Designing Networks that are Capable of Self-Healing and Adapting

DTIC Science & Technology

2017-04-01

from statistical mechanics, combinatorics, boolean networks, and numerical simulations, and inspired by design principles from biological networks, we... principles for self-healing networks, and applications, and construct an all-possible-paths model for network adaptation. 2015-11-16 UNIT CONVERSION...combinatorics, boolean networks, and numerical simulations, and inspired by design principles from biological networks, we will undertake the fol

Identification of control targets in Boolean molecular network models via computational algebra.

PubMed

Murrugarra, David; Veliz-Cuba, Alan; Aguilar, Boris; Laubenbacher, Reinhard

2016-09-23

Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network. Supplementary data is available online and our code in Macaulay2 and Matlab are available via http://www.ms.uky.edu/~dmu228/ControlAlg . This paper presents a novel method for the identification of intervention targets in Boolean network models. The results in this paper show that the proposed methods are useful and efficient for moderately large networks.

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

PubMed

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.

Identification of Boolean Network Models From Time Series Data Incorporating Prior Knowledge.

PubMed

Leifeld, Thomas; Zhang, Zhihua; Zhang, Ping

2018-01-01

Motivation: Mathematical models take an important place in science and engineering. A model can help scientists to explain dynamic behavior of a system and to understand the functionality of system components. Since length of a time series and number of replicates is limited by the cost of experiments, Boolean networks as a structurally simple and parameter-free logical model for gene regulatory networks have attracted interests of many scientists. In order to fit into the biological contexts and to lower the data requirements, biological prior knowledge is taken into consideration during the inference procedure. In the literature, the existing identification approaches can only deal with a subset of possible types of prior knowledge. Results: We propose a new approach to identify Boolean networks from time series data incorporating prior knowledge, such as partial network structure, canalizing property, positive and negative unateness. Using vector form of Boolean variables and applying a generalized matrix multiplication called the semi-tensor product (STP), each Boolean function can be equivalently converted into a matrix expression. Based on this, the identification problem is reformulated as an integer linear programming problem to reveal the system matrix of Boolean model in a computationally efficient way, whose dynamics are consistent with the important dynamics captured in the data. By using prior knowledge the number of candidate functions can be reduced during the inference. Hence, identification incorporating prior knowledge is especially suitable for the case of small size time series data and data without sufficient stimuli. The proposed approach is illustrated with the help of a biological model of the network of oxidative stress response. Conclusions: The combination of efficient reformulation of the identification problem with the possibility to incorporate various types of prior knowledge enables the application of computational model inference to systems with limited amount of time series data. The general applicability of this methodological approach makes it suitable for a variety of biological systems and of general interest for biological and medical research.

Discrete dynamic modeling of cellular signaling networks.

PubMed

Albert, Réka; Wang, Rui-Sheng

2009-01-01

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

Stabilizing Motifs in Autonomous Boolean Networks and the Yeast Cell Cycle Oscillator

NASA Astrophysics Data System (ADS)

Sevim, Volkan; Gong, Xinwei; Socolar, Joshua

2009-03-01

Synchronously updated Boolean networks are widely used to model gene regulation. Some properties of these model networks are known to be artifacts of the clocking in the update scheme. Autonomous updating is a less artificial scheme that allows one to introduce small timing perturbations and study stability of the attractors. We argue that the stabilization of a limit cycle in an autonomous Boolean network requires a combination of motifs such as feed-forward loops and auto-repressive links that can correct small fluctuations in the timing of switching events. A recently published model of the transcriptional cell-cycle oscillator in yeast contains the motifs necessary for stability under autonomous updating [1]. [1] D. A. Orlando, et al. Nature (London), 4530 (7197):0 944--947, 2008.

Evolution of canalizing Boolean networks

NASA Astrophysics Data System (ADS)

Szejka, A.; Drossel, B.

2007-04-01

Boolean networks with canalizing functions are used to model gene regulatory networks. In order to learn how such networks may behave under evolutionary forces, we simulate the evolution of a single Boolean network by means of an adaptive walk, which allows us to explore the fitness landscape. Mutations change the connections and the functions of the nodes. Our fitness criterion is the robustness of the dynamical attractors against small perturbations. We find that with this fitness criterion the global maximum is always reached and that there is a huge neutral space of 100% fitness. Furthermore, in spite of having such a high degree of robustness, the evolved networks still share many features with “chaotic” networks.

Modeling stochasticity and robustness in gene regulatory networks.

PubMed

Garg, Abhishek; Mohanram, Kartik; Di Cara, Alessandro; De Micheli, Giovanni; Xenarios, Ioannis

2009-06-15

Understanding gene regulation in biological processes and modeling the robustness of underlying regulatory networks is an important problem that is currently being addressed by computational systems biologists. Lately, there has been a renewed interest in Boolean modeling techniques for gene regulatory networks (GRNs). However, due to their deterministic nature, it is often difficult to identify whether these modeling approaches are robust to the addition of stochastic noise that is widespread in gene regulatory processes. Stochasticity in Boolean models of GRNs has been addressed relatively sparingly in the past, mainly by flipping the expression of genes between different expression levels with a predefined probability. This stochasticity in nodes (SIN) model leads to over representation of noise in GRNs and hence non-correspondence with biological observations. In this article, we introduce the stochasticity in functions (SIF) model for simulating stochasticity in Boolean models of GRNs. By providing biological motivation behind the use of the SIF model and applying it to the T-helper and T-cell activation networks, we show that the SIF model provides more biologically robust results than the existing SIN model of stochasticity in GRNs. Algorithms are made available under our Boolean modeling toolbox, GenYsis. The software binaries can be downloaded from http://si2.epfl.ch/ approximately garg/genysis.html.

Controllability and observability of Boolean networks arising from biology

NASA Astrophysics Data System (ADS)

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.

"Antelope": a hybrid-logic model checker for branching-time Boolean GRN analysis

PubMed Central

2011-01-01

Background In Thomas' formalism for modeling gene regulatory networks (GRNs), branching time, where a state can have more than one possible future, plays a prominent role. By representing a certain degree of unpredictability, branching time can model several important phenomena, such as (a) asynchrony, (b) incompletely specified behavior, and (c) interaction with the environment. Introducing more than one possible future for a state, however, creates a difficulty for ordinary simulators, because infinitely many paths may appear, limiting ordinary simulators to statistical conclusions. Model checkers for branching time, by contrast, are able to prove properties in the presence of infinitely many paths. Results We have developed Antelope ("Analysis of Networks through TEmporal-LOgic sPEcifications", http://turing.iimas.unam.mx:8080/AntelopeWEB/), a model checker for analyzing and constructing Boolean GRNs. Currently, software systems for Boolean GRNs use branching time almost exclusively for asynchrony. Antelope, by contrast, also uses branching time for incompletely specified behavior and environment interaction. We show the usefulness of modeling these two phenomena in the development of a Boolean GRN of the Arabidopsis thaliana root stem cell niche. There are two obstacles to a direct approach when applying model checking to Boolean GRN analysis. First, ordinary model checkers normally only verify whether or not a given set of model states has a given property. In comparison, a model checker for Boolean GRNs is preferable if it reports the set of states having a desired property. Second, for efficiency, the expressiveness of many model checkers is limited, resulting in the inability to express some interesting properties of Boolean GRNs. Antelope tries to overcome these two drawbacks: Apart from reporting the set of all states having a given property, our model checker can express, at the expense of efficiency, some properties that ordinary model checkers (e.g., NuSMV) cannot. This additional expressiveness is achieved by employing a logic extending the standard Computation-Tree Logic (CTL) with hybrid-logic operators. Conclusions We illustrate the advantages of Antelope when (a) modeling incomplete networks and environment interaction, (b) exhibiting the set of all states having a given property, and (c) representing Boolean GRN properties with hybrid CTL. PMID:22192526

Optimal stabilization of Boolean networks through collective influence

NASA Astrophysics Data System (ADS)

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.

Boolean Dynamic Modeling Approaches to Study Plant Gene Regulatory Networks: Integration, Validation, and Prediction.

PubMed

Velderraín, José Dávila; Martínez-García, Juan Carlos; Álvarez-Buylla, Elena R

2017-01-01

Mathematical models based on dynamical systems theory are well-suited tools for the integration of available molecular experimental data into coherent frameworks in order to propose hypotheses about the cooperative regulatory mechanisms driving developmental processes. Computational analysis of the proposed models using well-established methods enables testing the hypotheses by contrasting predictions with observations. Within such framework, Boolean gene regulatory network dynamical models have been extensively used in modeling plant development. Boolean models are simple and intuitively appealing, ideal tools for collaborative efforts between theorists and experimentalists. In this chapter we present protocols used in our group for the study of diverse plant developmental processes. We focus on conceptual clarity and practical implementation, providing directions to the corresponding technical literature.

Emergence of diversity in homogeneous coupled Boolean networks

NASA Astrophysics Data System (ADS)

Kang, Chris; Aguilar, Boris; Shmulevich, Ilya

2018-05-01

The origin of multicellularity in metazoa is one of the fundamental questions of evolutionary biology. We have modeled the generic behaviors of gene regulatory networks in isogenic cells as stochastic nonlinear dynamical systems—coupled Boolean networks with perturbation. Model simulations under a variety of dynamical regimes suggest that the central characteristic of multicellularity, permanent spatial differentiation (diversification), indeed can arise. Additionally, we observe that diversification is more likely to occur near the critical regime of Lyapunov stability.

Boolean networks with veto functions

NASA Astrophysics Data System (ADS)

Ebadi, Haleh; Klemm, Konstantin

2014-08-01

Boolean networks are discrete dynamical systems for modeling regulation and signaling in living cells. We investigate a particular class of Boolean functions with inhibiting inputs exerting a veto (forced zero) on the output. We give analytical expressions for the sensitivity of these functions and provide evidence for their role in natural systems. In an intracellular signal transduction network [Helikar et al., Proc. Natl. Acad. Sci. USA 105, 1913 (2008), 10.1073/pnas.0705088105], the functions with veto are over-represented by a factor exceeding the over-representation of threshold functions and canalyzing functions in the same system. In Boolean networks for control of the yeast cell cycle [Li et al., Proc. Natl. Acad. Sci. USA 101, 4781 (2004), 10.1073/pnas.0305937101; Davidich et al., PLoS ONE 3, e1672 (2008), 10.1371/journal.pone.0001672], no or minimal changes to the wiring diagrams are necessary to formulate their dynamics in terms of the veto functions introduced here.

Synchronization of coupled large-scale Boolean networks

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

Li, Fangfei, E-mail: li-fangfei@163.com

2014-03-15

This paper investigates the complete synchronization and partial synchronization of two large-scale Boolean networks. First, the aggregation algorithm towards large-scale Boolean network is reviewed. Second, the aggregation algorithm is applied to study the complete synchronization and partial synchronization of large-scale Boolean networks. Finally, an illustrative example is presented to show the efficiency of the proposed results.

Verification and Optimal Control of Context-Sensitive Probabilistic Boolean Networks Using Model Checking and Polynomial Optimization

PubMed Central

Hiraishi, Kunihiko

2014-01-01

One of the significant topics in systems biology is to develop control theory of gene regulatory networks (GRNs). In typical control of GRNs, expression of some genes is inhibited (activated) by manipulating external stimuli and expression of other genes. It is expected to apply control theory of GRNs to gene therapy technologies in the future. In this paper, a control method using a Boolean network (BN) is studied. A BN is widely used as a model of GRNs, and gene expression is expressed by a binary value (ON or OFF). In particular, a context-sensitive probabilistic Boolean network (CS-PBN), which is one of the extended models of BNs, is used. For CS-PBNs, the verification problem and the optimal control problem are considered. For the verification problem, a solution method using the probabilistic model checker PRISM is proposed. For the optimal control problem, a solution method using polynomial optimization is proposed. Finally, a numerical example on the WNT5A network, which is related to melanoma, is presented. The proposed methods provide us useful tools in control theory of GRNs. PMID:24587766

State feedback controller design for the synchronization of Boolean networks with time delays

NASA Astrophysics Data System (ADS)

Li, Fangfei; Li, Jianning; Shen, Lijuan

2018-01-01

State feedback control design to make the response Boolean network synchronize with the drive Boolean network is far from being solved in the literature. Motivated by this, this paper studies the feedback control design for the complete synchronization of two coupled Boolean networks with time delays. A necessary condition for the existence of a state feedback controller is derived first. Then the feedback control design procedure for the complete synchronization of two coupled Boolean networks is provided based on the necessary condition. Finally, an example is given to illustrate the proposed design procedure.

Polynomial algebra of discrete models in systems biology.

PubMed

Veliz-Cuba, Alan; Jarrah, Abdul Salam; Laubenbacher, Reinhard

2010-07-01

An increasing number of discrete mathematical models are being published in Systems Biology, ranging from Boolean network models to logical models and Petri nets. They are used to model a variety of biochemical networks, such as metabolic networks, gene regulatory networks and signal transduction networks. There is increasing evidence that such models can capture key dynamic features of biological networks and can be used successfully for hypothesis generation. This article provides a unified framework that can aid the mathematical analysis of Boolean network models, logical models and Petri nets. They can be represented as polynomial dynamical systems, which allows the use of a variety of mathematical tools from computer algebra for their analysis. Algorithms are presented for the translation into polynomial dynamical systems. Examples are given of how polynomial algebra can be used for the model analysis. alanavc@vt.edu Supplementary data are available at Bioinformatics online.

Modeling gene regulatory networks: A network simplification algorithm

NASA Astrophysics Data System (ADS)

Ferreira, Luiz Henrique O.; de Castro, Maria Clicia S.; da Silva, Fabricio A. B.

2016-12-01

Boolean networks have been used for some time to model Gene Regulatory Networks (GRNs), which describe cell functions. Those models can help biologists to make predictions, prognosis and even specialized treatment when some disturb on the GRN lead to a sick condition. However, the amount of information related to a GRN can be huge, making the task of inferring its boolean network representation quite a challenge. The method shown here takes into account information about the interactome to build a network, where each node represents a protein, and uses the entropy of each node as a key to reduce the size of the network, allowing the further inferring process to focus only on the main protein hubs, the ones with most potential to interfere in overall network behavior.

Observability of Boolean multiplex control networks

NASA Astrophysics Data System (ADS)

Wu, Yuhu; Xu, Jingxue; Sun, Xi-Ming; Wang, Wei

2017-04-01

Boolean multiplex (multilevel) networks (BMNs) are currently receiving considerable attention as theoretical arguments for modeling of biological systems and system level analysis. Studying control-related problems in BMNs may not only provide new views into the intrinsic control in complex biological systems, but also enable us to develop a method for manipulating biological systems using exogenous inputs. In this article, the observability of the Boolean multiplex control networks (BMCNs) are studied. First, the dynamical model and structure of BMCNs with control inputs and outputs are constructed. By using of Semi-Tensor Product (STP) approach, the logical dynamics of BMCNs is converted into an equivalent algebraic representation. Then, the observability of the BMCNs with two different kinds of control inputs is investigated by giving necessary and sufficient conditions. Finally, examples are given to illustrate the efficiency of the obtained theoretical results.

Boolean network representation of contagion dynamics during a financial crisis

NASA Astrophysics Data System (ADS)

Caetano, Marco Antonio Leonel; Yoneyama, Takashi

2015-01-01

This work presents a network model for representation of the evolution of certain patterns of economic behavior. More specifically, after representing the agents as points in a space in which each dimension associated to a relevant economic variable, their relative "motions" that can be either stationary or discordant, are coded into a boolean network. Patterns with stationary averages indicate the maintenance of status quo, whereas discordant patterns represent aggregation of new agent into the cluster or departure from the former policies. The changing patterns can be embedded into a network representation, particularly using the concept of autocatalytic boolean networks. As a case study, the economic tendencies of the BRIC countries + Argentina were studied. Although Argentina is not included in the cluster formed by BRIC countries, it tends to follow the BRIC members because of strong commercial ties.

Intrinsic noise and deviations from criticality in Boolean gene-regulatory networks

NASA Astrophysics Data System (ADS)

Villegas, Pablo; Ruiz-Franco, José; Hidalgo, Jorge; Muñoz, Miguel A.

2016-10-01

Gene regulatory networks can be successfully modeled as Boolean networks. A much discussed hypothesis says that such model networks reproduce empirical findings the best if they are tuned to operate at criticality, i.e. at the borderline between their ordered and disordered phases. Critical networks have been argued to lead to a number of functional advantages such as maximal dynamical range, maximal sensitivity to environmental changes, as well as to an excellent tradeoff between stability and flexibility. Here, we study the effect of noise within the context of Boolean networks trained to learn complex tasks under supervision. We verify that quasi-critical networks are the ones learning in the fastest possible way -even for asynchronous updating rules- and that the larger the task complexity the smaller the distance to criticality. On the other hand, when additional sources of intrinsic noise in the network states and/or in its wiring pattern are introduced, the optimally performing networks become clearly subcritical. These results suggest that in order to compensate for inherent stochasticity, regulatory and other type of biological networks might become subcritical rather than being critical, all the most if the task to be performed has limited complexity.

Energy and criticality in random Boolean networks

NASA Astrophysics Data System (ADS)

Andrecut, M.; Kauffman, S. A.

2008-06-01

The central issue of the research on the Random Boolean Networks (RBNs) model is the characterization of the critical transition between ordered and chaotic phases. Here, we discuss an approach based on the ‘energy’ associated with the unsatisfiability of the Boolean functions in the RBNs model, which provides an upper bound estimation for the energy used in computation. We show that in the ordered phase the RBNs are in a ‘dissipative’ regime, performing mostly ‘downhill’ moves on the ‘energy’ landscape. Also, we show that in the disordered phase the RBNs have to ‘hillclimb’ on the ‘energy’ landscape in order to perform computation. The analytical results, obtained using Derrida's approximation method, are in complete agreement with numerical simulations.

Minimum energy control and optimal-satisfactory control of Boolean control network

NASA Astrophysics Data System (ADS)

Li, Fangfei; Lu, Xiwen

2013-12-01

In the literatures, to transfer the Boolean control network from the initial state to the desired state, the expenditure of energy has been rarely considered. Motivated by this, this Letter investigates the minimum energy control and optimal-satisfactory control of Boolean control network. Based on the semi-tensor product of matrices and Floyd's algorithm, minimum energy, constrained minimum energy and optimal-satisfactory control design for Boolean control network are given respectively. A numerical example is presented to illustrate the efficiency of the obtained results.

PyBoolNet: a python package for the generation, analysis and visualization of boolean networks.

PubMed

Klarner, Hannes; Streck, Adam; Siebert, Heike

2017-03-01

The goal of this project is to provide a simple interface to working with Boolean networks. Emphasis is put on easy access to a large number of common tasks including the generation and manipulation of networks, attractor and basin computation, model checking and trap space computation, execution of established graph algorithms as well as graph drawing and layouts. P y B ool N et is a Python package for working with Boolean networks that supports simple access to model checking via N u SMV, standard graph algorithms via N etwork X and visualization via dot . In addition, state of the art attractor computation exploiting P otassco ASP is implemented. The package is function-based and uses only native Python and N etwork X data types. https://github.com/hklarner/PyBoolNet. hannes.klarner@fu-berlin.de. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Generating probabilistic Boolean networks from a prescribed transition probability matrix.

PubMed

Ching, W-K; Chen, X; Tsing, N-K

2009-11-01

Probabilistic Boolean networks (PBNs) have received much attention in modeling genetic regulatory networks. A PBN can be regarded as a Markov chain process and is characterised by a transition probability matrix. In this study, the authors propose efficient algorithms for constructing a PBN when its transition probability matrix is given. The complexities of the algorithms are also analysed. This is an interesting inverse problem in network inference using steady-state data. The problem is important as most microarray data sets are assumed to be obtained from sampling the steady-state.

Transforming Boolean models to continuous models: methodology and application to T-cell receptor signaling

PubMed Central

Wittmann, Dominik M; Krumsiek, Jan; Saez-Rodriguez, Julio; Lauffenburger, Douglas A; Klamt, Steffen; Theis, Fabian J

2009-01-01

Background The understanding of regulatory and signaling networks has long been a core objective in Systems Biology. Knowledge about these networks is mainly of qualitative nature, which allows the construction of Boolean models, where the state of a component is either 'off' or 'on'. While often able to capture the essential behavior of a network, these models can never reproduce detailed time courses of concentration levels. Nowadays however, experiments yield more and more quantitative data. An obvious question therefore is how qualitative models can be used to explain and predict the outcome of these experiments. Results In this contribution we present a canonical way of transforming Boolean into continuous models, where the use of multivariate polynomial interpolation allows transformation of logic operations into a system of ordinary differential equations (ODE). The method is standardized and can readily be applied to large networks. Other, more limited approaches to this task are briefly reviewed and compared. Moreover, we discuss and generalize existing theoretical results on the relation between Boolean and continuous models. As a test case a logical model is transformed into an extensive continuous ODE model describing the activation of T-cells. We discuss how parameters for this model can be determined such that quantitative experimental results are explained and predicted, including time-courses for multiple ligand concentrations and binding affinities of different ligands. This shows that from the continuous model we may obtain biological insights not evident from the discrete one. Conclusion The presented approach will facilitate the interaction between modeling and experiments. Moreover, it provides a straightforward way to apply quantitative analysis methods to qualitatively described systems. PMID:19785753

Random Boolean networks for autoassociative memory: Optimization and sequential learning

NASA Astrophysics Data System (ADS)

Sherrington, D.; Wong, K. Y. M.

Conventional neural networks are based on synaptic storage of information, even when the neural states are discrete and bounded. In general, the set of potential local operations is much greater. Here we discuss some aspects of the properties of networks of binary neurons with more general Boolean functions controlling the local dynamics. Two specific aspects are emphasised; (i) optimization in the presence of noise and (ii) a simple model for short-term memory exhibiting primacy and recency in the recall of sequentially taught patterns.

Modeling and controlling the two-phase dynamics of the p53 network: a Boolean network approach

NASA Astrophysics Data System (ADS)

Lin, Guo-Qiang; Ao, Bin; Chen, Jia-Wei; Wang, Wen-Xu; Di, Zeng-Ru

2014-12-01

Although much empirical evidence has demonstrated that p53 plays a key role in tumor suppression, the dynamics and function of the regulatory network centered on p53 have not yet been fully understood. Here, we develop a Boolean network model to reproduce the two-phase dynamics of the p53 network in response to DNA damage. In particular, we map the fates of cells into two types of Boolean attractors, and we find that the apoptosis attractor does not exist for minor DNA damage, reflecting that the cell is reparable. As the amount of DNA damage increases, the basin of the repair attractor shrinks, accompanied by the rising of the apoptosis attractor and the expansion of its basin, indicating that the cell becomes more irreparable with more DNA damage. For severe DNA damage, the repair attractor vanishes, and the apoptosis attractor dominates the state space, accounting for the exclusive fate of death. Based on the Boolean network model, we explore the significance of links, in terms of the sensitivity of the two-phase dynamics, to perturbing the weights of links and removing them. We find that the links are either critical or ordinary, rather than redundant. This implies that the p53 network is irreducible, but tolerant of small mutations at some ordinary links, and this can be interpreted with evolutionary theory. We further devised practical control schemes for steering the system into the apoptosis attractor in the presence of DNA damage by pinning the state of a single node or perturbing the weight of a single link. Our approach offers insights into understanding and controlling the p53 network, which is of paramount importance for medical treatment and genetic engineering.

On spectral techniques in analysis of Boolean networks

NASA Astrophysics Data System (ADS)

Kesseli, Juha; Rämö, Pauli; Yli-Harja, Olli

2005-06-01

In this work we present results that can be used for analysis of Boolean networks. The results utilize Fourier spectra of the functions in the network. An accurate formula is given for Derrida plots of networks of finite size N based on a result on Boolean functions presented in another context. Derrida plots are widely used to examine the stability issues of Boolean networks. For the limit N→∞, we give a computationally simple form that can be used as a good approximation for rather small networks as well. A formula for Derrida plots of random Boolean networks (RBNs) presented earlier in the literature is given an alternative derivation. It is shown that the information contained in the Derrida plot is equal to the average Fourier spectrum of the functions in the network. In the case of random networks the mean Derrida plot can be obtained from the mean spectrum of the functions. The method is applied to real data by using the Boolean functions found in genetic regulatory networks of eukaryotic cells in an earlier study. Conventionally, Derrida plots and stability analysis have been computed with statistical sampling resulting in poorer accuracy.

On the inherent competition between valid and spurious inductive inferences in Boolean data

NASA Astrophysics Data System (ADS)

Andrecut, M.

Inductive inference is the process of extracting general rules from specific observations. This problem also arises in the analysis of biological networks, such as genetic regulatory networks, where the interactions are complex and the observations are incomplete. A typical task in these problems is to extract general interaction rules as combinations of Boolean covariates, that explain a measured response variable. The inductive inference process can be considered as an incompletely specified Boolean function synthesis problem. This incompleteness of the problem will also generate spurious inferences, which are a serious threat to valid inductive inference rules. Using random Boolean data as a null model, here we attempt to measure the competition between valid and spurious inductive inference rules from a given data set. We formulate two greedy search algorithms, which synthesize a given Boolean response variable in a sparse disjunct normal form, and respectively a sparse generalized algebraic normal form of the variables from the observation data, and we evaluate numerically their performance.

Jimena: efficient computing and system state identification for genetic regulatory networks.

PubMed

Karl, Stefan; Dandekar, Thomas

2013-10-11

Boolean networks capture switching behavior of many naturally occurring regulatory networks. For semi-quantitative modeling, interpolation between ON and OFF states is necessary. The high degree polynomial interpolation of Boolean genetic regulatory networks (GRNs) in cellular processes such as apoptosis or proliferation allows for the modeling of a wider range of node interactions than continuous activator-inhibitor models, but suffers from scaling problems for networks which contain nodes with more than ~10 inputs. Many GRNs from literature or new gene expression experiments exceed those limitations and a new approach was developed. (i) As a part of our new GRN simulation framework Jimena we introduce and setup Boolean-tree-based data structures; (ii) corresponding algorithms greatly expedite the calculation of the polynomial interpolation in almost all cases, thereby expanding the range of networks which can be simulated by this model in reasonable time. (iii) Stable states for discrete models are efficiently counted and identified using binary decision diagrams. As application example, we show how system states can now be sampled efficiently in small up to large scale hormone disease networks (Arabidopsis thaliana development and immunity, pathogen Pseudomonas syringae and modulation by cytokinins and plant hormones). Jimena simulates currently available GRNs about 10-100 times faster than the previous implementation of the polynomial interpolation model and even greater gains are achieved for large scale-free networks. This speed-up also facilitates a much more thorough sampling of continuous state spaces which may lead to the identification of new stable states. Mutants of large networks can be constructed and analyzed very quickly enabling new insights into network robustness and behavior.

Computing smallest intervention strategies for multiple metabolic networks in a boolean model.

PubMed

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

2015-02-01

This article considers the problem whereby, given two metabolic networks N1 and N2, a set of source compounds, and a set of target compounds, we must find the minimum set of reactions whose removal (knockout) ensures that the target compounds are not producible in N1 but are producible in N2. Similar studies exist for the problem of finding the minimum knockout with the smallest side effect for a single network. However, if technologies of external perturbations are advanced in the near future, it may be important to develop methods of computing the minimum knockout for multiple networks (MKMN). Flux balance analysis (FBA) is efficient if a well-polished model is available. However, that is not always the case. Therefore, in this article, we study MKMN in Boolean models and an elementary mode (EM)-based model. Integer linear programming (ILP)-based methods are developed for these models, since MKMN is NP-complete for both the Boolean model and the EM-based model. Computer experiments are conducted with metabolic networks of clostridium perfringens SM101 and bifidobacterium longum DJO10A, respectively known as bad bacteria and good bacteria for the human intestine. The results show that larger networks are more likely to have MKMN solutions. However, solving for these larger networks takes a very long time, and often the computation cannot be completed. This is reasonable, because small networks do not have many alternative pathways, making it difficult to satisfy the MKMN condition, whereas in large networks the number of candidate solutions explodes. Our developed software minFvskO is available online.

Computing preimages of Boolean networks.

PubMed

Klotz, Johannes; Bossert, Martin; Schober, Steffen

2013-01-01

In this paper we present an algorithm based on the sum-product algorithm that finds elements in the preimage of a feed-forward Boolean networks given an output of the network. Our probabilistic method runs in linear time with respect to the number of nodes in the network. We evaluate our algorithm for randomly constructed Boolean networks and a regulatory network of Escherichia coli and found that it gives a valid solution in most cases.

Altered Micro-RNA Degradation Promotes Tumor Heterogeneity: A Result from Boolean Network Modeling.

PubMed

Wu, Yunyi; Krueger, Gerhard R F; Wang, Guanyu

2016-02-01

Cancer heterogeneity may reflect differential dynamical outcomes of the regulatory network encompassing biomolecules at both transcriptional and post-transcriptional levels. In other words, differential gene-expression profiles may correspond to different stable steady states of a mathematical model for simulation of biomolecular networks. To test this hypothesis, we simplified a regulatory network that is important for soft-tissue sarcoma metastasis and heterogeneity, comprising of transcription factors, micro-RNAs, and signaling components of the NOTCH pathway. We then used a Boolean network model to simulate the dynamics of this network, and particularly investigated the consequences of differential miRNA degradation modes. We found that efficient miRNA degradation is crucial for sustaining a homogenous and healthy phenotype, while defective miRNA degradation may lead to multiple stable steady states and ultimately to carcinogenesis and heterogeneity. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Computing Smallest Intervention Strategies for Multiple Metabolic Networks in a Boolean Model

PubMed Central

Lu, Wei; Song, Jiangning; Akutsu, Tatsuya

2015-01-01

Abstract This article considers the problem whereby, given two metabolic networks N1 and N2, a set of source compounds, and a set of target compounds, we must find the minimum set of reactions whose removal (knockout) ensures that the target compounds are not producible in N1 but are producible in N2. Similar studies exist for the problem of finding the minimum knockout with the smallest side effect for a single network. However, if technologies of external perturbations are advanced in the near future, it may be important to develop methods of computing the minimum knockout for multiple networks (MKMN). Flux balance analysis (FBA) is efficient if a well-polished model is available. However, that is not always the case. Therefore, in this article, we study MKMN in Boolean models and an elementary mode (EM)-based model. Integer linear programming (ILP)-based methods are developed for these models, since MKMN is NP-complete for both the Boolean model and the EM-based model. Computer experiments are conducted with metabolic networks of clostridium perfringens SM101 and bifidobacterium longum DJO10A, respectively known as bad bacteria and good bacteria for the human intestine. The results show that larger networks are more likely to have MKMN solutions. However, solving for these larger networks takes a very long time, and often the computation cannot be completed. This is reasonable, because small networks do not have many alternative pathways, making it difficult to satisfy the MKMN condition, whereas in large networks the number of candidate solutions explodes. Our developed software minFvskO is available online. PMID:25684199

Computational complexity of Boolean functions

NASA Astrophysics Data System (ADS)

Korshunov, Aleksei D.

2012-02-01

Boolean functions are among the fundamental objects of discrete mathematics, especially in those of its subdisciplines which fall under mathematical logic and mathematical cybernetics. The language of Boolean functions is convenient for describing the operation of many discrete systems such as contact networks, Boolean circuits, branching programs, and some others. An important parameter of discrete systems of this kind is their complexity. This characteristic has been actively investigated starting from Shannon's works. There is a large body of scientific literature presenting many fundamental results. The purpose of this survey is to give an account of the main results over the last sixty years related to the complexity of computation (realization) of Boolean functions by contact networks, Boolean circuits, and Boolean circuits without branching. Bibliography: 165 titles.

Stability Depends on Positive Autoregulation in Boolean Gene Regulatory Networks

PubMed Central

Pinho, Ricardo; Garcia, Victor; Irimia, Manuel; Feldman, Marcus W.

2014-01-01

Network motifs have been identified as building blocks of regulatory networks, including gene regulatory networks (GRNs). The most basic motif, autoregulation, has been associated with bistability (when positive) and with homeostasis and robustness to noise (when negative), but its general importance in network behavior is poorly understood. Moreover, how specific autoregulatory motifs are selected during evolution and how this relates to robustness is largely unknown. Here, we used a class of GRN models, Boolean networks, to investigate the relationship between autoregulation and network stability and robustness under various conditions. We ran evolutionary simulation experiments for different models of selection, including mutation and recombination. Each generation simulated the development of a population of organisms modeled by GRNs. We found that stability and robustness positively correlate with autoregulation; in all investigated scenarios, stable networks had mostly positive autoregulation. Assuming biological networks correspond to stable networks, these results suggest that biological networks should often be dominated by positive autoregulatory loops. This seems to be the case for most studied eukaryotic transcription factor networks, including those in yeast, flies and mammals. PMID:25375153

Perturbation propagation in random and evolved Boolean networks

NASA Astrophysics Data System (ADS)

Fretter, Christoph; Szejka, Agnes; Drossel, Barbara

2009-03-01

In this paper, we investigate the propagation of perturbations in Boolean networks by evaluating the Derrida plot and its modifications. We show that even small random Boolean networks agree well with the predictions of the annealed approximation, but nonrandom networks show a very different behaviour. We focus on networks that were evolved for high dynamical robustness. The most important conclusion is that the simple distinction between frozen, critical and chaotic networks is no longer useful, since such evolved networks can display the properties of all three types of networks. Furthermore, we evaluate a simplified empirical network and show how its specific state space properties are reflected in the modified Derrida plots.

Inferring Boolean network states from partial information

PubMed Central

2013-01-01

Networks of molecular interactions regulate key processes in living cells. Therefore, understanding their functionality is a high priority in advancing biological knowledge. Boolean networks are often used to describe cellular networks mathematically and are fitted to experimental datasets. The fitting often results in ambiguities since the interpretation of the measurements is not straightforward and since the data contain noise. In order to facilitate a more reliable mapping between datasets and Boolean networks, we develop an algorithm that infers network trajectories from a dataset distorted by noise. We analyze our algorithm theoretically and demonstrate its accuracy using simulation and microarray expression data. PMID:24006954

On the number of different dynamics in Boolean networks with deterministic update schedules.

PubMed

Aracena, J; Demongeot, J; Fanchon, E; Montalva, M

2013-04-01

Deterministic Boolean networks are a type of discrete dynamical systems widely used in the modeling of genetic networks. The dynamics of such systems is characterized by the local activation functions and the update schedule, i.e., the order in which the nodes are updated. In this paper, we address the problem of knowing the different dynamics of a Boolean network when the update schedule is changed. We begin by proving that the problem of the existence of a pair of update schedules with different dynamics is NP-complete. However, we show that certain structural properties of the interaction diagraph are sufficient for guaranteeing distinct dynamics of a network. In [1] the authors define equivalence classes which have the property that all the update schedules of a given class yield the same dynamics. In order to determine the dynamics associated to a network, we develop an algorithm to efficiently enumerate the above equivalence classes by selecting a representative update schedule for each class with a minimum number of blocks. Finally, we run this algorithm on the well known Arabidopsis thaliana network to determine the full spectrum of its different dynamics. Copyright © 2013 Elsevier Inc. All rights reserved.

General method to find the attractors of discrete dynamic models of biological systems.

PubMed

Gan, Xiao; Albert, Réka

2018-04-01

Analyzing the long-term behaviors (attractors) of dynamic models of biological networks can provide valuable insight. We propose a general method that can find the attractors of multilevel discrete dynamical systems by extending a method that finds the attractors of a Boolean network model. The previous method is based on finding stable motifs, subgraphs whose nodes' states can stabilize on their own. We extend the framework from binary states to any finite discrete levels by creating a virtual node for each level of a multilevel node, and describing each virtual node with a quasi-Boolean function. We then create an expanded representation of the multilevel network, find multilevel stable motifs and oscillating motifs, and identify attractors by successive network reduction. In this way, we find both fixed point attractors and complex attractors. We implemented an algorithm, which we test and validate on representative synthetic networks and on published multilevel models of biological networks. Despite its primary motivation to analyze biological networks, our motif-based method is general and can be applied to any finite discrete dynamical system.

General method to find the attractors of discrete dynamic models of biological systems

NASA Astrophysics Data System (ADS)

Gan, Xiao; Albert, Réka

2018-04-01

Analyzing the long-term behaviors (attractors) of dynamic models of biological networks can provide valuable insight. We propose a general method that can find the attractors of multilevel discrete dynamical systems by extending a method that finds the attractors of a Boolean network model. The previous method is based on finding stable motifs, subgraphs whose nodes' states can stabilize on their own. We extend the framework from binary states to any finite discrete levels by creating a virtual node for each level of a multilevel node, and describing each virtual node with a quasi-Boolean function. We then create an expanded representation of the multilevel network, find multilevel stable motifs and oscillating motifs, and identify attractors by successive network reduction. In this way, we find both fixed point attractors and complex attractors. We implemented an algorithm, which we test and validate on representative synthetic networks and on published multilevel models of biological networks. Despite its primary motivation to analyze biological networks, our motif-based method is general and can be applied to any finite discrete dynamical system.

BoolNet--an R package for generation, reconstruction and analysis of Boolean networks.

PubMed

Müssel, Christoph; Hopfensitz, Martin; Kestler, Hans A

2010-05-15

As the study of information processing in living cells moves from individual pathways to complex regulatory networks, mathematical models and simulation become indispensable tools for analyzing the complex behavior of such networks and can provide deep insights into the functioning of cells. The dynamics of gene expression, for example, can be modeled with Boolean networks (BNs). These are mathematical models of low complexity, but have the advantage of being able to capture essential properties of gene-regulatory networks. However, current implementations of BNs only focus on different sub-aspects of this model and do not allow for a seamless integration into existing preprocessing pipelines. BoolNet efficiently integrates methods for synchronous, asynchronous and probabilistic BNs. This includes reconstructing networks from time series, generating random networks, robustness analysis via perturbation, Markov chain simulations, and identification and visualization of attractors. The package BoolNet is freely available from the R project at http://cran.r-project.org/ or http://www.informatik.uni-ulm.de/ni/mitarbeiter/HKestler/boolnet/ under Artistic License 2.0. hans.kestler@uni-ulm.de Supplementary data are available at Bioinformatics online.

Investigating Cell Criticality

NASA Astrophysics Data System (ADS)

Serra, R.; Villani, M.; Damiani, C.; Graudenzi, A.; Ingrami, P.; Colacci, A.

Random Boolean networks provide a way to give a precise meaning to the notion that living beings are in a critical state. Some phenomena which are observed in real biological systems (distribution of "avalanches" in gene knock-out experiments) can be modeled using random Boolean networks, and the results can be analytically proven to depend upon the Derrida parameter, which also determines whether the network is critical. By comparing observed and simulated data one can then draw inferences about the criticality of biological cells, although with some care because of the limited number of experimental observations. The relationship between the criticality of a single network and that of a set of interacting networks, which simulate a tissue or a bacterial colony, is also analyzed by computer simulations.

Phase transition of Boolean networks with partially nested canalizing functions

NASA Astrophysics Data System (ADS)

Jansen, Kayse; Matache, Mihaela Teodora

2013-07-01

We generate the critical condition for the phase transition of a Boolean network governed by partially nested canalizing functions for which a fraction of the inputs are canalizing, while the remaining non-canalizing inputs obey a complementary threshold Boolean function. Past studies have considered the stability of fully or partially nested canalizing functions paired with random choices of the complementary function. In some of those studies conflicting results were found with regard to the presence of chaotic behavior. Moreover, those studies focus mostly on ergodic networks in which initial states are assumed equally likely. We relax that assumption and find the critical condition for the sensitivity of the network under a non-ergodic scenario. We use the proposed mathematical model to determine parameter values for which phase transitions from order to chaos occur. We generate Derrida plots to show that the mathematical model matches the actual network dynamics. The phase transition diagrams indicate that both order and chaos can occur, and that certain parameters induce a larger range of values leading to order versus chaos. The edge-of-chaos curves are identified analytically and numerically. It is shown that the depth of canalization does not cause major dynamical changes once certain thresholds are reached; these thresholds are fairly small in comparison to the connectivity of the nodes.

Identifying a Probabilistic Boolean Threshold Network From Samples.

PubMed

Melkman, Avraham A; Cheng, Xiaoqing; Ching, Wai-Ki; Akutsu, Tatsuya

2018-04-01

This paper studies the problem of exactly identifying the structure of a probabilistic Boolean network (PBN) from a given set of samples, where PBNs are probabilistic extensions of Boolean networks. Cheng et al. studied the problem while focusing on PBNs consisting of pairs of AND/OR functions. This paper considers PBNs consisting of Boolean threshold functions while focusing on those threshold functions that have unit coefficients. The treatment of Boolean threshold functions, and triplets and -tuplets of such functions, necessitates a deepening of the theoretical analyses. It is shown that wide classes of PBNs with such threshold functions can be exactly identified from samples under reasonable constraints, which include: 1) PBNs in which any number of threshold functions can be assigned provided that all have the same number of input variables and 2) PBNs consisting of pairs of threshold functions with different numbers of input variables. It is also shown that the problem of deciding the equivalence of two Boolean threshold functions is solvable in pseudopolynomial time but remains co-NP complete.

A Semiquantitative Framework for Gene Regulatory Networks: Increasing the Time and Quantitative Resolution of Boolean Networks

PubMed Central

Kerkhofs, Johan; Geris, Liesbet

2015-01-01

Boolean models have been instrumental in predicting general features of gene networks and more recently also as explorative tools in specific biological applications. In this study we introduce a basic quantitative and a limited time resolution to a discrete (Boolean) framework. Quantitative resolution is improved through the employ of normalized variables in unison with an additive approach. Increased time resolution stems from the introduction of two distinct priority classes. Through the implementation of a previously published chondrocyte network and T helper cell network, we show that this addition of quantitative and time resolution broadens the scope of biological behaviour that can be captured by the models. Specifically, the quantitative resolution readily allows models to discern qualitative differences in dosage response to growth factors. The limited time resolution, in turn, can influence the reachability of attractors, delineating the likely long term system behaviour. Importantly, the information required for implementation of these features, such as the nature of an interaction, is typically obtainable from the literature. Nonetheless, a trade-off is always present between additional computational cost of this approach and the likelihood of extending the model’s scope. Indeed, in some cases the inclusion of these features does not yield additional insight. This framework, incorporating increased and readily available time and semi-quantitative resolution, can help in substantiating the litmus test of dynamics for gene networks, firstly by excluding unlikely dynamics and secondly by refining falsifiable predictions on qualitative behaviour. PMID:26067297

Adaptiveness in monotone pseudo-Boolean optimization and stochastic neural computation.

PubMed

Grossi, Giuliano

2009-08-01

Hopfield neural network (HNN) is a nonlinear computational model successfully applied in finding near-optimal solutions of several difficult combinatorial problems. In many cases, the network energy function is obtained through a learning procedure so that its minima are states falling into a proper subspace (feasible region) of the search space. However, because of the network nonlinearity, a number of undesirable local energy minima emerge from the learning procedure, significantly effecting the network performance. In the neural model analyzed here, we combine both a penalty and a stochastic process in order to enhance the performance of a binary HNN. The penalty strategy allows us to gradually lead the search towards states representing feasible solutions, so avoiding oscillatory behaviors or asymptotically instable convergence. Presence of stochastic dynamics potentially prevents the network to fall into shallow local minima of the energy function, i.e., quite far from global optimum. Hence, for a given fixed network topology, the desired final distribution on the states can be reached by carefully modulating such process. The model uses pseudo-Boolean functions both to express problem constraints and cost function; a combination of these two functions is then interpreted as energy of the neural network. A wide variety of NP-hard problems fall in the class of problems that can be solved by the model at hand, particularly those having a monotonic quadratic pseudo-Boolean function as constraint function. That is, functions easily derived by closed algebraic expressions representing the constraint structure and easy (polynomial time) to maximize. We show the asymptotic convergence properties of this model characterizing its state space distribution at thermal equilibrium in terms of Markov chain and give evidence of its ability to find high quality solutions on benchmarks and randomly generated instances of two specific problems taken from the computational graph theory.

Recent development and biomedical applications of probabilistic Boolean networks

PubMed Central

2013-01-01

Probabilistic Boolean network (PBN) modelling is a semi-quantitative approach widely used for the study of the topology and dynamic aspects of biological systems. The combined use of rule-based representation and probability makes PBN appealing for large-scale modelling of biological networks where degrees of uncertainty need to be considered. A considerable expansion of our knowledge in the field of theoretical research on PBN can be observed over the past few years, with a focus on network inference, network intervention and control. With respect to areas of applications, PBN is mainly used for the study of gene regulatory networks though with an increasing emergence in signal transduction, metabolic, and also physiological networks. At the same time, a number of computational tools, facilitating the modelling and analysis of PBNs, are continuously developed. A concise yet comprehensive review of the state-of-the-art on PBN modelling is offered in this article, including a comparative discussion on PBN versus similar models with respect to concepts and biomedical applications. Due to their many advantages, we consider PBN to stand as a suitable modelling framework for the description and analysis of complex biological systems, ranging from molecular to physiological levels. PMID:23815817

Networks and games for precision medicine.

PubMed

Biane, Célia; Delaplace, Franck; Klaudel, Hanna

2016-12-01

Recent advances in omics technologies provide the leverage for the emergence of precision medicine that aims at personalizing therapy to patient. In this undertaking, computational methods play a central role for assisting physicians in their clinical decision-making by combining data analysis and systems biology modelling. Complex diseases such as cancer or diabetes arise from the intricate interplay of various biological molecules. Therefore, assessing drug efficiency requires to study the effects of elementary perturbations caused by diseases on relevant biological networks. In this paper, we propose a computational framework called Network-Action Game applied to best drug selection problem combining Game Theory and discrete models of dynamics (Boolean networks). Decision-making is modelled using Game Theory that defines the process of drug selection among alternative possibilities, while Boolean networks are used to model the effects of the interplay between disease and drugs actions on the patient's molecular system. The actions/strategies of disease and drugs are focused on arc alterations of the interactome. The efficiency of this framework has been evaluated for drug prediction on a model of breast cancer signalling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Model of Yeast Cell-Cycle Regulation Based on a Standard Component Modeling Strategy for Protein Regulatory Networks.

PubMed

Laomettachit, Teeraphan; Chen, Katherine C; Baumann, William T; Tyson, John J

2016-01-01

To understand the molecular mechanisms that regulate cell cycle progression in eukaryotes, a variety of mathematical modeling approaches have been employed, ranging from Boolean networks and differential equations to stochastic simulations. Each approach has its own characteristic strengths and weaknesses. In this paper, we propose a "standard component" modeling strategy that combines advantageous features of Boolean networks, differential equations and stochastic simulations in a framework that acknowledges the typical sorts of reactions found in protein regulatory networks. Applying this strategy to a comprehensive mechanism of the budding yeast cell cycle, we illustrate the potential value of standard component modeling. The deterministic version of our model reproduces the phenotypic properties of wild-type cells and of 125 mutant strains. The stochastic version of our model reproduces the cell-to-cell variability of wild-type cells and the partial viability of the CLB2-dbΔ clb5Δ mutant strain. Our simulations show that mathematical modeling with "standard components" can capture in quantitative detail many essential properties of cell cycle control in budding yeast.

A Model of Yeast Cell-Cycle Regulation Based on a Standard Component Modeling Strategy for Protein Regulatory Networks

PubMed Central

Laomettachit, Teeraphan; Chen, Katherine C.; Baumann, William T.

2016-01-01

To understand the molecular mechanisms that regulate cell cycle progression in eukaryotes, a variety of mathematical modeling approaches have been employed, ranging from Boolean networks and differential equations to stochastic simulations. Each approach has its own characteristic strengths and weaknesses. In this paper, we propose a “standard component” modeling strategy that combines advantageous features of Boolean networks, differential equations and stochastic simulations in a framework that acknowledges the typical sorts of reactions found in protein regulatory networks. Applying this strategy to a comprehensive mechanism of the budding yeast cell cycle, we illustrate the potential value of standard component modeling. The deterministic version of our model reproduces the phenotypic properties of wild-type cells and of 125 mutant strains. The stochastic version of our model reproduces the cell-to-cell variability of wild-type cells and the partial viability of the CLB2-dbΔ clb5Δ mutant strain. Our simulations show that mathematical modeling with “standard components” can capture in quantitative detail many essential properties of cell cycle control in budding yeast. PMID:27187804

Characterizing short-term stability for Boolean networks over any distribution of transfer functions

DOE PAGES

Seshadhri, C.; Smith, Andrew M.; Vorobeychik, Yevgeniy; ...

2016-07-05

Here we present a characterization of short-term stability of random Boolean networks under arbitrary distributions of transfer functions. Given any distribution of transfer functions for a random Boolean network, we present a formula that decides whether short-term chaos (damage spreading) will happen. We provide a formal proof for this formula, and empirically show that its predictions are accurate. Previous work only works for special cases of balanced families. Finally, it has been observed that these characterizations fail for unbalanced families, yet such families are widespread in real biological networks.

Feedback topology and XOR-dynamics in Boolean networks with varying input structure

NASA Astrophysics Data System (ADS)

Ciandrini, L.; Maffi, C.; Motta, A.; Bassetti, B.; Cosentino Lagomarsino, M.

2009-08-01

We analyze a model of fixed in-degree random Boolean networks in which the fraction of input-receiving nodes is controlled by the parameter γ . We investigate analytically and numerically the dynamics of graphs under a parallel XOR updating scheme. This scheme is interesting because it is accessible analytically and its phenomenology is at the same time under control and as rich as the one of general Boolean networks. We give analytical formulas for the dynamics on general graphs, showing that with a XOR-type evolution rule, dynamic features are direct consequences of the topological feedback structure, in analogy with the role of relevant components in Kauffman networks. Considering graphs with fixed in-degree, we characterize analytically and numerically the feedback regions using graph decimation algorithms (Leaf Removal). With varying γ , this graph ensemble shows a phase transition that separates a treelike graph region from one in which feedback components emerge. Networks near the transition point have feedback components made of disjoint loops, in which each node has exactly one incoming and one outgoing link. Using this fact, we provide analytical estimates of the maximum period starting from topological considerations.

Feedback topology and XOR-dynamics in Boolean networks with varying input structure.

PubMed

Ciandrini, L; Maffi, C; Motta, A; Bassetti, B; Cosentino Lagomarsino, M

2009-08-01

We analyze a model of fixed in-degree random Boolean networks in which the fraction of input-receiving nodes is controlled by the parameter gamma. We investigate analytically and numerically the dynamics of graphs under a parallel XOR updating scheme. This scheme is interesting because it is accessible analytically and its phenomenology is at the same time under control and as rich as the one of general Boolean networks. We give analytical formulas for the dynamics on general graphs, showing that with a XOR-type evolution rule, dynamic features are direct consequences of the topological feedback structure, in analogy with the role of relevant components in Kauffman networks. Considering graphs with fixed in-degree, we characterize analytically and numerically the feedback regions using graph decimation algorithms (Leaf Removal). With varying gamma , this graph ensemble shows a phase transition that separates a treelike graph region from one in which feedback components emerge. Networks near the transition point have feedback components made of disjoint loops, in which each node has exactly one incoming and one outgoing link. Using this fact, we provide analytical estimates of the maximum period starting from topological considerations.

