemical evolution aptasensor system with good resettability for amplification detection of thrombin, controllable and selectable three-state logic computation, and keypad lock security operation. The aptasensor system combines the merits of DNA-functionalized nanoamplification architecture and simple dual-signal electroactive dye brilliant cresyl blue for sensitive and selective detection of thrombin with a wide linear response range of 0.02-100 nM and a detection limit of 1.92 pM. By using these aforementioned chemical events as inputs and the differential pulse voltammetry current changes at different voltages as dual outputs, a resettable three-input biomolecular keypad lock based on sequential logic is established. Moreover, the first example of controllable and selectable three-state molecular logic computation with active-high and active-low logic functions can be implemented and allows the output ports to assume a high impediment or nothing (Z) state in addition to the 0 and 1 logic levels, effectively controlling subsequent branchy logic computation processes. Our approach is helpful in developing the advanced controllable and selectable logic computing and sensing system in large-scale integration circuits for application in biomedical engineering, intelligent sensing, and control.

  1. On the generalization of constraint programming and boolean satisfiability solving techniques to schedule a resource-constrained project consisting of multi-mode jobs

    Directory of Open Access Journals (Sweden)

    Alexander Schnell

    Full Text Available In our paper, we analyze new exact approaches for the multi-mode resource-constrained project scheduling (MRCPSP problem with the aim of makespan minimization. For the single-mode RCPSP (SRCPSP recent exact algorithms combine a Branch and Bound algorithm with principles from Constraint Programming (CP and Boolean Satisfiability Solving (SAT. We extend the above principles for the solution of MRCPSP instances. This generalization is on the one hand achieved on the modeling level. We propose three CP-based formulations of the MRCPSP for the G12 CP platform and the optimization framework SCIP which both provide solution techniques combining CP and SAT principles. For one of the latter we implemented a new global constraint for SCIP, which generalizes the domain propagation and explanation generation principles for renewable resources in the context of multi-mode jobs. Our constraint applies the above principles in a more general way than the existing global constraint in SCIP. We compare our approaches with the state-of-the-art exact algorithm from the literature on MRCPSP instances with 20 and 30 jobs. Our computational experiments show that we can outperform the latter approach on these instances. Furthermore, we are the first to close (find the optimal solution and prove its optimality for 628 open instances with 50 and 100 jobs from the literature. In addition, we improve the best known lower bound of 2815 instances and the best known upper bound of 151 instances. Keywords: Multi-mode resource-constrained project scheduling, Constraint programming, SAT solving, SCIP, Lazy clause generation, Exact algorithm

  2. Mesoscopic biology

    Indian Academy of Sciences (India)

    Abstract. In this paper we present a qualitative outlook of mesoscopic biology where the typical length scale is of the order of nanometers and the energy scales comparable to thermal energy. ... National Center for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore 560 065, India ...

  3. Computational biology

    DEFF Research Database (Denmark)

    Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue

    2011-01-01

    Computation via biological devices has been the subject of close scrutiny since von Neumann’s early work some 60 years ago. In spite of the many relevant works in this field, the notion of programming biological devices seems to be, at best, ill-defined. While many devices are claimed or proved t...

  4. Mesoscopic biology

    Indian Academy of Sciences (India)

    In this paper we present a qualitative outlook of mesoscopic biology where the typical length scale is of the order of nanometers and the energy scales comparable to thermal energy. Novel biomolecular machines, governed by coded information at the level of DNA and proteins, operate at these length scales in biological ...

  5. 78 FR 1698 - Semiannual Regulatory Flexibility Agenda

    Science.gov (United States)

    2013-01-08

    ...: Regulatory Capital, Implementation of Basel III, Minimum Regulatory Capital Ratios, Capital Adequacy, and...--Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Minimum Regulatory Capital Ratios... Supervision (BCBS) in ``Basel III: A Global Regulatory Framework for More Resilient Banks and Banking Systems...

  6. The nomenclature of MHC class I gene regulatory regions - the case of two different downstream regulatory elements

    Czech Academy of Sciences Publication Activity Database

    Hatina, J.; Jansa, Petr; Forejt, Jiří

    2001-01-01

    Roč. 37, 12-13 (2001), s. 799-800 ISSN 0161-5890 Institutional research plan: CEZ:AV0Z5052915 Keywords : MHC I gene regulatory elements Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.973, year: 2001

  7. Systems Biology of Metabolic Networks: Uncovering Regulatory and stoichiometric Principles

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb

    2007-01-01

    . I et videre arbejde er det demonstreret hvordan metabolske modeller kan anvendes til design af nye cellefabrikker. Dette har involveret udvikling af en ny computer algoritme der identificerer hvilke gener der skal modificeres for at opnå en forbedret cellefabrik. Anvendelse af denne algoritme...... demonstreret anvendt for flere eksempler, og videre eksperimentel verifikation en computer forudsagt design strategi er kort beskrevet. Afhandlingen demonstrerer derfor anvendelse af metabolske modeller både til analyse af store datasæt, til anvendelse i systembiologi, og til design af nye cellefabrikker, til...

  8. News from the biological stain commission

    DEFF Research Database (Denmark)

    Kiernan, J.A.; Lyon, Hans Oluf

    2008-01-01

    In the three earlier editions of News from the Biological Stain Commission (BSC), under the heading of "Regulatory affairs," the BSC's International Affairs Committee reported on the work of Technical Committee 212, Clinical Laboratory Testing and in Vitro Diagnostic Test Systems of the Internati......In the three earlier editions of News from the Biological Stain Commission (BSC), under the heading of "Regulatory affairs," the BSC's International Affairs Committee reported on the work of Technical Committee 212, Clinical Laboratory Testing and in Vitro Diagnostic Test Systems...

  9. Programming Morphogenesis through Systems and Synthetic Biology.

    Science.gov (United States)

    Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

    2018-04-01

    Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Services of the Nuclear Regulatory Authority Library

    International Nuclear Information System (INIS)

    Carregado, M.A.; Wallingre, G.V.

    2011-01-01

    Full text; The main of this work is to present the services and activities of the ARN (Autoridad Regulatoria Nuclear) Library to potential users from the biological dosimetry area in the framework of the intercomparison Meeting of the Latin American Biological Dosimetry Network held in Buenos Aires from October 27-30 of 2008. It makes a short chronology of the library; the services offered to each type of users and the tasks related to technical and international cooperation with other organizations such as: the terminology Committee of IRAM (Instituto Argentino de Normalizacion y Certificacion); the input of national literature to the INIS Database of the IAEA; the retrospective digitalisation, indexing and bibliographic description of institutional publications to be submitted to the repository of the Ibero American Forum of Nuclear and Radiation Safety Regulatory Organizations and the participation in nuclear information networks. Finally it shown some relevant data from the internal statistics. (authors)

  11. Politically Induced Regulatory Risk and Independent Regulatory Agencies

    OpenAIRE

    Strausz, Roland

    2015-01-01

    Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

  12. Assessment of regulatory effectiveness. Peer discussions on regulatory practices

    International Nuclear Information System (INIS)

    1999-09-01

    This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

  13. Quantum Biology

    Directory of Open Access Journals (Sweden)

    Alessandro Sergi

    2009-06-01

    Full Text Available A critical assessment of the recent developmentsof molecular biology is presented.The thesis that they do not lead to a conceptualunderstanding of life and biological systems is defended.Maturana and Varela's concept of autopoiesis is briefly sketchedand its logical circularity avoided by postulatingthe existence of underlying living processes,entailing amplification from the microscopic to the macroscopic scale,with increasing complexity in the passage from one scale to the other.Following such a line of thought, the currently accepted model of condensed matter, which is based on electrostatics and short-ranged forces,is criticized. It is suggested that the correct interpretationof quantum dispersion forces (van der Waals, hydrogen bonding, and so onas quantum coherence effects hints at the necessity of includinglong-ranged forces (or mechanisms for them incondensed matter theories of biological processes.Some quantum effects in biology are reviewedand quantum mechanics is acknowledged as conceptually important to biology since withoutit most (if not all of the biological structuresand signalling processes would not even exist. Moreover, it is suggested that long-rangequantum coherent dynamics, including electron polarization,may be invoked to explain signal amplificationprocess in biological systems in general.

  14. Biological Oceanography

    Science.gov (United States)

    Dyhrman, Sonya

    2004-10-01

    The ocean is arguably the largest habitat on the planet, and it houses an astounding array of life, from microbes to whales. As a testament to this diversity and its importance, the discipline of biological oceanography spans studies of all levels of biological organization, from that of single genes, to organisms, to their population dynamics. Biological oceanography also includes studies on how organisms interact with, and contribute to, essential global processes. Students of biological oceanography are often as comfortable looking at satellite images as they are electron micrographs. This diversity of perspective begins the textbook Biological Oceanography, with cover graphics including a Coastal Zone Color Scanner image representing chlorophyll concentration, an electron micrograph of a dinoflagellate, and a photograph of a copepod. These images instantly capture the reader's attention and illustrate some of the different scales on which budding oceanographers are required to think. Having taught a core graduate course in biological oceanography for many years, Charlie Miller has used his lecture notes as the genesis for this book. The text covers the subject of biological oceanography in a manner that is targeted to introductory graduate students, but it would also be appropriate for advanced undergraduates.

