888 research outputs found

    Stability of Intercelular Exchange of Biochemical Substances Affected by Variability of Environmental Parameters

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    Communication between cells is realized by exchange of biochemical substances. Due to internal organization of living systems and variability of external parameters, the exchange is heavily influenced by perturbations of various parameters at almost all stages of the process. Since communication is one of essential processes for functioning of living systems it is of interest to investigate conditions for its stability. Using previously developed simplified model of bacterial communication in a form of coupled difference logistic equations we investigate stability of exchange of signaling molecules under variability of internal and external parameters.Comment: 11 pages, 3 figure

    A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

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    Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

    Extension of Lorenz Unpredictability

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    It is found that Lorenz systems can be unidirectionally coupled such that the chaos expands from the drive system. This is true if the response system is not chaotic, but admits a global attractor, an equilibrium or a cycle. The extension of sensitivity and period-doubling cascade are theoretically proved, and the appearance of cyclic chaos as well as intermittency in interconnected Lorenz systems are demonstrated. A possible connection of our results with the global weather unpredictability is provided.Comment: 32 pages, 13 figure

    Renormalization Group Functional Equations

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    Functional conjugation methods are used to analyze the global structure of various renormalization group trajectories, and to gain insight into the interplay between continuous and discrete rescaling. With minimal assumptions, the methods produce continuous flows from step-scaling {\sigma} functions, and lead to exact functional relations for the local flow {\beta} functions, whose solutions may have novel, exotic features, including multiple branches. As a result, fixed points of {\sigma} are sometimes not true fixed points under continuous changes in scale, and zeroes of {\beta} do not necessarily signal fixed points of the flow, but instead may only indicate turning points of the trajectories.Comment: A physical model with a limit cycle added as section IV, along with reference

    Cryptographic requirements for chaotic secure communications

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    In recent years, a great amount of secure communications systems based on chaotic synchronization have been published. Most of the proposed schemes fail to explain a number of features of fundamental importance to all cryptosystems, such as key definition, characterization, and generation. As a consequence, the proposed ciphers are difficult to realize in practice with a reasonable degree of security. Likewise, they are seldom accompanied by a security analysis. Thus, it is hard for the reader to have a hint about their security. In this work we provide a set of guidelines that every new cryptosystems would benefit from adhering to. The proposed guidelines address these two main gaps, i.e., correct key management and security analysis, to help new cryptosystems be presented in a more rigorous cryptographic way. Also some recommendations are offered regarding some practical aspects of communications, such as channel noise, limited bandwith, and attenuation.Comment: 13 pages, 3 figure

    Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

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    The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

    On the density of periodic configurations in strongly irreducible subshifts

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    Let GG be a residually finite group and let AA be a finite set. We prove that if XAGX \subset A^G is a strongly irreducible subshift of finite type containing a periodic configuration then periodic configurations are dense in XX. The density of periodic configurations implies in particular that every injective endomorphism of XX is surjective and that the group of automorphisms of XX is residually finite. We also introduce a class of subshifts XAZX \subset A^\Z, including all strongly irreducible subshifts and all irreducible sofic subshifts, in which periodic configurations are dense

    Invariant varieties of periodic points for some higher dimensional integrable maps

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    By studying various rational integrable maps on C^d\mathbf{\hat C}^d with pp invariants, we show that periodic points form an invariant variety of dimension p\ge p for each period, in contrast to the case of nonintegrable maps in which they are isolated. We prove the theorem: {\it `If there is an invariant variety of periodic points of some period, there is no set of isolated periodic points of other period in the map.'}Comment: 24 page
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