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

EPA Science Inventory

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

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

Rivera-Durón, R. R., E-mail: roberto.rivera@ipicyt.edu.mx; Campos-Cantón, E., E-mail: eric.campos@ipicyt.edu.mx; Campos-Cantón, I.

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 enablemore » 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.« less

Stabilization of perturbed Boolean network attractors through compensatory interactions

PubMed Central

2014-01-01

Background Understanding and ameliorating the effects of network damage are of significant interest, due in part to the variety of applications in which network damage is relevant. For example, the effects of genetic mutations can cascade through within-cell signaling and regulatory networks and alter the behavior of cells, possibly leading to a wide variety of diseases. The typical approach to mitigating network perturbations is to consider the compensatory activation or deactivation of system components. Here, we propose a complementary approach wherein interactions are instead modified to alter key regulatory functions and prevent the network damage from triggering a deregulatory cascade. Results We implement this approach in a Boolean dynamic framework, which has been shown to effectively model the behavior of biological regulatory and signaling networks. We show that the method can stabilize any single state (e.g., fixed point attractors or time-averaged representations of multi-state attractors) to be an attractor of the repaired network. We show that the approach is minimalistic in that few modifications are required to provide stability to a chosen attractor and specific in that interventions do not have undesired effects on the attractor. We apply the approach to random Boolean networks, and further show that the method can in some cases successfully repair synchronous limit cycles. We also apply the methodology to case studies from drought-induced signaling in plants and T-LGL leukemia and find that it is successful in both stabilizing desired behavior and in eliminating undesired outcomes. Code is made freely available through the software package BooleanNet. Conclusions The methodology introduced in this report offers a complementary way to manipulating node expression levels. A comprehensive approach to evaluating network manipulation should take an "all of the above" perspective; we anticipate that theoretical studies of interaction modification, coupled with empirical advances, will ultimately provide researchers with greater flexibility in influencing system behavior. PMID:24885780

Fisher information at the edge of chaos in random Boolean networks.

PubMed

Wang, X Rosalind; Lizier, Joseph T; Prokopenko, Mikhail

2011-01-01

We study the order-chaos phase transition in random Boolean networks (RBNs), which have been used as models of gene regulatory networks. In particular we seek to characterize the phase diagram in information-theoretic terms, focusing on the effect of the control parameters (activity level and connectivity). Fisher information, which measures how much system dynamics can reveal about the control parameters, offers a natural interpretation of the phase diagram in RBNs. We report that this measure is maximized near the order-chaos phase transitions in RBNs, since this is the region where the system is most sensitive to its parameters. Furthermore, we use this study of RBNs to clarify the relationship between Shannon and Fisher information measures.

Using computer algebra and SMT solvers in algebraic biology

NASA Astrophysics Data System (ADS)

Pineda Osorio, Mateo

2014-05-01

Biologic processes are represented as Boolean networks, in a discrete time. The dynamics within these networks are approached with the help of SMT Solvers and the use of computer algebra. Software such as Maple and Z3 was used in this case. The number of stationary states for each network was calculated. The network studied here corresponds to the immune system under the effects of drastic mood changes. Mood is considered as a Boolean variable that affects the entire dynamics of the immune system, changing the Boolean satisfiability and the number of stationary states of the immune network. Results obtained show Z3's great potential as a SMT Solver. Some of these results were verified in Maple, even though it showed not to be as suitable for the problem approach. The solving code was constructed using Z3-Python and Z3-SMT-LiB. Results obtained are important in biology systems and are expected to help in the design of immune therapies. As a future line of research, more complex Boolean network representations of the immune system as well as the whole psychological apparatus are suggested.

Implementing neural nets with programmable logic

NASA Technical Reports Server (NTRS)

Vidal, Jacques J.

1988-01-01

Networks of Boolean programmable logic modules are presented as one purely digital class of artificial neural nets. The approach contrasts with the continuous analog framework usually suggested. Programmable logic networks are capable of handling many neural-net applications. They avoid some of the limitations of threshold logic networks and present distinct opportunities. The network nodes are called dynamically programmable logic modules. They can be implemented with digitally controlled demultiplexers. Each node performs a Boolean function of its inputs which can be dynamically assigned. The overall network is therefore a combinational circuit and its outputs are Boolean global functions of the network's input variables. The approach offers definite advantages for VLSI implementation, namely, a regular architecture with limited connectivity, simplicity of the control machinery, natural modularity, and the support of a mature technology.

Discriminate the response of Acute Myeloid Leukemia patients to treatment by using proteomics data and Answer Set Programming.

PubMed

Chebouba, Lokmane; Miannay, Bertrand; Boughaci, Dalila; Guziolowski, Carito

2018-03-08

During the last years, several approaches were applied on biomedical data to detect disease specific proteins and genes in order to better target drugs. It was shown that statistical and machine learning based methods use mainly clinical data and improve later their results by adding omics data. This work proposes a new method to discriminate the response of Acute Myeloid Leukemia (AML) patients to treatment. The proposed approach uses proteomics data and prior regulatory knowledge in the form of networks to predict cancer treatment outcomes by finding out the different Boolean networks specific to each type of response to drugs. To show its effectiveness we evaluate our method on a dataset from the DREAM 9 challenge. The results are encouraging and demonstrate the benefit of our approach to distinguish patient groups with different response to treatment. In particular each treatment response group is characterized by a predictive model in the form of a signaling Boolean network. This model describes regulatory mechanisms which are specific to each response group. The proteins in this model were selected from the complete dataset by imposing optimization constraints that maximize the difference in the logical response of the Boolean network associated to each group of patients given the omic dataset. This mechanistic and predictive model also allow us to classify new patients data into the two different patient response groups. We propose a new method to detect the most relevant proteins for understanding different patient responses upon treatments in order to better target drugs using a Prior Knowledge Network and proteomics data. The results are interesting and show the effectiveness of our method.

ASP-G: an ASP-based method for finding attractors in genetic regulatory networks

PubMed Central

Mushthofa, Mushthofa; Torres, Gustavo; Van de Peer, Yves; Marchal, Kathleen; De Cock, Martine

2014-01-01

Motivation: Boolean network models are suitable to simulate GRNs in the absence of detailed kinetic information. However, reducing the biological reality implies making assumptions on how genes interact (interaction rules) and how their state is updated during the simulation (update scheme). The exact choice of the assumptions largely determines the outcome of the simulations. In most cases, however, the biologically correct assumptions are unknown. An ideal simulation thus implies testing different rules and schemes to determine those that best capture an observed biological phenomenon. This is not trivial because most current methods to simulate Boolean network models of GRNs and to compute their attractors impose specific assumptions that cannot be easily altered, as they are built into the system. Results: To allow for a more flexible simulation framework, we developed ASP-G. We show the correctness of ASP-G in simulating Boolean network models and obtaining attractors under different assumptions by successfully recapitulating the detection of attractors of previously published studies. We also provide an example of how performing simulation of network models under different settings help determine the assumptions under which a certain conclusion holds. The main added value of ASP-G is in its modularity and declarativity, making it more flexible and less error-prone than traditional approaches. The declarative nature of ASP-G comes at the expense of being slower than the more dedicated systems but still achieves a good efficiency with respect to computational time. Availability and implementation: The source code of ASP-G is available at http://bioinformatics.intec.ugent.be/kmarchal/Supplementary_Information_Musthofa_2014/asp-g.zip. Contact: Kathleen.Marchal@UGent.be or Martine.DeCock@UGent.be Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25028722

Floral Morphogenesis: Stochastic Explorations of a Gene Network Epigenetic Landscape

PubMed Central

Aldana, Maximino; Benítez, Mariana; Cortes-Poza, Yuriria; Espinosa-Soto, Carlos; Hartasánchez, Diego A.; Lotto, R. Beau; Malkin, David; Escalera Santos, Gerardo J.; Padilla-Longoria, Pablo

2008-01-01

In contrast to the classical view of development as a preprogrammed and deterministic process, recent studies have demonstrated that stochastic perturbations of highly non-linear systems may underlie the emergence and stability of biological patterns. Herein, we address the question of whether noise contributes to the generation of the stereotypical temporal pattern in gene expression during flower development. We modeled the regulatory network of organ identity genes in the Arabidopsis thaliana flower as a stochastic system. This network has previously been shown to converge to ten fixed-point attractors, each with gene expression arrays that characterize inflorescence cells and primordial cells of sepals, petals, stamens, and carpels. The network used is binary, and the logical rules that govern its dynamics are grounded in experimental evidence. We introduced different levels of uncertainty in the updating rules of the network. Interestingly, for a level of noise of around 0.5–10%, the system exhibited a sequence of transitions among attractors that mimics the sequence of gene activation configurations observed in real flowers. We also implemented the gene regulatory network as a continuous system using the Glass model of differential equations, that can be considered as a first approximation of kinetic-reaction equations, but which are not necessarily equivalent to the Boolean model. Interestingly, the Glass dynamics recover a temporal sequence of attractors, that is qualitatively similar, although not identical, to that obtained using the Boolean model. Thus, time ordering in the emergence of cell-fate patterns is not an artifact of synchronous updating in the Boolean model. Therefore, our model provides a novel explanation for the emergence and robustness of the ubiquitous temporal pattern of floral organ specification. It also constitutes a new approach to understanding morphogenesis, providing predictions on the population dynamics of cells with different genetic configurations during development. PMID:18978941

Phase transition in NK-Kauffman networks and its correction for Boolean irreducibility

NASA Astrophysics Data System (ADS)

Zertuche, Federico

2014-05-01

In a series of articles published in 1986, Derrida and his colleagues studied two mean field treatments (the quenched and the annealed) for NK-Kauffman networks. Their main results lead to a phase transition curve Kc 2 pc(1-pc)=1 (0

The value of less connected agents in Boolean networks

NASA Astrophysics Data System (ADS)

Epstein, Daniel; Bazzan, Ana L. C.

2013-11-01

In multiagent systems, agents often face binary decisions where one seeks to take either the minority or the majority side. Examples are minority and congestion games in general, i.e., situations that require coordination among the agents in order to depict efficient decisions. In minority games such as the El Farol Bar Problem, previous works have shown that agents may reach appropriate levels of coordination, mostly by looking at the history of past decisions. Not many works consider any kind of structure of the social network, i.e., how agents are connected. Moreover, when structure is indeed considered, it assumes some kind of random network with a given, fixed connectivity degree. The present paper departs from the conventional approach in some ways. First, it considers more realistic network topologies, based on preferential attachments. This is especially useful in social networks. Second, the formalism of random Boolean networks is used to help agents to make decisions given their attachments (for example acquaintances). This is coupled with a reinforcement learning mechanism that allows agents to select strategies that are locally and globally efficient. Third, we use agent-based modeling and simulation, a microscopic approach, which allows us to draw conclusions about individuals and/or classes of individuals. Finally, for the sake of illustration we use two different scenarios, namely the El Farol Bar Problem and a binary route choice scenario. With this approach we target systems that adapt dynamically to changes in the environment, including other adaptive decision-makers. Our results using preferential attachments and random Boolean networks are threefold. First we show that an efficient equilibrium can be achieved, provided agents do experimentation. Second, microscopic analysis show that influential agents tend to consider few inputs in their Boolean functions. Third, we have also conducted measurements related to network clustering and centrality that help to see how agents are organized.

On the robustness of complex heterogeneous gene expression networks.

PubMed

Gómez-Gardeñes, Jesús; Moreno, Yamir; Floría, Luis M

2005-04-01

We analyze a continuous gene expression model on the underlying topology of a complex heterogeneous network. Numerical simulations aimed at studying the chaotic and periodic dynamics of the model are performed. The results clearly indicate that there is a region in which the dynamical and structural complexity of the system avoid chaotic attractors. However, contrary to what has been reported for Random Boolean Networks, the chaotic phase cannot be completely suppressed, which has important bearings on network robustness and gene expression modeling.

Tracking perturbations in Boolean networks with spectral methods

NASA Astrophysics Data System (ADS)

Kesseli, Juha; Rämö, Pauli; Yli-Harja, Olli

2005-08-01

In this paper we present a method for predicting the spread of perturbations in Boolean networks. The method is applicable to networks that have no regular topology. The prediction of perturbations can be performed easily by using a presented result which enables the efficient computation of the required iterative formulas. This result is based on abstract Fourier transform of the functions in the network. In this paper the method is applied to show the spread of perturbations in networks containing a distribution of functions found from biological data. The advances in the study of the spread of perturbations can directly be applied to enable ways of quantifying chaos in Boolean networks. Derrida plots over an arbitrary number of time steps can be computed and thus distributions of functions compared with each other with respect to the amount of order they create in random networks.

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

NASA Astrophysics Data System (ADS)

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.

Phase diagram of restricted Boltzmann machines and generalized Hopfield networks with arbitrary priors.

PubMed

Barra, Adriano; Genovese, Giuseppe; Sollich, Peter; Tantari, Daniele

2018-02-01

Restricted Boltzmann machines are described by the Gibbs measure of a bipartite spin glass, which in turn can be seen as a generalized Hopfield network. This equivalence allows us to characterize the state of these systems in terms of their retrieval capabilities, both at low and high load, of pure states. We study the paramagnetic-spin glass and the spin glass-retrieval phase transitions, as the pattern (i.e., weight) distribution and spin (i.e., unit) priors vary smoothly from Gaussian real variables to Boolean discrete variables. Our analysis shows that the presence of a retrieval phase is robust and not peculiar to the standard Hopfield model with Boolean patterns. The retrieval region becomes larger when the pattern entries and retrieval units get more peaked and, conversely, when the hidden units acquire a broader prior and therefore have a stronger response to high fields. Moreover, at low load retrieval always exists below some critical temperature, for every pattern distribution ranging from the Boolean to the Gaussian case.

The computational core and fixed point organization in Boolean networks

NASA Astrophysics Data System (ADS)

Correale, L.; Leone, M.; Pagnani, A.; Weigt, M.; Zecchina, R.

2006-03-01

In this paper, we analyse large random Boolean networks in terms of a constraint satisfaction problem. We first develop an algorithmic scheme which allows us to prune simple logical cascades and underdetermined variables, returning thereby the computational core of the network. Second, we apply the cavity method to analyse the number and organization of fixed points. We find in particular a phase transition between an easy and a complex regulatory phase, the latter being characterized by the existence of an exponential number of macroscopically separated fixed point clusters. The different techniques developed are reinterpreted as algorithms for the analysis of single Boolean networks, and they are applied in the analysis of and in silico experiments on the gene regulatory networks of baker's yeast (Saccharomyces cerevisiae) and the segment-polarity genes of the fruitfly Drosophila melanogaster.

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

NASA Astrophysics Data System (ADS)

Zeng, Chen

2012-02-01

For a given dynamic process, identifying the putative interaction networks to achieve it is the inference problem. In this talk, we address the computational complexity of inference problem in the context of Boolean networks under dominant inhibition condition. The first is a proof that the feasibility problem (is there a network that explains the dynamics?) can be solved in polynomial-time. Second, while the minimality problem (what is the smallest network that explains the dynamics?) is shown to be NP-hard, a simple polynomial-time heuristic is shown to produce near-minimal solutions, as demonstrated by simulation. Third, the theoretical framework also leads to a fast polynomial-time heuristic to estimate the number of network solutions with reasonable accuracy. We will apply these approaches to two simplified Boolean network models for the cell cycle process of budding yeast (Li 2004) and fission yeast (Davidich 2008). Our results demonstrate that each of these networks contains a giant backbone motif spanning all the network nodes that provides the desired main functionality, while the remaining edges in the network form smaller motifs whose role is to confer stability properties rather than provide function. Moreover, we show that the bioprocesses of these two cell cycle models differ considerably from a typically generated process and are intrinsically cascade-like.

Counting and classifying attractors in high dimensional dynamical systems.

PubMed

Bagley, R J; Glass, L

1996-12-07

Randomly connected Boolean networks have been used as mathematical models of neural, genetic, and immune systems. A key quantity of such networks is the number of basins of attraction in the state space. The number of basins of attraction changes as a function of the size of the network, its connectivity and its transition rules. In discrete networks, a simple count of the number of attractors does not reveal the combinatorial structure of the attractors. These points are illustrated in a reexamination of dynamics in a class of random Boolean networks considered previously by Kauffman. We also consider comparisons between dynamics in discrete networks and continuous analogues. A continuous analogue of a discrete network may have a different number of attractors for many different reasons. Some attractors in discrete networks may be associated with unstable dynamics, and several different attractors in a discrete network may be associated with a single attractor in the continuous case. Special problems in determining attractors in continuous systems arise when there is aperiodic dynamics associated with quasiperiodicity of deterministic chaos.

Using Synchronous Boolean Networks to Model Several Phenomena of Collective Behavior

PubMed Central

Kochemazov, Stepan; Semenov, Alexander

2014-01-01

In this paper, we propose an approach for modeling and analysis of a number of phenomena of collective behavior. By collectives we mean multi-agent systems that transition from one state to another at discrete moments of time. The behavior of a member of a collective (agent) is called conforming if the opinion of this agent at current time moment conforms to the opinion of some other agents at the previous time moment. We presume that at each moment of time every agent makes a decision by choosing from the set (where 1-decision corresponds to action and 0-decision corresponds to inaction). In our approach we model collective behavior with synchronous Boolean networks. We presume that in a network there can be agents that act at every moment of time. Such agents are called instigators. Also there can be agents that never act. Such agents are called loyalists. Agents that are neither instigators nor loyalists are called simple agents. We study two combinatorial problems. The first problem is to find a disposition of instigators that in several time moments transforms a network from a state where the majority of simple agents are inactive to a state with the majority of active agents. The second problem is to find a disposition of loyalists that returns the network to a state with the majority of inactive agents. Similar problems are studied for networks in which simple agents demonstrate the contrary to conforming behavior that we call anticonforming. We obtained several theoretical results regarding the behavior of collectives of agents with conforming or anticonforming behavior. In computational experiments we solved the described problems for randomly generated networks with several hundred vertices. We reduced corresponding combinatorial problems to the Boolean satisfiability problem (SAT) and used modern SAT solvers to solve the instances obtained. PMID:25526612

Boolean dynamics of genetic regulatory networks inferred from microarray time series data

DOE PAGES

Martin, Shawn; Zhang, Zhaoduo; Martino, Anthony; ...

2007-01-31

Methods available for the inference of genetic regulatory networks strive to produce a single network, usually by optimizing some quantity to fit the experimental observations. In this paper we investigate the possibility that multiple networks can be inferred, all resulting in similar dynamics. This idea is motivated by theoretical work which suggests that biological networks are robust and adaptable to change, and that the overall behavior of a genetic regulatory network might be captured in terms of dynamical basins of attraction. We have developed and implemented a method for inferring genetic regulatory networks for time series microarray data. Our methodmore » first clusters and discretizes the gene expression data using k-means and support vector regression. We then enumerate Boolean activation–inhibition networks to match the discretized data. In conclusion, the dynamics of the Boolean networks are examined. We have tested our method on two immunology microarray datasets: an IL-2-stimulated T cell response dataset and a LPS-stimulated macrophage response dataset. In both cases, we discovered that many networks matched the data, and that most of these networks had similar dynamics.« less

Evolution of Boolean networks under selection for a robust response to external inputs yields an extensive neutral space

NASA Astrophysics Data System (ADS)

Szejka, Agnes; Drossel, Barbara

2010-02-01

We study the evolution of Boolean networks as model systems for gene regulation. Inspired by biological networks, we select simultaneously for robust attractors and for the ability to respond to external inputs by changing the attractor. Mutations change the connections between the nodes and the update functions. In order to investigate the influence of the type of update functions, we perform our simulations with canalizing as well as with threshold functions. We compare the properties of the fitness landscapes that result for different versions of the selection criterion and the update functions. We find that for all studied cases the fitness landscape has a plateau with maximum fitness resulting in the fact that structurally very different networks are able to fulfill the same task and are connected by neutral paths in network (“genotype”) space. We find furthermore a connection between the attractor length and the mutational robustness, and an extremely long memory of the initial evolutionary stage.

Qualitatively modelling and analysing genetic regulatory networks: a Petri net approach.

PubMed

Steggles, L Jason; Banks, Richard; Shaw, Oliver; Wipat, Anil

2007-02-01

New developments in post-genomic technology now provide researchers with the data necessary to study regulatory processes in a holistic fashion at multiple levels of biological organization. One of the major challenges for the biologist is to integrate and interpret these vast data resources to gain a greater understanding of the structure and function of the molecular processes that mediate adaptive and cell cycle driven changes in gene expression. In order to achieve this biologists require new tools and techniques to allow pathway related data to be modelled and analysed as network structures, providing valuable insights which can then be validated and investigated in the laboratory. We propose a new technique for constructing and analysing qualitative models of genetic regulatory networks based on the Petri net formalism. We take as our starting point the Boolean network approach of treating genes as binary switches and develop a new Petri net model which uses logic minimization to automate the construction of compact qualitative models. Our approach addresses the shortcomings of Boolean networks by providing access to the wide range of existing Petri net analysis techniques and by using non-determinism to cope with incomplete and inconsistent data. The ideas we present are illustrated by a case study in which the genetic regulatory network controlling sporulation in the bacterium Bacillus subtilis is modelled and analysed. The Petri net model construction tool and the data files for the B. subtilis sporulation case study are available at http://bioinf.ncl.ac.uk/gnapn.

Modeling integrated cellular machinery using hybrid Petri-Boolean networks.

PubMed

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

2013-01-01

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

Modeling Integrated Cellular Machinery Using Hybrid Petri-Boolean Networks

PubMed Central

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

2013-01-01

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

Origins of Chaos in Autonomous Boolean Networks

NASA Astrophysics Data System (ADS)

Socolar, Joshua; Cavalcante, Hugo; Gauthier, Daniel; Zhang, Rui

2010-03-01

Networks with nodes consisting of ideal Boolean logic gates are known to display either steady states, periodic behavior, or an ultraviolet catastrophe where the number of logic-transition events circulating in the network per unit time grows as a power-law. In an experiment, non-ideal behavior of the logic gates prevents the ultraviolet catastrophe and may lead to deterministic chaos. We identify certain non-ideal features of real logic gates that enable chaos in experimental networks. We find that short-pulse rejection and the asymmetry between the logic states tends to engender periodic behavior. On the other hand, a memory effect termed ``degradation'' can generate chaos. Our results strongly suggest that deterministic chaos can be expected in a large class of experimental Boolean-like networks. Such devices may find application in a variety of technologies requiring fast complex waveforms or flat power spectra. The non-ideal effects identified here also have implications for the statistics of attractors in large complex networks.

Theory and calculus of cubical complexes

NASA Technical Reports Server (NTRS)

Perlman, M.

1973-01-01

Combination switching networks with multiple outputs may be represented by Boolean functions. Report has been prepared which describes derivation and use of extraction algorithm that may be adapted to simplification of such simultaneous Boolean functions.

Attractor controllability of Boolean networks by flipping a subset of their nodes

NASA Astrophysics Data System (ADS)

Rafimanzelat, Mohammad Reza; Bahrami, Fariba

2018-04-01

The controllability analysis of Boolean networks (BNs), as models of biomolecular regulatory networks, has drawn the attention of researchers in recent years. In this paper, we aim at governing the steady-state behavior of BNs using an intervention method which can easily be applied to most real system, which can be modeled as BNs, particularly to biomolecular regulatory networks. To this end, we introduce the concept of attractor controllability of a BN by flipping a subset of its nodes, as the possibility of making a BN converge from any of its attractors to any other one, by one-time flipping members of a subset of BN nodes. Our approach is based on the algebraic state-space representation of BNs using semi-tensor product of matrices. After introducing some new matrix tools, we use them to derive necessary and sufficient conditions for the attractor controllability of BNs. A forward search algorithm is then suggested to identify the minimal perturbation set for attractor controllability of a BN. Next, a lower bound is derived for the cardinality of this set. Two new indices are also proposed for quantifying the attractor controllability of a BN and the influence of each network variable on the attractor controllability of the network and the relationship between them is revealed. Finally, we confirm the efficiency of the proposed approach by applying it to the BN models of some real biomolecular networks.

Boolean decision problems with competing interactions on scale-free networks: Equilibrium and nonequilibrium behavior in an external bias

NASA Astrophysics Data System (ADS)

Zhu, Zheng; Andresen, Juan Carlos; Moore, M. A.; Katzgraber, Helmut G.

2014-02-01

We study the equilibrium and nonequilibrium properties of Boolean decision problems with competing interactions on scale-free networks in an external bias (magnetic field). Previous studies at zero field have shown a remarkable equilibrium stability of Boolean variables (Ising spins) with competing interactions (spin glasses) on scale-free networks. When the exponent that describes the power-law decay of the connectivity of the network is strictly larger than 3, the system undergoes a spin-glass transition. However, when the exponent is equal to or less than 3, the glass phase is stable for all temperatures. First, we perform finite-temperature Monte Carlo simulations in a field to test the robustness of the spin-glass phase and show that the system has a spin-glass phase in a field, i.e., exhibits a de Almeida-Thouless line. Furthermore, we study avalanche distributions when the system is driven by a field at zero temperature to test if the system displays self-organized criticality. Numerical results suggest that avalanches (damage) can spread across the whole system with nonzero probability when the decay exponent of the interaction degree is less than or equal to 2, i.e., that Boolean decision problems on scale-free networks with competing interactions can be fragile when not in thermal equilibrium.

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

PubMed

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

2012-08-29

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. 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. 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 translated in a set of ordinary differential equations on probability distributions. We developed a C++ software, MaBoSS, that is able to simulate such a system by applying Kinetic Monte-Carlo (or Gillespie algorithm) on the Boolean state space. This software, parallelized and optimized, computes the temporal evolution of probability distributions and estimates stationary distributions. Applications of the Boolean Kinetic Monte-Carlo are demonstrated for three qualitative models: a toy model, a published model of p53/Mdm2 interaction and a published model of the mammalian cell cycle. Our approach allows to describe kinetic phenomena which were difficult to handle in the original models. In particular, transient effects are represented by time dependent probability distributions, interpretable in terms of cell populations.

Multilayer neural networks with extensively many hidden units.

PubMed

Rosen-Zvi, M; Engel, A; Kanter, I

2001-08-13

The information processing abilities of a multilayer neural network with a number of hidden units scaling as the input dimension are studied using statistical mechanics methods. The mapping from the input layer to the hidden units is performed by general symmetric Boolean functions, whereas the hidden layer is connected to the output by either discrete or continuous couplings. Introducing an overlap in the space of Boolean functions as order parameter, the storage capacity is found to scale with the logarithm of the number of implementable Boolean functions. The generalization behavior is smooth for continuous couplings and shows a discontinuous transition to perfect generalization for discrete ones.

Understanding genetic regulatory networks

NASA Astrophysics Data System (ADS)

Kauffman, Stuart

2003-04-01

Random Boolean networks (RBM) were introduced about 35 years ago as first crude models of genetic regulatory networks. RBNs are comprised of N on-off genes, connected by a randomly assigned regulatory wiring diagram where each gene has K inputs, and each gene is controlled by a randomly assigned Boolean function. This procedure samples at random from the ensemble of all possible NK Boolean networks. The central ideas are to study the typical, or generic properties of this ensemble, and see 1) whether characteristic differences appear as K and biases in Boolean functions are introducted, and 2) whether a subclass of this ensemble has properties matching real cells. Such networks behave in an ordered or a chaotic regime, with a phase transition, "the edge of chaos" between the two regimes. Networks with continuous variables exhibit the same two regimes. Substantial evidence suggests that real cells are in the ordered regime. A key concept is that of an attractor. This is a reentrant trajectory of states of the network, called a state cycle. The central biological interpretation is that cell types are attractors. A number of properties differentiate the ordered and chaotic regimes. These include the size and number of attractors, the existence in the ordered regime of a percolating "sea" of genes frozen in the on or off state, with a remainder of isolated twinkling islands of genes, a power law distribution of avalanches of gene activity changes following perturbation to a single gene in the ordered regime versus a similar power law distribution plus a spike of enormous avalanches of gene changes in the chaotic regime, and the existence of branching pathway of "differentiation" between attractors induced by perturbations in the ordered regime. Noise is serious issue, since noise disrupts attractors. But numerical evidence suggests that attractors can be made very stable to noise, and meanwhile, metaplasias may be a biological manifestation of noise. As we learn more about the wiring diagram and constraints on rules controlling real genes, we can build refined ensembles reflecting these properties, study the generic properties of the refined ensembles, and hope to gain insight into the dynamics of real cells.

Generalization and capacity of extensively large two-layered perceptrons.

PubMed

Rosen-Zvi, Michal; Engel, Andreas; Kanter, Ido

2002-09-01

The generalization ability and storage capacity of a treelike two-layered neural network with a number of hidden units scaling as the input dimension is examined. The mapping from the input to the hidden layer is via Boolean functions; the mapping from the hidden layer to the output is done by a perceptron. The analysis is within the replica framework where an order parameter characterizing the overlap between two networks in the combined space of Boolean functions and hidden-to-output couplings is introduced. The maximal capacity of such networks is found to scale linearly with the logarithm of the number of Boolean functions per hidden unit. The generalization process exhibits a first-order phase transition from poor to perfect learning for the case of discrete hidden-to-output couplings. The critical number of examples per input dimension, alpha(c), at which the transition occurs, again scales linearly with the logarithm of the number of Boolean functions. In the case of continuous hidden-to-output couplings, the generalization error decreases according to the same power law as for the perceptron, with the prefactor being different.

Feedback Controller Design for the Synchronization of Boolean Control Networks.

PubMed

Liu, Yang; Sun, Liangjie; Lu, Jianquan; Liang, Jinling

2016-09-01

This brief investigates the partial and complete synchronization of two Boolean control networks (BCNs). Necessary and sufficient conditions for partial and complete synchronization are established by the algebraic representations of logical dynamics. An algorithm is obtained to construct the feedback controller that guarantees the synchronization of master and slave BCNs. Two biological examples are provided to illustrate the effectiveness of the obtained results.

A Boolean Network Model of Nuclear Receptor Mediated Cell Cycle Progression

EPA Science Inventory

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate a broad range of cellular processes. Hormones, lipids and xenobiotics have been shown to activate NRs with a range of consequences on development, metabolism, oxidative stress, apoptosis, and prolif...

A Boolean Network Model of Nuclear Receptor Mediated Cell Cycle Progression (S)

EPA Science Inventory

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate a broad range of cellular processes. Hormones, lipids and xenobiotics have been shown to activate NRs with a range of consequences on development, metabolism, oxidative stress, apoptosis, and prolif...

Analysis Tools for Interconnected Boolean Networks With Biological Applications.

PubMed

Chaves, Madalena; Tournier, Laurent

2018-01-01

Boolean networks with asynchronous updates are a class of logical models particularly well adapted to describe the dynamics of biological networks with uncertain measures. The state space of these models can be described by an asynchronous state transition graph, which represents all the possible exits from every single state, and gives a global image of all the possible trajectories of the system. In addition, the asynchronous state transition graph can be associated with an absorbing Markov chain, further providing a semi-quantitative framework where it becomes possible to compute probabilities for the different trajectories. For large networks, however, such direct analyses become computationally untractable, given the exponential dimension of the graph. Exploiting the general modularity of biological systems, we have introduced the novel concept of asymptotic graph , computed as an interconnection of several asynchronous transition graphs and recovering all asymptotic behaviors of a large interconnected system from the behavior of its smaller modules. From a modeling point of view, the interconnection of networks is very useful to address for instance the interplay between known biological modules and to test different hypotheses on the nature of their mutual regulatory links. This paper develops two new features of this general methodology: a quantitative dimension is added to the asymptotic graph, through the computation of relative probabilities for each final attractor and a companion cross-graph is introduced to complement the method on a theoretical point of view.

Stochastic model simulation using Kronecker product analysis and Zassenhaus formula approximation.

PubMed

Caglar, Mehmet Umut; Pal, Ranadip

2013-01-01

Probabilistic Models are regularly applied in Genetic Regulatory Network modeling to capture the stochastic behavior observed in the generation of biological entities such as mRNA or proteins. Several approaches including Stochastic Master Equations and Probabilistic Boolean Networks have been proposed to model the stochastic behavior in genetic regulatory networks. It is generally accepted that Stochastic Master Equation is a fundamental model that can describe the system being investigated in fine detail, but the application of this model is computationally enormously expensive. On the other hand, Probabilistic Boolean Network captures only the coarse-scale stochastic properties of the system without modeling the detailed interactions. We propose a new approximation of the stochastic master equation model that is able to capture the finer details of the modeled system including bistabilities and oscillatory behavior, and yet has a significantly lower computational complexity. In this new method, we represent the system using tensors and derive an identity to exploit the sparse connectivity of regulatory targets for complexity reduction. The algorithm involves an approximation based on Zassenhaus formula to represent the exponential of a sum of matrices as product of matrices. We derive upper bounds on the expected error of the proposed model distribution as compared to the stochastic master equation model distribution. Simulation results of the application of the model to four different biological benchmark systems illustrate performance comparable to detailed stochastic master equation models but with considerably lower computational complexity. The results also demonstrate the reduced complexity of the new approach as compared to commonly used Stochastic Simulation Algorithm for equivalent accuracy.

Equilibrium and nonequilibrium properties of Boolean decision problems on scale-free graphs with competing interactions with external biases

NASA Astrophysics Data System (ADS)

Zhu, Zheng; Andresen, Juan Carlos; Janzen, Katharina; Katzgraber, Helmut G.

2013-03-01

We study the equilibrium and nonequilibrium properties of Boolean decision problems with competing interactions on scale-free graphs in a magnetic field. Previous studies at zero field have shown a remarkable equilibrium stability of Boolean variables (Ising spins) with competing interactions (spin glasses) on scale-free networks. When the exponent that describes the power-law decay of the connectivity of the network is strictly larger than 3, the system undergoes a spin-glass transition. However, when the exponent is equal to or less than 3, the glass phase is stable for all temperatures. First we perform finite-temperature Monte Carlo simulations in a field to test the robustness of the spin-glass phase and show, in agreement with analytical calculations, that the system exhibits a de Almeida-Thouless line. Furthermore, we study avalanches in the system at zero temperature to see if the system displays self-organized criticality. This would suggest that damage (avalanches) can spread across the whole system with nonzero probability, i.e., that Boolean decision problems on scale-free networks with competing interactions are fragile when not in thermal equilibrium.

Damage spreading in spatial and small-world random Boolean networks

NASA Astrophysics Data System (ADS)

Lu, Qiming; Teuscher, Christof

2014-02-01

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 as 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 nonrandom 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 Hamming distance at very low connectivities (K¯≪1) and that the critical connectivity of stability Ks changes compared to random networks. At higher K¯, this scaling remains unchanged. We also show that the Hamming distance 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 arguments for small-world networks are obtained with respect to the system sizes and strength of spatially local connections. 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.

Predictive computation of genomic logic processing functions in embryonic development

PubMed Central

Peter, Isabelle S.; Faure, Emmanuel; Davidson, Eric H.

2012-01-01

Gene regulatory networks (GRNs) control the dynamic spatial patterns of regulatory gene expression in development. Thus, in principle, GRN models may provide system-level, causal explanations of developmental process. To test this assertion, we have transformed a relatively well-established GRN model into a predictive, dynamic Boolean computational model. This Boolean model computes spatial and temporal gene expression according to the regulatory logic and gene interactions specified in a GRN model for embryonic development in the sea urchin. Additional information input into the model included the progressive embryonic geometry and gene expression kinetics. The resulting model predicted gene expression patterns for a large number of individual regulatory genes each hour up to gastrulation (30 h) in four different spatial domains of the embryo. Direct comparison with experimental observations showed that the model predictively computed these patterns with remarkable spatial and temporal accuracy. In addition, we used this model to carry out in silico perturbations of regulatory functions and of embryonic spatial organization. The model computationally reproduced the altered developmental functions observed experimentally. Two major conclusions are that the starting GRN model contains sufficiently complete regulatory information to permit explanation of a complex developmental process of gene expression solely in terms of genomic regulatory code, and that the Boolean model provides a tool with which to test in silico regulatory circuitry and developmental perturbations. PMID:22927416

Modeling Nuclear Receptor-Mediated Activity and Hepatotoxicity with Boolean Networks

EPA Science Inventory

Predicting the human health risk of chronic exposure to environmental contaminants remains an open problem. Chronic exposure to a wide array of chemicals – e.g., conazoles, perfluourinated chemicals and phthalates – has been associated with a range of hepatic lesions in rodents t...

Introduction to focus issue: quantitative approaches to genetic networks.

PubMed

Albert, Réka; Collins, James J; Glass, Leon

2013-06-01

All cells of living organisms contain similar genetic instructions encoded in the organism's DNA. In any particular cell, the control of the expression of each different gene is regulated, in part, by binding of molecular complexes to specific regions of the DNA. The molecular complexes are composed of protein molecules, called transcription factors, combined with various other molecules such as hormones and drugs. Since transcription factors are coded by genes, cellular function is partially determined by genetic networks. Recent research is making large strides to understand both the structure and the function of these networks. Further, the emerging discipline of synthetic biology is engineering novel gene circuits with specific dynamic properties to advance both basic science and potential practical applications. Although there is not yet a universally accepted mathematical framework for studying the properties of genetic networks, the strong analogies between the activation and inhibition of gene expression and electric circuits suggest frameworks based on logical switching circuits. This focus issue provides a selection of papers reflecting current research directions in the quantitative analysis of genetic networks. The work extends from molecular models for the binding of proteins, to realistic detailed models of cellular metabolism. Between these extremes are simplified models in which genetic dynamics are modeled using classical methods of systems engineering, Boolean switching networks, differential equations that are continuous analogues of Boolean switching networks, and differential equations in which control is based on power law functions. The mathematical techniques are applied to study: (i) naturally occurring gene networks in living organisms including: cyanobacteria, Mycoplasma genitalium, fruit flies, immune cells in mammals; (ii) synthetic gene circuits in Escherichia coli and yeast; and (iii) electronic circuits modeling genetic networks using field-programmable gate arrays. Mathematical analyses will be essential for understanding naturally occurring genetic networks in diverse organisms and for providing a foundation for the improved development of synthetic genetic networks.

Introduction to Focus Issue: Quantitative Approaches to Genetic Networks

NASA Astrophysics Data System (ADS)

Albert, Réka; Collins, James J.; Glass, Leon

2013-06-01

All cells of living organisms contain similar genetic instructions encoded in the organism's DNA. In any particular cell, the control of the expression of each different gene is regulated, in part, by binding of molecular complexes to specific regions of the DNA. The molecular complexes are composed of protein molecules, called transcription factors, combined with various other molecules such as hormones and drugs. Since transcription factors are coded by genes, cellular function is partially determined by genetic networks. Recent research is making large strides to understand both the structure and the function of these networks. Further, the emerging discipline of synthetic biology is engineering novel gene circuits with specific dynamic properties to advance both basic science and potential practical applications. Although there is not yet a universally accepted mathematical framework for studying the properties of genetic networks, the strong analogies between the activation and inhibition of gene expression and electric circuits suggest frameworks based on logical switching circuits. This focus issue provides a selection of papers reflecting current research directions in the quantitative analysis of genetic networks. The work extends from molecular models for the binding of proteins, to realistic detailed models of cellular metabolism. Between these extremes are simplified models in which genetic dynamics are modeled using classical methods of systems engineering, Boolean switching networks, differential equations that are continuous analogues of Boolean switching networks, and differential equations in which control is based on power law functions. The mathematical techniques are applied to study: (i) naturally occurring gene networks in living organisms including: cyanobacteria, Mycoplasma genitalium, fruit flies, immune cells in mammals; (ii) synthetic gene circuits in Escherichia coli and yeast; and (iii) electronic circuits modeling genetic networks using field-programmable gate arrays. Mathematical analyses will be essential for understanding naturally occurring genetic networks in diverse organisms and for providing a foundation for the improved development of synthetic genetic networks.

Modeling formalisms in Systems Biology

PubMed Central

2011-01-01

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

A framework to find the logic backbone of a biological network.

PubMed

Maheshwari, Parul; Albert, Réka

2017-12-06

Cellular behaviors are governed by interaction networks among biomolecules, for example gene regulatory and signal transduction networks. An often used dynamic modeling framework for these networks, Boolean modeling, can obtain their attractors (which correspond to cell types and behaviors) and their trajectories from an initial state (e.g. a resting state) to the attractors, for example in response to an external signal. The existing methods however do not elucidate the causal relationships between distant nodes in the network. In this work, we propose a simple logic framework, based on categorizing causal relationships as sufficient or necessary, as a complement to Boolean networks. We identify and explore the properties of complex subnetworks that are distillable into a single logic relationship. We also identify cyclic subnetworks that ensure the stabilization of the state of participating nodes regardless of the rest of the network. We identify the logic backbone of biomolecular networks, consisting of external signals, self-sustaining cyclic subnetworks (stable motifs), and output nodes. Furthermore, we use the logic framework to identify crucial nodes whose override can drive the system from one steady state to another. We apply these techniques to two biological networks: the epithelial-to-mesenchymal transition network corresponding to a developmental process exploited in tumor invasion, and the network of abscisic acid induced stomatal closure in plants. We find interesting subnetworks with logical implications in these networks. Using these subgraphs and motifs, we efficiently reduce both networks to succinct backbone structures. The logic representation identifies the causal relationships between distant nodes and subnetworks. This knowledge can form the basis of network control or used in the reverse engineering of networks.

Reveal, A General Reverse Engineering Algorithm for Inference of Genetic Network Architectures

NASA Technical Reports Server (NTRS)

Liang, Shoudan; Fuhrman, Stefanie; Somogyi, Roland

1998-01-01

Given the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.

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

PubMed

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.

An algebra-based method for inferring gene regulatory networks.

PubMed

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 dynamic patterns present in the network. Boolean polynomial dynamical systems provide a powerful modeling framework for the reverse engineering of gene regulatory networks, that enables a rich mathematical structure on the model search space. A C++ implementation of the method, distributed under LPGL license, is available, together with the source code, at http://www.paola-vera-licona.net/Software/EARevEng/REACT.html.

Boolean gates on actin filaments

NASA Astrophysics Data System (ADS)

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.

Training Signaling Pathway Maps to Biochemical Data with Constrained Fuzzy Logic: Quantitative Analysis of Liver Cell Responses to Inflammatory Stimuli

PubMed Central

Morris, Melody K.; Saez-Rodriguez, Julio; Clarke, David C.; Sorger, Peter K.; Lauffenburger, Douglas A.

2011-01-01

Predictive understanding of cell signaling network operation based on general prior knowledge but consistent with empirical data in a specific environmental context is a current challenge in computational biology. Recent work has demonstrated that Boolean logic can be used to create context-specific network models by training proteomic pathway maps to dedicated biochemical data; however, the Boolean formalism is restricted to characterizing protein species as either fully active or inactive. To advance beyond this limitation, we propose a novel form of fuzzy logic sufficiently flexible to model quantitative data but also sufficiently simple to efficiently construct models by training pathway maps on dedicated experimental measurements. Our new approach, termed constrained fuzzy logic (cFL), converts a prior knowledge network (obtained from literature or interactome databases) into a computable model that describes graded values of protein activation across multiple pathways. We train a cFL-converted network to experimental data describing hepatocytic protein activation by inflammatory cytokines and demonstrate the application of the resultant trained models for three important purposes: (a) generating experimentally testable biological hypotheses concerning pathway crosstalk, (b) establishing capability for quantitative prediction of protein activity, and (c) prediction and understanding of the cytokine release phenotypic response. Our methodology systematically and quantitatively trains a protein pathway map summarizing curated literature to context-specific biochemical data. This process generates a computable model yielding successful prediction of new test data and offering biological insight into complex datasets that are difficult to fully analyze by intuition alone. PMID:21408212

Form and function in gene regulatory networks: the structure of network motifs determines fundamental properties of their dynamical state space.

PubMed

Ahnert, S E; Fink, T M A

2016-07-01

Network motifs have been studied extensively over the past decade, and certain motifs, such as the feed-forward loop, play an important role in regulatory networks. Recent studies have used Boolean network motifs to explore the link between form and function in gene regulatory networks and have found that the structure of a motif does not strongly determine its function, if this is defined in terms of the gene expression patterns the motif can produce. Here, we offer a different, higher-level definition of the 'function' of a motif, in terms of two fundamental properties of its dynamical state space as a Boolean network. One is the basin entropy, which is a complexity measure of the dynamics of Boolean networks. The other is the diversity of cyclic attractor lengths that a given motif can produce. Using these two measures, we examine all 104 topologically distinct three-node motifs and show that the structural properties of a motif, such as the presence of feedback loops and feed-forward loops, predict fundamental characteristics of its dynamical state space, which in turn determine aspects of its functional versatility. We also show that these higher-level properties have a direct bearing on real regulatory networks, as both basin entropy and cycle length diversity show a close correspondence with the prevalence, in neural and genetic regulatory networks, of the 13 connected motifs without self-interactions that have been studied extensively in the literature. © 2016 The Authors.

A stochastic and dynamical view of pluripotency in mouse embryonic stem cells

PubMed Central

Lee, Esther J.

2018-01-01

Pluripotent embryonic stem cells are of paramount importance for biomedical sciences because of their innate ability for self-renewal and differentiation into all major cell lines. The fateful decision to exit or remain in the pluripotent state is regulated by complex genetic regulatory networks. The rapid growth of single-cell sequencing data has greatly stimulated applications of statistical and machine learning methods for inferring topologies of pluripotency regulating genetic networks. The inferred network topologies, however, often only encode Boolean information while remaining silent about the roles of dynamics and molecular stochasticity inherent in gene expression. Herein we develop a framework for systematically extending Boolean-level network topologies into higher resolution models of networks which explicitly account for the promoter architectures and gene state switching dynamics. We show the framework to be useful for disentangling the various contributions that gene switching, external signaling, and network topology make to the global heterogeneity and dynamics of transcription factor populations. We find the pluripotent state of the network to be a steady state which is robust to global variations of gene switching rates which we argue are a good proxy for epigenetic states of individual promoters. The temporal dynamics of exiting the pluripotent state, on the other hand, is significantly influenced by the rates of genetic switching which makes cells more responsive to changes in extracellular signals. PMID:29451874

Two classes of ODE models with switch-like behavior.

PubMed

Just, Winfried; Korb, Mason; Elbert, Ben; Young, Todd

2013-12-01

In cases where the same real-world system can be modeled both by an ODE system ⅅ and a Boolean system , it is of interest to identify conditions under which the two systems will be consistent, that is, will make qualitatively equivalent predictions. In this note we introduce two broad classes of relatively simple models that provide a convenient framework for studying such questions. In contrast to the widely known class of Glass networks, the right-hand sides of our ODEs are Lipschitz-continuous. We prove that if has certain structures, consistency between ⅅ and is implied by sufficient separation of time scales in one class of our models. Namely, if the trajectories of are "one-stepping" then we prove a strong form of consistency and if has a certain monotonicity property then there is a weaker consistency between ⅅ and . These results appear to point to more general structure properties that favor consistency between ODE and Boolean models.

Boolean logic tree of graphene-based chemical system for molecular computation and intelligent molecular search query.

PubMed

Huang, Wei Tao; Luo, Hong Qun; Li, Nian Bing

2014-05-06

The most serious, and yet unsolved, problem of constructing molecular computing devices consists in connecting all of these molecular events into a usable device. This report demonstrates the use of Boolean logic tree for analyzing the chemical event network based on graphene, organic dye, thrombin aptamer, and Fenton reaction, organizing and connecting these basic chemical events. And this chemical event network can be utilized to implement fluorescent combinatorial logic (including basic logic gates and complex integrated logic circuits) and fuzzy logic computing. On the basis of the Boolean logic tree analysis and logic computing, these basic chemical events can be considered as programmable "words" and chemical interactions as "syntax" logic rules to construct molecular search engine for performing intelligent molecular search query. Our approach is helpful in developing the advanced logic program based on molecules for application in biosensing, nanotechnology, and drug delivery.

DSGRN: Examining the Dynamics of Families of Logical Models.

PubMed

Cummins, Bree; Gedeon, Tomas; Harker, Shaun; Mischaikow, Konstantin

2018-01-01

We present a computational tool DSGRN for exploring the dynamics of a network by computing summaries of the dynamics of switching models compatible with the network across all parameters. The network can arise directly from a biological problem, or indirectly as the interaction graph of a Boolean model. This tool computes a finite decomposition of parameter space such that for each region, the state transition graph that describes the coarse dynamical behavior of a network is the same. Each of these parameter regions corresponds to a different logical description of the network dynamics. The comparison of dynamics across parameters with experimental data allows the rejection of parameter regimes or entire networks as viable models for representing the underlying regulatory mechanisms. This in turn allows a search through the space of perturbations of a given network for networks that robustly fit the data. These are the first steps toward discovering a network that optimally matches the observed dynamics by searching through the space of networks.

Co Modeling and Co Synthesis of Safety Critical Multi threaded Embedded Software for Multi Core Embedded Platforms

DTIC Science & Technology

2017-03-20

computation, Prime Implicates, Boolean Abstraction, real- time embedded software, software synthesis, correct by construction software design , model...types for time -dependent data-flow networks". J.-P. Talpin, P. Jouvelot, S. Shukla. ACM-IEEE Conference on Methods and Models for System Design ...information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing   data sources, gathering and

Adaptation and survivors in a random Boolean network.

PubMed

Nakamura, Ikuo

2002-04-01

We introduce the competitive agent with imitation strategy in a random Boolean network, in which the agent plays a competitive game that rewards those in minority. After a long time interval, the worst performer changes its strategy to the one of the best and the process is repeated. The network, initially in a chaotic state, evolves to an intermittent state and finally reaches a frozen state. Time series of survived species (whose strategies are imitated by other agents) in the system depend on the connectivity of each agent. In a system with various connectivity groups, the low connectivity groups win the minority game over the high connectivity groups. We also compared the result with mutation strategy system.

Synchronization Analysis of Master-Slave Probabilistic Boolean Networks.

PubMed

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.

Synchronization Analysis of Master-Slave Probabilistic Boolean Networks

PubMed Central

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

2015-01-01

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. PMID:26315380

Mathematical modeling of gene expression: a guide for the perplexed biologist

PubMed Central

Ay, Ahmet; Arnosti, David N.

2011-01-01

The detailed analysis of transcriptional networks holds a key for understanding central biological processes, and interest in this field has exploded due to new large-scale data acquisition techniques. Mathematical modeling can provide essential insights, but the diversity of modeling approaches can be a daunting prospect to investigators new to this area. For those interested in beginning a transcriptional mathematical modeling project we provide here an overview of major types of models and their applications to transcriptional networks. In this discussion of recent literature on thermodynamic, Boolean and differential equation models we focus on considerations critical for choosing and validating a modeling approach that will be useful for quantitative understanding of biological systems. PMID:21417596

Order or chaos in Boolean gene networks depends on the mean fraction of canalizing functions

NASA Astrophysics Data System (ADS)

Karlsson, Fredrik; Hörnquist, Michael

2007-10-01

We explore the connection between order/chaos in Boolean networks and the naturally occurring fraction of canalizing functions in such systems. This fraction turns out to give a very clear indication of whether the system possesses ordered or chaotic dynamics, as measured by Derrida plots, and also the degree of order when we compare different networks with the same number of vertices and edges. By studying also a wide distribution of indegrees in a network, we show that the mean probability of canalizing functions is a more reliable indicator of the type of dynamics for a finite network than the classical result on stability relating the bias to the mean indegree. Finally, we compare by direct simulations two biologically derived networks with networks of similar sizes but with power-law and Poisson distributions of indegrees, respectively. The biologically motivated networks are not more ordered than the latter, and in one case the biological network is even chaotic while the others are not.

