Boolean modeling in systems biology: an overview of methodology and applications
Mathematical modeling of biological processes provides deep insights into complex cellular systems. While quantitative and continuous models such as differential equations have been widely used, their use is obstructed in systems wherein the knowledge of mechanistic details and kinetic parameters is scarce. On the other hand, a wealth of molecular level qualitative data on individual components and interactions can be obtained from the experimental literature and high-throughput technologies, making qualitative approaches such as Boolean network modeling extremely useful. In this paper, we build on our research to provide a methodology overview of Boolean modeling in systems biology, including Boolean dynamic modeling of cellular networks, attractor analysis of Boolean dynamic models, as well as inferring biological regulatory mechanisms from high-throughput data using Boolean models. We finally demonstrate how Boolean models can be applied to perform the structural analysis of cellular networks. This overview aims to acquaint life science researchers with the basic steps of Boolean modeling and its applications in several areas of systems biology. (paper)
Dynamical modeling of the cholesterol regulatory pathway with Boolean networks
Corcos Laurent
2008-11-01
Full Text Available Abstract Background Qualitative dynamics of small gene regulatory networks have been studied in quite some details both with synchronous and asynchronous analysis. However, both methods have their drawbacks: synchronous analysis leads to spurious attractors and asynchronous analysis lacks computational efficiency, which is a problem to simulate large networks. We addressed this question through the analysis of a major biosynthesis pathway. Indeed the cholesterol synthesis pathway plays a pivotal role in dislypidemia and, ultimately, in cancer through intermediates such as mevalonate, farnesyl pyrophosphate and geranyl geranyl pyrophosphate, but no dynamic model of this pathway has been proposed until now. Results We set up a computational framework to dynamically analyze large biological networks. This framework associates a classical and computationally efficient synchronous Boolean analysis with a newly introduced method based on Markov chains, which identifies spurious cycles among the results of the synchronous simulation. Based on this method, we present here the results of the analysis of the cholesterol biosynthesis pathway and its physiological regulation by the Sterol Response Element Binding Proteins (SREBPs, as well as the modeling of the action of statins, inhibitor drugs, on this pathway. The in silico experiments show the blockade of the cholesterol endogenous synthesis by statins and its regulation by SREPBs, in full agreement with the known biochemical features of the pathway. Conclusion We believe that the method described here to identify spurious cycles opens new routes to compute large and biologically relevant models, thanks to the computational efficiency of synchronous simulation. Furthermore, to the best of our knowledge, we present here the first dynamic systems biology model of the human cholesterol pathway and several of its key regulatory control elements, hoping it would provide a good basis to perform in silico
Polynomial-Time Algorithm for Controllability Test of a Class of Boolean Biological Networks
Koichi Kobayashi
2010-01-01
Full Text Available In recent years, Boolean-network-model-based approaches to dynamical analysis of complex biological networks such as gene regulatory networks have been extensively studied. One of the fundamental problems in control theory of such networks is the problem of determining whether a given substance quantity can be arbitrarily controlled by operating the other substance quantities, which we call the controllability problem. This paper proposes a polynomial-time algorithm for solving this problem. Although the algorithm is based on a sufficient condition for controllability, it is easily computable for a wider class of large-scale biological networks compared with the existing approaches. A key to this success in our approach is to give up computing Boolean operations in a rigorous way and to exploit an adjacency matrix of a directed graph induced by a Boolean network. By applying the proposed approach to a neurotransmitter signaling pathway, it is shown that it is effective.
Boolean Models of Biological Processes Explain Cascade-Like Behavior.
Chen, Hao; Wang, Guanyu; Simha, Rahul; Du, Chenghang; Zeng, Chen
2016-01-01
Biological networks play a key role in determining biological function and therefore, an understanding of their structure and dynamics is of central interest in systems biology. In Boolean models of such networks, the status of each molecule is either "on" or "off" and along with the molecules interact with each other, their individual status changes from "on" to "off" or vice-versa and the system of molecules in the network collectively go through a sequence of changes in state. This sequence of changes is termed a biological process. In this paper, we examine the common perception that events in biomolecular networks occur sequentially, in a cascade-like manner, and ask whether this is likely to be an inherent property. In further investigations of the budding and fission yeast cell-cycle, we identify two generic dynamical rules. A Boolean system that complies with these rules will automatically have a certain robustness. By considering the biological requirements in robustness and designability, we show that those Boolean dynamical systems, compared to an arbitrary dynamical system, statistically present the characteristics of cascadeness and sequentiality, as observed in the budding and fission yeast cell- cycle. These results suggest that cascade-like behavior might be an intrinsic property of biological processes. PMID:26821940
Analysis of Boolean Functions based on Interaction Graphs and their influence in System Biology
Das, Jayanta Kumar; Rout, Ranjeet Kumar; Choudhury, Pabitra Pal
2014-01-01
Interaction graphs provide an important qualitative modeling approach for System Biology. This paper presents a novel approach for construction of interaction graph with the help of Boolean function decomposition. Each decomposition part (Consisting of 2-bits) of the Boolean functions has some important significance. In the dynamics of a biological system, each variable or node is nothing but gene or protein. Their regulation has been explored in terms of interaction graphs which are generate...
Dynamical modeling of the cholesterol regulatory pathway with Boolean networks
Corcos Laurent; Kervizic Gwenael
2008-01-01
Abstract Background Qualitative dynamics of small gene regulatory networks have been studied in quite some details both with synchronous and asynchronous analysis. However, both methods have their drawbacks: synchronous analysis leads to spurious attractors and asynchronous analysis lacks computational efficiency, which is a problem to simulate large networks. We addressed this question through the analysis of a major biosynthesis pathway. Indeed the cholesterol synthesis pathway plays a pivo...
Boolean nested canalizing functions: a comprehensive analysis
Li, Yuan; Murrugarra, David; Aguilar, Boris; Laubenbacher, Reinhard
2012-01-01
Boolean network models of molecular regulatory networks have been used successfully in computational systems biology. The Boolean functions that appear in published models tend to have special properties, in particular the property of being nested canalizing, a property inspired by the concept of canalization in evolutionary biology. It has been shown that networks comprised of nested canalizing functions have dynamic properties that make them suitable for modeling molecular regulatory networks, namely a small number of (large) attractors, as well as relatively short limit cycles. This paper contains a detailed analysis of this class of functions, based on a novel normal form as polynomial functions over the Boolean field. The concept of layer is introduced that stratifies variables into different classes depending on their level of dominance. Using this layer concept a closed form formula is derived for the number of nested canalizing functions with a given number of variables. Additional metrics analyzed in...
Lovrics, Anna
2014-11-14
We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.
Reverter Antonio
2011-02-01
Full Text Available Abstract Background Cancer has remarkable complexity at the molecular level, with multiple genes, proteins, pathways and regulatory interconnections being affected. We introduce a systems biology approach to study cancer that formally integrates the available genetic, transcriptomic, epigenetic and molecular knowledge on cancer biology and, as a proof of concept, we apply it to colorectal cancer. Results We first classified all the genes in the human genome into cancer-associated and non-cancer-associated genes based on extensive literature mining. We then selected a set of functional attributes proven to be highly relevant to cancer biology that includes protein kinases, secreted proteins, transcription factors, post-translational modifications of proteins, DNA methylation and tissue specificity. These cancer-associated genes were used to extract 'common cancer fingerprints' through these molecular attributes, and a Boolean logic was implemented in such a way that both the expression data and functional attributes could be rationally integrated, allowing for the generation of a guilt-by-association algorithm to identify novel cancer-associated genes. Finally, these candidate genes are interlaced with the known cancer-related genes in a network analysis aimed at identifying highly conserved gene interactions that impact cancer outcome. We demonstrate the effectiveness of this approach using colorectal cancer as a test case and identify several novel candidate genes that are classified according to their functional attributes. These genes include the following: 1 secreted proteins as potential biomarkers for the early detection of colorectal cancer (FXYD1, GUCA2B, REG3A; 2 kinases as potential drug candidates to prevent tumor growth (CDC42BPB, EPHB3, TRPM6; and 3 potential oncogenic transcription factors (CDK8, MEF2C, ZIC2. Conclusion We argue that this is a holistic approach that faithfully mimics cancer characteristics, efficiently predicts
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.
Propagation of external regulation and asynchronous dynamics in random Boolean networks
Mahmoudi, Hamed; Pagnani, Andrea; Weigt, Martin; Zecchina, Riccardo
2007-01-01
Boolean Networks and their dynamics are of great interest as abstract modeling schemes in various disciplines, ranging from biology to computer science. Whereas parallel update schemes have been studied extensively in past years, the level of understanding of asynchronous updates schemes is still very poor. In this paper we study the propagation of external information given by regulatory input variables into a random Boolean network. We compute both analytically and numerically the time evol...
Boolean network model predicts knockout mutant phenotypes of fission yeast.
Maria I Davidich
Full Text Available BOOLEAN NETWORKS (OR: networks of switches are extremely simple mathematical models of biochemical signaling networks. Under certain circumstances, Boolean networks, despite their simplicity, are capable of predicting dynamical activation patterns of gene regulatory networks in living cells. For example, the temporal sequence of cell cycle activation patterns in yeasts S. pombe and S. cerevisiae are faithfully reproduced by Boolean network models. An interesting question is whether this simple model class could also predict a more complex cellular phenomenology as, for example, the cell cycle dynamics under various knockout mutants instead of the wild type dynamics, only. Here we show that a Boolean network model for the cell cycle control network of yeast S. pombe correctly predicts viability of a large number of known mutants. So far this had been left to the more detailed differential equation models of the biochemical kinetics of the yeast cell cycle network and was commonly thought to be out of reach for models as simplistic as Boolean networks. The new results support our vision that Boolean networks may complement other mathematical models in systems biology to a larger extent than expected so far, and may fill a gap where simplicity of the model and a preference for an overall dynamical blueprint of cellular regulation, instead of biochemical details, are in the focus.
Boolean Differential Operators
Catumba, Jorge; Diaz, Rafael
2012-01-01
We consider four combinatorial interpretations for the algebra of Boolean differential operators. We show that each interpretation yields an explicit matrix representation for Boolean differential operators.
Fast Gr\\"obner Basis Computation for Boolean Polynomials
Hinkelmann, Franziska
2010-01-01
We introduce the Macaulay2 package BooleanGB, which computes a Gr\\"obner basis for Boolean polynomials using a binary representation rather than symbolic. We compare the runtime of several Boolean models from systems in biology and give an application to Sudoku.
Combinatorics of Boolean automata circuits dynamics
Demongeot, Jacques; Noual, Mathilde; Sené, Sylvain
2012-01-01
International audience In line with fields of theoretical computer science and biology that study Boolean automata networks to model regulation networks, we present some results concerning the dynamics of networks whose underlying structures are oriented cycles, that is, Boolean automata circuits. In the context of biological regulation, former studies have highlighted the importance of circuits on the asymptotic dynamical behaviour of the biological networks that contain them. Our work fo...
Montanaro, Ashley; Osborne, Tobias J.
2008-01-01
In this paper we introduce the study of quantum boolean functions, which are unitary operators f whose square is the identity: f^2 = I. We describe several generalisations of well-known results in the theory of boolean functions, including quantum property testing; a quantum version of the Goldreich-Levin algorithm for finding the large Fourier coefficients of boolean functions; and two quantum versions of a theorem of Friedgut, Kalai and Naor on the Fourier spectra of boolean functions. In o...
Boolean reasoning the logic of boolean equations
Brown, Frank Markham
2012-01-01
A systematic treatment of Boolean reasoning, this concise, newly revised edition combines the works of early logicians with recent investigations, including previously unpublished research results. Brown begins with an overview of elementary mathematical concepts and outlines the theory of Boolean algebras. Two concluding chapters deal with applications. 1990 edition.
Andersen, Henrik Reif; Hulgaard, Henrik
2002-01-01
This paper presents a new data structure called boolean expression diagrams (BEDs) for representing and manipulating Boolean functions. BEDs are a generalization of binary decision diagrams (BDDs) which can represent any Boolean circuit in linear space. Two algorithms are described for transforming...
Solomon, Alan D
2012-01-01
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Boolean Algebra includes set theory, sentential calculus, fundamental ideas of Boolean algebras, lattices, rings and Boolean algebras, the structure of a Boolean algebra, and Boolean
Mining TCGA data using Boolean implications.
Subarna Sinha
Full Text Available 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/.
Monotone Boolean functions are an important object in discrete mathematics and mathematical cybernetics. Topics related to these functions have been actively studied for several decades. Many results have been obtained, and many papers published. However, until now there has been no sufficiently complete monograph or survey of results of investigations concerning monotone Boolean functions. The object of this survey is to present the main results on monotone Boolean functions obtained during the last 50 years
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.
Andersen, Henrik Reif; Hulgaard, Henrik
This paper presents a new data structure called Boolean Expression Diagrams (BEDs) for representing and manipulating Boolean functions. BEDs are a generalization of Binary Decision Diagrams (BDDs) which can represent any Boolean circuit in linear space and still maintain many of the desirable...... properties of BDDs. Two algorithms are described for transforming a BED into a reduced ordered BDD. One closely mimics the BDD apply-operator while the other can exploit the structural information of the Boolean expression. The efficacy of the BED representation is demonstrated by verifying that the...
Effect of memory in non-Markovian Boolean networks
Ebadi, Haleh; Ausloos, Marcel; Jafari, GholamReza
2016-01-01
One successful model of interacting biological systems is the Boolean network. The dynamics of a Boolean network, controlled with Boolean functions, is usually considered to be a Markovian (memory-less) process. However, both self organizing features of biological phenomena and their intelligent nature should raise some doubt about ignoring the history of their time evolution. Here, we extend the Boolean network Markovian approach: we involve the effect of memory on the dynamics. This can be explored by modifying Boolean functions into non-Markovian functions, for example, by investigating the usual non-Markovian threshold function, - one of the most applied Boolean functions. By applying the non-Markovian threshold function on the dynamical process of a cell cycle network, we discover a power law memory with a more robust dynamics than the Markovian dynamics.
Bayesian variable selection and data integration for biological regulatory networks
Jensen, Shane T; Chen, Guang; Stoeckert, Jr, Christian J.
2007-01-01
A substantial focus of research in molecular biology are gene regulatory networks: the set of transcription factors and target genes which control the involvement of different biological processes in living cells. Previous statistical approaches for identifying gene regulatory networks have used gene expression data, ChIP binding data or promoter sequence data, but each of these resources provides only partial information. We present a Bayesian hierarchical model that integrates all three dat...
Exploring phospholipase C-coupled Ca(2+) signalling networks using Boolean modelling.
Bhardwaj, G; Wells, C P; Albert, R; van Rossum, D B; Patterson, R L
2011-05-01
In this study, the authors explored the utility of a descriptive and predictive bionetwork model for phospholipase C-coupled calcium signalling pathways, built with non-kinetic experimental information. Boolean models generated from these data yield oscillatory activity patterns for both the endoplasmic reticulum resident inositol-1,4,5-trisphosphate receptor (IP(3)R) and the plasma-membrane resident canonical transient receptor potential channel 3 (TRPC3). These results are specific as randomisation of the Boolean operators ablates oscillatory pattern formation. Furthermore, knock-out simulations of the IP(3)R, TRPC3 and multiple other proteins recapitulate experimentally derived results. The potential of this approach can be observed by its ability to predict previously undescribed cellular phenotypes using in vitro experimental data. Indeed, our cellular analysis of the developmental and calcium-regulatory protein, DANGER1a, confirms the counter-intuitive predictions from our Boolean models in two highly relevant cellular models. Based on these results, the authors theorise that with sufficient legacy knowledge and/or computational biology predictions, Boolean networks can provide a robust method for predictive modelling of any biological system. [Includes supplementary material]. PMID:21639591
Boolean filters of distributive lattices
M. Sambasiva Rao
2013-07-01
Full Text Available In this paper we introduce the notion of Boolean filters in a pseudo-complemented distributive lattice and characterize the class of all Boolean filters. Further a set of equivalent conditions are derived for a proper filter to become a prime Boolean filter. Also a set of equivalent conditions is derived for a pseudo-complemented distributive lattice to become a Boolean algebra. Finally, a Boolean filter is characterized in terms of congruences.
Boolean Models of Biosurfactants Production in Pseudomonas fluorescens
Richard, Adrien; Rossignol, Gaelle; Comet, Jean-Paul; Bernot, Gilles; Guespin-Michel, Jannine; Merieau, Annabelle
2012-01-01
Cyclolipopeptides (CLPs) are biosurfactants produced by numerous Pseudomonas fluorescens strains. CLP production is known to be regulated at least by the GacA/GacS two-component pathway, but the full regulatory network is yet largely unknown. In the clinical strain MFN1032, CLP production is abolished by a mutation in the phospholipase C gene () and not restored by complementation. Their production is also subject to phenotypic variation. We used a modelling approach with Boolean networks, which takes into account all these observations concerning CLP production without any assumption on the topology of the considered network. Intensive computation yielded numerous models that satisfy these properties. All models minimizing the number of components point to a bistability in CLP production, which requires the presence of a yet unknown key self-inducible regulator. Furthermore, all suggest that a set of yet unexplained phenotypic variants might also be due to this epigenetic switch. The simplest of these Boolean networks was used to propose a biological regulatory network for CLP production. This modelling approach has allowed a possible regulation to be unravelled and an unusual behaviour of CLP production in P. fluorescens to be explained. PMID:22303435
Boolean networks as modelling framework
Florian eGreil
2012-08-01
Full Text Available In a network, the components of a given system are represented as nodes, the interactions are abstracted as links between the nodes. Boolean networks refer to a class of dynamics on networks, in fact it is the simplest possible dynamics where each node has a value 0 or 1. This allows to investigate extensively the dynamics both analytically and by numerical experiments. The present article focuses on the theoretical concept of relevant components and the immediate application in plant biology, references for more in-depths treatment of the mathematical details are also given.
On the number of attractors of Boolean automata circuits
Demongeot, Jacques; Noual, Mathilde; Sené, Sylvain
2009-01-01
In line with fields of theoretical computer science and biology that study Boolean automata networks often seen as models of regulation networks, we present some results concerning the dynamics of networks whose underlying interaction graphs are circuits, that is Boolean automata circuits. In the context of biological regulation, former studies have highlighted the importance of circuits on the asymptotic dynamical behaviour of the biological networks that contain them. Our work focuses on th...
Kaushik, Aman Chandra; Sahi, Shakti
2015-06-01
Systems biology addresses challenges in the analysis of genomics data, especially for complex genes and protein interactions using Meta data approach on various signaling pathways. In this paper, we report systems biology and biological circuits approach to construct pathway and identify early gene and protein interactions for predicting GPR142 responses in Type 2 diabetes. The information regarding genes, proteins and other molecules involved in Type 2 diabetes were retrieved from literature and kinetic simulation of GPR142 was carried out in order to determine the dynamic interactions. The major objective of this work was to design a GPR142 biochemical pathway using both systems biology as well as biological circuits synthetically. The term 'synthetically' refers to building biological circuits for cell signaling pathway especially for hormonal pathway disease. The focus of the paper is on logical components and logical circuits whereby using these applications users can create complex virtual circuits. Logic gates process represents only true or false and investigates whether biological regulatory circuits are active or inactive. The basic gates used are AND, NAND, OR, XOR and NOT gates and Integrated circuit composition of many such basic gates and some derived gates. Biological circuits may have a futuristic application in biomedical sciences which may involve placing a micro chip in human cells to modulate the down or up regulation of hormonal disease. PMID:25972988
Stratification and enumeration of Boolean functions by canalizing depth
He, Qijun; Macauley, Matthew
2016-01-01
Boolean network models have gained popularity in computational systems biology over the last dozen years. Many of these networks use canalizing Boolean functions, which has led to increased interest in the study of these functions. The canalizing depth of a function describes how many canalizing variables can be recursively "picked off", until a non-canalizing function remains. In this paper, we show how every Boolean function has a unique algebraic form involving extended monomial layers and a well-defined core polynomial. This generalizes recent work on the algebraic structure of nested canalizing functions, and it yields a stratification of all Boolean functions by their canalizing depth. As a result, we obtain closed formulas for the number of n-variable Boolean functions with depth k, which simultaneously generalizes enumeration formulas for canalizing, and nested canalizing functions.
Stratification and enumeration of Boolean functions by canalizing depth
He, Qijun
2015-01-01
Boolean network models have gained popularity in computational systems biology over the last dozen years. Many of these networks use canalizing Boolean functions, which has led to increased interest in the study of these functions. The canalizing depth of a function describes how many canalizing variables can be recursively picked off, until a non-canalizing function remains. In this paper, we show how every Boolean function has a unique algebraic form involving extended monomial layers and a well-defined core polynomial. This generalizes recent work on the algebraic structure of nested canalizing functions, and it yields a stratification of all Boolean functions by their canalizing depth. As a result, we obtain closed formulas for the number of n-variable Boolean functions with depth k, which simultaneously generalizes enumeration formulas for canalizing, and nested canalizing functions.
