15 research outputs found

    Improvement and analysis of a pseudo random bit generator by means of cellular automata

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    In this paper, we implement a revised pseudo random bit generator based on a rule-90 cellular automaton. For this purpose, we introduce a sequence matrix H_N with the aim of calculating the pseudo random sequences of N bits employing the algorithm related to the automaton backward evolution. In addition, a multifractal structure of the matrix H_N is revealed and quantified according to the multifractal formalism. The latter analysis could help to disentangle what kind of automaton rule is used in the randomization process and therefore it could be useful in cryptanalysis. Moreover, the conditions are found under which this pseudo random generator passes all the statistical tests provided by the National Institute of Standards and Technology (NIST)Comment: 20 pages, 12 figure

    A Single Amino Acid Substitution, Found in Mammals with Low Susceptibility to Prion Diseases, Delays Propagation of Two Prion Strains in Highly Susceptible Transgenic Mouse Models

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    Specific variations in the amino acid sequence of prion protein (PrP) are key determinants of susceptibility to prion diseases. We previously showed that an amino acid substitution specific to canids confers resistance to prion diseases when expressed in mice and demonstrated its dominant-negative protective effect against a variety of infectious prion strains of different origins and characteristics. Here, we show that expression of this single amino acid change significantly increases survival time in transgenic mice expressing bank vole cellular prion protein (PrP C ), which is inherently prone to misfolding, following inoculation with two distinct prion strains (the CWD-vole strain and an atypical strain of spontaneous origin). This amino acid substitution hinders the propagation of both prion strains, even when expressed in the context of a PrP C uniquely susceptible to a wide range of prion isolates. Non-inoculated mice expressing this substitution experience spontaneous prion formation, but showing an increase in survival time comparable to that observed in mutant mice inoculated with the atypical strain. Our results underscore the importance of this PrP variant in the search for molecules with therapeutic potential against prion diseases

    Homozygous R136S mutation in PRNP gene causes inherited early onset prion disease

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    Altres ajuts: Fundació la Marató de TV3/201821-31Background: More than 40 pathogenic heterozygous PRNP mutations causing inherited prion diseases have been identified to date. Recessive inherited prion disease has not been described to date. Methods: We describe the clinical and neuropathological data of inherited early-onset prion disease caused by the rare PRNP homozygous mutation R136S. In vitro PrP propagation studies were performed using recombinant-adapted protein misfolding cyclic amplification technique. Brain material from two R136S homozygous patients was intracranially inoculated in TgMet129 and TgVal129 transgenic mice to assess the transmissibility of this rare inherited form of prion disease. Results: The index case presented symptoms of early-onset dementia beginning at the age of 49 and died at the age of 53. Neuropathological evaluation of the proband revealed abundant multicentric PrP plaques and Western blotting revealed a ~ 8 kDa protease-resistant, unglycosylated PrP fragment, consistent with a Gerstmann-Sträussler-Scheinker phenotype. Her youngest sibling suffered from progressive cognitive decline, motor impairment, and myoclonus with onset in her late 30s and died at the age of 48. Genetic analysis revealed the presence of the R136S mutation in homozygosis in the two affected subjects linked to homozygous methionine at codon 129. One sibling carrying the heterozygous R136S mutation, linked to homozygous methionine at codon 129, is still asymptomatic at the age of 74. The inoculation of human brain homogenates from our index case and an independent case from a Portuguese family with the same mutation in transgenic mice expressing human PrP and in vitro propagation of PrP studies failed to show disease transmissibility. Conclusion: In conclusion, biallelic R136S substitution is a rare variant that produces inherited early-onset human prion disease with a Gerstmann-Sträussler-Scheinker neuropathological and molecular signature. Even if the R136S variant is predicted to be "probably damaging", heterozygous carriers are protected, at least from an early onset providing evidence for a potentially recessive pattern of inheritance in human prion diseases

    Metaheuristic to Optimize Computational Convergence in Convection-Diffusion and Driven-Cavity Problems

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    This work presents an optimization proposal to better the computational convergence time in convection-diffusion and driven-cavity problems by applying a simulated annealing (SA) metaheuristic, obtaining optimal values in relaxation factors (RF) that optimize the problem convergence during its numerical execution. These relaxation factors are tested in numerical models to accelerate their computational convergence in a shorter time. The experimental results show that the relaxation factors obtained by the SA algorithm improve the computational time of the problem convergence regardless of user experience in the initial low-quality RF proposal

    Grid-Based Hybrid Genetic Approach to Relaxed Flexible Flow Shop with Sequence-Dependent Setup Times

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    In this paper, a hybrid genetic algorithm implemented in a grid environment to solve hard instances of the flexible flow shop scheduling problem with sequence-dependent setup times is introduced. The genetic algorithm takes advantage of the distributed computing power on the grid to apply a hybrid local search to each individual in the population and reach a near optimal solution in a reduced number of generations. Ant colony systems and simulated annealing are used to apply a combination of iterative and cooperative local searches, respectively. This algorithm is implemented using a master–slave scheme, where the master process distributes the population on the slave process and coordinates the communication on the computational grid elements. The experimental results point out that the proposed scheme obtains the upper bound in a broad set of test instances. Also, an efficiency analysis of the proposed algorithm indicates its competitive use of the computational resources of the grid

    Exploring the risks of a putative transmission of BSE to new species

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    The prion responsible for the Bovine Spongiform Encephalopathy (BSE) shows unique features when compared with other prions. One of these features is its ability to infect almost all experimentally tested animal models. In the paper published in The Journal of Neuroscience1 we describe a series of experiments directed toward elucidating which would be the in vivo behavior of BSE if it would infect dogs and rabbits, two alleged prion resistant species. Protein misfolding cyclic amplification (PMCA) was used to generate canidae and leporidae in vitro adapted BSE prions. A characterization of their in vivo pathobiological properties showed that BSE prions were capable not only of adapting to new species but they maintained, in the case of rabbits, their ability to infect transgenic mice expressing human PrP. The remarkable adaptation ability of certain prions implies that any new host species could lead to the emergence of new infectious agents with unpredictable transmission potential. Our results suggest that caution must be taken when considering the use of any mammal-derived protein in feedstuffs. © 2013 Landes Bioscience

    Grid-Based Hybrid Genetic Approach to Relaxed Flexible Flow Shop with Sequence-Dependent Setup Times

    No full text
    In this paper, a hybrid genetic algorithm implemented in a grid environment to solve hard instances of the flexible flow shop scheduling problem with sequence-dependent setup times is introduced. The genetic algorithm takes advantage of the distributed computing power on the grid to apply a hybrid local search to each individual in the population and reach a near optimal solution in a reduced number of generations. Ant colony systems and simulated annealing are used to apply a combination of iterative and cooperative local searches, respectively. This algorithm is implemented using a master–slave scheme, where the master process distributes the population on the slave process and coordinates the communication on the computational grid elements. The experimental results point out that the proposed scheme obtains the upper bound in a broad set of test instances. Also, an efficiency analysis of the proposed algorithm indicates its competitive use of the computational resources of the grid
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