Stability of Boolean multilevel networks.

PubMed

Cozzo, Emanuele; Arenas, Alex; Moreno, Yamir

2012-09-01

The study of the interplay between the structure and dynamics of complex multilevel systems is a pressing challenge nowadays. In this paper, we use a semiannealed approximation to study the stability properties of random Boolean networks in multiplex (multilayered) graphs. Our main finding is that the multilevel structure provides a mechanism for the stabilization of the dynamics of the whole system even when individual layers work on the chaotic regime, therefore identifying new ways of feedback between the structure and the dynamics of these systems. Our results point out the need for a conceptual transition from the physics of single-layered networks to the physics of multiplex networks. Finally, the fact that the coupling modifies the phase diagram and the critical conditions of the isolated layers suggests that interdependency can be used as a control mechanism.

An autocatalytic network model for stock markets

NASA Astrophysics Data System (ADS)

Caetano, Marco Antonio Leonel; Yoneyama, Takashi

2015-02-01

The stock prices of companies with businesses that are closely related within a specific sector of economy might exhibit movement patterns and correlations in their dynamics. The idea in this work is to use the concept of autocatalytic network to model such correlations and patterns in the trends exhibited by the expected returns. The trends are expressed in terms of positive or negative returns within each fixed time interval. The time series derived from these trends is then used to represent the movement patterns by a probabilistic boolean network with transitions modeled as an autocatalytic network. The proposed method might be of value in short term forecasting and identification of dependencies. The method is illustrated with a case study based on four stocks of companies in the field of natural resource and technology.

An algebra-based method for inferring gene regulatory networks

PubMed Central

2014-01-01

Background 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. Results 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 dynamic patterns present in the network. Conclusions Boolean polynomial dynamical systems provide a powerful modeling framework for the reverse engineering of gene regulatory networks, that enables a rich mathematical structure on the model search space. A C++ implementation of the method, distributed under LPGL license, is available, together with the source code, at http://www.paola-vera-licona.net/Software/EARevEng/REACT.html. PMID:24669835

Adaptive Neuro-Fuzzy Determination of the Effect of Experimental Parameters on Vehicle Agent Speed Relative to Vehicle Intruder.

PubMed

Shamshirband, Shahaboddin; Banjanovic-Mehmedovic, Lejla; Bosankic, Ivan; Kasapovic, Suad; Abdul Wahab, Ainuddin Wahid Bin

2016-01-01

Intelligent Transportation Systems rely on understanding, predicting and affecting the interactions between vehicles. The goal of this paper is to choose a small subset from the larger set so that the resulting regression model is simple, yet have good predictive ability for Vehicle agent speed relative to Vehicle intruder. The method of ANFIS (adaptive neuro fuzzy inference system) was applied to the data resulting from these measurements. The ANFIS process for variable selection was implemented in order to detect the predominant variables affecting the prediction of agent speed relative to intruder. This process includes several ways to discover a subset of the total set of recorded parameters, showing good predictive capability. The ANFIS network was used to perform a variable search. Then, it was used to determine how 9 parameters (Intruder Front sensors active (boolean), Intruder Rear sensors active (boolean), Agent Front sensors active (boolean), Agent Rear sensors active (boolean), RSSI signal intensity/strength (integer), Elapsed time (in seconds), Distance between Agent and Intruder (m), Angle of Agent relative to Intruder (angle between vehicles °), Altitude difference between Agent and Intruder (m)) influence prediction of agent speed relative to intruder. The results indicated that distance between Vehicle agent and Vehicle intruder (m) and angle of Vehicle agent relative to Vehicle Intruder (angle between vehicles °) is the most influential parameters to Vehicle agent speed relative to Vehicle intruder.

Satisfiability of logic programming based on radial basis function neural networks

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

Hamadneh, Nawaf; Sathasivam, Saratha; Tilahun, Surafel Luleseged

2014-07-10

In this paper, we propose a new technique to test the Satisfiability of propositional logic programming and quantified Boolean formula problem in radial basis function neural networks. For this purpose, we built radial basis function neural networks to represent the proportional logic which has exactly three variables in each clause. We used the Prey-predator algorithm to calculate the output weights of the neural networks, while the K-means clustering algorithm is used to determine the hidden parameters (the centers and the widths). Mean of the sum squared error function is used to measure the activity of the two algorithms. We appliedmore » the developed technique with the recurrent radial basis function neural networks to represent the quantified Boolean formulas. The new technique can be applied to solve many applications such as electronic circuits and NP-complete problems.« less

Stationary and structural control in gene regulatory networks: basic concepts

NASA Astrophysics Data System (ADS)

Dougherty, Edward R.; Pal, Ranadip; Qian, Xiaoning; Bittner, Michael L.; Datta, Aniruddha

2010-01-01

A major reason for constructing gene regulatory networks is to use them as models for determining therapeutic intervention strategies by deriving ways of altering their long-run dynamics in such a way as to reduce the likelihood of entering undesirable states. In general, two paradigms have been taken for gene network intervention: (1) stationary external control is based on optimally altering the status of a control gene (or genes) over time to drive network dynamics; and (2) structural intervention involves an optimal one-time change of the network structure (wiring) to beneficially alter the long-run behaviour of the network. These intervention approaches have mainly been developed within the context of the probabilistic Boolean network model for gene regulation. This article reviews both types of intervention and applies them to reducing the metastatic competence of cells via intervention in a melanoma-related network.

Two classes of ODE models with switch-like behavior

PubMed Central

Just, Winfried; Korb, Mason; Elbert, Ben; Young, Todd

2013-01-01

In cases where the same real-world system can be modeled both by an ODE system ⅅ and a Boolean system 𝔹, it is of interest to identify conditions under which the two systems will be consistent, that is, will make qualitatively equivalent predictions. In this note we introduce two broad classes of relatively simple models that provide a convenient framework for studying such questions. In contrast to the widely known class of Glass networks, the right-hand sides of our ODEs are Lipschitz-continuous. We prove that if 𝔹 has certain structures, consistency between ⅅ and 𝔹 is implied by sufficient separation of time scales in one class of our models. Namely, if the trajectories of 𝔹 are “one-stepping” then we prove a strong form of consistency and if 𝔹 has a certain monotonicity property then there is a weaker consistency between ⅅ and 𝔹. These results appear to point to more general structure properties that favor consistency between ODE and Boolean models. PMID:24244061

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

D'Huys, Otti, E-mail: otti.dhuys@phy.duke.edu; Haynes, Nicholas D.; Lohmann, Johannes

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 delaysmore » 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.« less

Reconstruction of an Immune Dynamic Model to Simulate the Contrasting Role of Auxin and Cytokinin in Plant Immunity.

PubMed

Kaltdorf, Martin; Dandekar, Thomas; Naseem, Muhammad

2017-01-01

In order to increase our understanding of biological dependencies in plant immune signaling pathways, the known interactions involved in plant immune networks are modeled. This allows computational analysis to predict the functions of growth related hormones in plant-pathogen interaction. The SQUAD (Standardized Qualitative Dynamical Systems) algorithm first determines stable system states in the network and then use them to compute continuous dynamical system states. Our reconstructed Boolean model encompassing hormone immune networks of Arabidopsis thaliana (Arabidopsis) and pathogenicity factors injected by model pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) can be exploited to determine the impact of growth hormones in plant immunity. We describe a detailed working protocol how to use the modified SQUAD-package by exemplifying the contrasting effects of auxin and cytokinins in shaping plant-pathogen interaction.

Evolution of a designless nanoparticle network into reconfigurable Boolean logic

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

Spatial features of synaptic adaptation affecting learning performance.

PubMed

Berger, Damian L; de Arcangelis, Lucilla; Herrmann, Hans J

2017-09-08

Recent studies have proposed that the diffusion of messenger molecules, such as monoamines, can mediate the plastic adaptation of synapses in supervised learning of neural networks. Based on these findings we developed a model for neural learning, where the signal for plastic adaptation is assumed to propagate through the extracellular space. We investigate the conditions allowing learning of Boolean rules in a neural network. Even fully excitatory networks show very good learning performances. Moreover, the investigation of the plastic adaptation features optimizing the performance suggests that learning is very sensitive to the extent of the plastic adaptation and the spatial range of synaptic connections.

On construction of stochastic genetic networks based on gene expression sequences.

PubMed

Ching, Wai-Ki; Ng, Michael M; Fung, Eric S; Akutsu, Tatsuya

2005-08-01

Reconstruction of genetic regulatory networks from time series data of gene expression patterns is an important research topic in bioinformatics. Probabilistic Boolean Networks (PBNs) have been proposed as an effective model for gene regulatory networks. PBNs are able to cope with uncertainty, corporate rule-based dependencies between genes and discover the sensitivity of genes in their interactions with other genes. However, PBNs are unlikely to use directly in practice because of huge amount of computational cost for obtaining predictors and their corresponding probabilities. In this paper, we propose a multivariate Markov model for approximating PBNs and describing the dynamics of a genetic network for gene expression sequences. The main contribution of the new model is to preserve the strength of PBNs and reduce the complexity of the networks. The number of parameters of our proposed model is O(n2) where n is the number of genes involved. We also develop efficient estimation methods for solving the model parameters. Numerical examples on synthetic data sets and practical yeast data sequences are given to demonstrate the effectiveness of the proposed model.

A sparse matrix algorithm on the Boolean vector machine

NASA Technical Reports Server (NTRS)

Wagner, Robert A.; Patrick, Merrell L.

1988-01-01

VLSI technology is being used to implement a prototype Boolean Vector Machine (BVM), which is a large network of very small processors with equally small memories that operate in SIMD mode; these use bit-serial arithmetic, and communicate via cube-connected cycles network. The BVM's bit-serial arithmetic and the small memories of individual processors are noted to compromise the system's effectiveness in large numerical problem applications. Attention is presently given to the implementation of a basic matrix-vector iteration algorithm for space matrices of the BVM, in order to generate over 1 billion useful floating-point operations/sec for this iteration algorithm. The algorithm is expressed in a novel language designated 'BVM'.

Optical Neural Classification Of Binary Patterns

NASA Astrophysics Data System (ADS)

Gustafson, Steven C.; Little, Gordon R.

1988-05-01

Binary pattern classification that may be implemented using optical hardware and neural network algorithms is considered. Pattern classification problems that have no concise description (as in classifying handwritten characters) or no concise computation (as in NP-complete problems) are expected to be particularly amenable to this approach. For example, optical processors that efficiently classify binary patterns in accordance with their Boolean function complexity might be designed. As a candidate for such a design, an optical neural network model is discussed that is designed for binary pattern classification and that consists of an optical resonator with a dynamic multiplex-recorded reflection hologram and a phase conjugate mirror with thresholding and gain. In this model, learning or training examples of binary patterns may be recorded on the hologram such that one bit in each pattern marks the pattern class. Any input pattern, including one with an unknown class or marker bit, will be modified by a large number of parallel interactions with the reflection hologram and nonlinear mirror. After perhaps several seconds and 100 billion interactions, a steady-state pattern may develop with a marker bit that represents a minimum-Boolean-complexity classification of the input pattern. Computer simulations are presented that illustrate progress in understanding the behavior of this model and in developing a processor design that could have commanding and enduring performance advantages compared to current pattern classification techniques.

Construction and analysis of gene-gene dynamics influence networks based on a Boolean model.

PubMed

Mazaya, Maulida; Trinh, Hung-Cuong; Kwon, Yung-Keun

2017-12-21

Identification of novel gene-gene relations is a crucial issue to understand system-level biological phenomena. To this end, many methods based on a correlation analysis of gene expressions or structural analysis of molecular interaction networks have been proposed. They have a limitation in identifying more complicated gene-gene dynamical relations, though. To overcome this limitation, we proposed a measure to quantify a gene-gene dynamical influence (GDI) using a Boolean network model and constructed a GDI network to indicate existence of a dynamical influence for every ordered pair of genes. It represents how much a state trajectory of a target gene is changed by a knockout mutation subject to a source gene in a gene-gene molecular interaction (GMI) network. Through a topological comparison between GDI and GMI networks, we observed that the former network is denser than the latter network, which implies that there exist many gene pairs of dynamically influencing but molecularly non-interacting relations. In addition, a larger number of hub genes were generated in the GDI network. On the other hand, there was a correlation between these networks such that the degree value of a node was positively correlated to each other. We further investigated the relationships of the GDI value with structural properties and found that there are negative and positive correlations with the length of a shortest path and the number of paths, respectively. In addition, a GDI network could predict a set of genes whose steady-state expression is affected in E. coli gene-knockout experiments. More interestingly, we found that the drug-targets with side-effects have a larger number of outgoing links than the other genes in the GDI network, which implies that they are more likely to influence the dynamics of other genes. Finally, we found biological evidences showing that the gene pairs which are not molecularly interacting but dynamically influential can be considered for novel gene-gene relationships. Taken together, construction and analysis of the GDI network can be a useful approach to identify novel gene-gene relationships in terms of the dynamical influence.

Exploiting Data Missingness in Bayesian Network Modeling

NASA Astrophysics Data System (ADS)

Rodrigues de Morais, Sérgio; Aussem, Alex

This paper proposes a framework built on the use of Bayesian networks (BN) for representing statistical dependencies between the existing random variables and additional dummy boolean variables, which represent the presence/absence of the respective random variable value. We show how augmenting the BN with these additional variables helps pinpoint the mechanism through which missing data contributes to the classification task. The missing data mechanism is thus explicitly taken into account to predict the class variable using the data at hand. Extensive experiments on synthetic and real-world incomplete data sets reveals that the missingness information improves classification accuracy.

Boolean network inference from time series data incorporating prior biological knowledge.

PubMed

Haider, Saad; Pal, Ranadip

2012-01-01

Numerous approaches exist for modeling of genetic regulatory networks (GRNs) but the low sampling rates often employed in biological studies prevents the inference of detailed models from experimental data. In this paper, we analyze the issues involved in estimating a model of a GRN from single cell line time series data with limited time points. We present an inference approach for a Boolean Network (BN) model of a GRN from limited transcriptomic or proteomic time series data based on prior biological knowledge of connectivity, constraints on attractor structure and robust design. We applied our inference approach to 6 time point transcriptomic data on Human Mammary Epithelial Cell line (HMEC) after application of Epidermal Growth Factor (EGF) and generated a BN with a plausible biological structure satisfying the data. We further defined and applied a similarity measure to compare synthetic BNs and BNs generated through the proposed approach constructed from transitions of various paths of the synthetic BNs. We have also compared the performance of our algorithm with two existing BN inference algorithms. Through theoretical analysis and simulations, we showed the rarity of arriving at a BN from limited time series data with plausible biological structure using random connectivity and absence of structure in data. The framework when applied to experimental data and data generated from synthetic BNs were able to estimate BNs with high similarity scores. Comparison with existing BN inference algorithms showed the better performance of our proposed algorithm for limited time series data. The proposed framework can also be applied to optimize the connectivity of a GRN from experimental data when the prior biological knowledge on regulators is limited or not unique.

Collective dynamics in heterogeneous networks of neuronal cellular automata

NASA Astrophysics Data System (ADS)

Manchanda, Kaustubh; Bose, Amitabha; Ramaswamy, Ramakrishna

2017-12-01

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

Android malware detection based on evolutionary super-network

NASA Astrophysics Data System (ADS)

Yan, Haisheng; Peng, Lingling

2018-04-01

In the paper, an android malware detection method based on evolutionary super-network is proposed in order to improve the precision of android malware detection. Chi square statistics method is used for selecting characteristics on the basis of analyzing android authority. Boolean weighting is utilized for calculating characteristic weight. Processed characteristic vector is regarded as the system training set and test set; hyper edge alternative strategy is used for training super-network classification model, thereby classifying test set characteristic vectors, and it is compared with traditional classification algorithm. The results show that the detection method proposed in the paper is close to or better than traditional classification algorithm. The proposed method belongs to an effective Android malware detection means.

Enumeration and extension of non-equivalent deterministic update schedules in Boolean networks.

PubMed

Palma, Eduardo; Salinas, Lilian; Aracena, Julio

2016-03-01

Boolean networks (BNs) are commonly used to model genetic regulatory networks (GRNs). Due to the sensibility of the dynamical behavior to changes in the updating scheme (order in which the nodes of a network update their state values), it is increasingly common to use different updating rules in the modeling of GRNs to better capture an observed biological phenomenon and thus to obtain more realistic models.In Aracena et al. equivalence classes of deterministic update schedules in BNs, that yield exactly the same dynamical behavior of the network, were defined according to a certain label function on the arcs of the interaction digraph defined for each scheme. Thus, the interaction digraph so labeled (update digraphs) encode the non-equivalent schemes. We address the problem of enumerating all non-equivalent deterministic update schedules of a given BN. First, we show that it is an intractable problem in general. To solve it, we first construct an algorithm that determines the set of update digraphs of a BN. For that, we use divide and conquer methodology based on the structural characteristics of the interaction digraph. Next, for each update digraph we determine a scheme associated. This algorithm also works in the case where there is a partial knowledge about the relative order of the updating of the states of the nodes. We exhibit some examples of how the algorithm works on some GRNs published in the literature. An executable file of the UpdateLabel algorithm made in Java and the files with the outputs of the algorithms used with the GRNs are available at: www.inf.udec.cl/ ∼lilian/UDE/ CONTACT: lilisalinas@udec.cl Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

PubMed

Wilczynski, Bartek; Furlong, Eileen E M

2010-04-15

Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Evolution of regulatory networks towards adaptability and stability in a changing environment

NASA Astrophysics Data System (ADS)

Lee, Deok-Sun

2014-11-01

Diverse biological networks exhibit universal features distinguished from those of random networks, calling much attention to their origins and implications. Here we propose a minimal evolution model of Boolean regulatory networks, which evolve by selectively rewiring links towards enhancing adaptability to a changing environment and stability against dynamical perturbations. We find that sparse and heterogeneous connectivity patterns emerge, which show qualitative agreement with real transcriptional regulatory networks and metabolic networks. The characteristic scaling behavior of stability reflects the balance between robustness and flexibility. The scaling of fluctuation in the perturbation spread shows a dynamic crossover, which is analyzed by investigating separately the stochasticity of internal dynamics and the network structure differences depending on the evolution pathways. Our study delineates how the ambivalent pressure of evolution shapes biological networks, which can be helpful for studying general complex systems interacting with environments.

A model for cancer tissue heterogeneity.

PubMed

Mohanty, Anwoy Kumar; Datta, Aniruddha; Venkatraj, Vijayanagaram

2014-03-01

An important problem in the study of cancer is the understanding of the heterogeneous nature of the cell population. The clonal evolution of the tumor cells results in the tumors being composed of multiple subpopulations. Each subpopulation reacts differently to any given therapy. This calls for the development of novel (regulatory network) models, which can accommodate heterogeneity in cancerous tissues. In this paper, we present a new approach to model heterogeneity in cancer. We model heterogeneity as an ensemble of deterministic Boolean networks based on prior pathway knowledge. We develop the model considering the use of qPCR data. By observing gene expressions when the tissue is subjected to various stimuli, the compositional breakup of the tissue under study can be determined. We demonstrate the viability of this approach by using our model on synthetic data, and real-world data collected from fibroblasts.

Learning Boolean Networks in HepG2 cells using ToxCast High-Content Imaging Data (SOT annual meeting)

EPA Science Inventory

Cells adapt to their environment via homeostatic processes that are regulated by complex molecular networks. Our objective was to learn key elements of these networks in HepG2 cells using ToxCast High-content imaging (HCI) measurements taken over three time points (1, 24, and 72h...

Structures and Boolean Dynamics in Gene Regulatory Networks

NASA Astrophysics Data System (ADS)

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 process. Futher development of these and other theoretical and computational tools is necessary to analyze the deluge of experimental data produced by modern and future biological high throughput methods. (Abstract shortened by ProQuest.).

Analysis and logical modeling of biological signaling transduction networks

NASA Astrophysics Data System (ADS)

Sun, Zhongyao

The study of network theory and its application span across a multitude of seemingly disparate fields of science and technology: computer science, biology, social science, linguistics, etc. It is the intrinsic similarities embedded in the entities and the way they interact with one another in these systems that link them together. In this dissertation, I present from both the aspect of theoretical analysis and the aspect of application three projects, which primarily focus on signal transduction networks in biology. In these projects, I assembled a network model through extensively perusing literature, performed model-based simulations and validation, analyzed network topology, and proposed a novel network measure. The application of network modeling to the system of stomatal opening in plants revealed a fundamental question about the process that has been left unanswered in decades. The novel measure of the redundancy of signal transduction networks with Boolean dynamics by calculating its maximum node-independent elementary signaling mode set accurately predicts the effect of single node knockout in such signaling processes. The three projects as an organic whole advance the understanding of a real system as well as the behavior of such network models, giving me an opportunity to take a glimpse at the dazzling facets of the immense world of network science.

Solving a discrete model of the lac operon using Z3

NASA Astrophysics Data System (ADS)

Gutierrez, Natalia A.

2014-05-01

A discrete model for the Lcac Operon is solved using the SMT-solver Z3. Traditionally the Lac Operon is formulated in a continuous math model. This model is a system of ordinary differential equations. Here, it was considerated as a discrete model, based on a Boolean red. The biological problem of Lac Operon is enunciated as a problem of Boolean satisfiability, and it is solved using an STM-solver named Z3. Z3 is a powerful solver that allows understanding the basic dynamic of the Lac Operon in an easier and more efficient way. The multi-stability of the Lac Operon can be easily computed with Z3. The code that solves the Boolean red can be written in Python language or SMT-Lib language. Both languages were used in local version of the program as online version of Z3. For future investigations it is proposed to solve the Boolean red of Lac Operon using others SMT-solvers as cvc4, alt-ergo, mathsat and yices.

Neural Network Model For Fast Learning And Retrieval

NASA Astrophysics Data System (ADS)

Arsenault, Henri H.; Macukow, Bohdan

1989-05-01

An approach to learning in a multilayer neural network is presented. The proposed network learns by creating interconnections between the input layer and the intermediate layer. In one of the new storage prescriptions proposed, interconnections are excitatory (positive) only and the weights depend on the stored patterns. In the intermediate layer each mother cell is responsible for one stored pattern. Mutually interconnected neurons in the intermediate layer perform a winner-take-all operation, taking into account correlations between stored vectors. The performance of networks using this interconnection prescription is compared with two previously proposed schemes, one using inhibitory connections at the output and one using all-or-nothing interconnections. The network can be used as a content-addressable memory or as a symbolic substitution system that yields an arbitrarily defined output for any input. The training of a model to perform Boolean logical operations is also described. Computer simulations using the network as an autoassociative content-addressable memory show the model to be efficient. Content-addressable associative memories and neural logic modules can be combined to perform logic operations on highly corrupted data.

Genetic Network Inference: From Co-Expression Clustering to Reverse Engineering

NASA Technical Reports Server (NTRS)

Dhaeseleer, Patrik; Liang, Shoudan; Somogyi, Roland

2000-01-01

Advances in molecular biological, analytical, and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-duster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e., who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting, and bioengineering.

Complexity of generic biochemical circuits: topology versus strength of interactions.

PubMed

Tikhonov, Mikhail; Bialek, William

2016-12-06

The historical focus on network topology as a determinant of biological function is still largely maintained today, illustrated by the rise of structure-only approaches to network analysis. However, biochemical circuits and genetic regulatory networks are defined both by their topology and by a multitude of continuously adjustable parameters, such as the strength of interactions between nodes, also recognized as important. Here we present a class of simple perceptron-based Boolean models within which comparing the relative importance of topology versus interaction strengths becomes a quantitatively well-posed problem. We quantify the intuition that for generic networks, optimization of interaction strengths is a crucial ingredient of achieving high complexity, defined here as the number of fixed points the network can accommodate. We propose a new methodology for characterizing the relative role of parameter optimization for topologies of a given class.

Matrix product algorithm for stochastic dynamics on networks applied to nonequilibrium Glauber dynamics

NASA Astrophysics Data System (ADS)

Barthel, Thomas; De Bacco, Caterina; Franz, Silvio

2018-01-01

We introduce and apply an efficient method for the precise simulation of stochastic dynamical processes on locally treelike graphs. Networks with cycles are treated in the framework of the cavity method. Such models correspond, for example, to spin-glass systems, Boolean networks, neural networks, or other technological, biological, and social networks. Building upon ideas from quantum many-body theory, our approach is based on a matrix product approximation of the so-called edge messages—conditional probabilities of vertex variable trajectories. Computation costs and accuracy can be tuned by controlling the matrix dimensions of the matrix product edge messages (MPEM) in truncations. In contrast to Monte Carlo simulations, the algorithm has a better error scaling and works for both single instances as well as the thermodynamic limit. We employ it to examine prototypical nonequilibrium Glauber dynamics in the kinetic Ising model. Because of the absence of cancellation effects, observables with small expectation values can be evaluated accurately, allowing for the study of decay processes and temporal correlations.

Discrete Logic Modelling Optimization to Contextualize Prior Knowledge Networks Using PRUNET

PubMed Central

Androsova, Ganna; del Sol, Antonio

2015-01-01

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

An Automated Design Framework for Multicellular Recombinase Logic.

PubMed

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

2018-05-18

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

Information Resources Usage in Project Management Digital Learning System

ERIC Educational Resources Information Center

Davidovitch, Nitza; Belichenko, Margarita; Kravchenko, Yurii

2017-01-01

The article combines a theoretical approach to structuring knowledge that is based on the integrated use of fuzzy semantic network theory predicates, Boolean functions, theory of complexity of network structures and some practical aspects to be considered in the distance learning at the university. The paper proposes a methodological approach that…

Stability and structural properties of gene regulation networks with coregulation rules.

PubMed

Warrell, Jonathan; Mhlanga, Musa

2017-05-07

Coregulation of the expression of groups of genes has been extensively demonstrated empirically in bacterial and eukaryotic systems. Such coregulation can arise through the use of shared regulatory motifs, which allow the coordinated expression of modules (and module groups) of functionally related genes across the genome. Coregulation can also arise through the physical association of multi-gene complexes through chromosomal looping, which are then transcribed together. We present a general formalism for modeling coregulation rules in the framework of Random Boolean Networks (RBN), and develop specific models for transcription factor networks with modular structure (including module groups, and multi-input modules (MIM) with autoregulation) and multi-gene complexes (including hierarchical differentiation between multi-gene complex members). We develop a mean-field approach to analyse the dynamical stability of large networks incorporating coregulation, and show that autoregulated MIM and hierarchical gene-complex models can achieve greater stability than networks without coregulation whose rules have matching activation frequency. We provide further analysis of the stability of small networks of both kinds through simulations. We also characterize several general properties of the transients and attractors in the hierarchical coregulation model, and show using simulations that the steady-state distribution factorizes hierarchically as a Bayesian network in a Markov Jump Process analogue of the RBN model. Copyright © 2017. Published by Elsevier Ltd.

Monotone Boolean approximation

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

Hulme, B.L.

1982-12-01

This report presents a theory of approximation of arbitrary Boolean functions by simpler, monotone functions. Monotone increasing functions can be expressed without the use of complements. Nonconstant monotone increasing functions are important in their own right since they model a special class of systems known as coherent systems. It is shown here that when Boolean expressions for noncoherent systems become too large to treat exactly, then monotone approximations are easily defined. The algorithms proposed here not only provide simpler formulas but also produce best possible upper and lower monotone bounds for any Boolean function. This theory has practical application formore » the analysis of noncoherent fault trees and event tree sequences.« less

A network model for biofilm development in Escherichia coli K-12.

PubMed

Shalá, Andrew A; Restrepo, Silvia; González Barrios, Andrés F

2011-09-22

In nature, bacteria often exist as biofilms. Biofilms are communities of microorganisms attached to a surface. It is clear that biofilm-grown cells harbor properties remarkably distinct from planktonic cells. Biofilms frequently complicate treatments of infections by protecting bacteria from the immune system, decreasing antibiotic efficacy and dispersing planktonic cells to distant body sites. In this work, we employed enhanced Boolean algebra to model biofilm formation. The network obtained describes biofilm formation successfully, assuming - in accordance with the literature - that when the negative regulators (RscCD and EnvZ/OmpR) are off, the positive regulator (FlhDC) is on. The network was modeled under three different conditions through time with satisfactory outcomes. Each cluster was constructed using the K-means/medians Clustering Support algorithm on the basis of published Affymetrix microarray gene expression data from biofilm-forming bacteria and the planktonic state over four time points for Escherichia coli K-12. The different phenotypes obtained demonstrate that the network model of biofilm formation can simulate the formation or repression of biofilm efficiently in E. coli K-12.

Bounds on the number of hidden neurons in three-layer binary neural networks.

PubMed

Zhang, Zhaozhi; Ma, Xiaomin; Yang, Yixian

2003-09-01

This paper investigates an important problem concerning the complexity of three-layer binary neural networks (BNNs) with one hidden layer. The neuron in the studied BNNs employs a hard limiter activation function with only integer weights and an integer threshold. The studies are focused on implementations of arbitrary Boolean functions which map from [0, 1]n into [0, 1]. A deterministic algorithm called set covering algorithm (SCA) is proposed for the construction of a three-layer BNN to implement an arbitrary Boolean function. The SCA is based on a unit sphere covering (USC) of the Hamming space (HS) which is chosen in advance. It is proved that for the implementation of an arbitrary Boolean function of n-variables (n > or = 3) by using SCA, [3L/2] hidden neurons are necessary and sufficient, where L is the number of unit spheres contained in the chosen USC of the n-dimensional HS. It is shown that by using SCA, the number of hidden neurons required is much less than that by using a two-parallel hyperplane method. In order to indicate the potential ability of three-layer BNNs, a lower bound on the required number of hidden neurons which is derived by using the method of estimating the Vapnik-Chervonenkis (VC) dimension is also given.

Towards Symbolic Model Checking for Multi-Agent Systems via OBDDs

NASA Technical Reports Server (NTRS)

Raimondi, Franco; Lomunscio, Alessio

2004-01-01

We present an algorithm for model checking temporal-epistemic properties of multi-agent systems, expressed in the formalism of interpreted systems. We first introduce a technique for the translation of interpreted systems into boolean formulae, and then present a model-checking algorithm based on this translation. The algorithm is based on OBDD's, as they offer a compact and efficient representation for boolean formulae.

Economic networks: Heterogeneity-induced vulnerability and loss of synchronization

NASA Astrophysics Data System (ADS)

Colon, Célian; Ghil, Michael

2017-12-01

Interconnected systems are prone to propagation of disturbances, which can undermine their resilience to external perturbations. Propagation dynamics can clearly be affected by potential time delays in the underlying processes. We investigate how such delays influence the resilience of production networks facing disruption of supply. Interdependencies between economic agents are modeled using systems of Boolean delay equations (BDEs); doing so allows us to introduce heterogeneity in production delays and in inventories. Complex network topologies are considered that reproduce realistic economic features, including a network of networks. Perturbations that would otherwise vanish can, because of delay heterogeneity, amplify and lead to permanent disruptions. This phenomenon is enabled by the interactions between short cyclic structures. Difference in delays between two interacting, and otherwise resilient, structures can in turn lead to loss of synchronization in damage propagation and thus prevent recovery. Finally, this study also shows that BDEs on complex networks can lead to metastable relaxation oscillations, which are damped out in one part of a network while moving on to another part.

Interpolation of the Extended Boolean Retrieval Model.

ERIC Educational Resources Information Center

Zanger, Daniel Z.

2002-01-01

Presents an interpolation theorem for an extended Boolean information retrieval model. Results show that whenever two or more documents are similarly ranked at any two points for a query containing exactly two terms, then they are similarly ranked at all points in between; and that results can fail for queries with more than two terms. (Author/LRW)

Effects of topology on network evolution

NASA Astrophysics Data System (ADS)

Oikonomou, Panos; Cluzel, Philippe

2006-08-01

The ubiquity of scale-free topology in nature raises the question of whether this particular network design confers an evolutionary advantage. A series of studies has identified key principles controlling the growth and the dynamics of scale-free networks. Here, we use neuron-based networks of boolean components as a framework for modelling a large class of dynamical behaviours in both natural and artificial systems. Applying a training algorithm, we characterize how networks with distinct topologies evolve towards a pre-established target function through a process of random mutations and selection. We find that homogeneous random networks and scale-free networks exhibit drastically different evolutionary paths. Whereas homogeneous random networks accumulate neutral mutations and evolve by sparse punctuated steps, scale-free networks evolve rapidly and continuously. Remarkably, this latter property is robust to variations of the degree exponent. In contrast, homogeneous random networks require a specific tuning of their connectivity to optimize their ability to evolve. These results highlight an organizing principle that governs the evolution of complex networks and that can improve the design of engineered systems.

3D Boolean operations in virtual surgical planning.

PubMed

Charton, Jerome; Laurentjoye, Mathieu; Kim, Youngjun

2017-10-01

Boolean operations in computer-aided design or computer graphics are a set of operations (e.g. intersection, union, subtraction) between two objects (e.g. a patient model and an implant model) that are important in performing accurate and reproducible virtual surgical planning. This requires accurate and robust techniques that can handle various types of data, such as a surface extracted from volumetric data, synthetic models, and 3D scan data. This article compares the performance of the proposed method (Boolean operations by a robust, exact, and simple method between two colliding shells (BORES)) and an existing method based on the Visualization Toolkit (VTK). In all tests presented in this article, BORES could handle complex configurations as well as report impossible configurations of the input. In contrast, the VTK implementations were unstable, do not deal with singular edges and coplanar collisions, and have created several defects. The proposed method of Boolean operations, BORES, is efficient and appropriate for virtual surgical planning. Moreover, it is simple and easy to implement. In future work, we will extend the proposed method to handle non-colliding components.

The informational architecture of the cell.

PubMed

Walker, Sara Imari; Kim, Hyunju; Davies, Paul C W

2016-03-13

We compare the informational architecture of biological and random networks to identify informational features that may distinguish biological networks from random. The study presented here focuses on the Boolean network model for regulation of the cell cycle of the fission yeast Schizosaccharomyces pombe. We compare calculated values of local and global information measures for the fission yeast cell cycle to the same measures as applied to two different classes of random networks: Erdös-Rényi and scale-free. We report patterns in local information processing and storage that do indeed distinguish biological from random, associated with control nodes that regulate the function of the fission yeast cell-cycle network. Conversely, we find that integrated information, which serves as a global measure of 'emergent' information processing, does not differ from random for the case presented. We discuss implications for our understanding of the informational architecture of the fission yeast cell-cycle network in particular, and more generally for illuminating any distinctive physics that may be operative in life. © 2016 The Author(s).

Boolean Modeling of Neural Systems with Point-Process Inputs and Outputs. Part I: Theory and Simulations

PubMed Central

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

2010-01-01

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). PMID:19517238

Extreme hydroclimatic events and their socio-economic consequences

NASA Astrophysics Data System (ADS)

Ghil, Michael

2017-04-01

This talk will quickly summarize some earlier work reported in [1,2] and then focus on recent work in progress. The former will include two complementary views on the classical, 1300-year long Nile River records. The latter will cover studies of damage propagation in production-and-supply networks [3,4]. Here we use Boolean delay equations (BDEs), a semi-discrete type of dynamical systems [5], to explore the effect of network topology and of the delays in the supply on network resilience. [1] M. Ghil et al., Nonlin. Processes Geophys. (2011) [2] M. Chavez, M. Ghil & J. Urrutia Fucugauchi, Extreme Events: Observations, Modeling and Economics, Geophys. Monograph 214, AGU & Wiley (2015) [3] B. Coluzzi et al., Intl. J. Bifurcation Chaos (2011) [4] C. Colon & M. Ghil, Chaos, submitted (2017) [5] M. Ghil et al., Physica D (2008)

Exploiting Surroundedness for Saliency Detection: A Boolean Map Approach.

PubMed

Zhang, Jianming; Sclaroff, Stan

2016-05-01

We demonstrate the usefulness of surroundedness for eye fixation prediction by proposing a Boolean Map based Saliency model (BMS). In our formulation, an image is characterized by a set of binary images, which are generated by randomly thresholding the image's feature maps in a whitened feature space. Based on a Gestalt principle of figure-ground segregation, BMS computes a saliency map by discovering surrounded regions via topological analysis of Boolean maps. Furthermore, we draw a connection between BMS and the Minimum Barrier Distance to provide insight into why and how BMS can properly captures the surroundedness cue via Boolean maps. The strength of BMS is verified by its simplicity, efficiency and superior performance compared with 10 state-of-the-art methods on seven eye tracking benchmark datasets.

Spatial Rule-Based Modeling: A Method and Its Application to the Human Mitotic Kinetochore

PubMed Central

Ibrahim, Bashar; Henze, Richard; Gruenert, Gerd; Egbert, Matthew; Huwald, Jan; Dittrich, Peter

2013-01-01

A common problem in the analysis of biological systems is the combinatorial explosion that emerges from the complexity of multi-protein assemblies. Conventional formalisms, like differential equations, Boolean networks and Bayesian networks, are unsuitable for dealing with the combinatorial explosion, because they are designed for a restricted state space with fixed dimensionality. To overcome this problem, the rule-based modeling language, BioNetGen, and the spatial extension, SRSim, have been developed. Here, we describe how to apply rule-based modeling to integrate experimental data from different sources into a single spatial simulation model and how to analyze the output of that model. The starting point for this approach can be a combination of molecular interaction data, reaction network data, proximities, binding and diffusion kinetics and molecular geometries at different levels of detail. We describe the technique and then use it to construct a model of the human mitotic inner and outer kinetochore, including the spindle assembly checkpoint signaling pathway. This allows us to demonstrate the utility of the procedure, show how a novel perspective for understanding such complex systems becomes accessible and elaborate on challenges that arise in the formulation, simulation and analysis of spatial rule-based models. PMID:24709796

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

PubMed

Ramírez, Carlos; Mendoza, Luis

2018-04-01

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

Simulating Quantitative Cellular Responses Using Asynchronous Threshold Boolean Network Ensembles

EPA Science Inventory

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

Synchronous versus asynchronous modeling of gene regulatory networks.

PubMed

Garg, Abhishek; Di Cara, Alessandro; Xenarios, Ioannis; Mendoza, Luis; De Micheli, Giovanni

2008-09-01

In silico modeling of gene regulatory networks has gained some momentum recently due to increased interest in analyzing the dynamics of biological systems. This has been further facilitated by the increasing availability of experimental data on gene-gene, protein-protein and gene-protein interactions. The two dynamical properties that are often experimentally testable are perturbations and stable steady states. Although a lot of work has been done on the identification of steady states, not much work has been reported on in silico modeling of cellular differentiation processes. In this manuscript, we provide algorithms based on reduced ordered binary decision diagrams (ROBDDs) for Boolean modeling of gene regulatory networks. Algorithms for synchronous and asynchronous transition models have been proposed and their corresponding computational properties have been analyzed. These algorithms allow users to compute cyclic attractors of large networks that are currently not feasible using existing software. Hereby we provide a framework to analyze the effect of multiple gene perturbation protocols, and their effect on cell differentiation processes. These algorithms were validated on the T-helper model showing the correct steady state identification and Th1-Th2 cellular differentiation process. The software binaries for Windows and Linux platforms can be downloaded from http://si2.epfl.ch/~garg/genysis.html.

Discrete Dynamics Lab

NASA Astrophysics Data System (ADS)

Wuensche, Andrew

DDLab is interactive graphics software for creating, visualizing, and analyzing many aspects of Cellular Automata, Random Boolean Networks, and Discrete Dynamical Networks in general and studying their behavior, both from the time-series perspective — space-time patterns, and from the state-space perspective — attractor basins. DDLab is relevant to research, applications, and education in the fields of complexity, self-organization, emergent phenomena, chaos, collision-based computing, neural networks, content addressable memory, genetic regulatory networks, dynamical encryption, generative art and music, and the study of the abstract mathematical/physical/dynamical phenomena in their own right.

Adaptive parallel logic networks

NASA Technical Reports Server (NTRS)

Martinez, Tony R.; Vidal, Jacques J.

1988-01-01

Adaptive, self-organizing concurrent systems (ASOCS) that combine self-organization with massive parallelism for such applications as adaptive logic devices, robotics, process control, and system malfunction management, are presently discussed. In ASOCS, an adaptive network composed of many simple computing elements operating in combinational and asynchronous fashion is used and problems are specified by presenting if-then rules to the system in the form of Boolean conjunctions. During data processing, which is a different operational phase from adaptation, the network acts as a parallel hardware circuit.

MONOMIALS AND BASIN CYLINDERS FOR NETWORK DYNAMICS.

PubMed

Austin, Daniel; Dinwoodie, Ian H

We describe methods to identify cylinder sets inside a basin of attraction for Boolean dynamics of biological networks. Such sets are used for designing regulatory interventions that make the system evolve towards a chosen attractor, for example initiating apoptosis in a cancer cell. We describe two algebraic methods for identifying cylinders inside a basin of attraction, one based on the Groebner fan that finds monomials that define cylinders and the other on primary decomposition. Both methods are applied to current examples of gene networks.

MONOMIALS AND BASIN CYLINDERS FOR NETWORK DYNAMICS

PubMed Central

AUSTIN, DANIEL; DINWOODIE, IAN H

2014-01-01

We describe methods to identify cylinder sets inside a basin of attraction for Boolean dynamics of biological networks. Such sets are used for designing regulatory interventions that make the system evolve towards a chosen attractor, for example initiating apoptosis in a cancer cell. We describe two algebraic methods for identifying cylinders inside a basin of attraction, one based on the Groebner fan that finds monomials that define cylinders and the other on primary decomposition. Both methods are applied to current examples of gene networks. PMID:25620893

Inferring Toxicological Responses of HepG2 Cells from ...

EPA Pesticide Factsheets

Understanding the dynamic perturbation of cell states by chemicals can aid in for predicting their adverse effects. High-content imaging (HCI) was used to measure the state of HepG2 cells over three time points (1, 24, and 72 h) in response to 976 ToxCast chemicals for 10 different concentrations (0.39-200µM). Cell state was characterized by p53 activation (p53), c-Jun activation (SK), phospho-Histone H2A.x (OS), phospho-Histone H3 (MA), alpha tubulin (Mt), mitochondrial membrane potential (MMP), mitochondrial mass (MM), cell cycle arrest (CCA), nuclear size (NS) and cell number (CN). Dynamic cell state perturbations due to each chemical concentration were utilized to infer coarse-grained dependencies between cellular functions as Boolean networks (BNs). BNs were inferred from data in two steps. First, the data for each state variable were discretized into changed/active (> 1 standard deviation), and unchanged/inactive values. Second, the discretized data were used to learn Boolean relationships between variables. In our case, a BN is a wiring diagram between nodes that represent 10 previously described observable phenotypes. Functional relationships between nodes were represented as Boolean functions. We found that inferred BN show that HepG2 cell response is chemical and concentration specific. We observed presence of both point and cycle BN attractors. In addition, there are instances where Boolean functions were not found. We believe that this may be either

Presentation of Repeated Phrases in a Computer-Assisted Abstracting Tool Kit.

ERIC Educational Resources Information Center

Craven, Timothy C.

2001-01-01

Discusses automatic indexing methods and describes the development of a prototype computerized abstractor's assistant. Highlights include the text network management system, TEXNET; phrase selection that follows indexing; phrase display, including Boolean capabilities; results of preliminary testing; and availability of TEXNET software. (LRW)

Hierarchy of models: From qualitative to quantitative analysis of circadian rhythms in cyanobacteria

NASA Astrophysics Data System (ADS)

Chaves, M.; Preto, M.

2013-06-01

A hierarchy of models, ranging from high to lower levels of abstraction, is proposed to construct "minimal" but predictive and explanatory models of biological systems. Three hierarchical levels will be considered: Boolean networks, piecewise affine differential (PWA) equations, and a class of continuous, ordinary, differential equations' models derived from the PWA model. This hierarchy provides different levels of approximation of the biological system and, crucially, allows the use of theoretical tools to more exactly analyze and understand the mechanisms of the system. The Kai ABC oscillator, which is at the core of the cyanobacterial circadian rhythm, is analyzed as a case study, showing how several fundamental properties—order of oscillations, synchronization when mixing oscillating samples, structural robustness, and entrainment by external cues—can be obtained from basic mechanisms.

Control of complex networks requires both structure and dynamics

NASA Astrophysics Data System (ADS)

Gates, Alexander J.; Rocha, Luis M.

2016-04-01

The study of network structure has uncovered signatures of the organization of complex systems. However, there is also a need to understand how to control them; for example, identifying strategies to revert a diseased cell to a healthy state, or a mature cell to a pluripotent state. Two recent methodologies suggest that the controllability of complex systems can be predicted solely from the graph of interactions between variables, without considering their dynamics: structural controllability and minimum dominating sets. We demonstrate that such structure-only methods fail to characterize controllability when dynamics are introduced. We study Boolean network ensembles of network motifs as well as three models of biochemical regulation: the segment polarity network in Drosophila melanogaster, the cell cycle of budding yeast Saccharomyces cerevisiae, and the floral organ arrangement in Arabidopsis thaliana. We demonstrate that structure-only methods both undershoot and overshoot the number and which sets of critical variables best control the dynamics of these models, highlighting the importance of the actual system dynamics in determining control. Our analysis further shows that the logic of automata transition functions, namely how canalizing they are, plays an important role in the extent to which structure predicts dynamics.

Comparison of stationary and oscillatory dynamics described by differential equations and Boolean maps in transcriptional regulatory circuits

NASA Astrophysics Data System (ADS)

Ye, Weiming; Li, Pengfei; Huang, Xuhui; Xia, Qinzhi; Mi, Yuanyuan; Chen, Runsheng; Hu, Gang

2010-10-01

Exploring the principle and relationship of gene transcriptional regulations (TR) has been becoming a generally researched issue. So far, two major mathematical methods, ordinary differential equation (ODE) method and Boolean map (BM) method have been widely used for these purposes. It is commonly believed that simplified BMs are reasonable approximations of more realistic ODEs, and both methods may reveal qualitatively the same essential features though the dynamical details of both systems may show some differences. In this Letter we exhaustively enumerated all the 3-gene networks and many autonomous randomly constructed TR networks with more genes by using both the ODE and BM methods. In comparison we found that both methods provide practically identical results in most of cases of steady solutions. However, to our great surprise, most of network structures showing periodic cycles with the BM method possess only stationary states in ODE descriptions. These observations strongly suggest that many periodic oscillations and other complicated oscillatory states revealed by the BM rule may be related to the computational errors of variable and time discretizations and rarely have correspondence in realistic biology transcriptional regulatory circuits.

The value of prior knowledge in machine learning of complex network systems.

PubMed

Ferranti, Dana; Krane, David; Craft, David

2017-11-15

Our overall goal is to develop machine-learning approaches based on genomics and other relevant accessible information for use in predicting how a patient will respond to a given proposed drug or treatment. Given the complexity of this problem, we begin by developing, testing and analyzing learning methods using data from simulated systems, which allows us access to a known ground truth. We examine the benefits of using prior system knowledge and investigate how learning accuracy depends on various system parameters as well as the amount of training data available. The simulations are based on Boolean networks-directed graphs with 0/1 node states and logical node update rules-which are the simplest computational systems that can mimic the dynamic behavior of cellular systems. Boolean networks can be generated and simulated at scale, have complex yet cyclical dynamics and as such provide a useful framework for developing machine-learning algorithms for modular and hierarchical networks such as biological systems in general and cancer in particular. We demonstrate that utilizing prior knowledge (in the form of network connectivity information), without detailed state equations, greatly increases the power of machine-learning algorithms to predict network steady-state node values ('phenotypes') and perturbation responses ('drug effects'). Links to codes and datasets here: https://gray.mgh.harvard.edu/people-directory/71-david-craft-phd. dcraft@broadinstitute.org. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Programming Cell Adhesion for On-Chip Sequential Boolean Logic Functions.

PubMed

Qu, Xiangmeng; Wang, Shaopeng; Ge, Zhilei; Wang, Jianbang; Yao, Guangbao; Li, Jiang; Zuo, Xiaolei; Shi, Jiye; Song, Shiping; Wang, Lihua; Li, Li; Pei, Hao; Fan, Chunhai

2017-08-02

Programmable remodelling of cell surfaces enables high-precision regulation of cell behavior. In this work, we developed in vitro constructed DNA-based chemical reaction networks (CRNs) to program on-chip cell adhesion. We found that the RGD-functionalized DNA CRNs are entirely noninvasive when interfaced with the fluidic mosaic membrane of living cells. DNA toehold with different lengths could tunably alter the release kinetics of cells, which shows rapid release in minutes with the use of a 6-base toehold. We further demonstrated the realization of Boolean logic functions by using DNA strand displacement reactions, which include multi-input and sequential cell logic gates (AND, OR, XOR, and AND-OR). This study provides a highly generic tool for self-organization of biological systems.

A procedure concept for local reflex control of grasping

NASA Technical Reports Server (NTRS)

Fiorini, Paolo; Chang, Jeffrey

1989-01-01

An architecture is proposed for the control of robotic devices, and in particular of anthropomorphic hands, characterized by a hierarchical structure in which every level of the architecture contains data and control function with varying degree of abstraction. Bottom levels of the hierarchy interface directly with sensors and actuators, and process raw data and motor commands. Higher levels perform more symbolic types of tasks, such as application of boolean rules and general planning operations. Layers implementation has to be consistent with the type of operation and its requirements for real time control. It is proposed to implement the rule level with a Boolean Artificial Neural Network characterized by a response time sufficient for producing reflex corrective action at the actuator level.

Qualitative dynamics semantics for SBGN process description.

PubMed

Rougny, Adrien; Froidevaux, Christine; Calzone, Laurence; Paulevé, Loïc

2016-06-16

Qualitative dynamics semantics provide a coarse-grain modeling of networks dynamics by abstracting away kinetic parameters. They allow to capture general features of systems dynamics, such as attractors or reachability properties, for which scalable analyses exist. The Systems Biology Graphical Notation Process Description language (SBGN-PD) has become a standard to represent reaction networks. However, no qualitative dynamics semantics taking into account all the main features available in SBGN-PD had been proposed so far. We propose two qualitative dynamics semantics for SBGN-PD reaction networks, namely the general semantics and the stories semantics, that we formalize using asynchronous automata networks. While the general semantics extends standard Boolean semantics of reaction networks by taking into account all the main features of SBGN-PD, the stories semantics allows to model several molecules of a network by a unique variable. The obtained qualitative models can be checked against dynamical properties and therefore validated with respect to biological knowledge. We apply our framework to reason on the qualitative dynamics of a large network (more than 200 nodes) modeling the regulation of the cell cycle by RB/E2F. The proposed semantics provide a direct formalization of SBGN-PD networks in dynamical qualitative models that can be further analyzed using standard tools for discrete models. The dynamics in stories semantics have a lower dimension than the general one and prune multiple behaviors (which can be considered as spurious) by enforcing the mutual exclusiveness between the activity of different nodes of a same story. Overall, the qualitative semantics for SBGN-PD allow to capture efficiently important dynamical features of reaction network models and can be exploited to further refine them.

Modeling bidirectional reflectance of forests and woodlands using Boolean models and geometric optics

NASA Technical Reports Server (NTRS)

Strahler, Alan H.; Jupp, David L. B.