Enhancing Boolean networks with fuzzy operators and edge tuning
Poret, Arnaud; Monteiro Sousa, Claudio; Boissel, Jean-Pierre
2014-01-01
Quantitative modeling in systems biology can be difficult due to the scarcity of quantitative details about biological phenomenons, especially at the subcellular scale. An alternative to escape this difficulty is qualitative modeling since it requires few to no quantitative information. Among the qualitative modeling approaches, the Boolean network formalism is one of the most popular. However, Boolean models allow variables to be valued at only true or false, which can appear too simplistic ...
Drossel, Barbara
2007-01-01
This review explains in a self-contained way the properties of random Boolean networks and their attractors, with a special focus on critical networks. Using small example networks, analytical calculations, phenomenological arguments, and problems to solve, the basic concepts are introduced and important results concerning phase diagrams, numbers of relevant nodes and attractor properties are derived.
Relative stability of network states in Boolean network models of gene regulation in development.
Zhou, Joseph Xu; Samal, Areejit; d'Hérouël, Aymeric Fouquier; Price, Nathan D; Huang, Sui
2016-01-01
Progress in cell type reprogramming has revived the interest in Waddington's concept of the epigenetic landscape. Recently researchers developed the quasi-potential theory to represent the Waddington's landscape. The Quasi-potential U(x), derived from interactions in the gene regulatory network (GRN) of a cell, quantifies the relative stability of network states, which determine the effort required for state transitions in a multi-stable dynamical system. However, quasi-potential landscapes, originally developed for continuous systems, are not suitable for discrete-valued networks which are important tools to study complex systems. In this paper, we provide a framework to quantify the landscape for discrete Boolean networks (BNs). We apply our framework to study pancreas cell differentiation where an ensemble of BN models is considered based on the structure of a minimal GRN for pancreas development. We impose biologically motivated structural constraints (corresponding to specific type of Boolean functions) and dynamical constraints (corresponding to stable attractor states) to limit the space of BN models for pancreas development. In addition, we enforce a novel functional constraint corresponding to the relative ordering of attractor states in BN models to restrict the space of BN models to the biological relevant class. We find that BNs with canalyzing/sign-compatible Boolean functions best capture the dynamics of pancreas cell differentiation. This framework can also determine the genes' influence on cell state transitions, and thus can facilitate the rational design of cell reprogramming protocols. PMID:26965665
Fault Tolerant Boolean Satisfiability
Roy, A
2011-01-01
A delta-model is a satisfying assignment of a Boolean formula for which any small alteration, such as a single bit flip, can be repaired by flips to some small number of other bits, yielding a new satisfying assignment. These satisfying assignments represent robust solutions to optimization problems (e.g., scheduling) where it is possible to recover from unforeseen events (e.g., a resource becoming unavailable). The concept of delta-models was introduced by Ginsberg, Parkes and Roy (AAAI 1998), where it was proved that finding delta-models for general Boolean formulas is NP-complete. In this paper, we extend that result by studying the complexity of finding delta-models for classes of Boolean formulas which are known to have polynomial time satisfiability solvers. In particular, we examine 2-SAT, Horn-SAT, Affine-SAT, dual-Horn-SAT, 0-valid and 1-valid SAT. We see a wide variation in the complexity of finding delta-models, e.g., while 2-SAT and Affine-SAT have polynomial time tests for delta-models, testing w...
Computational complexity of Boolean functions
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.
Geometric Operators on Boolean Functions
Frisvad, Jeppe Revall; Falster, Peter
2007-01-01
In truth-functional propositional logic, any propositional formula represents a Boolean function (according to some valuation of the formula). We describe operators based on Decartes' concept of constructing coordinate systems, for translation of a propositional formula to the image of a Boolean function. With this image of a Boolean function corresponding to a propositional formula, we prove that the orthogonal projection operator leads to a theorem describing all rules of inference in propo...
Algorithms for Weighted Boolean Optimization
Manquinho, Vasco; Marques-Silva, Joao; Planes Cid, Jordi
2009-01-01
The Pseudo-Boolean Optimization (PBO) and Maximum Satisfiability (MaxSAT) problems are natural optimization extensions of Boolean Satisfiability (SAT). In the recent past, different algorithms have been proposed for PBO and for MaxSAT, despite the existence of straightforward mappings from PBO to MaxSAT and viceversa. This papers proposes Weighted Boolean Optimization (WBO), a new uni- fied framework that aggregates and extends PBO and MaxSAT. In addition, the paper proposes...
T Regulatory Cell Biology in Health and Disease.
Alroqi, Fayhan J; Chatila, Talal A
2016-04-01
Regulatory T (Treg) cells that express the transcription factor forkhead box protein P3 (FOXP3) play an essential role in enforcing immune tolerance to self tissues, regulating host-commensal flora interaction, and facilitating tissue repair. Their deficiency and/or dysfunction trigger unbridled autoimmunity and inflammation. A growing number of monogenic defects have been recognized that adversely impact Treg cell development, differentiation, and/or function, leading to heritable diseases of immune dysregulation and autoimmunity. In this article, we review recent insights into Treg cell biology and function, with particular attention to lessons learned from newly recognized clinical disorders of Treg cell deficiency. PMID:26922942
Symmetry in Boolean Satisfiability
Fadi A. Aloul
2010-06-01
Full Text Available This paper reviews recent approaches on how to accelerate Boolean Satisfiability (SAT search by exploiting symmetries in the problem space. SAT search algorithms traverse an exponentially large search space looking for an assignment that satisfies a set of constraints. The presence of symmetries in the search space induces equivalence classes on the set of truth assignments. The goal is to use symmetries to avoid traversing all assignments by constraining the search to visit a few representative assignments in each equivalence class. This can lead to a significant reduction in search runtime without affecting the completeness of the search.
Boolean Orthogonalizing Combination Methods
Yavuz Can
2015-05-01
Full Text Available In this paper a new logical operation method called “ presented. It is used to calculate the difference, but also the complement of a function as well as the EXOR and EXNOR of two minterms respectively two ternary respectively two ternary-vector logical operation method called “orthogonal OR advantages of both methods are their results, which are already available form that has an essential advantage for continuing calculations. Since it applies, an orthogonal disjunctive normal form is equal to orthogonal antivalence normal form, subsequent Boolean differential calculus will be simplified.
Investigating Boolean Matrix Factorization
Snášel, V.; Platoš, J.; Krömer, P.; Húsek, Dušan; Neruda, Roman; Frolov, A. A.
- : ACM, 2008 - (Ding, C.; Li, T.; Zhu, S.), s. 18-25 ISBN 978-1-60558-307-5. [DMMT'08. Workshop in Conjunction with SIGKDD 2008 /14./. Las Vegas (US), 24.08.2008-24.08.2008] Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean factor analysis * nonnegative matrix factorization * neural networks * information retrieval * data mining * binary data Subject RIV: BB - Applied Statistics, Operational Research http://users.cs.fiu.edu/~taoli/kdd08-workshop/DMMT08-Proceedings.pdf
Fault Tolerant Boolean Satisfiability
Roy, A
2011-01-01
A delta-model is a satisfying assignment of a Boolean formula for which any small alteration, such as a single bit flip, can be repaired by flips to some small number of other bits, yielding a new satisfying assignment. These satisfying assignments represent robust solutions to optimization problems (e.g., scheduling) where it is possible to recover from unforeseen events (e.g., a resource becoming unavailable). The concept of delta-models was introduced by Ginsberg, Parkes and Roy (AAAI 1998...
Approximate Reasoning with Fuzzy Booleans
Broek, van den P.M.; Noppen, J.A.R.
2004-01-01
This paper introduces, in analogy to the concept of fuzzy numbers, the concept of fuzzy booleans, and examines approximate reasoning with the compositional rule of inference using fuzzy booleans. It is shown that each set of fuzzy rules is equivalent to a set of fuzzy rules with singleton crisp ante
Geometric Operators on Boolean Functions
Frisvad, Jeppe Revall; Falster, Peter
of a few geometric operators working on the images of Boolean functions. The operators we describe, arise from the niche area of array-based logic and have previously been tightly bound to an array-based representation of Boolean functions. We redefine the operators in an abstract form to make them...
Cryptographic Boolean functions and applications
Cusick, Thomas W
2009-01-01
Boolean functions are the building blocks of symmetric cryptographic systems. Symmetrical cryptographic algorithms are fundamental tools in the design of all types of digital security systems (i.e. communications, financial and e-commerce).Cryptographic Boolean Functions and Applications is a concise reference that shows how Boolean functions are used in cryptography. Currently, practitioners who need to apply Boolean functions in the design of cryptographic algorithms and protocols need to patch together needed information from a variety of resources (books, journal articles and other sources). This book compiles the key essential information in one easy to use, step-by-step reference. Beginning with the basics of the necessary theory the book goes on to examine more technical topics, some of which are at the frontier of current research.-Serves as a complete resource for the successful design or implementation of cryptographic algorithms or protocols using Boolean functions -Provides engineers and scient...
Cardinal invariants on Boolean algebras
Monk, J Donald
2014-01-01
This book is concerned with cardinal number valued functions defined for any Boolean algebra. Examples of such functions are independence, which assigns to each Boolean algebra the supremum of the cardinalities of its free subalgebras, and cellularity, which gives the supremum of cardinalities of sets of pairwise disjoint elements. Twenty-one such functions are studied in detail, and many more in passing. The questions considered are the behaviour of these functions under algebraic operations such as products, free products, ultraproducts, and their relationships to one another. Assuming familiarity with only the basics of Boolean algebras and set theory, through simple infinite combinatorics and forcing, the book reviews current knowledge about these functions, giving complete proofs for most facts. A special feature of the book is the attention given to open problems, of which 185 are formulated. Based on Cardinal Functions on Boolean Algebras (1990) and Cardinal Invariants on Boolean Algebras (1996) by the...
Statins as Modulators of Regulatory T-Cell Biology
David A. Forero-Peña
2013-01-01
Full Text Available Statins are pharmacological inhibitors of the activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR, an enzyme responsible for the synthesis of cholesterol. Some recent experimental studies have shown that besides their effects on the primary and secondary prevention of cardiovascular diseases, statins may also have beneficial anti-inflammatory effects through diverse mechanisms. On the other hand, the induction and activity of regulatory T cells (Treg are key processes in the prevention of pathology during chronic inflammatory and autoimmune diseases. Hence, strategies oriented towards the therapeutic expansion of Tregs are gaining special attention among biomedical researchers. The potential effects of statins on the biology of Treg are of particular importance because of their eventual application as in vivo inducers of Treg in the treatment of multiple conditions. In this paper we review the experimental evidence pointing out to a potential effect of statins on the role of regulatory T cells in different conditions and discuss its potential clinical significance.
What does biologically meaningful mean? A perspective on gene regulatory network validation
Walhout, Albertha JM
2011-01-01
Gene regulatory networks (GRNs) are rapidly being delineated, but their quality and biological meaning are often questioned. Here, I argue that biological meaning is challenging to define and discuss reasons why GRN validation should be interpreted cautiously.
Techniques for solving Boolean equation systems
Keinänen, Misa
2006-01-01
Boolean equation systems are ordered sequences of Boolean equations decorated with least and greatest fixpoint operators. Boolean equation systems provide a useful framework for formal verification because various specification and verification problems, for instance, μ-calculus model checking can be represented as the problem of solving Boolean equation systems. The general problem of solving a Boolean equation system is a computationally hard task, and no polynomial time solution technique ...
A more robust Boolean model describing inhibitor binding
Zhaoqian Steven XIE; Chao TANG
2008-01-01
From the first application of the Boolean model to the cell cycle regulation network of budding yeast, new regulative pathways have been discovered, par-ticularly in the G1/S transition circuit. This discovery called for finer modeling to study the essential biology, and the resulting outcomes are first introduced in the ar-ticle. A traditional Boolean network model set up for the new G1/S transition circuit shows that it cannot correctly simulate real biology unless the model parameters are fine tuned. The deficiency is caused by an overly coarse-grained description of the inhibitor binding process, which shall be overcome by a two-vector model proposed whose robustness is surveyed using random perturba-tions. Simulations show that the proposed two-vector model is much more robust in describing inhibitor binding processes within the Boolean framework.
A Note on the Inversion Complexity of Boolean Functions in Boolean Formulas
Morizumi, Hiroki
2008-01-01
In this note, we consider the minimum number of NOT operators in a Boolean formula representing a Boolean function. In circuit complexity theory, the minimum number of NOT gates in a Boolean circuit computing a Boolean function $f$ is called the inversion complexity of $f$. In 1958, Markov determined the inversion complexity of every Boolean function and particularly proved that $\\lceil \\log_2(n+1) \\rceil$ NOT gates are sufficient to compute any Boolean function on $n$ variables. As far as we...
On the Number of Attractors of Positive and Negative Boolean Automata Circuits.
Demongeot, Jacques; Noual, Mathilde; Sené, Sylvain
2010-01-01
International audience In line with fields of theoretical computer science and biology that study Boolean automata networks often seen as models of regulation networks, we present some results concerning the dynamics of networks whose underlying interaction graphs are circuits, that is, Boolean automata circuits. In the context of biological regulation, former studies have highlighted the importance of circuits on the asymptotic dynamical behaviour of the biological networks that contain t...
Kaushik, Aman Chandra; Sahi, Shakti
2015-01-01
Systems biology addresses challenges in the analysis of genomics data, especially for complex genes and protein interactions using Meta data approach on various signaling pathways. In this paper, we report systems biology and biological circuits approach to construct pathway and identify early gene and protein interactions for predicting GPR142 responses in Type 2 diabetes. The information regarding genes, proteins and other molecules involved in Type 2 diabetes were retrieved from literature...
Generalized join-hemimorphisms on Boolean algebras
Sergio Celani
2003-01-01
We introduce the notions of generalized join-hemimorphism and generalized Boolean relation as an extension of the notions of join-hemimorphism and Boolean relation, respectively. We prove a duality between these two notions. We will also define a generalization of the notion of Boolean algebra with operators by considering a finite family of Boolean algebras endowed with a generalized join-hemimorphism. Finally, we define suitable notions of subalgebra, congruences, Boole...
Kauffman, L H
2002-01-01
In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.
Boolean Operations on Conic Polygons
Yong-Xi Gong; Yu Liu; Lun Wu; Yu-Bo Xie
2009-01-01
An algorithm for Boolean operations on conic polygons is proposed. Conic polygons are polygons consisting of conic segments or bounded conics with directions. Preliminaries of Boolean operations on general polygons are presented. In our algorithm, the intersection points and the topological relationships between two conic polygons are computed. Boundaries are obtained by tracking path and selecting uncrossed boundaries following rule tables to build resulting conic polygons.We define a set of rules for the intersection, union, and subtraction operations on conic polygons. The algorithm considers degeneration cases such as homology, complement, interior, and exterior. The algorithm is also evaluated and implemented.
Cardinal invariants on Boolean algebras
Monk, J Donald
2009-01-01
Deals with cardinal number valued functions defined for any Boolean algebra. This title considers the behavior of these functions under algebraic operations such as products, free products, ultraproducts, and their relationships to one another. It covers topics such as ultraproducts and Fedorchukis theorem
Boolean-Valued Belief Functions
Kramosil, Ivan
2002-01-01
Roč. 31, č. 2 (2002), s. 153-181. ISSN 0308-1079 R&D Projects: GA AV ČR IAA1030803 Institutional research plan: AV0Z1030915 Keywords : Dempster-Schafer theory * Boolean algebra Subject RIV: BA - General Mathematics Impact factor: 0.241, year: 2002
Evolutionary Design of Boolean Functions
WANG Zhang-yi; ZHANG Huan-guo; QIN Zhong-ping; MENG Qing-shu
2005-01-01
We use evolutionary computing to synthesize Boolean functions randomly. By using specific crossover and mutation operator in evolving process and modifying search space and fitness function, we get some high non-linearity functions which have other good cryptography characteristics such as autocorrelation etc. Comparing to other heuristic search techniques, evolutionary computing approach is more effective because of global search strategy and implicit parallelism.
Boolean Delay Equations: A simple way of looking at complex systems
Ghil, Michael; Zaliapin, Ilya; Coluzzi, Barbara
2006-01-01
Boolean Delay Equations (BDEs) are semi-discrete dynamical models with Boolean-valued variables that evolve in continuous time. Systems of BDEs can be classified into conservative or dissipative, in a manner that parallels the classification of ordinary or partial differential equations. Solutions to certain conservative BDEs exhibit growth of complexity in time. They represent therewith metaphors for biological evolution or human history. Dissipative BDEs are structurally stable and exhibit ...
Quantum algorithms for testing Boolean functions
Erika Andersson
2010-06-01
Full Text Available We discuss quantum algorithms, based on the Bernstein-Vazirani algorithm, for finding which variables a Boolean function depends on. There are 2^n possible linear Boolean functions of n variables; given a linear Boolean function, the Bernstein-Vazirani quantum algorithm can deterministically identify which one of these Boolean functions we are given using just one single function query. The same quantum algorithm can also be used to learn which input variables other types of Boolean functions depend on, with a success probability that depends on the form of the Boolean function that is tested, but does not depend on the total number of input variables. We also outline a procedure to futher amplify the success probability, based on another quantum algorithm, the Grover search.
Algorithms for Finding Small Attractors in Boolean Networks
Hayashida Morihiro
2007-01-01
Full Text Available A Boolean network is a model used to study the interactions between different genes in genetic regulatory networks. In this paper, we present several algorithms using gene ordering and feedback vertex sets to identify singleton attractors and small attractors in Boolean networks. We analyze the average case time complexities of some of the proposed algorithms. For instance, it is shown that the outdegree-based ordering algorithm for finding singleton attractors works in time for , which is much faster than the naive time algorithm, where is the number of genes and is the maximum indegree. We performed extensive computational experiments on these algorithms, which resulted in good agreement with theoretical results. In contrast, we give a simple and complete proof for showing that finding an attractor with the shortest period is NP-hard.
Boolean Reasoning with Graphs of Partitions
Goossens, Daniel
2010-01-01
version longue du papier court "A Dynamic Boolean Knowledge Base" accepté à ICTAI 2010. This paper presents an implemented architecture for easy learning, reorganizing and navigation into a Boolean knowledge base. As the base grows with new definitions and constraints, it is normalized by the closure of a completion operator. This normalization allows arbitrary formats for Boolean expressions. It ensures basic reasoning abilities and spontaneously organizes intermingled taxonomies of conce...
Model Checking of Boolean Process Models
Schneider, Christoph; Wehler, Joachim
2011-01-01
In the field of Business Process Management formal models for the control flow of business processes have been designed since more than 15 years. Which methods are best suited to verify the bulk of these models? The first step is to select a formal language which fixes the semantics of the models. We adopt the language of Boolean systems as reference language for Boolean process models. Boolean systems form a simple subclass of coloured Petri nets. Their characteristics are low tokens to mode...
Progress in Applications of Boolean Functions
Sasao, Tsutomu
2010-01-01
This book brings together five topics on the application of Boolean functions. They are 1. Equivalence classes of Boolean functions: The number of n-variable functions is large, even for values as small as n = 6, and there has been much research on classifying functions. There are many classifications, each with their own distinct merit. 2. Boolean functions for cryptography: The process of encrypting/decrypting plain text messages often depends on Boolean functions with specific properties. For example, highly nonlinear functions are valued because they are less susceptible to linear attacks.
Information theory in systems biology. Part I: Gene regulatory and metabolic networks.
Mousavian, Zaynab; Kavousi, Kaveh; Masoudi-Nejad, Ali
2016-03-01
"A Mathematical Theory of Communication", was published in 1948 by Claude Shannon to establish a framework that is now known as information theory. In recent decades, information theory has gained much attention in the area of systems biology. The aim of this paper is to provide a systematic review of those contributions that have applied information theory in inferring or understanding of biological systems. Based on the type of system components and the interactions between them, we classify the biological systems into 4 main classes: gene regulatory, metabolic, protein-protein interaction and signaling networks. In the first part of this review, we attempt to introduce most of the existing studies on two types of biological networks, including gene regulatory and metabolic networks, which are founded on the concepts of information theory. PMID:26701126
A SAT-based algorithm for finding attractors in synchronous Boolean networks.
