Asymptotic geometry of high-density smooth-grained Boolean models in bounded domains

We study the complexity of query satisfiability and entailment for the Boolean information retrieval models WP and AWV using techniques from propositional logic and computational complexity. WP and AWV can be used to represent and query textual information under the Boolean model using the concept of attribute with values of type text, the concept of word, and word proximity constraints. Variations of WP and AWP are in use in most deployed digital libraries using the Boolean model, text extenders for relational database systems (e.g., Oracle 10g), search engines, and P2P systems for information retrieval and filtering

BackgroundCellular decision-making is governed by molecular networks that are highly complex. An integrative understanding of these networks on a genome wide level is essential to understand cellular health and disease. In most cases however, such an understanding is beyond human comprehension and requires computational modeling. Mathematical modeling of biological networks at the level of biochemical details has hitherto relied on state transition models. These are typically based on enumeration of all relevant model states, and hence become very complex unless severely – and often arbitrarily – reduced. Furthermore, the parameters required for genome wide networks will remain underdetermined for the conceivable future. Alternatively, networks can be simulated by Boolean models, although these typically sacrifice molecular detail as well as distinction between different levels or modes of activity. However, the modeling community still lacks methods that can simulate genome scale networks on the level of biochemical reaction detail in a quantitative or semi quantitative manner.ResultsHere, we present a probabilistic bipartite Boolean modeling method that addresses these issues. The method is based on the reaction-contingency formalism, and enables fast simulation of large networks. We demonstrate its scalability by applying it to the yeast mitogen-activated protein kinase (MAPK) network consisting of 140 proteins and 608 nodes.ConclusionThe probabilistic Boolean model can be generated and parameterized automatically from a rxncon network description, using only two global parameters, and its qualitative behavior is robust against order of magnitude variation in these parameters. Our method can hence be used to simulate the outcome of large signal transduction network reconstruction, with little or no overhead in model creation or parameterization.

Minkowski tensor density formulas for Boolean models

In Systems Biology, Boolean models are gaining popularity in modeling and analysis of qualitative dynamics of gene regulatory mechanisms. With the development of advanced high-throughput technologies, the availability of experimental data on gene-gene, gene-protein interactions is ever increasing. Consequently, modern Boolean models are increasing in size and complexity. Software simulation of Boolean models does not scale for such state-of-the-art complex Boolean models. We propose Field Programmable Gate Arrays (FPGAs) for emulation of Boolean models, exploiting the highly parallel nature of FPGAs. Our emulation framework consists of converting a Boolean model to Verilog, connecting it to an execution core, which runs on an FPGA coherently attached to a POWER8 processor. We report an order of magnitude speed up over a multi-threaded software simulation tool running on the same processor.

IntroductionPseudomonas aeruginosa infections are one of the leading causes of death in immunocompromised patients with cystic fibrosis, diabetes, and lung diseases such as pneumonia and bronchiectasis. Furthermore, P. aeruginosa is one of the main multidrug-resistant bacteria responsible for nosocomial infections worldwide, including the multidrug-resistant CCBH4851 strain isolated in Brazil.MethodsOne way to analyze their dynamic cellular behavior is through computational modeling of the gene regulatory network, which represents interactions between regulatory genes and their targets. For this purpose, Boolean models are important predictive tools to analyze these interactions. They are one of the most commonly used methods for studying complex dynamic behavior in biological systems.Results and discussionTherefore, this research consists of building a Boolean model of the gene regulatory network of P. aeruginosa CCBH4851 using data from RNA-seq experiments. Next, the basins of attraction are estimated, as these regions and the transitions between them can help identify the attractors, representing long-term behavior in the Boolean model. The essential genes of the basins were associated with the phenotypes of the bacteria for two conditions: biofilm formation and polymyxin B treatment. Overall, the Boolean model and the analysis method proposed in this work can identify promising control actions and indicate potential therapeutic targets, which can help pinpoint new drugs and intervention strategies.

In the face of incomplete data on a system of interest, constraint-based Boolean modeling still allows for elucidating system characteristics by analyzing sets of models consistent with the available information. In this setting, methods not depending on consideration of every single model in the set are necessary for efficient analysis. Drawing from ideas developed in qualitative differential equation theory, we present an approach to analyze sets of monotonic Boolean models consistent with given signed interactions between systems components. We show that for each such model constraints on its behavior can be derived from a universally constructed state transition graph essentially capturing possible sign changes of the derivative. Reachability results of the modeled system, e.g., concerning trap or no-return sets, can then be derived without enumerating and analyzing all models in the set. The close correspondence of the graph to similar objects for differential equations furthermore opens up ways to relate Boolean and continuous models.