1990-01-01

Geometric-optical discrete-element mathematical models for forest canopies have been developed using the Boolean logic and models of Serra. The geometric-optical approach is considered to be particularly well suited to describing the bidirectional reflectance of forest woodland canopies, where the concentration of leaf material within crowns and the resulting between-tree gaps make plane-parallel, radiative-transfer models inappropriate. The approach leads to invertible formulations, in which the spatial and directional variance provides the means for remote estimation of tree crown size, shape, and total cover from remotedly sensed imagery.

A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis

PubMed Central

Walko, Gernot; Viswanathan, Priyalakshmi; Tihy, Matthieu; Nijjher, Jagdeesh; Dunn, Sara-Jane; Lamond, Angus I

2017-01-01

Epidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition between the two cell states, termed commitment, is poorly understood. Here, we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension to induce differentiation. Cell detachment induces several protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA – promote differentiation by negatively regulating ERK MAPK and positively regulating AP1 transcription factors. Conversely, DUSP10 expression antagonises commitment. The phosphatases form a dynamic network of transient positive and negative interactions that change over time, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem and differentiated) via an unstable (committed) state. Phosphatase expression is also spatially regulated in vivo and in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment. PMID:29043977

A Clinical Decision Support System for Breast Cancer Patients

NASA Astrophysics Data System (ADS)

Fernandes, Ana S.; Alves, Pedro; Jarman, Ian H.; Etchells, Terence A.; Fonseca, José M.; Lisboa, Paulo J. G.

This paper proposes a Web clinical decision support system for clinical oncologists and for breast cancer patients making prognostic assessments, using the particular characteristics of the individual patient. This system comprises three different prognostic modelling methodologies: the clinically widely used Nottingham prognostic index (NPI); the Cox regression modelling and a partial logistic artificial neural network with automatic relevance determination (PLANN-ARD). All three models yield a different prognostic index that can be analysed together in order to obtain a more accurate prognostic assessment of the patient. Missing data is incorporated in the mentioned models, a common issue in medical data that was overcome using multiple imputation techniques. Risk group assignments are also provided through a methodology based on regression trees, where Boolean rules can be obtained expressed with patient characteristics.

Boolean and brain-inspired computing using spin-transfer torque devices

NASA Astrophysics Data System (ADS)

Fan, Deliang

Several completely new approaches (such as spintronic, carbon nanotube, graphene, TFETs, etc.) to information processing and data storage technologies are emerging to address the time frame beyond current Complementary Metal-Oxide-Semiconductor (CMOS) roadmap. The high speed magnetization switching of a nano-magnet due to current induced spin-transfer torque (STT) have been demonstrated in recent experiments. Such STT devices can be explored in compact, low power memory and logic design. In order to truly leverage STT devices based computing, researchers require a re-think of circuit, architecture, and computing model, since the STT devices are unlikely to be drop-in replacements for CMOS. The potential of STT devices based computing will be best realized by considering new computing models that are inherently suited to the characteristics of STT devices, and new applications that are enabled by their unique capabilities, thereby attaining performance that CMOS cannot achieve. The goal of this research is to conduct synergistic exploration in architecture, circuit and device levels for Boolean and brain-inspired computing using nanoscale STT devices. Specifically, we first show that the non-volatile STT devices can be used in designing configurable Boolean logic blocks. We propose a spin-memristor threshold logic (SMTL) gate design, where memristive cross-bar array is used to perform current mode summation of binary inputs and the low power current mode spintronic threshold device carries out the energy efficient threshold operation. Next, for brain-inspired computing, we have exploited different spin-transfer torque device structures that can implement the hard-limiting and soft-limiting artificial neuron transfer functions respectively. We apply such STT based neuron (or 'spin-neuron') in various neural network architectures, such as hierarchical temporal memory and feed-forward neural network, for performing "human-like" cognitive computing, which show more than two orders of lower energy consumption compared to state of the art CMOS implementation. Finally, we show the dynamics of injection locked Spin Hall Effect Spin-Torque Oscillator (SHE-STO) cluster can be exploited as a robust multi-dimensional distance metric for associative computing, image/ video analysis, etc. Our simulation results show that the proposed system architecture with injection locked SHE-STOs and the associated CMOS interface circuits can be suitable for robust and energy efficient associative computing and pattern matching.

Managing biological networks by using text mining and computer-aided curation

NASA Astrophysics Data System (ADS)

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.

Core regulatory network motif underlies the ocellar complex patterning in Drosophila melanogaster

NASA Astrophysics Data System (ADS)

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.

The Boolean Is Dead, Long Live the Boolean! Natural Language versus Boolean Searching in Introductory Undergraduate Instruction

ERIC Educational Resources Information Center

Lowe, M. Sara; Maxson, Bronwen K.; Stone, Sean M.; Miller, Willie; Snajdr, Eric; Hanna, Kathleen

2018-01-01

Boolean logic can be a difficult concept for first-year, introductory students to grasp. This paper compares the results of Boolean and natural language searching across several databases with searches created from student research questions. Performance differences between databases varied. Overall, natural search language is at least as good as…

Discovery of Boolean metabolic networks: integer linear programming based approach.

PubMed

Qiu, Yushan; Jiang, Hao; Ching, Wai-Ki; Cheng, Xiaoqing

2018-04-11

Traditional drug discovery methods focused on the efficacy of drugs rather than their toxicity. However, toxicity and/or lack of efficacy are produced when unintended targets are affected in metabolic networks. Thus, identification of biological targets which can be manipulated to produce the desired effect with minimum side-effects has become an important and challenging topic. Efficient computational methods are required to identify the drug targets while incurring minimal side-effects. In this paper, we propose a graph-based computational damage model that summarizes the impact of enzymes on compounds in metabolic networks. An efficient method based on Integer Linear Programming formalism is then developed to identify the optimal enzyme-combination so as to minimize the side-effects. The identified target enzymes for known successful drugs are then verified by comparing the results with those in the existing literature. Side-effects reduction plays a crucial role in the study of drug development. A graph-based computational damage model is proposed and the theoretical analysis states the captured problem is NP-completeness. The proposed approaches can therefore contribute to the discovery of drug targets. Our developed software is available at " http://hkumath.hku.hk/~wkc/APBC2018-metabolic-network.zip ".

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation.

PubMed

Polak, Marta E; Ung, Chuin Ying; Masapust, Joanna; Freeman, Tom C; Ardern-Jones, Michael R

2017-04-06

Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis. Applying Boolean logic we assembled a Petri net-based model of the IRF-GRN which provides molecular pathway predictions for the induction of different transcriptional programmes in LCs. In silico simulations performed after model parameterisation with transcription factor expression values predicted that human LC activation of antigen-specific CD8 T cells would be differentially regulated by epidermal cytokine induction of specific IRF-controlled pathways. This was confirmed by in vitro measurement of IFN-γ production by activated T cells. As a proof of concept, this approach shows that stochastic modelling of a specific immune networks renders transcriptome data valuable for the prediction of functional outcomes of immune responses.

Network Frontier Workshop 2013

DTIC Science & Technology

2014-11-11

between Resources on Nodes and Weighted Connections 3:45 – 4:15 Coffee Break Schedule 4:15 – 5:00 Bruce J . West (Army Research Office, USA)Tutorial...of Boolean Networks: The Joint Effect of Topology and Update Rules 3:40 – 4:10 Coffee Break 4:10 – 4:45 Peter J . Mucha (University of North Carolina...indicates a crucial smart design principle for tomorrow’s sustainable power grids: add just a few more lines to avoid dead ends. Reference: P. Menck, J

Cryptographic Boolean Functions with Biased Inputs

DTIC Science & Technology

2015-07-31

theory of random graphs developed by Erdős and Rényi [2]. The graph properties in a random graph expressed as such Boolean functions are used by...distributed Bernoulli variates with the parameter p. Since our scope is within the area of cryptography , we initiate an analysis of cryptographic...Boolean functions with biased inputs, which we refer to as µp-Boolean functions, is a common generalization of Boolean functions which stems from the

Evolutionary Algorithms for Boolean Functions in Diverse Domains of Cryptography.

PubMed

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.

A Simple Blueprint for Automatic Boolean Query Processing.

ERIC Educational Resources Information Center

Salton, G.

1988-01-01

Describes a new Boolean retrieval environment in which an extended soft Boolean logic is used to automatically construct queries from original natural language formulations provided by users. Experimental results that compare the retrieval effectiveness of this method to conventional Boolean and vector processing are discussed. (27 references)…

Neurotrophic factors switch between two signaling pathways that trigger axonal growth.

PubMed

Paveliev, Mikhail; Lume, Maria; Velthut, Agne; Phillips, Matthew; Arumäe, Urmas; Saarma, Mart

2007-08-01

Integration of multiple inputs from the extracellular environment, such as extracellular matrix molecules and growth factors, is a crucial process for cell function and information processing in multicellular organisms. Here we demonstrate that co-stimulation of dorsal root ganglion neurons with neurotrophic factors (NTFs) - glial-cell-line-derived neurotrophic factor, neurturin or nerve growth factor - and laminin leads to axonal growth that requires activation of Src family kinases (SFKs). A different, SFK-independent signaling pathway evokes axonal growth on laminin in the absence of the NTFs. By contrast, axonal branching is regulated by SFKs both in the presence and in the absence of NGF. We propose and experimentally verify a Boolean model of the signaling network triggered by NTFs and laminin. Our results demonstrate that NTFs provide an environmental cue that triggers a switch between separate pathways in the cell signaling network.

Target Control in Logical Models Using the Domain of Influence of Nodes.

PubMed

Yang, Gang; Gómez Tejeda Zañudo, Jorge; Albert, Réka

2018-01-01

Dynamical models of biomolecular networks are successfully used to understand the mechanisms underlying complex diseases and to design therapeutic strategies. Network control and its special case of target control, is a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system's state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis (programmed cell death). From the experimental perspective, gene knockout, pharmacological inhibition of proteins, and providing sustained external signals are among practical intervention techniques. We identify methodologies to use the stabilizing effect of sustained interventions for target control in Boolean network models of biomolecular networks. Specifically, we define the domain of influence (DOI) of a node (in a certain state) to be the nodes (and their corresponding states) that will be ultimately stabilized by the sustained state of this node regardless of the initial state of the system. We also define the related concept of the logical domain of influence (LDOI) of a node, and develop an algorithm for its identification using an auxiliary network that incorporates the regulatory logic. This way a solution to the target control problem is a set of nodes whose DOI can cover the desired target node states. We perform greedy randomized adaptive search in node state space to find such solutions. We apply our strategy to in silico biological network models of real systems to demonstrate its effectiveness.

CellNOptR: a flexible toolkit to train protein signaling networks to data using multiple logic formalisms.

PubMed

Terfve, Camille; Cokelaer, Thomas; Henriques, David; MacNamara, Aidan; Goncalves, Emanuel; Morris, Melody K; van Iersel, Martijn; Lauffenburger, Douglas A; Saez-Rodriguez, Julio

2012-10-18

Cells process signals using complex and dynamic networks. Studying how this is performed in a context and cell type specific way is essential to understand signaling both in physiological and diseased situations. Context-specific medium/high throughput proteomic data measured upon perturbation is now relatively easy to obtain but formalisms that can take advantage of these features to build models of signaling are still comparatively scarce. Here we present CellNOptR, an open-source R software package for building predictive logic models of signaling networks by training networks derived from prior knowledge to signaling (typically phosphoproteomic) data. CellNOptR features different logic formalisms, from Boolean models to differential equations, in a common framework. These different logic model representations accommodate state and time values with increasing levels of detail. We provide in addition an interface via Cytoscape (CytoCopteR) to facilitate use and integration with Cytoscape network-based capabilities. Models generated with this pipeline have two key features. First, they are constrained by prior knowledge about the network but trained to data. They are therefore context and cell line specific, which results in enhanced predictive and mechanistic insights. Second, they can be built using different logic formalisms depending on the richness of the available data. Models built with CellNOptR are useful tools to understand how signals are processed by cells and how this is altered in disease. They can be used to predict the effect of perturbations (individual or in combinations), and potentially to engineer therapies that have differential effects/side effects depending on the cell type or context.

CellNOptR: a flexible toolkit to train protein signaling networks to data using multiple logic formalisms

PubMed Central

2012-01-01

Background Cells process signals using complex and dynamic networks. Studying how this is performed in a context and cell type specific way is essential to understand signaling both in physiological and diseased situations. Context-specific medium/high throughput proteomic data measured upon perturbation is now relatively easy to obtain but formalisms that can take advantage of these features to build models of signaling are still comparatively scarce. Results Here we present CellNOptR, an open-source R software package for building predictive logic models of signaling networks by training networks derived from prior knowledge to signaling (typically phosphoproteomic) data. CellNOptR features different logic formalisms, from Boolean models to differential equations, in a common framework. These different logic model representations accommodate state and time values with increasing levels of detail. We provide in addition an interface via Cytoscape (CytoCopteR) to facilitate use and integration with Cytoscape network-based capabilities. Conclusions Models generated with this pipeline have two key features. First, they are constrained by prior knowledge about the network but trained to data. They are therefore context and cell line specific, which results in enhanced predictive and mechanistic insights. Second, they can be built using different logic formalisms depending on the richness of the available data. Models built with CellNOptR are useful tools to understand how signals are processed by cells and how this is altered in disease. They can be used to predict the effect of perturbations (individual or in combinations), and potentially to engineer therapies that have differential effects/side effects depending on the cell type or context. PMID:23079107

On the Computation of Comprehensive Boolean Gröbner Bases

NASA Astrophysics Data System (ADS)

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.

Mining TCGA Data Using Boolean Implications

PubMed Central

Sinha, Subarna; Tsang, Emily K.; Zeng, Haoyang; Meister, Michela; Dill, David L.

2014-01-01

Boolean implications (if-then rules) provide a conceptually simple, uniform and highly scalable way to find associations between pairs of random variables. In this paper, we propose to use Boolean implications to find relationships between variables of different data types (mutation, copy number alteration, DNA methylation and gene expression) from the glioblastoma (GBM) and ovarian serous cystadenoma (OV) data sets from The Cancer Genome Atlas (TCGA). We find hundreds of thousands of Boolean implications from these data sets. A direct comparison of the relationships found by Boolean implications and those found by commonly used methods for mining associations show that existing methods would miss relationships found by Boolean implications. Furthermore, many relationships exposed by Boolean implications reflect important aspects of cancer biology. Examples of our findings include cis relationships between copy number alteration, DNA methylation and expression of genes, a new hierarchy of mutations and recurrent copy number alterations, loss-of-heterozygosity of well-known tumor suppressors, and the hypermethylation phenotype associated with IDH1 mutations in GBM. The Boolean implication results used in the paper can be accessed at http://crookneck.stanford.edu/microarray/TCGANetworks/. PMID:25054200

Hybrid Modeling of Cell Signaling and Transcriptional Reprogramming and Its Application in C. elegans Development.

PubMed

Fertig, Elana J; Danilova, Ludmila V; Favorov, Alexander V; Ochs, Michael F

2011-01-01

Modeling of signal driven transcriptional reprogramming is critical for understanding of organism development, human disease, and cell biology. Many current modeling techniques discount key features of the biological sub-systems when modeling multiscale, organism-level processes. We present a mechanistic hybrid model, GESSA, which integrates a novel pooled probabilistic Boolean network model of cell signaling and a stochastic simulation of transcription and translation responding to a diffusion model of extracellular signals. We apply the model to simulate the well studied cell fate decision process of the vulval precursor cells (VPCs) in C. elegans, using experimentally derived rate constants wherever possible and shared parameters to avoid overfitting. We demonstrate that GESSA recovers (1) the effects of varying scaffold protein concentration on signal strength, (2) amplification of signals in expression, (3) the relative external ligand concentration in a known geometry, and (4) feedback in biochemical networks. We demonstrate that setting model parameters based on wild-type and LIN-12 loss-of-function mutants in C. elegans leads to correct prediction of a wide variety of mutants including partial penetrance of phenotypes. Moreover, the model is relatively insensitive to parameters, retaining the wild-type phenotype for a wide range of cell signaling rate parameters.

A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle.

PubMed

Linke, Christian; Chasapi, Anastasia; González-Novo, Alberto; Al Sawad, Istabrak; Tognetti, Silvia; Klipp, Edda; Loog, Mart; Krobitsch, Sylvia; Posas, Francesc; Xenarios, Ioannis; Barberis, Matteo

2017-01-01

Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates their expression in a timely fashion. Here, we demonstrate that a Clb/Cdk1-mediated regulation of the Fkh2 transcription factor synchronizes the temporal mitotic CLB expression in budding yeast. A simplified kinetic model of the cyclin/Cdk network predicts a linear cascade where a Clb/Cdk1-mediated regulation of an activator molecule drives CLB3 and CLB2 expression. Experimental validation highlights Fkh2 as modulator of CLB3 transcript levels, besides its role in regulating CLB2 expression. A Boolean model based on the minimal number of interactions needed to capture the information flow of the Clb/Cdk1 network supports the role of an activator molecule in the sequential activation, and oscillatory behavior, of mitotic Clb cyclins. This work illustrates how transcription and phosphorylation networks can be coupled by a Clb/Cdk1-mediated regulation that synchronizes them.

Cut set-based risk and reliability analysis for arbitrarily interconnected networks

DOEpatents

Wyss, Gregory D.

2000-01-01

Method for computing all-terminal reliability for arbitrarily interconnected networks such as the United States public switched telephone network. The method includes an efficient search algorithm to generate minimal cut sets for nonhierarchical networks directly from the network connectivity diagram. Efficiency of the search algorithm stems in part from its basis on only link failures. The method also includes a novel quantification scheme that likewise reduces computational effort associated with assessing network reliability based on traditional risk importance measures. Vast reductions in computational effort are realized since combinatorial expansion and subsequent Boolean reduction steps are eliminated through analysis of network segmentations using a technique of assuming node failures to occur on only one side of a break in the network, and repeating the technique for all minimal cut sets generated with the search algorithm. The method functions equally well for planar and non-planar networks.

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

PubMed

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.

Combinatorial explosion in model gene networks

NASA Astrophysics Data System (ADS)

Edwards, R.; Glass, L.

2000-09-01

The explosive growth in knowledge of the genome of humans and other organisms leaves open the question of how the functioning of genes in interacting networks is coordinated for orderly activity. One approach to this problem is to study mathematical properties of abstract network models that capture the logical structures of gene networks. The principal issue is to understand how particular patterns of activity can result from particular network structures, and what types of behavior are possible. We study idealized models in which the logical structure of the network is explicitly represented by Boolean functions that can be represented by directed graphs on n-cubes, but which are continuous in time and described by differential equations, rather than being updated synchronously via a discrete clock. The equations are piecewise linear, which allows significant analysis and facilitates rapid integration along trajectories. We first give a combinatorial solution to the question of how many distinct logical structures exist for n-dimensional networks, showing that the number increases very rapidly with n. We then outline analytic methods that can be used to establish the existence, stability and periods of periodic orbits corresponding to particular cycles on the n-cube. We use these methods to confirm the existence of limit cycles discovered in a sample of a million randomly generated structures of networks of 4 genes. Even with only 4 genes, at least several hundred different patterns of stable periodic behavior are possible, many of them surprisingly complex. We discuss ways of further classifying these periodic behaviors, showing that small mutations (reversal of one or a few edges on the n-cube) need not destroy the stability of a limit cycle. Although these networks are very simple as models of gene networks, their mathematical transparency reveals relationships between structure and behavior, they suggest that the possibilities for orderly dynamics in such networks are extremely rich and they offer novel ways to think about how mutations can alter dynamics.

Combinatorial explosion in model gene networks.

PubMed

Edwards, R.; Glass, L.

2000-09-01

The explosive growth in knowledge of the genome of humans and other organisms leaves open the question of how the functioning of genes in interacting networks is coordinated for orderly activity. One approach to this problem is to study mathematical properties of abstract network models that capture the logical structures of gene networks. The principal issue is to understand how particular patterns of activity can result from particular network structures, and what types of behavior are possible. We study idealized models in which the logical structure of the network is explicitly represented by Boolean functions that can be represented by directed graphs on n-cubes, but which are continuous in time and described by differential equations, rather than being updated synchronously via a discrete clock. The equations are piecewise linear, which allows significant analysis and facilitates rapid integration along trajectories. We first give a combinatorial solution to the question of how many distinct logical structures exist for n-dimensional networks, showing that the number increases very rapidly with n. We then outline analytic methods that can be used to establish the existence, stability and periods of periodic orbits corresponding to particular cycles on the n-cube. We use these methods to confirm the existence of limit cycles discovered in a sample of a million randomly generated structures of networks of 4 genes. Even with only 4 genes, at least several hundred different patterns of stable periodic behavior are possible, many of them surprisingly complex. We discuss ways of further classifying these periodic behaviors, showing that small mutations (reversal of one or a few edges on the n-cube) need not destroy the stability of a limit cycle. Although these networks are very simple as models of gene networks, their mathematical transparency reveals relationships between structure and behavior, they suggest that the possibilities for orderly dynamics in such networks are extremely rich and they offer novel ways to think about how mutations can alter dynamics. (c) 2000 American Institute of Physics.

A methodology for risk analysis based on hybrid Bayesian networks: application to the regasification system of liquefied natural gas onboard a floating storage and regasification unit.

PubMed

Martins, Marcelo Ramos; Schleder, Adriana Miralles; Droguett, Enrique López

2014-12-01

This article presents an iterative six-step risk analysis methodology based on hybrid Bayesian networks (BNs). In typical risk analysis, systems are usually modeled as discrete and Boolean variables with constant failure rates via fault trees. Nevertheless, in many cases, it is not possible to perform an efficient analysis using only discrete and Boolean variables. The approach put forward by the proposed methodology makes use of BNs and incorporates recent developments that facilitate the use of continuous variables whose values may have any probability distributions. Thus, this approach makes the methodology particularly useful in cases where the available data for quantification of hazardous events probabilities are scarce or nonexistent, there is dependence among events, or when nonbinary events are involved. The methodology is applied to the risk analysis of a regasification system of liquefied natural gas (LNG) on board an FSRU (floating, storage, and regasification unit). LNG is becoming an important energy source option and the world's capacity to produce LNG is surging. Large reserves of natural gas exist worldwide, particularly in areas where the resources exceed the demand. Thus, this natural gas is liquefied for shipping and the storage and regasification process usually occurs at onshore plants. However, a new option for LNG storage and regasification has been proposed: the FSRU. As very few FSRUs have been put into operation, relevant failure data on FSRU systems are scarce. The results show the usefulness of the proposed methodology for cases where the risk analysis must be performed under considerable uncertainty. © 2014 Society for Risk Analysis.

Stochasticity versus determinism: consequences for realistic gene regulatory network modelling and evolution.

PubMed

Jenkins, Dafyd J; Stekel, Dov J

2010-02-01

Gene regulation is one important mechanism in producing observed phenotypes and heterogeneity. Consequently, the study of gene regulatory network (GRN) architecture, function and evolution now forms a major part of modern biology. However, it is impossible to experimentally observe the evolution of GRNs on the timescales on which living species evolve. In silico evolution provides an approach to studying the long-term evolution of GRNs, but many models have either considered network architecture from non-adaptive evolution, or evolution to non-biological objectives. Here, we address a number of important modelling and biological questions about the evolution of GRNs to the realistic goal of biomass production. Can different commonly used simulation paradigms, in particular deterministic and stochastic Boolean networks, with and without basal gene expression, be used to compare adaptive with non-adaptive evolution of GRNs? Are these paradigms together with this goal sufficient to generate a range of solutions? Will the interaction between a biological goal and evolutionary dynamics produce trade-offs between growth and mutational robustness? We show that stochastic basal gene expression forces shrinkage of genomes due to energetic constraints and is a prerequisite for some solutions. In systems that are able to evolve rates of basal expression, two optima, one with and one without basal expression, are observed. Simulation paradigms without basal expression generate bloated networks with non-functional elements. Further, a range of functional solutions was observed under identical conditions only in stochastic networks. Moreover, there are trade-offs between efficiency and yield, indicating an inherent intertwining of fitness and evolutionary dynamics.

Determining the transport mechanism of an enzyme-catalytic complex metabolic network based on biological robustness.

PubMed

Wang, Lei

2013-04-01

Understanding the transport mechanism of 1,3-propanediol (1,3-PD) is of critical importance to do further research on gene regulation. Due to the lack of intracellular information, on the basis of enzyme-catalytic system, using biological robustness as performance index, we present a system identification model to infer the most possible transport mechanism of 1,3-PD, in which the performance index consists of the relative error of the extracellular substance concentrations and biological robustness of the intracellular substance concentrations. We will not use a Boolean framework but prefer a model description based on ordinary differential equations. Among other advantages, this also facilitates the robustness analysis, which is the main goal of this paper. An algorithm is constructed to seek the solution of the identification model. Numerical results show that the most possible transport way is active transport coupled with passive diffusion.

Development of Boolean calculus and its application

NASA Technical Reports Server (NTRS)

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.

Quantifying Performance Bias in Label Fusion

DTIC Science & Technology

2012-08-21

detect ), may provide the end-user with the means to appropriately adjust the performance and optimal thresholds for performance by fusing legacy systems...boolean combination of classification systems in ROC space: An application to anomaly detection with HMMs. Pattern Recognition, 43(8), 2732-2752. 10...Shamsuddin, S. (2009). An overview of neural networks use in anomaly intrusion detection systems. Paper presented at the Research and Development (SCOReD

Boolean integral calculus

NASA Technical Reports Server (NTRS)

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.

Criticality Is an Emergent Property of Genetic Networks that Exhibit Evolvability

PubMed Central

Torres-Sosa, Christian; Huang, Sui; Aldana, Maximino

2012-01-01

Accumulating experimental evidence suggests that the gene regulatory networks of living organisms operate in the critical phase, namely, at the transition between ordered and chaotic dynamics. Such critical dynamics of the network permits the coexistence of robustness and flexibility which are necessary to ensure homeostatic stability (of a given phenotype) while allowing for switching between multiple phenotypes (network states) as occurs in development and in response to environmental change. However, the mechanisms through which genetic networks evolve such critical behavior have remained elusive. Here we present an evolutionary model in which criticality naturally emerges from the need to balance between the two essential components of evolvability: phenotype conservation and phenotype innovation under mutations. We simulated the Darwinian evolution of random Boolean networks that mutate gene regulatory interactions and grow by gene duplication. The mutating networks were subjected to selection for networks that both (i) preserve all the already acquired phenotypes (dynamical attractor states) and (ii) generate new ones. Our results show that this interplay between extending the phenotypic landscape (innovation) while conserving the existing phenotypes (conservation) suffices to cause the evolution of all the networks in a population towards criticality. Furthermore, the networks produced by this evolutionary process exhibit structures with hubs (global regulators) similar to the observed topology of real gene regulatory networks. Thus, dynamical criticality and certain elementary topological properties of gene regulatory networks can emerge as a byproduct of the evolvability of the phenotypic landscape. PMID:22969419

Automatic query formulations in information retrieval.

PubMed

Salton, G; Buckley, C; Fox, E A

1983-07-01

Modern information retrieval systems are designed to supply relevant information in response to requests received from the user population. In most retrieval environments the search requests consist of keywords, or index terms, interrelated by appropriate Boolean operators. Since it is difficult for untrained users to generate effective Boolean search requests, trained search intermediaries are normally used to translate original statements of user need into useful Boolean search formulations. Methods are introduced in this study which reduce the role of the search intermediaries by making it possible to generate Boolean search formulations completely automatically from natural language statements provided by the system patrons. Frequency considerations are used automatically to generate appropriate term combinations as well as Boolean connectives relating the terms. Methods are covered to produce automatic query formulations both in a standard Boolean logic system, as well as in an extended Boolean system in which the strict interpretation of the connectives is relaxed. Experimental results are supplied to evaluate the effectiveness of the automatic query formulation process, and methods are described for applying the automatic query formulation process in practice.

Sig2GRN: a software tool linking signaling pathway with gene regulatory network for dynamic simulation.

PubMed

Zhang, Fan; Liu, Runsheng; Zheng, Jie

2016-12-23

Linking computational models of signaling pathways to predicted cellular responses such as gene expression regulation is a major challenge in computational systems biology. In this work, we present Sig2GRN, a Cytoscape plugin that is able to simulate time-course gene expression data given the user-defined external stimuli to the signaling pathways. A generalized logical model is used in modeling the upstream signaling pathways. Then a Boolean model and a thermodynamics-based model are employed to predict the downstream changes in gene expression based on the simulated dynamics of transcription factors in signaling pathways. Our empirical case studies show that the simulation of Sig2GRN can predict changes in gene expression patterns induced by DNA damage signals and drug treatments. As a software tool for modeling cellular dynamics, Sig2GRN can facilitate studies in systems biology by hypotheses generation and wet-lab experimental design. http://histone.scse.ntu.edu.sg/Sig2GRN/.

Proposed method to construct Boolean functions with maximum possible annihilator immunity

NASA Astrophysics Data System (ADS)

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.

New scaling relation for information transfer in biological networks

PubMed Central

Kim, Hyunju; Davies, Paul; Walker, Sara Imari

2015-01-01

We quantify characteristics of the informational architecture of two representative biological networks: the Boolean network model for the cell-cycle regulatory network of the fission yeast Schizosaccharomyces pombe (Davidich et al. 2008 PLoS ONE 3, e1672 (doi:10.1371/journal.pone.0001672)) and that of the budding yeast Saccharomyces cerevisiae (Li et al. 2004 Proc. Natl Acad. Sci. USA 101, 4781–4786 (doi:10.1073/pnas.0305937101)). We compare our results for these biological networks with the same analysis performed on ensembles of two different types of random networks: Erdös–Rényi and scale-free. We show that both biological networks share features in common that are not shared by either random network ensemble. In particular, the biological networks in our study process more information than the random networks on average. Both biological networks also exhibit a scaling relation in information transferred between nodes that distinguishes them from random, where the biological networks stand out as distinct even when compared with random networks that share important topological properties, such as degree distribution, with the biological network. We show that the most biologically distinct regime of this scaling relation is associated with a subset of control nodes that regulate the dynamics and function of each respective biological network. Information processing in biological networks is therefore interpreted as an emergent property of topology (causal structure) and dynamics (function). Our results demonstrate quantitatively how the informational architecture of biologically evolved networks can distinguish them from other classes of network architecture that do not share the same informational properties. PMID:26701883

Elementary signaling modes predict the essentiality of signal transduction network components

PubMed Central

2011-01-01

Background Understanding how signals propagate through signaling pathways and networks is a central goal in systems biology. Quantitative dynamic models help to achieve this understanding, but are difficult to construct and validate because of the scarcity of known mechanistic details and kinetic parameters. Structural and qualitative analysis is emerging as a feasible and useful alternative for interpreting signal transduction. Results In this work, we present an integrative computational method for evaluating the essentiality of components in signaling networks. This approach expands an existing signaling network to a richer representation that incorporates the positive or negative nature of interactions and the synergistic behaviors among multiple components. Our method simulates both knockout and constitutive activation of components as node disruptions, and takes into account the possible cascading effects of a node's disruption. We introduce the concept of elementary signaling mode (ESM), as the minimal set of nodes that can perform signal transduction independently. Our method ranks the importance of signaling components by the effects of their perturbation on the ESMs of the network. Validation on several signaling networks describing the immune response of mammals to bacteria, guard cell abscisic acid signaling in plants, and T cell receptor signaling shows that this method can effectively uncover the essentiality of components mediating a signal transduction process and results in strong agreement with the results of Boolean (logical) dynamic models and experimental observations. Conclusions This integrative method is an efficient procedure for exploratory analysis of large signaling and regulatory networks where dynamic modeling or experimental tests are impractical. Its results serve as testable predictions, provide insights into signal transduction and regulatory mechanisms and can guide targeted computational or experimental follow-up studies. The source codes for the algorithms developed in this study can be found at http://www.phys.psu.edu/~ralbert/ESM. PMID:21426566

Robust optimization with transiently chaotic dynamical systems

NASA Astrophysics Data System (ADS)

Sumi, R.; Molnár, B.; Ercsey-Ravasz, M.

2014-05-01

Efficiently solving hard optimization problems has been a strong motivation for progress in analog computing. In a recent study we presented a continuous-time dynamical system for solving the NP-complete Boolean satisfiability (SAT) problem, with a one-to-one correspondence between its stable attractors and the SAT solutions. While physical implementations could offer great efficiency, the transiently chaotic dynamics raises the question of operability in the presence of noise, unavoidable on analog devices. Here we show that the probability of finding solutions is robust to noise intensities well above those present on real hardware. We also developed a cellular neural network model realizable with analog circuits, which tolerates even larger noise intensities. These methods represent an opportunity for robust and efficient physical implementations.

Mammalian synthetic biology: emerging medical applications

PubMed Central

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

All optical logic for optical pattern recognition and networking applications

NASA Astrophysics Data System (ADS)

Khoury, Jed

2017-05-01

In this paper, we propose architectures for the implementation 16 Boolean optical gates from two inputs using externally pumped phase- conjugate Michelson interferometer. Depending on the gate to be implemented, some require single stage interferometer and others require two stages interferometer. The proposed optical gates can be used in several applications in optical networks including, but not limited to, all-optical packet routers switching, and all-optical error detection. The optical logic gates can also be used in recognition of noiseless rotation and scale invariant objects such as finger prints for home land security applications.

Improvements in metabolic flux analysis using carbon bond labeling experiments: bondomer balancing and Boolean function mapping.

PubMed

Sriram, Ganesh; Shanks, Jacqueline V

2004-04-01

The biosynthetically directed fractional (13)C labeling method for metabolic flux evaluation relies on performing a 2-D [(13)C, (1)H] NMR experiment on extracts from organisms cultured on a uniformly labeled carbon substrate. This article focuses on improvements in the interpretation of data obtained from such an experiment by employing the concept of bondomers. Bondomers take into account the natural abundance of (13)C; therefore many bondomers in a real network are zero, and can be precluded a priori--thus resulting in fewer balances. Using this method, we obtained a set of linear equations which can be solved to obtain analytical formulas for NMR-measurable quantities in terms of fluxes in glycolysis and the pentose phosphate pathways. For a specific case of this network with four degrees of freedom, a priori identifiability of the fluxes was shown possible for any set of fluxes. For a more general case with five degrees of freedom, the fluxes were shown identifiable for a representative set of fluxes. Minimal sets of measurements which best identify the fluxes are listed. Furthermore, we have delineated Boolean function mapping, a new method to iteratively simulate bondomer abundances or efficiently convert carbon skeleton rearrangement information to mapping matrices. The efficiency of this method is expected to be valuable while analyzing metabolic networks which are not completely known (such as in plant metabolism) or while implementing iterative bondomer balancing methods.

Model Checking of a Diabetes-Cancer Model

NASA Astrophysics Data System (ADS)

Gong, Haijun; Zuliani, Paolo; Clarke, Edmund M.

2011-06-01

Accumulating evidence suggests that cancer incidence might be associated with diabetes mellitus, especially Type II diabetes which is characterized by hyperinsulinaemia, hyperglycaemia, obesity, and overexpression of multiple WNT pathway components. These diabetes risk factors can activate a number of signaling pathways that are important in the development of different cancers. To systematically understand the signaling components that link diabetes and cancer risk, we have constructed a single-cell, Boolean network model by integrating the signaling pathways that are influenced by these risk factors to study insulin resistance, cancer cell proliferation and apoptosis. Then, we introduce and apply the Symbolic Model Verifier (SMV), a formal verification tool, to qualitatively study some temporal logic properties of our diabetes-cancer model. The verification results show that the diabetes risk factors might not increase cancer risk in normal cells, but they will promote cell proliferation if the cell is in a precancerous or cancerous stage characterized by losses of the tumor-suppressor proteins ARF and INK4a.

The Event Based Language and Its Multiple Processor Implementations.

DTIC Science & Technology

1980-01-01

10 6.1 "Recursive" Linear Fibonacci ................................................ 105 6.2 The Readers Writers Problem...kinds. Examples of such systems are: C.mmp [Wu-72], Pluribus [He-73], Data Flow [ De -75], the boolean n-cube parallel machine [Su-77], and the MuNet [Wa...concurrency within programs; therefore, we hate concentrated on two types of systems which seem suitable: a processor network, and a data flow processor [ De -77

Consistent Correlations for Parameterised Boolean Equation Systems with Applications in Correctness Proofs for Manipulations

NASA Astrophysics Data System (ADS)

Willemse, Tim A. C.

We introduce the concept of consistent correlations for parameterised Boolean equation systems (PBESs), motivated largely by the laborious proofs of correctness required for most manipulations in this setting. Consistent correlations focus on relating the equations that occur in PBESs, rather than their solutions. For a fragment of PBESs, consistent correlations are shown to coincide with a recently introduced form of bisimulation. Finally, we show that bisimilarity on processes induces consistent correlations on PBESs encoding model checking problems. We apply our theory to two example manipulations from the literature.

Mathematical Model of a Telomerase Transcriptional Regulatory Network Developed by Cell-Based Screening: Analysis of Inhibitor Effects and Telomerase Expression Mechanisms

PubMed Central

Bilsland, Alan E.; Stevenson, Katrina; Liu, Yu; Hoare, Stacey; Cairney, Claire J.; Roffey, Jon; Keith, W. Nicol

2014-01-01

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability. PMID:24550717

Boolean function applied to Mimosa pudica movements.

PubMed

De Luccia, Thiago Paes de Barros; Friedman, Pedro

2011-09-01

Seismonastic or thigmonastic movements of Mimosa pudica L. is mostly because of the fast loss of water from swollen motor cells, resulting in temporary collapse of cells and quick curvature in the parts where these cells are located. Because of this, the plant has been much studied since the 18th century, leading us to think about the classical binomial stimulus-response (action-reaction) when compared to animals. Mechanic and electrical stimuli were used to investigate the analogy of mimosa branch with an artificial neuron model and to observe the action potential propagation through the mimosa branch. Boolean function applied to the mimosa branch in analogy with an artificial neuron model is one of the peculiarities of our hypothesis.

To Boolean or Not To Boolean.

ERIC Educational Resources Information Center

Hildreth, Charles R.

1983-01-01

This editorial addresses the issue of whether or not to provide free-text, keyword/boolean search capabilities in the information retrieval mechanisms of online public access catalogs and discusses online catalogs developed prior to 1980--keyword searching, phrase searching, and precoordination and postcoordination. (EJS)

Calculating the bidirectional reflectance of natural vegetation covers using Boolean models and geometric optics

NASA Technical Reports Server (NTRS)

Strahler, Alan H.; Li, Xiao-Wen; Jupp, David L. B.

1991-01-01

The bidirectional radiance or reflectance of a forest or woodland can be modeled using principles of geometric optics and Boolean models for random sets in a three dimensional space. This model may be defined at two levels, the scene includes four components; sunlight and shadowed canopy, and sunlit and shadowed background. The reflectance of the scene is modeled as the sum of the reflectances of the individual components as weighted by their areal proportions in the field of view. At the leaf level, the canopy envelope is an assemblage of leaves, and thus the reflectance is a function of the areal proportions of sunlit and shadowed leaf, and sunlit and shadowed background. Because the proportions of scene components are dependent upon the directions of irradiance and exitance, the model accounts for the hotspot that is well known in leaf and tree canopies.

A solution to the surface intersection problem. [Boolean functions in geometric modeling

NASA Technical Reports Server (NTRS)

Timer, H. G.

1977-01-01

An application-independent geometric model within a data base framework should support the use of Boolean operators which allow the user to construct a complex model by appropriately combining a series of simple models. The use of these operators leads to the concept of implicitly and explicitly defined surfaces. With an explicitly defined model, the surface area may be computed by simply summing the surface areas of the bounding surfaces. For an implicitly defined model, the surface area computation must deal with active and inactive regions. Because the surface intersection problem involves four unknowns and its solution is a space curve, the parametric coordinates of each surface must be determined as a function of the arc length. Various subproblems involved in the general intersection problem are discussed, and the mathematical basis for their solution is presented along with a program written in FORTRAN IV for implementation on the IBM 370 TSO system.

The logic of the floral transition: Reverse-engineering the switch controlling the identity of lateral organs.

PubMed

Dinh, Jean-Louis; Farcot, Etienne; Hodgman, Charlie

2017-09-01

Much laboratory work has been carried out to determine the gene regulatory network (GRN) that results in plant cells becoming flowers instead of leaves. However, this also involves the spatial distribution of different cell types, and poses the question of whether alternative networks could produce the same set of observed results. This issue has been addressed here through a survey of the published intercellular distribution of expressed regulatory genes and techniques both developed and applied to Boolean network models. This has uncovered a large number of models which are compatible with the currently available data. An exhaustive exploration had some success but proved to be unfeasible due to the massive number of alternative models, so genetic programming algorithms have also been employed. This approach allows exploration on the basis of both data-fitting criteria and parsimony of the regulatory processes, ruling out biologically unrealistic mechanisms. One of the conclusions is that, despite the multiplicity of acceptable models, an overall structure dominates, with differences mostly in alternative fine-grained regulatory interactions. The overall structure confirms the known interactions, including some that were not present in the training set, showing that current data are sufficient to determine the overall structure of the GRN. The model stresses the importance of relative spatial location, through explicit references to this aspect. This approach also provides a quantitative indication of how likely some regulatory interactions might be, and can be applied to the study of other developmental transitions.

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

PubMed

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

2012-08-17

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

Discrete interference modeling via boolean algebra.

PubMed

Beckhoff, Gerhard

2011-01-01

Two types of boolean functions are considered, the locus function of n variables, and the interval function of ν = n - 1 variables. A 1-1 mapping is given that takes elements (cells) of the interval function to antidual pairs of elements in the locus function, and vice versa. A set of ν binary codewords representing the intervals are defined and used to generate the codewords of all genomic regions. Next a diallelic three-point system is reviewed in the light of boolean functions, which leads to redefining complete interference by a logic function. Together with the upper bound of noninterference already defined by a boolean function, it confines the region of interference. Extensions of these two functions to any finite number of ν are straightforward, but have been also made in terms of variables taken from the inclusion-exclusion principle (expressing "at least" and "exactly equal to" a decimal integer). Two coefficients of coincidence for systems with more than three loci are defined and discussed, one using the average of several individual coefficients and the other taking as coefficient a real number between zero and one. Finally, by way of a malfunction of the mod-2 addition, it is shown that a four-point system may produce two different functions, one of which exhibiting loss of a class of odd recombinants.

Combinatorial optimization in foundry practice

NASA Astrophysics Data System (ADS)

Antamoshkin, A. N.; Masich, I. S.

2016-04-01

The multicriteria mathematical model of foundry production capacity planning is suggested in the paper. The model is produced in terms of pseudo-Boolean optimization theory. Different search optimization methods were used to solve the obtained problem.

On the Run-Time Optimization of the Boolean Logic of a Program.

ERIC Educational Resources Information Center

Cadolino, C.; Guazzo, M.

1982-01-01

Considers problem of optimal scheduling of Boolean expression (each Boolean variable represents binary outcome of program module) on single-processor system. Optimization discussed consists of finding operand arrangement that minimizes average execution costs representing consumption of resources (elapsed time, main memory, number of…

Boolean integral calculus for digital systems

NASA Technical Reports Server (NTRS)

Tucker, J. H.; Tapia, M. A.; Bennett, A. W.

1985-01-01

The concept of Boolean integration is introduced and developed. When the changes in a desired function are specified in terms of changes in its arguments, then ways of 'integrating' (i.e., realizing) the function, if it exists, are presented. Boolean integral calculus has applications in design of logic circuits.

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

PubMed

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.

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

PubMed Central

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

2017-01-01

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. PMID:29267315

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

PubMed

Frolov, Alexander A; Húsek, Dušan; Polyakov, Pavel Yu

2016-03-01

An usual task in large data set analysis is searching for an appropriate data representation in a space of fewer dimensions. One of the most efficient methods to solve this task is factor analysis. In this paper, we compare seven methods for Boolean factor analysis (BFA) in solving the so-called bars problem (BP), which is a BFA benchmark. The performance of the methods is evaluated by means of information gain. Study of the results obtained in solving BP of different levels of complexity has allowed us to reveal strengths and weaknesses of these methods. It is shown that the Likelihood maximization Attractor Neural Network with Increasing Activity (LANNIA) is the most efficient BFA method in solving BP in many cases. Efficacy of the LANNIA method is also shown, when applied to the real data from the Kyoto Encyclopedia of Genes and Genomes database, which contains full genome sequencing for 1368 organisms, and to text data set R52 (from Reuters 21578) typically used for label categorization.

A Comparison of Two Methods for Boolean Query Relevancy Feedback.

ERIC Educational Resources Information Center

Salton, G.; And Others

1984-01-01

Evaluates and compares two recently proposed automatic methods for relevance feedback of Boolean queries (Dillon method, which uses probabilistic approach as basis, and disjunctive normal form method). Conclusions are drawn concerning the use of effective feedback methods in a Boolean query environment. Nineteen references are included. (EJS)

Representing Network Trust and Using It to Improve Anonymous Communication

DTIC Science & Technology

2014-07-01

identified by that behavior . References 1. Augustin, B., Krishnamurthy, B., Willinger, W.: IXPs: Mapped? In: Internet Mea- surement Conference ( IMC ’09...empty attributes (e.g., labeling countries by their larger geographic region). The user’s beliefs may incorporate boolean predicates that are evaluated on...and behaviors are. The most useful information about Tor relays for setting a default level of trust is probably relay longevity. Running a relay in

Modeling of the hypothalamic-pituitary-adrenal axis-mediated interaction between the serotonin regulation pathway and the stress response using a Boolean approximation: a novel study of depression

PubMed Central

2013-01-01

Major depressive disorder (MDD) is a multifactorial disorder known to be influenced by both genetic and environmental factors. MDD presents a heritability of 37%, and a genetic contribution has also been observed in studies of family members of individuals with MDD that imply that the probability of suffering the disorder is approximately three times higher if a first-degree family member is affected. Childhood maltreatment and stressful life events (SLEs) have been established as critical environmental factors that profoundly influence the onset of MDD. The serotonin pathway has been a strong candidate for genetic studies, but it only explains a small proportion of the heritability of the disorder, which implies the involvement of other pathways. The serotonin (5-HT) pathway interacts with the stress response pathway in a manner mediated by the hypothalamic-pituitary-adrenal (HPA) axis. To analyze the interaction between the pathways, we propose the use of a synchronous Boolean network (SBN) approximation. The principal aim of this work was to model the interaction between these pathways, taking into consideration the presence of selective serotonin reuptake inhibitors (SSRIs), in order to observe how the pathways interact and to examine if the system is stable. Additionally, we wanted to study which genes or metabolites have the greatest impact on model stability when knocked out in silico. We observed that the biological model generated predicts steady states (attractors) for each of the different runs performed, thereby proving that the system is stable. These attractors changed in shape, especially when anti-depressive drugs were also included in the simulation. This work also predicted that the genes with the greatest impact on model stability were those involved in the neurotrophin pathway, such as CREB, BDNF (which has been associated with major depressive disorder in a variety of studies) and TRkB, followed by genes and metabolites related to 5-HT synthesis. PMID:24093582

Boolean function applied to Mimosa pudica movements

PubMed Central

Friedman, Pedro

2011-01-01

Seismonastic or thigmonastic movements of Mimosa pudica L. is mostly because of the fast loss of water from swollen motor cells, resulting in temporary collapse of cells and quick curvature in the parts where these cells are located. Because of this, the plant has been much studied since the 18th century, leading us to think about the classical binomial stimulus-response (action-reaction) when compared to animals. Mechanic and electrical stimuli were used to investigate the analogy of mimosa branch with an artificial neuron model and to observe the action potential propagation through the mimosa branch. Boolean function applied to the mimosa branch in analogy with an artificial neuron model is one of the peculiarities of our hypothesis. PMID:21847029

Boolean Classes and Qualitative Inquiry. WCER Working Paper No. 2006-3

ERIC Educational Resources Information Center

Nathan, Mitchell J.; Jackson, Kristi

2006-01-01

The prominent role of Boolean classes in qualitative data analysis software is viewed by some as an encroachment of logical positivism on qualitative research methodology. The authors articulate an embodiment perspective, in which Boolean classes are viewed as conceptual metaphors for apprehending and manipulating data, concepts, and categories in…

Nonlinear dynamics based digital logic and circuits.

PubMed

Kia, Behnam; Lindner, John F; Ditto, William L

2015-01-01

We discuss the role and importance of dynamics in the brain and biological neural networks and argue that dynamics is one of the main missing elements in conventional Boolean logic and circuits. We summarize a simple dynamics based computing method, and categorize different techniques that we have introduced to realize logic, functionality, and programmability. We discuss the role and importance of coupled dynamics in networks of biological excitable cells, and then review our simple coupled dynamics based method for computing. In this paper, for the first time, we show how dynamics can be used and programmed to implement computation in any given base, including but not limited to base two.

Control of cancer-related signal transduction networks

NASA Astrophysics Data System (ADS)

Albert, Reka

2013-03-01

Intra-cellular signaling networks are crucial to the maintenance of cellular homeostasis and for cell behavior (growth, survival, apoptosis, movement). Mutations or alterations in the expression of elements of cellular signaling networks can lead to incorrect behavioral decisions that could result in tumor development and/or the promotion of cell migration and metastasis. Thus, mitigation of the cascading effects of such dysregulations is an important control objective. My group at Penn State is collaborating with wet-bench biologists to develop and validate predictive models of various biological systems. Over the years we found that discrete dynamic modeling is very useful in molding qualitative interaction information into a predictive model. We recently demonstrated the effectiveness of network-based targeted manipulations on mitigating the disease T cell large granular lymphocyte (T-LGL) leukemia. The root of this disease is the abnormal survival of T cells which, after successfully fighting an infection, should undergo programmed cell death. We synthesized the relevant network of within-T-cell interactions from the literature, integrated it with qualitative knowledge of the dysregulated (abnormal) states of several network components, and formulated a Boolean dynamic model. The model indicated that the system possesses a steady state corresponding to the normal cell death state and a T-LGL steady state corresponding to the abnormal survival state. For each node, we evaluated the restorative manipulation consisting of maintaining the node in the state that is the opposite of its T-LGL state, e.g. knocking it out if it is overexpressed in the T-LGL state. We found that such control of any of 15 nodes led to the disappearance of the T-LGL steady state, leaving cell death as the only potential outcome from any initial condition. In four additional cases the probability of reaching the T-LGL state decreased dramatically, thus these nodes are also possible control targets. Our collaborators validated two of these predicted control mechanisms experimentally. Our work suggests that external control of a single node can be a fruitful therapeutic strategy.

Defense of Cyber Infrastructures Against Cyber-Physical Attacks Using Game-Theoretic Models

DOE PAGES

Rao, Nageswara S. V.; Poole, Stephen W.; Ma, Chris Y. T.; ...