Dubrova, Elena; Teslenko, Maxim
2011-01-01
This paper addresses the problem of finding attractors in synchronous Boolean networks. The existing Boolean decision diagram-based algorithms have limited capacity due to the excessive memory requirements of decision diagrams. The simulation-based algorithms can be applied to larger networks, however, they are incomplete. We present an algorithm, which uses a SAT-based bounded model checking to find all attractors in a Boolean network. The efficiency of the presented algorithm is evaluated by analyzing seven networks models of real biological processes, as well as 150,000 randomly generated Boolean networks of sizes between 100 and 7,000. The results show that our approach has a potential to handle an order of magnitude larger models than currently possible. PMID:21778527
A novel generalized design methodology and realization of Boolean operations using DNA.
Zoraida, B S E; Arock, Michael; Ronald, B S M; Ponalagusamy, R
2009-09-01
The biological deoxyribonucleic acid (DNA) strand has been increasingly seen as a promising computing unit. A new algorithm is formulated in this paper to design any DNA Boolean operator with molecular beacons (MBs) as its input. Boolean operators realized using the proposed design methodology is presented. The developed operators adopt a uniform representation for logical 0 and 1 for any Boolean operator. The Boolean operators designed in this work employ only a hybridization operation at each stage. Further, this paper for the first time brings out the realization of a binary adder and subtractor using molecular beacons. Simulation results of the DNA-based binary adder and subtractor are given to validate the design. PMID:19505531
Guixia Liu; Lei Liu; Chunyu Liu; Ming Zheng; Lanying Su; Chunguang Zhou
2011-01-01
Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actual regulatory conditions in gene regulatory networks, especially when strong regulators do work significantly, in this paper, we propose a novel approach based on combining neuro-fuzzy network models with biological knowledge to infer strong regulators and interrelated fuzzy rules. The hybrid neuro-fuzzy architecture can not only infer the fuzzy rules, which are suitable for describing the regulatory conditions in regulatory networks, but also explain the meaning of nodes and weight value in the neural network. It can get useful rules automatically without factitious judgments. At the same time, it does not add recursive layers to the model, and the model can also strengthen the relationships among genes and reduce calculation. We use the proposed approach to reconstruct a partial gene regulatory network of yeast. The results show that this approach can work effectively.
Boolean Search: Current State and Perspectives.
Frants, Valery I.; Shapiro, Jacob; Taksa, Isak; Voiskunskii, Vladimir G.
1999-01-01
Discusses the use of Boolean logic in information-retrieval systems and analyzes existing criticisms of operational systems. Considers users' ability to use and understand Boolean operators, ranking, the quality of query formulations, and negative effects of criticism; and concludes that criticism is directed at the methodology employed in…
Version Spaces and Generalized Monotone Boolean Functions
J.C. Bioch (Cor); T. Ibaraki
2002-01-01
textabstractWe consider generalized monotone functions f: X --> {0,1} defined for an arbitrary binary relation <= on X by the property x <= y implies f(x) <= f(y). These include the standard monotone (or positive) Boolean functions, regular Boolean functions and other interesting functions as speci
Low doses of ionizing radiation: Biological effects and regulatory control. Contributed papers
The International Atomic Energy Agency and the World Health Organization, in cooperation with the United Nations Scientific Committee on the Effects of Atomic Radiation, organized an international conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, held in seville, Spain, from 17 to 21 November 1997. This technical document contains concise papers submitted to the conference
Boolean gates on actin filaments
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.
Analysis and Control of Boolean Networks:A Semi-tensor Product Approach%布尔网络的分析与控制-矩阵半张量积方法
程代展; 齐洪胜; 赵寅
2011-01-01
布尔网络是描述基因调控网络的一个有力工具.由于系统生物学的发展,布尔网络的分析与控制成为生物学与系统控制学科的交叉热点.本文综述作者用其原创的矩阵半张量积方法在布尔网络的分析与控制中得到的一系列结果.内容包括:布尔网络的拓扑结构,布尔控制网络的能控、能观性与实现,布尔网络的稳定性和布尔控制网络的镇定,布尔控制网络的干扰解耦,布尔(控制)网络的辨识,以及布尔网络的最优控制等.%Boolean network is a powerful tool for describing gene regulatory network. With the development of the systems biology, the analysis and control of Boolean networks become a hot topic for multidisciplinary research. This paper surveys some recent results obtained in the analysis and control of Boolean networks using semi-tensor product of matrices. The contents of this paper include the topological structure of Boolean networks, the controllability and observability, realization, stability and stabilization, disturbance decoupling, identification, and optimal control of Boolean (control) networks.
Generalizing Boolean Satisfiability II: Theory
Dixon, H E; Luks, E M; Parkes, A J; 10.1613/jair.1555
2011-01-01
This is the second of three planned papers describing ZAP, a satisfiability engine that substantially generalizes existing tools while retaining the performance characteristics of modern high performance solvers. The fundamental idea underlying ZAP is that many problems passed to such engines contain rich internal structure that is obscured by the Boolean representation used; our goal is to define a representation in which this structure is apparent and can easily be exploited to improve computational performance. This paper presents the theoretical basis for the ideas underlying ZAP, arguing that existing ideas in this area exploit a single, recurring structure in that multiple database axioms can be obtained by operating on a single axiom using a subgroup of the group of permutations on the literals in the problem. We argue that the group structure precisely captures the general structure at which earlier approaches hinted, and give numerous examples of its use. We go on to extend the Davis-Putnam-Logemann-...
Boolean networks with reliable dynamics
Peixoto, Tiago P
2009-01-01
We investigated the properties of Boolean networks that follow a given reliable trajectory in state space. A reliable trajectory is defined as a sequence of states which is independent of the order in which the nodes are updated. We explored numerically the topology, the update functions, and the state space structure of these networks, which we constructed using a minimum number of links and the simplest update functions. We found that the clustering coefficient is larger than in random networks, and that the probability distribution of three-node motifs is similar to that found in gene regulation networks. Among the update functions, only a subset of all possible functions occur, and they can be classified according to their probability. More homogeneous functions occur more often, leading to a dominance of canalyzing functions. Finally, we studied the entire state space of the networks. We observed that with increasing systems size, fixed points become more dominant, moving the networks close to the frozen...
Local Correction of Boolean Functions
Alon, Noga
2011-01-01
A Boolean function f over n variables is said to be q-locally correctable if, given a black-box access to a function g which is "close" to an isomorphism f_sigma of f, we can compute f_sigma(x) for any x in Z_2^n with good probability using q queries to g. We observe that any k-junta, that is, any function which depends only on k of its input variables, is O(2^k)-locally correctable. Moreover, we show that there are examples where this is essentially best possible, and locally correcting some k-juntas requires a number of queries which is exponential in k. These examples, however, are far from being typical, and indeed we prove that for almost every k-junta, O(k log k) queries suffice.
Densities of mixed volumes for Boolean models
Weil, Wolfgang
2001-01-01
In generalization of the well-known formulae for quermass densities of stationary and isotropic Boolean models, we prove corresponding results for densities of mixed volumes in the stationary situation and show how they can be used to determine the intensity of non-isotropic Boolean models Z in d-dimensional space for d = 2, 3, 4. We then consider non-stationary Boolean models and extend results of Fallert on quermass densities to densities of mixed volumes. In particular, we present explicit...
Translating Pseudo-Boolean Constraints into CNF
Aavani, Amir
2011-01-01
A Pseudo-Boolean constraint is a linear constraint over Boolean variables. This kind of constraints has been widely used in expressing NP-complete problems. This paper introduces a new algorithm for translating Pseudo-Boolean constraints into CNF clauses. The CNF produced by the proposed encoding has small size, and we also characterize the constraints for which one can expect the SAT solvers to perform well on the produced CNF. We show that there are many constraints for which the proposed encoding has a good performance.
Mysler, Eduardo; Pineda, Carlos; Horiuchi, Takahiko; Singh, Ena; Mahgoub, Ehab; Coindreau, Javier; Jacobs, Ira
2016-05-01
Biologics are vital to the management of patients with rheumatic and musculoskeletal diseases such as rheumatoid arthritis and other inflammatory and autoimmune conditions. Nevertheless, access to these highly effective treatments remains an unmet medical need for many people around the world. As patents expire for existing licensed biologic (originator) products, biosimilar products can be approved by regulatory authorities and enter clinical use. Biosimilars are highly similar copies of originator biologics approved through defined and stringent regulatory processes after having undergone rigorous analytical, non-clinical, and clinical evaluations. The introduction of high-quality, safe, and effective biosimilars has the potential to expand access to these important medicines. Biosimilars are proven to be similar to the originator biologic in terms of safety and efficacy and to have no clinically meaningful differences. In contrast, "intended copies" are copies of originator biologics that have not undergone rigorous comparative evaluations according to the World Health Organization recommendations, but are being commercialized in some countries. There is a lack of information about the efficacy and safety of intended copies compared with the originator. Furthermore, they may have clinically significant differences in formulation, dosages, efficacy, or safety. In this review, we explore the differences between biosimilars and intended copies and describe key concepts related to biosimilars. Familiarity with these topics may facilitate decision making about the appropriate use of biosimilars for patients with rheumatic and musculoskeletal diseases. PMID:26920148
A Systems’ Biology Approach to Study MicroRNA-Mediated Gene Regulatory Networks
Xin Lai
2013-01-01
Full Text Available MicroRNAs (miRNAs are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. Such an approach is characterized by an iterative process, including biological data acquisition and integration, network construction, mathematical modeling and experimental validation. To demonstrate the application of this approach, we adopt it to investigate mechanisms of collective repression on p21 by multiple miRNAs. We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. Based on the network structure, a detailed mechanistic model is established and its parameter values are determined using data. Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts.
Boolean Logic with Fault Tolerant Coding
Alagoz, B. Baykant
2009-01-01
Error detectable and error correctable coding in Hamming space was researched to discover possible fault tolerant coding constellations, which can implement Boolean logic with fault tolerant property. Basic logic operators of the Boolean algebra were developed to apply fault tolerant coding in the logic circuits. It was shown that application of three-bit fault tolerant codes have provided the digital system skill of auto-recovery without need for designing additional-fault tolerance mechanisms.
Sensitivity versus block sensitivity of Boolean functions
Virza, Madars
2010-01-01
Determining relationship between sensitivity and block sensitivity of Boolean functions is of interest for computational complexity theory. We construct a sequence of Boolean functions with bs(f) = 1/2 (s(f))^2+ 1/2 s(f). The best known separation previously was bs(f) = 1/2 (s(f))^2 due to Rubinstein (1995). We also report results of computer search for functions with at most 12 variables.
Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering
He, Fei; Murabito, Ettore; Westerhoff, Hans V
2016-01-01
Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased...
Early history of regulatory requirements for poultry biologics in the United States.
Espeseth, David A; Lasher, Hiram
2010-12-01
Congress passed the Virus-Serum-Toxin Act in 1913, giving the U.S. Department of Agriculture (USDA) authority to prevent the importation or interstate shipment of worthless, contaminated, dangerous, or harmful veterinary biological products. The passage of this act marked the beginning of regulatory requirements for veterinary biological products in the United States. In 1913, only a few biologics establishments produced products for the poultry industry. The first license issued by the USDA for a poultry product was in 1918 to the University of California, Berkeley, for fowlpox vaccine. The list of biological products for poultry grew slowly in the 1920s. However, this began to change with the licensing of laryngotracheitis vaccine in 1933; pigeonpox vaccine in 1939; several Newcastle disease vaccines (inactivated in 1946, Roakin strain in 1948, B1 strain in 1950, and La Sota strain in 1952); and the first bronchitis vaccine in 1953. With the development of these and other new products, the biologics industry began to move its emphasis on hog cholera serum and virus to one based on the production of numerous new vaccines and bacterial products. The USDA's approach to the regulation of biologics in the early 1950s was still geared to the production of hog cholera products; however, as a result of the intervention of a group of dedicated poultry scientists, who were concerned about the poor performance of Newcastle disease vaccines, this soon changed. This presentation describes the initiation and development of modern standards for poultry biologics that occurred as a result of this intervention. The development and improvement of standards and regulatory requirements to address mycoplasma, leukosis, and other extraneous virus contaminations in chicken embryo origin products are reviewed. The licensing of products to meet new and emerging disease problems in the poultry industry and the close interaction among research scientists, poultry industry, biologics
He, Fei; Murabito, Ettore; Westerhoff, Hans V
2016-04-01
Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out throughin silicotheoretical studies with the aim to guide and complement furtherin vitroandin vivoexperimental efforts. Clearly, what counts is the resultin vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. PMID:27075000
Evolution and Controllability of Cancer Networks: A Boolean Perspective.
Srihari, Sriganesh; Raman, Venkatesh; Leong, Hon Wai; Ragan, Mark A
2014-01-01
Cancer forms a robust system capable of maintaining stable functioning (cell sustenance and proliferation) despite perturbations. Cancer progresses as stages over time typically with increasing aggressiveness and worsening prognosis. Characterizing these stages and identifying the genes driving transitions between them is critical to understand cancer progression and to develop effective anti-cancer therapies. In this work, we propose a novel model for the `cancer system' as a Boolean state space in which a Boolean network, built from protein-interaction and gene-expression data from different stages of cancer, transits between Boolean satisfiability states by "editing" interactions and "flipping" genes. Edits reflect rewiring of the PPI network while flipping of genes reflect activation or silencing of genes between stages. We formulate a minimization problem min flip to identify these genes driving the transitions. The application of our model (called BoolSpace) on three case studies-pancreatic and breast tumours in human and post spinal-cord injury (SCI) in rats-reveals valuable insights into the phenomenon of cancer progression: (i) interactions involved in core cell-cycle and DNA-damage repair pathways are significantly rewired in tumours, indicating significant impact to key genome-stabilizing mechanisms; (ii) several of the genes flipped are serine/threonine kinases which act as biological switches, reflecting cellular switching mechanisms between stages; and (iii) different sets of genes are flipped during the initial and final stages indicating a pattern to tumour progression. Based on these results, we hypothesize that robustness of cancer partly stems from "passing of the baton" between genes at different stages-genes from different biological processes and/or cellular components are involved in different stages of tumour progression thereby allowing tumour cells to evade targeted therapy, and therefore an effective therapy should target a "cover set" of
Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options
Carter, Sarah R. [J. Craig Venter Institute; Rodemeyer, Michael [University of Virginia; Garfinkel, Michele S. [EMBO; Friedman, Robert M [J. Craig Venter Institute
2014-05-01
Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options Sarah R. Carter, Ph.D., J. Craig Venter Institute; Michael Rodemeyer, J.D., University of Virginia; Michele S. Garfinkel, Ph.D., EMBO; Robert M. Friedman, Ph.D., J. Craig Venter Institute In recent years, a range of genetic engineering techniques referred to as “synthetic biology” has significantly expanded the tool kit available to scientists and engineers, providing them with far greater capabilities to engineer organisms than previous techniques allowed. The field of synthetic biology includes the relatively new ability to synthesize long pieces of DNA from chemicals, as well as improved methods for genetic manipulation and design of genetic pathways to achieve more precise control of biological systems. These advances will help usher in a new generation of genetically engineered microbes, plants, and animals. The JCVI Policy Center team, along with researchers at the University of Virginia and EMBO, examined how well the current U.S. regulatory system for genetically engineered products will handle the near-term introduction of organisms engineered using synthetic biology. In particular, the focus was on those organisms intended to be used or grown directly in the environment, outside of a contained facility. The study concludes that the U.S. regulatory agencies have adequate legal authority to address most, but not all, potential environmental, health and safety concerns posed by these organisms. Such near-term products are likely to represent incremental changes rather than a marked departure from previous genetically engineered organisms. However, the study also identified two key challenges for the regulatory system, which are detailed in the report. First, USDA’s authority over genetically engineered plants depends on the use of an older engineering technique that is no longer necessary for many applications. The shift to synthetic biology and other newer genetic
Forced synchronization of autonomous dynamical Boolean networks
We present the design of an autonomous time-delay Boolean network realized with readily available electronic components. Through simulations and experiments that account for the detailed nonlinear response of each circuit element, we demonstrate that a network with five Boolean nodes displays complex behavior. Furthermore, we show that the dynamics of two identical networks display near-instantaneous synchronization to a periodic state when forced by a common periodic Boolean signal. A theoretical analysis of the network reveals the conditions under which complex behavior is expected in an individual network and the occurrence of synchronization in the forced networks. This research will enable future experiments on autonomous time-delay networks using readily available electronic components with dynamics on a slow enough time-scale so that inexpensive data collection systems can faithfully record the dynamics
Forced synchronization of autonomous dynamical Boolean networks
Rivera-Durón, R. R., E-mail: roberto.rivera@ipicyt.edu.mx; Campos-Cantón, E., E-mail: eric.campos@ipicyt.edu.mx [División de Matemáticas Aplicadas, Instituto Potosino de Investigación Científica y Tecnológica A. C., Camino a la Presa San José 2055, Col. Lomas 4 Sección, C.P. 78216, San Luis Potosí, S.L.P. (Mexico); Campos-Cantón, I. [Facultad de Ciencias, Universidad Autónoma de San Luis Potosí, Álvaro Obregón 64, C.P. 78000, San Luis Potosí, S.L.P. (Mexico); Gauthier, Daniel J. [Department of Physics and Center for Nonlinear and Complex Systems, Duke University, Box 90305, Durham, North Carolina 27708 (United States)
2015-08-15
We present the design of an autonomous time-delay Boolean network realized with readily available electronic components. Through simulations and experiments that account for the detailed nonlinear response of each circuit element, we demonstrate that a network with five Boolean nodes displays complex behavior. Furthermore, we show that the dynamics of two identical networks display near-instantaneous synchronization to a periodic state when forced by a common periodic Boolean signal. A theoretical analysis of the network reveals the conditions under which complex behavior is expected in an individual network and the occurrence of synchronization in the forced networks. This research will enable future experiments on autonomous time-delay networks using readily available electronic components with dynamics on a slow enough time-scale so that inexpensive data collection systems can faithfully record the dynamics.
Duality theories for Boolean algebras with operators
Givant, Steven
2014-01-01
In this new text, Steven Givant—the author of several acclaimed books, including works co-authored with Paul Halmos and Alfred Tarski—develops three theories of duality for Boolean algebras with operators. Givant addresses the two most recognized dualities (one algebraic and the other topological) and introduces a third duality, best understood as a hybrid of the first two. This text will be of interest to graduate students and researchers in the fields of mathematics, computer science, logic, and philosophy who are interested in exploring special or general classes of Boolean algebras with operators. Readers should be familiar with the basic arithmetic and theory of Boolean algebras, as well as the fundamentals of point-set topology.
Kim Man-Sun
2012-05-01
Full Text Available Abstract Background Network motifs provided a “conceptual tool” for understanding the functional principles of biological networks, but such motifs have primarily been used to consider static network structures. Static networks, however, cannot be used to reveal time- and region-specific traits of biological systems. To overcome this limitation, we proposed the concept of a “spatiotemporal network motif,” a spatiotemporal sequence of network motifs of sub-networks which are active only at specific time points and body parts. Results On the basis of this concept, we analyzed the developmental gene regulatory network of the Drosophila melanogaster embryo. We identified spatiotemporal network motifs and investigated their distribution pattern in time and space. As a result, we found how key developmental processes are temporally and spatially regulated by the gene network. In particular, we found that nested feedback loops appeared frequently throughout the entire developmental process. From mathematical simulations, we found that mutual inhibition in the nested feedback loops contributes to the formation of spatial expression patterns. Conclusions Taken together, the proposed concept and the simulations can be used to unravel the design principle of developmental gene regulatory networks.
New Measure of Boolean Factor Analysis Quality
Frolov, A. A.; Húsek, Dušan; Polyakov, P.Y.
Vol. 1. Heidelberg: Springer, 2011 - (Dobnikar, A.; Lotrič, U.; Šter, B.), s. 100-109. (Lecture Notes in Computer Science. 6593). ISBN 978-3-642-20281-0. ISSN 0302-9743. [ICANNGA'2011. International Conference /10./. Ljubljana (SI), 14.04.2011-16.04.2011] R&D Projects: GA ČR GAP202/10/0262; GA ČR GA205/09/1079 Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean factor analysis * information gain * expectation-maximization * associative memory * neural network application * Boolean matrix factorization * bars problem * Hopfield neural network Subject RIV: IN - Informatics, Computer Science
Algorithms for Boolean Function Query Properties
Aaronson, Scott
2001-01-01
We present new algorithms to compute fundamental properties of a Boolean function given in truth-table form. Specifically, we give an O(N^2.322 log N) algorithm for block sensitivity, an O(N^1.585 log N) algorithm for `tree decomposition,' and an O(N) algorithm for `quasisymmetry.' These algorithms are based on new insights into the structure of Boolean functions that may be of independent interest. We also give a subexponential-time algorithm for the space-bounded quantum query complexity of...
A finite alternation result for reversible boolean circuits
Selinger, Peter
2016-01-01
We say that a reversible boolean function on n bits has alternation depth d if it can be written as the sequential composition of d reversible boolean functions, each of which acts only on the top n-1 bits or on the bottom n-1 bits. We show that every reversible boolean function of n >= 4 bits has alternation depth 9.