  15. Modeling Dynamic Regulatory Processes in Stroke

    Science.gov (United States)

    McDermott, Jason E.; Jarman, Kenneth; Taylor, Ronald; Lancaster, Mary; Shankaran, Harish; Vartanian, Keri B.; Stevens, Susan L.; Stenzel-Poore, Mary P.; Sanfilippo, Antonio

    2012-01-01

    The ability to examine the behavior of biological systems in silico has the potential to greatly accelerate the pace of discovery in diseases, such as stroke, where in vivo analysis is time intensive and costly. In this paper we describe an approach for in silico examination of responses of the blood transcriptome to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs) from the data relating these functional clusters to each other in terms of their regulatory influence on one another. Dynamic models were developed by coupling these ODEs into a model that simulates the expression of regulated functional clusters. By changing the magnitude of gene expression in the initial input state it was possible to assess the behavior of the networks through time under varying conditions since the dynamic model only requires an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. We discuss the implications of our models on neuroprotection in stroke, explore the limitations of the approach, and report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different neuroprotective paradigms. PMID:23071432

  16. Modeling dynamic regulatory processes in stroke.

    Directory of Open Access Journals (Sweden)

    Jason E McDermott

    Full Text Available The ability to examine the behavior of biological systems in silico has the potential to greatly accelerate the pace of discovery in diseases, such as stroke, where in vivo analysis is time intensive and costly. In this paper we describe an approach for in silico examination of responses of the blood transcriptome to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs from the data relating these functional clusters to each other in terms of their regulatory influence on one another. Dynamic models were developed by coupling these ODEs into a model that simulates the expression of regulated functional clusters. By changing the magnitude of gene expression in the initial input state it was possible to assess the behavior of the networks through time under varying conditions since the dynamic model only requires an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. We discuss the implications of our models on neuroprotection in stroke, explore the limitations of the approach, and report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different neuroprotective paradigms.

  17. The role of veterinary medicine regulatory agencies.

    Science.gov (United States)

    Smith, M V

    2013-08-01

    An effective animal medicine regulatory programme includes a systematic, evidence-based means of documenting the safety and effectiveness of products before they are produced, marketed or used in a particular country or region. The programme must also include adequate monitoring and controls over the use of these substances. It is clearthat such programmes provide veterinarians, farmers and other animal medicine users with greater assurance that veterinary drugs and biologicals will be safe and effective in preventing and mitigating disease. It is important that these regulatory controls include programmes to ensure that human food obtained from treated animals is safe and that all potential toxicological and microbiological hazards that may be associated with the use of veterinary medicines have been adequately evaluated. There is a great need worldwide for veterinary medicines that provide needed therapies for vast numbers of animals and animal species and, in the case of food-producing animals, for medicinal products that enhance the productivity and efficiency of food production and ensure food safety when they are used in accordance with their approval specifications. The public health mission of regulatory agencies succeeds when they are able to put into the hands of the user an approved, safe and effective, well-manufactured and appropriately labelled medicine, and when there are adequate controls in place to assure proper compliance.

  18. Visions of regulatory renewal

    International Nuclear Information System (INIS)

    Edgeworth, A.

    1998-01-01

    The economic contribution of the CEPA (Canadian Energy Pipeline Association) member companies to Canada's trade balance was discussed. CEPA member companies transport 95 per cent of the crude oil and natural gas produced in Canada to domestic and export markets. This represents a total of 5.6 Tcf of gas annually. Half of Canada's natural gas and oil production is exported to U.S. markets. All of these exports are transported by pipeline. CEPA member companies operate 90,000 km of pipeline from British Columbia to Quebec. Expansions are needed as a result of a significant increase in demand for natural gas and crude oil since 1990. Several issues exist for regulatory renewal. They include the need to create a level playing field, the overseeing of tolls and contract renewal terms, changing risk/reward trade-offs, the right to confidentiality of information and price discovery mechanism. The drivers for regulatory reform at Westcoast Energy are the need for pricing flexibility, customers desire for toll certainty, decontracting and opposition to rolled-in expansions for gathering and processing. An overview of Westcoast Energy's negotiated toll settlement, its implications, and the components of Westcoast Energy's 'light handed regulation' (LHR) was presented

  19. The regulatory dynamic

    International Nuclear Information System (INIS)

    Dybwad, C.

    2001-01-01

    An outline of the activities and efforts expanded by the National Energy Board to adjust to the changing natural gas market was provided in this presentation. The author began by defining the role of the National Energy Board in energy markets. It must ensure the adoption of rules and procedures that result in a more competitive and efficient market. Light-handed regulatory techniques are the norm, and the National Energy Board is now committed to facilitating the availability and flow of information so that all parties know where opportunities exist, the terms offered to buy or sell goods and services, their quality and costs. It will specialize in providing new participants with information on the workings of the market, who the players are, the regulatory processes in place, and how, when and where the market can be accessed. The manner in which the Board deals with information was reviewed, providing examples along the way to clarify some points. Some of the documents produced by the National Energy Board are being reviewed with the intent of making them easier to read and understand. Audio streaming over the Internet is another avenue being pursued to ensure individuals can listen in real time to hearings without having to be present in the room. The National Energy Board is also exploring alternative dispute resolution techniques. Consultation with energy market participants represents another facet of these efforts to be more accessible and responsive

  20. Automated Identification of Core Regulatory Genes in Human Gene Regulatory Networks.

    Directory of Open Access Journals (Sweden)

    Vipin Narang

    Full Text Available Human gene regulatory networks (GRN can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs. Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data accompanying this manuscript.

  1. Biological Pathways

    Science.gov (United States)

    Skip to main content Biological Pathways Fact Sheet Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News Features ...

  2. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2012-01-01

    This section gathers the following national legislative and regulatory activities sorted by country: Bulgaria: General legislation; Czech Republic: General legislation; France: General legislation, Regulatory infrastructure and activity; Germany: General legislation; India: Liability and compensation, Organisation and structure; Ireland: Radiation protection, General legislation; Korea (Republic of): Organisation and structure; Lithuania: Regulatory infrastructure and activity, Radioactive waste management, Radiation protection, international cooperation, Nuclear safety; Poland: General legislation; Romania: Environmental protection; Russian Federation: Radioactive waste management; Slovenia: Nuclear safety; Spain: Liability and compensation, Nuclear security; Sweden: Nuclear safety; Turkey: Radiation protection, Regulatory infrastructure and activity, Nuclear safety, Liability and compensation; United States: General legislation

  3. Towards a predictive theory for genetic regulatory networks

    Science.gov (United States)

    Tkacik, Gasper

    When cells respond to changes in the environment by regulating the expression levels of their genes, we often draw parallels between these biological processes and engineered information processing systems. One can go beyond this qualitative analogy, however, by analyzing information transmission in biochemical ``hardware'' using Shannon's information theory. Here, gene regulation is viewed as a transmission channel operating under restrictive constraints set by the resource costs and intracellular noise. We present a series of results demonstrating that a theory of information transmission in genetic regulatory circuits feasibly yields non-trivial, testable predictions. These predictions concern strategies by which individual gene regulatory elements, e.g., promoters or enhancers, read out their signals; as well as strategies by which small networks of genes, independently or in spatially coupled settings, respond to their inputs. These predictions can be quantitatively compared to the known regulatory networks and their function, and can elucidate how reproducible biological processes, such as embryonic development, can be orchestrated by networks built out of noisy components. Preliminary successes in the gap gene network of the fruit fly Drosophila indicate that a full ab initio theoretical prediction of a regulatory network is possible, a feat that has not yet been achieved for any real regulatory network. We end by describing open challenges on the path towards such a prediction.

  4. Characterization of regulatory features of housekeeping and tissue-specific regulators within tissue regulatory networks.

    Science.gov (United States)

    Li, Pengping; Hua, Xu; Zhang, Zhen; Li, Jie; Wang, Jin

    2013-10-31

    importance to biological functions in their respective tissues. The topological differences between disease and non-disease genes may aid the discovery of new disease genes or drug targets. Determining the network properties of these regulatory factors will help define the basic principles of human gene regulation and the molecular mechanisms of disease.

