46 research outputs found

    Complexity of the Ruminococcus flavefaciens FD-1 cellulosome reflects an expansion of family-related protein-protein interactions

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    This work was supported in part by the European Union, Area NMP.2013.1.1–2: Self-assembly of naturally occurring nanosystems: CellulosomePlus Project number: 604530, and by the EU Seventh Framework Programme (FP7 2007–2013) under the WallTraC project (Grant Agreement no 263916), and BioStruct-X (grant agreement no 283570). This paper reflects the author’s views only. The European Community is not liable for any use that may be made of the information contained herein. CMGAF is also supported by Fundação para a Ciência e a Tecnologia (Lisbon, Portugal) through grants PTDC/BIA-PRO/103980/2008 and EXPL/BIA-MIC/1176/2012. EAB is also funded by a grant (No. 1349/13) from the Israel Science Foundation (ISF), Jerusalem, Israel and by a grant (No. 2013284) from the U.S.-Israel Binational Science Foundation (BSF). E.A.B. is the incumbent of The Maynard I. and Elaine Wishner Chair of Bio-organic Chemistry.Peer reviewedPublisher PD

    USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response

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    Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy

    An Infinite Automaton Characterization of Double Exponential Time

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    Infinite-state automata are a new invention: they are automata that have an infinite number of states represented by words, transitions defined using rewriting, and with sets of initial and final states. Infinite-state automata have gained recent interest due to a remarkable result by Morvan and Stirling, which shows that automata with transitions defined using rational rewriting precisely capture context-sensitive (NLinSpace) languages. In this paper, we show that infinite automata defined using a form of multi-stack rewriting precisely defines double exponential time (more precisely, 2ETime, the class of problems solvable in 22O(n) time). The salient aspect of this characterization is that the automata have no ostensible limits on time nor space, and neither direction of containment with respect to 2ETime is obvious. In this sense, the result captures the complexity class qualitatively, by restricting the power of rewriting

    An Algorithm for Searching a Polygonal Region with a Flashlight

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    We present an algorithm for a single pursuer with one ashlight that searches for an unpredictable, moving target with unbounded speed in a polygonal environment. The algorithm decides whether a simple polygon with n edges and m concave regions (m is typically much less than n, and always bounded by n) can be cleared by the pursuer, and if so, constructs a search schedule in time O(m 2 + m log n + n). The key ideas in this algorithm include a representation called the \visibility obstruction diagram" and its \skeleton," which is a combinatorial decomposition based on a number of critical visibility events. An implementation is presented along with a computed example. 1 Introduction Consider the following scenario: in a dark polygonal region there are two moving points. The rst one, called the pursuer, has the task to nd the second one, called the evader. The evader can move arbitrarily fast, and his movements are unpredictable by the pursuer. The pursuer is equipped with a..

    Pursuit-Evasion Using Beam Detection

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    We present an algorithm for searching a 2D environment for unpredictable moving targets using only beambased detection. One or more pursuers move along the environment boundary, and carry a rotating beam that detects evaders. The beam could correspond in practice to a laser or a camera. The task is to compute motions for pursuers and their beams that ensure that all evaders will be detected. For a 2D polygonal environment, we solve a long-standing open problem by presenting a complete O(n 3 )-time algorithm that is guaranteed to nd a successful motion strategy for a single pursuer and its beam, if a solution exists. This algorithm is extended to the case of coordinating multiple pursuers, but the number of pursuers used in a solution is not necessarily optimal. An implementation is presented, and several computed examples are shown. 1 Introduction In recent years there has been a rising interest in robotics and computational geometry in designing motion strategies for pursuit-evas..

    c ○ World Scientific Publishing Company Clearing a Polygon with Two 1-searchers ∗

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    We present an algorithm for a pair of pursuers, each with one flashlight, searching for an unpredictable, moving target in a 2D environment (simple polygon). Given a polygon with n edges and m concave regions, the algorithm decides in time O(n 2 + nm 2 + m 4) whether the polygon can be cleared by the two 1-searchers, and if so, constructs a search schedule. The pursuers are allowed to move on the boundary and in the interior of the polygon. They are not required to maintain mutual visibility throughout the pursuit

    CLEARING A POLYGON WITH TWO 1-SEARCHERS

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    An automata-theoretic approach to branching-time model checking

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    Translating linear temporal logic formulas to automata has proven to be an effective approach for implementing linear-time model-checking, and for obtaining many extensions and improvements to this verification method. On the other hand, for branching temporal logic, automate-theoretic techniques have long been thought to introduce an exponential penalty, making them essentially useless for model-checking. Recently, Bernholtz and Grumberg [1993] have shown that this exponential penalty can be avoided, though they did not match the linear complexity of non-automata-theoretic algorithms. In this paper, we show that alternating tree automata are the key to a comprehensive automata-theoretic framework for branching temporal logics. Not only can they be used to obtain optimal decision procedures, as was shown by Muller ct al., but, as we show here, they also make it possible to derive optimal model-checking algorithms. Moreover, the simple combinatorial structure that emerges from the automata-theoretic approach opens up new possibilities for the implementation of branching-time model checking, and has enabled us to derive improved space complexity bounds for this long-standing problem
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