Some Aspects of Boolean Valued Analysis
Kusraev, A. G.; Kutateladze, S. S.
2015-01-01
This is a survey of some recent applications of Boolean valued analysis to operator theory and harmonic analysis. Under consideration are pseudoembedding operators, the noncommutative Wickstead problem, the Radon-Nikodym Theorem for JB-algebras, and the Bochner Theorem for lattice-valued positive definite mappings on locally compact groups.
Demonstrating Boolean Logic Using Simple Electrical Circuits
McElhaney, Kevin W.
2004-01-01
While exploring the subject of geometric proofs, boolean logic operators AND and OR can be used to allow students to visualize their true-or-false patterns. An activity in the form of constructing electrical circuits is illustrated to explain the concept.
Boolean Queries Optimization by Genetic Algorithms
Húsek, Dušan; Owais, S.S.J.; Krömer, P.; Snášel, Václav
2005-01-01
Roč. 15, - (2005), s. 395-409. ISSN 1210-0552 R&D Projects: GA AV ČR 1ET100300414 Institutional research plan: CEZ:AV0Z10300504 Keywords : evolutionary algorithms * genetic algorithms * genetic programming * information retrieval * Boolean query Subject RIV: BB - Applied Statistics, Operational Research
Evolutionary Algorithms for Boolean Queries Optimization
Húsek, Dušan; Snášel, Václav; Neruda, Roman; Owais, S.S.J.; Krömer, P.
2006-01-01
Roč. 3, č. 1 (2006), s. 15-20. ISSN 1790-0832 R&D Projects: GA AV ČR 1ET100300414 Institutional research plan: CEZ:AV0Z10300504 Keywords : evolutionary algorithms * genetic algorithms * information retrieval * Boolean query Subject RIV: BA - General Mathematics
A complexity theory based on Boolean algebra
Skyum, Sven; Valiant, Leslie
1985-01-01
A projection of a Boolean function is a function obtained by substituting for each of its variables a variable, the negation of a variable, or a constant. Reducibilities among computational problems under this relation of projection are considered. It is shown that much of what is of everyday rel...
A Boolean Map Theory of Visual Attention
Huang, Liqiang; Pashler, Harold
2007-01-01
A theory is presented that attempts to answer two questions. What visual contents can an observer consciously access at one moment? Answer: only one feature value (e.g., green) per dimension, but those feature values can be associated (as a group) with multiple spatially precise locations (comprising a single labeled Boolean map). How can an…
Thiosulfoxide (Sulfane Sulfur: New Chemistry and New Regulatory Roles in Biology
John I. Toohey
2014-08-01
Full Text Available The understanding of sulfur bonding is undergoing change. Old theories on hypervalency of sulfur and the nature of the chalcogen-chalcogen bond are now questioned. At the same time, there is a rapidly expanding literature on the effects of sulfur in regulating biological systems. The two fields are inter-related because the new understanding of the thiosulfoxide bond helps to explain the newfound roles of sulfur in biology. This review examines the nature of thiosulfoxide (sulfane, S0 sulfur, the history of its regulatory role, its generation in biological systems, and its functions in cells. The functions include synthesis of cofactors (molybdenum cofactor, iron-sulfur clusters, sulfuration of tRNA, modulation of enzyme activities, and regulating the redox environment by several mechanisms (including the enhancement of the reductive capacity of glutathione. A brief review of the analogous form of selenium suggests that the toxicity of selenium may be due to over-reduction caused by the powerful reductive activity of glutathione perselenide.
Hu, Mingxiao; Shen, Liangzhong; Zan, Xiangzhen; Shang, Xuequn; Liu, Wenbin
2016-01-01
Boolean networks are widely used to model gene regulatory networks and to design therapeutic intervention strategies to affect the long-term behavior of systems. In this paper, we investigate the less-studied one-bit perturbation, which falls under the category of structural intervention. Previous works focused on finding the optimal one-bit perturbation to maximally alter the steady-state distribution (SSD) of undesirable states through matrix perturbation theory. However, the application of the SSD is limited to Boolean networks with about ten genes. In 2007, Xiao et al. proposed to search the optimal one-bit perturbation by altering the sizes of the basin of attractions (BOAs). However, their algorithm requires close observation of the state-transition diagram. In this paper, we propose an algorithm that efficiently determines the BOA size after a perturbation. Our idea is that, if we construct the basin of states for all states, then the size of the BOA of perturbed networks can be obtained just by updating the paths of the states whose transitions have been affected. Results from both synthetic and real biological networks show that the proposed algorithm performs better than the exhaustive SSD-based algorithm and can be applied to networks with about 25 genes. PMID:27196530
Xia Wang
Full Text Available Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.
Regulatory inhibition of biological tissue mineralization through post-nucleation shielding
Chang, Joshua; Miura, Robert
In vertebrates, insufficient availability of calcium and phosphate ions in extracellular fluids leads to loss of bone density and neuronal hyper-excitability. To counteract this problem, calcium ions are present at high concentrations throughout body fluids - at concentrations exceeding the saturation point. This condition leads to the opposite situation where unwanted mineral sedimentation may occur. Remarkably, ectopic or out-of-place sedimentation into soft tissues is rare, in spite of the thermodynamic driving factors. This fortunate fact is due to the presence of auto-regulatory proteins that are found in abundance in bodily fluids. Yet, many important inflammatory disorders such as atherosclerosis and osteoarthritis are associated with this undesired calcification. Hence, it is important to gain an understanding of the regulatory process and the conditions under which it can go awry. We adapted mean-field classical nucleation theory to the case of surface-shielding in order to study the regulation of sedimentation of calcium phosphate salts in biological tissues. Mathematical Biosciences Institute, NSF DMS-1021818, National Institutes of Health, Rehab Medicine.
Tóthfalusi, Lászlo; Endrényi, László; Chow, Shein-Chung
2014-05-01
When the patent of a brand-name, marketed drug expires, new, generic products are usually offered. Small-molecule generic and originator drug products are expected to be chemically identical. Their pharmaceutical similarity can be typically assessed by simple regulatory criteria such as the expectation that the 90% confidence interval for the ratio of geometric means of some pharmacokinetic parameters be between 0.80 and 1.25. When such criteria are satisfied, the drug products are generally considered to exhibit therapeutic equivalence. They are then usually interchanged freely within individual patients. Biological drugs are complex proteins, for instance, because of their large size, intricate structure, sensitivity to environmental conditions, difficult manufacturing procedures, and the possibility of immunogenicity. Generic and brand-name biologic products can be expected to show only similarity but not identity in their various features and clinical effects. Consequently, the determination of biosimilarity is also a complicated process which involves assessment of the totality of the evidence for the close similarity of the two products. Moreover, even when biosimilarity has been established, it may not be assumed that the two biosimilar products can be automatically substituted by pharmacists. This generally requires additional, careful considerations. Without declaring interchangeability, a new product could be prescribed, i.e. it is prescribable. However, two products can be automatically substituted only if they are interchangeable. Interchangeability is a statistical term and it means that products can be used in any order in the same patient without considering the treatment history. The concepts of interchangeability and prescribability have been widely discussed in the past but only in relation to small molecule generics. In this paper we apply these concepts to biosimilars and we discuss: definitions of prescribability and interchangeability and
Simulating Quantitative Cellular Responses Using Asynchronous Threshold Boolean Network Ensembles
Shah Imran
2011-07-01
Full Text Available Abstract Background With increasing knowledge about the potential mechanisms underlying cellular functions, it is becoming feasible to predict the response of biological systems to genetic and environmental perturbations. Due to the lack of homogeneity in living tissues it is difficult to estimate the physiological effect of chemicals, including potential toxicity. Here we investigate a biologically motivated model for estimating tissue level responses by aggregating the behavior of a cell population. We assume that the molecular state of individual cells is independently governed by discrete non-deterministic signaling mechanisms. This results in noisy but highly reproducible aggregate level responses that are consistent with experimental data. Results We developed an asynchronous threshold Boolean network simulation algorithm to model signal transduction in a single cell, and then used an ensemble of these models to estimate the aggregate response across a cell population. Using published data, we derived a putative crosstalk network involving growth factors and cytokines - i.e., Epidermal Growth Factor, Insulin, Insulin like Growth Factor Type 1, and Tumor Necrosis Factor α - to describe early signaling events in cell proliferation signal transduction. Reproducibility of the modeling technique across ensembles of Boolean networks representing cell populations is investigated. Furthermore, we compare our simulation results to experimental observations of hepatocytes reported in the literature. Conclusion A systematic analysis of the results following differential stimulation of this model by growth factors and cytokines suggests that: (a using Boolean network ensembles with asynchronous updating provides biologically plausible noisy individual cellular responses with reproducible mean behavior for large cell populations, and (b with sufficient data our model can estimate the response to different concentrations of extracellular ligands. Our
"Antelope": a hybrid-logic model checker for branching-time Boolean GRN analysis
Arellano Gustavo
2011-12-01
Full Text Available Abstract 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
Boolean representations of simplicial complexes and matroids
Rhodes, John
2015-01-01
This self-contained monograph explores a new theory centered around boolean representations of simplicial complexes leading to a new class of complexes featuring matroids as central to the theory. The book illustrates these new tools to study the classical theory of matroids as well as their important geometric connections. Moreover, many geometric and topological features of the theory of matroids find their counterparts in this extended context. Graduate students and researchers working in the areas of combinatorics, geometry, topology, algebra and lattice theory will find this monograph appealing due to the wide range of new problems raised by the theory. Combinatorialists will find this extension of the theory of matroids useful as it opens new lines of research within and beyond matroids. The geometric features and geometric/topological applications will appeal to geometers. Topologists who desire to perform algebraic topology computations will appreciate the algorithmic potential of boolean represent...
Fast Vertical Mining Using Boolean Algebra
Hosny M. Ibrahim
2015-01-01
Full Text Available The vertical association rules mining algorithm is an efficient mining method, which makes use of support sets of frequent itemsets to calculate the support of candidate itemsets. It overcomes the disadvantage of scanning database many times like Apriori algorithm. In vertical mining, frequent itemsets can be represented as a set of bit vectors in memory, which enables for fast computation. The sizes of bit vectors for itemsets are the main space expense of the algorithm that restricts its expansibility. Therefore, in this paper, a proposed algorithm that compresses the bit vectors of frequent itemsets will be presented. The new bit vector schema presented here depends on Boolean algebra rules to compute the intersection of two compressed bit vectors without making any costly decompression operation. The experimental results show that the proposed algorithm, Vertical Boolean Mining (VBM algorithm is better than both Apriori algorithm and the classical vertical association rule mining algorithm in the mining time and the memory usage.
Boolean network robotics: a proof of concept
Roli, Andrea; Pinciroli, Carlo; Birattari, Mauro
2011-01-01
Dynamical systems theory and complexity science provide powerful tools for analysing artificial agents and robots. Furthermore, they have been recently proposed also as a source of design principles and guidelines. Boolean networks are a prominent example of complex dynamical systems and they have been shown to effectively capture important phenomena in gene regulation. From an engineering perspective, these models are very compelling, because they can exhibit rich and complex behaviours, in spite of the compactness of their description. In this paper, we propose the use of Boolean networks for controlling robots' behaviour. The network is designed by means of an automatic procedure based on stochastic local search techniques. We show that this approach makes it possible to design a network which enables the robot to accomplish a task that requires the capability of navigating the space using a light stimulus, as well as the formation and use of an internal memory.
Chaos synchronization of two stochastically coupled random Boolean networks
Hung, Y.-C. [Department of Physics, National Sun Yat-sen University, Kaohsiung, Taiwan (China) and Nonlinear Science Group, Department of Physics, National Kaohsiung Normal University, Kaohsiung, Taiwan (China)]. E-mail: d9123801@student.nsysu.edu.tw; Ho, M.-C. [Nonlinear Science Group, Department of Physics, National Kaohsiung Normal University, Kaohsiung, Taiwan (China)]. E-mail: t1603@nknucc.nknu.edu.tw; Lih, J.-S. [Department of Physics and Geoscience, National Pingtung University of Education, Pingtung, Taiwan (China); Nonlinear Science Group, Department of Physics, National Kaohsiung Normal University, Kaohsiung, Taiwan (China); Jiang, I-M. [Department of Physics, National Sun Yat-sen University, Kaohsiung, Taiwan (China); Nonlinear Science Group, Department of Physics, National Kaohsiung Normal University, Kaohsiung, Taiwan (China)
2006-07-24
In this Letter, we study the chaos synchronization of two stochastically coupled random Boolean networks (RBNs). Instead of using the 'site-by-site and all-to-all' coupling, the coupling mechanism we consider here is that: the nth cell in a network is linked by an arbitrarily chosen cell in the other network with probability {rho}, and it possesses no links with probability 1-{rho}. The mechanism is useful to investigate the coevolution of biological species via horizontal genetic exchange. We show that the density evolution of networks can be described by two deterministic coupled polynomial maps. The complete synchronization occurs when the coupling parameter exceeds a critical value. Moreover, the reverse bifurcations in inhomogeneous condition are observed and under our discussion.
Efficient Analog Circuits for Boolean Satisfiability
Yin, Xunzhao; Sedighi, Behnam; Varga, Melinda; Ercsey-Ravasz, Maria; Toroczkai, Zoltan; Hu, Xiaobo Sharon
2016-01-01
Efficient solutions to NP-complete problems would significantly benefit both science and industry. However, such problems are intractable on digital computers based on the von Neumann architecture, thus creating the need for alternative solutions to tackle such problems. Recently, a deterministic, continuous-time dynamical system (CTDS) was proposed (Nature Physics, 7(12), 966 (2011)) to solve a representative NP-complete problem, Boolean Satisfiability (SAT). This solver shows polynomial ana...
Using Genetic Algorithms for Boolean Queries Optimization
Húsek, Dušan; Snášel, Václav; Owais, S.S.J.; Krömer, P.
Calgary: ACTA Press, 2005 - (Hamza, M.), s. 178-184 ISBN 0-88986-510-8. [IASTED International Conference on Internet and Multimedia Systems and Applications /9./. Honolulu (US), 15.08.2005-17.08.2005] R&D Projects: GA AV ČR 1ET100300419 Institutional research plan: CEZ:AV0Z10300504 Keywords : genetic algorithms * information retrieval * Boolean query * genetic programming Subject RIV: BA - General Mathematics
On the Implementation of Boolean Matrix Factorization
Snášel, V.; Krömer, P.; Platoš, J.; Húsek, Dušan
Los Alamitos: IEEE, 2008, s. 554-558. ISBN 978-0-7695-3299-8. [ETID '08. International Workshop on Evolutionary Techniques /2./, in collocation with DEXA 2008 International Conference /19./. Turin (IT), 01.09.2008-05.09.2008] Institutional research plan: CEZ:AV0Z10300504 Keywords : data mining * genetic algorithms * Boolean factorization * binary data * machine learning * feature extraction Subject RIV: IN - Informatics, Computer Science
Boolean Logic Optimization in Majority-Inverter Graphs
Amarù, Luca; Gaillardon, Pierre-Emmanuel; De Micheli, Giovanni
2015-01-01
We present a Boolean logic optimization framework based on Majority-Inverter Graph (MIG). An MIG is a directed acyclic graph consisting of three-input majority nodes and regular/complemented edges. Current MIG optimization is supported by a consistent algebraic framework. However, when algebraic methods cannot improve a result quality, stronger Boolean methods are needed to attain further optimization. For this purpose, we propose MIG Boolean methods exploiting the error masking property of m...
ON REDUCED SCALAR EQUATIONS FOR SYNCHRONOUS BOOLEAN NETWORKS
Ali Muhammad Ali Rushdi; Adnan Ahmad Alsogati
2013-01-01
A total description of a synchronous Boolean network is typically achieved by a matrix recurrence relation. A simpler alternative is to use a scalar equation which is a possibly nonlinear equation that involves two or more instances of a single scalar variable and some Boolean operator(s). Further simplification is possible in terms of a linear reduced scalar equation which is the simplest two-term scalar equation that includes no Boolean operators and equates the value of a scalar variable a...
Using Boolean Constraint Propagation for Sub-clause Deduction
Darras, Sylvain; Dequen, Gilles; Devendeville, Laure; Mazure, Bertrand; Ostrowski, Richard; Sais, Lahkdar
2005-01-01
Boolean Constraint Propagation (BCP) is recognized as one of the most use- ful technique for efficient satisfiability checking. In this paper a new extension of the scope of boolean constraint propagation is proposed. It makes an original use of BCP to achieve further reduction of boolean formulas. Considering the impli- cation graph generated by the constraint propagation process as a resolution tree, sub-clauses from the original formula can be deduced. Then, we show how such extension can ...
From Boolean Network Model to Continuous Model Helps in Design of Functional Circuits
Bin Shao; Xiang Liu; Dongliang Zhang; Jiayi Wu; Qi Ouyang
2015-01-01
Computational circuit design with desired functions in a living cell is a challenging task in synthetic biology. To achieve this task, numerous methods that either focus on small scale networks or use evolutionary algorithms have been developed. Here, we propose a two-step approach to facilitate the design of functional circuits. In the first step, the search space of possible topologies for target functions is reduced by reverse engineering using a Boolean network model. In the second step, ...
Combinational Logic-Level Verification using Boolean Expression Diagrams
Hulgaard, Henrik; Williams, Poul Frederick; Andersen, Henrik Reif
1997-01-01
Boolean Expression Diagrams (BEDs) is a new data structure for representing and manipulating Boolean functions. BEDs are a generalization of Binary Decision Diagrams (BDDs) that are capable of representing any Boolean circuit in linear space and still maintain many of the desirable properties of...... BDDs. This paper demonstrates that BEDs are well suited for solving the combinational logic-level verification problem which is, given two combinational circuits, to determine whether they implement the same Boolean functions. Based on all combinational circuits in the ISCAS 85 and LGSynth 91...
Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance
Regulatory T cells (Tregs) were initially described as “suppressive” lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches
Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance
Mougiakakos, Dimitrios [Department of Oncology and Pathology, Immune and Gene Therapy Unit, Cancer Centre Karolinska, CCK R8:01, 17176 Stockholm (Sweden)
2011-03-29
Regulatory T cells (Tregs) were initially described as “suppressive” lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.
Maurer, Matthew J.
Science literacy has been at the heart of current reform efforts in science education. The focus on developing essential skills needed for individual ability to be literate in science has been at the forefront of most K--12 science curricula. Reform efforts have begun to stretch into the postsecondary arena as well, with an ever increasing dialogue regarding the need for attention to science literacy by college students, especially non-science majors. This study set out to investigate how the use of self-regulatory interventions (specifically, goal setting, concept mapping, and reflective writing) affected student biology self-efficacy and biological literacy. This study employed a qualitative research design, analyzing three case studies. Participants in the study received ten self-regulatory interventions as a set of portfolio assignments. Portfolio work was qualitatively analyzed and coded for self-efficacy, as well as evidence of biological literacy. A biology self-efficacy survey was administered pre- and post- to provide a means of self-efficacy data triangulation. Literacy data was supported via a biological literacy rubric, constructed specifically for this study. Results indicated that mastery experiences were the source of biology self-efficacy. Self-efficacy for specific tasks increased over time, and changes in self-efficacy were corroborated by the self-efficacy survey. Students were found to express biological literacy at nominal, functional, or conceptual levels depending on the specific task. This was supported by data from the biological literacy rubric scores. Final conclusions and implications for the study indicated the need for further research with more samples of students in similar and different contexts. Given the fact that the literature in this area is sparse, the results obtained here have only begun to delve into this area of research. Generalization to other biology courses or contexts outside of the one presented in this study was
May, Elebeoba Eni; Rintoul, Mark Daniel; Johnston, Anna Marie; Pryor, Richard J.; Hart, William Eugene; Watson, Jean-Paul
2003-10-01
A fundamental challenge for all communication systems, engineered or living, is the problem of achieving efficient, secure, and error-free communication over noisy channels. Information theoretic principals have been used to develop effective coding theory algorithms to successfully transmit information in engineering systems. Living systems also successfully transmit biological information through genetic processes such as replication, transcription, and translation, where the genome of an organism is the contents of the transmission. Decoding of received bit streams is fairly straightforward when the channel encoding algorithms are efficient and known. If the encoding scheme is unknown or part of the data is missing or intercepted, how would one design a viable decoder for the received transmission? For such systems blind reconstruction of the encoding/decoding system would be a vital step in recovering the original message. Communication engineers may not frequently encounter this situation, but for computational biologists and biotechnologist this is an immediate challenge. The goal of this work is to develop methods for detecting and reconstructing the encoder/decoder system for engineered and biological data. Building on Sandia's strengths in discrete mathematics, algorithms, and communication theory, we use linear programming and will use evolutionary computing techniques to construct efficient algorithms for modeling the coding system for minimally errored engineered data stream and genomic regulatory DNA and RNA sequences. The objective for the initial phase of this project is to construct solid parallels between biological literature and fundamental elements of communication theory. In this light, the milestones for FY2003 were focused on defining genetic channel characteristics and providing an initial approximation for key parameters, including coding rate, memory length, and minimum distance values. A secondary objective addressed the question of
Learning Boolean functions with concentrated spectra
Mixon, Dustin G.; Peterson, Jesse
2015-08-01
This paper discusses the theory and application of learning Boolean functions that are concentrated in the Fourier domain. We first estimate the VC dimension of this function class in order to establish a small sample complexity of learning in this case. Next, we propose a computationally efficient method of empirical risk minimization, and we apply this method to the MNIST database of handwritten digits. These results demonstrate the effectiveness of our model for modern classification tasks. We conclude with a list of open problems for future investigation.