  5. Intervention in gene regulatory networks via a stationary mean-first-passage-time control policy.

    Science.gov (United States)

    Vahedi, Golnaz; Faryabi, Babak; Chamberland, Jean-Francois; Datta, Aniruddha; Dougherty, Edward R

    2008-10-01

    A prime objective of modeling genetic regulatory networks is the identification of potential targets for therapeutic intervention. To date, optimal stochastic intervention has been studied in the context of probabilistic Boolean networks, with the control policy based on the transition probability matrix of the associated Markov chain and dynamic programming used to find optimal control policies. Dynamical programming algorithms are problematic owing to their high computational complexity. Two additional computationally burdensome issues that arise are the potential for controlling the network and identifying the best gene for intervention. This paper proposes an algorithm based on mean first-passage time that assigns a stationary control policy for each gene candidate. It serves as an approximation to an optimal control policy and, owing to its reduced computational complexity, can be used to predict the best control gene. Once the best control gene is identified, one can derive an optimal policy or simply utilize the approximate policy for this gene when the network size precludes a direct application of dynamic programming algorithms. A salient point is that the proposed algorithm can be model-free. It can be directly designed from time-course data without having to infer the transition probability matrix of the network.

  6. Core regulatory network motif underlies the ocellar complex patterning in Drosophila melanogaster

    Science.gov (United States)

    Aguilar-Hidalgo, D.; Lemos, M. C.; Córdoba, A.

    2015-03-01

    During organogenesis, developmental programs governed by Gene Regulatory Networks (GRN) define the functionality, size and shape of the different constituents of living organisms. Robustness, thus, is an essential characteristic that GRNs need to fulfill in order to maintain viability and reproducibility in a species. In the present work we analyze the robustness of the patterning for the ocellar complex formation in Drosophila melanogaster fly. We have systematically pruned the GRN that drives the development of this visual system to obtain the minimum pathway able to satisfy this pattern. We found that the mechanism underlying the patterning obeys to the dynamics of a 3-nodes network motif with a double negative feedback loop fed by a morphogenetic gradient that triggers the inhibition in a French flag problem fashion. A Boolean modeling of the GRN confirms robustness in the patterning mechanism showing the same result for different network complexity levels. Interestingly, the network provides a steady state solution in the interocellar part of the patterning and an oscillatory regime in the ocelli. This theoretical result predicts that the ocellar pattern may underlie oscillatory dynamics in its genetic regulation.

  7. Robustness in Regulatory Interaction Networks. A Generic Approach with Applications at Different Levels: Physiologic, Metabolic and Genetic

    Science.gov (United States)

    Demongeot, Jacques; Ben Amor, Hedi; Elena, Adrien; Gillois, Pierre; Noual, Mathilde; Sené, Sylvain

    2009-01-01

    Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability). We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode) of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression). We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime) or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control. PMID:20057955

  8. Systems Biology of Metabolism: Annual Review of Biochemistry

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2017-01-01

    Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology......, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed....

  9. Nuclear Regulatory Commission Issuances

    International Nuclear Information System (INIS)

    1992-01-01

    This is the thirty-sixth volume of issuances (1-396) of the Nuclear Regulatory Commission and its Atomic Safety and Licensing Boards, Administrative Law Judges, and Office Directors. It covers the period from July 1, 1992-December 31, 1992. Atomic Safety and Licensing Boards are authorized by Section 191 of the Atomic Energy Act of 1954. These Boards, comprised of three members conduct adjudicatory hearings on applications to construct and operate nuclear power plants and related facilities and issue initial decisions which, subject to internal review and appellate procedures, become the final Commission action with respect to those applications. Boards are drawn from the Atomic Safety and Licensing Board Panel, comprised of lawyers, nuclear physicists and engineers, environmentalists, chemists, and economists. The Atomic Energy Commission first established Licensing Boards in 1962 and the Panel in 1967

  10. Regulatory mark; Marco regulatorio

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter is based on a work performed in distinct phases. The first phase consisted in of the analysis regulatory legislation existent in Brazil for the sugar-alcohol sector since the beginning of the X X century. This analysis allowed the identification of non existent points and legal devices related to the studied aspects, and that were considered as problematic for the sector expansion. In the second phase, related treaties and international agreements was studied and possible obstacles for the brazilian bio ethanol exportation for the international market. Initiatives were examined at European Union, United States of America, Caribbean and countries of the sub-Saharan Africa. In this phase, policies were identified related to the incentives and adoption of use of bio fuels added to the gasoline in countries or group of countries considered as key for the consolidation of bio ethanol as a world commodity.

  11. Regulatory actions post - Fukushima

    International Nuclear Information System (INIS)

    Ciurea Ercau, C.

    2013-01-01

    The paper presents the results of the safety reviews performed in Romania after the Fukushima accident and the resulting actions for improving the safety. The actions taken by the National Commission for Nuclear Activities Control (CNCAN) to improve the regulatory framework include the development of new regulations and the enhancement of inspection practices, taking account of the lessons learned from the Fukushima accident. A regulation on the response to transients, accidents and emergency situations at nuclear power plants has been developed, which includes requirements on transient and accident scenarios that have to be covered by the Emergency Operating Procedures (EOPs), accident scenarios to be covered by the Severe Accident Management Guidelines (SAMGs), emergency situations to be covered by the on-site emergency response plan and emergency response procedures. (authors)

  12. Human biology of taste.

    Science.gov (United States)

    Gravina, Stephen A; Yep, Gregory L; Khan, Mehmood

    2013-01-01

    Taste or gustation is one of the 5 traditional senses including hearing, sight, touch, and smell. The sense of taste has classically been limited to the 5 basic taste qualities: sweet, salty, sour, bitter, and umami or savory. Advances from the Human Genome Project and others have allowed the identification and determination of many of the genes and molecular mechanisms involved in taste biology. The ubiquitous G protein-coupled receptors (GPCRs) make up the sweet, umami, and bitter receptors. Although less clear in humans, transient receptor potential ion channels are thought to mediate salty and sour taste; however, other targets have been identified. Furthermore, taste receptors have been located throughout the body and appear to be involved in many regulatory processes. An emerging interplay is revealed between chemical sensing in the periphery, cortical processing, performance, and physiology and likely the pathophysiology of diseases such as diabetes.

  13. FDA Regulation of Follow-On Biologics

    Science.gov (United States)

    2009-02-24

    are mostly hormones: glucagon, human growth hormone, hormones to treat infertility, hormones used to manage menopause and osteoporosis , and certain... related regulatory actions for biologics approved in the United States and the European Union.19 It found that 41 of 174 biologics approved since 1995...black box” warnings on product labels but no product withdrawals. The October 2008 study found that the probability of a first safety- related

  14. In silico discovery of transcription regulatory elements in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Le Roch Karine G

    2008-02-01

    Full Text Available Abstract Background With the sequence of the Plasmodium falciparum genome and several global mRNA and protein life cycle expression profiling projects now completed, elucidating the underlying networks of transcriptional control important for the progression of the parasite life cycle is highly pertinent to the development of new anti-malarials. To date, relatively little is known regarding the specific mechanisms the parasite employs to regulate gene expression at the mRNA level, with studies of the P. falciparum genome sequence having revealed few cis-regulatory elements and associated transcription factors. Although it is possible the parasite may evoke mechanisms of transcriptional control drastically different from those used by other eukaryotic organisms, the extreme AT-rich nature of P. falciparum intergenic regions (~90% AT presents significant challenges to in silico cis-regulatory element discovery. Results We have developed an algorithm called Gene Enrichment Motif Searching (GEMS that uses a hypergeometric-based scoring function and a position-weight matrix optimization routine to identify with high-confidence regulatory elements in the nucleotide-biased and repeat sequence-rich P. falciparum genome. When applied to promoter regions of genes contained within 21 co-expression gene clusters generated from P. falciparum life cycle microarray data using the semi-supervised clustering algorithm Ontology-based Pattern Identification, GEMS identified 34 putative cis-regulatory elements associated with a variety of parasite processes including sexual development, cell invasion, antigenic variation and protein biosynthesis. Among these candidates were novel motifs, as well as many of the elements for which biological experimental evidence already exists in the Plasmodium literature. To provide evidence for the biological relevance of a cell invasion-related element predicted by GEMS, reporter gene and electrophoretic mobility shift assays

  15. Regulatory focus in groupt contexts

    NARCIS (Netherlands)

    Faddegon, Krispijn Johannes

    2009-01-01

    The thesis examines the influence of group processes on the regulatory focus of individual group members. It is demonstrated that the group situation can affect group members' regulatory focus both in a top-down fashion (via the identitiy of the group) and in a bottom-up fashion (emerging from the

  16. Regulatory Quality and Competition Policy

    OpenAIRE

    International Finance Corporation; Multilateral Investment Guarantee Agency; World Bank

    2010-01-01

    Regulatory reform and competition policy are two important and inter-related areas of regulatory policy and public administration. Both can play a key role in improving the quality of regulation, and creating healthy and competitive markets and an attractive investment climate. This in turn leads to greater economic growth, employment and incomes. Part one of this paper discusses definitio...

