Evaluating the semantic web: a task-based approach

The increased availability of online knowledge has led to the design of several algorithms that solve a variety of tasks by harvesting the Semantic Web, i.e. by dynamically selecting and exploring a multitude of online ontologies. Our hypothesis is that the performance of such novel algorithms implicity provides an insight into the quality of the used ontologies and thus opens the way to a task-based evaluation of the Semantic Web. We have investigated this hypothesis by studying the lessons learnt about online ontologies when used to solve three tasks: ontology matching, folksonomy enrichment, and word sense disambiguation. Our analysis leads to a suit of conclusions about the status of the Semantic Web, which highlight a number of strengths and weaknesses of the semantic information available online and complement the findings of other analysis of the Semantic Web landscape

Politics versus Policies: Fourth Wave Feminist Critiques of Higher Education’s Response to Sexual Violence

This article uses the lens of fourth wave feminism to examine media accounts of institutional and student responses in two cases of sexual violence at institutions of higher education. Competing discourses reveal a disconnect between what institutions say they do and students’ actual experiences of the institutional handling of sexual violence cases. When policies, actions, and values are not fully aligned, institutions of higher education are unable to respond to societal and institutional injustices. Hence, recommendations for better alignment between institutional values and actions are proposed

DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3′-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5′-terminated strand of the DNA break and to inhibit 3′ to 5′ degradation by Dna2, actions that generate and protect the 3′-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes

Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery

An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks

The Ecm11-Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast

During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation

GAPS-megacities: A new global platform for investigating persistent organic pollutants and chemicals of emerging concern in urban air

A pilot study was initiated in 2018 under the Global Atmospheric Passive Sampling (GAPS) Network named GAPS-Megacities. This study included 20 megacities/major cities across the globe with the goal of better understanding and comparing ambient air levels of persistent organic pollutants and other chemicals of emerging concern, to which humans residing in large cities are exposed. The first results from the initial period of sampling are reported for 19 cities for several classes of flame retardants (FRs) including organophosphate esters (OPEs), polybrominated diphenyl ethers (PBDEs), and halogenated flame retardants (HFRs) including new flame retardants (NFRs), tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCDD). The two cities, New York (USA) and London (UK) stood out with ∼3.5 to 30 times higher total FR concentrations as compared to other major cities, with total concentrations of OPEs of 15,100 and 14,100 pg/m, respectively. Atmospheric concentrations of OPEs significantly dominated the FR profile at all sites, with total concentrations in air that were 2–5 orders of magnitude higher compared to other targeted chemical classes. A moderately strong and significant correlation (r = 0.625, p < 0.001) was observed for Gross Domestic Product index of the cities with total OPEs levels. Although large differences in FR levels were observed between some cities, when averaged across the five United Nations regions, the FR classes were more evenly distributed and varied by less than a factor of five. Results for Toronto, which is a ‘reference city’ for this study, agreed well with a more in-depth investigation of the level of FRs over different seasons and across eight sites representing different urban source sectors (e.g. traffic, industrial, residential and background). Future sampling periods under this project will investigate trace metals and other contaminant classes, linkages to toxicology, non-targeted analysis, and eventually temporal trends. The study provides a unique urban platform for evaluating global exposome.A global study across 20 megacities/major cities reporting urban air concentrations of flame retardants and plasticizers.Authors thank the United Nations Environment Programme (UNEP) and the Chemicals Management Plan (CMP) for financial support. The worldwide implementation of the Global Monitoring Plan is made possible thanks to the generous contributions to the Stockholm Convention Voluntary Trust Fund from the Governments of Japan, Norway, Sweden, and through the European Commission’s Thematic Programme for Environment andSustainable Management of Natural Resources, including Energy (ENRTP). Further, the contribution of the projects to support POPs monitoring activities in regions, funded through the Global Environment Facility (GEF) and the Strategic Approach to International Chemicals Management (SAICM), is greatly acknowledged. Monitoring activities and data collection and analysis are implemented in the five UN regions in cooperation with strategic partners and through the involvement of Regional Organization Groups and Global Coordination Group. We also thank Yasuyuki Shibata and Yoshikatsu Takazawa (Tokyo, Japan); Juan Mu~noz-Arnanz (Madrid, Spain) and Dilek €Ozkan and Sinan Kızıltug (_Istanbul, Turkey) for their help and assistance in the sampling campaign