Boolean Factor Analysis by Attractor Neural Network
Frolov, A. A.; Húsek, Dušan; Muraviev, I. P.; Polyakov, P.Y.
2007-01-01
Roč. 18, č. 3 (2007), s. 698-707. ISSN 1045-9227 R&D Projects: GA AV ČR 1ET100300419; GA ČR GA201/05/0079 Institutional research plan: CEZ:AV0Z10300504 Keywords : recurrent neural network * Hopfield-like neural network * associative memory * unsupervised learning * neural network architecture * neural network application * statistics * Boolean factor analysis * dimensionality reduction * features clustering * concepts search * information retrieval Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.769, year: 2007
Neural Network Boolean Factor Analysis and Applications
Húsek, Dušan; Frolov, A.; Polyakov, P.Y.; Snášel, V.
-: WSEAS Press, 2007 - (Katehakis, M.; And ina, D.; Mastorakis, M.), s. 30-35. (Electrical and Computer Engineering Series). ISBN 978-960-6766-21-3. [CIMMACS'07. WSEAS International Conference on Computational Intelligence, Man-Machine Systems and Cybernetics. Tenerife (ES), 14.12.2007-16.12.2007] R&D Projects: GA MŠk 1M0567; GA AV ČR 1ET100300414; GA ČR GA201/05/0079 Institutional research plan: CEZ:AV0Z10300504 Keywords : Hopfield neural network * boolean factor analysis * unsupervised learning * dimension reduction * data mining Subject RIV: BB - Applied Statistics, Operational Research
Towards boolean operations with thermal photons
Ben-Abdallah, Philippe
2016-01-01
The Boolean algebra is the natural theoretical framework for a classical information treatment. The basic logical operations are usually performed using logic gates. In this Letter we demonstrate that NOT, OR and AND gates can be realized exploiting the near-field radiative interaction in N-body systems with phase change materials. With the recent development of a photon thermal transistor and thermal memory, this result paves the way for a full information treatment and smart solutions for active thermal management at nanoscale with photons.
Solving the Satisfiability Problem Through Boolean Networks
Roli, Andrea; Milano, Michela
2011-01-01
In this paper we present a new approach to solve the satisfiability problem (SAT), based on boolean networks (BN). We define a mapping between a SAT instance and a BN, and we solve SAT problem by simulating the BN dynamics. We prove that BN fixed points correspond to the SAT solutions. The mapping presented allows to develop a new class of algorithms to solve SAT. Moreover, this new approach suggests new ways to combine symbolic and connectionist computation and provides a general framework f...
Solving the Satisfiability Problem Through Boolean Networks
Roli, Andrea
2011-01-01
In this paper we present a new approach to solve the satisfiability problem (SAT), based on boolean networks (BN). We define a mapping between a SAT instance and a BN, and we solve SAT problem by simulating the BN dynamics. We prove that BN fixed points correspond to the SAT solutions. The mapping presented allows to develop a new class of algorithms to solve SAT. Moreover, this new approach suggests new ways to combine symbolic and connectionist computation and provides a general framework for local search algorithms.
Representations of Boolean Functions by Perceptron Networks
Kůrková, Věra
Prague : Institute of Computer Science AS CR, 2014 - (Kůrková, V.; Bajer, L.; Peška, L.; Vojtáš, R.; Holeňa, M.; Nehéz, M.), s. 68-70 ISBN 978-80-87136-19-5. [ITAT 2014. European Conference on Information Technologies - Applications and Theory /14./. Demänovská dolina (SK), 25.09.2014-29.09.2014] R&D Projects: GA MŠk(CZ) LD13002 Institutional support: RVO:67985807 Keywords : perceptron networks * model complexity * Boolean functions Subject RIV: IN - Informatics, Computer Science
Constructions of vector output Boolean functions with high generalized nonlinearity
KE Pin-hui; ZHANG Sheng-yuan
2008-01-01
Carlet et al. recently introduced generalized nonlinearity to measure the ability to resist the improved correlation attack of a vector output Boolean function. This article presents a construction of vector output Boolean functions with high generalized nonlinearity using the sample space. The relation between the resilient order and generalized nonlinearity is also discussed.
E-Referencer: Transforming Boolean OPACs to Web Search Engines.
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.…
Detecting small attractors of large Boolean networks by function-reduction-based strategy.
Zheng, Qiben; Shen, Liangzhong; Shang, Xuequn; Liu, Wenbin
2016-04-01
Boolean networks (BNs) are widely used to model gene regulatory networks and to design therapeutic intervention strategies to affect the long-term behaviour of systems. A central aim of Boolean-network analysis is to find attractors that correspond to various cellular states, such as cell types or the stage of cell differentiation. This problem is NP-hard and various algorithms have been used to tackle it with considerable success. The idea is that a singleton attractor corresponds to n consistent subsequences in the truth table. To find these subsequences, the authors gradually reduce the entire truth table of Boolean functions by extending a partial gene activity profile (GAP). Not only does this process delete inconsistent subsequences in truth tables, it also directly determines values for some nodes not extended, which means it can abandon the partial GAPs that cannot lead to an attractor as early as possible. The results of simulation show that the proposed algorithm can detect small attractors with length p = 4 in BNs of up to 200 nodes with average indegree K = 2. PMID:26997659
Reverse engineering Boolean networks: from Bernoulli mixture models to rule based systems.
Mehreen Saeed
Full Text Available A Boolean network is a graphical model for representing and analyzing the behavior of gene regulatory networks (GRN. In this context, the accurate and efficient reconstruction of a Boolean network is essential for understanding the gene regulation mechanism and the complex relations that exist therein. In this paper we introduce an elegant and efficient algorithm for the reverse engineering of Boolean networks from a time series of multivariate binary data corresponding to gene expression data. We call our method ReBMM, i.e., reverse engineering based on Bernoulli mixture models. The time complexity of most of the existing reverse engineering techniques is quite high and depends upon the indegree of a node in the network. Due to the high complexity of these methods, they can only be applied to sparsely connected networks of small sizes. ReBMM has a time complexity factor, which is independent of the indegree of a node and is quadratic in the number of nodes in the network, a big improvement over other techniques and yet there is little or no compromise in accuracy. We have tested ReBMM on a number of artificial datasets along with simulated data derived from a plant signaling network. We also used this method to reconstruct a network from real experimental observations of microarray data of the yeast cell cycle. Our method provides a natural framework for generating rules from a probabilistic model. It is simple, intuitive and illustrates excellent empirical results.
Hvidsten Torgeir R; Jansson Stefan; Street Nathaniel
2011-01-01
Abstract Background Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods ...
Multiple Sequence Alignment using Boolean Algebra and Fuzzy Logic:A Comparative Study
Nivit Gill
2011-09-01
Full Text Available Multiple sequence alignment is the most fundamental and essential task of computational biology, and forms the base for other tasks of bioinformatics. In this paper, two different approaches to sequence alignment have been discussed and compared. The first method employs Boolean algebra which is a two-valued logic whereas the second is based on Fuzzy logic which is a multi-valued logic. Both the methods perform sequence matching by direct comparison method using the operations of Boolean algebra and fuzzy logic respectively. To ensure the optimal alignment, dynamic programming is employed to align multiple sequences progressively. Both the methods are implemented and then tested on various sets of real genome sequences taken from NCBI bank. The processing time for both the methods on these data sets have been computed and compared.
Terse Integer Linear Programs for Boolean Optimization
Christoph Buchheim
2009-05-01
Full Text Available We present a new polyhedral approach to nonlinear Boolean optimization. Compared to other methods, it produces much smaller integer programming models, making it more efficient from a practical point of view. We mainly obtain this by two different ideas: first, we do not require the objective function to be in any normal form. The transformation into a normal form usually leads to the introduction of many additional variables or constraints. Second, we reduce the problem to the degree-two case in a very efficient way, by slightly extending the dimension of the original variable space. The resulting model turns out to be closely related to the maximum cut problem; we show that the corresponding polytope is a face of a suitable cut polytope in most cases. In particular, our separation problem reduces to the one for the maximum cut problem. In practice, the approach appears to be very competitive for unconstrained Boolean optimization problems. First experimental results, which have been obtained for some particularly hard instances of the Max-SAT Evaluation 2007, show that our very general implementation can outperform even special-purpose Max-SAT solvers. The software is accessible online under “we.logoptimize.it”.
Tholen Stefan
2011-01-01
Full Text Available Abstract Background Several computational methods exist to suggest rational genetic interventions that improve the productivity of industrial strains. Nonetheless, these methods are less effective to predict possible genetic responses of the strain after the intervention. This problem requires a better understanding of potential alternative metabolic and regulatory pathways able to counteract the targeted intervention. Results Here we present SPABBATS, an algorithm based on Boolean satisfiability (SAT that computes alternative metabolic pathways between input and output species in a reconstructed network. The pathways can be constructed iteratively in order of increasing complexity. SPABBATS allows the accumulation of intermediates in the pathways, which permits discovering pathways missed by most traditional pathway analysis methods. In addition, we provide a proof of concept experiment for the validity of the algorithm. We deleted the genes for the glutamate dehydrogenases of the Gram-positive bacterium Bacillus subtilis and isolated suppressor mutant strains able to grow on glutamate as single carbon source. Our SAT approach proposed candidate alternative pathways which were decisive to pinpoint the exact mutation of the suppressor strain. Conclusions SPABBATS is the first application of SAT techniques to metabolic problems. It is particularly useful for the characterization of metabolic suppressor mutants and can be used in a synthetic biology setting to design new pathways with specific input-output requirements.
Coevolution of Information Processing and Topology in Hierarchical Adaptive Random Boolean Networks
Gorski, Piotr J; Holyst, Janusz A
2015-01-01
Random Boolean networks (RBNs) are frequently employed for modelling complex systems driven by information processing, e.g. for gene regulatory networks (GRNs). Here we propose a hierarchical adaptive RBN (HARBN) as a system consisting of distinct adaptive RBNs - subnetworks - connected by a set of permanent interlinks. Information measures and internal subnetworks topology of HARBN coevolve and reach steady-states that are specific for a given network structure. We investigate mean node information, mean edge information as well as a mean node degree as functions of model parameters and demonstrate HARBN's ability to describe complex hierarchical systems.
Melissa A Metzler
Full Text Available The transcription factor networks that drive parotid salivary gland progenitor cells to terminally differentiate, remain largely unknown and are vital to understanding the regeneration process.A systems biology approach was taken to measure mRNA and microRNA expression in vivo across acinar cell terminal differentiation in the rat parotid salivary gland. Laser capture microdissection (LCM was used to specifically isolate acinar cell RNA at times spanning the month-long period of parotid differentiation.Clustering of microarray measurements suggests that expression occurs in four stages. mRNA expression patterns suggest a novel role for Pparg which is transiently increased during mid postnatal differentiation in concert with several target gene mRNAs. 79 microRNAs are significantly differentially expressed across time. Profiles of statistically significant changes of mRNA expression, combined with reciprocal correlations of microRNAs and their target mRNAs, suggest a putative network involving Klf4, a differentiation inhibiting transcription factor, which decreases as several targeting microRNAs increase late in differentiation. The network suggests a molecular switch (involving Prdm1, Sox11, Pax5, miR-200a, and miR-30a progressively decreases repression of Xbp1 gene transcription, in concert with decreased translational repression by miR-214. The transcription factor Xbp1 mRNA is initially low, increases progressively, and may be maintained by a positive feedback loop with Atf6. Transfection studies show that Xbp1 activates the Mist1 promoter [corrected]. In addition, Xbp1 and Mist1 each activate the parotid secretory protein (Psp gene, which encodes an abundant salivary protein, and is a marker of terminal differentiation.This study identifies novel expression patterns of Pparg, Klf4, and Sox11 during parotid acinar cell differentiation, as well as numerous differentially expressed microRNAs. Network analysis identifies a novel stemness arm, a
Social insect colony as a biological regulatory system: Information flow in dominance networks
Nandi, Anjan K.; Sumana, Annagiri; Bhattacharya, Kunal
2014-01-01
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...
Ordered Boolean List (OBL): reducing the footprint for evaluating Boolean expressions.
Rossignac, Jaroslaw Jarek
2011-09-01
An Expanded Boolean Expression (EBE) does not contain any XOR or EQUAL operators. The occurrence of each variable is a different literal. We provide a linear time algorithm that converts an EBE of n literals into a logically equivalent Ordered Boolean List (OBL) and show how to use the OBL to evaluate the EBE in n steps and O(log log n) space, if the values of the literals are each read once in the order prescribed by the OBL. (An evaluation workspace of 5 bits suffices for all EBEs of up to six billion literals.) The primary application is the SIMD architecture, where the same EBE is evaluated in parallel for different input vectors when rendering solid models on the GPU directly from their Constructive Solid Geometry (CSG) representation. We compare OBL to the Reduced Ordered Binary Decision Diagram (ROBDD) and suggest possible applications of OBL to logic verification and to circuit design. PMID:21737862
Polynomial threshold functions and Boolean threshold circuits
Hansen, Kristoffer Arnsfelt; Podolskii, Vladimir V.
2013-01-01
secondary interest. We show that PTFs on general Boolean domains are tightly connected to depth two threshold circuits. Our main results in regard to this connection are: PTFs of polynomial length and polynomial degree compute exactly the functions computed by THRMAJ circuits. An exponential length lower...... bound for PTFs that holds regardless of degree, thereby extending known lower bounds for THRMAJ circuits. We generalize two-party unbounded error communication complexity to the multi-party number-on-the-forehead setting, and show that communication lower bounds for 3-player protocols would yield size...... lower bounds for THRTHR circuits. We obtain several other results about PTFs. These include relationships between weight and degree of PTFs, and a degree lower bound for PTFs of constant length. We also consider a variant of PTFs over the max-plus algebra. We show that they are connected to PTFs over...
Representing Boolean Functions by Decision Trees
Chikalov, Igor
2011-01-01
A Boolean or discrete function can be represented by a decision tree. A compact form of decision tree named binary decision diagram or branching program is widely known in logic design [2, 40]. This representation is equivalent to other forms, and in some cases it is more compact than values table or even the formula [44]. Representing a function in the form of decision tree allows applying graph algorithms for various transformations [10]. Decision trees and branching programs are used for effective hardware [15] and software [5] implementation of functions. For the implementation to be effective, the function representation should have minimal time and space complexity. The average depth of decision tree characterizes the expected computing time, and the number of nodes in branching program characterizes the number of functional elements required for implementation. Often these two criteria are incompatible, i.e. there is no solution that is optimal on both time and space complexity. © Springer-Verlag Berlin Heidelberg 2011.
Robust Boolean Operation for Sculptured Models
无
2000-01-01
To enhance the ability of current modeling system, an uniformed representation is designed to represent wire-frame, solid, surface models. We present an algorithm for Boolean operation between the models under this representation. Accuracy, efficiency and robustness are the main consideration. The geometric information is represented with trimmed parametric patches and trimmed parametric splines. The topological information is represented with an extended half-edge data structure. In the process of intersection calculation, hierarchy intersection method is applied for unified classification. Tracing the intersection curve to overcome degenerate cases that occur frequently in practice. The algorithm has been implemented as the modeling kernel of a feature based modeling system named GS-CAD98, which was developed on Windows/NT platform.
Consistent stabilizability of switched Boolean networks.
Li, Haitao; Wang, Yuzhen
2013-10-01
This paper investigates the consistent stabilizability of switched Boolean networks (SBNs) by using the semi-tensor product method, and presents a number of new results. First, an algebraic expression of SBNs is obtained by the semi-tensor product, based on which the consistent stabilizability is then studied for SBNs and some necessary and sufficient conditions are presented for the design of free-form and state-feedback switching signals, respectively. Finally, the consistent stabilizability of SBNs with state constraints is considered and some necessary and sufficient conditions are proposed. The study of illustrative examples shows that the new results obtained in this paper are very effective in designing switching signals for the consistent stabilizability of SBNs. PMID:23787170
Boolean delay equations: A simple way of looking at complex systems
Ghil, Michael; Zaliapin, Ilya; Coluzzi, Barbara
2008-12-01
Boolean Delay Equations (BDEs) are semi-discrete dynamical models with Boolean-valued variables that evolve in continuous time. Systems of BDEs can be classified into conservative or dissipative, in a manner that parallels the classification of ordinary or partial differential equations. Solutions to certain conservative BDEs exhibit growth of complexity in time; such BDEs can be seen therefore as metaphors for biological evolution or human history. Dissipative BDEs are structurally stable and exhibit multiple equilibria and limit cycles, as well as more complex, fractal solution sets, such as Devil’s staircases and “fractal sunbursts.” All known solutions of dissipative BDEs have stationary variance. BDE systems of this type, both free and forced, have been used as highly idealized models of climate change on interannual, interdecadal and paleoclimatic time scales. BDEs are also being used as flexible, highly efficient models of colliding cascades of loading and failure in earthquake modeling and prediction, as well as in genetics. In this paper we review the theory of systems of BDEs and illustrate their applications to climatic and solid-earth problems. The former have used small systems of BDEs, while the latter have used large hierarchical networks of BDEs. We moreover introduce BDEs with an infinite number of variables distributed in space (“partial BDEs”) and discuss connections with other types of discrete dynamical systems, including cellular automata and Boolean networks. This research-and-review paper concludes with a set of open questions.
Boolean Delay Equations: A Simple Way of Looking at Interactions and Extreme Events
Ghil, Michael
2013-04-01
Boolean Delay Equations (BDEs) are semi-discrete dynamical models with Boolean-valued variables that evolve in continuous time. Systems of BDEs can be classified into conservative or dissipative, in a manner that parallels the classification of ordinary or partial differential equations. Solutions to certain conservative BDEs exhibit growth of complexity in time; such BDEs can be seen therefore as metaphors for biological evolution or human history. Dissipative BDEs are structurally stable and exhibit multiple equilibria and limit cycles, as well as more complex, fractal solution sets, such as Devil's staircases and ``fractal sunbursts.'' BDE systems have been used as highly idealized models of climate change on several time scales, as well as in earthquake modeling and prediction, and in genetics. BDEs with an infinite number of variables on a regular spatial grid have been called "partial BDEs" and we discuss connections with other types of discrete dynamical systems, including cellular automata and Boolean networks. We present recent BDE work on damage propagation in networks, with an emphasis on production-chain models. This formalism turns out to be well adapted to investigating propagation of an initial damage due to a climatic or other natural disaster. It thus serves to study economic impacts of extreme events, as well as extreme disruption of a network of interactions.
PARAMETER ESTIMATION IN NON-HOMOGENEOUS BOOLEAN MODELS: AN APPLICATION TO PLANT DEFENSE RESPONSE
Maria Angeles Gallego
2014-11-01
Full Text Available Many medical and biological problems require to extract information from microscopical images. Boolean models have been extensively used to analyze binary images of random clumps in many scientific fields. In this paper, a particular type of Boolean model with an underlying non-stationary point process is considered. The intensity of the underlying point process is formulated as a fixed function of the distance to a region of interest. A method to estimate the parameters of this Boolean model is introduced, and its performance is checked in two different settings. Firstly, a comparative study with other existent methods is done using simulated data. Secondly, the method is applied to analyze the longleaf data set, which is a very popular data set in the context of point processes included in the R package spatstat. Obtained results show that the new method provides as accurate estimates as those obtained with more complex methods developed for the general case. Finally, to illustrate the application of this model and this method, a particular type of phytopathological images are analyzed. These images show callose depositions in leaves of Arabidopsis plants. The analysis of callose depositions, is very popular in the phytopathological literature to quantify activity of plant immunity.