  17. Reconsidering Styles of Regulatory Enforcement

    DEFF Research Database (Denmark)

    May, Peter J.; Winter, Søren

    2000-01-01

    This study addresses enforcement styles of regulatory inspectors, based on an examination of the municipal enforcement of agro-environmental policies in Denmark. Our findings make three contributions to the regulatory literature. One contribution is to add empirical support for theorizing about...

  18. Systems biology of cellular rhythms.

    Science.gov (United States)

    Goldbeter, A; Gérard, C; Gonze, D; Leloup, J-C; Dupont, G

    2012-08-31

    Rhythms abound in biological systems, particularly at the cellular level where they originate from the feedback loops present in regulatory networks. Cellular rhythms can be investigated both by experimental and modeling approaches, and thus represent a prototypic field of research for systems biology. They have also become a major topic in synthetic biology. We review advances in the study of cellular rhythms of biochemical rather than electrical origin by considering a variety of oscillatory processes such as Ca++ oscillations, circadian rhythms, the segmentation clock, oscillations in p53 and NF-κB, synthetic oscillators, and the oscillatory dynamics of cyclin-dependent kinases driving the cell cycle. Finally we discuss the coupling between cellular rhythms and their robustness with respect to molecular noise.

  19. Biological preconcentrator

    Science.gov (United States)

    Manginell, Ronald P [Albuquerque, NM; Bunker, Bruce C [Albuquerque, NM; Huber, Dale L [Albuquerque, NM

    2008-09-09

    A biological preconcentrator comprises a stimulus-responsive active film on a stimulus-producing microfabricated platform. The active film can comprise a thermally switchable polymer film that can be used to selectively absorb and desorb proteins from a protein mixture. The biological microfabricated platform can comprise a thin membrane suspended on a substrate with an integral resistive heater and/or thermoelectric cooler for thermal switching of the active polymer film disposed on the membrane. The active polymer film can comprise hydrogel-like polymers, such as poly(ethylene oxide) or poly(n-isopropylacrylamide), that are tethered to the membrane. The biological preconcentrator can be fabricated with semiconductor materials and technologies.

  20. Virginia Power's regulatory reduction program

    International Nuclear Information System (INIS)

    Miller, G.D.

    1996-01-01

    Virginia Power has two nuclear plants, North Anna and Surry Power Stations, which have two units each for a total of four nuclear units. In 1992, the Nuclear Regulatory Commission solicited comments from the nuclear industry to obtain their ideas for reducing the regulatory burden on nuclear facilities. Pursuant to the new regulatory climate, Virginia Power developed an internal program to evaluate and assess the regulatory and self-imposed requirements to which they were committed, and to pursue regulatory relief or internal changes where possible and appropriate. The criteria were that public safety must be maintained, and savings must be significant. Up to the date of the conference, over US$22 million of one-time saving had been effected, and US$2.75 million in annual savings

  1. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...... responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune...... reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells...

  2. Biological rhythms

    Science.gov (United States)

    Halberg, F.

    1975-01-01

    An overview is given of basic features of biological rhythms. The classification of periodic behavior of physical and psychological characteristics as circadian, circannual, diurnal, and ultradian is discussed, and the notion of relativistic time as it applies in biology is examined. Special attention is given to circadian rhythms which are dependent on the adrenocortical cycle. The need for adequate understanding of circadian variations in the basic physiological indicators of an individual (heart rate, body temperature, systolic and diastolic blood pressure, etc.) to ensure the effectiveness of prophylactic and therapeutic measures is stressed.

  3. Managing biological networks by using text mining and computer-aided curation

    Science.gov (United States)

    Yu, Seok Jong; Cho, Yongseong; Lee, Min-Ho; Lim, Jongtae; Yoo, Jaesoo

    2015-11-01

    In order to understand a biological mechanism in a cell, a researcher should collect a huge number of protein interactions with experimental data from experiments and the literature. Text mining systems that extract biological interactions from papers have been used to construct biological networks for a few decades. Even though the text mining of literature is necessary to construct a biological network, few systems with a text mining tool are available for biologists who want to construct their own biological networks. We have developed a biological network construction system called BioKnowledge Viewer that can generate a biological interaction network by using a text mining tool and biological taggers. It also Boolean simulation software to provide a biological modeling system to simulate the model that is made with the text mining tool. A user can download PubMed articles and construct a biological network by using the Multi-level Knowledge Emergence Model (KMEM), MetaMap, and A Biomedical Named Entity Recognizer (ABNER) as a text mining tool. To evaluate the system, we constructed an aging-related biological network that consist 9,415 nodes (genes) by using manual curation. With network analysis, we found that several genes, including JNK, AP-1, and BCL-2, were highly related in aging biological network. We provide a semi-automatic curation environment so that users can obtain a graph database for managing text mining results that are generated in the server system and can navigate the network with BioKnowledge Viewer, which is freely available at http://bioknowledgeviewer.kisti.re.kr.

  4. Discovery of Chemical Toxicity via Biological Networks and Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, Edward; Habib, Tanwir; Guan, Xin; Escalon, Barbara; Falciani, Francesco; Chipman, J.K.; Antczak, Philipp; Edwards, Stephen; Taylor, Ronald C.; Vulpe, Chris; Loguinov, Alexandre; Van Aggelen, Graham; Villeneuve, Daniel L.; Garcia-Reyero, Natalia

    2010-09-30

    Both soldiers and animals are exposed to many chemicals as the result of military activities. Tools are needed to understand the hazards and risks that chemicals and new materials pose to soldiers and the environment. We have investigated the potential of global gene regulatory networks in understanding the impact of chemicals on reproduction. We characterized effects of chemicals on ovaries of the model animal system, the Fathead minnow (Pimopheles promelas) connecting chemical impacts on gene expression to circulating blood levels of the hormones testosterone and estradiol in addition to the egg yolk protein vitellogenin. We describe the application of reverse engineering complex interaction networks from high dimensional gene expression data to characterize chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis that governs reproduction in fathead minnows. The construction of global gene regulatory networks provides deep insights into how drugs and chemicals effect key organs and biological pathways.

  5. Regulatory Streamlining and Improvement

    Energy Technology Data Exchange (ETDEWEB)

    Mark A. Carl

    2006-07-11

    The Interstate Oil and Gas Compact Commission (IOGCC) engaged in numerous projects outlined under the scope of work discussed in the United States Department of Energy (DOE) grant number DE-FC26-04NT15456 awarded to the IOGCC. Numerous projects were completed that were extremely valuable to state oil and gas agencies as a result of work performed utilizing resources provided by the grant. There are numerous areas in which state agencies still need assistance. This additional assistance will need to be addressed under future scopes of work submitted annually to DOE's Project Officer for this grant. This report discusses the progress of the projects outlined under the grant scope of work for the 2005-2006 areas of interest, which are as follows: Area of Interest No. 1--Regulatory Streamlining and Improvement: This area of interest continues to support IOGCC's regulatory streamlining efforts that include the identification and elimination of unnecessary duplications of efforts between and among state and federal programs dealing with exploration and production on public lands. Area of Interest No. 2--Technology: This area of interest seeks to improve efficiency in states through the identification of technologies that can reduce costs. Area of Interest No. 3--Training and Education: This area of interest is vital to upgrading the skills of regulators and industry alike. Within the National Energy Policy, there are many appropriate training and education opportunities. Education was strongly endorsed by the President's National Energy Policy Development group. Acting through the governors offices, states are very effective conduits for the dissemination of energy education information. While the IOGCC favors the development of a comprehensive, long-term energy education plan, states are also supportive of immediate action on important concerns, such as energy prices, availability and conservation. Area of Interest No. 4--Resource Assessment and

  6. Kolmogorov complexity of epithelial pattern formation: the role of regulatory network configuration.

    Science.gov (United States)

    Flann, Nicholas S; Mohamadlou, Hamid; Podgorski, Gregory J

    2013-05-01

    The tissues of multicellular organisms are made of differentiated cells arranged in organized patterns. This organization emerges during development from the coupling of dynamic intra- and intercellular regulatory networks. This work applies the methods of information theory to understand how regulatory network structure both within and between cells relates to the complexity of spatial patterns that emerge as a consequence of network operation. A computational study was performed in which undifferentiated cells were arranged in a two dimensional lattice, with gene expression in each cell regulated by identical intracellular randomly generated Boolean networks. Cell-cell contact signalling between embryonic cells is modeled as coupling among intracellular networks so that gene expression in one cell can influence the expression of genes in adjacent cells. In this system, the initially identical cells differentiate and form patterns of different cell types. The complexity of network structure, temporal dynamics and spatial organization is quantified through the Kolmogorov-based measures of normalized compression distance and set complexity. Results over sets of random networks that operate in the ordered, critical and chaotic domains demonstrate that: (1) ordered and critical networks tend to create the most information-rich patterns; (2) signalling configurations in which cell-to-cell communication is non-directional mostly produce simple patterns irrespective of the internal network domain; and (3) directional signalling configurations, similar to those that function in planar cell polarity, produce the most complex patterns, but only when the intracellular networks function in non-chaotic domains. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Marine Biology

    Science.gov (United States)

    Dewees, Christopher M.; Hooper, Jon K.

