173,789 research outputs found

    On homologous recombination in Aspergillus nidulans

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    This thesis deals with the molecular mechanisms that underlie homologous recombination in eukaryotes. Most molecular genetic studies on homologous recombination have been performed in budding yeast ( Saccharomyces cerevisiae ). However, it remains to be investigated to what extent the results obtained in this unicellular organism can be extrapolated to other eukaryotes. We therefore initiated a series of molecular genetic studies on homologous recombination in Aspergillus nidulans . This filamentous fungus is amenable to most molecular techniques and is phylogenetically closer to higher eukaryotes than S. cerevisiae ; A. nidulans may thus provide a powerful eukaryotic model system. We have examined meiotic and mitotic recombination events in the nii A- nia D genomic region of A. nidulans . The nii A and nia D genes encode nitrite and nitrate reductase respectively, and are both required for the utilization of nitrate as a nitrogen source.The nii A- nia D region was chosen after a preliminary genetic analysis of meiotic recombination, which suggested the presence of an initiation site for meiotic recombination nearby, possibly in the intergenic promoter region (chapter 2). Subsequently, we designed an assay to analyze the products of recombination in more detail. As parental strains for a series of two-point crosses, we constructed nii A and nia D mutant strains that differed by nonsense or missense mutations in the nii A and/or nia D gene and by a series of 11 silent point mutations. We analyzed recombinants selected on nitrate for the presence or absence of individual mutations to determine the position and endpoints of conversion tracts.We found evidence for an initiation site for meiotic recombination in the promoter region located between the nii A and the nia D gene. Such initiation sites have also been found in the promoter regions of several genes of S. cerevisiae. Conversion tracts with an average length of 1.5 kb extended from this site into the nii A gene, the nia D gene or both. Meiotic conversion tracts were continuous in almost all recombinants. Co-conversion of markers declined steeply with distance from the proposed initiation site. In crosses where one of the parents harbored an ectopic copy of the nii A- nia D region instead of the allelic copy, conversion tracts were similar in size and position to those observed in allelic crosses. Ectopic recombinants were detected at a significantly lower frequency. The majority of the allelic recombinants but not of the ectopic recombinants harbored a crossover within the nii A- nia D region (chapter 3).Some initial molecular genetic studies on meiotic recombination in a higher plant (maize) have recently been published. In chapter 4, we draw attention to an important similarity between meiotic recombination in fungi and maize, namely a 5' to 3' polarity of gene conversion in the loci analyzed. It is thus possible that maize, like A. nidulans and S. cerevisiae , has specific initiation sites for meiotic recombination at the 5' ends of its genes.We also examined mitotic recombination in a diploid A. nidulans strain with the same assay system (chapter 5). The observed patterns of mutations in the haploid derivatives of the mitotic recombinants suggest that the initiation site for meiotic recombination that we found in the nii A- nia D locus, does not function in mitotic recombination; furthermore, the patterns suggested that long heteroduplex tracts (> 8.4 kb) are formed during mitotic recombination, and that conversion occurs in patches within these tracts. Mitotic recombination differs in these respects from meiotic recombination in A. nidulans .</p

    Diagnostic reasoning and diagnostic error in medicine

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    Timmermans, D.R.M. [Promotor]Wal, G. van der [Promotor]Thijs, A. [Copromotor]Wagner, C. [Copromotor

    Introduction

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    Morina C, Thijs K. Introduction. In: Morina C, Thijs K, eds. Probing the Limits of Categorization. The Bystander in Holocaust History. Studies on War and Genocide. Vol 27. New York, NY: Berghahn Books; 2018: 1-14

    Measuring industry-science links through inventor-author relations: A profiling method

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    In this pilot study we examine the performance of text-based profiling in recovering a set of validated inventor-author links. In a first step we match patents and publications solely based on their similarity in content. Next, we compare inventor and author names on the highest ranked matches for the occurrence of name matches. Finally, we compare these candidate matches with the names listed in a validated set of inventor-author names. Our text-based profile methodology performs significantly better than a random matching of patents and publications, suggesting that text-based profiling is a valuable complementary tool to the name searches used in previous studies.innovation; industry-science links; text-based profiling;

    Hypercube LSH for Approximate near Neighbors

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    A celebrated technique for finding near neighbors for the angular distance involves using a set of random hyperplanes to partition the space into hash regions [Charikar, STOC 2002]. Experiments later showed that using a set of orthogonal hyperplanes, thereby partitioning the space into the Voronoi regions induced by a hypercube, leads to even better results [Terasawa and Tanaka, WADS 2007]. However, no theoretical explanation for this improvement was ever given, and it remained unclear how the resulting hypercube hash method scales in high dimensions. In this work, we provide explicit asymptotics for the collision probabilities when using hypercubes to partition the space. For instance, two near-orthogonal vectors are expected to collide with probability (1/pi)^d in dimension d, compared to (1/2)^d when using random hyperplanes. Vectors at angle pi/3 collide with probability (sqrt[3]/pi)^d, compared to (2/3)^d for random hyperplanes, and near-parallel vectors collide with similar asymptotic probabilities in both cases. For c-approximate nearest neighbor searching, this translates to a decrease in the exponent rho of locality-sensitive hashing (LSH) methods of a factor up to log2(pi) ~ 1.652 compared to hyperplane LSH. For c = 2, we obtain rho ~ 0.302 for hypercube LSH, improving upon the rho ~ 0.377 for hyperplane LSH. We further describe how to use hypercube LSH in practice, and we consider an example application in the area of lattice algorithms

    Probing the Limits of Categorization. The Bystander in Holocaust History

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    Morina C, Thijs K, eds. Probing the Limits of Categorization. The Bystander in Holocaust History. Studies on War and Genocide . Vol 27. New York, NY: Berghahn Books; 2018

    Epiloog: Lastige balans. Een politieke cultuurgeschiedenis van Duitsland sinds de jaren tachtig

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    Morina C. Epiloog: Lastige balans. Een politieke cultuurgeschiedenis van Duitsland sinds de jaren tachtig. In: Thijs K, ed. Duitsland 1918-1991. Twintig vensters op en bewogen eeuw. Amsterdam: Boom; 2020: 225-235
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