Claudia Stötzel
Full Text Available In this paper, we present a systematic transition scheme for a large class of ordinary differential equations (ODEs into Boolean networks. Our transition scheme can be applied to any system of ODEs whose right hand sides can be written as sums and products of monotone functions. It performs an Euler-like step which uses the signs of the right hand sides to obtain the Boolean update functions for every variable of the corresponding discrete model. The discrete model can, on one hand, be considered as another representation of the biological system or, alternatively, it can be used to further the analysis of the original ODE model. Since the generic transformation method does not guarantee any property conservation, a subsequent validation step is required. Depending on the purpose of the model this step can be based on experimental data or ODE simulations and characteristics. Analysis of the resulting Boolean model, both on its own and in comparison with the ODE model, then allows to investigate system properties not accessible in a purely continuous setting. The method is exemplarily applied to a previously published model of the bovine estrous cycle, which leads to new insights regarding the regulation among the components, and also indicates strongly that the system is tailored to generate stable oscillations.
Random Boolean Networks and Attractors of their Intersecting Circuits
Demongeot, Jacques; Elena, Adrien; Noual, Mathilde; Sené, Sylvain
2011-01-01
International audience The multi-scale strategy in studying biological regulatory networks analysis is based on two level of analysis. The first level is structural and consists in examining the architecture of the interaction graph underlying the network and the second level is functional and analyse the regulatory properties of the network. We apply this dual approach to the "immunetworks" involved in the control of the immune system. As a result, we show that the small number of attract...
The levels and biological effects resulting from exposure to ionizing radiation are continuously reviewed by the United Nations Committee on the Effects of Atomic Radiation (UNSCEAR). Since its creation in 1928, the International Commission on Radiological Protection (ICRP) has issued recommendations on protection against ionizing radiation. The UNSCEAR estimates and the ICRP recommendations have served as the basis for national and international safety standards on radiation safety, including those developed by the International Atomic Energy Agency (IAEA) and the World Health Organization (WHO). Concerning health effects of low doses of ionizing radiation, the international standards are based on the plausible assumption that, above the unavoidable background radiation dose, the probability of effects increases linearly with dose, i.e. on a 'linear, no threshold' (LNT) assumption. However, in recent years the biological estimates of health effects of low doses of ionizing radiation and the regulatory approach to the control of low level radiation exposure have been much debated. To foster information exchange on the relevant issues, an International Conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, jointly sponsored by the IAEA and WHO in co-operation with UNSCEAR, was held from 17-21 November 1997 at Seville, Spain. These Proceedings contain the invited special reports, keynote papers, summaries of discussions, session summaries and addresses presented at the opening and closing of the Conference
Martin, O. C.; Krzywicki, A.; Zagorski, M.
2016-07-01
Living cells can maintain their internal states, react to changing environments, grow, differentiate, divide, etc. All these processes are tightly controlled by what can be called a regulatory program. The logic of the underlying control can sometimes be guessed at by examining the network of influences amongst genetic components. Some associated gene regulatory networks have been studied in prokaryotes and eukaryotes, unveiling various structural features ranging from broad distributions of out-degrees to recurrent "motifs", that is small subgraphs having a specific pattern of interactions. To understand what factors may be driving such structuring, a number of groups have introduced frameworks to model the dynamics of gene regulatory networks. In that context, we review here such in silico approaches and show how selection for phenotypes, i.e., network function, can shape network structure.
Evolution of regulatory networks towards adaptability and stability in a changing environment.
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. PMID:25493848
Evolution of regulatory networks towards adaptability and stability in a changing environment
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.
Approximate Counting for Complex-Weighted Boolean Constraint Satisfaction Problems
Yamakami, Tomoyuki
2010-01-01
Constraint satisfaction problems (or CSPs) have been extensively studied in AI, database theory, graph theory, etc. From an approximation viewpoint, it has been important to approximate the total number of assignments that satisfy all given Boolean constraints. There is a trichotomy theorem for such approximate counting for (non-weighted) Boolean CSPs; namely, all such counting problems are neatly classified into three categories under polynomial-time approximation-preserving reductions [Dyer, Goldberg, and Jerrum, 2010]. We extend this result to approximate counting for complex-weighted Boolean CSPs, provided that all arity-1 constraints are freely available to use. This makes a significant progress in the quest for the approximation classification of all counting Boolean CSPs in the most general form. To deal with complex weights, we employ proof techniques along the line of solving Holant problems [Valiant, 2002, 2008]. Our result also gives an approximation version of the dichotomy theorem of the complexi...
Automatic Ranked Output from Boolean Searches in SIRE
Noreault, Terry; And Others
1977-01-01
This study examined the effectiveness using an automatic algorithm to rank the results of Boolean searches of an inverted file design document retrieval system. Relevant documents were ranked significantly higher than nonrelevant documents on output lists. (Author/KP)
Boolean Burritos: How the Faculty Ate Up Keyword Searching.
York, Sherry
1999-01-01
Describes an activity that librarians can use to acquaint teachers with keyword searching and Boolean operators to more successfully use the library's online catalog. Uses food ingredients to represent various possible combinations. (LRW)
Boolean functions with a vertex-transitive group of automorphisms
Savický, Petr
-, submitted 2015 (2016) R&D Projects: GA ČR GAP202/10/1333 Institutional support: RVO:67985807 Keywords : Boolean Functions * hypercube * isometric transformation * vertex-transitive group of automorphisms Subject RIV: BA - General Mathematics
Linear Programming Formulation of the Boolean Satisfiability Problem
Diaby, Moustapha
2008-01-01
In this paper, we present a new, graph-based modeling approach and a polynomial-sized linear programming (LP) formulation of the Boolean satisfiability problem (SAT). The approach is illustrated with a numerical example.
Boolean Equi-propagation for Optimized SAT Encoding
Metodi, Amit; Lagoon, Vitaly; Stuckey, Peter J
2011-01-01
We present an approach to propagation based solving, Boolean equi-propagation, where constraints are modelled as propagators of information about equalities between Boolean literals. Propagation based solving applies this information as a form of partial evaluation resulting in optimized SAT encodings. We demonstrate for a variety of benchmarks that our approach results in smaller CNF encodings and leads to speed-ups in solving times.
Inadmissible Class of Boolean Functions under Stuck-at Faults
Das, Debesh K.; Chowdhury, Debabani; Bhattacharya, Bhargab B; Sasao, Tsutomu
2013-01-01
Many underlying structural and functional factors that determine the fault behavior of a combinational network, are not yet fully understood. In this paper, we show that there exists a large class of Boolean functions, called root functions, which can never appear as faulty response in irredundant two-level circuits even when any arbitrary multiple stuck-at faults are injected. Conversely, we show that any other Boolean function can appear as a faulty response from an irredundant realization ...
Integrating Boolean and Mathematical Solving: Foundations, Basic Algorithms and Requirements
Audemard, Gilles; Bertoli, Piergiorgio; Cimatti, Alessandro; Kornilowicz, Artur; Sebastiani, Roberto
2002-01-01
In the last years we have witnessed an impressive advance in the efficiency of boolean solving techniques, which has brought large previously intractable problems at the reach of state-of-the-art solvers. Unfortunately, simple boolean expressions are not expressive enough for representing many real-world problems, which require handling also integer or real values and operators. On the other hand, mathematical solvers, like computer-algebra systems or constraint solvers, cannot handle efficie...
IMS Algorithm for Learning Representations in Boolean Neural Networks
Biswas, Nripendra N; Murthy, TVMK; Chandrasekhar, M.
1991-01-01
A new algorithm for learning representations in Boolean neural networks, where the inputs and outputs are binary bits, is presented. The algorithm has become feasible because of a newly discovered theorem which states that any non-linearly separable Boolean function can be expressed as a convergent series of linearly separable functions connected by the logical OR (+) and the logical INHIBIT (-) operators. The formation of the series is carried out by many important properties exhibited by th...
Chang, Joshua C; Miura, Robert M
2016-04-21
In vertebrates, insufficient availability of calcium and inorganic phosphate ions in extracellular fluids leads to loss of bone density and neuronal hyper-excitability. To counteract this problem, calcium ions are usually present at high concentrations throughout bodily fluids-at concentrations exceeding the saturation point. This condition leads to the opposite situation where unwanted mineral sedimentation may occur. Remarkably, ectopic or out-of-place sedimentation into soft tissues is rare, in spite of the thermodynamic driving factors. This fortunate fact is due to the presence of auto-regulatory proteins that are found in abundance in bodily fluids. Yet, many important inflammatory disorders such as atherosclerosis and osteoarthritis are associated with this undesired calcification. Hence, it is important to gain an understanding of the regulatory process and the conditions under which it can go awry. In this manuscript, we extend mean-field continuum classical nucleationtheory of the growth of clusters to encompass surface shielding. We use this formulation to study the regulation of sedimentation of calcium phosphate salts in biological tissues through the mechanism of post-nuclear shielding of nascent mineral particles by binding proteins. We develop a mathematical description of this phenomenon using a countable system of hyperbolic partial differential equations. A critical concentration of regulatory protein is identified as a function of the physical parameters that describe the system. PMID:27389239
Chang, Joshua C.; Miura, Robert M.
2016-04-01
In vertebrates, insufficient availability of calcium and inorganic phosphate ions in extracellular fluids leads to loss of bone density and neuronal hyper-excitability. To counteract this problem, calcium ions are usually present at high concentrations throughout bodily fluids—at concentrations exceeding the saturation point. This condition leads to the opposite situation where unwanted mineral sedimentation may occur. Remarkably, ectopic or out-of-place sedimentation into soft tissues is rare, in spite of the thermodynamic driving factors. This fortunate fact is due to the presence of auto-regulatory proteins that are found in abundance in bodily fluids. Yet, many important inflammatory disorders such as atherosclerosis and osteoarthritis are associated with this undesired calcification. Hence, it is important to gain an understanding of the regulatory process and the conditions under which it can go awry. In this manuscript, we extend mean-field continuum classical nucleation theory of the growth of clusters to encompass surface shielding. We use this formulation to study the regulation of sedimentation of calcium phosphate salts in biological tissues through the mechanism of post-nuclear shielding of nascent mineral particles by binding proteins. We develop a mathematical description of this phenomenon using a countable system of hyperbolic partial differential equations. A critical concentration of regulatory protein is identified as a function of the physical parameters that describe the system.
Inferring Biologically Relevant Models: Nested Canalyzing Functions
Hinkelmann, Franziska
2010-01-01
Inferring dynamic biochemical networks is one of the main challenges in systems biology. Given experimental data, the objective is to identify the rules of interaction among the different entities of the network. However, the number of possible models fitting the available data is huge and identifying a biologically relevant model is of great interest. Nested canalyzing functions, where variables in a given order dominate the function, have recently been proposed as a framework for modeling gene regulatory networks. Previously we described this class of functions as an algebraic toric variety. In this paper, we present an algorithm that identifies all nested canalyzing models that fit the given data. We demonstrate our methods using a well-known Boolean model of the cell cycle in budding yeast.
Modeling integrated cellular machinery using hybrid Petri-Boolean networks.
Natalie Berestovsky
Full Text Available The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them
Efficient Analog Circuits for Boolean Satisfiability
Yin, Xunzhao; Varga, Melinda; Ercsey-Ravasz, Maria; Toroczkai, Zoltan; Hu, Xiaobo Sharon
2016-01-01
Efficient solutions to NP-complete problems would significantly benefit both science and industry. However, such problems are intractable on digital computers based on the von Neumann architecture, thus creating the need for alternative solutions to tackle such problems. Recently, a deterministic, continuous-time dynamical system (CTDS) was proposed (Nature Physics, 7(12), 966 (2011)) to solve a representative NP-complete problem, Boolean Satisfiability (SAT). This solver shows polynomial analog time-complexity on even the hardest benchmark $k$-SAT ($k \\geq 3$) formulas, but at an energy cost through exponentially driven auxiliary variables. With some modifications to the CTDS equations, here we present a novel analog hardware SAT solver, AC-SAT, implementing the CTDS. AC-SAT is intended to be used as a co-processor, and with its modular design can be readily extended to different problem sizes. The circuit is designed and simulated based on a 32nm CMOS technology. SPICE simulation results show speedup factor...
Measuring Mutual Information in Random Boolean Networks
Luque, B; Luque, Bartolo; Ferrera, Antonio
1999-01-01
During the last few years an area of active research in the field of complex systems is that of their information storing and processing abilities. Common opinion has it that the most interesting beaviour of these systems is found ``at the edge of chaos'', which would seem to suggest that complex systems may have inherently non-trivial information proccesing abilities in the vicinity of sharp phase transitions. A comprenhensive, quantitative understanding of why this is the case is however still lacking. Indeed, even ``experimental'' (i.e., often numerical) evidence that this is so has been questioned for a number of systems. In this paper we will investigate, both numerically and analitically, the behavior of Random Boolean Networks (RBN's) as they undergo their order-disorder phase transition. We will use a simple mean field approximation to treat the problem, and without lack of generality we will concentrate on a particular value for the connectivity of the system. In spite of the simplicity of our argume...
This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information
2013-11-15
... Patent Term Restoration Act of 1984, Public Law 98-417, 98 Stat. 1585 (codified as amended in scattered... diseases as cancer, diabetes, and multiple sclerosis.\\2\\ ``Biologics'' include, for ] example, vaccines....''). \\30\\ FTC FOB Report, supra note 11, at 12; accord Mandy Jackson, Pharma Recovering from Patent...
Second moment method for a family of boolean CSP
Boufkhad, Yacine
2011-01-01
The estimation of phase transitions in random boolean Constraint Satisfaction Problems (CSP) is based on two fundamental tools: the first and second moment methods. While the first moment method on the number of solutions permits to compute upper bounds on any boolean CSP, the second moment method used for computing lower bounds proves to be more tricky and in most cases gives only the trivial lower bound 0. In this paper, we define a subclass of boolean CSP covering the monotone versions of many known NP-Complete boolean CSPs. We give a method for computing non trivial lower bounds for any member of this subclass. This is achieved thanks to an application of the second moment method to some selected solutions called characteristic solutions that depend on the boolean CSP considered. We apply, as an example, this method to establish that the threshold r_{k} of monotone 1-in-k-SAT is \\log k/k\\leq r_{k}\\leq\\log^{2}k/k
Efficient Algorithms for Membership in Boolean Hierarchies of Regular Languages
Glasser, Christian; Selivanov, Victor
2008-01-01
The purpose of this paper is to provide efficient algorithms that decide membership for classes of several Boolean hierarchies for which efficiency (or even decidability) were previously not known. We develop new forbidden-chain characterizations for the single levels of these hierarchies and obtain the following results: - The classes of the Boolean hierarchy over level $\\Sigma_1$ of the dot-depth hierarchy are decidable in $NL$ (previously only the decidability was known). The same remains true if predicates mod $d$ for fixed $d$ are allowed. - If modular predicates for arbitrary $d$ are allowed, then the classes of the Boolean hierarchy over level $\\Sigma_1$ are decidable. - For the restricted case of a two-letter alphabet, the classes of the Boolean hierarchy over level $\\Sigma_2$ of the Straubing-Th\\'erien hierarchy are decidable in $NL$. This is the first decidability result for this hierarchy. - The membership problems for all mentioned Boolean-hierarchy classes are logspace many-one hard for $NL$. - T...
Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection
Christopher S. Anderson
2016-01-01
Full Text Available Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection.
MicroRNA-1 properties in cancer regulatory networks and tumor biology.
Weiss, Martin; Brandenburg, Lars-Ove; Burchardt, Martin; Stope, Matthias B
2016-08-01
Short non-coding microRNAs have been identified to orchestrate crucial mechanisms in cancer progression and treatment resistance. MicroRNAs are involved in posttranscriptional modulation of gene expression and therefore represent promising targets for anticancer therapy. As mircoRNA-1 (miR-1) exerted to be predominantly downregulated in the majority of examined tumors, miR-1 is classified to be a tumor suppressor with high potential to diminish tumor development and therapy resistance. Here we review the complex functionality of miR-1 in tumor biology. PMID:27286699
The Influence of Canalization on the Robustness of Boolean Networks
Kadelka, Claus; Laubenbacher, Reinhard
2016-01-01
Time- and state-discrete dynamical systems are frequently used to model molecular networks. This paper provides a collection of mathematical and computational tools for the study of robustness in Boolean network models. The focus is on networks governed by $k$-canalizing functions, a recently introduced class of Boolean functions that contains the well-studied class of nested canalizing functions. The activities and sensitivity of a function quantify the impact of input changes on the function output. This paper generalizes the latter concept to $c$-sensitivity and provides formulas for the activities and $c$-sensitivity of general $k$-canalizing functions as well as canalizing functions with more precisely defined structure. A popular measure for the robustness of a network, the Derrida value, can be expressed as a weighted sum of the $c$-sensitivities of the governing canalizing functions, and can also be calculated for a stochastic extension of Boolean networks. These findings provide a computationally eff...
Optimal Computation of Symmetric Boolean Functions in Collocated Networks
Kowshik, Hemant
2011-01-01
We consider collocated wireless sensor networks, where each node has a Boolean measurement and the goal is to compute a given Boolean function of these measurements. We first consider the worst case setting and study optimal block computation strategies for computing symmetric Boolean functions. We study three classes of functions: threshold functions, delta functions and interval functions. We provide exactly optimal strategies for the first two classes, and a scaling law order-optimal strategy with optimal preconstant for interval functions. We also extend the results to the case of integer measurements and certain integer-valued functions. We use lower bounds from communication complexity theory, and provide an achievable scheme using information theoretic tools. Next, we consider the case where nodes measurements are random and drawn from independent Bernoulli distributions. We address the problem of optimal function computation so as to minimize the expected total number of bits that are transmitted. In ...
Exploiting Surroundedness for Saliency Detection: A Boolean Map Approach.
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. PMID:26336114
Dynamic regulatory on/off minimization for biological systems under internal temporal perturbations
Kleessen Sabrina
2012-03-01
Full Text Available Abstract Background Flux balance analysis (FBA together with its extension, dynamic FBA, have proven instrumental for analyzing the robustness and dynamics of metabolic networks by employing only the stoichiometry of the included reactions coupled with adequately chosen objective function. In addition, under the assumption of minimization of metabolic adjustment, dynamic FBA has recently been employed to analyze the transition between metabolic states. Results Here, we propose a suite of novel methods for analyzing the dynamics of (internally perturbed metabolic networks and for quantifying their robustness with limited knowledge of kinetic parameters. Following the biochemically meaningful premise that metabolite concentrations exhibit smooth temporal changes, the proposed methods rely on minimizing the significant fluctuations of metabolic profiles to predict the time-resolved metabolic state, characterized by both fluxes and concentrations. By conducting a comparative analysis with a kinetic model of the Calvin-Benson cycle and a model of plant carbohydrate metabolism, we demonstrate that the principle of regulatory on/off minimization coupled with dynamic FBA can accurately predict the changes in metabolic states. Conclusions Our methods outperform the existing dynamic FBA-based modeling alternatives, and could help in revealing the mechanisms for maintaining robustness of dynamic processes in metabolic networks over time.
A Boolean Approach to Airline Business Model Innovation
Hvass, Kristian Anders
Research in business model innovation has identified its significance in creating a sustainable competitive advantage for a firm, yet there are few empirical studies identifying which combination of business model activities lead to success and therefore deserve innovative attention. This study...... analyzes the business models of North America low-cost carriers from 2001 to 2010 using a Boolean minimization algorithm to identify which combinations of business model activities lead to operational profitability. The research aim is threefold: complement airline literature in the realm of business model...... innovation, introduce Boolean minimization methods to the field, and propose alternative business model activities to North American carriers striving for positive operating results....
On Kolmogorov's superpositions and Boolean functions
Beiu, V.
1998-12-31
The paper overviews results dealing with the approximation capabilities of neural networks, as well as bounds on the size of threshold gate circuits. Based on an explicit numerical (i.e., constructive) algorithm for Kolmogorov's superpositions they will show that for obtaining minimum size neutral networks for implementing any Boolean function, the activation function of the neurons is the identity function. Because classical AND-OR implementations, as well as threshold gate implementations require exponential size (in the worst case), it will follow that size-optimal solutions for implementing arbitrary Boolean functions require analog circuitry. Conclusions and several comments on the required precision are ending the paper.
Experimental Comparison of Schemes for Interpreting Boolean Queries
Lee, Whay C.; Edward A Fox
1988-01-01
The standard interpretation of the logical operators in a Boolean retrieval system is in general too strict. A standard Boolean query rarely comes close to retrieving all and only those documents which are relevant to the user. An AND query is often too narrow and an OR query is often too broad. The choice of the AND results in retrieving on the left end of a typical average recall-precision graph, while the choice of the OR results in retrieving on the right end, implying a tradeoff between ...