    1976-01-01

    A variety of informational material for a course in marine biology or oceanology at the secondary level is presented. Among the topics discussed are: food webs and pyramids, planktonic blooms, marine life, plankton nets, food chains, phytoplankton, zooplankton, larval plankton and filter feeders. (BT)

  8. Mesoscopic biology

    Indian Academy of Sciences (India)

    Abstract. In this paper we present a qualitative outlook of mesoscopic biology where the typical length scale is of the order of nanometers and the energy scales comparable to thermal energy. Novel biomolecular machines, governed by coded information at the level of DNA and proteins, operate at these length scales in ...

  9. Scaffolded biology.

    Science.gov (United States)

    Minelli, Alessandro

    2016-09-01

    Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.

  10. Biological digestion

    International Nuclear Information System (INIS)

    Rosevear, A.

    1988-01-01

    This paper discusses the biological degradation of non-radioactive organic material occurring in radioactive wastes. The biochemical steps are often performed using microbes or isolated enzymes in combination with chemical steps and the aim is to oxidise the carbon, hydrogen, nitrogen and sulphur to their respective oxides. (U.K.)

  11. Biology Notes.

    Science.gov (United States)

    School Science Review, 1981

    1981-01-01

    Outlines a variety of laboratory procedures, techniques, and materials including construction of a survey frame for field biology, a simple tidal system, isolation and applications of plant protoplasts, tropisms, teaching lung structure, and a key to statistical methods for biologists. (DS)

  12. Stochastic Pseudo-Boolean Optimization

    Science.gov (United States)

    2011-07-31

    equivalence of (P1) and (P2). In the case r = 2, we explore how to improve the computational efficiency in terms of solving the proposed La - grangian...a general guideline for branching, our La - grangian relaxation method naturally lends itself to an efficient branching rule. For each xi, let wi = ∑ j...program- ming. Informatica , 3:225–240, 1992. [112] G. Palubeckis. Multistart tabu search strategies for the unconstrained binary quadratic opti

  13. Generalized Boolean Functions as Combiners

    Science.gov (United States)

    2017-06-01

    backbone of many computer functions. Cryptography drives online commerce and allows privileged information safe transit between two parties as well as many...the backbone of many computer functions. Cryptography drives online commerce and allows privileged information safe transit be- tween two parties as...Functions 5 2.1 Linear Feedback Shift Registers . . . . . . . . . . . . . . . . . . 5 2.2 Combiners . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

  14. Review of Biological Network Data and Its Applications

    Directory of Open Access Journals (Sweden)

    Donghyeon Yu

    2013-12-01

    Full Text Available Studying biological networks, such as protein-protein interactions, is key to understanding complex biological activities. Various types of large-scale biological datasets have been collected and analyzed with high-throughput technologies, including DNA microarray, next-generation sequencing, and the two-hybrid screening system, for this purpose. In this review, we focus on network-based approaches that help in understanding biological systems and identifying biological functions. Accordingly, this paper covers two major topics in network biology: reconstruction of gene regulatory networks and network-based applications, including protein function prediction, disease gene prioritization, and network-based genome-wide association study.

  15. 76 FR 32878 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2011-06-07

    ...; ] NUCLEAR REGULATORY COMMISSION 10 CFR Part 50 Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG...

  16. Regulatory risk coherence

    International Nuclear Information System (INIS)

    Remick, F.J.

    1992-01-01

    As one of the most progressive users of risk assessment in decision making, the US Nuclear Regulatory Commission (NRC) is in a position to play an important role in influencing the development of standard government wide policies for the application of risk assessment in decision making. The NRC, with the support of the nuclear industry, should use the opportunity provided by its experience with risk assessment to actively encourage the adoption of standard national and international health-based safety goals and at the same time accelerate its own efforts to implement the safety goals it has already developed for itself. There are signs of increased recognition of the need for consistency and coherence in the application of risk assessment in government decision making. The NRC and the nuclear industry have recently taken a great step toward establishing a consistant and coherent risk assessment-based culture in the US nuclear industry. As a result of Generic Letter 88-20, which asks each commercial nuclear power plant licensee to perform an individual plant examination by September 1992, for the first time a risk assessment characterizing initiating events in each plant will exist

  17. Internationalization of regulatory requirements.

    Science.gov (United States)

    Juillet, Y

    2003-02-01

    The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

  18. Discrete and ultradiscrete models for biological rhythms comprising a simple negative feedback loop.

    Science.gov (United States)

    Gibo, Shingo; Ito, Hiroshi

    2015-08-07

    Many biological rhythms are generated by negative feedback regulation. Griffith (1968) proved that a negative feedback model with two variables expressed by ordinary differential equations do not generate self-sustained oscillations. Kurosawa et al. (2002) expanded Griffith׳s result to the general type of negative feedback model with two variables. In this paper, we propose discrete and ultradiscrete feedback models with two variables that exhibit self-sustained oscillations. To obtain the model, we applied tropical discretization and ultradiscretization to a continuous model with two variables and then investigated its bifurcation structures and the conditions of parameters for oscillations. We found that when the degradation rate of the variables is lower than their synthesis rate, the proposed models generate oscillations by Neimark-Sacker bifurcation. We further demonstrate that the ultradiscrete model can be reduced to a Boolean system under some conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. A stochastic differential equation model for transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    Quirk Michelle D

    2007-05-01

    Full Text Available Abstract Background This work explores the quantitative characteristics of the local transcriptional regulatory network based on the availability of time dependent gene expression data sets. The dynamics of the gene expression level are fitted via a stochastic differential equation model, yielding a set of specific regulators and their contribution. Results We show that a beta sigmoid function that keeps track of temporal parameters is a novel prototype of a regulatory function, with the effect of improving the performance of the profile prediction. The stochastic differential equation model follows well the dynamic of the gene expression levels. Conclusion When adapted to biological hypotheses and combined with a promoter analysis, the method proposed here leads to improved models of the transcriptional regulatory networks.

  20. A modulator based regulatory network for ERα signaling pathway.

    Science.gov (United States)

    Wu, Heng-Yi; Zheng, Pengyue; Jiang, Guanglong; Liu, Yunlong; Nephew, Kenneth P; Huang, Tim H M; Li, Lang

    2012-01-01

    Estrogens control multiple functions of hormone-responsive breast cancer cells. They regulate diverse physiological processes in various tissues through genomic and non-genomic mechanisms that result in activation or repression of gene expression. Transcription regulation upon estrogen stimulation is a critical biological process underlying the onset and progress of the majority of breast cancer. ERα requires distinct co-regulator or modulators for efficient transcriptional regulation, and they form a regulatory network. Knowing this regulatory network will enable systematic study of the effect of ERα on breast cancer. To investigate the regulatory network of ERα and discover novel modulators of ERα functions, we proposed an analytical method based on a linear regression model to identify translational modulators and their network relationships. In the network analysis, a group of specific modulator and target genes were selected according to the functionality of modulator and the ERα binding. Network formed from targets genes with ERα binding was called ERα genomic regulatory network; while network formed from targets genes without ERα binding was called ERα non-genomic regulatory network. Considering the active or repressive function of ERα, active or repressive function of a modulator, and agonist or antagonist effect of a modulator on ERα, the ERα/modulator/target relationships were categorized into 27 classes. Using the gene expression data and ERα Chip-seq data from the MCF-7 cell line, the ERα genomic/non-genomic regulatory networks were built by merging ERα/ modulator/target triplets (TF, M, T), where TF refers to the ERα, M refers to the modulator, and T refers to the target. Comparing these two networks, ERα non-genomic network has lower FDR than the genomic network. In order to validate these two networks, the same network analysis was performed in the gene expression data from the ZR-75.1 cell. The network overlap analysis between two

  1. Strengthening Regulatory Competence in Pakistan

    International Nuclear Information System (INIS)

    Sadiq, M.

    2016-01-01

    Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

  2. The Danish Regulatory Reform of Telecommunications

    DEFF Research Database (Denmark)

    Skouby, Knud Erik

    1998-01-01

    An overview of the liberalisation process and regulatory reform of telecommunications in Denmark......An overview of the liberalisation process and regulatory reform of telecommunications in Denmark...

  3. News from the Biological Stain Commission No. 10

    DEFF Research Database (Denmark)

    Lyon, H O

    2011-01-01

    In the 10th issue of News from the Biological Stain Commission (BSC), under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the meeting of ISO/TC 212/WG 1 held in London, UK, on 16-17 November 2009. Furthermore...

  4. News from the Biological Stain Commission no. 12

    DEFF Research Database (Denmark)

    Lyon, H O

    2012-01-01

    In this 12(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the meetings of ISO/TC 212/WG 1 Quality and competence in the medical laboratory and ISO...