In this paper, we establish several proper separation theorems for an element and a convex set and for two convex sets in terms of their quasi-relative interiors. Then, we prove that the separation theorem given by [Cammaroto, F and B Di Bella (2007). On a separation theorem involving the quasi-relative. Proceedings of the Edinburgh Mathematical Society, 50(3), 605–610] in Theorem 2.5, is in fact a proper separation theorem for two convex sets in which the classical interior is replaced by the quasi-relative interior. Besides, we extend some known results in the literature, such as [Adán, M and V Novo (2004). Proper efficiency in vector optimization on real linear spaces. Journal of Optimization Theory and Applications, 121, 515–540] in Theorem 2.1 and [Edwards, R (1965). Functional Analysis: Theory and Applications. New York: Reinhart and Winston] in Corollary 2.2.2, through the quasi-relative interior and the quasi-interior, respectively. As an application, we provide Karush–Kuhn–Tucker multipliers for quasi-relative solutions of vector optimization problems. Several examples are given to illustrate the obtained results.

We develop a theory of best simultaneous approximation for closed convex sets in a conditionally complete lattice Banach space X with a strong unit. We study best simultaneous approximation in X by elements of closed convex sets, and give necessary and sufficient conditions for the uniqueness of best simultaneous approximation. We give a characterization of simultaneous pseudo-Chebyshev and quasi-Chebyshev closed convex sets in X. Also, we present various characterizations of best simultaneous approximation of elements by closed convex sets in terms of the extremal points of the closed unit ball B X* of X*.

The aim of the paper is to generalize the Palais-Smale condition for nonsmooth function s over closed and convex sets in terms of th e lower Dini direct ion al derivative. For an important family of functions we prove th e Palais-Smale condition on every closed and convex set. As an example we consider a boundary value problem with lower a nd upper solutions

Consider a continuum percolation model in which, at each point of a d-dimensional Poisson process of rate λ, a ball of radius 1 is centred. We show that, for any d ≧ 3, there exists a phase where both the regions, occupied and vacant, contain unbounded components. The proof uses the concept of enhancement for the Boolean model, and along the way we prove that the critical intensity of a Boolean model defined on a slab is strictly larger than the critical intensity of a Boolean model defined on the whole space.

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

Dynamic Boolean models

In this dissertation, we consider wireless multi-hop networks, where the nodes are randomly placed. We are particularly interested in their asymptotic properties when the number of nodes tends to infinity. We use percolation theory as our main tool of analysis. As a first model, we assume that nodes have a fixed connectivity range, and can establish wireless links to all nodes within this range, but no other (Boolean model). We compute for one-dimensional networks the probability that two nodes are connected, given the distance between them. We show that this probability tends exponentially to zero when the distance increases, proving that pure multi-hopping does not work in large networks. In two dimensions however, an unbounded cluster of connected nodes forms if the node density is above a critical threshold (super-critical phase). This is known as the percolation phenomenon. This cluster contains a positive fraction of the nodes that depends on the node density, and remains constant as the network size increases. Furthermore, the fraction of connected nodes tends rapidly to one when the node density is above the threshold. We compare this partial connectivity to full connectivity, and show that the requirement for full connectivity leads to vanishing throughput when the network size increases. In contrast, partial connectivity is perfectly scalable, at the cost of a tiny fraction of the nodes being disconnected. We consider two other connectivity models. The first one is a signal-to-interference- plus-noise-ratio based connectivity graph (STIRG). In this model, we assume deterministic attenuation of the signals as a function of distance. We prove that percolation occurs in this model in a similar way as in the previous model, and study in detail the domain of parameters where it occurs. We show in particular that the assumptions on the attenuation function dramatically impact the results: the commonly used power-law attenuation leads to particular symmetry properties. However, physics imposes that the received signal cannot be stronger than the emitted signal, implying a bounded attenuation function. We observe that percolation is harder to achieve in most cases with such an attenuation function. The second model is an information theoretic view on connectivity, where two arbitrary nodes are considered connected if it is possible to transmit data from one to the other at a given rate. We show that in this model the same partial connectivity can be achieved in a scalable way as in the Boolean model. This result is however a pure connectivity result in the sense that there is no competition and interferences between data flows. We also look at the other extreme, the Gupta and Kumar scenario, where all nodes want to transmit data simultaneously. We show first that under point-to-point communication and bounded attenuation function the total transport capacity of a fixed area network is bounded from above by a constant, whatever the number of nodes may be. However, if the network area increases linearly with the number of nodes (constant density), or if we assume power-law attenuation function, a throughput per node of order 1/√n can be achieved. This latter result improves the existing results about random networks by a factor (log n)1/2. In the last part of this dissertation, we address two problems related to latency. The first one is an intruder detection scenario, where a static sensor network has to detect an intruder that moves with constant speed along a straight line. We compute an upper bound to the time needed to detect the intruder, under the assumption that detection by disconnected sensors does not count. In the second scenario, sensors switch off their radio device for random periods, in order to save energy. This affects the delivery of alert messages, since they may have to wait for relays to turn on their radio to move further. We show that asymptotically, alert messages propagate with constant, deterministic speed in such networks.

Convex Envelope and Representation of Convex Sets

We are interested in estimating the intensity parameter of a Boolean model of discs (the bombing model) from a single realization. To do so, we derive the conditional distribution of the points (germs) of the underlying Poisson process. We demonstrate how to apply coupling from the past to generate samples from this distribution, and use the samples thus obtained to approximate the maximum likelihood estimator of the intensity. We discuss and compare two methods: one based on a Monte Carlo approximation of the likelihood function, the other a stochastic version of the EM algorithm.