ON REDUCED SCALAR EQUATIONS FOR SYNCHRONOUS BOOLEAN NETWORKS
Ali Muhammad Ali Rushdi
2013-01-01
Full Text Available A total description of a synchronous Boolean network is typically achieved by a matrix recurrence relation. A simpler alternative is to use a scalar equation which is a possibly nonlinear equation that involves two or more instances of a single scalar variable and some Boolean operator(s. Further simplification is possible in terms of a linear reduced scalar equation which is the simplest two-term scalar equation that includes no Boolean operators and equates the value of a scalar variable at a latter instance t2 to its value at an earlier instance t1. This equation remains valid when the times t1 and t2 are both augmented by any integral multiple of the underlying time period. In other words, there are infinitely many versions of a reduced scalar equation, any of which is useful for deducing information about the cyclic behavior of the network. However, to obtain correct information about the transient behavior of the network, one must find the true reduced scalar equation for which instances t1 and t2 are minimal. This study investigates the nature, derivation and utilization of reduced scalar equations. It relies on Boolean-algebraic manipulations for the derivation of such equations and suggests that this derivation can be facilitated by seeking certain orthogonality relations among certain successive (albeit not necessarily consecutive instances of the same scalar variable. We demonstrate, contrary to previously published assumptions or assertions, that there is typically no common reduced scalar equation for all the scalar variables. Each variable usually satisfies its own distinct reduced scalar equation. We also demonstrate that the derivation of a reduced scalar equation is achieved not only by proving it but also by disproving an immediately preceding version of it when such a version might exist. We also demonstrate that, despite the useful insight supplied by the reduced scalar equations, they do not provide a total solution like the
Some Properties of Inclusions of Multisets and Contractive Boolean Operators
Hyvernat, Pierre
2011-01-01
10 pages, including appendix Consider the following curious puzzle: call an n-tuple X=(X_1, ..., X_n) of sets smaller than another n-tuple Y if it has fewer //unordered sections//. We show that equivalence classes for this preorder are very easy to describe and characterize the preorder in terms of the simpler pointwise inclusion and the existence of a special increasing boolean operator f:B^n -> B^n. We also show that contrary to increasing boolean operators, the relevant operators are no...
Constant-Overhead Secure Computation of Boolean Circuits using Preprocessing
Damgård, Ivan Bjerre; Zakarias, Sarah Nouhad Haddad
We present a protocol for securely computing a Boolean circuit $C$ in presence of a dishonest and malicious majority. The protocol is unconditionally secure, assuming access to a preprocessing functionality that is not given the inputs to compute on. For a large number of players the work done by...... each player is the same as the work needed to compute the circuit in the clear, up to a constant factor. Our protocol is the first to obtain these properties for Boolean circuits. On the technical side, we develop new homomorphic authentication schemes based on asymptotically good codes with an...
Eugenio eAzpeitia
2013-04-01
Full Text Available AbstractOver the last few decades, the Arabidopsis thaliana root stem cell niche has become a model system for the study of plant development and the stem cell niche. Currently, many of the molecular mechanisms involved in root stem cell niche maintenance and development have been described. A few years ago, we published a gene regulatory network model integrating this information. This model suggested that there were missing components or interactions. Upon updating the model, the observed stable gene configurations of the root stem cell niche could not be recovered, indicating that there are additional missing components or interactions in the model. In fact, due to the lack of experimental data, gene regulatory networks inferred from published data are usually incomplete. However, predicting the location and nature of the missing data is a not trivial task. Here, we propose a set of procedures for detecting and predicting missing interactions in Boolean networks. We used these procedures to predict putative missing interactions in the A. thaliana root stem cell niche network model. Using our approach, we identified three necessary interactions to recover the reported gene activation configurations that have been experimentally uncovered for the different cell types within the root stem cell niche: 1 a regulation of PHABULOSA to restrict its expression domain to the vascular cells, 2 a self-regulation of WOX5, possibly by an indirect mechanism through the auxin signalling pathway and 3 a positive regulation of JACKDAW by MAGPIE. The procedures proposed here greatly reduce the number of possible Boolean functions that are biologically meaningful and experimentally testable and that do not contradict previous data. We believe that these procedures can be used on any Boolean network. However, because the procedures were designed for the specific case of the root stem cell niche, formal demonstrations of the procedures should be shown in future
Boolean Logic: An Aid for Searching Computer Databases in Special Education and Rehabilitation.
Summers, Edward G.
1989-01-01
The article discusses using Boolean logic as a tool for searching computerized information retrieval systems in special education and rehabilitation technology. It includes discussion of the Boolean search operators AND, OR, and NOT; Venn diagrams; and disambiguating parentheses. Six suggestions are offered for development of good Boolean logic…
HSP70 mediates survival in apoptotic cells – Boolean network prediction and experimental validation
Suhas Vasaikar
2015-08-01
Full Text Available Neuronal stress or injury results in the activation of proteins, which regulate the balance between survival and apoptosis. However, the complex mechanism of cell signalling involving cell death and survival, activated in response to cellular stress is not yet completely understood. To bring more clarity about these mechanisms, a Boolean network was constructed that represented the apoptotic pathway in neuronal cells. FasL and neurotrophic growth factor (NGF were considered as inputs in the absence and presence of heat shock proteins known to shift the balance towards survival by rescuing pro-apoptotic cells. The probabilities of survival, DNA repair and apoptosis as cellular fates, in the presence of either the growth factor or FasL, revealed a survival bias encoded in the network. Boolean predictions tested by measuring the mRNA expression level of caspase-3, caspase-8 and BAX in neuronal Neuro2a (N2a cell line with NGF and FasL as external input, showed positive correlation with the observed experimental results for survival and apoptotic states. It was observed that HSP70 contributed more towards rescuing cells from apoptosis in comparison to HSP27, HSP40 and HSP90. Overexpression of HSP70 in N2a transfected cells showed reversal of cellular fate from FasL-induced apoptosis to survival. Further, the pro-survival role of the proteins BCL2, IAP, cFLIP and NFκB determined by vertex perturbation analysis was experimentally validated through protein inhibition experiments using EM20-25, Embelin and Wedelolactone, which resulted in 1.27-fold, 1.26-fold and 1.46-fold increase in apoptosis of N2a cells. The existence of a one-to-one correspondence between cellular fates and attractor states shows that Boolean networks may be employed with confidence in qualitative analytical studies of biological networks.
Mushak, Paul; Elliott, Kevin C
2015-12-01
The ability of powerful and well-funded interest groups to steer scientific research in ways that advance their goals has become a significant social concern. This steering ability is increasingly being recognized in the peer-reviewed scientific literature and in findings of deliberative scientific bodies. This paper provides a case study that illustrates some of the major strategies that can be used to structure and advance a controversial research field. It focuses on hormesis, described as a type of dose-response relationship in toxicology and biology showing low-dose stimulation but high-dose inhibition, or the reverse. Hormesis proponents tout its significance, arguing that substances toxic at high doses and beneficial at lower doses should be regulated less stringently. We identify five strategies employed by hormesis proponents to foster its acceptance: (1) creating institutions focused on supporting hormesis; (2) developing terminology, study designs, and data interpretations that cast it in a favorable light; (3) using bibliometric techniques and surveys to attract attention; (4) aggressively advocating for the phenomenon and challenging critics; and (5) working with outside interest groups to apply the hormesis phenomenon in the economic and political spheres. We also suggest a number of oversight strategies that can be implemented to help promote credible and socially responsible research in cases like this one. PMID:26775877
Milk Leptin Surge and Biological Rhythms of Leptin and Other Regulatory Proteins in Breastmilk
Nozhenko, Yuriy; Asnani-Kishnani, Madhu; Rodríguez, Ana M.; Palou, Andreu
2015-01-01
A significant number of chronic diseases are linked to perinatal nutrition, and prevention may be associated to naturally occurring components of breast milk. One key hormone in breast milk is leptin, related with the protection from obesity in the adulthood, thus knowing its changes through the day or lactation is crucial. We aimed to investigate the daily rhythms in the milk levels of leptin, together with other two related hormones, ghrelin and adiponectin, during lactation (days 5, 10 and 15) in rat dams, and the relation with morphometric parameters (dams and pups). Summarizing the main results, the existence of biological rhythms, but not daily and maybe circasemidian, was confirmed for the three hormones at the earliest period of lactation. The correlations performed generally showed a possible dependence of milk hormone levels on plasma levels at the early phase of lactation, while with the progression of lactation this dependence may fade and the hormone levels are suggested to be more dependent on mammary gland production/maturation. There was also a correlation between milk leptin and adiponectin levels, especially in the first half of lactation, suggesting a possible parallel regulation. Interestingly, we describe a milk leptin surge around the mid of lactation (at day 10) which may be related with pup´s growth (males and females) and with the well-known (in the literature) plasma leptin surge in pups. All this knowledge may be crucial for future applications in the development of formula milk and in relation with the role of leptin surge during lactation. PMID:26680765
A Pseudo-Boolean Solution to the Maximum Quartet Consistency Problem
Morgado, Antonio
2008-01-01
Determining the evolutionary history of a given biological data is an important task in biological sciences. Given a set of quartet topologies over a set of taxa, the Maximum Quartet Consistency (MQC) problem consists of computing a global phylogeny that satisfies the maximum number of quartets. A number of solutions have been proposed for the MQC problem, including Dynamic Programming, Constraint Programming, and more recently Answer Set Programming (ASP). ASP is currently the most efficient approach for optimally solving the MQC problem. This paper proposes encoding the MQC problem with pseudo-Boolean (PB) constraints. The use of PB allows solving the MQC problem with efficient PB solvers, and also allows considering different modeling approaches for the MQC problem. Initial results are promising, and suggest that PB can be an effective alternative for solving the MQC problem.
Boolean approaches to graph embeddings related to VLSI
刘彦佩
2001-01-01
This paper discusses the development of Boolean methods in some topics on graph em-beddings which are related to VLSI. They are mainly the general theory of graph embeddability, the orientabilities of a graph and the rectilinear layout of an electronic circuit.
On the Road to Genetic Boolean Matrix Factorization
Snášel, V.; Platoš, J.; Krömer, P.; Húsek, Dušan; Frolov, A.
2007-01-01
Roč. 17, č. 6 (2007), s. 675-688. ISSN 1210-0552 Institutional research plan: CEZ:AV0Z10300504 Keywords : data mining * genetic algorithms * Boolean factorization * binary data * machine learning * feature extraction Subject RIV: IN - Informatics, Computer Science Impact factor: 0.280, year: 2007
On the Road to Genetic Boolean Matrix Factorization
Snášel, V.; Platoš, J.; Krömer, P.; Húsek, Dušan; Frolov, A.
2007-01-01
Roč. 17, č. 6 (2007), s. 675-688. ISSN 1210-0552 Institutional research plan: CEZ:AV0Z10300504 Keywords : data mining * genetic algorithm s * Boolean factorization * binary data * machine learning * feature extraction Subject RIV: IN - Informatics, Computer Science Impact factor: 0.280, year: 2007
Boolean linear differential operators on elementary cellular automata
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.
Pointwise Approximation for the Iterated Boolean Sums of Bernstein Operators
HUO Xiao-yan; LI Cui-xiang; YAO Qiu-mei
2013-01-01
In this paper,with the help of modulus of smoothness ω2r(4)(f,t),we discuss the pointwise approximation properties for the iterated Boolean sums of Bernstein operator Bnn and obtain direct and inverse theorems when 1-1/r ≤ λ ≤ 1,r ∈ N.
Constant-overhead secure computation of Boolean circuits using preprocessing
Damgård, Ivan Bjerre; Zakarias, S.
2013-01-01
We present a protocol for securely computing a Boolean circuit C in presence of a dishonest and malicious majority. The protocol is unconditionally secure, assuming a preprocessing functionality that is not given the inputs. For a large number of players the work for each player is the same as...
New Considerations for Spectral Classification of Boolean Switching Functions
J. E. Rice
2011-01-01
Full Text Available This paper presents some new considerations for spectral techniques for classification of Boolean functions. These considerations incorporate discussions of the feasibility of extending this classification technique beyond n=5. A new implementation is presented along with a basic analysis of the complexity of the problem. We also note a correction to results in this area that were reported in previous work.
Graphical interpretation of Boolean operators for protein NMR assignments
Verdegem, Dries; Dijkstra, Klaas; Hanoulle, Xavier; Lippens, Guy
2008-01-01
We have developed a graphics based algorithm for semi-automated protein NMR assignments. Using the basic sequential triple resonance assignment strategy, the method is inspired by the Boolean operators as it applies "AND"-, "OR"- and "NOT"-like operations on planes pulled out of the classical three-
On the Prime Whales of a Boolean Algebra
Holland, Jason
2013-01-01
In this note, we introduce objects called prime whales and use them to represent a Boolean algebra as an algebra of sets in a way that is analogous to Stone's Representation Theorem. We also characterize the existence of prime whales in terms of the existence of prime ideals.
Paolo Martini
2013-11-01
Full Text Available Genome-wide experiments are routinely used to increase the understanding of the biological processes involved in the development and maintenance of a variety of pathologies. Although the technical feasibility of this type of experiment has improved in recent years, data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. Here, we review strategies used in the gene set approach, and using datasets for the pig cardiocirculatory system as a case study, we demonstrate how the use of a combination of these strategies can enhance the interpretation of results. Gene set analyses are able to distinguish vessels from the heart and arteries from veins in a manner that is consistent with the different cellular composition of smooth muscle cells. By integrating microRNA elements in the regulatory circuits identified, we find that vessel specificity is maintained through specific miRNAs, such as miR-133a and miR-143, which show anti-correlated expression with their mRNA targets.
borealis - A generalized global update algorithm for Boolean optimization problems
Zhu, Zheng; Katzgraber, Helmut G
2016-01-01
Optimization problems with Boolean variables that fall into the nondeterministic polynomial (NP) class are of fundamental importance in computer science, mathematics, physics and industrial applications. Most notably, solving constraint-satisfaction problems, which are related to spin-glass-like Hamiltonians in physics, remains a difficult numerical task. As such, there has been great interest in designing efficient heuristics to solve these computationally difficult problems. Inspired by parallel tempering Monte Carlo in conjunction with the rejection-free isoenergetic cluster algorithm developed for Ising spin glasses, we present a generalized global update optimization heuristic that can be applied to different NP-complete problems with Boolean variables. The global cluster updates allow for a wide-spread sampling of phase space, thus considerably speeding up optimization. By carefully tuning the pseudo-temperature (needed to randomize the configurations) of the problem, we show that the method can efficie...
High Quality Test Pattern Generation and Boolean Satisfiability
Eggersglüß, Stephan
2012-01-01
This book provides an overview of automatic test pattern generation (ATPG) and introduces novel techniques to complement classical ATPG, based on Boolean Satisfiability (SAT). A fast and highly fault efficient SAT-based ATPG framework is presented which is also able to generate high-quality delay tests such as robust path delay tests, as well as tests with long propagation paths to detect small delay defects. The aim of the techniques and methodologies presented in this book is to improve SAT-based ATPG, in order to make it applicable in industrial practice. Readers will learn to improve the performance and robustness of the overall test generation process, so that the ATPG algorithm reliably will generate test patterns for most targeted faults in acceptable run time to meet the high fault coverage demands of industry. The techniques and improvements presented in this book provide the following advantages: Provides a comprehensive introduction to test generation and Boolean Satisfiability (SAT); Describes a...
Boolean network representation of contagion dynamics during a financial crisis
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.
Complexity of Propositional Abduction for Restricted Sets of Boolean Functions
Creignou, Nadia; Thomas, Michael
2009-01-01
Abduction is a fundamental and important form of non-monotonic reasoning. Given a knowledge base explaining how the world behaves it aims at finding an explanation for some observed manifestation. In this paper we focus on propositional abduction, where the knowledge base and the manifestation are represented by propositional formulae. The problem of deciding whether there exists an explanation has been shown to be SigmaP2-complete in general. We consider variants obtained by restricting the allowed connectives in the formulae to certain sets of Boolean functions. We give a complete classification of the complexity for all considerable sets of Boolean functions. In this way, we identify easier cases, namely NP-complete and polynomial cases; and we highlight sources of intractability. Further, we address the problem of counting the explanations and draw a complete picture for the counting complexity.
Sparse combinatorial inference with an application in cancer biology
Mukherjee, Sach; Pelech, Steven; Neve, Richard M.; Kuo, Wen-Lin; Ziyad, Safiyyah; Spellman, Paul T.; Joe W Gray; Speed, Terence P.
2008-01-01
Motivation: Combinatorial effects, in which several variables jointly influence an output or response, play an important role in biological systems. In many settings, Boolean functions provide a natural way to describe such influences. However, biochemical data using which we may wish to characterize such influences are usually subject to much variability. Furthermore, in high-throughput biological settings Boolean relationships of interest are very often sparse, in the sense of being embedde...
Worst-Case Groundness Analysis Using Definite Boolean Functions
Genaim, Samir; Codish, Michael; Howe, Jacob M.
2004-01-01
This note illustrates theoretical worst-case scenarios for groundness analyses obtained through abstract interpretation over the abstract domains of definite (Def) and positive (Pos) Boolean functions. For Def, an example is given for which any Def-based abstract interpretation for groundness analysis follows a chain which is exponential in the number of argument positions as well as in the number of clauses but sub-exponential in the size of the program. For Pos, we strengthen a previous res...
Estimation of Boolean Factor Analysis Performance by Informational Gain
Frolov, A.; Húsek, Dušan; Polyakov, P.Y.
Berlin : Springer, 2010 - (Snášel, V.; Szczepaniak, P.; Abraham, A.; Kacprzyk, J.), s. 83-94 ISBN 978-3-642-10686-6. - (Advances in Intelligent and Soft Computing. 67). [AWIC 2009. Atlantic Web Intelligence Conference /6./. Prague (CZ), 09.09.2009-11.09.2009] Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean factor analysis * informational gain * Hopfield-like network Subject RIV: IN - Informatics, Computer Science
Reduction of Database Independence to Dividing in Atomless Boolean Algebras
Hyttinen, Tapani; Paolini, Gianluca
2014-01-01
We prove that the form of conditional independence at play in database theory and independence logic is reducible to the first-order dividing calculus in the theory of atomless Boolean algebras. This establishes interesting connections between independence in database theory and stochastic independence. As indeed, in light of the aforementioned reduction and recent work of Ben-Yaacov [4], the former case of independence can be seen as the discrete version of the latter.
Yes/No/Maybe: A Boolean attempt at feedback
12130478 - Louw, Henk; 10095519 - Van Rooy, Albertus Jacobus
2010-01-01
This paper describes an experiment in which Boolean feedback (a kind of checklist) was used to provide feedback on the paragraph structures of first year students in an Academic Literacy course. We begin by introducing the major problems with feedback on L2 writing and establishing why a focus on paragraph structures in particular is of importance. The experiment conducted was a two-draft assignment in which three different kinds of feedback (technique A: handwritten comments, B: consciousnes...
A Boolean Approach to Airline Business Model Innovation
Hvass, Kristian
2012-01-01
Research in business model innovation has identified its significance in creating a sustainable competitive advantage for a firm, yet there are few empirical studies identifying which combination of business model activities lead to success and therefore deserve innovative attention. This study analyzes the business models of North America low-cost carriers from 2001 to 2010 using a Boolean minimization algorithm to identify which combinations of business model activities le...
A Boolean algebra approach to the construction of snarks
Fiol Mora, Miquel Àngel
1991-01-01
This work deals with the construction of snarks, that is, cubic graphs that cannot be 3-edge-colored. A natural generalization of the concept of "color", that describes in a simple way the coloring ("0" or "1") of any set of (semi)edges, is introduced. This approach allows us to apply the Boolean logic theory to find an ample family of snarks, which includes many of the previous known constructions and also some interesting ones. Peer Reviewed
Boolean logic device done with DFB laser diode
Hurtado Villavieja, Antonio; González Marcos, Ana; Martín Pereda, José Antonio
2004-01-01
We present simulation results on how power output-input characteristic Instability in Distributed FeedBack -DFB semiconductor laser diode SLA can be employed to implemented Boolean logic device. Two configurations of DFB Laser diode under external optical injection, either in the transmission or in the reflective mode of operation, is used to implement different Optical Logic Cells (OLCs), called the Q- and the P-Device OLCs. The external optical injection correspond to two inputs data plus a...
Mapping Complex Networks: Exploring Boolean Modeling of Signal Transduction Pathways
Bhardwaj, Gaurav; Wells, Christine P.; Albert, Reka; van Rossum, Damian B.; Patterson, Randen L
2009-01-01
In this study, we explored the utility of a descriptive and predictive bionetwork model for phospholipase C-coupled calcium signaling pathways, built with non-kinetic experimental information. Boolean models generated from these data yield oscillatory activity patterns for both the endoplasmic reticulum resident inositol-1,4,5-trisphosphate receptor (IP3R) and the plasma-membrane resident canonical transient receptor potential channel 3 (TRPC3). These results are specific as randomization of ...