  5. News from the Biological Stain Commission no. 13

    DEFF Research Database (Denmark)

    Lyon, H O

    2013-01-01

    In the 13(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the first plenary meeting of the International Standards Organization ISO/TC 212 Clinical lab...... laboratory testing and in vitro diagnostic test systems held on 17-19 October 2011 in Las Vegas, Nevada....

  6. Measuring the evolutionary rewiring of biological networks.

    Directory of Open Access Journals (Sweden)

    Chong Shou

    Full Text Available We have accumulated a large amount of biological network data and expect even more to come. Soon, we anticipate being able to compare many different biological networks as we commonly do for molecular sequences. It has long been believed that many of these networks change, or "rewire", at different rates. It is therefore important to develop a framework to quantify the differences between networks in a unified fashion. We developed such a formalism based on analogy to simple models of sequence evolution, and used it to conduct a systematic study of network rewiring on all the currently available biological networks. We found that, similar to sequences, biological networks show a decreased rate of change at large time divergences, because of saturation in potential substitutions. However, different types of biological networks consistently rewire at different rates. Using comparative genomics and proteomics data, we found a consistent ordering of the rewiring rates: transcription regulatory, phosphorylation regulatory, genetic interaction, miRNA regulatory, protein interaction, and metabolic pathway network, from fast to slow. This ordering was found in all comparisons we did of matched networks between organisms. To gain further intuition on network rewiring, we compared our observed rewirings with those obtained from simulation. We also investigated how readily our formalism could be mapped to other network contexts; in particular, we showed how it could be applied to analyze changes in a range of "commonplace" networks such as family trees, co-authorships and linux-kernel function dependencies.

  7. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2004-01-01

    The 48. session of the IAEA general conference was held in Vienna from 20 to 24 september 2004 with the participation of delegates from 125 members states and representatives of various international organisations. A number of resolutions were adopted by the conference in the following fields: nuclear safety, radiation, transport and waste safety. The general conference also adopted a resolution on measures to protect against nuclear terrorism. The Director General decided in 2003 to appoint a group of experts to explore and advise on issues related to nuclear liability. This group called the International Expert Group on Nuclear Liability (I.N.L.E.X.) consists of 20 experts members from nuclear power and non nuclear power countries and from shipping and non shipping states. It serves three major functions: to create a forum of expertise to explore and advise on issues related to nuclear liability; to enhance global adherence by nuclear and non nuclear states to an effective nuclear liability regime, inter alia, on the basis of the convention on supplementary compensation for nuclear damage and the annex thereto, the Vienna convention on civil liability for nuclear damage, the Paris convention on third party liability in the field of nuclear energy, the joint protocol relating to the application of the vienna convention and the paris convention and the amendments thereto; and to assist in the development and strengthening of the national nuclear liability legal frameworks in IAEA members states to protect the public and the environment and to enhance nuclear safety. The second part of international regulatory concerns a directive on public access to environmental information made by the European Parliament. (N.C.)

  8. Biologic Scaffolds.

    Science.gov (United States)

    Costa, Alessandra; Naranjo, Juan Diego; Londono, Ricardo; Badylak, Stephen F

    2017-09-01

    Biologic scaffold materials composed of allogeneic or xenogeneic extracellular matrix are commonly used for the repair and functional reconstruction of injured and missing tissues. These naturally occurring bioscaffolds are manufactured by the removal of the cellular content from source tissues while preserving the structural and functional molecular units of the remaining extracellular matrix (ECM). The mechanisms by which these bioscaffolds facilitate constructive remodeling and favorable clinical outcomes include release or creation of effector molecules that recruit endogenous stem/progenitor cells to the site of scaffold placement and modulation of the innate immune response, specifically the activation of an anti-inflammatory macrophage phenotype. The methods by which ECM biologic scaffolds are prepared, the current understanding of in vivo scaffold remodeling, and the associated clinical outcomes are discussed in this article. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  9. Biological radioprotector

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    According to the patent description, the biological radioprotector is deuterium depleted water, DDW, produced by vacuum distillation with an isotopic content lower than natural value. It appears as such or in a mixture with natural water and carbon dioxide. It can be used for preventing and reducing the ionizing radiation effects upon humans or animal organisms, exposed therapeutically, professionally or accidentally to radiation. The most significant advantage of using DDW as biological radioprotector results from its way of administration. Indeed no one of the radioprotectors currently used today can be orally administrated, what reduces the patients' compliance to prophylactic administrations. The biological radioprotector is an unnoxious product obtained from natural water, which can be administrated as food additive instead of drinking water. Dose modification factor is according to initial estimates around 1.9, what is a remarkable feature when one takes into account that the product is toxicity-free and side effect-free and can be administrated prophylactically as a food additive. A net radioprotective action of the deuterium depletion was evidenced experimentally in laboratory animals (rats) hydrated with DDW of 30 ppm D/(D+H) concentration as compared with normally hydrated control animals. Knowing the effects of irradiation and mechanisms of the acute radiation disease as well as the effects of administration of radiomimetic chemicals upon cellular lines of fast cell division, it appears that the effects of administrating DDW result from stimulation of the immunity system. In conclusion, the biological radioprotector DDW presents the following advantages: - it is obtained from natural products without toxicity; - it is easy to be administrated as a food additive, replacing the drinking water; - besides radioprotective effects, the product has also immunostimulative and antitumoral effects

  10. Crusts: biological

    Science.gov (United States)

    Belnap, Jayne; Elias, Scott A.

    2013-01-01

    Biological soil crusts, a community of cyanobacteria, lichens, mosses, and fungi, are an essential part of dryland ecosystems. They are critical in the stabilization of soils, protecting them from wind and water erosion. Similarly, these soil surface communities also stabilized soils on early Earth, allowing vascular plants to establish. They contribute nitrogen and carbon to otherwise relatively infertile dryland soils, and have a strong influence on hydrologic cycles. Their presence can also influence vascular plant establishment and nutrition.

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

    CERN Document Server

    Knabe, Johannes F

    2013-01-01

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

  12. The future of yogurt: scientific and regulatory needs1234

    Science.gov (United States)

    German, J Bruce

    2014-01-01

    Lactation biology, microbial selection, and human diversity are central themes that could guide investment in scientific research, industrial innovation, and regulatory policy oversight to propel yogurt into the central role for health-promoting food products. The ability of yogurt to provide the nourishing properties of milk together with the live microorganisms from fermentation provides a unique combination of food assets. Academic research must now define the various targets on which these biological assets act to improve health and develop the metrics that can quantitatively document their benefits. The food industry must reconcile that yogurt and its microorganisms cannot be expected to provide measurable benefits for all consumers, at all doses, and at all times. A supportive regulatory oversight must demand safety and yet encourage innovations that support a value proposition for yogurt in health. Health valuation in the marketplace will be driven by parallel innovations, including accurate assessment technologies, validated microbial ingredients, and health-aware consumers. PMID:24695899

  13. MicroRNAs as regulatory elements in psoriasis

    Directory of Open Access Journals (Sweden)

    Liu Yuan

    2016-01-01

    Full Text Available Psoriasis is a chronic, autoimmune, and complex genetic disorder that affects 23% of the European population. The symptoms of Psoriatic skin are inflammation, raised and scaly lesions. microRNA, which is short, nonprotein-coding, regulatory RNAs, plays critical roles in psoriasis. microRNA participates in nearly all biological processes, such as cell differentiation, development and metabolism. Recent researches reveal that multitudinous novel microRNAs have been identified in skin. Some of these substantial novel microRNAs play as a class of posttranscriptional gene regulator in skin disease, such as psoriasis. In order to insight into microRNAs biological functions and verify microRNAs biomarker, we review diverse references about characterization, profiling and subtype of microRNAs. Here we will share our opinions about how and which microRNAs are as regulatory in psoriasis.

  14. Marine biology

    International Nuclear Information System (INIS)

    Thurman, H.V.; Webber, H.H.

    1984-01-01

    This book discusses both taxonomic and ecological topics on marine biology. Full coverage of marine organisms of all five kingdoms is provided, along with interesting and thorough discussion of all major marine habitats. Organization into six major parts allows flexibility. It also provides insight into important topics such as disposal of nuclear waste at sea, the idea that life began on the ocean floor, and how whales, krill, and people interact. A full-color photo chapter reviews questions, and exercises. The contents are: an overview marine biology: fundamental concepts/investigating life in the ocean; the physical ocean, the ocean floor, the nature of water, the nature and motion of ocean water; general ecology, conditions for life in the sea, biological productivity and energy transfer; marine organisms; monera, protista, mycota and metaphyta; the smaller marine animals, the large animals marine habitats, the intertidal zone/benthos of the continental shelf, the photic zone, the deep ocean, the ocean under stress, marine pollution, appendix a: the metric system and conversion factors/ appendix b: prefixes and suffixes/ appendix c: taxonomic classification of common marine organisms, and glossary, and index

  15. Recent regulatory issues in Finland

    International Nuclear Information System (INIS)

    Laaksonen, J.; Tiipana, P.