2015-04-06

The operation of cyber infrastructures relies on both cyber and physical components, which are subject to incidental and intentional degradations of different kinds. Within the context of network and computing infrastructures, we study the strategic interactions between an attacker and a defender using game-theoretic models that take into account both cyber and physical components. The attacker and defender optimize their individual utilities expressed as sums of cost and system terms. First, we consider a Boolean attack-defense model, wherein the cyber and physical sub-infrastructures may be attacked and reinforced as individual units. Second, we consider a component attack-defense model wherein theirmore » components may be attacked and defended, and the infrastructure requires minimum numbers of both to function. We show that the Nash equilibrium under uniform costs in both cases is computable in polynomial time, and it provides high-level deterministic conditions for the infrastructure survival. When probabilities of successful attack and defense, and of incidental failures are incorporated into the models, the results favor the attacker but otherwise remain qualitatively similar. This approach has been motivated and validated by our experiences with UltraScience Net infrastructure, which was built to support high-performance network experiments. In conclusion, the analytical results, however, are more general, and we apply them to simplified models of cloud and high-performance computing infrastructures.« less

Defense of Cyber Infrastructures Against Cyber-Physical Attacks Using Game-Theoretic Models

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

Rao, Nageswara S. V.; Poole, Stephen W.; Ma, Chris Y. T.

The operation of cyber infrastructures relies on both cyber and physical components, which are subject to incidental and intentional degradations of different kinds. Within the context of network and computing infrastructures, we study the strategic interactions between an attacker and a defender using game-theoretic models that take into account both cyber and physical components. The attacker and defender optimize their individual utilities expressed as sums of cost and system terms. First, we consider a Boolean attack-defense model, wherein the cyber and physical sub-infrastructures may be attacked and reinforced as individual units. Second, we consider a component attack-defense model wherein theirmore » components may be attacked and defended, and the infrastructure requires minimum numbers of both to function. We show that the Nash equilibrium under uniform costs in both cases is computable in polynomial time, and it provides high-level deterministic conditions for the infrastructure survival. When probabilities of successful attack and defense, and of incidental failures are incorporated into the models, the results favor the attacker but otherwise remain qualitatively similar. This approach has been motivated and validated by our experiences with UltraScience Net infrastructure, which was built to support high-performance network experiments. In conclusion, the analytical results, however, are more general, and we apply them to simplified models of cloud and high-performance computing infrastructures.« less

Defense of Cyber Infrastructures Against Cyber-Physical Attacks Using Game-Theoretic Models.

PubMed

Rao, Nageswara S V; Poole, Stephen W; Ma, Chris Y T; He, Fei; Zhuang, Jun; Yau, David K Y

2016-04-01

The operation of cyber infrastructures relies on both cyber and physical components, which are subject to incidental and intentional degradations of different kinds. Within the context of network and computing infrastructures, we study the strategic interactions between an attacker and a defender using game-theoretic models that take into account both cyber and physical components. The attacker and defender optimize their individual utilities, expressed as sums of cost and system terms. First, we consider a Boolean attack-defense model, wherein the cyber and physical subinfrastructures may be attacked and reinforced as individual units. Second, we consider a component attack-defense model wherein their components may be attacked and defended, and the infrastructure requires minimum numbers of both to function. We show that the Nash equilibrium under uniform costs in both cases is computable in polynomial time, and it provides high-level deterministic conditions for the infrastructure survival. When probabilities of successful attack and defense, and of incidental failures, are incorporated into the models, the results favor the attacker but otherwise remain qualitatively similar. This approach has been motivated and validated by our experiences with UltraScience Net infrastructure, which was built to support high-performance network experiments. The analytical results, however, are more general, and we apply them to simplified models of cloud and high-performance computing infrastructures. © 2015 Society for Risk Analysis.

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

PubMed

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.

Topology of Document Retrieval Systems.

ERIC Educational Resources Information Center

Everett, Daniel M.; Cater, Steven C.

1992-01-01

Explains the use of a topological structure to examine the closeness between documents in retrieval systems and analyzes the topological structure of a vector-space model, a fuzzy-set model, an extended Boolean model, a probabilistic model, and a TIRS (Topological Information Retrieval System) model. Proofs for the results are appended. (17…

E-Referencer: Transforming Boolean OPACs to Web Search Engines.

ERIC Educational Resources Information Center

Khoo, Christopher S. G.; Poo, Danny C. C.; Toh, Teck-Kang; Hong, Glenn

E-Referencer is an expert intermediary system for searching library online public access catalogs (OPACs) on the World Wide Web. It is implemented as a proxy server that mediates the interaction between the user and Boolean OPACs. It transforms a Boolean OPAC into a retrieval system with many of the search capabilities of Web search engines.…

Communication Policies in Knowledge Networks

NASA Astrophysics Data System (ADS)

Ioannidis, Evangelos; Varsakelis, Nikos; Antoniou, Ioannis

2018-02-01

Faster knowledge attainment within organizations leads to improved innovation, and therefore competitive advantage. Interventions on the organizational network may be risky or costly or time-demanding. We investigate several communication policies in knowledge networks, which reduce the knowledge attainment time without interventions. We examine the resulting knowledge dynamics for real organizational networks, as well as for artificial networks. More specifically, we investigate the dependence of knowledge dynamics on: (1) the Selection Rule of agents for knowledge acquisition, and (2) the Order of implementation of "Selection" and "Filtering". Significant decrease of the knowledge attainment time (up to -74%) can be achieved by: (1) selecting agents of both high knowledge level and high knowledge transfer efficiency, and (2) implementing "Selection" after "Filtering" in contrast to the converse, implicitly assumed, conventional prioritization. The Non-Commutativity of "Selection" and "Filtering", reveals a Non-Boolean Logic of the Network Operations. The results demonstrate that significant improvement of knowledge dynamics can be achieved by implementing "fruitful" communication policies, by raising the awareness of agents, without any intervention on the network structure.

Piezo-phototronic Boolean logic and computation using photon and strain dual-gated nanowire transistors.

PubMed

Yu, Ruomeng; Wu, Wenzhuo; Pan, Caofeng; Wang, Zhaona; Ding, Yong; Wang, Zhong Lin

2015-02-04

Using polarization charges created at the metal-cadmium sulfide interface under strain to gate/modulate electrical transport and optoelectronic processes of charge carriers, the piezo-phototronic effect is applied to process mechanical and optical stimuli into electronic controlling signals. The cascade nanowire networks are demonstrated for achieving logic gates, binary computations, and gated D latches to store information carried by these stimuli. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Information processing in dendrites I. Input pattern generalisation.

PubMed

Gurney, K N

2001-10-01

In this paper and its companion, we address the question as to whether there are any general principles underlying information processing in the dendritic trees of biological neurons. In order to address this question, we make two assumptions. First, the key architectural feature of dendrites responsible for many of their information processing abilities is the existence of independent sub-units performing local non-linear processing. Second, any general functional principles operate at a level of abstraction in which neurons are modelled by Boolean functions. To accommodate these assumptions, we therefore define a Boolean model neuron-the multi-cube unit (MCU)-which instantiates the notion of the discrete functional sub-unit. We then use this model unit to explore two aspects of neural functionality: generalisation (in this paper) and processing complexity (in its companion). Generalisation is dealt with from a geometric viewpoint and is quantified using a new metric-the set of order parameters. These parameters are computed for threshold logic units (TLUs), a class of random Boolean functions, and MCUs. Our interpretation of the order parameters is consistent with our knowledge of generalisation in TLUs and with the lack of generalisation in randomly chosen functions. Crucially, the order parameters for MCUs imply that these functions possess a range of generalisation behaviour. We argue that this supports the general thesis that dendrites facilitate input pattern generalisation despite any local non-linear processing within functionally isolated sub-units.

BEAT: A Web-Based Boolean Expression Fault-Based Test Case Generation Tool

ERIC Educational Resources Information Center

Chen, T. Y.; Grant, D. D.; Lau, M. F.; Ng, S. P.; Vasa, V. R.

2006-01-01

BEAT is a Web-based system that generates fault-based test cases from Boolean expressions. It is based on the integration of our several fault-based test case selection strategies. The generated test cases are considered to be fault-based, because they are aiming at the detection of particular faults. For example, when the Boolean expression is in…

SETS. Set Equation Transformation System

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

Worrell, R.B.

1992-01-13

SETS is used for symbolic manipulation of Boolean equations, particularly the reduction of equations by the application of Boolean 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 noncoherent 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 throughmore » nullification of sensors in its protection system.« less

Mammalian synthetic biology: emerging medical applications.

PubMed

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

2015-05-06

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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Diagnostic reasoning techniques for selective monitoring

NASA Technical Reports Server (NTRS)

Homem-De-mello, L. S.; Doyle, R. J.

1991-01-01

An architecture for using diagnostic reasoning techniques in selective monitoring is presented. Given the sensor readings and a model of the physical system, a number of assertions are generated and expressed as Boolean equations. The resulting system of Boolean equations is solved symbolically. Using a priori probabilities of component failure and Bayes' rule, revised probabilities of failure can be computed. These will indicate what components have failed or are the most likely to have failed. This approach is suitable for systems that are well understood and for which the correctness of the assertions can be guaranteed. Also, the system must be such that changes are slow enough to allow the computation.

Boolean Minimization and Algebraic Factorization Procedures for Fully Testable Sequential Machines

DTIC Science & Technology

1989-09-01

Boolean Minimization and Algebraic Factorization Procedures for Fully Testable Sequential Machines Srinivas Devadas and Kurt Keutzer F ( Abstract In this...Projects Agency under contract number N00014-87-K-0825. Author Information Devadas : Department of Electrical Engineering and Computer Science, Room 36...MA 02139; (617) 253-0292. 0 * Boolean Minimization and Algebraic Factorization Procedures for Fully Testable Sequential Machines Siivas Devadas

Multi-enzyme logic network architectures for assessing injuries: digital processing of biomarkers.

PubMed

Halámek, Jan; Bocharova, Vera; Chinnapareddy, Soujanya; Windmiller, Joshua Ray; Strack, Guinevere; Chuang, Min-Chieh; Zhou, Jian; Santhosh, Padmanabhan; Ramirez, Gabriela V; Arugula, Mary A; Wang, Joseph; Katz, Evgeny

2010-12-01

A multi-enzyme biocatalytic cascade processing simultaneously five biomarkers characteristic of traumatic brain injury (TBI) and soft tissue injury (STI) was developed. The system operates as a digital biosensor based on concerted function of 8 Boolean AND logic gates, resulting in the decision about the physiological conditions based on the logic analysis of complex patterns of the biomarkers. The system represents the first example of a multi-step/multi-enzyme biosensor with the built-in logic for the analysis of complex combinations of biochemical inputs. The approach is based on recent advances in enzyme-based biocomputing systems and the present paper demonstrates the potential applicability of biocomputing for developing novel digital biosensor networks.

The Systems Biology Markup Language (SBML) Level 3 Package: Qualitative Models, Version 1, Release 1.

PubMed

Chaouiya, Claudine; Keating, Sarah M; Berenguier, Duncan; Naldi, Aurélien; Thieffry, Denis; van Iersel, Martijn P; Le Novère, Nicolas; Helikar, Tomáš

2015-09-04

Quantitative methods for modelling biological networks require an in-depth knowledge of the biochemical reactions and their stoichiometric and kinetic parameters. In many practical cases, this knowledge is missing. This has led to the development of several qualitative modelling methods using information such as, for example, gene expression data coming from functional genomic experiments. The SBML Level 3 Version 1 Core specification does not provide a mechanism for explicitly encoding qualitative models, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactical constructs. The SBML Qualitative Models package for SBML Level 3 adds features so that qualitative models can be directly and explicitly encoded. The approach taken in this package is essentially based on the definition of regulatory or influence graphs. The SBML Qualitative Models package defines the structure and syntax necessary to describe qualitative models that associate discrete levels of activities with entity pools and the transitions between states that describe the processes involved. This is particularly suited to logical models (Boolean or multi-valued) and some classes of Petri net models can be encoded with the approach.

Logic circuits from zero forcing.

PubMed

Burgarth, Daniel; Giovannetti, Vittorio; Hogben, Leslie; Severini, Simone; Young, Michael

We design logic circuits based on the notion of zero forcing on graphs; each gate of the circuits is a gadget in which zero forcing is performed. We show that such circuits can evaluate every monotone Boolean function. By using two vertices to encode each logical bit, we obtain universal computation. We also highlight a phenomenon of "back forcing" as a property of each function. Such a phenomenon occurs in a circuit when the input of gates which have been already used at a given time step is further modified by a computation actually performed at a later stage. Finally, we show that zero forcing can be also used to implement reversible computation. The model introduced here provides a potentially new tool in the analysis of Boolean functions, with particular attention to monotonicity. Moreover, in the light of applications of zero forcing in quantum mechanics, the link with Boolean functions may suggest a new directions in quantum control theory and in the study of engineered quantum spin systems. It is an open technical problem to verify whether there is a link between zero forcing and computation with contact circuits.

Inference of combinatorial Boolean rules of synergistic gene sets from cancer microarray datasets.

PubMed

Park, Inho; Lee, Kwang H; Lee, Doheon

2010-06-15

Gene set analysis has become an important tool for the functional interpretation of high-throughput gene expression datasets. Moreover, pattern analyses based on inferred gene set activities of individual samples have shown the ability to identify more robust disease signatures than individual gene-based pattern analyses. Although a number of approaches have been proposed for gene set-based pattern analysis, the combinatorial influence of deregulated gene sets on disease phenotype classification has not been studied sufficiently. We propose a new approach for inferring combinatorial Boolean rules of gene sets for a better understanding of cancer transcriptome and cancer classification. To reduce the search space of the possible Boolean rules, we identify small groups of gene sets that synergistically contribute to the classification of samples into their corresponding phenotypic groups (such as normal and cancer). We then measure the significance of the candidate Boolean rules derived from each group of gene sets; the level of significance is based on the class entropy of the samples selected in accordance with the rules. By applying the present approach to publicly available prostate cancer datasets, we identified 72 significant Boolean rules. Finally, we discuss several identified Boolean rules, such as the rule of glutathione metabolism (down) and prostaglandin synthesis regulation (down), which are consistent with known prostate cancer biology. Scripts written in Python and R are available at http://biosoft.kaist.ac.kr/~ihpark/. The refined gene sets and the full list of the identified Boolean rules are provided in the Supplementary Material. Supplementary data are available at Bioinformatics online.

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

PubMed Central

Dragović, Ivana; Turajlić, Nina; Pilčević, Dejan; Petrović, Bratislav; Radojević, Dragan

2015-01-01

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. PMID:27069500

A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity

PubMed Central

Martinez-Sanchez, Mariana Esther; Mendoza, Luis; Villarreal, Carlos; Alvarez-Buylla, Elena R.

2015-01-01

CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes) versus extrinsic (produced by other cells) components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells). This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-β and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular regulatory core and the micro-environment. We discuss the broader use of this approach for other plastic systems and possible therapeutic interventions. PMID:26090929

Criticality in finite dynamical networks

NASA Astrophysics Data System (ADS)

Rohlf, Thimo; Gulbahce, Natali; Teuscher, Christof

2007-03-01

It has been shown analytically and experimentally that both random boolean and random threshold networks show a transition from ordered to chaotic dynamics at a critical average connectivity Kc in the thermodynamical limit [1]. By looking at the statistical distributions of damage spreading (damage sizes), we go beyond this extensively studied mean-field approximation. We study the scaling properties of damage size distributions as a function of system size N and initial perturbation size d(t=0). We present numerical evidence that another characteristic point, Kd exists for finite system sizes, where the expectation value of damage spreading in the network is independent of the system size N. Further, the probability to obtain critical networks is investigated for a given system size and average connectivity k. Our results suggest that, for finite size dynamical networks, phase space structure is very complex and may not exhibit a sharp order-disorder transition. Finally, we discuss the implications of our findings for evolutionary processes and learning applied to networks which solve specific computational tasks. [1] Derrida, B. and Pomeau, Y. (1986), Europhys. Lett., 1, 45-49

The Local Minima Problem in Hierarchical Classes Analysis: An Evaluation of a Simulated Annealing Algorithm and Various Multistart Procedures

ERIC Educational Resources Information Center

Ceulemans, Eva; Van Mechelen, Iven; Leenen, Iwin

2007-01-01

Hierarchical classes models are quasi-order retaining Boolean decomposition models for N-way N-mode binary data. To fit these models to data, rationally started alternating least squares (or, equivalently, alternating least absolute deviations) algorithms have been proposed. Extensive simulation studies showed that these algorithms succeed quite…

An Investigation of the Mathematical Models of Piaget's Psychological Theory of Cognitive Learning. Final Report.

ERIC Educational Resources Information Center

Kalechofsky, Robert

This research paper proposes several mathematical models which help clarify Piaget's theory of cognition on the concrete and formal operational stages. Some modified lattice models were used for the concrete stage and a combined Boolean Algebra and group theory model was used for the formal stage. The researcher used experiments cited in the…

Dynamic Boolean Mathematics

ERIC Educational Resources Information Center

Bossé, Michael J.; Adu-Gyamfi, Kwaku; Chandler, Kayla; Lynch-Davis, Kathleen

2016-01-01

Dynamic mathematical environments allow users to reify mathematical concepts through multiple representations, transform mathematical relations and organically explore mathematical properties, investigate integrated mathematics, and develop conceptual understanding. Herein, we integrate Boolean algebra, the functionalities of a dynamic…

Total Parenteral Nutrition

MedlinePlus

... Boolean useRights, FileShare share, Int32 bufferSize, FileOptions options, SECURITY_ATTRIBUTES secAttrs, String msgPath, Boolean bFromProxy) at System.IO.FileStream..ctor(String path, FileMode mode, FileAccess ...

Toward synthesizing executable models in biology.

PubMed

Fisher, Jasmin; Piterman, Nir; Bodik, Rastislav

2014-01-01

Over the last decade, executable models of biological behaviors have repeatedly provided new scientific discoveries, uncovered novel insights, and directed new experimental avenues. These models are computer programs whose execution mechanistically simulates aspects of the cell's behaviors. If the observed behavior of the program agrees with the observed biological behavior, then the program explains the phenomena. This approach has proven beneficial for gaining new biological insights and directing new experimental avenues. One advantage of this approach is that techniques for analysis of computer programs can be applied to the analysis of executable models. For example, one can confirm that a model agrees with experiments for all possible executions of the model (corresponding to all environmental conditions), even if there are a huge number of executions. Various formal methods have been adapted for this context, for example, model checking or symbolic analysis of state spaces. To avoid manual construction of executable models, one can apply synthesis, a method to produce programs automatically from high-level specifications. In the context of biological modeling, synthesis would correspond to extracting executable models from experimental data. We survey recent results about the usage of the techniques underlying synthesis of computer programs for the inference of biological models from experimental data. We describe synthesis of biological models from curated mutation experiment data, inferring network connectivity models from phosphoproteomic data, and synthesis of Boolean networks from gene expression data. While much work has been done on automated analysis of similar datasets using machine learning and artificial intelligence, using synthesis techniques provides new opportunities such as efficient computation of disambiguating experiments, as well as the ability to produce different kinds of models automatically from biological data.

A Note about Information Science Research.

ERIC Educational Resources Information Center

Salton, Gerard

1985-01-01

Discusses the relationship between information science research and practice and briefly describes current research on 10 topics in information retrieval literature: vector processing retrieval strategy, probabilistic retrieval models, inverted file procedures, relevance feedback, Boolean query formulations, front-end procedures, citation…

A genetic code Boolean structure. II. The genetic information system as a Boolean information system.

PubMed

Sanchez, Robersy; Grau, Ricardo

2005-09-01

A Boolean structure of the genetic code where Boolean deductions have biological and physicochemical meanings was discussed in a previous paper. Now, from these Boolean deductions we propose to define the value of amino acid information in order to consider the genetic information system as a communication system and to introduce the semantic content of information ignored by the conventional information theory. In this proposal, the value of amino acid information is proportional to the molecular weight of amino acids with a proportional constant of about 1.96 x 10(25) bits per kg. In addition to this, for the experimental estimations of the minimum energy dissipation in genetic logic operations, we present two postulates: (1) the energy Ei (i=1,2,...,20) of amino acids in the messages conveyed by proteins is proportional to the value of information, and (2) amino acids are distributed according to their energy Ei so the amino acid population in proteins follows a Boltzmann distribution. Specifically, in the genetic message carried by the DNA from the genomes of living organisms, we found that the minimum energy dissipation in genetic logic operations was close to kTLn(2) joules per bit.

Improving the quantum cost of reversible Boolean functions using reorder algorithm

NASA Astrophysics Data System (ADS)

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.

Volumetric T-spline Construction Using Boolean Operations

DTIC Science & Technology

2013-07-01

SUBTITLE Volumetric T-spline Construction Using Boolean Operations 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...Acknowledgements The work of L. Liu and Y. Zhang was supported by ONR-YIP award N00014- 10-1-0698 and an ONR Grant N00014-08-1-0653. T. J.R. Hughes was sup- 16...T-spline Construction Using Boolean Operations 17 ported by ONR Grant N00014-08-1-0992, NSF GOALI CMI-0700807/0700204, NSF CMMI-1101007 and a SINTEF

The logical primitives of thought: Empirical foundations for compositional cognitive models.

PubMed

Piantadosi, Steven T; Tenenbaum, Joshua B; Goodman, Noah D

2016-07-01

The notion of a compositional language of thought (LOT) has been central in computational accounts of cognition from earliest attempts (Boole, 1854; Fodor, 1975) to the present day (Feldman, 2000; Penn, Holyoak, & Povinelli, 2008; Fodor, 2008; Kemp, 2012; Goodman, Tenenbaum, & Gerstenberg, 2015). Recent modeling work shows how statistical inferences over compositionally structured hypothesis spaces might explain learning and development across a variety of domains. However, the primitive components of such representations are typically assumed a priori by modelers and theoreticians rather than determined empirically. We show how different sets of LOT primitives, embedded in a psychologically realistic approximate Bayesian inference framework, systematically predict distinct learning curves in rule-based concept learning experiments. We use this feature of LOT models to design a set of large-scale concept learning experiments that can determine the most likely primitives for psychological concepts involving Boolean connectives and quantification. Subjects' inferences are most consistent with a rich (nonminimal) set of Boolean operations, including first-order, but not second-order, quantification. Our results more generally show how specific LOT theories can be distinguished empirically. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Utilization of Large Scale Surface Models for Detailed Visibility Analyses

NASA Astrophysics Data System (ADS)

Caha, J.; Kačmařík, M.

2017-11-01

This article demonstrates utilization of large scale surface models with small spatial resolution and high accuracy, acquired from Unmanned Aerial Vehicle scanning, for visibility analyses. The importance of large scale data for visibility analyses on the local scale, where the detail of the surface model is the most defining factor, is described. The focus is not only the classic Boolean visibility, that is usually determined within GIS, but also on so called extended viewsheds that aims to provide more information about visibility. The case study with examples of visibility analyses was performed on river Opava, near the Ostrava city (Czech Republic). The multiple Boolean viewshed analysis and global horizon viewshed were calculated to determine most prominent features and visibility barriers of the surface. Besides that, the extended viewshed showing angle difference above the local horizon, which describes angular height of the target area above the barrier, is shown. The case study proved that large scale models are appropriate data source for visibility analyses on local level. The discussion summarizes possible future applications and further development directions of visibility analyses.

Logic-Based and Cellular Pharmacodynamic Modeling of Bortezomib Responses in U266 Human Myeloma Cells

PubMed Central

Chudasama, Vaishali L.; Ovacik, Meric A.; Abernethy, Darrell R.

2015-01-01

Systems models of biological networks show promise for informing drug target selection/qualification, identifying lead compounds and factors regulating disease progression, rationalizing combinatorial regimens, and explaining sources of intersubject variability and adverse drug reactions. However, most models of biological systems are qualitative and are not easily coupled with dynamical models of drug exposure-response relationships. In this proof-of-concept study, logic-based modeling of signal transduction pathways in U266 multiple myeloma (MM) cells is used to guide the development of a simple dynamical model linking bortezomib exposure to cellular outcomes. Bortezomib is a commonly used first-line agent in MM treatment; however, knowledge of the signal transduction pathways regulating bortezomib-mediated cell cytotoxicity is incomplete. A Boolean network model of 66 nodes was constructed that includes major survival and apoptotic pathways and was updated using responses to several chemical probes. Simulated responses to bortezomib were in good agreement with experimental data, and a reduction algorithm was used to identify key signaling proteins. Bortezomib-mediated apoptosis was not associated with suppression of nuclear factor κB (NFκB) protein inhibition in this cell line, which contradicts a major hypothesis of bortezomib pharmacodynamics. A pharmacodynamic model was developed that included three critical proteins (phospho-NFκB, BclxL, and cleaved poly (ADP ribose) polymerase). Model-fitted protein dynamics and cell proliferation profiles agreed with experimental data, and the model-predicted IC50 (3.5 nM) is comparable to the experimental value (1.5 nM). The cell-based pharmacodynamic model successfully links bortezomib exposure to MM cellular proliferation via protein dynamics, and this model may show utility in exploring bortezomib-based combination regimens. PMID:26163548

Inference of gene regulatory networks from time series by Tsallis entropy

PubMed Central

2011-01-01

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 ≤ q ≤ 3.5 (hence, subextensive entropy), which opens new perspectives for GRNs inference methods based on information theory and for investigation of the nonextensivity of such networks. The inference algorithm and criterion function proposed here were implemented and included in the DimReduction software, which is freely available at http://sourceforge.net/projects/dimreduction and http://code.google.com/p/dimreduction/. PMID:21545720

Acoustic logic gates and Boolean operation based on self-collimating acoustic beams

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

Zhang, Ting; Xu, Jian-yi; Cheng, Ying, E-mail: chengying@nju.edu.cn

2015-03-16

The reveal of self-collimation effect in two-dimensional (2D) photonic or acoustic crystals has opened up possibilities for signal manipulation. In this paper, we have proposed acoustic logic gates based on the linear interference of self-collimated beams in 2D sonic crystals (SCs) with line-defects. The line defects on the diagonal of the 2D square SCs are actually functioning as a 3 dB splitter. By adjusting the phase difference between two input signals, the basic Boolean logic functions such as XOR, OR, AND, and NOT are achieved both theoretically and experimentally. Due to the non-diffracting property of self-collimation beams, more complex Boolean logicmore » and algorithms such as NAND, NOR, and XNOR can be realized by cascading the basic logic gates. The achievement of acoustic logic gates and Boolean operation provides a promising approach for acoustic signal computing and manipulations.« less

Data-Driven Sampling Matrix Boolean Optimization for Energy-Efficient Biomedical Signal Acquisition by Compressive Sensing.

PubMed

Wang, Yuhao; Li, Xin; Xu, Kai; Ren, Fengbo; Yu, Hao

2017-04-01

Compressive sensing is widely used in biomedical applications, and the sampling matrix plays a critical role on both quality and power consumption of signal acquisition. It projects a high-dimensional vector of data into a low-dimensional subspace by matrix-vector multiplication. An optimal sampling matrix can ensure accurate data reconstruction and/or high compression ratio. Most existing optimization methods can only produce real-valued embedding matrices that result in large energy consumption during data acquisition. In this paper, we propose an efficient method that finds an optimal Boolean sampling matrix in order to reduce the energy consumption. Compared to random Boolean embedding, our data-driven Boolean sampling matrix can improve the image recovery quality by 9 dB. Moreover, in terms of sampling hardware complexity, it reduces the energy consumption by 4.6× and the silicon area by 1.9× over the data-driven real-valued embedding.

Critical Dynamics in Genetic Regulatory Networks: Examples from Four Kingdoms

PubMed Central

Balleza, Enrique; Alvarez-Buylla, Elena R.; Chaos, Alvaro; Kauffman, Stuart; Shmulevich, Ilya; Aldana, Maximino

2008-01-01

The coordinated expression of the different genes in an organism is essential to sustain functionality under the random external perturbations to which the organism might be subjected. To cope with such external variability, the global dynamics of the genetic network must possess two central properties. (a) It must be robust enough as to guarantee stability under a broad range of external conditions, and (b) it must be flexible enough to recognize and integrate specific external signals that may help the organism to change and adapt to different environments. This compromise between robustness and adaptability has been observed in dynamical systems operating at the brink of a phase transition between order and chaos. Such systems are termed critical. Thus, criticality, a precise, measurable, and well characterized property of dynamical systems, makes it possible for robustness and adaptability to coexist in living organisms. In this work we investigate the dynamical properties of the gene transcription networks reported for S. cerevisiae, E. coli, and B. subtilis, as well as the network of segment polarity genes of D. melanogaster, and the network of flower development of A. thaliana. We use hundreds of microarray experiments to infer the nature of the regulatory interactions among genes, and implement these data into the Boolean models of the genetic networks. Our results show that, to the best of the current experimental data available, the five networks under study indeed operate close to criticality. The generality of this result suggests that criticality at the genetic level might constitute a fundamental evolutionary mechanism that generates the great diversity of dynamically robust living forms that we observe around us. PMID:18560561

A transition calculus for Boolean functions. [logic circuit analysis

NASA Technical Reports Server (NTRS)

Tucker, J. H.; Bennett, A. W.

1974-01-01

A transition calculus is presented for analyzing the effect of input changes on the output of logic circuits. The method is closely related to the Boolean difference, but it is more powerful. Both differentiation and integration are considered.

Integrating machine learning techniques into robust data enrichment approach and its application to gene expression data.

PubMed

Erdoğdu, Utku; Tan, Mehmet; Alhajj, Reda; Polat, Faruk; Rokne, Jon; Demetrick, Douglas

2013-01-01

The availability of enough samples for effective analysis and knowledge discovery has been a challenge in the research community, especially in the area of gene expression data analysis. Thus, the approaches being developed for data analysis have mostly suffered from the lack of enough data to train and test the constructed models. We argue that the process of sample generation could be successfully automated by employing some sophisticated machine learning techniques. An automated sample generation framework could successfully complement the actual sample generation from real cases. This argument is validated in this paper by describing a framework that integrates multiple models (perspectives) for sample generation. We illustrate its applicability for producing new gene expression data samples, a highly demanding area that has not received attention. The three perspectives employed in the process are based on models that are not closely related. The independence eliminates the bias of having the produced approach covering only certain characteristics of the domain and leading to samples skewed towards one direction. The first model is based on the Probabilistic Boolean Network (PBN) representation of the gene regulatory network underlying the given gene expression data. The second model integrates Hierarchical Markov Model (HIMM) and the third model employs a genetic algorithm in the process. Each model learns as much as possible characteristics of the domain being analysed and tries to incorporate the learned characteristics in generating new samples. In other words, the models base their analysis on domain knowledge implicitly present in the data itself. The developed framework has been extensively tested by checking how the new samples complement the original samples. The produced results are very promising in showing the effectiveness, usefulness and applicability of the proposed multi-model framework.

High-Density Liquid-State Machine Circuitry for Time-Series Forecasting.

PubMed

Rosselló, Josep L; Alomar, Miquel L; Morro, Antoni; Oliver, Antoni; Canals, Vincent

2016-08-01

Spiking neural networks (SNN) are the last neural network generation that try to mimic the real behavior of biological neurons. Although most research in this area is done through software applications, it is in hardware implementations in which the intrinsic parallelism of these computing systems are more efficiently exploited. Liquid state machines (LSM) have arisen as a strategic technique to implement recurrent designs of SNN with a simple learning methodology. In this work, we show a new low-cost methodology to implement high-density LSM by using Boolean gates. The proposed method is based on the use of probabilistic computing concepts to reduce hardware requirements, thus considerably increasing the neuron count per chip. The result is a highly functional system that is applied to high-speed time series forecasting.

A Max-Flow Based Algorithm for Connected Target Coverage with Probabilistic Sensors

PubMed Central

Shan, Anxing; Xu, Xianghua; Cheng, Zongmao; Wang, Wensheng

2017-01-01

Coverage is a fundamental issue in the research field of wireless sensor networks (WSNs). Connected target coverage discusses the sensor placement to guarantee the needs of both coverage and connectivity. Existing works largely leverage on the Boolean disk model, which is only a coarse approximation to the practical sensing model. In this paper, we focus on the connected target coverage issue based on the probabilistic sensing model, which can characterize the quality of coverage more accurately. In the probabilistic sensing model, sensors are only be able to detect a target with certain probability. We study the collaborative detection probability of target under multiple sensors. Armed with the analysis of collaborative detection probability, we further formulate the minimum ϵ-connected target coverage problem, aiming to minimize the number of sensors satisfying the requirements of both coverage and connectivity. We map it into a flow graph and present an approximation algorithm called the minimum vertices maximum flow algorithm (MVMFA) with provable time complex and approximation ratios. To evaluate our design, we analyze the performance of MVMFA theoretically and also conduct extensive simulation studies to demonstrate the effectiveness of our proposed algorithm. PMID:28587084

A Max-Flow Based Algorithm for Connected Target Coverage with Probabilistic Sensors.

PubMed

Shan, Anxing; Xu, Xianghua; Cheng, Zongmao; Wang, Wensheng

2017-05-25

Coverage is a fundamental issue in the research field of wireless sensor networks (WSNs). Connected target coverage discusses the sensor placement to guarantee the needs of both coverage and connectivity. Existing works largely leverage on the Boolean disk model, which is only a coarse approximation to the practical sensing model. In this paper, we focus on the connected target coverage issue based on the probabilistic sensing model, which can characterize the quality of coverage more accurately. In the probabilistic sensing model, sensors are only be able to detect a target with certain probability. We study the collaborative detection probability of target under multiple sensors. Armed with the analysis of collaborative detection probability, we further formulate the minimum ϵ -connected target coverage problem, aiming to minimize the number of sensors satisfying the requirements of both coverage and connectivity. We map it into a flow graph and present an approximation algorithm called the minimum vertices maximum flow algorithm (MVMFA) with provable time complex and approximation ratios. To evaluate our design, we analyze the performance of MVMFA theoretically and also conduct extensive simulation studies to demonstrate the effectiveness of our proposed algorithm.

A Model of Knowledge Based Information Retrieval with Hierarchical Concept Graph.

ERIC Educational Resources Information Center

Kim, Young Whan; Kim, Jin H.

1990-01-01

Proposes a model of knowledge-based information retrieval (KBIR) that is based on a hierarchical concept graph (HCG) which shows relationships between index terms and constitutes a hierarchical thesaurus as a knowledge base. Conceptual distance between a query and an object is discussed and the use of Boolean operators is described. (25…

Development of a computer-aided design software for dental splint in orthognathic surgery

NASA Astrophysics Data System (ADS)

Chen, Xiaojun; Li, Xing; Xu, Lu; Sun, Yi; Politis, Constantinus; Egger, Jan

2016-12-01

In the orthognathic surgery, dental splints are important and necessary to help the surgeon reposition the maxilla or mandible. However, the traditional methods of manual design of dental splints are difficult and time-consuming. The research on computer-aided design software for dental splints is rarely reported. Our purpose is to develop a novel special software named EasySplint to design the dental splints conveniently and efficiently. The design can be divided into two steps, which are the generation of initial splint base and the Boolean operation between it and the maxilla-mandibular model. The initial splint base is formed by ruled surfaces reconstructed using the manually picked points. Then, a method to accomplish Boolean operation based on the distance filed of two meshes is proposed. The interference elimination can be conducted on the basis of marching cubes algorithm and Boolean operation. The accuracy of the dental splint can be guaranteed since the original mesh is utilized to form the result surface. Using EasySplint, the dental splints can be designed in about 10 minutes and saved as a stereo lithography (STL) file for 3D printing in clinical applications. Three phantom experiments were conducted and the efficiency of our method was demonstrated.

Development of a computer-aided design software for dental splint in orthognathic surgery

PubMed Central

Chen, Xiaojun; Li, Xing; Xu, Lu; Sun, Yi; Politis, Constantinus; Egger, Jan

2016-01-01

In the orthognathic surgery, dental splints are important and necessary to help the surgeon reposition the maxilla or mandible. However, the traditional methods of manual design of dental splints are difficult and time-consuming. The research on computer-aided design software for dental splints is rarely reported. Our purpose is to develop a novel special software named EasySplint to design the dental splints conveniently and efficiently. The design can be divided into two steps, which are the generation of initial splint base and the Boolean operation between it and the maxilla-mandibular model. The initial splint base is formed by ruled surfaces reconstructed using the manually picked points. Then, a method to accomplish Boolean operation based on the distance filed of two meshes is proposed. The interference elimination can be conducted on the basis of marching cubes algorithm and Boolean operation. The accuracy of the dental splint can be guaranteed since the original mesh is utilized to form the result surface. Using EasySplint, the dental splints can be designed in about 10 minutes and saved as a stereo lithography (STL) file for 3D printing in clinical applications. Three phantom experiments were conducted and the efficiency of our method was demonstrated. PMID:27966601

Development of a computer-aided design software for dental splint in orthognathic surgery.

PubMed

Chen, Xiaojun; Li, Xing; Xu, Lu; Sun, Yi; Politis, Constantinus; Egger, Jan

2016-12-14

In the orthognathic surgery, dental splints are important and necessary to help the surgeon reposition the maxilla or mandible. However, the traditional methods of manual design of dental splints are difficult and time-consuming. The research on computer-aided design software for dental splints is rarely reported. Our purpose is to develop a novel special software named EasySplint to design the dental splints conveniently and efficiently. The design can be divided into two steps, which are the generation of initial splint base and the Boolean operation between it and the maxilla-mandibular model. The initial splint base is formed by ruled surfaces reconstructed using the manually picked points. Then, a method to accomplish Boolean operation based on the distance filed of two meshes is proposed. The interference elimination can be conducted on the basis of marching cubes algorithm and Boolean operation. The accuracy of the dental splint can be guaranteed since the original mesh is utilized to form the result surface. Using EasySplint, the dental splints can be designed in about 10 minutes and saved as a stereo lithography (STL) file for 3D printing in clinical applications. Three phantom experiments were conducted and the efficiency of our method was demonstrated.

Quantum algorithms on Walsh transform and Hamming distance for Boolean functions

NASA Astrophysics Data System (ADS)

Xie, Zhengwei; Qiu, Daowen; Cai, Guangya

2018-06-01

Walsh spectrum or Walsh transform is an alternative description of Boolean functions. In this paper, we explore quantum algorithms to approximate the absolute value of Walsh transform W_f at a single point z0 (i.e., |W_f(z0)|) for n-variable Boolean functions with probability at least 8/π 2 using the number of O(1/|W_f(z_{0)|ɛ }) queries, promised that the accuracy is ɛ , while the best known classical algorithm requires O(2n) queries. The Hamming distance between Boolean functions is used to study the linearity testing and other important problems. We take advantage of Walsh transform to calculate the Hamming distance between two n-variable Boolean functions f and g using O(1) queries in some cases. Then, we exploit another quantum algorithm which converts computing Hamming distance between two Boolean functions to quantum amplitude estimation (i.e., approximate counting). If Ham(f,g)=t≠0, we can approximately compute Ham( f, g) with probability at least 2/3 by combining our algorithm and {Approx-Count(f,ɛ ) algorithm} using the expected number of Θ( √{N/(\\lfloor ɛ t\\rfloor +1)}+√{t(N-t)}/\\lfloor ɛ t\\rfloor +1) queries, promised that the accuracy is ɛ . Moreover, our algorithm is optimal, while the exact query complexity for the above problem is Θ(N) and the query complexity with the accuracy ɛ is O(1/ɛ 2N/(t+1)) in classical algorithm, where N=2n. Finally, we present three exact quantum query algorithms for two promise problems on Hamming distance using O(1) queries, while any classical deterministic algorithm solving the problem uses Ω(2n) queries.

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

NASA Technical Reports Server (NTRS)

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.

Advanced Feedback Methods in Information Retrieval.

ERIC Educational Resources Information Center

Salton, G.; And Others

1985-01-01

In this study, automatic feedback techniques are applied to Boolean query statements in online information retrieval to generate improved query statements based on information contained in previously retrieved documents. Feedback operations are carried out using conventional Boolean logic and extended logic. Experimental output is included to…

Compact universal logic gates realized using quantization of current in nanodevices.

PubMed

Zhang, Wancheng; Wu, Nan-Jian; Yang, Fuhua

2007-12-12

This paper proposes novel universal logic gates using the current quantization characteristics of nanodevices. In nanodevices like the electron waveguide (EW) and single-electron (SE) turnstile, the channel current is a staircase quantized function of its control voltage. We use this unique characteristic to compactly realize Boolean functions. First we present the concept of the periodic-threshold threshold logic gate (PTTG), and we build a compact PTTG using EW and SE turnstiles. We show that an arbitrary three-input Boolean function can be realized with a single PTTG, and an arbitrary four-input Boolean function can be realized by using two PTTGs. We then use one PTTG to build a universal programmable two-input logic gate which can be used to realize all two-input Boolean functions. We also build a programmable three-input logic gate by using one PTTG. Compared with linear threshold logic gates, with the PTTG one can build digital circuits more compactly. The proposed PTTGs are promising for future smart nanoscale digital system use.

Boolean linear differential operators on elementary cellular automata

NASA Astrophysics Data System (ADS)

Martín Del Rey, Ángel

2014-12-01

In this paper, the notion of boolean linear differential operator (BLDO) on elementary cellular automata (ECA) is introduced and some of their more important properties are studied. Special attention is paid to those differential operators whose coefficients are the ECA with rule numbers 90 and 150.

Application of a Discrete Nonlinear Spectral Model to Ideal Cases of Wind Wave Generation.

DTIC Science & Technology

1982-04-01

WRITE (6965)) bBD ODRM4T (IHII C SKI ’> 3 LINS i AND WRITE PLOT TITLE (IDOCHAR S PER LINE t 10 LINES AXI4CH-,(NClkR*9) /10 dRJTE (660) (TJL..EfI),I-I...A*CaGE.D.)JPP-J>P 𔃻 I F ( 8 D Do)) jpp-j P?+2 MiFPPeE)’i)&O TO 44 73 40JT-NPr(NIN,JPP) ;o TD (72, 14,7b,7BhNOUT 44 IF(A*3)q46q4b47 46 JPP-2 ;0 TO 73...EXTEZNAL FJNrI3N LAND IJS 13 THE BOOLEAN I.EoLDGICAL$ AND 01’ Td C FULLWORD INTEGCRS. C EXTEtNAL FJN:TION LOR, I,JS 1)7 THE BOOLEAN OR OF TWO FULLWORD

Describing the What and Why of Students' Difficulties in Boolean Logic

ERIC Educational Resources Information Center

Herman, Geoffrey L.; Loui, Michael C.; Kaczmarczyk, Lisa; Zilles, Craig

2012-01-01

The ability to reason with formal logic is a foundational skill for computer scientists and computer engineers that scaffolds the abilities to design, debug, and optimize. By interviewing students about their understanding of propositional logic and their ability to translate from English specifications to Boolean expressions, we characterized…

Analysis of a dynamic model of guard cell signaling reveals the stability of signal propagation

NASA Astrophysics Data System (ADS)

Gan, Xiao; Albert, RéKa

Analyzing the long-term behaviors (attractors) of dynamic models of biological systems can provide valuable insight into biological phenotypes and their stability. We identified the long-term behaviors of a multi-level, 70-node discrete dynamic model of the stomatal opening process in plants. We reduce the model's huge state space by reducing unregulated nodes and simple mediator nodes, and by simplifying the regulatory functions of selected nodes while keeping the model consistent with experimental observations. We perform attractor analysis on the resulting 32-node reduced model by two methods: 1. converting it into a Boolean model, then applying two attractor-finding algorithms; 2. theoretical analysis of the regulatory functions. We conclude that all nodes except two in the reduced model have a single attractor; and only two nodes can admit oscillations. The multistability or oscillations do not affect the stomatal opening level in any situation. This conclusion applies to the original model as well in all the biologically meaningful cases. We further demonstrate the robustness of signal propagation by showing that a large percentage of single-node knockouts does not affect the stomatal opening level. Thus, we conclude that the complex structure of this signal transduction network provides multiple information propagation pathways while not allowing extensive multistability or oscillations, resulting in robust signal propagation. Our innovative combination of methods offers a promising way to analyze multi-level models.

Gene network analysis: from heart development to cardiac therapy.

PubMed

Ferrazzi, Fulvia; Bellazzi, Riccardo; Engel, Felix B

2015-03-01

Networks offer a flexible framework to represent and analyse the complex interactions between components of cellular systems. In particular gene networks inferred from expression data can support the identification of novel hypotheses on regulatory processes. In this review we focus on the use of gene network analysis in the study of heart development. Understanding heart development will promote the elucidation of the aetiology of congenital heart disease and thus possibly improve diagnostics. Moreover, it will help to establish cardiac therapies. For example, understanding cardiac differentiation during development will help to guide stem cell differentiation required for cardiac tissue engineering or to enhance endogenous repair mechanisms. We introduce different methodological frameworks to infer networks from expression data such as Boolean and Bayesian networks. Then we present currently available temporal expression data in heart development and discuss the use of network-based approaches in published studies. Collectively, our literature-based analysis indicates that gene network analysis constitutes a promising opportunity to infer therapy-relevant regulatory processes in heart development. However, the use of network-based approaches has so far been limited by the small amount of samples in available datasets. Thus, we propose to acquire high-resolution temporal expression data to improve the mathematical descriptions of regulatory processes obtained with gene network inference methodologies. Especially probabilistic methods that accommodate the intrinsic variability of biological systems have the potential to contribute to a deeper understanding of heart development.

ADAM: analysis of discrete models of biological systems using computer algebra.

PubMed

Hinkelmann, Franziska; Brandon, Madison; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard

2011-07-20

Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web-based tool for several different input formats, and it makes analysis of complex models accessible to a larger community, as it is platform independent as a web-service and does not require understanding of the underlying mathematics.

Circulant Matrices and Affine Equivalence of Monomial Rotation Symmetric Boolean Functions

DTIC Science & Technology

2015-01-01

definitions , including monomial rotation symmetric (MRS) Boolean functions and affine equivalence, and a known result for such quadratic functions...degree of the MRS is, we have a similar result as [40, Theorem 1.1] for n = 4p (p prime), or squarefree integers n, which along with our Theorem 5.2

User Practices in Keyword and Boolean Searching on an Online Public Access Catalog.

ERIC Educational Resources Information Center

Ensor, Pat

1992-01-01

Discussion of keyword and Boolean searching techniques in online public access catalogs (OPACs) focuses on a study conducted at Indiana State University that examined users' attitudes toward searching on NOTIS (Northwestern Online Total Integrated System). Relevant literature is reviewed, and implications for library instruction are suggested. (17…

Using Vector and Extended Boolean Matching in an Expert System for Selecting Foster Homes.

ERIC Educational Resources Information Center

Fox, Edward A.; Winett, Sheila G.

1990-01-01

Describes FOCES (Foster Care Expert System), a prototype expert system for choosing foster care placements for children which integrates information retrieval techniques with artificial intelligence. The use of prototypes and queries in Prolog routines, extended Boolean matching, and vector correlation are explained, as well as evaluation by…

A Construction of Boolean Functions with Good Cryptographic Properties

DTIC Science & Technology

2014-01-01

be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT...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

Graphene-based non-Boolean logic circuits

NASA Astrophysics Data System (ADS)

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.

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

ERIC Educational Resources Information Center

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…

Optical programmable Boolean logic unit.

PubMed

Chattopadhyay, Tanay

2011-11-10

Logic units are the building blocks of many important computational operations likes arithmetic, multiplexer-demultiplexer, radix conversion, parity checker cum generator, etc. Multifunctional logic operation is very much essential in this respect. Here a programmable Boolean logic unit is proposed that can perform 16 Boolean logical operations from a single optical input according to the programming input without changing the circuit design. This circuit has two outputs. One output is complementary to the other. Hence no loss of data can occur. The circuit is basically designed by a 2×2 polarization independent optical cross bar switch. Performance of the proposed circuit has been achieved by doing numerical simulations. The binary logical states (0,1) are represented by the absence of light (null) and presence of light, respectively.

Recognition vs Reverse Engineering in Boolean Concepts Learning

ERIC Educational Resources Information Center

Shafat, Gabriel; Levin, Ilya

2012-01-01

This paper deals with two types of logical problems--recognition problems and reverse engineering problems, and with the interrelations between these types of problems. The recognition problems are modeled in the form of a visual representation of various objects in a common pattern, with a composition of represented objects in the pattern.…

Algebraic grid adaptation method using non-uniform rational B-spline surface modeling

NASA Technical Reports Server (NTRS)

Yang, Jiann-Cherng; Soni, B. K.

1992-01-01

An algebraic adaptive grid system based on equidistribution law and utilized by the Non-Uniform Rational B-Spline (NURBS) surface for redistribution is presented. A weight function, utilizing a properly weighted boolean sum of various flow field characteristics is developed. Computational examples are presented to demonstrate the success of this technique.

Two Methods for Efficient Solution of the Hitting-Set Problem

NASA Technical Reports Server (NTRS)

Vatan, Farrokh; Fijany, Amir

2005-01-01

A paper addresses much of the same subject matter as that of Fast Algorithms for Model-Based Diagnosis (NPO-30582), which appears elsewhere in this issue of NASA Tech Briefs. However, in the paper, the emphasis is more on the hitting-set problem (also known as the transversal problem), which is well known among experts in combinatorics. The authors primary interest in the hitting-set problem lies in its connection to the diagnosis problem: it is a theorem of model-based diagnosis that in the set-theory representation of the components of a system, the minimal diagnoses of a system are the minimal hitting sets of the system. In the paper, the hitting-set problem (and, hence, the diagnosis problem) is translated from a combinatorial to a computational problem by mapping it onto the Boolean satisfiability and integer- programming problems. The paper goes on to describe developments nearly identical to those summarized in the cited companion NASA Tech Briefs article, including the utilization of Boolean-satisfiability and integer- programming techniques to reduce the computation time and/or memory needed to solve the hitting-set problem.

Data Auditor: Analyzing Data Quality Using Pattern Tableaux

NASA Astrophysics Data System (ADS)

Srivastava, Divesh

Monitoring databases maintain configuration and measurement tables about computer systems, such as networks and computing clusters, and serve important business functions, such as troubleshooting customer problems, analyzing equipment failures, planning system upgrades, etc. These databases are prone to many data quality issues: configuration tables may be incorrect due to data entry errors, while measurement tables may be affected by incorrect, missing, duplicate and delayed polls. We describe Data Auditor, a tool for analyzing data quality and exploring data semantics of monitoring databases. Given a user-supplied constraint, such as a boolean predicate expected to be satisfied by every tuple, a functional dependency, or an inclusion dependency, Data Auditor computes "pattern tableaux", which are concise summaries of subsets of the data that satisfy or fail the constraint. We discuss the architecture of Data Auditor, including the supported types of constraints and the tableau generation mechanism. We also show the utility of our approach on an operational network monitoring database.