Boolean Functions, Projection Operators and Quantum Error Correcting Codes
Aggarwal, Vaneet; Calderbank, A. Robert
2006-01-01
This paper describes a fundamental correspondence between Boolean functions and projection operators in Hilbert space. The correspondence is widely applicable, and it is used in this paper to provide a common mathematical framework for the design of both additive and non-additive quantum error correcting codes. The new framework leads to the construction of a variety of codes including an infinite class of codes that extend the original ((5,6,2)) code found by Rains [21]. It also extends to o...
Matroids, hereditary collections and simplicial complexes having boolean representations
Rhodes, John; Silva, Pedro V.
2012-01-01
Inspired by the work of Izakhian and Rhodes, a theory of representation of hereditary collections by boolean matrices is developed. This corresponds to representation by finite $\\vee$-generated lattices. The lattice of flats, defined for hereditary collections, lattices and matrices, plays a central role in the theory. The representations constitute a lattice and the minimal and strictly join irreducible elements are studied, as well as various closure operators.
Soft Rough Approximation Operators on a Complete Atomic Boolean Lattice
Heba I. Mustafa
2013-01-01
The concept of soft sets based on complete atomic Boolean lattice, which can be seen as a generalization of soft sets, is introduced. Some operations on these soft sets are discussed, and new types of soft sets such as full, keeping infimum, and keeping supremum are defined and supported by some illustrative examples. Two pairs of new soft rough approximation operators are proposed and the relationship among soft set is investigated, and their related properties are given. We show that Järvin...
Boolean Functions with a Simple Certificate for CNF Complexity
Čepek, O.; Kučera, P.; Savický, Petr
2012-01-01
Roč. 160, 4-5 (2012), s. 365-382. ISSN 0166-218X R&D Projects: GA MŠk(CZ) 1M0545 Grant ostatní: GA ČR(CZ) GP201/07/P168; GA ČR(CZ) GAP202/10/1188 Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean functions * CNF representations Subject RIV: BA - General Mathematics Impact factor: 0.718, year: 2012
Constant communication complexity protocols for multiparty accumulative boolean functions
pal, S P; Kumar, S; Das, Sima; Kumar, Somesh; pal, Sudebkumar Prasant
2005-01-01
Generalizing a boolean function from Cleve and Buhrman \\cite{cb:sqec}, we consider the class of {\\it accumulative boolean functions} of the form $f_B(X_1,X_2,..., X_m)=\\bigoplus_{i=1}^n t_B(x_i^1x_i^2... x_i^m)$, where $X_j=(x^j_1,x^j_2,..., x^j_n), 1\\leq j\\leq m$ and $t_B(x_i^1x_i^2... x_i^m)=1$ for input $m$-tuples $x_i^1x_i^2...x_i^m\\in B\\subseteq A\\subseteq \\{0,1\\}^n$, and 0, otherwise. Here the set $A$ is the promise set for function $f_B$. The input vectors $X_j, 1\\leq j\\leq m$ are given to the $m\\geq 2$ parties respectively, who communicate classical bits in a distributed environment so that one of them (say Alice) comes up with the value of the function. We algebraically characterize entanglement assisted LOCC protocols requiring only $m-1$ cbits of communication, for certain classes of such multiparty boolean functions for $m\\geq 2$ parties under appropriate uniform parity promise restrictions on input $m$-tuples $x_i^1x_i^2...x_i^m, 1\\leq i\\leq n$. In contrast, for certain $m$-party accumulative boo...
MILES FORMULAE FOR BOOLEAN MODELS OBSERVED ON LATTICES
Joachim Ohser
2011-05-01
Full Text Available The densities of the intrinsic volumes – in 3D the volume density, surface density, the density of the integral of the mean curvature and the density of the Euler number – are a very useful collection of geometric characteristics of random sets. Combining integral and digital geometry we develop a method for efficient and simultaneous calculation of the intrinsic volumes of random sets observed in binary images in arbitrary dimensions. We consider isotropic and reflection invariant Boolean models sampled on homogeneous lattices and compute the expectations of the estimators of the intrinsic volumes. It turns out that the estimator for the surface density is proved to be asymptotically unbiased and thusmultigrid convergent for Boolean models with convex grains. The asymptotic bias of the estimators for the densities of the integral of the mean curvature and of the Euler number is assessed for Boolean models of balls of random diameters. Miles formulae with corresponding correction terms are derived for the 3D case.
Binary higher order neural networks for realizing Boolean functions.
Zhang, Chao; Yang, Jie; Wu, Wei
2011-05-01
In order to more efficiently realize Boolean functions by using neural networks, we propose a binary product-unit neural network (BPUNN) and a binary π-ς neural network (BPSNN). The network weights can be determined by one-step training. It is shown that the addition " σ," the multiplication " π," and two kinds of special weighting operations in BPUNN and BPSNN can implement the logical operators " ∨," " ∧," and " ¬" on Boolean algebra 〈Z(2),∨,∧,¬,0,1〉 (Z(2)={0,1}), respectively. The proposed two neural networks enjoy the following advantages over the existing networks: 1) for a complete truth table of N variables with both truth and false assignments, the corresponding Boolean function can be realized by accordingly choosing a BPUNN or a BPSNN such that at most 2(N-1) hidden nodes are needed, while O(2(N)), precisely 2(N) or at most 2(N), hidden nodes are needed by existing networks; 2) a new network BPUPS based on a collaboration of BPUNN and BPSNN can be defined to deal with incomplete truth tables, while the existing networks can only deal with complete truth tables; and 3) the values of the weights are all simply -1 or 1, while the weights of all the existing networks are real numbers. Supporting numerical experiments are provided as well. Finally, we present the risk bounds of BPUNN, BPSNN, and BPUPS, and then analyze their probably approximately correct learnability. PMID:21427020
Development of an effective regulatory system for genetically engineered animals and their products has been the subject of increasing discussion among researchers, industry and policy developers, as well as the public. Since transgenesis and cloning are relatively new scientific techniques, transgenic animals are new organisms for which there is limited information. The issues associated with the regulation and biosafety of transgenic animals pertain to environmental impact, human food safety, animal health and welfare, trade and ethics. To regulate this new and powerful technology predicated on limited background information is a challenge not only for the regulators, but also for the developers of such animals, who strive to prove that the animals are safe and merit bio-equivalency to their conventional counterparts. In principle, an effective regulatory sieve should permit safe products while forming a formidable barrier for those assessed of posing an unacceptable risk. Adoption of transgenic technology for use in agriculture will depend upon various factors that range from perceived benefits for humans and animals, to safe propagation, animal welfare considerations and integrity of species, as well as effects on bio-diversity. A regulatory framework designed to address the concerns connected with the environmental release of transgenic animals needs to also take into account the ability of genetically modified animals to survive and compete with conventional populations. Regulatory initiatives for biotechnology-derived animals and their products should ensure high standards for human and animal health; a sound scientific basis for evaluation; transparency and public involvement; and maintenance of genetic diversity. Feeds obtained by use of biotechnology have to be evaluated for animal and human safety by using parameters that define their molecular characterization, nutritional qualities and toxicological aspects, while veterinary biologics derived from
Deutsch-Jozsa Algorithm Revisited in the Domain of Cryptographically Significant Boolean Functions
Maitra, S; Maitra, Subhamoy; Mukhopadhyay, Partha
2004-01-01
Boolean functions are important building blocks in cryptography for their wide application in both stream and block cipher systems. For cryptanalysis of such systems one tries to find out linear functions that are correlated to the Boolean functions used in the crypto system. Let $f$ be an $n$-variable Boolean function and its Walsh spectra is denoted by $W_f(\\omega)$ at the point $\\omega \\in \\{0, 1\\}^n$. The Boolean function is available in the form of an oracle. We like to find an $\\omega$ such that $W_f(\\omega) \
Modeling and controlling the two-phase dynamics of the p53 network: a Boolean network approach
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. (paper)
Klauser, Benedikt; Saragliadis, Athanasios; Ausländer, Simon; Wieland, Markus; Berthold, Michael R; Hartig, Jörg S
2012-09-01
In cellular systems environmental and metabolic signals are integrated for the conditional control of gene expression. On the other hand, artificial manipulation of gene expression is of high interest for metabolic and genetic engineering. Especially the reprogramming of gene expression patterns to orchestrate cellular responses in a predictable fashion is considered to be of great importance. Here we introduce a highly modular RNA-based system for performing Boolean logic computation at a post-transcriptional level in Escherichia coli. We have previously shown that artificial riboswitches can be constructed by utilizing ligand-dependent Hammerhead ribozymes (aptazymes). Employing RNA self-cleavage as the expression platform-mechanism of an artificial riboswitch has the advantage that it can be applied to control several classes of RNAs such as mRNAs, tRNAs, and rRNAs. Due to the highly modular and orthogonal nature of these switches it is possible to combine aptazyme regulation of activating a suppressor tRNA with the regulation of mRNA translation initiation. The different RNA classes can be controlled individually by using distinct aptamers for individual RNA switches. Boolean logic devices are assembled by combining such switches in order to act on the expression of a single mRNA. In order to demonstrate the high modularity, a series of two-input Boolean logic operators were constructed. For this purpose, we expanded our aptazyme toolbox with switches comprising novel behaviours with respect to the small molecule triggers thiamine pyrophosphate (TPP) and theophylline. Then, individual switches were combined to yield AND, NOR, and ANDNOT gates. This study demonstrates that post-transcriptional aptazyme-based switches represent versatile tools for engineering advanced genetic devices and circuits without the need for regulatory protein cofactors. PMID:22777205
Modeling and controlling the two-phase dynamics of the p53 network: a Boolean network approach
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.
Hoeyer, Klaus
2015-01-01
This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... arise. In short, I expose the regulatory anatomy of the policy landscape....
Robust Design of Biological Circuits: Evolutionary Systems Biology Approach
Bor-Sen Chen; Chih-Yuan Hsu; Jing-Jia Liou
2011-01-01
Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter ...
The value of less connected agents in Boolean networks
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
Expectation-Maximization Approach to Boolean Factor Analysis
Frolov, A. A.; Húsek, Dušan; Polyakov, P.Y.
Piscataway: IEEE, 2011, s. 559-566. ISBN 978-1-4244-9636-5. [IJCNN 2011. International Joint Conference on Neural Networks. San Jose (US), 31.07.2011-05.08.2011] R&D Projects: GA ČR GAP202/10/0262; GA ČR GA205/09/1079; GA MŠk(CZ) 1M0567 Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean factor analysis * bars problem * dendritic inhibition * expectation-maximization * neural network application * statistics Subject RIV: IN - Informatics, Computer Science
Neural Network Based Boolean Factor Analysis of Parliament Voting
Frolov, A. A.; Polyakov, P.Y.; Húsek, Dušan; Řezanková, H.
Heidelberg : Springer, 2006 - (Rizzi, A.; Vichi, M.), s. 861-868 ISBN 3-7908-1708-2. [COMPSTAT 2006. Symposium /17./. Rome (IN), 28.08.2006-01.09.2006] R&D Projects: GA AV ČR 1ET100300419; GA ČR GA201/05/0079 Grant ostatní: RFBR(RU) 05-07-90049 Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean factor analysis * neural networks * social networks Subject RIV: BB - Applied Statistics, Operational Research
Self-organized networks of competing boolean agents
Paczuski; Bassler; Corral
2000-04-01
A model of Boolean agents competing in a market is presented where each agent bases his action on information obtained from a small group of other agents. The agents play a competitive game that rewards those in the minority. After a long time interval, the poorest player's strategy is changed randomly, and the process is repeated. Eventually the network evolves to a stationary but intermittent state where random mutation of the worst strategy can change the behavior of the entire network, often causing a switch in the dynamics between attractors of vastly different lengths. PMID:11019043
Symmetric Groups and Quotient Complexity of Boolean Operations
Bell, Jason; Brzozowski, Janusz; Moreira, Nelma; Reis, Rogério
2013-01-01
The quotient complexity of a regular language L is the number of left quotients of L, which is the same as the state complexity of L. Suppose that L and L' are binary regular languages with quotient complexities m and n, and that the transition semigroups of the minimal deterministic automata accepting L and L' are the symmetric groups S_m and S_n of degrees m and n, respectively. Denote by o any binary boolean operation that is not a constant and not a function of one argument only. For m,n ...
Dimensionality Reduction in Boolean Data: Comparison of Four BMF Methods
Bartl, E.; Bělohlávek, R.; Osicka, P.; Řezanková, Hana
Berlin: Springer, 2015 - (Masulli, F.; Petrosino, A.; Rovetta, S.), s. 118-133. (Lecture Notes in Computer Science. 7627). ISBN 978-3-662-48576-7. ISSN 0302-9743. [CHDD 2012. Clustering High-Dimensional Data. International Workshop /1./. Naples (IT), 15.05.2012-15.05.2012] R&D Projects: GA ČR GAP202/10/0262 Grant ostatní: GA MŠk CZ.1.07/2.3.00/20.0059 Keywords : binary data * dimensionality reduction * Boolean factor analysis * matrix decomposition Subject RIV: BB - Applied Statistics, Operational Research
Two Expectation-Maximization Algorithms for Boolean Factor Analysis
Frolov, A. A.; Húsek, Dušan; Polyakov, P.Y.
2014-01-01
Roč. 130, 23 April (2014), s. 83-97. ISSN 0925-2312 R&D Projects: GA ČR GAP202/10/0262 Grant ostatní: GA MŠk(CZ) ED1.1.00/02.0070; GA MŠk(CZ) EE.2.3.20.0073 Institutional research plan: CEZ:AV0Z10300504 Keywords : Boolean Factor analysis * Binary Matrix factorization * Neural networks * Binary data model * Dimension reduction * Bars problem Subject RIV: IN - Informatics, Computer Science Impact factor: 2.083, year: 2014
C*-algebras associated to Boolean dynamical systems
Pardo Espino, Enrique
2016-01-01
The goal of this talk is to present the C*-algebra $C^*(\\mathcal{B}, \\mathcal{L}, \\theta)$ of a Boolean dynamical system $(\\mathcal{B}, \\mathcal{L}, \\theta)$, that generalizes the $C^*$-algebra associated to a labelled graph introduced by Bates and Pask, and to determine its simplicity, its gauge invariant ideals, as well as compute its K-Theory. This is a joint work with Toke Meier Carlsen (Department of Science and Technology, University of the Faroe Islands) and Eduard Ortega (Departme...
Comparison of Two Neural Networks Approaches to Boolean Matrix Factorization
Polyakov, P.Y.; Frolov, A. A.; Húsek, Dušan
Los Alamitos: IEEE Computer Society, 2009 - (Snášel, V.; Pokorný, J.; Pichappan, P.; El-Qawasmeh, E.), s. 316-321 ISBN 978-1-4244-4614-8. [NDT 2009. International Conference on Networked Digital Technologies /1./. Ostrava (CZ), 29.07.2009-31.07.2009] R&D Projects: GA ČR GA205/09/1079; GA MŠk(CZ) 1M0567 Institutional research plan: CEZ:AV0Z10300504 Keywords : data mining * artificial inteligence * neural networks * multivariate statistics * Boolean factor analysis * Hopfield-like neural networks * feed forward neural network Subject RIV: BB - Applied Statistics, Operational Research
Boolean approaches to graph embeddings related to VLSI
LIU; Yanpei(
2001-01-01
［1］Hu, T. C., Kuh, S. E., Theory and concepts of circuit layout, in VLSI Circuit Layout: Theory and Design, New York:IEEE Press, 1985, 3-18.［2］Liu Yanpei, Embeddability in Graphs, Boston-Beijing: Kluwer Science, 1995.［3］Liu Yanpei, Some combinatorial optimization problems arising from VLSI circuit design, Applied Math. -JCU, 1993, 38:218-235.［4］Liu Yanpei, Marchioro, P. , Petreschi, R., At most single bend embeddings of cubic graphs, Applied Math. -CJU, 1994,39: 127-142.［5］Liu Yanpei, Marchioro, P. , Petreschi, R. et al. , Theoretical results on at most 1-bend embeddability of graphs, Acta Math.Appl. Sinica, 1992, 8: 188-192.［6］Liu Yanpei, Morgana, A., Simeone, B., General theoretical results on rectilinear embeddability of graphs, Acta Math. Ap- pl. Simca, 1991, 7: 187-192.［7］Calamoneri, T., Petreschi, R., Liu Yanpei, Optimally Extending Bistandard Graphs on the Orthogonal Grid, ASCM2000 Symposium, Tailand, Dec.17-21, 2000.［8］Liu Yanpei, Morgana, A., Simeone, B., A graph partition problem, Acta Math. Appl. Sinica, 1996, 12: 393-400.［9］Liu Yanpei, Morgana, A. , Simeone, B. , A linear algorithm for 2-bend embeddings of planar graphs in the two dimensional grid, Discrete Appl. Math., 1998, 81: 69-91.［10］Liu Yanpei, Boolean approach to planar embeddings of a graph, Acta Math. Sinica, New Series, 1989, 5: 64-79.［11］Hammer, P. L., Liu Yanpei, Simeone, B., Boolean approaches to combinatorial optimization, J. Math. Res. Expos.,1990, 10: 300-312, 455-468, 619-628.［12］Liu Yanpei, Boolean planarity characterization of graphs, Acta Math. Sinica, New Series, 1988, 4: 316-329.［13］Liu Yanpei, Boolean characterizations of planarity and planar embeddings of graphs, Ann. O. R., 1990, 24: 165-174.
Soft Rough Approximation Operators on a Complete Atomic Boolean Lattice
Heba I. Mustafa
2013-01-01
Full Text Available The concept of soft sets based on complete atomic Boolean lattice, which can be seen as a generalization of soft sets, is introduced. Some operations on these soft sets are discussed, and new types of soft sets such as full, keeping infimum, and keeping supremum are defined and supported by some illustrative examples. Two pairs of new soft rough approximation operators are proposed and the relationship among soft set is investigated, and their related properties are given. We show that Järvinen's approximations can be viewed as a special case of our approximation. If , then our soft approximations coincide with crisp soft rough approximations (Feng et al. 2011.
The number system hidden inside the Boolean satisfiability problem
Cho, Keum-Bae
2014-01-01
The Boolean satisfiability (SAT) problem is the first known example of an NP-complete problem, and thousands of NP-compete problems have been identified by reducing the SAT to the problems. Researchers have tried to find a definite mathematical expression that distinguishes among NL-complete, P-complete, and NP-complete problems such as 2-SAT, Horn-SAT, and 3-SAT. In this paper, we introduce the natural number system hidden inside the SAT structure. We reduce a SAT instance to an integer-prog...
Graphical interpretation of Boolean operators for protein NMR assignments.
Verdegem, Dries; Dijkstra, Klaas; Hanoulle, Xavier; Lippens, Guy
2008-09-01
We have developed a graphics based algorithm for semi-automated protein NMR assignments. Using the basic sequential triple resonance assignment strategy, the method is inspired by the Boolean operators as it applies "AND"-, "OR"- and "NOT"-like operations on planes pulled out of the classical three-dimensional spectra to obtain its functionality. The method's strength lies in the continuous graphical presentation of the spectra, allowing both a semi-automatic peaklist construction and sequential assignment. We demonstrate here its general use for the case of a folded protein with a well-dispersed spectrum, but equally for a natively unfolded protein where spectral resolution is minimal. PMID:18762868
Boolean Functions, Quantum Gates, Hamilton Operators, Spin Systems and Computer Algebra
Hardy, Yorick; Steeb, Willi-Hans
2014-01-01
We describe the construction of quantum gates (unitary operators) from boolean functions and give a number of applications. Both non-reversible and reversible boolean functions are considered. The construction of the Hamilton operator for a quantum gate is also described with the Hamilton operator expressed as spin system. Computer algebra implementations are provided.
Boolean Operators and the Naive End-User: Moving to AND.
Proctor, Edward
2002-01-01
Discusses the confusion among end users in using Boolean operators when searching electronic resources. Highlights include search engines; site-specific search engines; the counterintuitive nature of Boolean logic; hidden defaults; the problem of conceptualization; reprogramming defaults; and a lack of user education. (LRW)
Young, Degi; Shneiderman, Ben
1993-01-01
Literature showing the disadvantages of Boolean logic in online searching is reviewed, and research comparing the Filter/Flow visual interface (i.e., a graphical representation of Boolean operators) with a text-only interface is described. A significant difference in the total number of correct queries is reported that favored Filter/Flow. (16…
Disjunctive normal forms for any class of Boolean algebras with operators
Khaled, Mohamed
2015-01-01
Disjunctive normal forms can provide elegant and constructive proofs of many standard results such as completeness, decidability and so on. They were also used to show non atomicity of some free algebras of specific Boolean algebras with operators. Here, we generalize the normal forms for any class of Boolean algebras with operators.