    2001-01-01

    This paper presents general regulatory issues from Finland since the last WWER Regulators Forum meeting in Odessa 11-13 October 2000. More specific issues concerning Loviisa NPP are described in the Annex of this paper. (author)

  16. Quality assurance within regulatory bodies

    International Nuclear Information System (INIS)

    1999-06-01

    The IAEA directed extensive efforts during the years 1991 to 1995 to the integral revision of all NUSS quality assurance publications, which were approved and issued as Safety Series No.50-C/SG-Q, Quality Assurance for Safety in Nuclear Power Plants and other Nuclear Installations (1996). When these quality assurance publications were developed, their prime focus was on requirements against which work performed by the licensees could be measured and assessed by the regulatory bodies. In this way, they only helped to facilitate the functions of regulators. No requirements or recommendations were provided on how the regulators should ensure the effective implementation of their own activities. The present publication is a first attempt to collect, integrate and offer available experience to directly support performance of regulatory activities. It presents a comprehensive compilation on the application of quality assurance principles and methods by regulatory bodies to their activities. The aim is consistent good performance of regulatory activities through a systematic approach

  17. Regulatory facility guide for Ohio

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, S.S.; Bock, R.E.; Francis, M.W.; Gove, R.M.; Johnson, P.E.; Kovac, F.M.; Mynatt, J.O. [Oak Ridge National Lab., TN (United States); Rymer, A.C. [Transportation Consulting Services, Knoxville, TN (United States)

    1994-02-28

    The Regulatory Facility Guide (RFG) has been developed for the DOE and contractor facilities located in the state of Ohio. It provides detailed compilations of international, federal, and state transportation-related regulations applicable to shipments originating at destined to Ohio facilities. This RFG was developed as an additional resource tool for use both by traffic managers who must ensure that transportation operations are in full compliance with all applicable regulatory requirements and by oversight personnel who must verify compliance activities.

  18. Fan-out in gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Sauro Herbert M

    2010-12-01

    Full Text Available Abstract Background In synthetic biology, gene regulatory circuits are often constructed by combining smaller circuit components. Connections between components are achieved by transcription factors acting on promoters. If the individual components behave as true modules and certain module interface conditions are satisfied, the function of the composite circuits can in principle be predicted. Results In this paper, we investigate one of the interface conditions: fan-out. We quantify the fan-out, a concept widely used in electrical engineering, to indicate the maximum number of the downstream inputs that an upstream output transcription factor can regulate. The fan-out is shown to be closely related to retroactivity studied by Del Vecchio, et al. An efficient operational method for measuring the fan-out is proposed and shown to be applied to various types of module interfaces. The fan-out is also shown to be enhanced by self-inhibitory regulation on the output. The potential role of an inhibitory regulation is discussed. Conclusions The proposed estimation method for fan-out not only provides an experimentally efficient way for quantifying the level of modularity in gene regulatory circuits but also helps characterize and design module interfaces, enabling the modular construction of gene circuits.

  19. Information transmission in genetic regulatory networks: a review

    International Nuclear Information System (INIS)

    Tkacik, Gasper; Walczak, Aleksandra M

    2011-01-01

    Genetic regulatory networks enable cells to respond to changes in internal and external conditions by dynamically coordinating their gene expression profiles. Our ability to make quantitative measurements in these biochemical circuits has deepened our understanding of what kinds of computations genetic regulatory networks can perform, and with what reliability. These advances have motivated researchers to look for connections between the architecture and function of genetic regulatory networks. Transmitting information between a network's inputs and outputs has been proposed as one such possible measure of function, relevant in certain biological contexts. Here we summarize recent developments in the application of information theory to gene regulatory networks. We first review basic concepts in information theory necessary for understanding recent work. We then discuss the functional complexity of gene regulation, which arises from the molecular nature of the regulatory interactions. We end by reviewing some experiments that support the view that genetic networks responsible for early development of multicellular organisms might be maximizing transmitted 'positional information'. (topical review)

  20. Regulatory options for genetically modified crops in India.

    Science.gov (United States)

    Choudhary, Bhagirath; Gheysen, Godelieve; Buysse, Jeroen; van der Meer, Piet; Burssens, Sylvia

    2014-02-01

    The introduction of semi-dwarfing, high-yielding and nutrients-responsive crop varieties in the 1960s and 1970s alleviated the suffering of low crop yield, food shortages and epidemics of famine in India and other parts of the Asian continent. Two semi-dwarfing genes, Rht in wheat and Sd-1 in rice heralded the green revolution for which Dr. Norman Borlaug was awarded the Nobel Peace Prize in 1970. In contrast, the revolutionary new genetics of crop improvement shamble over formidable obstacles of regulatory delays, political interferences and public misconceptions. India benefited immensely from the green revolution and is now grappling to deal with the nuances of GM crops. The development of GM mustard discontinued prematurely in 2001 and insect-resistant Bt cotton varieties were successfully approved for commercial cultivation in 2002 in an evolving nature of regulatory system. However, the moratorium on Bt brinjal by MOEF in 2010 meant a considerable detour from an objective, science-based, rigorous institutional process of regulatory approval to a more subjective, nonscience-driven, political decision-making process. This study examines what ails the regulatory system of GM crops in India and the steps that led to the regulatory logjam. Responding to the growing challenges and impediments of existing biosafety regulation, it suggests options that are critical for GM crops to take roots for a multiplier harvest. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  1. European regulatory tools for advanced therapy medicinal products.

    Science.gov (United States)

    Flory, Egbert; Reinhardt, Jens

    2013-12-01

    Increasing scientific knowledge and technical innovations in the areas of cell biology, biotechnology and medicine resulted in the development of promising therapeutic approaches for the prevention and treatment of human diseases. Advanced therapy medicinal products (ATMPs) reflect a complex and innovative class of biopharmaceuticals as these products are highly research-driven, characterised by innovative manufacturing processes and heterogeneous with regard to their origin, type and complexity. This class of ATMP integrates gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineering products and are often individualized and patient-specific products. Multiple challenges arise from the nature of ATMPs, which are often developed by micro, small and medium sized enterprises, university and academia, for whom regulatory experiences are limited and regulatory requirements are challenging. Regulatory guidance such as the reflection paper on classification of ATMPs and guidelines highlighting product-specific issues support academic research groups and pharmaceutical companies to foster the development of safe and effective ATMPs. This review provides an overview on the European regulatory aspects of ATMPs and highlights specific regulatory tools such as the ATMP classification procedure, a discussion on the hospital exemption for selected ATMPs as well as borderline issues towards transplants/transfusion products.

  2. Differential Regulatory Analysis Based on Coexpression Network in Cancer Research

    Directory of Open Access Journals (Sweden)

    Junyi Li

    2016-01-01

    Full Text Available With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA based on gene coexpression network (GCN increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies.

  3. 78 FR 44399 - Semiannual Regulatory Flexibility Agenda

    Science.gov (United States)

    2013-07-23

    ... of Basel III, Minimum Regulatory Capital Ratios, Capital Adequacy, and Transition Provisions. (Docket.... Regulations H and Y--Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Minimum... Committee on Banking Supervision (BCBS) in ``Basel III: A Global Regulatory Framework for More Resilient...

  4. 75 FR 61530 - Issuance of Regulatory Guides

    Science.gov (United States)

    2010-10-05

    ... NUCLEAR REGULATORY COMMISSION [NRC-2010-0312] Issuance of Regulatory Guides AGENCY: Nuclear... of the issuance and availability of Regulatory Guides 1.84, Rev. 35, ``Design, Fabrication, and... . SUPPLEMENTARY INFORMATION: I. Introduction The NRC is issuing two final Regulatory Guides (RGs) in the agency's...