Application of stochastic processes in random growth and evolutionary dynamics

NASA Astrophysics Data System (ADS)

Oikonomou, Panagiotis

We study the effect of power-law distributed randomness on the dynamical behavior of processes such as stochastic growth patterns and evolution. First, we examine the geometrical properties of random shapes produced by a generalized stochastic Loewner Evolution driven by a superposition of a Brownian motion and a stable Levy process. The situation is defined by the usual stochastic Loewner Evolution parameter, kappa, as well as alpha which defines the power-law tail of the stable Levy distribution. We show that the properties of these patterns change qualitatively and singularly at critical values of kappa and alpha. It is reasonable to call such changes "phase transitions". These transitions occur as kappa passes through four and as alpha passes through one. Numerical simulations are used to explore the global scaling behavior of these patterns in each "phase". We show both analytically and numerically that the growth continues indefinitely in the vertical direction for alpha greater than 1, goes as logarithmically with time for alpha equals to 1, and saturates for alpha smaller than 1. The probability density has two different scales corresponding to directions along and perpendicular to the boundary. Scaling functions for the probability density are given for various limiting cases. Second, we study the effect of the architecture of biological networks on their evolutionary dynamics. In recent years, studies of the architecture of large networks have unveiled a common topology, called scale-free, in which a majority of the elements are poorly connected except for a small fraction of highly connected components. We ask how networks with distinct topologies can evolve towards a pre-established target phenotype through a process of random mutations and selection. We use networks of Boolean components as a framework to model a large class of phenotypes. Within this approach, we find that homogeneous random networks and scale-free networks exhibit drastically different evolutionary paths. While homogeneous random networks accumulate neutral mutations and evolve by sparse punctuated steps, scale-free networks evolve rapidly and continuously towards the target phenotype. Moreover, we show that scale-free networks always evolve faster than homogeneous random networks; remarkably, this property does not depend on the precise value of the topological parameter. By contrast, homogeneous random networks require a specific tuning of their topological parameter in order to optimize their fitness. This model suggests that the evolutionary paths of biological networks, punctuated or continuous, may solely be determined by the network topology.

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

PubMed

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.

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

PubMed Central

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

Modeling hormonal control of cambium proliferation.

PubMed

Oles, Vladyslav; Panchenko, Alexander; Smertenko, Andrei

2017-01-01

Rise of atmospheric CO2 is one of the main causes of global warming. Catastrophic climate change can be avoided by reducing emissions and increasing sequestration of CO2. Trees are known to sequester CO2 during photosynthesis, and then store it as wood biomass. Thus, breeding of trees with higher wood yield would mitigate global warming as well as augment production of renewable construction materials, energy, and industrial feedstock. Wood is made of cellulose-rich xylem cells produced through proliferation of a specialized stem cell niche called cambium. Importance of cambium in xylem cells production makes it an ideal target for the tree breeding programs; however our knowledge about control of cambium proliferation remains limited. The morphology and regulation of cambium are different from those of stem cell niches that control axial growth. For this reason, translating the knowledge about axial growth to radial growth has limited use. Furthermore, genetic approaches cannot be easily applied because overlaying tissues conceal cambium from direct observation and complicate identification of mutants. To overcome the paucity of experimental tools in cambium biology, we constructed a Boolean network CARENET (CAmbium REgulation gene NETwork) for modelling cambium activity, which includes the key transcription factors WOX4 and HD-ZIP III as well as their potential regulators. Our simulations predict that: (1) auxin, cytokinin, gibberellin, and brassinosteroids act cooperatively in promoting transcription of WOX4 and HD-ZIP III; (2) auxin and cytokinin pathways negatively regulate each other; (3) hormonal pathways act redundantly in sustaining cambium activity; (4) individual cambium cells can have diverse molecular identities. CARENET can be extended to include components of other signalling pathways and be integrated with models of xylem and phloem differentiation. Such extended models would facilitate breeding trees with higher wood yield.

Multiple neural network approaches to clinical expert systems

NASA Astrophysics Data System (ADS)

Stubbs, Derek F.

1990-08-01

We briefly review the concept of computer aided medical diagnosis and more extensively review the the existing literature on neural network applications in the field. Neural networks can function as simple expert systems for diagnosis or prognosis. Using a public database we develop a neural network for the diagnosis of a major presenting symptom while discussing the development process and possible approaches. MEDICAL EXPERTS SYSTEMS COMPUTER AIDED DIAGNOSIS Biomedicine is an incredibly diverse and multidisciplinary field and it is not surprising that neural networks with their many applications are finding more and more applications in the highly non-linear field of biomedicine. I want to concentrate on neural networks as medical expert systems for clinical diagnosis or prognosis. Expert Systems started out as a set of computerized " ifthen" rules. Everything was reduced to boolean logic and the promised land of computer experts was said to be in sight. It never came. Why? First the computer code explodes as the number of " ifs" increases. All the " ifs" have to interact. Second experts are not very good at reducing expertise to language. It turns out that experts recognize patterns and have non-verbal left-brain intuition decision processes. Third learning by example rather than learning by rule is the way natural brains works and making computers work by rule-learning is hideously labor intensive. Neural networks can learn from example. They learn the results

Compile-Time Schedulability Analysis of Communicating Concurrent Programs

DTIC Science & Technology

2006-06-28

synchronize via the read and write operations on the FIFO channels. These operations have been implemented with the help of semaphores , which...3 1.1.2 Synchronous Dataflow . . . . . . . . . . . . . . . . . . . . . . . . . . 8 1.1.3 Boolean Dataflow...described by concurrent programs . . . . . . . . . 4 1.3 A synchronous dataflow model, its topology matrix, and repetition vector . 10 1.4 Select and

Robustness in Regulatory Interaction Networks. A Generic Approach with Applications at Different Levels: Physiologic, Metabolic and Genetic

PubMed Central

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

Computer Aided Instruction for a Course in Boolean Algebra and Logic Design. Final Report (Revised).

ERIC Educational Resources Information Center

Roy, Rob

The use of computers to prepare deficient college and graduate students for courses that build upon previously acquired information would solve the growing problem of professors who must spend up to one third of their class time in review of material. But examination of students who were taught Boolean Algebra and Logic Design by means of Computer…

Intervention in gene regulatory networks with maximal phenotype alteration.

PubMed

Yousefi, Mohammadmahdi R; Dougherty, Edward R

2013-07-15

A basic issue for translational genomics is to model gene interaction via gene regulatory networks (GRNs) and thereby provide an informatics environment to study the effects of intervention (say, via drugs) and to derive effective intervention strategies. Taking the view that the phenotype is characterized by the long-run behavior (steady-state distribution) of the network, we desire interventions to optimally move the probability mass from undesirable to desirable states Heretofore, two external control approaches have been taken to shift the steady-state mass of a GRN: (i) use a user-defined cost function for which desirable shift of the steady-state mass is a by-product and (ii) use heuristics to design a greedy algorithm. Neither approach provides an optimal control policy relative to long-run behavior. We use a linear programming approach to optimally shift the steady-state mass from undesirable to desirable states, i.e. optimization is directly based on the amount of shift and therefore must outperform previously proposed methods. Moreover, the same basic linear programming structure is used for both unconstrained and constrained optimization, where in the latter case, constraints on the optimization limit the amount of mass that may be shifted to 'ambiguous' states, these being states that are not directly undesirable relative to the pathology of interest but which bear some perceived risk. We apply the method to probabilistic Boolean networks, but the theory applies to any Markovian GRN. Supplementary materials, including the simulation results, MATLAB source code and description of suboptimal methods are available at http://gsp.tamu.edu/Publications/supplementary/yousefi13b. edward@ece.tamu.edu Supplementary data are available at Bioinformatics online.

Deriving Laws from Ordering Relations

NASA Technical Reports Server (NTRS)

Knuth, Kevin H.

2003-01-01

It took much effort in the early days of non-Euclidean geometry to break away from the mindset that all spaces are flat and that two distinct parallel lines do not cross. Up to that point, all that was known was Euclidean geometry, and it was difficult to imagine anything else. We have suffered a similar handicap brought on by the enormous relevance of Boolean algebra to the problems of our age-logic and set theory. Previously, I demonstrated that the algebra of questions is not Boolean, but rather is described by the free distributive algebra. To get to this stage took much effort, as many obstacles-most self-placed-had to be overcome. As Boolean algebras were all I had ever known, it was almost impossible for me to imagine working with an algebra where elements do not have complements. With this realization, it became very clear that the sum and product rules of probability theory at the most basic level had absolutely nothing to do with the Boolean algebra of logical statements. Instead, a measure of degree of inclusion can be invented for many different partially ordered sets, and the sum and product rules fall out of the associativity and distributivity of the algebra. To reinforce this very important idea, this paper will go over how these constructions are made, while focusing on the underlying assumptions. I will derive the sum and product rules for a distributive lattice in general and demonstrate how this leads to probability theory on the Boolean lattice and is related to the calculus of quantum mechanical amplitudes on the partially ordered set of experimental setups. I will also discuss the rules that can be derived from modular lattices and their relevance to the cross-ratio of projective geometry.

Beyond the "I" in the obesity epidemic: a review of social relational and network interventions on obesity.

PubMed

Leroux, Janette S; Moore, Spencer; Dubé, Laurette

2013-01-01

Recent research has shown the importance of networks in the spread of obesity. Yet, the translation of research on social networks and obesity into health promotion practice has been slow. To review the types of obesity interventions targeting social relational factors. Six databases were searched in January 2013. A Boolean search was employed with the following sets of terms: (1) social dimensions: social capital, cohesion, collective efficacy, support, social networks, or trust; (2) intervention type: intervention, experiment, program, trial, or policy; and (3) obesity in the title or abstract. Titles and abstracts were reviewed. Articles were included if they described an obesity intervention with the social relational component central. Articles were assessed on the social relational factor(s) addressed, social ecological level(s) targeted, the intervention's theoretical approach, and the conceptual placement of the social relational component in the intervention. Database searches and final article screening yielded 30 articles. Findings suggested that (1) social support was most often targeted; (2) few interventions were beyond the individual level; (3) most interventions were framed on behaviour change theories; and (4) the social relational component tended to be conceptually ancillary to the intervention. Theoretically and practically, social networks remain marginal to current interventions addressing obesity.

Verification of VLSI designs

NASA Technical Reports Server (NTRS)

Windley, P. J.

1991-01-01

In this paper we explore the specification and verification of VLSI designs. The paper focuses on abstract specification and verification of functionality using mathematical logic as opposed to low-level boolean equivalence verification such as that done using BDD's and Model Checking. Specification and verification, sometimes called formal methods, is one tool for increasing computer dependability in the face of an exponentially increasing testing effort.

Artificial neural networks using complex numbers and phase encoded weights.

PubMed

Michel, Howard E; Awwal, Abdul Ahad S

2010-04-01

The model of a simple perceptron using phase-encoded inputs and complex-valued weights is proposed. The aggregation function, activation function, and learning rule for the proposed neuron are derived and applied to Boolean logic functions and simple computer vision tasks. The complex-valued neuron (CVN) is shown to be superior to traditional perceptrons. An improvement of 135% over the theoretical maximum of 104 linearly separable problems (of three variables) solvable by conventional perceptrons is achieved without additional logic, neuron stages, or higher order terms such as those required in polynomial logic gates. The application of CVN in distortion invariant character recognition and image segmentation is demonstrated. Implementation details are discussed, and the CVN is shown to be very attractive for optical implementation since optical computations are naturally complex. The cost of the CVN is less in all cases than the traditional neuron when implemented optically. Therefore, all the benefits of the CVN can be obtained without additional cost. However, on those implementations dependent on standard serial computers, CVN will be more cost effective only in those applications where its increased power can offset the requirement for additional neurons.

The Statistical Mechanics of Dilute, Disordered Systems

NASA Astrophysics Data System (ADS)

Blackburn, Roger Michael

Available from UMI in association with The British Library. Requires signed TDF. A graph partitioning problem with variable inter -partition costs is studied by exploiting its mapping on to the Ashkin-Teller spin glass. The cavity method is used to derive the TAP equations and free energy for both extensively connected and dilute systems. Unlike Ising and Potts spin glasses, the self-consistent equation for the distribution of effective fields does not have a solution solely made up of delta functions. Numerical integration is used to find the stable solution, from which the ground state energy is calculated. Simulated annealing is used to test the results. The retrieving activity distribution for networks of boolean functions trained as associative memories for optimal capacity is derived. For infinite networks, outputs are shown to be frozen, in contrast to dilute asymmetric networks trained with the Hebb rule. For finite networks, a steady leaking to the non-retrieving attractor is demonstrated. Simulations of quenched networks are reported which show a departure from this picture: some configurations remain frozen for all time, while others follow cycles of small periods. An estimate of the critical capacity from the simulations is found to be in broad agreement with recent analytical results. The existing theory is extended to include noise on recall, and the behaviour is found to be robust to noise up to order 1/c^2 for networks with connectivity c.

Lithographically fabricated gold nanowire waveguides for plasmonic routers and logic gates.

PubMed

Gao, Long; Chen, Li; Wei, Hong; Xu, Hongxing

2018-06-14

Fabricating plasmonic nanowire waveguides and circuits by lithographic fabrication methods is highly desired for nanophotonic circuitry applications. Here we report an approach for fabricating metal nanowire networks by using electron beam lithography and metal film deposition techniques. The gold nanowire structures are fabricated on quartz substrates without using any adhesion layer but coated with a thin layer of Al2O3 film for immobilization. The thermal annealing during the Al2O3 deposition process decreases the surface plasmon loss. In a Y-shaped gold nanowire network, the surface plasmons can be routed to different branches by controlling the polarization of the excitation light, and the routing behavior is dependent on the length of the main nanowire. Simulated electric field distributions show that the zigzag distribution of the electric field in the nanowire network determines the surface plasmon routing. By using two laser beams to excite surface plasmons in a Y-shaped nanowire network, the output intensity can be modulated by the interference of surface plasmons, which can be used to design Boolean logic gates. We experimentally demonstrate that AND, OR, XOR and NOT gates can be realized in three-terminal nanowire networks, and NAND, NOR and XNOR gates can be realized in four-terminal nanowire networks. This work takes a step toward the fabrication of on-chip integrated plasmonic circuits.

Discrete Dynamical Modeling of Influenza Virus Infection Suggests Age-Dependent Differences in Immunity.

PubMed

Keef, Ericka; Zhang, Li Ang; Swigon, David; Urbano, Alisa; Ermentrout, G Bard; Matuszewski, Michael; Toapanta, Franklin R; Ross, Ted M; Parker, Robert S; Clermont, Gilles

2017-12-01

Immunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit a delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and a greater likelihood of death. Our study applies a rule-based model to infer which components of the immune response are most changed in an aged host. Two groups of BALB/c mice (aged 12 to 16 weeks and 72 to 76 weeks) were infected with 2 inocula: a survivable dose of 50 PFU and a lethal dose of 500 PFU. Data were measured at 10 points over 19 days in the sublethal case and at 6 points over 7 days in the lethal case, after which all mice had died. Data varied primarily in the onset of immunity, particularly the inflammatory response, which led to a 2-day delay in the clearance of the virus from older hosts in the sublethal cohort. We developed a Boolean model to describe the interactions between the virus and 21 immune components, including cells, chemokines, and cytokines, of innate and adaptive immunity. The model identifies distinct sets of rules for each age group by using Boolean operators to describe the complex series of interactions that activate and deactivate immune components. Our model accurately simulates the immune responses of mice of both ages and with both inocula included in the data (95% accurate for younger mice and 94% accurate for older mice) and shows distinct rule choices for the innate immunity arm of the model between younger and aging mice in response to influenza A virus infection. IMPORTANCE Influenza virus infection causes high morbidity and mortality rates every year, especially in the elderly. The elderly tend to have a delayed onset of many immune responses as well as prolonged inflammatory responses, leading to an overall weakened response to infection. Many of the details of immune mechanisms that change with age are currently not well understood. We present a rule-based model of the intrahost immune response to influenza virus infection. The model is fit to experimental data for young and old mice infected with influenza virus. We generated distinct sets of rules for each age group to capture the temporal differences seen in the immune responses of these mice. These rules describe a network of interactions leading to either clearance of the virus or death of the host, depending on the initial dosage of the virus. Our models clearly demonstrate differences in these two age groups, particularly in the innate immune responses. Copyright © 2017 American Society for Microbiology.

PSPVDC: An Adaptation of the PSP that Incorporates Verified Design by Contract

DTIC Science & Technology

2013-05-01

characteristics mentioned above, including the following: • Java Modeling Language (JML) implements DbC in Java . VDbC can then be carried out using tools like...Extended Static Checking (ESC/ Java ) [Cok 2005] or TACO [Galeotti 2010]. • Perfect Developer [Crocker 2003] is a specification and modeling language...These are written in the language employed in the environment (e.g., as Java Boolean expressions, if JML is used) which we call the carrier lan

Exact Algorithms for Output Encoding, State Assignment and Four-Level Boolean Minimization

DTIC Science & Technology

1989-10-01

APPROVED FOR PUBLIC DISTRIBUTION • DTIC MASSACHUSETTS INTITUTE OF TECHNOLOGY M VLSI PUBLICATIONSJAN 17 1990 VLSI Memo No. 89-569 JN. 9October 1989...nunijize large funclions exacly within reasonable amocunt. of CPt targeting twro-level logic imnplemientations involve finding ap- time. However, thle ,, m ...0(NV!) m ~iimizations . n5 10 The inptut encoding problemt can be exactly solved using mrultiple-valued Boolean nimuization. We present an exact (a) (b

A single-layer platform for Boolean logic and arithmetic through DNA excision in mammalian cells

PubMed Central

Weinberg, Benjamin H.; Hang Pham, N. T.; Caraballo, Leidy D.; Lozanoski, Thomas; Engel, Adrien; Bhatia, Swapnil; Wong, Wilson W.

2017-01-01

Genetic circuits engineered for mammalian cells often require extensive fine-tuning to perform their intended functions. To overcome this problem, we present a generalizable biocomputing platform that can engineer genetic circuits which function in human cells with minimal optimization. We used our Boolean Logic and Arithmetic through DNA Excision (BLADE) platform to build more than 100 multi-input-multi-output circuits. We devised a quantitative metric to evaluate the performance of the circuits in human embryonic kidney and Jurkat T cells. Of 113 circuits analysed, 109 functioned (96.5%) with the correct specified behavior without any optimization. We used our platform to build a three-input, two-output Full Adder and six-input, one-output Boolean Logic Look Up Table. We also used BLADE to design circuits with temporal small molecule-mediated inducible control and circuits that incorporate CRISPR/Cas9 to regulate endogenous mammalian genes. PMID:28346402

ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

PubMed Central

2011-01-01

Background Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. Results We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Conclusions Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web-based tool for several different input formats, and it makes analysis of complex models accessible to a larger community, as it is platform independent as a web-service and does not require understanding of the underlying mathematics. PMID:21774817

Orientational analysis of planar fibre systems observed as a Poisson shot-noise process.

PubMed

Kärkkäinen, Salme; Lantuéjoul, Christian

2007-10-01

We consider two-dimensional fibrous materials observed as a digital greyscale image. The problem addressed is to estimate the orientation distribution of unobservable thin fibres from a greyscale image modelled by a planar Poisson shot-noise process. The classical stereological approach is not straightforward, because the point intensities of thin fibres along sampling lines may not be observable. For such cases, Kärkkäinen et al. (2001) suggested the use of scaled variograms determined from grey values along sampling lines in several directions. Their method is based on the assumption that the proportion between the scaled variograms and point intensities in all directions of sampling lines is constant. This assumption is proved to be valid asymptotically for Boolean models and dead leaves models, under some regularity conditions. In this work, we derive the scaled variogram and its approximations for a planar Poisson shot-noise process using the modified Bessel function. In the case of reasonable high resolution of the observed image, the scaled variogram has an approximate functional relation to the point intensity, and in the case of high resolution the relation is proportional. As the obtained relations are approximative, they are tested on simulations. The existing orientation analysis method based on the proportional relation is further experimented on images with different resolutions. The new result, the asymptotic proportionality between the scaled variograms and the point intensities for a Poisson shot-noise process, completes the earlier results for the Boolean models and for the dead leaves models.

Numerical simulation of dynamics of brushless dc motors for aerospace and other applications. Volume 1: Model development and applications, part A

NASA Technical Reports Server (NTRS)

Demerdash, N. A. O.; Nehl, T. W.

1979-01-01

The development, fabrication and evaluation of a prototype electromechanical actuator (EMA) is discussed. Application of the EMA as a motor for control surfaces in aerospace flight is examined. A mathematical model of the EMA is developed for design optimization. Nonlinearities which complicate the mathematical model are discussed. The dynamics of the EMA from the underlying physical principles are determined and a discussion of similating the control logic by means of equivalent boolean expressions is presented.

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

PubMed Central

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

INM Integrated Noise Model Version 2. Programmer’s Guide

DTIC Science & Technology

1979-09-01

cost, turnaround time, and system-dependent limitations. 3.2 CONVERSION PROBLEMS Item Item Item No. Desciption Category 1 BLOCK DATA Initialization IBM ...Restricted 2 Boolean Operations Differences Call Statement Parameters Extensions 4 Data Initialization IBM Restricted 5 ENTRY Differences 6 EQUIVALENCE...Machine Dependent 7 Format: A CDC Extension 8 Hollerith Strings IBM Restricted 9 Hollerith Variables IBM Restricted 10 Identifier Names CDC Extension

Designing Experiments to Discriminate Families of Logic Models.

PubMed

Videla, Santiago; Konokotina, Irina; Alexopoulos, Leonidas G; Saez-Rodriguez, Julio; Schaub, Torsten; Siegel, Anne; Guziolowski, Carito

2015-01-01

Logic models of signaling pathways are a promising way of building effective in silico functional models of a cell, in particular of signaling pathways. The automated learning of Boolean logic models describing signaling pathways can be achieved by training to phosphoproteomics data, which is particularly useful if it is measured upon different combinations of perturbations in a high-throughput fashion. However, in practice, the number and type of allowed perturbations are not exhaustive. Moreover, experimental data are unavoidably subjected to noise. As a result, the learning process results in a family of feasible logical networks rather than in a single model. This family is composed of logic models implementing different internal wirings for the system and therefore the predictions of experiments from this family may present a significant level of variability, and hence uncertainty. In this paper, we introduce a method based on Answer Set Programming to propose an optimal experimental design that aims to narrow down the variability (in terms of input-output behaviors) within families of logical models learned from experimental data. We study how the fitness with respect to the data can be improved after an optimal selection of signaling perturbations and how we learn optimal logic models with minimal number of experiments. The methods are applied on signaling pathways in human liver cells and phosphoproteomics experimental data. Using 25% of the experiments, we obtained logical models with fitness scores (mean square error) 15% close to the ones obtained using all experiments, illustrating the impact that our approach can have on the design of experiments for efficient model calibration.

American College of Rheumatology/European League Against Rheumatism remission criteria for rheumatoid arthritis maintain reliable performance when evaluated in 44 joints.

PubMed

Kaneko, Yuko; Kondo, Harumi; Takeuchi, Tsutomu

2013-08-01

To investigate the performance of the new remission criteria for rheumatoid arthritis (RA) in daily clinical practice and the effect of possible misclassification of remission when 44 joints are assessed. Disease activity and remission rate were calculated according to the Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and a Boolean-based definition for 1402 patients with RA in Keio University Hospital. Characteristics of patients in remission were investigated, and the number of misclassified patients was determined--those classified as being in remission based on 28-joint count but as nonremission based on a 44-joint count for each definition criterion. Of all patients analyzed, 46.6%, 45.9%, 41.0%, and 31.5% were classified as in remission in the DAS28, SDAI, CDAI, and Boolean definitions, respectively. Patients classified into remission based only on the DAS28 showed relatively low erythrocyte sedimentation rates but greater swollen joint counts than those classified into remission based on the other definitions. In patients classified into remission based only on the Boolean criteria, the mean physician global assessment was greater than the mean patient global assessment. Although 119 patients had ≤ 1 involved joint in the 28-joint count but > 1 in the 44-joint count, only 34 of these 119 (2.4% of all subjects) were found to have been misclassified into remission. In practice, about half of patients with RA can achieve clinical remission within the DAS28, SDAI, and CDAI; and one-third according to the Boolean-based definition. Patients classified in remission based on a 28-joint count may have pain and swelling in the feet, but misclassification of remission was relatively rare and was seen in only 2.4% of patients under a Boolean definition. The 28-joint count can be sufficient for assessing clinical remission based on the new remission criteria.

Study on the tumor-induced angiogenesis using mathematical models.

PubMed

Suzuki, Takashi; Minerva, Dhisa; Nishiyama, Koichi; Koshikawa, Naohiko; Chaplain, Mark Andrew Joseph

2018-01-01

We studied angiogenesis using mathematical models describing the dynamics of tip cells. We reviewed the basic ideas of angiogenesis models and its numerical simulation technique to produce realistic computer graphics images of sprouting angiogenesis. We examined the classical model of Anderson-Chaplain using fundamental concepts of mass transport and chemical reaction with ECM degradation included. We then constructed two types of numerical schemes, model-faithful and model-driven ones, where new techniques of numerical simulation are introduced, such as transient probability, particle velocity, and Boolean variables. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Security analysis of boolean algebra based on Zhang-Wang digital signature scheme

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

Zheng, Jinbin, E-mail: jbzheng518@163.com

2014-10-06

In 2005, Zhang and Wang proposed an improvement signature scheme without using one-way hash function and message redundancy. In this paper, we show that this scheme exits potential safety concerns through the analysis of boolean algebra, such as bitwise exclusive-or, and point out that mapping is not one to one between assembly instructions and machine code actually by means of the analysis of the result of the assembly program segment, and which possibly causes safety problems unknown to the software.

Realization of a quantum Hamiltonian Boolean logic gate on the Si(001):H surface.

PubMed

Kolmer, Marek; Zuzak, Rafal; Dridi, Ghassen; Godlewski, Szymon; Joachim, Christian; Szymonski, Marek

2015-08-07

The design and construction of the first prototypical QHC (Quantum Hamiltonian Computing) atomic scale Boolean logic gate is reported using scanning tunnelling microscope (STM) tip-induced atom manipulation on an Si(001):H surface. The NOR/OR gate truth table was confirmed by dI/dU STS (Scanning Tunnelling Spectroscopy) tracking how the surface states of the QHC quantum circuit on the Si(001):H surface are shifted according to the input logical status.

How causal analysis can reveal autonomy in models of biological systems

NASA Astrophysics Data System (ADS)

Marshall, William; Kim, Hyunju; Walker, Sara I.; Tononi, Giulio; Albantakis, Larissa

2017-11-01

Standard techniques for studying biological systems largely focus on their dynamical or, more recently, their informational properties, usually taking either a reductionist or holistic perspective. Yet, studying only individual system elements or the dynamics of the system as a whole disregards the organizational structure of the system-whether there are subsets of elements with joint causes or effects, and whether the system is strongly integrated or composed of several loosely interacting components. Integrated information theory offers a theoretical framework to (1) investigate the compositional cause-effect structure of a system and to (2) identify causal borders of highly integrated elements comprising local maxima of intrinsic cause-effect power. Here we apply this comprehensive causal analysis to a Boolean network model of the fission yeast (Schizosaccharomyces pombe) cell cycle. We demonstrate that this biological model features a non-trivial causal architecture, whose discovery may provide insights about the real cell cycle that could not be gained from holistic or reductionist approaches. We also show how some specific properties of this underlying causal architecture relate to the biological notion of autonomy. Ultimately, we suggest that analysing the causal organization of a system, including key features like intrinsic control and stable causal borders, should prove relevant for distinguishing life from non-life, and thus could also illuminate the origin of life problem. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Cross-talk between Rho and Rac GTPases drives deterministic exploration of cellular shape space and morphological heterogeneity.

PubMed

Sailem, Heba; Bousgouni, Vicky; Cooper, Sam; Bakal, Chris

2014-01-22

One goal of cell biology is to understand how cells adopt different shapes in response to varying environmental and cellular conditions. Achieving a comprehensive understanding of the relationship between cell shape and environment requires a systems-level understanding of the signalling networks that respond to external cues and regulate the cytoskeleton. Classical biochemical and genetic approaches have identified thousands of individual components that contribute to cell shape, but it remains difficult to predict how cell shape is generated by the activity of these components using bottom-up approaches because of the complex nature of their interactions in space and time. Here, we describe the regulation of cellular shape by signalling systems using a top-down approach. We first exploit the shape diversity generated by systematic RNAi screening and comprehensively define the shape space a migratory cell explores. We suggest a simple Boolean model involving the activation of Rac and Rho GTPases in two compartments to explain the basis for all cell shapes in the dataset. Critically, we also generate a probabilistic graphical model to show how cells explore this space in a deterministic, rather than a stochastic, fashion. We validate the predictions made by our model using live-cell imaging. Our work explains how cross-talk between Rho and Rac can generate different cell shapes, and thus morphological heterogeneity, in genetically identical populations.

Self-Organized Link State Aware Routing for Multiple Mobile Agents in Wireless Network

NASA Astrophysics Data System (ADS)

Oda, Akihiro; Nishi, Hiroaki

Recently, the importance of data sharing structures in autonomous distributed networks has been increasing. A wireless sensor network is used for managing distributed data. This type of distributed network requires effective information exchanging methods for data sharing. To reduce the traffic of broadcasted messages, reduction of the amount of redundant information is indispensable. In order to reduce packet loss in mobile ad-hoc networks, QoS-sensitive routing algorithm have been frequently discussed. The topology of a wireless network is likely to change frequently according to the movement of mobile nodes, radio disturbance, or fading due to the continuous changes in the environment. Therefore, a packet routing algorithm should guarantee QoS by using some quality indicators of the wireless network. In this paper, a novel information exchanging algorithm developed using a hash function and a Boolean operation is proposed. This algorithm achieves efficient information exchanges by reducing the overhead of broadcasting messages, and it can guarantee QoS in a wireless network environment. It can be applied to a routing algorithm in a mobile ad-hoc network. In the proposed routing algorithm, a routing table is constructed by using the received signal strength indicator (RSSI), and the neighborhood information is periodically broadcasted depending on this table. The proposed hash-based routing entry management by using an extended MAC address can eliminate the overhead of message flooding. An analysis of the collision of hash values contributes to the determination of the length of the hash values, which is minimally required. Based on the verification of a mathematical theory, an optimum hash function for determining the length of hash values can be given. Simulations are carried out to evaluate the effectiveness of the proposed algorithm and to validate the theory in a general wireless network routing algorithm.

Experimental Clocking of Nanomagnets with Strain for Ultralow Power Boolean Logic.

PubMed

D'Souza, Noel; Salehi Fashami, Mohammad; Bandyopadhyay, Supriyo; Atulasimha, Jayasimha

2016-02-10

Nanomagnetic implementations of Boolean logic have attracted attention because of their nonvolatility and the potential for unprecedented overall energy-efficiency. Unfortunately, the large dissipative losses that occur when nanomagnets are switched with a magnetic field or spin-transfer-torque severely compromise the energy-efficiency. Recently, there have been experimental reports of utilizing the Spin Hall effect for switching magnets, and theoretical proposals for strain induced switching of single-domain magnetostrictive nanomagnets, that might reduce the dissipative losses significantly. Here, we experimentally demonstrate, for the first time that strain-induced switching of single-domain magnetostrictive nanomagnets of lateral dimensions ∼200 nm fabricated on a piezoelectric substrate can implement a nanomagnetic Boolean NOT gate and steer bit information unidirectionally in dipole-coupled nanomagnet chains. On the basis of the experimental results with bulk PMN-PT substrates, we estimate that the energy dissipation for logic operations in a reasonably scaled system using thin films will be a mere ∼1 aJ/bit.

An operator calculus for surface and volume modeling

NASA Technical Reports Server (NTRS)

Gordon, W. J.

1984-01-01

The mathematical techniques which form the foundation for most of the surface and volume modeling techniques used in practice are briefly described. An outline of what may be termed an operator calculus for the approximation and interpolation of functions of more than one independent variable is presented. By considering the linear operators associated with bivariate and multivariate interpolation/approximation schemes, it is shown how they can be compounded by operator multiplication and Boolean addition to obtain a distributive lattice of approximation operators. It is then demonstrated via specific examples how this operator calculus leads to practical techniques for sculptured surface and volume modeling.

A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion

PubMed Central

Hetmanski, Joseph H. R.; Zindy, Egor; Schwartz, Jean-Marc; Caswell, Patrick T.

2016-01-01

Cell migration in 3D microenvironments is fundamental to development, homeostasis and the pathobiology of diseases such as cancer. Rab-coupling protein (RCP) dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin (FN) containing extracellular matrix (ECM), by potentiating EGFR1 signalling at the front of invasive cells. This promotes a switch in RhoGTPase signalling to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3) pathway and generate filopodial actin-spike protrusions which drive invasion. To further understand the signalling network that drives RCP-driven invasive migration, we generated a Boolean logical model based on existing network pathways/models, where each node can be interrogated by computational simulation. The model predicted an unanticipated feedback loop, whereby Raf/MEK/ERK signalling maintains suppression of Rac1 by inhibiting the Rac-activating Sos1-Eps8-Abi1 complex, allowing RhoA activity to predominate in invasive protrusions. MEK inhibition was sufficient to promote lamellipodia formation and oppose filopodial actin-spike formation, and led to activation of Rac and inactivation of RhoA at the leading edge of cells moving in 3D matrix. Furthermore, MEK inhibition abrogated RCP/α5β1/EGFR1-driven invasive migration. However, upon knockdown of Eps8 (to suppress the Sos1-Abi1-Eps8 complex), MEK inhibition had no effect on RhoGTPase activity and did not oppose invasive migration, suggesting that MEK-ERK signalling suppresses the Rac-activating Sos1-Abi1-Eps8 complex to maintain RhoA activity and promote filopodial actin-spike formation and invasive migration. Our study highlights the predictive potential of mathematical modelling approaches, and demonstrates that a simple intervention (MEK-inhibition) could be of therapeutic benefit in preventing invasive migration and metastasis. PMID:27138333

Modeling of High-Quality Factor XNOR Gate Using Quantum-Dot Semiconductor Optical Amplifiers at 1 Tb/s

NASA Astrophysics Data System (ADS)

Kotb, Amer

2015-06-01

The modeling of all-optical logic XNOR gate is realized by a series combination of XOR and INVERT gates. This Boolean function is simulated by using Mach-Zehnder interferometers (MZIs) utilizing quantum-dots semiconductor optical amplifiers (QDs-SOAs). The study is carried out when the effect of amplified spontaneous emission (ASE) is included. The dependence of the output quality factor ( Q-factor) on signals and QDs-SOAs' parameters is also investigated and discussed. The simulation is conducted under a repetition rate of ˜1 Tb/s.

Symbolic Boolean Manipulation with Ordered Binary Decision Diagrams

DTIC Science & Technology

1992-07-01

memories , where careful attention has been given to programming the memory management routines [Brace et al 19901. To extract maximum performance, it...OBDDs) represent Boolean functions as directed acyclic graphs. They form a canonical representation, making testing of functional properties such as...indicated 3 X X2 X3 f 000 0 0 01 0X22 0 10 0 0 11 1 d 1 0 0 0 X3 X 3X 1 01 1 1 10 0 - i"o11 10o 1 1 Figure 1: Truth Table and Decison Tree Repremmtatios

A Parallel Approach in Computing Correlation Immunity up to Six Variables

DTIC Science & Technology

2015-03-10

their nonlinearity is divisible by 4. Let CI(n, k) (respectively, BCI (n, k)) be the number of exact order k correlation im- mune, (respectively...further balanced) n-variable Boolean functions. The notations CI(n, k, d), BCI (n, k, d) restricts the previous count to degree d Boolean functions...Theorem 3. The following are true: (i) BCI (n, n, 0) = 0, CI(n, n, 0) = 2, CI(n, k, 1) = BCI (n, k, 1) = 2 ( n k+1 ) , 0 ≤ k ≤ n− 1. (ii) BCI (n, n− 2) = 2

On Weak and Strong 2k- bent Boolean Functions

DTIC Science & Technology

2016-01-01

U.S.A. Email: pstanica@nps.edu Abstract—In this paper we introduce a sequence of discrete Fourier transforms and define new versions of bent...denotes the complex conjugate of z. An important tool in our analysis is the discrete Fourier transform , known in Boolean functions literature, as Walsh...Hadamard, or Walsh–Hadamard transform , which is the func- tion Wf : Fn2 → C, defined by Wf (u) = 2− n 2 ∑ x∈Vn (−1)f(x)⊕u·x. Any f ∈ Bn can be

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

NASA Astrophysics Data System (ADS)

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.

Novel Prostate Cancer Pathway Modeling using Boolean Implication

DTIC Science & Technology

2012-09-01

cause of cancer deaths in men. Diagnosis and pathogenesis of this disease is poorly understood. Prostate specific antigen (PSA) test is still the... specific database, I combined 14 different datasets (global prostate cancer database, total n=891) that are in Affymetrix U133A (n=456), U133A 2.0...immunohistochemistry and flow cytometry are limited by the availability of antigen - specific monoclonal antibodies and by the small number of parallel

Fredkin and Toffoli Gates Implemented in Oregonator Model of Belousov-Zhabotinsky Medium

NASA Astrophysics Data System (ADS)

Adamatzky, Andrew

A thin-layer Belousov-Zhabotinsky (BZ) medium is a powerful computing device capable for implementing logical circuits, memory, image processors, robot controllers, and neuromorphic architectures. We design the reversible logical gates — Fredkin gate and Toffoli gate — in a BZ medium network of excitable channels with subexcitable junctions. Local control of the BZ medium excitability is an important feature of the gates’ design. An excitable thin-layer BZ medium responds to a localized perturbation with omnidirectional target or spiral excitation waves. A subexcitable BZ medium responds to an asymmetric perturbation by producing traveling localized excitation wave-fragments similar to dissipative solitons. We employ interactions between excitation wave-fragments to perform the computation. We interpret the wave-fragments as values of Boolean variables. The presence of a wave-fragment at a given site of a circuit represents the logical truth, absence of the wave-fragment — logically false. Fredkin gate consists of ten excitable channels intersecting at 11 junctions, eight of which are subexcitable. Toffoli gate consists of six excitable channels intersecting at six junctions, four of which are subexcitable. The designs of the gates are verified using numerical integration of two-variable Oregonator equations.

Classification of Genes and Putative Biomarker Identification Using Distribution Metrics on Expression Profiles

PubMed Central

Huang, Hung-Chung; Jupiter, Daniel; VanBuren, Vincent

2010-01-01

Background Identification of genes with switch-like properties will facilitate discovery of regulatory mechanisms that underlie these properties, and will provide knowledge for the appropriate application of Boolean networks in gene regulatory models. As switch-like behavior is likely associated with tissue-specific expression, these gene products are expected to be plausible candidates as tissue-specific biomarkers. Methodology/Principal Findings In a systematic classification of genes and search for biomarkers, gene expression profiles (GEPs) of more than 16,000 genes from 2,145 mouse array samples were analyzed. Four distribution metrics (mean, standard deviation, kurtosis and skewness) were used to classify GEPs into four categories: predominantly-off, predominantly-on, graded (rheostatic), and switch-like genes. The arrays under study were also grouped and examined by tissue type. For example, arrays were categorized as ‘brain group’ and ‘non-brain group’; the Kolmogorov-Smirnov distance and Pearson correlation coefficient were then used to compare GEPs between brain and non-brain for each gene. We were thus able to identify tissue-specific biomarker candidate genes. Conclusions/Significance The methodology employed here may be used to facilitate disease-specific biomarker discovery. PMID:20140228

Shape-dependent control of cell growth, differentiation, and apoptosis: switching between attractors in cell regulatory networks

NASA Technical Reports Server (NTRS)

Huang, S.; Ingber, D. E.

2000-01-01

Development of characteristic tissue patterns requires that individual cells be switched locally between different phenotypes or "fates;" while one cell may proliferate, its neighbors may differentiate or die. Recent studies have revealed that local switching between these different gene programs is controlled through interplay between soluble growth factors, insoluble extracellular matrix molecules, and mechanical forces which produce cell shape distortion. Although the precise molecular basis remains unknown, shape-dependent control of cell growth and function appears to be mediated by tension-dependent changes in the actin cytoskeleton. However, the question remains: how can a generalized physical stimulus, such as cell distortion, activate the same set of genes and signaling proteins that are triggered by molecules which bind to specific cell surface receptors. In this article, we use computer simulations based on dynamic Boolean networks to show that the different cell fates that a particular cell can exhibit may represent a preprogrammed set of common end programs or "attractors" which self-organize within the cell's regulatory networks. In this type of dynamic network model of information processing, generalized stimuli (e.g., mechanical forces) and specific molecular cues elicit signals which follow different trajectories, but eventually converge onto one of a small set of common end programs (growth, quiescence, differentiation, apoptosis, etc.). In other words, if cells use this type of information processing system, then control of cell function would involve selection of preexisting (latent) behavioral modes of the cell, rather than instruction by specific binding molecules. Importantly, the results of the computer simulation closely mimic experimental data obtained with living endothelial cells. The major implication of this finding is that current methods used for analysis of cell function that rely on characterization of linear signaling pathways or clusters of genes with common activity profiles may overlook the most critical features of cellular information processing which normally determine how signal specificity is established and maintained in living cells. Copyright 2000 Academic Press.

Using narrative inquiry to listen to the voices of adolescent mothers in relation to their use of social networking sites (SNS).

PubMed

Nolan, Samantha; Hendricks, Joyce; Williamson, Moira; Ferguson, Sally

2018-03-01

This article presents a discussion highlighting the relevance and strengths of using narrative inquiry to explore experiences of social networking site (SNS) use by adolescent mothers. Narrative inquiry as a method reveals truths about holistic human experience. Knowledge gleaned from personal narratives informs nursing knowledge and clinical practice. This approach gives voice to adolescent mothers in relation to their experiences with SNS as a means of providing social support. Discussion paper. This paper draws and reflects on the author's experiences using narrative inquiry and is supported by literature and theory. The following databases were searched: CINAHL, Cochrane Library, Medline, Scopus, ERIC, ProQuest, PsychINFO, Web of Science and Health Collection (Informit). Key terms and Boolean search operators were used to broaden the search criteria. Search terms included: adolescent mother, teenage mother, "social networking sites", online, social media, Facebook, social support, social capital and information. Dates for the search were limited to January 1995-June 2017. Narrative research inherently values the individual "story" of experience. This approach facilitates rapport building and methodological flexibility with an often difficult to engage sample group, adolescents. Narrative inquiry reveals a deep level of insight into social networking site use by adolescent mothers. The flexibility afforded by use of a narrative approach allows for fluidity and reflexivity in the research process. © 2017 John Wiley & Sons Ltd.

Proposal for an All-Spin Artificial Neural Network: Emulating Neural and Synaptic Functionalities Through Domain Wall Motion in Ferromagnets.

PubMed

Sengupta, Abhronil; Shim, Yong; Roy, Kaushik

2016-12-01

Non-Boolean computing based on emerging post-CMOS technologies can potentially pave the way for low-power neural computing platforms. However, existing work on such emerging neuromorphic architectures have either focused on solely mimicking the neuron, or the synapse functionality. While memristive devices have been proposed to emulate biological synapses, spintronic devices have proved to be efficient at performing the thresholding operation of the neuron at ultra-low currents. In this work, we propose an All-Spin Artificial Neural Network where a single spintronic device acts as the basic building block of the system. The device offers a direct mapping to synapse and neuron functionalities in the brain while inter-layer network communication is accomplished via CMOS transistors. To the best of our knowledge, this is the first demonstration of a neural architecture where a single nanoelectronic device is able to mimic both neurons and synapses. The ultra-low voltage operation of low resistance magneto-metallic neurons enables the low-voltage operation of the array of spintronic synapses, thereby leading to ultra-low power neural architectures. Device-level simulations, calibrated to experimental results, was used to drive the circuit and system level simulations of the neural network for a standard pattern recognition problem. Simulation studies indicate energy savings by  ∼  100× in comparison to a corresponding digital/analog CMOS neuron implementation.

Piecewise linear approximations to model the dynamics of adaptation to osmotic stress by food-borne pathogens.

PubMed

Métris, Aline; George, Susie M; Ropers, Delphine

2017-01-02

Addition of salt to food is one of the most ancient and most common methods of food preservation. However, little is known of how bacterial cells adapt to such conditions. We propose to use piecewise linear approximations to model the regulatory adaptation of Escherichiacoli to osmotic stress. We apply the method to eight selected genes representing the functions known to be at play during osmotic adaptation. The network is centred on the general stress response factor, sigma S, and also includes a module representing the catabolic repressor CRP-cAMP. Glutamate, potassium and supercoiling are combined to represent the intracellular regulatory signal during osmotic stress induced by salt. The output is a module where growth is represented by the concentration of stable RNAs and the transcription of the osmotic gene osmY. The time course of gene expression of transport of osmoprotectant represented by the symporter proP and of the osmY is successfully reproduced by the network. The behaviour of the rpoS mutant predicted by the model is in agreement with experimental data. We discuss the application of the model to food-borne pathogens such as Salmonella; although the genes considered have orthologs, it seems that supercoiling is not regulated in the same way. The model is limited to a few selected genes, but the regulatory interactions are numerous and span different time scales. In addition, they seem to be condition specific: the links that are important during the transition from exponential to stationary phase are not all needed during osmotic stress. This model is one of the first steps towards modelling adaptation to stress in food safety and has scope to be extended to other genes and pathways, other stresses relevant to the food industry, and food-borne pathogens. The method offers a good compromise between systems of ordinary differential equations, which would be unmanageable because of the size of the system and for which insufficient data are available, and the more abstract Boolean methods. Copyright © 2016 Elsevier B.V. All rights reserved.

Towards A Topological Framework for Integrating Semantic Information Sources

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

Joslyn, Cliff A.; Hogan, Emilie A.; Robinson, Michael

2014-09-07

In this position paper we argue for the role that topological modeling principles can play in providing a framework for sensor integration. While used successfully in standard (quantitative) sensors, we are developing this methodology in new directions to make it appropriate specifically for semantic information sources, including keyterms, ontology terms, and other general Boolean, categorical, ordinal, and partially-ordered data types. We illustrate the basics of the methodology in an extended use case/example, and discuss path forward.

Continuous variables logic via coupled automata using a DNAzyme cascade with feedback.

PubMed

Lilienthal, S; Klein, M; Orbach, R; Willner, I; Remacle, F; Levine, R D

2017-03-01

The concentration of molecules can be changed by chemical reactions and thereby offer a continuous readout. Yet computer architecture is cast in textbooks in terms of binary valued, Boolean variables. To enable reactive chemical systems to compute we show how, using the Cox interpretation of probability theory, one can transcribe the equations of chemical kinetics as a sequence of coupled logic gates operating on continuous variables. It is discussed how the distinct chemical identity of a molecule allows us to create a common language for chemical kinetics and Boolean logic. Specifically, the logic AND operation is shown to be equivalent to a bimolecular process. The logic XOR operation represents chemical processes that take place concurrently. The values of the rate constants enter the logic scheme as inputs. By designing a reaction scheme with a feedback we endow the logic gates with a built in memory because their output then depends on the input and also on the present state of the system. Technically such a logic machine is an automaton. We report an experimental realization of three such coupled automata using a DNAzyme multilayer signaling cascade. A simple model verifies analytically that our experimental scheme provides an integrator generating a power series that is third order in time. The model identifies two parameters that govern the kinetics and shows how the initial concentrations of the substrates are the coefficients in the power series.

A survey of SAT solver

NASA Astrophysics Data System (ADS)

Gong, Weiwei; Zhou, Xu

2017-06-01

In Computer Science, the Boolean Satisfiability Problem(SAT) is the problem of determining if there exists an interpretation that satisfies a given Boolean formula. SAT is one of the first problems that was proven to be NP-complete, which is also fundamental to artificial intelligence, algorithm and hardware design. This paper reviews the main algorithms of the SAT solver in recent years, including serial SAT algorithms, parallel SAT algorithms, SAT algorithms based on GPU, and SAT algorithms based on FPGA. The development of SAT is analyzed comprehensively in this paper. Finally, several possible directions for the development of the SAT problem are proposed.

A Parallel Approach in Computing Correlation Immunity up to Six Variables

DTIC Science & Technology

2015-07-24

nonlinearity is divisible by 4. Let CI(n, k) (respectively, BCI (n, k)) be the number of exact order k corre- lation immune, (respectively, further...balanced) n-variable Boolean functions. The notations CI(n, k, d), BCI (n, k, d) restricts the previous count to degree d Boolean functions. Theorem 3...The following are true: (i) BCI (n, n, 0) = 0, CI(n, n, 0) = 2, CI(n, k, 1) = BCI (n, k, 1) = 2 ( n k+1 ) , 0 ≤ k ≤ n− 1. (ii) BCI (n, n− 2) = 2 ( n n−1

High speed all optical logic gates based on quantum dot semiconductor optical amplifiers.

PubMed

Ma, Shaozhen; Chen, Zhe; Sun, Hongzhi; Dutta, Niloy K

2010-03-29

A scheme to realize all-optical Boolean logic functions AND, XOR and NOT using semiconductor optical amplifiers with quantum-dot active layers is studied. nonlinear dynamics including carrier heating and spectral hole-burning are taken into account together with the rate equations scheme. Results show with QD excited state and wetting layer serving as dual-reservoir of carriers, as well as the ultra fast carrier relaxation of the QD device, this scheme is suitable for high speed Boolean logic operations. Logic operation can be carried out up to speed of 250 Gb/s.

Simulation model for a seven-phase BLDCM drive system

NASA Astrophysics Data System (ADS)

Park, Sang-Hoon; Lee, Won-Cheol; Lee, Jung-Hyo; Yu, Jae-Sung; Kim, Gyu-Sik; Won, Chung-Yuen

2007-12-01

BLDC motors have many advantages over brushed DC motors and induction motors. So, BLDC motors extend their application to many industrial fields. In this paper, the digital simulation and modeling of a 7-phase brushless DC motor have been presented. The 14-switch inverter and a 7-phase brushless DC motor drive system are simulated using hysteresis current controller and logic of switching pattern with the Boolean¡s function. Through some simulations, we found that our modeling and analysis of a 7-phase BLDCM with PWM inverter would be helpful for the further studies of the multi-phase BLDCM drive systems.

Enzyme-regulated the changes of pH values for assembling a colorimetric and multistage interconnection logic network with multiple readouts.

PubMed

Huang, Yanyan; Ran, Xiang; Lin, Youhui; Ren, Jinsong; Qu, Xiaogang

2015-04-22

Based on enzymatic reactions-triggered changes of pH values and biocomputing, a novel and multistage interconnection biological network with multiple easy-detectable signal outputs has been developed. Compared with traditional chemical computing, the enzyme-based biological system could overcome the interference between reactions or the incompatibility of individual computing gates and offer a unique opportunity to assemble multicomponent/multifunctional logic circuitries. Our system included four enzyme inputs: β-galactosidase (β-gal), glucose oxidase (GOx), esterase (Est) and urease (Ur). With the assistance of two signal transducers (gold nanoparticles and acid-base indicators) or pH meter, the outputs of the biological network could be conveniently read by the naked eyes. In contrast to current methods, the approach present here could realize cost-effective, label-free and colorimetric logic operations without complicated instrument. By designing a series of Boolean logic operations, we could logically make judgment of the compositions of the samples on the basis of visual output signals. Our work offered a promising paradigm for future biological computing technology and might be highly useful in future intelligent diagnostics, prodrug activation, smart drug delivery, process control, and electronic applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Social networking site (SNS) use by adolescent mothers: Can social support and social capital be enhanced by online social networks? - A structured review of the literature.