Regulatory control of DNA end resection by Sae2 phosphorylation

DNA end resection plays a critical function in DNA double-strand break repair pathway choice. Resected DNA ends are refractory to end-joining mechanisms and are instead channeled to homology-directed repair. Using biochemical, genetic, and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity to promote the Mre11-Rad50-Xrs2 (MRX) nuclease to initiate resection of blocked DNA ends by at least two distinct mechanisms. First, DNA damage and cell cycle-dependent phosphorylation leads to Sae2 tetramerization. Second, and independently, phosphorylation of the conserved C-terminal domain of Sae2 is a prerequisite for its physical interaction with Rad50, which is also crucial to promote the MRX endonuclease. The lack of this interaction explains the phenotype of rad50S mutants defective in the processing of Spo11-bound DNA ends during meiotic recombination. Our results define how phosphorylation controls the initiation of DNA end resection and therefore the choice between the key DNA double-strand break repair mechanisms

Indistinguishable Landscapes of Meiotic DNA Breaks in rad50+ and rad50S Strains of Fission Yeast Revealed by a Novel rad50+ Recombination Intermediate

The fission yeast Schizosaccharomyces pombe Rec12 protein, the homolog of Spo11 in other organisms, initiates meiotic recombination by creating DNA double-strand breaks (DSBs) and becoming covalently linked to the DNA ends of the break. This protein–DNA linkage has previously been detected only in mutants such as rad50S in which break repair is impeded and DSBs accumulate. In the budding yeast Saccharomyces cerevisiae, the DSB distribution in a rad50S mutant is markedly different from that in wild-type (RAD50) meiosis, and it was suggested that this might also be true for other organisms. Here, we show that we can detect Rec12-DNA linkages in Sc. pombe rad50+ cells, which are proficient for DSB repair. In contrast to the results from Sa. cerevisiae, genome-wide microarray analysis of Rec12-DNA reveals indistinguishable meiotic DSB distributions in rad50+ and rad50S strains of Sc. pombe. These results confirm our earlier findings describing the occurrence of widely spaced DSBs primarily in large intergenic regions of DNA and demonstrate the relevance and usefulness of fission yeast studies employing rad50S. We propose that the differential behavior of rad50S strains reflects a major difference in DSB regulation between the two species—specifically, the requirement for the Rad50-containing complex for DSB formation in budding yeast but not in fission yeast. Use of rad50S and related mutations may be a useful method for DSB analysis in other species

High-resolution measurements of face-to-face contact patterns in a primary school

Little quantitative information is available on the mixing patterns of children in school environments. Describing and understanding contacts between children at school would help quantify the transmission opportunities of respiratory infections and identify situations within schools where the risk of transmission is higher. We report on measurements carried out in a French school (6-12 years children), where we collected data on the time-resolved face-to-face proximity of children and teachers using a proximity-sensing infrastructure based on radio frequency identification devices. Data on face-to-face interactions were collected on October 1st and 2nd, 2009. We recorded 77,602 contact events between 242 individuals. Each child has on average 323 contacts per day with 47 other children, leading to an average daily interaction time of 176 minutes. Most contacts are brief, but long contacts are also observed. Contacts occur mostly within each class, and each child spends on average three times more time in contact with classmates than with children of other classes. We describe the temporal evolution of the contact network and the trajectories followed by the children in the school, which constrain the contact patterns. We determine an exposure matrix aimed at informing mathematical models. This matrix exhibits a class and age structure which is very different from the homogeneous mixing hypothesis. The observed properties of the contact patterns between school children are relevant for modeling the propagation of diseases and for evaluating control measures. We discuss public health implications related to the management of schools in case of epidemics and pandemics. Our results can help define a prioritization of control measures based on preventive measures, case isolation, classes and school closures, that could reduce the disruption to education during epidemics