  5. Chemically induced proximity in biology and medicine.

    Science.gov (United States)

    Stanton, Benjamin Z; Chory, Emma J; Crabtree, Gerald R

    2018-03-09

    Proximity, or the physical closeness of molecules, is a pervasive regulatory mechanism in biology. For example, most posttranslational modifications such as phosphorylation, methylation, and acetylation promote proximity of molecules to play deterministic roles in cellular processes. To understand the role of proximity in biologic mechanisms, chemical inducers of proximity (CIPs) were developed to synthetically model biologically regulated recruitment. Chemically induced proximity allows for precise temporal control of transcription, signaling cascades, chromatin regulation, protein folding, localization, and degradation, as well as a host of other biologic processes. A systematic analysis of CIPs in basic research, coupled with recent technological advances utilizing CRISPR, distinguishes roles of causality from coincidence and allows for mathematical modeling in synthetic biology. Recently, induced proximity has provided new avenues of gene therapy and emerging advances in cancer treatment. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  6. Biological biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Jorge-Herrero, E. [Servicio de Cirugia Experimental. Clinica Puerta de Hierro, Madrid (Spain)

    1997-05-01

    There are a number of situations in which substances of biological origin are employed as biomaterials. Most of them are macromolecules derived from isolated connective tissue or the connective tissue itself in membrane form, in both cases, the tissue can be used in its natural form or be chemically treated. In other cases, certain blood vessels can be chemically pretreated and used as vascular prostheses. Proteins such as albumin, collagen and fibrinogen are employed to coat vascular prostheses. Certain polysaccharides have also been tested for use in controlled drug release systems. Likewise, a number of tissues, such as dura mater, bovine pericardium, procine valves and human valves, are used in the preparation of cardiac prostheses. We also use veins from animals or humans in arterial replacement. In none of these cases are the tissues employed dissimilar to the native tissues as they have been chemically modified, becoming a new bio material with different physical and biochemical properties. In short, we find that natural products are being utilized as biomaterials and must be considered as such; thus, it is necessary to study both their chemicobiological and physicomechanical properties. In the present report, we review the current applications, problems and future prospects of some of these biological biomaterials. (Author) 84 refs.

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

    OpenAIRE

    Khan, Jehandad; Bouaynaya, Nidhal; Fathallah-Shaykh, Hassan M

    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 inf...

  8. Reconstruction of gene regulatory network related to photosynthesis in Arabidopsis thaliana

    OpenAIRE

    Yu, X.; Zheng, G.; Shan, L.; Meng, G.; Vingron, M.; Liu, Q.; Zhu, X.

    2014-01-01

    Photosynthesis is one of the most important biological processes on the earth. So far, though the molecular mechanisms underlying photosynthesis is well understood, however, the regulatory networks of photosynthesis are poorly studied. Given the current interest in improving photosynthetic efficiency for greater crop yield, elucidating the detailed regulatory networks controlling the construction and maintenance of photosynthetic machinery is not only scientifically significant but also holdi...

  9. Reconstruction of gene regulatory network related to photosynthesis in Arabidopsis thaliana

    OpenAIRE

    Xianbin eYu; Guangyong eZheng; Lanlan eShan; Guofeng eMeng; Martin eVingron; Qi eLiu; Xin-Guang eZhu; Xin-Guang eZhu

    2014-01-01

    Photosynthesis is one of the most important biological processes on the earth. So far, though the molecular mechanisms underlying photosynthesis is well understood, however, the regulatory networks of photosynthesis is poorly studied. Given the current interest in improving photosynthetic efficiency for greater crop yield, elucidating the detailed regulatory networks controlling the construction and maintenance of photosynthetic machinery is not only scientifically significant but also holdin...

  10. The Regulatory Independence of FANR

    International Nuclear Information System (INIS)

    ALNuaimi, Fatema; Choi, Kwang Shik

    2012-01-01

    Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

  11. Regulatory Expectations for Safety Culture

    International Nuclear Information System (INIS)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung

    2014-01-01

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety

  12. Regulatory Expectations for Safety Culture

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-05-15

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

  13. Radioactive waste below regulatory concern

    International Nuclear Information System (INIS)

    Neuder, S.M.

    1987-01-01

    The U.S. Nuclear Regulatory Commission (NRC) published two notices in the Federal Register concerning radioactive waste below regulatory concern. The first, a Commission Policy Statement and Implementation Plan published August 29, 1986, concerns petition to exempt specific radioactive waste streams from the regulations. The second, an Advanced Notice of Proposed Rulemaking published Decemger 2, 1986, addresses the concept of generic rulemaking by the NRC on radioactive wastes that are below regulatory concern. Radioactive waste determined to be below regulatory concern would not be subject to regulatory control and would not need to go to a licensed low-level radioactive waste disposal site. The Policy Statement and Implementation Plan describe (1) the information a petitioner should file in support of a petition to exempt a specific waste stream, (2) the decision criteria the Commission intends to use for judging the petition, and (3) the internal administrative procedures to use be followed in order to permit the Commission to act upon the petition in an expedited manner

  14. Biological effects

    International Nuclear Information System (INIS)

    Trott, K.R.

    1973-01-01

    Following an introduction into the field of cellular radiation effect considering the most important experimental results, the biological significance of the colony formation ability is brought out. The inactivation concept of stem cells does not only prove to be good, according to the present results, in the interpretation of the pathogenesis of acute radiation effects on moult tissue, it also enables chronicle radiation injuries to be interpreted through changes in the fibrous part of the organs. Radiation therapy of tumours can also be explained to a large extent by the radiation effect on the unlimited reproductiveness of tumour cells. The more or less similar dose effect curves for healthy and tumour tissue in practice lead to intermittent irradiation. The dependence of the intermittent doses and intervals on factors such as Elkind recovery, synchronisation, redistribution, reoxygenation, repopulation and regeneration are reviewed. (ORU/LH) [de

  15. Regulatory authority information system RAIS

    International Nuclear Information System (INIS)

    Ortiz, P.; Mrabit, K.; Miaw, S.

    2000-01-01

    In this lecture the principles of the regulatory authority information system (RAIS) are presented. RAIS is a tool currently being developed by the IAEA for the Regulatory Authorities. It is a part of a set of supporting actions designed to assist member states in achieving the objectives of the Model project on radiation and waste safety infrastructure. RAIS is a tool that provides the management of the Regulatory Authority with the key information needed for the planning and implementation of activities and to ensure confidence that resources are optimally used. The RAIS contains five modules: Inventory of installations and radiation sources; Authorization process; Inspection and follow-up actions; Information on personal dosimetry; Assessment of effectiveness by means of performance indicators

  16. Regulatory authority infrastructure for Namibia

    International Nuclear Information System (INIS)

    Shangula, K.

    2001-01-01

    The Republic of Namibia is participating in the International Atomic Energy Agency's Model Project for the Improvement of National Regulatory Authority Infrastructures in Member States. The paper illustrates our experience in solving problems and difficulties confronted in establishing an effective regulatory authority operating within the existing national infrastructure that should be supported by the Government. An effective regulatory authority is seen as part of the wider administrative scope of our Government through ministerial mandates given by the State from time to time, guaranteeing its independence when implementing legal provisions under statutes. Sections of the report illustrate our experience in the following areas: 1. National radiation protection policy 2. Structure of our national regulatory authority 3. Laws and regulations 4. Provisions for notification, authorization and registration 5. In-depth security measures for radiation sources and radioactive material 6. Systems for the inspection of radiation sources, radioactive materials, enforcement of legal provisions 7. Extent of the applications of radiation sources and radioactive materials in the country. The paper provides information regarding existing Government policy on radiation protection; structure and legal aspects of the national regulatory, including statutes and regulations; the extent of application and uses of radiation sources and security of radioactive materials; human resources: strengths and constraints; management practices and financing of regulatory authority; and plans for emergency recovery of orphan sources. National plans for management of disused sources, recovery of orphan sources, abnormal emergencies, communication of information to affected persons on exposure effects, and the safety training of persons using these applications are discussed. the paper provides a summary and some suggestions of the way forward for Namibia. (author)

  17. Regulatory processes in Aspergillus niger

    DEFF Research Database (Denmark)

    Poulsen, Lars

    some disadvantages as well, those are byproduct formation, secretion of proteolytic enzymes and formation of mycotoxins. The aim of this project was to reduce these disadvantages, though investigating the regulatory processes. The first objective was to study the regulatory events leading to A. niger...... characteristics, as a lower oxalic ii acid formation and wild type growth performance; it was therefore argued that this strain could be an attractive alternative to ΔprtT. Finally, in order to characterize the formation of the carcinogenic mycotoxin fumonisin, a reporter strain of A. niger was constructed, where...

  18. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section treats of the following activities sorted by country: 1 - Belarus: International cooperation, Organisation and structure, Licensing and regulatory infrastructure, Nuclear safety and radiological protection; 2 - France: Nuclear safety and radiological protection, Radioactive waste management, Environmental protection, Liability and compensation, International co-operation; 3 - Hungary: General legislation, Radioactive waste management, Nuclear security; 4 - Ireland: Nuclear safety and radiological protection (including emergency planning); 5 - Lithuania: Licensing and regulatory infrastructure; 6 - Moldova: Nuclear safety and radiological protection; 7 - Portugal: Radioactive waste management, Nuclear safety and radiological protection; 8 - Slovak Republic: Radioactive waste management, Liability and compensation; 9 - Spain: Radioactive waste management; 10 - Ukraine: Radioactive waste management; 11 - United Kingdom: Organisation and structure

  19. Creating biological nanomaterials using synthetic biology.

    Science.gov (United States)

    Rice, MaryJoe K; Ruder, Warren C

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  20. Creating biological nanomaterials using synthetic biology

    International Nuclear Information System (INIS)

    Rice, MaryJoe K; Ruder, Warren C

    2014-01-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems. (review)