PubMed

Nolan, Samantha; Hendricks, Joyce; Ferguson, Sally; Towell, Amanda

2017-05-01

to critically appraise the available literature and summarise the evidence relating to adolescent mothers' use of social networking sites in terms of any social support and social capital they may provide and to identify areas for future exploration. social networking sites have been demonstrated to provide social support to marginalised individuals and provide psycho-social benefits to members of such groups. Adolescent mothers are at risk of; social marginalisation; anxiety disorders and depressive symptoms; and poorer health and educational outcomes for their children. Social support has been shown to benefit adolescent mothers thus online mechanisms require consideration. a review of original research articles METHOD: key terms and Boolean operators identified research reports across a 20-year timeframe pertaining to the area of enquiry in: CINAHL, Cochrane Library, Medline, Scopus, ERIC, ProQuest, PsychINFO, Web of Science, Health Collection (Informit) and Google Scholar databases. Eight original research articles met the inclusion criteria for this review. studies demonstrate that adolescent mothers actively search for health information using the Internet and social networking sites, and that social support and social capital can be attributed to their use of specifically created online groups from within targeted health interventions. Use of a message board forum for pregnant and parenting adolescents also demonstrates elements of social support. There are no studies to date pertaining to adolescent mothers' use of globally accessible social networking sites in terms of social support provision and related outcomes. further investigation is warranted to explore the potential benefits of adolescent mothers' use of globally accessible social networking sites in terms of any social support provision and social capital they may provide. Copyright © 2017 Elsevier Ltd. All rights reserved.

3D GIS spatial operation based on extended Euler operators

NASA Astrophysics Data System (ADS)

Xu, Hongbo; Lu, Guonian; Sheng, Yehua; Zhou, Liangchen; Guo, Fei; Shang, Zuoyan; Wang, Jing

2008-10-01

The implementation of 3 dimensions spatial operations, based on certain data structure, has a lack of universality and is not able to treat with non-manifold cases, at present. ISO/DIS 19107 standard just presents the definition of Boolean operators and set operators for topological relationship query, and OGC GeoXACML gives formal definitions for several set functions without implementation detail. Aiming at these problems, based mathematical foundation on cell complex theory, supported by non-manifold data structure and using relevant research in the field of non-manifold geometry modeling for reference, firstly, this paper according to non-manifold Euler-Poincaré formula constructs 6 extended Euler operators and inverse operators to carry out creating, updating and deleting 3D spatial elements, as well as several pairs of supplementary Euler operators to convenient for implementing advanced functions. Secondly, we change topological element operation sequence of Boolean operation and set operation as well as set functions defined in GeoXACML into combination of extended Euler operators, which separates the upper functions and lower data structure. Lastly, we develop underground 3D GIS prototype system, in which practicability and credibility of extended Euler operators faced to 3D GIS presented by this paper are validated.

Effect of remission definition on healthcare cost savings estimates for patients with rheumatoid arthritis treated with biologic therapies.

PubMed

Barnabe, Cheryl; Thanh, Nguyen Xuan; Ohinmaa, Arto; Homik, Joanne; Barr, Susan G; Martin, Liam; Maksymowych, Walter P

2014-08-01

Sustained remission in rheumatoid arthritis (RA) results in healthcare utilization cost savings. We evaluated the variation in estimates of savings when different definitions of remission [2011 American College of Rheumatology/European League Against Rheumatism Boolean Definition, Simplified Disease Activity Index (SDAI) ≤ 3.3, Clinical Disease Activity Index (CDAI) ≤ 2.8, and Disease Activity Score-28 (DAS28) ≤ 2.6] are applied. The annual mean healthcare service utilization costs were estimated from provincial physician billing claims, outpatient visits, and hospitalizations, with linkage to clinical data from the Alberta Biologics Pharmacosurveillance Program (ABioPharm). Cost savings in patients who had a 1-year continuous period of remission were compared to those who did not, using 4 definitions of remission. In 1086 patients, sustained remission rates were 16.1% for DAS28, 8.8% for Boolean, 5.5% for CDAI, and 4.2% for SDAI. The estimated mean annual healthcare cost savings per patient achieving remission (relative to not) were SDAI $1928 (95% CI 592, 3264), DAS28 $1676 (95% CI 987, 2365), and Boolean $1259 (95% CI 417, 2100). The annual savings by CDAI remission per patient were not significant at $423 (95% CI -1757, 2602). For patients in DAS28, Boolean, and SDAI remission, savings were seen both in costs directly related to RA and its comorbidities, and in costs for non-RA-related conditions. The magnitude of the healthcare cost savings varies according to the remission definition used in classifying patient disease status. The highest point estimate for cost savings was observed in patients attaining SDAI remission and the least with the CDAI; confidence intervals for these estimates do overlap. Future pharmacoeconomic analyses should employ all response definitions in assessing the influence of treatment.

The DAS28-ESR cutoff value necessary to achieve remission under the new Boolean-based remission criteria in patients receiving tocilizumab.

PubMed

Hirabayashi, Yasuhiko; Ishii, Tomonori

2013-01-01

To seek the cutoff value of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) that is necessary to achieve remission under the new Boolean-based criteria, we analyzed the data for 285 patients with rheumatoid arthritis registered between May 2008 and November 2009 by the Michinoku Tocilizumab Study Group and observed for 1 year after receiving tocilizumab (TCZ) in real clinical practice. Remission rates under the DAS28-ESR criteria and the Boolean criteria were assessed every 6 months after the first TCZ dose. The DAS28-ESR cutoff value necessary to achieve remission under the new criteria was analyzed by receiver operating characteristic (ROC) analysis. Data were analyzed using last observation carried forward. After 12 months of TCZ use, remission was achieved in 164 patients (57.5 %) by DAS28-ESR and 71 patients (24.9 %) under the new criteria for clinical trials. CRP levels scarcely affected remission rates, and the difference between remission rates defined by DAS28-ESR and by the new criteria was mainly due to patient global assessment (PGA). Improvement of PGA was inversely related to disease duration. ROC analysis revealed that the DAS28-ESR cutoff value necessary to predict remission under the new criteria for clinical trials was 1.54, with a sensitivity of 88.7 %, specificity of 85.5 %, positive predictive value of 67.0 %, and negative predictive value of 95.8 %. A DAS28-ESR cutoff value of 1.54 may be reasonable to predict achievement of remission under the new Boolean-based criteria for clinical trials in patients receiving TCZ.

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

Miyadera, Takayuki; Imai, Hideki; Graduate School of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551

This paper discusses the no-cloning theorem in a logicoalgebraic approach. In this approach, an orthoalgebra is considered as a general structure for propositions in a physical theory. We proved that an orthoalgebra admits cloning operation if and only if it is a Boolean algebra. That is, only classical theory admits the cloning of states. If unsharp propositions are to be included in the theory, then a notion of effect algebra is considered. We proved that an atomic Archimedean effect algebra admitting cloning operation is a Boolean algebra. This paper also presents a partial result, indicating a relation between the cloningmore » on effect algebras and hidden variables.« less

Computer Program Development Specification for Ada Integrated Environment. Ada Compiler Phases B5-AIE (1). COMP (1).

DTIC Science & Technology

1982-11-05

routines required by the Back End. 3.3 Detailed Functional Requirements 3.3.1 Front End 3.3.1.1 DRIVER The DRIVER is the primary user interface to the...Main 2. Exam ple" !.i ,, , ,vari able • id -: go for B Boolean Ai ’ A" ’ I type d 1 I , for Boolean I (from Standard) i I - - for A function i fuction ...TN in. If a TN cannot be allocated to the primary area of storage it needs(such as a register) it is allocated to the spill area reserved in the local

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

PubMed

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.

A comparison of Boolean-based retrieval to the WAIS system for retrieval of aeronautical information

NASA Technical Reports Server (NTRS)

Marchionini, Gary; Barlow, Diane

1994-01-01

An evaluation of an information retrieval system using a Boolean-based retrieval engine and inverted file architecture and WAIS, which uses a vector-based engine, was conducted. Four research questions in aeronautical engineering were used to retrieve sets of citations from the NASA Aerospace Database which was mounted on a WAIS server and available through Dialog File 108 which served as the Boolean-based system (BBS). High recall and high precision searches were done in the BBS and terse and verbose queries were used in the WAIS condition. Precision values for the WAIS searches were consistently above the precision values for high recall BBS searches and consistently below the precision values for high precision BBS searches. Terse WAIS queries gave somewhat better precision performance than verbose WAIS queries. In every case, a small number of relevant documents retrieved by one system were not retrieved by the other, indicating the incomplete nature of the results from either retrieval system. Relevant documents in the WAIS searches were found to be randomly distributed in the retrieved sets rather than distributed by ranks. Advantages and limitations of both types of systems are discussed.

Boolean logic analysis for flow regime recognition of gas-liquid horizontal flow

NASA Astrophysics Data System (ADS)

Ramskill, Nicholas P.; Wang, Mi

2011-10-01

In order to develop a flowmeter for the accurate measurement of multiphase flows, it is of the utmost importance to correctly identify the flow regime present to enable the selection of the optimal method for metering. In this study, the horizontal flow of air and water in a pipeline was studied under a multitude of conditions using electrical resistance tomography but the flow regimes that are presented in this paper have been limited to plug and bubble air-water flows. This study proposes a novel method for recognition of the prevalent flow regime using only a fraction of the data, thus rendering the analysis more efficient. By considering the average conductivity of five zones along the central axis of the tomogram, key features can be identified, thus enabling the recognition of the prevalent flow regime. Boolean logic and frequency spectrum analysis has been applied for flow regime recognition. Visualization of the flow using the reconstructed images provides a qualitative comparison between different flow regimes. Application of the Boolean logic scheme enables a quantitative comparison of the flow patterns, thus reducing the subjectivity in the identification of the prevalent flow regime.

A simplified GIS-based model for large wood recruitment and connectivity in mountain basins

NASA Astrophysics Data System (ADS)

Lucía, Ana; Antonello, Andrea; Campana, Daniela; Cavalli, Marco; Crema, Stefano; Franceschi, Silvia; Marchese, Enrico; Niedrist, Martin; Schneiderbauer, Stefan; Comiti, Francesco

2014-05-01

The mobilization of large wood (LW) elements in mountain rivers channels during floods may increase their hazard potential, especially by clogging narrow sections such as bridges. However, the prediction of LW transport magnitude during flood events is a challenging topic. Although some models on LW transport have been recently developed, the objective of this work was to generate a simplified GIS-based model to identify along the channel network the most likely LW-related critical sections during high-magnitude flood events in forested mountain basins. Potential LW contribution generated by landsliding occurring on hillslopes is assessed using SHALSTAB stability model coupled to a GIS-based connectivity index, developed as a modification of the index proposed by Cavalli et al (2013). Connected slope-derived LW volumes are then summed at each raster cell to LW volumes generated by bank erosion along the erodibile part of river corridors, where bank erosion processes are estimated based on user-defined channel widening ratios stemming from observations following recent extreme events in mountain basins. LW volume in the channel is then routed through the stream network applying simple Boolean rules meant to capture the most important limiting transport condition in these high-energy systems at flood stage, i.e. flow width relative to log length. In addition, the role of bridges and retention check-dams in blocking floating logs is accounted for in the model, in particular bridge length and height are used to characterize their clogging susceptibility for different levels of expected LW volumes and size. The model has been tested in the Rienz and Ahr basins (about 630 km2 each), located in the Eastern Italian Alps. Sixty percent of the basin area is forested, and elevations range from 811 m a.s.l. to 3488 m a.s.l.. We used a 2.5 m resolution DTM and DSM, and their difference was used to calculate the canopy height. Data from 35 plots of the National Forest Inventory were used to estimate forest stand volume by a semi-empirical model. Ddatabase on shallow landslides along with precipitation depth was utilized to calibrate the parameters for the SHALSTAB model. Orthophotos (0.5 m pixel resolution) and existing technical maps were used to delimitate the channel banks, which were used to calculate automatically channel width for each grid cell. The model output provided information about the expected volume and mean size of LW recruited and transported during a 300 yr flood event in the test basins, as well as the location of the most probable clogged sections (mostly related to infrastructures) along the channel network. The model thus shows the capability to assist river managers in identifying the most critical sections of river networks and to assess the effectiveness and location of different mitigation options such as wood retention structures or forest management practices.

Predictable turn-around time for post tape-out flow

NASA Astrophysics Data System (ADS)

Endo, Toshikazu; Park, Minyoung; Ghosh, Pradiptya

2012-03-01

A typical post-out flow data path at the IC Fabrication has following major components of software based processing - Boolean operations before the application of resolution enhancement techniques (RET) and optical proximity correctin (OPC), the RET and OPC step [etch retargeting, sub-resolution assist feature insertion (SRAF) and OPC], post-OPCRET Boolean operations and sometimes in the same flow simulation based verification. There are two objectives that an IC Fabrication tapeout flow manager wants to achieve with the flow - predictable completion time and fastest turn-around time (TAT). At times they may be competing. There have been studies in the literature modeling the turnaround time from historical data for runs with the same recipe and later using that to derive the resource allocation for subsequent runs. [3]. This approach is more feasible in predominantly simulation dominated tools but for edge operation dominated flow it may not be possible especially if some processing acceleration methods like pattern matching or hierarchical processing is involved. In this paper, we suggest an alternative method of providing target turnaround time and managing the priority of jobs while not doing any upfront resource modeling and resource planning. The methodology then systematically either meets the turnaround time need and potentially lets the user know if it will not as soon as possible. This builds on top of the Calibre Cluster Management (CalCM) resource management work previously published [1][2]. The paper describes the initial demonstration of the concept.

Biosensors with Built-In Biomolecular Logic Gates for Practical Applications

PubMed Central

Lai, Yu-Hsuan; Sun, Sin-Cih; Chuang, Min-Chieh

2014-01-01

Molecular logic gates, designs constructed with biological and chemical molecules, have emerged as an alternative computing approach to silicon-based logic operations. These molecular computers are capable of receiving and integrating multiple stimuli of biochemical significance to generate a definitive output, opening a new research avenue to advanced diagnostics and therapeutics which demand handling of complex factors and precise control. In molecularly gated devices, Boolean logic computations can be activated by specific inputs and accurately processed via bio-recognition, bio-catalysis, and selective chemical reactions. In this review, we survey recent advances of the molecular logic approaches to practical applications of biosensors, including designs constructed with proteins, enzymes, nucleic acids, nanomaterials, and organic compounds, as well as the research avenues for future development of digitally operating “sense and act” schemes that logically process biochemical signals through networked circuits to implement intelligent control systems. PMID:25587423

Post optimization paradigm in maximum 3-satisfiability logic programming

NASA Astrophysics Data System (ADS)

Mansor, Mohd. Asyraf; Sathasivam, Saratha; Kasihmuddin, Mohd Shareduwan Mohd

2017-08-01

Maximum 3-Satisfiability (MAX-3SAT) is a counterpart of the Boolean satisfiability problem that can be treated as a constraint optimization problem. It deals with a conundrum of searching the maximum number of satisfied clauses in a particular 3-SAT formula. This paper presents the implementation of enhanced Hopfield network in hastening the Maximum 3-Satisfiability (MAX-3SAT) logic programming. Four post optimization techniques are investigated, including the Elliot symmetric activation function, Gaussian activation function, Wavelet activation function and Hyperbolic tangent activation function. The performances of these post optimization techniques in accelerating MAX-3SAT logic programming will be discussed in terms of the ratio of maximum satisfied clauses, Hamming distance and the computation time. Dev-C++ was used as the platform for training, testing and validating our proposed techniques. The results depict the Hyperbolic tangent activation function and Elliot symmetric activation function can be used in doing MAX-3SAT logic programming.

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

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

Li, Y.; Zhong, Y. P.; Deng, Y. F.

2013-12-21

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.

Reservoir computing with a single time-delay autonomous Boolean node

NASA Astrophysics Data System (ADS)

Haynes, Nicholas D.; Soriano, Miguel C.; Rosin, David P.; Fischer, Ingo; Gauthier, Daniel J.

2015-02-01

We demonstrate reservoir computing with a physical system using a single autonomous Boolean logic element with time-delay feedback. The system generates a chaotic transient with a window of consistency lasting between 30 and 300 ns, which we show is sufficient for reservoir computing. We then characterize the dependence of computational performance on system parameters to find the best operating point of the reservoir. When the best parameters are chosen, the reservoir is able to classify short input patterns with performance that decreases over time. In particular, we show that four distinct input patterns can be classified for 70 ns, even though the inputs are only provided to the reservoir for 7.5 ns.

Questions Revisited: A Close Examination of Calculus of Inference and Inquiry

NASA Technical Reports Server (NTRS)

Knuth, Kevin H.; Koga, Dennis (Technical Monitor)

2003-01-01

In this paper I examine more closely the way in which probability theory, the calculus of inference, is derived from the Boolean lattice structure of logical assertions ordered by implication. I demonstrate how the duality between the logical conjunction and disjunction in Boolean algebra is lost when deriving the probability calculus. In addition, I look more closely at the other lattice identities to verify that they are satisfied by the probability calculus. Last, I look towards developing the calculus of inquiry demonstrating that there is a sum and product rule for the relevance measure as well as a Bayes theorem. Current difficulties in deriving the complete inquiry calculus will also be discussed.

Optical reversible programmable Boolean logic unit.

PubMed

Chattopadhyay, Tanay

2012-07-20

Computing with reversibility is the only way to avoid dissipation of energy associated with bit erase. So, a reversible microprocessor is required for future computing. In this paper, a design of a simple all-optical reversible programmable processor is proposed using a polarizing beam splitter, liquid crystal-phase spatial light modulators, a half-wave plate, and plane mirrors. This circuit can perform 16 logical operations according to three programming inputs. Also, inputs can be easily recovered from the outputs. It is named the "reversible programmable Boolean logic unit (RPBLU)." The logic unit is the basic building block of many complex computational operations. Hence the design is important in sense. Two orthogonally polarized lights are defined here as two logical states, respectively.

Extending Clause Learning of SAT Solvers with Boolean Gröbner Bases

NASA Astrophysics Data System (ADS)

Zengler, Christoph; Küchlin, Wolfgang

We extend clause learning as performed by most modern SAT Solvers by integrating the computation of Boolean Gröbner bases into the conflict learning process. Instead of learning only one clause per conflict, we compute and learn additional binary clauses from a Gröbner basis of the current conflict. We used the Gröbner basis engine of the logic package Redlog contained in the computer algebra system Reduce to extend the SAT solver MiniSAT with Gröbner basis learning. Our approach shows a significant reduction of conflicts and a reduction of restarts and computation time on many hard problems from the SAT 2009 competition.

Medical image processing using neural networks based on multivalued and universal binary neurons

NASA Astrophysics Data System (ADS)

Aizenberg, Igor N.; Aizenberg, Naum N.; Gotko, Eugen S.; Sochka, Vladimir A.

1998-06-01

Cellular Neural Networks (CNN) has become a very good mean for solution of the different kind of image processing problems. CNN based on multi-valued neurons (CNN-MVN) and CNN based on universal binary neurons (CNN-UBN) are the specific kinds of the CNN. MVN and UBN are neurons with complex-valued weights, and complex internal arithmetic. Their main feature is possibility of implementation of the arbitrary mapping between inputs and output described by the MVN, and arbitrary (not only threshold) Boolean function (UBN). Great advantage of the CNN is possibility of implementation of the any linear and many non-linear filters in spatial domain. Together with noise removing using CNN it is possible to implement filters, which can amplify high and medium frequencies. These filters are a very good mean for solution of the enhancement problem, and problem of details extraction against complex background. So, CNN make it possible to organize all the processing process from filtering until extraction of the important details. Organization of this process for medical image processing is considered in the paper. A major attention will be concentrated on the processing of the x-ray and ultrasound images corresponding to different oncology (or closed to oncology) pathologies. Additionally we will consider new structure of the neural network for solution of the problem of differential diagnostics of breast cancer.

Chaotic dynamics in nanoscale NbO2 Mott memristors for analogue computing

NASA Astrophysics Data System (ADS)

Kumar, Suhas; Strachan, John Paul; Williams, R. Stanley

2017-08-01

At present, machine learning systems use simplified neuron models that lack the rich nonlinear phenomena observed in biological systems, which display spatio-temporal cooperative dynamics. There is evidence that neurons operate in a regime called the edge of chaos that may be central to complexity, learning efficiency, adaptability and analogue (non-Boolean) computation in brains. Neural networks have exhibited enhanced computational complexity when operated at the edge of chaos, and networks of chaotic elements have been proposed for solving combinatorial or global optimization problems. Thus, a source of controllable chaotic behaviour that can be incorporated into a neural-inspired circuit may be an essential component of future computational systems. Such chaotic elements have been simulated using elaborate transistor circuits that simulate known equations of chaos, but an experimental realization of chaotic dynamics from a single scalable electronic device has been lacking. Here we describe niobium dioxide (NbO2) Mott memristors each less than 100 nanometres across that exhibit both a nonlinear-transport-driven current-controlled negative differential resistance and a Mott-transition-driven temperature-controlled negative differential resistance. Mott materials have a temperature-dependent metal-insulator transition that acts as an electronic switch, which introduces a history-dependent resistance into the device. We incorporate these memristors into a relaxation oscillator and observe a tunable range of periodic and chaotic self-oscillations. We show that the nonlinear current transport coupled with thermal fluctuations at the nanoscale generates chaotic oscillations. Such memristors could be useful in certain types of neural-inspired computation by introducing a pseudo-random signal that prevents global synchronization and could also assist in finding a global minimum during a constrained search. We specifically demonstrate that incorporating such memristors into the hardware of a Hopfield computing network can greatly improve the efficiency and accuracy of converging to a solution for computationally difficult problems.

Specialty functions singularity mechanics problems

NASA Technical Reports Server (NTRS)

Sarigul, Nesrin

1989-01-01

The focus is in the development of more accurate and efficient advanced methods for solution of singular problems encountered in mechanics. At present, finite element methods in conjunction with special functions, boolean sum and blending interpolations are being considered. In dealing with systems which contain a singularity, special finite elements are being formulated to be used in singular regions. Further, special transition elements are being formulated to couple the special element to the mesh that models the rest of the system, and to be used in conjunction with 1-D, 2-D and 3-D elements within the same mesh. Computational simulation with a least squares fit is being utilized to construct special elements, if there is an unknown singularity in the system. A novel approach is taken in formulation of the elements in that: (1) the material properties are modified to include time, temperature, coordinate and stress dependant behavior within the element; (2) material properties vary at nodal points of the elements; (3) a hidden-symbolic computation scheme is developed and utilized in formulating the elements; and (4) special functions and boolean sum are utilized in order to interpolate the field variables and their derivatives along the boundary of the elements. It may be noted that the proposed methods are also applicable to fluids and coupled problems.

Emergence of homeostasis and “noise imprinting” in an evolution model

PubMed Central

Stern, Michael D.

1999-01-01

Homeostasis, the creation of a stabilized internal milieu, is ubiquitous in biological evolution, despite the entropic cost of excluding noise information from a region. The advantages of stability seem self evident, but the alternatives are not so clear. This issue was studied by means of numerical experiments on a simple evolution model: a population of Boolean network “organisms” selected for performance of a curve-fitting task while subjected to noise. During evolution, noise sensitivity increased with fitness. Noise exclusion evolved spontaneously, but only if the noise was sufficiently unpredictable. Noise that was limited to one or a few stereotyped patterns caused symmetry breaking that prevented noise exclusion. Instead, the organisms incorporated the noise into their function at little cost in ultimate fitness and became totally noise dependent. This “noise imprinting” suggests caution when interpreting apparent adaptations seen in nature. If the noise was totally random from generation to generation, noise exclusion evolved reliably and irreversibly, but if the noise was correlated over several generations, maladaptive selection of noise-dependent traits could reverse noise exclusion, with catastrophic effect on population fitness. Noise entering the selection process rather than the organism had a different effect: adaptive evolution was totally abolished above a critical noise amplitude, in a manner resembling a thermodynamic phase transition. Evolutionary adaptation to noise involves the creation of a subsystem screened from noise information but increasingly vulnerable to its effects. Similar considerations may apply to information channeling in human cultural evolution. PMID:10485897

Toward using games to teach fundamental computer science concepts

NASA Astrophysics Data System (ADS)

Edgington, Jeffrey Michael

Video and computer games have become an important area of study in the field of education. Games have been designed to teach mathematics, physics, raise social awareness, teach history and geography, and train soldiers in the military. Recent work has created computer games for teaching computer programming and understanding basic algorithms. We present an investigation where computer games are used to teach two fundamental computer science concepts: boolean expressions and recursion. The games are intended to teach the concepts and not how to implement them in a programming language. For this investigation, two computer games were created. One is designed to teach basic boolean expressions and operators and the other to teach fundamental concepts of recursion. We describe the design and implementation of both games. We evaluate the effectiveness of these games using before and after surveys. The surveys were designed to ascertain basic understanding, attitudes and beliefs regarding the concepts. The boolean game was evaluated with local high school students and students in a college level introductory computer science course. The recursion game was evaluated with students in a college level introductory computer science course. We present the analysis of the collected survey information for both games. This analysis shows a significant positive change in student attitude towards recursion and modest gains in student learning outcomes for both topics.

Digital Charge Coupled Device (CCD) Camera System Architecture

NASA Astrophysics Data System (ADS)

Babey, S. K.; Anger, C. D.; Green, B. D.

1987-03-01

We propose a modeling system for generic objects in order to recognize different objects from the same category with only one generic model. The representation consists of a prototype, represented by parts and their configuration. Parts are modeled by superquadric volumetric primitives which are combined via Boolean operations to form objects. Variations between objects within a category are described by allowable changes in structure and shape deformations of prototypical parts. Each prototypical part and relation has a set of associated features that can be recognized in the images. These features are used for selecting models from the model data base. The selected hypothetical models are then verified on the geometric level by deforming the prototype in allowable ways to match the data. We base our design of the modeling system upon the current psychological theories of categorization and of human visual perception.

Fast and Exact Continuous Collision Detection with Bernstein Sign Classification

PubMed Central

Tang, Min; Tong, Ruofeng; Wang, Zhendong; Manocha, Dinesh

2014-01-01

We present fast algorithms to perform accurate CCD queries between triangulated models. Our formulation uses properties of the Bernstein basis and Bézier curves and reduces the problem to evaluating signs of polynomials. We present a geometrically exact CCD algorithm based on the exact geometric computation paradigm to perform reliable Boolean collision queries. Our algorithm is more than an order of magnitude faster than prior exact algorithms. We evaluate its performance for cloth and FEM simulations on CPUs and GPUs, and highlight the benefits. PMID:25568589

Disparity between ultrasound and clinical findings in psoriatic arthritis.

PubMed

Husic, Rusmir; Gretler, Judith; Felber, Anja; Graninger, Winfried B; Duftner, Christina; Hermann, Josef; Dejaco, Christian

2014-08-01

To investigate the association between psoriatic arthritis (PsA)-specific clinical composite scores and ultrasound-verified pathology as well as comparison of clinical and ultrasound definitions of remission. We performed a prospective study on 70 consecutive PsA patients. Clinical assessments included components of Disease Activity Index for Psoriatic Arthritis (DAPSA) and the Composite Psoriatic Disease Activity Index (CPDAI). Minimal disease activity (MDA) and the following remission criteria were applied: CPDAI joint, entheses and dactylitis domains (CPDAI-JED)=0, DAPSA≤3.3, Boolean's remission definition and physician-judged remission (rem-phys). B-mode and power Doppler (PD-) ultrasound findings were semiquantitatively scored at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses. Ultrasound remission and minimal ultrasound disease activity (MUDA) were defined as PD-score=0 and PD-score ≤1, respectively, at joints, peritendinous tissue, tendons and entheses. DAPSA but not CPDAI correlated with B-mode and PD-synovitis. Ultrasound signs of enthesitis, dactylitis, tenosynovitis and perisynovitis were not linked with clinical composites. Clinical remission or MDA was observed in 15.7% to 47.1% of PsA patients. Ultrasound remission and MUDA were present in 4.3% and 20.0% of patients, respectively. Joint and tendon-related PD-scores were higher in patients with active versus inactive disease according to CPDAI-JED, DAPSA, Boolean's and rem-phys, whereas no difference was observed regarding enthesitis and perisynovitis. DAPSA≤3.3 (OR 3.9, p=0.049) and Boolean's definition (OR 4.6, p=0.03) were more useful to predict MUDA than other remission criteria. PsA-specific composite scores partially reflect ultrasound findings. DAPSA and Boolean's remission definitions better identify MUDA patients than other clinical criteria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Quantum gates with controlled adiabatic evolutions

NASA Astrophysics Data System (ADS)

Hen, Itay

2015-02-01

We introduce a class of quantum adiabatic evolutions that we claim may be interpreted as the equivalents of the unitary gates of the quantum gate model. We argue that these gates form a universal set and may therefore be used as building blocks in the construction of arbitrary "adiabatic circuits," analogously to the manner in which gates are used in the circuit model. One implication of the above construction is that arbitrary classical boolean circuits as well as gate model circuits may be directly translated to adiabatic algorithms with no additional resources or complexities. We show that while these adiabatic algorithms fail to exhibit certain aspects of the inherent fault tolerance of traditional quantum adiabatic algorithms, they may have certain other experimental advantages acting as quantum gates.

Reliable computation from contextual correlations

NASA Astrophysics Data System (ADS)

Oestereich, André L.; Galvão, Ernesto F.

2017-12-01

An operational approach to the study of computation based on correlations considers black boxes with one-bit inputs and outputs, controlled by a limited classical computer capable only of performing sums modulo-two. In this setting, it was shown that noncontextual correlations do not provide any extra computational power, while contextual correlations were found to be necessary for the deterministic evaluation of nonlinear Boolean functions. Here we investigate the requirements for reliable computation in this setting; that is, the evaluation of any Boolean function with success probability bounded away from 1 /2 . We show that bipartite CHSH quantum correlations suffice for reliable computation. We also prove that an arbitrarily small violation of a multipartite Greenberger-Horne-Zeilinger noncontextuality inequality also suffices for reliable computation.

The pseudo-Boolean optimization approach to form the N-version software structure

NASA Astrophysics Data System (ADS)

Kovalev, I. V.; Kovalev, D. I.; Zelenkov, P. V.; Voroshilova, A. A.

2015-10-01

The problem of developing an optimal structure of N-version software system presents a kind of very complex optimization problem. This causes the use of deterministic optimization methods inappropriate for solving the stated problem. In this view, exploiting heuristic strategies looks more rational. In the field of pseudo-Boolean optimization theory, the so called method of varied probabilities (MVP) has been developed to solve problems with a large dimensionality. Some additional modifications of MVP have been made to solve the problem of N-version systems design. Those algorithms take into account the discovered specific features of the objective function. The practical experiments have shown the advantage of using these algorithm modifications because of reducing a search space.

Algebra for Enterprise Ontology: towards analysis and synthesis of enterprise models

NASA Astrophysics Data System (ADS)

Suga, Tetsuya; Iijima, Junichi

2018-03-01

Enterprise modeling methodologies have made enterprises more likely to be the object of systems engineering rather than craftsmanship. However, the current state of research in enterprise modeling methodologies lacks investigations of the mathematical background embedded in these methodologies. Abstract algebra, a broad subfield of mathematics, and the study of algebraic structures may provide interesting implications in both theory and practice. Therefore, this research gives an empirical challenge to establish an algebraic structure for one aspect model proposed in Design & Engineering Methodology for Organizations (DEMO), which is a major enterprise modeling methodology in the spotlight as a modeling principle to capture the skeleton of enterprises for developing enterprise information systems. The results show that the aspect model behaves well in the sense of algebraic operations and indeed constructs a Boolean algebra. This article also discusses comparisons with other modeling languages and suggests future work.

Separating OR, SUM, and XOR Circuits.

PubMed

Find, Magnus; Göös, Mika; Järvisalo, Matti; Kaski, Petteri; Koivisto, Mikko; Korhonen, Janne H

2016-08-01

Given a boolean n × n matrix A we consider arithmetic circuits for computing the transformation x ↦ Ax over different semirings. Namely, we study three circuit models: monotone OR-circuits, monotone SUM-circuits (addition of non-negative integers), and non-monotone XOR-circuits (addition modulo 2). Our focus is on separating OR-circuits from the two other models in terms of circuit complexity: We show how to obtain matrices that admit OR-circuits of size O ( n ), but require SUM-circuits of size Ω( n 3/2 /log 2 n ).We consider the task of rewriting a given OR-circuit as a XOR-circuit and prove that any subquadratic-time algorithm for this task violates the strong exponential time hypothesis.

Modeling and implementation of concurrent logic controllers with use of Petri nets, LSMs, and sequent calculus

NASA Astrophysics Data System (ADS)

Tkacz, J.; Bukowiec, A.; Doligalski, M.

2017-08-01

The paper presentes the method of modeling and implementation of concurrent controllers. Concurrent controllers are specified by Petri nets. Then Petri nets are decomposed using symbolic deduction method of analysis. Formal methods like sequent calculus system with considered elements of Thelen's algorithm have been used here. As a result, linked state machines (LSMs) are received. Each FSM is implemented using methods of structural decomposition during process of logic synthesis. The method of multiple encoding of microinstruction has been applied. It leads to decreased number of Boolean function realized by combinational part of FSM. The additional decoder could be implemented with the use of memory blocks.

Continuous variables logic via coupled automata using a DNAzyme cascade with feedback† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc03892a Click here for additional data file.

PubMed Central

Lilienthal, S.; Klein, M.; Orbach, R.; Willner, I.; Remacle, F.

2017-01-01

The concentration of molecules can be changed by chemical reactions and thereby offer a continuous readout. Yet computer architecture is cast in textbooks in terms of binary valued, Boolean variables. To enable reactive chemical systems to compute we show how, using the Cox interpretation of probability theory, one can transcribe the equations of chemical kinetics as a sequence of coupled logic gates operating on continuous variables. It is discussed how the distinct chemical identity of a molecule allows us to create a common language for chemical kinetics and Boolean logic. Specifically, the logic AND operation is shown to be equivalent to a bimolecular process. The logic XOR operation represents chemical processes that take place concurrently. The values of the rate constants enter the logic scheme as inputs. By designing a reaction scheme with a feedback we endow the logic gates with a built in memory because their output then depends on the input and also on the present state of the system. Technically such a logic machine is an automaton. We report an experimental realization of three such coupled automata using a DNAzyme multilayer signaling cascade. A simple model verifies analytically that our experimental scheme provides an integrator generating a power series that is third order in time. The model identifies two parameters that govern the kinetics and shows how the initial concentrations of the substrates are the coefficients in the power series. PMID:28507669

A Note on a Sampling Theorem for Functions over GF(q)n Domain

NASA Astrophysics Data System (ADS)

Ukita, Yoshifumi; Saito, Tomohiko; Matsushima, Toshiyasu; Hirasawa, Shigeichi

In digital signal processing, the sampling theorem states that any real valued function ƒ can be reconstructed from a sequence of values of ƒ that are discretely sampled with a frequency at least twice as high as the maximum frequency of the spectrum of ƒ. This theorem can also be applied to functions over finite domain. Then, the range of frequencies of ƒ can be expressed in more detail by using a bounded set instead of the maximum frequency. A function whose range of frequencies is confined to a bounded set is referred to as bandlimited function. And a sampling theorem for bandlimited functions over Boolean domain has been obtained. Here, it is important to obtain a sampling theorem for bandlimited functions not only over Boolean domain (GF(q)n domain) but also over GF(q)n domain, where q is a prime power and GF(q) is Galois field of order q. For example, in experimental designs, although the model can be expressed as a linear combination of the Fourier basis functions and the levels of each factor can be represented by GF(q)n, the number of levels often take a value greater than two. However, the sampling theorem for bandlimited functions over GF(q)n domain has not been obtained. On the other hand, the sampling points are closely related to the codewords of a linear code. However, the relation between the parity check matrix of a linear code and any distinct error vectors has not been obtained, although it is necessary for understanding the meaning of the sampling theorem for bandlimited functions. In this paper, we generalize the sampling theorem for bandlimited functions over Boolean domain to a sampling theorem for bandlimited functions over GF(q)n domain. We also present a theorem for the relation between the parity check matrix of a linear code and any distinct error vectors. Lastly, we clarify the relation between the sampling theorem for functions over GF(q)n domain and linear codes.

Attractor-Based Obstructions to Growth in Homogeneous Cyclic Boolean Automata.

PubMed

Khan, Bilal; Cantor, Yuri; Dombrowski, Kirk

2015-11-01

We consider a synchronous Boolean organism consisting of N cells arranged in a circle, where each cell initially takes on an independently chosen Boolean value. During the lifetime of the organism, each cell updates its own value by responding to the presence (or absence) of diversity amongst its two neighbours' values. We show that if all cells eventually take a value of 0 (irrespective of their initial values) then the organism necessarily has a cell count that is a power of 2. In addition, the converse is also proved: if the number of cells in the organism is a proper power of 2, then no matter what the initial values of the cells are, eventually all cells take on a value of 0 and then cease to change further. We argue that such an absence of structure in the dynamical properties of the organism implies a lack of adaptiveness, and so is evolutionarily disadvantageous. It follows that as the organism doubles in size (say from m to 2m) it will necessarily encounter an intermediate size that is a proper power of 2, and suffers from low adaptiveness. Finally we show, through computational experiments, that one way an organism can grow to more than twice its size and still avoid passing through intermediate sizes that lack structural dynamics, is for the organism to depart from assumptions of homogeneity at the cellular level.

Integrating Multiple Data Sources for Combinatorial Marker Discovery: A Study in Tumorigenesis.

PubMed

Bandyopadhyay, Sanghamitra; Mallik, Saurav

2018-01-01

Identification of combinatorial markers from multiple data sources is a challenging task in bioinformatics. Here, we propose a novel computational framework for identifying significant combinatorial markers ( s) using both gene expression and methylation data. The gene expression and methylation data are integrated into a single continuous data as well as a (post-discretized) boolean data based on their intrinsic (i.e., inverse) relationship. A novel combined score of methylation and expression data (viz., ) is introduced which is computed on the integrated continuous data for identifying initial non-redundant set of genes. Thereafter, (maximal) frequent closed homogeneous genesets are identified using a well-known biclustering algorithm applied on the integrated boolean data of the determined non-redundant set of genes. A novel sample-based weighted support ( ) is then proposed that is consecutively calculated on the integrated boolean data of the determined non-redundant set of genes in order to identify the non-redundant significant genesets. The top few resulting genesets are identified as potential s. Since our proposed method generates a smaller number of significant non-redundant genesets than those by other popular methods, the method is much faster than the others. Application of the proposed technique on an expression and a methylation data for Uterine tumor or Prostate Carcinoma produces a set of significant combination of markers. We expect that such a combination of markers will produce lower false positives than individual markers.

Attractor-Based Obstructions to Growth in Homogeneous Cyclic Boolean Automata

PubMed Central

Khan, Bilal; Cantor, Yuri; Dombrowski, Kirk

2016-01-01

We consider a synchronous Boolean organism consisting of N cells arranged in a circle, where each cell initially takes on an independently chosen Boolean value. During the lifetime of the organism, each cell updates its own value by responding to the presence (or absence) of diversity amongst its two neighbours’ values. We show that if all cells eventually take a value of 0 (irrespective of their initial values) then the organism necessarily has a cell count that is a power of 2. In addition, the converse is also proved: if the number of cells in the organism is a proper power of 2, then no matter what the initial values of the cells are, eventually all cells take on a value of 0 and then cease to change further. We argue that such an absence of structure in the dynamical properties of the organism implies a lack of adaptiveness, and so is evolutionarily disadvantageous. It follows that as the organism doubles in size (say from m to 2m) it will necessarily encounter an intermediate size that is a proper power of 2, and suffers from low adaptiveness. Finally we show, through computational experiments, that one way an organism can grow to more than twice its size and still avoid passing through intermediate sizes that lack structural dynamics, is for the organism to depart from assumptions of homogeneity at the cellular level. PMID:27660398

Building the 3D Geological Model of Wall Rock of Salt Caverns Based on Integration Method of Multi-source data

NASA Astrophysics Data System (ADS)

Yongzhi, WANG; hui, WANG; Lixia, LIAO; Dongsen, LI

2017-02-01

In order to analyse the geological characteristics of salt rock and stability of salt caverns, rough three-dimensional (3D) models of salt rock stratum and the 3D models of salt caverns on study areas are built by 3D GIS spatial modeling technique. During implementing, multi-source data, such as basic geographic data, DEM, geological plane map, geological section map, engineering geological data, and sonar data are used. In this study, the 3D spatial analyzing and calculation methods, such as 3D GIS intersection detection method in three-dimensional space, Boolean operations between three-dimensional space entities, three-dimensional space grid discretization, are used to build 3D models on wall rock of salt caverns. Our methods can provide effective calculation models for numerical simulation and analysis of the creep characteristics of wall rock in salt caverns.

Design of a Nanoscale, CMOS-Integrable, Thermal-Guiding Structure for Boolean-Logic and Neuromorphic Computation.

PubMed

Loke, Desmond; Skelton, Jonathan M; Chong, Tow-Chong; Elliott, Stephen R

2016-12-21

One of the requirements for achieving faster CMOS electronics is to mitigate the unacceptably large chip areas required to steer heat away from or, more recently, toward the critical nodes of state-of-the-art devices. Thermal-guiding (TG) structures can efficiently direct heat by "meta-materials" engineering; however, some key aspects of the behavior of these systems are not fully understood. Here, we demonstrate control of the thermal-diffusion properties of TG structures by using nanometer-scale, CMOS-integrable, graphene-on-silica stacked materials through finite-element-methods simulations. It has been shown that it is possible to implement novel, controllable, thermally based Boolean-logic and spike-timing-dependent plasticity operations for advanced (neuromorphic) computing applications using such thermal-guide architectures.

Modeling and simulation of reliability of unmanned intelligent vehicles

NASA Astrophysics Data System (ADS)

Singh, Harpreet; Dixit, Arati M.; Mustapha, Adam; Singh, Kuldip; Aggarwal, K. K.; Gerhart, Grant R.

2008-04-01

Unmanned ground vehicles have a large number of scientific, military and commercial applications. A convoy of such vehicles can have collaboration and coordination. For the movement of such a convoy, it is important to predict the reliability of the system. A number of approaches are available in literature which describes the techniques for determining the reliability of the system. Graph theoretic approaches are popular in determining terminal reliability and system reliability. In this paper we propose to exploit Fuzzy and Neuro-Fuzzy approaches for predicting the node and branch reliability of the system while Boolean algebra approaches are used to determine terminal reliability and system reliability. Hence a combination of intelligent approaches like Fuzzy, Neuro-Fuzzy and Boolean approaches is used to predict the overall system reliability of a convoy of vehicles. The node reliabilities may correspond to the collaboration of vehicles while branch reliabilities will determine the terminal reliabilities between different nodes. An algorithm is proposed for determining the system reliabilities of a convoy of vehicles. The simulation of the overall system is proposed. Such simulation should be helpful to the commander to take an appropriate action depending on the predicted reliability in different terrain and environmental conditions. It is hoped that results of this paper will lead to more important techniques to have a reliable convoy of vehicles in a battlefield.

Social interaction as a heuristic for combinatorial optimization problems

NASA Astrophysics Data System (ADS)

Fontanari, José F.

2010-11-01

We investigate the performance of a variant of Axelrod’s model for dissemination of culture—the Adaptive Culture Heuristic (ACH)—on solving an NP-Complete optimization problem, namely, the classification of binary input patterns of size F by a Boolean Binary Perceptron. In this heuristic, N agents, characterized by binary strings of length F which represent possible solutions to the optimization problem, are fixed at the sites of a square lattice and interact with their nearest neighbors only. The interactions are such that the agents’ strings (or cultures) become more similar to the low-cost strings of their neighbors resulting in the dissemination of these strings across the lattice. Eventually the dynamics freezes into a homogeneous absorbing configuration in which all agents exhibit identical solutions to the optimization problem. We find through extensive simulations that the probability of finding the optimal solution is a function of the reduced variable F/N1/4 so that the number of agents must increase with the fourth power of the problem size, N∝F4 , to guarantee a fixed probability of success. In this case, we find that the relaxation time to reach an absorbing configuration scales with F6 which can be interpreted as the overall computational cost of the ACH to find an optimal set of weights for a Boolean binary perceptron, given a fixed probability of success.

OptFlux: an open-source software platform for in silico metabolic engineering.

PubMed

Rocha, Isabel; Maia, Paulo; Evangelista, Pedro; Vilaça, Paulo; Soares, Simão; Pinto, José P; Nielsen, Jens; Patil, Kiran R; Ferreira, Eugénio C; Rocha, Miguel

2010-04-19

Over the last few years a number of methods have been proposed for the phenotype simulation of microorganisms under different environmental and genetic conditions. These have been used as the basis to support the discovery of successful genetic modifications of the microbial metabolism to address industrial goals. However, the use of these methods has been restricted to bioinformaticians or other expert researchers. The main aim of this work is, therefore, to provide a user-friendly computational tool for Metabolic Engineering applications. OptFlux is an open-source and modular software aimed at being the reference computational application in the field. It is the first tool to incorporate strain optimization tasks, i.e., the identification of Metabolic Engineering targets, using Evolutionary Algorithms/Simulated Annealing metaheuristics or the previously proposed OptKnock algorithm. It also allows the use of stoichiometric metabolic models for (i) phenotype simulation of both wild-type and mutant organisms, using the methods of Flux Balance Analysis, Minimization of Metabolic Adjustment or Regulatory on/off Minimization of Metabolic flux changes, (ii) Metabolic Flux Analysis, computing the admissible flux space given a set of measured fluxes, and (iii) pathway analysis through the calculation of Elementary Flux Modes. OptFlux also contemplates several methods for model simplification and other pre-processing operations aimed at reducing the search space for optimization algorithms. The software supports importing/exporting to several flat file formats and it is compatible with the SBML standard. OptFlux has a visualization module that allows the analysis of the model structure that is compatible with the layout information of Cell Designer, allowing the superimposition of simulation results with the model graph. The OptFlux software is freely available, together with documentation and other resources, thus bridging the gap from research in strain optimization algorithms and the final users. It is a valuable platform for researchers in the field that have available a number of useful tools. Its open-source nature invites contributions by all those interested in making their methods available for the community. Given its plug-in based architecture it can be extended with new functionalities. Currently, several plug-ins are being developed, including network topology analysis tools and the integration with Boolean network based regulatory models.

OptFlux: an open-source software platform for in silico metabolic engineering

PubMed Central

2010-01-01

Background Over the last few years a number of methods have been proposed for the phenotype simulation of microorganisms under different environmental and genetic conditions. These have been used as the basis to support the discovery of successful genetic modifications of the microbial metabolism to address industrial goals. However, the use of these methods has been restricted to bioinformaticians or other expert researchers. The main aim of this work is, therefore, to provide a user-friendly computational tool for Metabolic Engineering applications. Results OptFlux is an open-source and modular software aimed at being the reference computational application in the field. It is the first tool to incorporate strain optimization tasks, i.e., the identification of Metabolic Engineering targets, using Evolutionary Algorithms/Simulated Annealing metaheuristics or the previously proposed OptKnock algorithm. It also allows the use of stoichiometric metabolic models for (i) phenotype simulation of both wild-type and mutant organisms, using the methods of Flux Balance Analysis, Minimization of Metabolic Adjustment or Regulatory on/off Minimization of Metabolic flux changes, (ii) Metabolic Flux Analysis, computing the admissible flux space given a set of measured fluxes, and (iii) pathway analysis through the calculation of Elementary Flux Modes. OptFlux also contemplates several methods for model simplification and other pre-processing operations aimed at reducing the search space for optimization algorithms. The software supports importing/exporting to several flat file formats and it is compatible with the SBML standard. OptFlux has a visualization module that allows the analysis of the model structure that is compatible with the layout information of Cell Designer, allowing the superimposition of simulation results with the model graph. Conclusions The OptFlux software is freely available, together with documentation and other resources, thus bridging the gap from research in strain optimization algorithms and the final users. It is a valuable platform for researchers in the field that have available a number of useful tools. Its open-source nature invites contributions by all those interested in making their methods available for the community. Given its plug-in based architecture it can be extended with new functionalities. Currently, several plug-ins are being developed, including network topology analysis tools and the integration with Boolean network based regulatory models. PMID:20403172

Rebounding droplet-droplet collisions on superhydrophobic surfaces: from the phenomenon to droplet logic.

PubMed

Mertaniemi, Henrikki; Forchheimer, Robert; Ikkala, Olli; Ras, Robin H A

2012-11-08

When water droplets impact each other while traveling on a superhydrophobic surface, we demonstrate that they are able to rebound like billiard balls. We present elementary Boolean logic operations and a flip-flop memory based on these rebounding water droplet collisions. Furthermore, bouncing or coalescence can be easily controlled by process parameters. Thus by the controlled coalescence of reactive droplets, here using the quenching of fluorescent metal nanoclusters as a model reaction, we also demonstrate an elementary operation for programmable chemistry. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Methods and means used in programming intelligent searches of technical documents

NASA Technical Reports Server (NTRS)

Gross, David L.

1993-01-01

In order to meet the data research requirements of the Safety, Reliability & Quality Assurance activities at Kennedy Space Center (KSC), a new computer search method for technical data documents was developed. By their very nature, technical documents are partially encrypted because of the author's use of acronyms, abbreviations, and shortcut notations. This problem of computerized searching is compounded at KSC by the volume of documentation that is produced during normal Space Shuttle operations. The Centralized Document Database (CDD) is designed to solve this problem. It provides a common interface to an unlimited number of files of various sizes, with the capability to perform any diversified types and levels of data searches. The heart of the CDD is the nature and capability of its search algorithms. The most complex form of search that the program uses is with the use of a domain-specific database of acronyms, abbreviations, synonyms, and word frequency tables. This database, along with basic sentence parsing, is used to convert a request for information into a relational network. This network is used as a filter on the original document file to determine the most likely locations for the data requested. This type of search will locate information that traditional techniques, (i.e., Boolean structured key-word searching), would not find.

Multiscale volatility duration characteristics on financial multi-continuum percolation dynamics

NASA Astrophysics Data System (ADS)

Wang, Min; Wang, Jun

A random stock price model based on the multi-continuum percolation system is developed to investigate the nonlinear dynamics of stock price volatility duration, in an attempt to explain various statistical facts found in financial data, and have a deeper understanding of mechanisms in the financial market. The continuum percolation system is usually referred to be a random coverage process or a Boolean model, it is a member of a class of statistical physics systems. In this paper, the multi-continuum percolation (with different values of radius) is employed to model and reproduce the dispersal of information among the investors. To testify the rationality of the proposed model, the nonlinear analyses of return volatility duration series are preformed by multifractal detrending moving average analysis and Zipf analysis. The comparison empirical results indicate the similar nonlinear behaviors for the proposed model and the actual Chinese stock market.

mRNA translation and protein synthesis: an analysis of different modelling methodologies and a new PBN based approach

PubMed Central

2014-01-01

Background mRNA translation involves simultaneous movement of multiple ribosomes on the mRNA and is also subject to regulatory mechanisms at different stages. Translation can be described by various codon-based models, including ODE, TASEP, and Petri net models. Although such models have been extensively used, the overlap and differences between these models and the implications of the assumptions of each model has not been systematically elucidated. The selection of the most appropriate modelling framework, and the most appropriate way to develop coarse-grained/fine-grained models in different contexts is not clear. Results We systematically analyze and compare how different modelling methodologies can be used to describe translation. We define various statistically equivalent codon-based simulation algorithms and analyze the importance of the update rule in determining the steady state, an aspect often neglected. Then a novel probabilistic Boolean network (PBN) model is proposed for modelling translation, which enjoys an exact numerical solution. This solution matches those of numerical simulation from other methods and acts as a complementary tool to analytical approximations and simulations. The advantages and limitations of various codon-based models are compared, and illustrated by examples with real biological complexities such as slow codons, premature termination and feedback regulation. Our studies reveal that while different models gives broadly similiar trends in many cases, important differences also arise and can be clearly seen, in the dependence of the translation rate on different parameters. Furthermore, the update rule affects the steady state solution. Conclusions The codon-based models are based on different levels of abstraction. Our analysis suggests that a multiple model approach to understanding translation allows one to ascertain which aspects of the conclusions are robust with respect to the choice of modelling methodology, and when (and why) important differences may arise. This approach also allows for an optimal use of analysis tools, which is especially important when additional complexities or regulatory mechanisms are included. This approach can provide a robust platform for dissecting translation, and results in an improved predictive framework for applications in systems and synthetic biology. PMID:24576337

Java PathFinder User Guide

NASA Technical Reports Server (NTRS)

Havelund, Klaus

1999-01-01

The JAVA PATHFINDER, JPF, is a translator from a subset of JAVA 1.0 to PROMELA, the programming language of the SPIN model checker. The purpose of JPF is to establish a framework for verification and debugging of JAVA programming based on model checking. The main goal is to automate program verification such that a programmer can apply it in the daily work without the need for a specialist to manually reformulate a program into a different notation in order to analyze the program. The system is especially suited for analyzing multi-threaded JAVA applications, where normal testing usually falls short. The system can find deadlocks and violations of boolean assertions stated by the programmer in a special assertion language. This document explains how to Use JPF.

