37 research outputs found

    Searching for patterns in Conway's Game of Life

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    Conway’s Game of Life (Life) is a simple cellular automaton, discovered by John Conway in 1970, that exhibits complex emergent behavior. Life-enthusiasts have been looking for building blocks with specific properties (patterns) to answer unsolved problems in Life for the past five decades. Finding patterns in Life is difficult due to the large search space. Current search algorithms use an explorative approach based on the rules of the game, but this can only sample a small fraction of the search space. More recently, people have used Sat solvers to search for patterns. These solvers are not specifically tuned to this problem and thus waste a lot of time processing Life’s rules in an engine that does not understand them. We propose a novel Sat-based approach that replaces the binary tree used by traditional Sat solvers with a grid-based approach, complemented by an injection of Game of Life specific knowledge. This leads to a significant speedup in searching. As a fortunate side effect, our solver can be generalized to solve general Sat problems. Because it is grid-based, all manipulations are embarrassingly parallel, allowing implementation on massively parallel hardware

    Structure-function analysis of the nsp14 N7-guanine methyltransferase reveals an essential role in Betacoronavirus replication.

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    As coronaviruses (CoVs) replicate in the host cell cytoplasm, they rely on their own capping machinery to ensure the efficient translation of their messenger RNAs (mRNAs), protect them from degradation by cellular 5' exoribonucleases (ExoNs), and escape innate immune sensing. The CoV nonstructural protein 14 (nsp14) is a bifunctional replicase subunit harboring an N-terminal 3'-to-5' ExoN domain and a C-terminal (N7-guanine)-methyltransferase (N7-MTase) domain that is presumably involved in viral mRNA capping. Here, we aimed to integrate structural, biochemical, and virological data to assess the importance of conserved N7-MTase residues for nsp14's enzymatic activities and virus viability. We revisited the crystal structure of severe acute respiratory syndrome (SARS)-CoV nsp14 to perform an in silico comparative analysis between betacoronaviruses. We identified several residues likely involved in the formation of the N7-MTase catalytic pocket, which presents a fold distinct from the Rossmann fold observed in most known MTases. Next, for SARS-CoV and Middle East respiratory syndrome CoV, site-directed mutagenesis of selected residues was used to assess their importance for in vitro enzymatic activity. Most of the engineered mutations abolished N7-MTase activity, while not affecting nsp14-ExoN activity. Upon reverse engineering of these mutations into different betacoronavirus genomes, we identified two substitutions (R310A and F426A in SARS-CoV nsp14) abrogating virus viability and one mutation (H424A) yielding a crippled phenotype across all viruses tested. Our results identify the N7-MTase as a critical enzyme for betacoronavirus replication and define key residues of its catalytic pocket that can be targeted to design inhibitors with a potential pan-coronaviral activity spectrum

    Onderzoek ten behoeve van het herstel en beheer van Nederlandse laagveenwateren; eindrapportage 2003-2006

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    Dit rapport presenteert de resultaten en conclusies van het onderzoek aan laagveenwateren binnen het kader van het Overlevingsplan Bos en Natuur in de eerste fase (obn, 2003-2006). In Hoofdstuk 3 wordt een overzicht gegeven van de onderzoekslocaties. Vervolgens worden in Hoofdstuk 4 de belangrijkste bevindingen van het correlatieve onderzoek naar de samenhang tusen biodiversiteit en milieukwaliteit gepresenteerd, met in Hoofdstuk 5 de rol van hydrologie in het laagveenlandschap. In de daaropvolgende hoofdstukken 6 tot en met 10 staan de onderzoeksvragen, methoden, resultaten en conclusies van de verschillende deelonderzoeken weergegeven met betrekking tot visstandsbeheer (Hoofdstuk 6), water- en veenkwaliteit (Hoofdstuk 7), verlanding en veenvorming (Hoofdstuk 8), voedselwebrelaties (Hoofdstuk 9) en fauna (Hoofdstuk 10). Ten slotte worden in Hoofdstuk 11 de belangrijkste conclusies van het onderzoek in de eerste fase samengebracht en bediscussieerd, in relatie tot de directe betekenis voor het laagveenbeheer. Dit zal uitgewerkt worden aan de hand van de nieuw gegenereerde kennis en bestaande literatuur over de betreffende milieuproblemen (‘ver’-thema’s), en de voor- en nadelen van beschikbare OBN-maatregelen. Als afsluiting wordt aan de hand van de resultaten in fase 1 aangegeven welke onderzoeksvragen geprioriteerd zijn voor de tweede fas

    Pdf- Bulletin of Indonesian Economic Studies Vol. 45, No. 3, 2009 : Conference Report : INDONESIA UPDATE 2009 DEMOCRACY IN PRACTICE: CAMPAIGNS, PARTIES AND PARLIAMENTS

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    The annual Indonesia Update Conference, now in its 27th year, was held at the Australian National University on 9–10 October 2009. It attracted an audience of well over 300 people from academia, government, non-government organisations and business. The conference was convened by Edward Aspinall and Marcus Mietzner of the ANU and featured speakers and discussants from Australia, Indonesia and the US. As the conference theme suggests, 2009 was ‘the year of voting frequently’ for Indonesia, with elections for parliaments and heads of government at all levels, culminating in President Susilo Bambang Yudhoyono’s re-election in Jul

    Onderzoek ten behoeve van het herstel en beheer van Nederlandse laagveenwateren. Tussentijdse OBN-rapportage (eerste onderzoeksjaar), maart 2004

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    Contains fulltext : 58864.pdf (publisher's version ) (Open Access)104 p

    Grazing on colonial and filamentous, toxic and non-toxic cyanobacteria by the zebra mussel Dreissena polymorpha

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    Colony forming and toxic cyanobacteria form a problem in surface waters of shallow lakes, both for recreation and wildlife. Zebra mussels, Dreissena polymorpha, have been employed to help to restore shallow lakes in the Netherlands, dominated by cyanobacteria, to their former clear state. Zebra mussels have been present in these lakes since they were created in the 19th century by the excavation of peat and are usually not considered to be an invasive species. Most grazing experiments using Dreissena have been performed with uni-cellular phytoplankton laboratory strains and information on grazing of larger phytoplankton taxa hardly exists. To gain more insight in to whether D. polymorpha is indeed able to decrease cyanobacteria in the phytoplankton, we therefore performed grazing experiments with zebra mussels and two species of cyanobacteria, that greatly differ in shape: colony forming strains of Microcystis aeruginosa and the filamentous species Planktothrix agardhii. For both species a toxic and a non-toxic strain was selected. We found that zebra mussels cleared toxic Planktothrix at a higher rate than non-toxic Planktothrix, toxic or non-toxic Microcystis. Clearance rates between the other strains were not significantly different. Both phytoplankton species, regardless of toxicity, size and shape, were found in equal amounts (based on chlorophyll concentrations) in the excreted products of the mussels (pseudofaeces). The results show that zebra mussels are capable of removing colonial and filamentous cyanobacteria from the water, regardless of whether the cyanobacteria are toxic or not. This implies that the mussels may be used as a biofilter for the removal of harmful cyanobacterial blooms in shallow (Dutch) lakes where the mussels are already present and not a nuisance. Providing more suitable substrate for zebra mussel attachment may lead to appropriate mussel densities capable of filtering large quantities of cyanobacteria.
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