Alternative probability theories for cognitive psychology.

PubMed

Narens, Louis

2014-01-01

Various proposals for generalizing event spaces for probability functions have been put forth in the mathematical, scientific, and philosophic literatures. In cognitive psychology such generalizations are used for explaining puzzling results in decision theory and for modeling the influence of context effects. This commentary discusses proposals for generalizing probability theory to event spaces that are not necessarily boolean algebras. Two prominent examples are quantum probability theory, which is based on the set of closed subspaces of a Hilbert space, and topological probability theory, which is based on the set of open sets of a topology. Both have been applied to a variety of cognitive situations. This commentary focuses on how event space properties can influence probability concepts and impact cognitive modeling. Copyright © 2013 Cognitive Science Society, Inc.

Separating OR, SUM, and XOR Circuits☆

PubMed Central

Find, Magnus; Göös, Mika; Järvisalo, Matti; Kaski, Petteri; Koivisto, Mikko; Korhonen, Janne H.

2017-01-01

Given a boolean n × n matrix A we consider arithmetic circuits for computing the transformation x ↦ Ax over different semirings. Namely, we study three circuit models: monotone OR-circuits, monotone SUM-circuits (addition of non-negative integers), and non-monotone XOR-circuits (addition modulo 2). Our focus is on separating OR-circuits from the two other models in terms of circuit complexity: We show how to obtain matrices that admit OR-circuits of size O(n), but require SUM-circuits of size Ω(n3/2/log2n).We consider the task of rewriting a given OR-circuit as a XOR-circuit and prove that any subquadratic-time algorithm for this task violates the strong exponential time hypothesis. PMID:28529379

Symbolic Computation Using Cellular Automata-Based Hyperdimensional Computing.

PubMed

Yilmaz, Ozgur

2015-12-01

This letter introduces a novel framework of reservoir computing that is capable of both connectionist machine intelligence and symbolic computation. A cellular automaton is used as the reservoir of dynamical systems. Input is randomly projected onto the initial conditions of automaton cells, and nonlinear computation is performed on the input via application of a rule in the automaton for a period of time. The evolution of the automaton creates a space-time volume of the automaton state space, and it is used as the reservoir. The proposed framework is shown to be capable of long-term memory, and it requires orders of magnitude less computation compared to echo state networks. As the focus of the letter, we suggest that binary reservoir feature vectors can be combined using Boolean operations as in hyperdimensional computing, paving a direct way for concept building and symbolic processing. To demonstrate the capability of the proposed system, we make analogies directly on image data by asking, What is the automobile of air?

Electrical Circuits in the Mathematics/Computer Science Classroom.

ERIC Educational Resources Information Center

McMillan, Robert D.

1988-01-01

Shows how, with little or no electrical background, students can apply Boolean algebra concepts to design and build integrated electrical circuits in the classroom that will reinforce important ideas in mathematics. (PK)

Topological Aspects of Information Retrieval.

ERIC Educational Resources Information Center

Egghe, Leo; Rousseau, Ronald

1998-01-01

Discusses topological aspects of theoretical information retrieval, including retrieval topology; similarity topology; pseudo-metric topology; document spaces as topological spaces; Boolean information retrieval as a subsystem of any topological system; and proofs of theorems. (LRW)

Defining of the BDX930 Assembly Language

NASA Technical Reports Server (NTRS)

Boyer, R. S.; Moore, J. S.

1983-01-01

A definition of the BDX930 assembly language is presented. Various definition problems and suggested solutions are included. A class of defined recognizers based on boolean valued nowrecursive functions is employed in preprocessing.

Analog Approach to Constraint Satisfaction Enabled by Spin Orbit Torque Magnetic Tunnel Junctions.

PubMed

Wijesinghe, Parami; Liyanagedera, Chamika; Roy, Kaushik

2018-05-02

Boolean satisfiability (k-SAT) is an NP-complete (k ≥ 3) problem that constitute one of the hardest classes of constraint satisfaction problems. In this work, we provide a proof of concept hardware based analog k-SAT solver, that is built using Magnetic Tunnel Junctions (MTJs). The inherent physics of MTJs, enhanced by device level modifications, is harnessed here to emulate the intricate dynamics of an analog satisfiability (SAT) solver. In the presence of thermal noise, the MTJ based system can successfully solve Boolean satisfiability problems. Most importantly, our results exhibit that, the proposed MTJ based hardware SAT solver is capable of finding a solution to a significant fraction (at least 85%) of hard 3-SAT problems, within a time that has a polynomial relationship with the number of variables(<50).

Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey.

PubMed

Wang, Guan-Ying; Zhang, Sa-Li; Wang, Xiu-Ru; Feng, Min; Li, Chun; An, Yuan; Li, Xiao-Feng; Wang, Li-Zhi; Wang, Cai-Hong; Wang, Yong-Fu; Yang, Rong; Yan, Hui-Ming; Wang, Guo-Chun; Lu, Xin; Liu, Xia; Zhu, Ping; Chen, Li-Na; Jin, Hong-Tao; Liu, Jin-Ting; Guo, Hui-Fang; Chen, Hai-Ying; Xie, Jian-Li; Wei, Ping; Wang, Jun-Xiang; Liu, Xiang-Yuan; Sun, Lin; Cui, Liu-Fu; Shu, Rong; Liu, Bai-Lu; Yu, Ping; Zhang, Zhuo-Li; Li, Guang-Tao; Li, Zhen-Bin; Yang, Jing; Li, Jun-Fang; Jia, Bin; Zhang, Feng-Xiao; Tao, Jie-Mei; Lin, Jin-Ying; Wei, Mei-Qiu; Liu, Xiao-Min; Ke, Dan; Hu, Shao-Xian; Ye, Cong; Han, Shu-Ling; Yang, Xiu-Yan; Li, Hao; Huang, Ci-Bo; Gao, Ming; Lai, Bei; Cheng, Yong-Jing; Li, Xing-Fu; Song, Li-Jun; Yu, Xiao-Xia; Wang, Ai-Xue; Wu, Li-Jun; Wang, Yan-Hua; He, Lan; Sun, Wen-Wen; Gong, Lu; Wang, Xiao-Yuan; Wang, Yi; Zhao, Yi; Li, Xiao-Xia; Wang, Yan; Zhang, Yan; Su, Yin; Zhang, Chun-Fang; Mu, Rong; Li, Zhan-Guo

2015-02-01

The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

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

PubMed

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.

Fuzzy logic application for modeling man-in-the-loop space shuttle proximity operations. M.S. Thesis - MIT

NASA Technical Reports Server (NTRS)

Brown, Robert B.

1994-01-01

A software pilot model for Space Shuttle proximity operations is developed, utilizing fuzzy logic. The model is designed to emulate a human pilot during the terminal phase of a Space Shuttle approach to the Space Station. The model uses the same sensory information available to a human pilot and is based upon existing piloting rules and techniques determined from analysis of human pilot performance. Such a model is needed to generate numerous rendezvous simulations to various Space Station assembly stages for analysis of current NASA procedures and plume impingement loads on the Space Station. The advantages of a fuzzy logic pilot model are demonstrated by comparing its performance with NASA's man-in-the-loop simulations and with a similar model based upon traditional Boolean logic. The fuzzy model is shown to respond well from a number of initial conditions, with results typical of an average human. In addition, the ability to model different individual piloting techniques and new piloting rules is demonstrated.

Noise-induced multistability in the regulation of cancer by genes and pseudogenes

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

Petrosyan, K. G., E-mail: pkaren@phys.sinica.edu.tw; Hu, Chin-Kun, E-mail: huck@phys.sinica.edu.tw; National Center for Theoretical Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan

2016-07-28

We extend a previously introduced model of stochastic gene regulation of cancer to a nonlinear case having both gene and pseudogene messenger RNAs (mRNAs) self-regulated. The model consists of stochastic Boolean genetic elements and possesses noise-induced multistability (multimodality). We obtain analytical expressions for probabilities for the case of constant but finite number of microRNA molecules which act as a noise source for the competing gene and pseudogene mRNAs. The probability distribution functions display both the global bistability regime as well as even-odd number oscillations for a certain range of model parameters. Statistical characteristics of the mRNA’s level fluctuations are evaluated.more » The obtained results of the extended model advance our understanding of the process of stochastic gene and pseudogene expressions that is crucial in regulation of cancer.« less

Automated Library System Specifications.

DTIC Science & Technology

1986-06-01

University), LIS (Georqetown Universitv Medical Center) 20 DiSTRI3UT!ON.. AVAILABILITY OF ABSTRACT 21 ABSTRACT SECURITY CLASSIFICATION :UNCLASSIFIED...Interface) acquisitions, patron access catalo. (Boolean search), authority Afiles, zana ~ezient reports. Serials control expected in 1985. INDIVIDUALIZATIOI

Phase transitions in restricted Boltzmann machines with generic priors

NASA Astrophysics Data System (ADS)

Barra, Adriano; Genovese, Giuseppe; Sollich, Peter; Tantari, Daniele

2017-10-01

We study generalized restricted Boltzmann machines with generic priors for units and weights, interpolating between Boolean and Gaussian variables. We present a complete analysis of the replica symmetric phase diagram of these systems, which can be regarded as generalized Hopfield models. We underline the role of the retrieval phase for both inference and learning processes and we show that retrieval is robust for a large class of weight and unit priors, beyond the standard Hopfield scenario. Furthermore, we show how the paramagnetic phase boundary is directly related to the optimal size of the training set necessary for good generalization in a teacher-student scenario of unsupervised learning.

A Module Language for Typing by Contracts

NASA Technical Reports Server (NTRS)

Glouche, Yann; Talpin, Jean-Pierre; LeGuernic, Paul; Gautier, Thierry

2009-01-01

Assume-guarantee reasoning is a popular and expressive paradigm for modular and compositional specification of programs. It is becoming a fundamental concept in some computer-aided design tools for embedded system design. In this paper, we elaborate foundations for contract-based embedded system design by proposing a general-purpose module language based on a Boolean algebra allowing to define contracts. In this framework, contracts are used to negotiate the correctness of assumptions made on the definition of a component at the point where it is used and provides guarantees to its environment. We illustrate this presentation with the specification of a simplified 4-stroke engine model.

Nonvolatile reconfigurable sequential logic in a HfO2 resistive random access memory array.

PubMed

Zhou, Ya-Xiong; Li, Yi; Su, Yu-Ting; Wang, Zhuo-Rui; Shih, Ling-Yi; Chang, Ting-Chang; Chang, Kuan-Chang; Long, Shi-Bing; Sze, Simon M; Miao, Xiang-Shui

2017-05-25

Resistive random access memory (RRAM) based reconfigurable logic provides a temporal programmable dimension to realize Boolean logic functions and is regarded as a promising route to build non-von Neumann computing architecture. In this work, a reconfigurable operation method is proposed to perform nonvolatile sequential logic in a HfO 2 -based RRAM array. Eight kinds of Boolean logic functions can be implemented within the same hardware fabrics. During the logic computing processes, the RRAM devices in an array are flexibly configured in a bipolar or complementary structure. The validity was demonstrated by experimentally implemented NAND and XOR logic functions and a theoretically designed 1-bit full adder. With the trade-off between temporal and spatial computing complexity, our method makes better use of limited computing resources, thus provides an attractive scheme for the construction of logic-in-memory systems.

Synthesizing Biomolecule-based Boolean Logic Gates

PubMed Central

Miyamoto, Takafumi; Razavi, Shiva; DeRose, Robert; Inoue, Takanari

2012-01-01

One fascinating recent avenue of study in the field of synthetic biology is the creation of biomolecule-based computers. The main components of a computing device consist of an arithmetic logic unit, the control unit, memory, and the input and output devices. Boolean logic gates are at the core of the operational machinery of these parts, hence to make biocomputers a reality, biomolecular logic gates become a necessity. Indeed, with the advent of more sophisticated biological tools, both nucleic acid- and protein-based logic systems have been generated. These devices function in the context of either test tubes or living cells and yield highly specific outputs given a set of inputs. In this review, we discuss various types of biomolecular logic gates that have been synthesized, with particular emphasis on recent developments that promise increased complexity of logic gate circuitry, improved computational speed, and potential clinical applications. PMID:23526588

Interconnect-free parallel logic circuits in a single mechanical resonator

PubMed Central

Mahboob, I.; Flurin, E.; Nishiguchi, K.; Fujiwara, A.; Yamaguchi, H.

2011-01-01

In conventional computers, wiring between transistors is required to enable the execution of Boolean logic functions. This has resulted in processors in which billions of transistors are physically interconnected, which limits integration densities, gives rise to huge power consumption and restricts processing speeds. A method to eliminate wiring amongst transistors by condensing Boolean logic into a single active element is thus highly desirable. Here, we demonstrate a novel logic architecture using only a single electromechanical parametric resonator into which multiple channels of binary information are encoded as mechanical oscillations at different frequencies. The parametric resonator can mix these channels, resulting in new mechanical oscillation states that enable the construction of AND, OR and XOR logic gates as well as multibit logic circuits. Moreover, the mechanical logic gates and circuits can be executed simultaneously, giving rise to the prospect of a parallel logic processor in just a single mechanical resonator. PMID:21326230

Interconnect-free parallel logic circuits in a single mechanical resonator.

PubMed

Mahboob, I; Flurin, E; Nishiguchi, K; Fujiwara, A; Yamaguchi, H

2011-02-15

In conventional computers, wiring between transistors is required to enable the execution of Boolean logic functions. This has resulted in processors in which billions of transistors are physically interconnected, which limits integration densities, gives rise to huge power consumption and restricts processing speeds. A method to eliminate wiring amongst transistors by condensing Boolean logic into a single active element is thus highly desirable. Here, we demonstrate a novel logic architecture using only a single electromechanical parametric resonator into which multiple channels of binary information are encoded as mechanical oscillations at different frequencies. The parametric resonator can mix these channels, resulting in new mechanical oscillation states that enable the construction of AND, OR and XOR logic gates as well as multibit logic circuits. Moreover, the mechanical logic gates and circuits can be executed simultaneously, giving rise to the prospect of a parallel logic processor in just a single mechanical resonator.

Synthesizing biomolecule-based Boolean logic gates.

PubMed

Miyamoto, Takafumi; Razavi, Shiva; DeRose, Robert; Inoue, Takanari

2013-02-15

One fascinating recent avenue of study in the field of synthetic biology is the creation of biomolecule-based computers. The main components of a computing device consist of an arithmetic logic unit, the control unit, memory, and the input and output devices. Boolean logic gates are at the core of the operational machinery of these parts, and hence to make biocomputers a reality, biomolecular logic gates become a necessity. Indeed, with the advent of more sophisticated biological tools, both nucleic acid- and protein-based logic systems have been generated. These devices function in the context of either test tubes or living cells and yield highly specific outputs given a set of inputs. In this review, we discuss various types of biomolecular logic gates that have been synthesized, with particular emphasis on recent developments that promise increased complexity of logic gate circuitry, improved computational speed, and potential clinical applications.

Simultaneous G-Quadruplex DNA Logic.

PubMed

Bader, Antoine; Cockroft, Scott L

2018-04-03

A fundamental principle of digital computer operation is Boolean logic, where inputs and outputs are described by binary integer voltages. Similarly, inputs and outputs may be processed on the molecular level as exemplified by synthetic circuits that exploit the programmability of DNA base-pairing. Unlike modern computers, which execute large numbers of logic gates in parallel, most implementations of molecular logic have been limited to single computing tasks, or sensing applications. This work reports three G-quadruplex-based logic gates that operate simultaneously in a single reaction vessel. The gates respond to unique Boolean DNA inputs by undergoing topological conversion from duplex to G-quadruplex states that were resolved using a thioflavin T dye and gel electrophoresis. The modular, addressable, and label-free approach could be incorporated into DNA-based sensors, or used for resolving and debugging parallel processes in DNA computing applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Some Applications Of Semigroups And Computer Algebra In Discrete Structures

NASA Astrophysics Data System (ADS)

Bijev, G.

2009-11-01

An algebraic approach to the pseudoinverse generalization problem in Boolean vector spaces is used. A map (p) is defined, which is similar to an orthogonal projection in linear vector spaces. Some other important maps with properties similar to those of the generalized inverses (pseudoinverses) of linear transformations and matrices corresponding to them are also defined and investigated. Let Ax = b be an equation with matrix A and vectors x and b Boolean. Stochastic experiments for solving the equation, which involves the maps defined and use computer algebra methods, have been made. As a result, the Hamming distance between vectors Ax = p(b) and b is equal or close to the least possible. We also share our experience in using computer algebra systems for teaching discrete mathematics and linear algebra and research. Some examples for computations with binary relations using Maple are given.

Lattice Theory, Measures and Probability

NASA Astrophysics Data System (ADS)

Knuth, Kevin H.

2007-11-01

In this tutorial, I will discuss the concepts behind generalizing ordering to measuring and apply these ideas to the derivation of probability theory. The fundamental concept is that anything that can be ordered can be measured. Since we are in the business of making statements about the world around us, we focus on ordering logical statements according to implication. This results in a Boolean lattice, which is related to the fact that the corresponding logical operations form a Boolean algebra. The concept of logical implication can be generalized to degrees of implication by generalizing the zeta function of the lattice. The rules of probability theory arise naturally as a set of constraint equations. Through this construction we are able to neatly connect the concepts of order, structure, algebra, and calculus. The meaning of probability is inherited from the meaning of the ordering relation, implication, rather than being imposed in an ad hoc manner at the start.

The Computer-Aided Analytic Process Model. Operations Handbook for the APM (Analytic Process Model) Demonstration Package. Appendix

DTIC Science & Technology

1986-01-01

CURSUBLINEREOLJNEANSER:STINGEBSO3 52 1 1:D 372 AWSMHo~iANS2,AMS:CHAR; 53 1 IM 375 DOKE,Owc9oVER,MEG: BOOLEAN; 54 1 1:0 379 NLENGTHLLENGTH~PPEI,NDATAIIII2...integer ogain’); 159 1 3:2 112 UNTIL LENGTN(ANSVER)0>O 160 1 3:2 120 IF (ANSMEREIJ-’H’) OR (ANSMERC13o’h) THEN I -161 1 3:3 135 BEGIN3 162 1 3:4 135...END; I 176 1 3:1 300 UNTIL TRUE; 179 1 3:1 303 I0:-llr;IIi 160 1 3:1 313 FOR I:-2 TO 4 DO 181 1 3:2 328 BEGIN 182 1 33 328 IF (IICIJ>=O) AND (IICIJ<=9

Generation of three-dimensional delaunay meshes from weakly structured and inconsistent data

NASA Astrophysics Data System (ADS)

Garanzha, V. A.; Kudryavtseva, L. N.

2012-03-01

A method is proposed for the generation of three-dimensional tetrahedral meshes from incomplete, weakly structured, and inconsistent data describing a geometric model. The method is based on the construction of a piecewise smooth scalar function defining the body so that its boundary is the zero isosurface of the function. Such implicit description of three-dimensional domains can be defined analytically or can be constructed from a cloud of points, a set of cross sections, or a "soup" of individual vertices, edges, and faces. By applying Boolean operations over domains, simple primitives can be combined with reconstruction results to produce complex geometric models without resorting to specialized software. Sharp edges and conical vertices on the domain boundary are reproduced automatically without using special algorithms. Refs. 42. Figs. 25.

Factors associated with sustained remission in patients with rheumatoid arthritis.

PubMed

Martire, María Victoria; Marino Claverie, Lucila; Duarte, Vanesa; Secco, Anastasia; Mammani, Marta

2015-01-01

To find out the factors that are associated with sustained remission measured by DAS28 and boolean ACR EULAR 2011 criteria at the time of diagnosis of rheumatoid arthritis. Medical records of patients with rheumatoid arthritis in sustained remission according to DAS28 were reviewed. They were compared with patients who did not achieved values of DAS28<2.6 in any visit during the first 3 years after diagnosis. We also evaluated if patients achieved the boolean ACR/EULAR criteria. Variables analyzed: sex, age, smoking, comorbidities, rheumatoid factor, anti-CCP, ESR, CRP, erosions, HAQ, DAS28, extra-articular manifestations, time to initiation of treatment, involvement of large joints, number of tender joints, number of swollen joints, pharmacological treatment. Forty five patients that achieved sustained remission were compared with 44 controls. The variables present at diagnosis that significantly were associated with remission by DAS28 were: lower values of DAS28, HAQ, ESR, NTJ, NSJ, negative CRP, absence of erosions, male sex and absence of involvement of large joints. Only 24.71% achieved the boolean criteria. The variables associated with sustained remission by these criteria were: lower values of DAS28, HAQ, ESR, number of tender joints and number of swollen joints, negative CRP and absence of erosions. The factors associated with sustained remission were the lower baseline disease activity, the low degree of functional disability and lower joint involvement. We consider it important to recognize these factors to optimize treatment. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Boolean Operations with Prism Algebraic Patches

PubMed Central

Bajaj, Chandrajit; Paoluzzi, Alberto; Portuesi, Simone; Lei, Na; Zhao, Wenqi

2009-01-01

In this paper we discuss a symbolic-numeric algorithm for Boolean operations, closed in the algebra of curved polyhedra whose boundary is triangulated with algebraic patches (A-patches). This approach uses a linear polyhedron as a first approximation of both the arguments and the result. On each triangle of a boundary representation of such linear approximation, a piecewise cubic algebraic interpolant is built, using a C1-continuous prism algebraic patch (prism A-patch) that interpolates the three triangle vertices, with given normal vectors. The boundary representation only stores the vertices of the initial triangulation and their external vertex normals. In order to represent also flat and/or sharp local features, the corresponding normal-per-face and/or normal-per-edge may be also given, respectively. The topology is described by storing, for each curved triangle, the two triples of pointers to incident vertices and to adjacent triangles. For each triangle, a scaffolding prism is built, produced by its extreme vertices and normals, which provides a containment volume for the curved interpolating A-patch. When looking for the result of a regularized Boolean operation, the 0-set of a tri-variate polynomial within each such prism is generated, and intersected with the analogous 0-sets of the other curved polyhedron, when two prisms have non-empty intersection. The intersection curves of the boundaries are traced and used to decompose each boundary into the 3 standard classes of subpatches, denoted in, out and on. While tracing the intersection curves, the locally refined triangulation of intersecting patches is produced, and added to the boundary representation. PMID:21516262

Bibliographic Instruction in the 21st Century.

ERIC Educational Resources Information Center

Poirier, Gayle

2000-01-01

Discusses bibliographic instruction in libraries. Topics include a history of bibliographic instruction; the Internet and electronic searching; librarians' use of technology; defining information needs; locating and accessing information, including classification systems and Boolean searching; evaluating information; using and communication…

How to Make a Synthetic Multicellular Computer

PubMed Central

Macia, Javier; Sole, Ricard

2014-01-01

Biological systems perform computations at multiple scales and they do so in a robust way. Engineering metaphors have often been used in order to provide a rationale for modeling cellular and molecular computing networks and as the basis for their synthetic design. However, a major constraint in this mapping between electronic and wet computational circuits is the wiring problem. Although wires are identical within electronic devices, they must be different when using synthetic biology designs. Moreover, in most cases the designed molecular systems cannot be reused for other functions. A new approximation allows us to simplify the problem by using synthetic cellular consortia where the output of the computation is distributed over multiple engineered cells. By evolving circuits in silico, we can obtain the minimal sets of Boolean units required to solve the given problem at the lowest cost using cellular consortia. Our analysis reveals that the basic set of logic units is typically non-standard. Among the most common units, the so called inverted IMPLIES (N-Implies) appears to be one of the most important elements along with the NOT and AND functions. Although NOR and NAND gates are widely used in electronics, evolved circuits based on combinations of these gates are rare, thus suggesting that the strategy of combining the same basic logic gates might be inappropriate in order to easily implement synthetic computational constructs. The implications for future synthetic designs, the general view of synthetic biology as a standard engineering domain, as well as potencial drawbacks are outlined. PMID:24586222

Software reliability through fault-avoidance and fault-tolerance

NASA Technical Reports Server (NTRS)

Vouk, Mladen A.; Mcallister, David F.

1993-01-01

Strategies and tools for the testing, risk assessment and risk control of dependable software-based systems were developed. Part of this project consists of studies to enable the transfer of technology to industry, for example the risk management techniques for safety-concious systems. Theoretical investigations of Boolean and Relational Operator (BRO) testing strategy were conducted for condition-based testing. The Basic Graph Generation and Analysis tool (BGG) was extended to fully incorporate several variants of the BRO metric. Single- and multi-phase risk, coverage and time-based models are being developed to provide additional theoretical and empirical basis for estimation of the reliability and availability of large, highly dependable software. A model for software process and risk management was developed. The use of cause-effect graphing for software specification and validation was investigated. Lastly, advanced software fault-tolerance models were studied to provide alternatives and improvements in situations where simple software fault-tolerance strategies break down.

Verification of Java Programs using Symbolic Execution and Invariant Generation

NASA Technical Reports Server (NTRS)

Pasareanu, Corina; Visser, Willem

2004-01-01

Software verification is recognized as an important and difficult problem. We present a norel framework, based on symbolic execution, for the automated verification of software. The framework uses annotations in the form of method specifications an3 loop invariants. We present a novel iterative technique that uses invariant strengthening and approximation for discovering these loop invariants automatically. The technique handles different types of data (e.g. boolean and numeric constraints, dynamically allocated structures and arrays) and it allows for checking universally quantified formulas. Our framework is built on top of the Java PathFinder model checking toolset and it was used for the verification of several non-trivial Java programs.

Automatic Query Formulations in Information Retrieval.

ERIC Educational Resources Information Center

Salton, G.; And Others

1983-01-01

Introduces methods designed to reduce role of search intermediaries by generating Boolean search formulations automatically using term frequency considerations from natural language statements provided by system patrons. Experimental results are supplied and methods are described for applying automatic query formulation process in practice.…

Digital Equipment Corporation's CRDOM Software and Database Publications.

ERIC Educational Resources Information Center

Adams, Michael Q.

1986-01-01

Acquaints information professionals with Digital Equipment Corporation's compact optical disk read-only-memory (CDROM) search and retrieval software and growing library of CDROM database publications (COMPENDEX, Chemical Abstracts Services). Highlights include MicroBASIS, boolean operators, range operators, word and phrase searching, proximity…

Topics for Mathematics Clubs.

ERIC Educational Resources Information Center

Dalton, LeRoy C., Ed.; Snyder, Henry D., Ed.

The ten chapters in this booklet cover topics not ordinarily discussed in the classroom: Fibonacci sequences, projective geometry, groups, infinity and transfinite numbers, Pascal's Triangle, topology, experiments with natural numbers, non-Euclidean geometries, Boolean algebras, and the imaginary and the infinite in geometry. Each chapter is…

On the Computing Potential of Intracellular Vesicles

PubMed Central

Mayne, Richard; Adamatzky, Andrew

2015-01-01

Collision-based computing (CBC) is a form of unconventional computing in which travelling localisations represent data and conditional routing of signals determines the output state; collisions between localisations represent logical operations. We investigated patterns of Ca2+-containing vesicle distribution within a live organism, slime mould Physarum polycephalum, with confocal microscopy and observed them colliding regularly. Vesicles travel down cytoskeletal ‘circuitry’ and their collisions may result in reflection, fusion or annihilation. We demonstrate through experimental observations that naturally-occurring vesicle dynamics may be characterised as a computationally-universal set of Boolean logical operations and present a ‘vesicle modification’ of the archetypal CBC ‘billiard ball model’ of computation. We proceed to discuss the viability of intracellular vesicles as an unconventional computing substrate in which we delineate practical considerations for reliable vesicle ‘programming’ in both in vivo and in vitro vesicle computing architectures and present optimised designs for both single logical gates and combinatorial logic circuits based on cytoskeletal network conformations. The results presented here demonstrate the first characterisation of intracelluar phenomena as collision-based computing and hence the viability of biological substrates for computing. PMID:26431435

Automatic Design of Digital Synthetic Gene Circuits

PubMed Central

Marchisio, Mario A.; Stelling, Jörg

2011-01-01

De novo computational design of synthetic gene circuits that achieve well-defined target functions is a hard task. Existing, brute-force approaches run optimization algorithms on the structure and on the kinetic parameter values of the network. However, more direct rational methods for automatic circuit design are lacking. Focusing on digital synthetic gene circuits, we developed a methodology and a corresponding tool for in silico automatic design. For a given truth table that specifies a circuit's input–output relations, our algorithm generates and ranks several possible circuit schemes without the need for any optimization. Logic behavior is reproduced by the action of regulatory factors and chemicals on the promoters and on the ribosome binding sites of biological Boolean gates. Simulations of circuits with up to four inputs show a faithful and unequivocal truth table representation, even under parametric perturbations and stochastic noise. A comparison with already implemented circuits, in addition, reveals the potential for simpler designs with the same function. Therefore, we expect the method to help both in devising new circuits and in simplifying existing solutions. PMID:21399700

CMOL: A New Concept for Nanoelectronics

NASA Astrophysics Data System (ADS)

Likharev, Konstantin

2005-03-01

I will review the recent work on devices and architectures for future hybrid semiconductor/molecular integrated circuits, in particular those of ``CMOL'' variety [1]. Such circuits would combine an advanced CMOS subsystem fabricated by the usual lithographic patterning, two layers of parallel metallic nanowires formed, e.g., by nanoimprint, and two-terminal molecular devices self-assembled on the nanowire crosspoints. Estimates show that this powerful combination may allow CMOL circuits to reach an unparalleled density (up to 10^12 functions per cm^2) and ultrahigh rate of information processing (up to 10^20 operations per second on a single chip), at acceptable power dissipation. The main challenges on the way toward practical CMOL technology are: (i) reliable chemically-directed self-assembly of mid-size organic molecules, and (ii) the development of efficient defect-tolerant architectures for CMOL circuits. Our recent work has shown that such architectures may be developed not only for terabit-scale memories and naturally defect-tolerant mixed-signal neuromorphic networks, but (rather unexpectedly) also for FPGA-style digital Boolean circuits. [1] For details, see http://rsfq1.physics.sunysb.edu/˜likharev/nano/Springer04.pdf

Biomolecular logic systems: applications to biosensors and bioactuators

NASA Astrophysics Data System (ADS)

Katz, Evgeny

2014-05-01

The paper presents an overview of recent advances in biosensors and bioactuators based on the biocomputing concept. Novel biosensors digitally process multiple biochemical signals through Boolean logic networks of coupled biomolecular reactions and produce output in the form of YES/NO response. Compared to traditional single-analyte sensing devices, biocomputing approach enables a high-fidelity multi-analyte biosensing, particularly beneficial for biomedical applications. Multi-signal digital biosensors thus promise advances in rapid diagnosis and treatment of diseases by processing complex patterns of physiological biomarkers. Specifically, they can provide timely detection and alert to medical emergencies, along with an immediate therapeutic intervention. Application of the biocomputing concept has been successfully demonstrated for systems performing logic analysis of biomarkers corresponding to different injuries, particularly exemplified for liver injury. Wide-ranging applications of multi-analyte digital biosensors in medicine, environmental monitoring and homeland security are anticipated. "Smart" bioactuators, for example for signal-triggered drug release, were designed by interfacing switchable electrodes and biocomputing systems. Integration of novel biosensing and bioactuating systems with the biomolecular information processing systems keeps promise for further scientific advances and numerous practical applications.

Role of biomolecular logic systems in biosensors and bioactuators

NASA Astrophysics Data System (ADS)

Mailloux, Shay; Katz, Evgeny

2014-09-01

An overview of recent advances in biosensors and bioactuators based on biocomputing systems is presented. Biosensors digitally process multiple biochemical signals through Boolean logic networks of coupled biomolecular reactions and produce an output in the form of a YES/NO response. Compared to traditional single-analyte sensing devices, the biocomputing approach enables high-fidelity multianalyte biosensing, which is particularly beneficial for biomedical applications. Multisignal digital biosensors thus promise advances in rapid diagnosis and treatment of diseases by processing complex patterns of physiological biomarkers. Specifically, they can provide timely detection and alert medical personnel of medical emergencies together with immediate therapeutic intervention. Application of the biocomputing concept has been successfully demonstrated for systems performing logic analysis of biomarkers corresponding to different injuries, particularly as exemplified for liver injury. Wide-ranging applications of multianalyte digital biosensors in medicine, environmental monitoring, and homeland security are anticipated. "Smart" bioactuators, for signal-triggered drug release, for example, were designed by interfacing switchable electrodes with biocomputing systems. Integration of biosensing and bioactuating systems with biomolecular information processing systems advances the potential for further scientific innovations and various practical applications.

Computing with motile bio-agents

NASA Astrophysics Data System (ADS)

Nicolau, Dan V., Jr.; Burrage, Kevin; Nicolau, Dan V.

2007-12-01

We describe a model of computation of the parallel type, which we call 'computing with bio-agents', based on the concept that motions of biological objects such as bacteria or protein molecular motors in confined spaces can be regarded as computations. We begin with the observation that the geometric nature of the physical structures in which model biological objects move modulates the motions of the latter. Consequently, by changing the geometry, one can control the characteristic trajectories of the objects; on the basis of this, we argue that such systems are computing devices. We investigate the computing power of mobile bio-agent systems and show that they are computationally universal in the sense that they are capable of computing any Boolean function in parallel. We argue also that using appropriate conditions, bio-agent systems can solve NP-complete problems in probabilistic polynomial time.

Intelligent Machines in the 21st Century: Automating the Processes of Inference and Inquiry

NASA Technical Reports Server (NTRS)

Knuth, Kevin H.

2003-01-01

The last century saw the application of Boolean algebra toward the construction of computing machines, which work by applying logical transformations to information contained in their memory. The development of information theory and the generalization of Boolean algebra to Bayesian inference have enabled these computing machines. in the last quarter of the twentieth century, to be endowed with the ability to learn by making inferences from data. This revolution is just beginning as new computational techniques continue to make difficult problems more accessible. However, modern intelligent machines work by inferring knowledge using only their pre-programmed prior knowledge and the data provided. They lack the ability to ask questions, or request data that would aid their inferences. Recent advances in understanding the foundations of probability theory have revealed implications for areas other than logic. Of relevance to intelligent machines, we identified the algebra of questions as the free distributive algebra, which now allows us to work with questions in a way analogous to that which Boolean algebra enables us to work with logical statements. In this paper we describe this logic of inference and inquiry using the mathematics of partially ordered sets and the scaffolding of lattice theory, discuss the far-reaching implications of the methodology, and demonstrate its application with current examples in machine learning. Automation of both inference and inquiry promises to allow robots to perform science in the far reaches of our solar system and in other star systems by enabling them to not only make inferences from data, but also decide which question to ask, experiment to perform, or measurement to take given what they have learned and what they are designed to understand.

A genetic programming approach for Burkholderia Pseudomallei diagnostic pattern discovery

PubMed Central

Yang, Zheng Rong; Lertmemongkolchai, Ganjana; Tan, Gladys; Felgner, Philip L.; Titball, Richard

2009-01-01

Motivation: Finding diagnostic patterns for fighting diseases like Burkholderia pseudomallei using biomarkers involves two key issues. First, exhausting all subsets of testable biomarkers (antigens in this context) to find a best one is computationally infeasible. Therefore, a proper optimization approach like evolutionary computation should be investigated. Second, a properly selected function of the antigens as the diagnostic pattern which is commonly unknown is a key to the diagnostic accuracy and the diagnostic effectiveness in clinical use. Results: A conversion function is proposed to convert serum tests of antigens on patients to binary values based on which Boolean functions as the diagnostic patterns are developed. A genetic programming approach is designed for optimizing the diagnostic patterns in terms of their accuracy and effectiveness. During optimization, it is aimed to maximize the coverage (the rate of positive response to antigens) in the infected patients and minimize the coverage in the non-infected patients while maintaining the fewest number of testable antigens used in the Boolean functions as possible. The final coverage in the infected patients is 96.55% using 17 of 215 (7.4%) antigens with zero coverage in the non-infected patients. Among these 17 antigens, BPSL2697 is the most frequently selected one for the diagnosis of Burkholderia Pseudomallei. The approach has been evaluated using both the cross-validation and the Jack–knife simulation methods with the prediction accuracy as 93% and 92%, respectively. A novel approach is also proposed in this study to evaluate a model with binary data using ROC analysis. Contact: z.r.yang@ex.ac.uk PMID:19561021

Selective monitoring

NASA Astrophysics Data System (ADS)

Homem-de-Mello, Luiz S.

1992-04-01

While in NASA's earlier space missions such as Voyager the number of sensors was in the hundreds, future platforms such as the Space Station Freedom will have tens of thousands sensors. For these planned missions it will be impossible to use the comprehensive monitoring strategy that was used in the past in which human operators monitored all sensors all the time. A selective monitoring strategy must be substituted for the current comprehensive strategy. This selective monitoring strategy uses computer tools to preprocess the incoming data and direct the operators' attention to the most critical parts of the physical system at any given time. There are several techniques that can be used to preprocess the incoming information. This paper presents an approach to using diagnostic reasoning techniques to preprocess the sensor data and detect which parts of the physical system require more attention because components have failed or are most likely to have failed. Given the sensor readings and a model of the physical system, a number of assertions are generated and expressed as Boolean equations. The resulting system of Boolean equations is solved symbolically. Using a priori probabilities of component failure and Bayes' rule, revised probabilities of failure can be computed. These will indicate what components have failed or are the most likely to have failed. This approach is suitable for systems that are well understood and for which the correctness of the assertions can be guaranteed. Also, the system must be such that assertions can be made from instantaneous measurements. And the system must be such that changes are slow enough to allow the computation.

Quantum Vertex Model for Reversible Classical Computing

NASA Astrophysics Data System (ADS)

Chamon, Claudio; Mucciolo, Eduardo; Ruckenstein, Andrei; Yang, Zhicheng

We present a planar vertex model that encodes the result of a universal reversible classical computation in its ground state. The approach involves Boolean variables (spins) placed on links of a two-dimensional lattice, with vertices representing logic gates. Large short-ranged interactions between at most two spins implement the operation of each gate. The lattice is anisotropic with one direction corresponding to computational time, and with transverse boundaries storing the computation's input and output. The model displays no finite temperature phase transitions, including no glass transitions, independent of circuit. The computational complexity is encoded in the scaling of the relaxation rate into the ground state with the system size. We use thermal annealing and a novel and more efficient heuristic \\x9Dannealing with learning to study various computational problems. To explore faster relaxation routes, we construct an explicit mapping of the vertex model into the Chimera architecture of the D-Wave machine, initiating a novel approach to reversible classical computation based on quantum annealing.

Make Mine a Metasearcher, Please!

ERIC Educational Resources Information Center

Repman, Judi; Carlson, Randal D.

2000-01-01

Describes metasearch tools and explains their value in helping library media centers improve students' Web searches. Discusses Boolean queries and the emphasis on speed at the expense of comprehensiveness; and compares four metasearch tools, including the number of search engines consulted, user control, and databases included. (LRW)

Boolean Approaches in Digital Diagnosis

DTIC Science & Technology

1989-12-04

Automation Conference, pages 64-70, 1983. 16. Barry W. Johnson. Design and A nalysis of Fault-Tolerant Digital Systems. Addison- Wesley Publishing...Mitchell. On a new algebra of logic. In C.S. Peirce, edhitor, Studies in Logic. Little, Brown. Boston. 1883. 2:3. Roger S. Pressman . Softwrare Engineering

Stochastic Pseudo-Boolean Optimization

DTIC Science & Technology

2011-07-31

Right-Hand Side,” 2009 IN- FORMS Annual Meeting, San Diego, CA, October 11-14, 2009. 113 References [1] A.-Ghouila-Houri. Caracterisation des matrices...Optimization, 10:7–21, 2005. [30] P. Camion. Caracterisation des matrices unimodulaires. Cahiers Centre Etudes Rech., 5(4), 1963. [31] P. Camion

Small fan-in is beautiful

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

Beiu, V.; Makaruk, H.E.

1997-09-01

The starting points of this paper are two size-optimal solutions: (1) one for implementing arbitrary Boolean functions; and (2) another one for implementing certain subclasses of Boolean functions. Because VLSI implementations do not cope well with highly interconnected nets -- the area of a chip grows with the cube of the fan-in -- this paper will analyze the influence of limited fan-in on the size optimality for the two solutions mentioned. First, the authors will extend a result from Horne and Hush valid for fan-in {Delta} = 2 to arbitrary fan-in. Second, they will prove that size-optimal solutions are obtainedmore » for small constant fan-ins for both constructions, while relative minimum size solutions can be obtained for fan-ins strictly lower that linear. These results are in agreement with similar ones proving that for small constant fan-ins ({Delta} = 6...9) there exist VLSI-optimal (i.e., minimizing AT{sup 2}) solutions, while there are similar small constants relating to the capacity of processing information.« less

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

PubMed

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

2016-07-07

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.

Passive dendrites enable single neurons to compute linearly non-separable functions.

PubMed

Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

2013-01-01

Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non-separable functions.

Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions

PubMed Central

Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

2013-01-01

Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non-separable functions. PMID:23468600

Guide to Human Factors Information Sources.

DTIC Science & Technology

1984-11-01

intermediary, a computer search is sometimes unnecessary. A lucid way of presenting a search objective is either by Boolean (and/or) expressions or by Venn...1965). Human factors evaluation in system development. New York: John Wiley & Sons. 56. Murray, E. J. (1965). Sleep, dreams , and arousal. New York

Probabilistic Relational Structures and Their Applications

ERIC Educational Resources Information Center

Domotor, Zoltan

The principal objects of the investigation reported were, first, to study qualitative probability relations on Boolean algebras, and secondly, to describe applications in the theories of probability logic, information, automata, and probabilistic measurement. The main contribution of this work is stated in 10 definitions and 20 theorems. The basic…

Massive Query Resolution for Rapid Selective Dissemination of Information.

ERIC Educational Resources Information Center

Cohen, Jonathan D.

1999-01-01

Outlines an efficient approach to performing query resolution which, when matched with a keyword scanner, offers rapid selecting and routing for massive Boolean queries, and which is suitable for implementation on a desktop computer. Demonstrates the system's operation with large examples in a practical setting. (AEF)

Construction of robust dynamic genome-scale metabolic model structures of Saccharomyces cerevisiae through iterative re-parameterization.

PubMed

Sánchez, Benjamín J; Pérez-Correa, José R; Agosin, Eduardo

2014-09-01

Dynamic flux balance analysis (dFBA) has been widely employed in metabolic engineering to predict the effect of genetic modifications and environmental conditions in the cell׳s metabolism during dynamic cultures. However, the importance of the model parameters used in these methodologies has not been properly addressed. Here, we present a novel and simple procedure to identify dFBA parameters that are relevant for model calibration. The procedure uses metaheuristic optimization and pre/post-regression diagnostics, fixing iteratively the model parameters that do not have a significant role. We evaluated this protocol in a Saccharomyces cerevisiae dFBA framework calibrated for aerobic fed-batch and anaerobic batch cultivations. The model structures achieved have only significant, sensitive and uncorrelated parameters and are able to calibrate different experimental data. We show that consumption, suboptimal growth and production rates are more useful for calibrating dynamic S. cerevisiae metabolic models than Boolean gene expression rules, biomass requirements and ATP maintenance. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Modeling stock price dynamics by continuum percolation system and relevant complex systems analysis

NASA Astrophysics Data System (ADS)

Xiao, Di; Wang, Jun

2012-10-01

The continuum percolation system is developed to model a random stock price process in this work. Recent empirical research has demonstrated various statistical features of stock price changes, the financial model aiming at understanding price fluctuations needs to define a mechanism for the formation of the price, in an attempt to reproduce and explain this set of empirical facts. The continuum percolation model is usually referred to as a random coverage process or a Boolean model, the local interaction or influence among traders is constructed by the continuum percolation, and a cluster of continuum percolation is applied to define the cluster of traders sharing the same opinion about the market. We investigate and analyze the statistical behaviors of normalized returns of the price model by some analysis methods, including power-law tail distribution analysis, chaotic behavior analysis and Zipf analysis. Moreover, we consider the daily returns of Shanghai Stock Exchange Composite Index from January 1997 to July 2011, and the comparisons of return behaviors between the actual data and the simulation data are exhibited.

Land Use, Land Conservation, and Wind Energy Development Outcomes in New England

NASA Astrophysics Data System (ADS)

Weimar, William Cameron

This dissertation provides three independent research inquiries. The first examines how inter-governmental policy, site-specific, and social factors lead to the success, prolonged delay, or failure of inland wind power projects in New England. The three case studies examined include the 48 megawatt Glebe Mountain Wind Farm proposal in southern Vermont, the 30 megawatt Hoosac Wind Farm in western Massachusetts, and the 24 megawatt Lempster Wind Farm in southern New Hampshire. To ascertain why the project outcomes varied, 45 semi-structured interviews were conducted with a range of stakeholders, including wind development firms, utility companies, state regulatory agencies, regional planning commissions, town officials, land conservation organizations, and opposition groups. The second study establishes a comprehensive set of thirty-seven explanatory variables to determine the amount of suitable land and the corresponding electricity generation potential within the prime wind resource areas of Western Massachusetts. The explanatory variables are incorporated into Boolean GIS suitability models which represent the two divergent positions towards wind power development in Massachusetts, and a third, balanced model. The third study determines that exurban residential development is not the only land use factor that reduces wind power development potential in Western Massachusetts. A set of Boolean GIS models for 1985 and 2009 find the onset of conservation easements on private lands having the largest impact. During this 25 year period a combination of land use conversion and land conservation has reduced the access to prime wind resource areas by 18% (11,601 hectares), an equivalent loss of 5,800--8,700 GWh/year of zero carbon electricity generation. The six main findings from this research are: (1) Visual aesthetics remain the main factor of opposition to specific projects; (2) The Not-in-my Backyard debate for wind power remains unsettled; (3) Widespread support exists for regional land use energy plans; (4) The wind resources of Western Massachusetts can significantly contribute to the state's current renewable portfolio standard while balancing conservation and renewable energy development objectives; However, (5) a combination of exurban residential development and conservation easements significantly reduces wind power development potential over time; and (6) a need exists to legally define wind as a publicly beneficial resource.

Dataflow Computation for the J-Machine

DTIC Science & Technology

1990-06-01

MOVE 8. 1 CALL ClrTVCTO1 ;((:LkBEL (:LITERAL (:SYIBOL : BBD -IF-4)))) ZIDIF.4: ROVE [1,133, 3.3 ROV 13. A2 ((:TERIXATM)) SUSPEND ;((:LAEL (:LITBUAL...deftostant syn 0) (detconstant int-tag ’int) (detconatant Int 1) (detconstant id-tag ’ td ) (defconstant td 9) (Aotconstaut boolean-tag lbool

Exploiting the Maximum Entropy Principle to Increase Retrieval Effectiveness.

ERIC Educational Resources Information Center

Cooper, William S.

1983-01-01

Presents information retrieval design approach in which queries of computer-based system consist of sets of terms, either unweighted or weighted with subjective term precision estimates, and retrieval outputs ranked by probability of usefulness estimated by "maximum entropy principle." Boolean and weighted request systems are discussed.…

"Back-Stage" Dissent: Student Twitter Use Addressing Instructor Ideology

ERIC Educational Resources Information Center

Linvill, Darren L.; Boatwright, Brandon C.; Grant, Will J.

2018-01-01

In this content analysis, we explored how students address instructor ideology in the university classroom through the social media platform Twitter. We employed Boolean search operators through Salesforce Marketing Cloud Radian6 software to gather tweets and identified English language tweets by how students referenced their instructor's…

Optimization of digital designs

NASA Technical Reports Server (NTRS)

Miles, Lowell H. (Inventor); Whitaker, Sterling R. (Inventor)

2009-01-01

An application specific integrated circuit is optimized by translating a first representation of its digital design to a second representation. The second representation includes multiple syntactic expressions that admit a representation of a higher-order function of base Boolean values. The syntactic expressions are manipulated to form a third representation of the digital design.

Must "Hard Problems" Be Hard?

ERIC Educational Resources Information Center

Kolata, Gina

1985-01-01

To determine how hard it is for computers to solve problems, researchers have classified groups of problems (polynomial hierarchy) according to how much time they seem to require for their solutions. A difficult and complex proof is offered which shows that a combinatorial approach (using Boolean circuits) may resolve the problem. (JN)

The Impact of Text Browsing on Text Retrieval Performance.

ERIC Educational Resources Information Center

Bodner, Richard C.; Chignell, Mark H.; Charoenkitkarn, Nipon; Golovchinsky, Gene; Kopak, Richard W.

2001-01-01

Compares empirical results from three experiments using Text Retrieval Conference (TREC) data and search topics that involved three different user interfaces. Results show that marking Boolean queries on text, which encourages browsing, and hypertext interfaces to text retrieval systems can benefit recall and can also benefit novice users.…

LISA's Move from SilverPlatter to Bowker--Looking at the Interface.

ERIC Educational Resources Information Center

Stein, Jonathan

1994-01-01

Compares LISA (Library and Information Science Abstracts) on SilverPlatter's CD-ROM with its replacement version, Bowker-Saur's LISA Plus. Features reviewed include entry to the databases; use of Boolean search facilities; indexes and browsing; displaying and printing records; subsidiary functions; on-screen help; and interfaces. (Contains eight…

Library Dream Machines: Helping Students Master Super Online Catalogs.

ERIC Educational Resources Information Center

Webb, T. D.

1992-01-01

Describes how automation has transformed the library and how super-catalogs have affected the process of doing research. Explains how faculty and librarians can work together to help students to use the available databases effectively, by teaching them Boolean logic, standard record formats, filing rules, etc. (DMM)

Fundamentals of Digital Logic.

ERIC Educational Resources Information Center

Noell, Monica L.

This course is designed to prepare electronics personnel for further training in digital techniques, presenting need to know information that is basic to any maintenance course on digital equipment. It consists of seven study units: (1) binary arithmetic; (2) boolean algebra; (3) logic gates; (4) logic flip-flops; (5) nonlogic circuits; (6)…