Dynamical attribution of oceanic prediction uncertainty in the North Atlantic: application to the design of optimal monitoring systems

In this study, the relation between two approaches to assess the ocean predictability on interannual to decadal time scales is investigated. The first pragmatic approach consists of sampling the initial condition uncertainty and assess the predictability through the divergence of this ensemble in time. The second approach is provided by a theoretical framework to determine error growth by estimating optimal linear growing modes. In this paper, it is shown that under the assumption of linearized dynamics and normal distributions of the uncertainty, the exact quantitative spread of ensemble can be determined from the theoretical framework. This spread is at least an order of magnitude less expensive to compute than the approximate solution given by the pragmatic approach. This result is applied to a state-of-the-art Ocean General Circulation Model to assess the predictability in the North Atlantic of four typical oceanic metrics: the strength of the Atlantic Meridional Overturning Circulation (AMOC), the intensity of its heat transport, the two-dimensional spatially-averaged Sea Surface Temperature (SST) over the North Atlantic, and the three-dimensional spatially-averaged temperature in the North Atlantic. For all tested metrics, except for SST

A new class of antibacterials, the imidazopyrazinones, reveal structural transitions involved in DNA gyrase poisoning and mechanisms of resistance

Imidazopyrazinones (IPYs) are a new class of compounds that target bacterial topoisomerases as a basis for their antibacterial activity. We have characterized the mechanism of these compounds through structural/mechanistic studies showing they bind and stabilize a cleavage complex between DNA gyrase and DNA (‘poisoning’) in an analogous fashion to fluoroquinolones, but without the requirement for the water–metal–ion bridge. Biochemical experiments and structural studies of cleavage complexes of IPYs compared with an uncleaved gyrase–DNA complex, reveal conformational transitions coupled to DNA cleavage at the DNA gate. These involve movement at the GyrA interface and tilting of the TOPRIM domains toward the scissile phosphate coupled to capture of the catalytic metal ion. Our experiments show that these structural transitions are involved generally in poisoning of gyrase by therapeutic compounds and resemble those undergone by the enzyme during its adenosine triphosphate-coupled strand-passage cycle. In addition to resistance mutations affecting residues that directly interact with the compounds, we characterized a mutant (D82N) that inhibits formation of the cleavage complex by the unpoisoned enzyme. The D82N mutant appears to act by stabilizing the binary conformation of DNA gyrase with uncleaved DNA without direct interaction with the compounds. This provides general insight into the resistance mechanisms to antibiotics targeting bacterial type II topoisomerases

Dynamical attribution of oceanic prediction uncertainty in the North Atlantic: application to the design of optimal monitoring systems

In this study, the relation between two approaches to assess the ocean predictability on interannual to decadal time scales is investigated. The first pragmatic approach consists of sampling the initial condition uncertainty and assess the predictability through the divergence of this ensemble in time. The second approach is provided by a theoretical framework to determine error growth by estimating optimal linear growing modes. In this paper, it is shown that under the assumption of linearized dynamics and normal distributions of the uncertainty, the exact quantitative spread of ensemble can be determined from the theoretical framework. This spread is at least an order of magnitude less expensive to compute than the approximate solution given by the pragmatic approach. This result is applied to a state-of-the-art Ocean General Circulation Model to assess the predictability in the North Atlantic of four typical oceanic metrics: the strength of the Atlantic Meridional Overturning Circulation (AMOC), the intensity of its heat transport, the two-dimensional spatially-averaged Sea Surface Temperature (SST) over the North Atlantic, and the three-dimensional spatially-averaged temperature in the North Atlantic. For all tested metrics, except for SST, (Formula presented.) 75% of the total uncertainty on interannual time scales can be attributed to oceanic initial condition uncertainty rather than atmospheric stochastic forcing. The theoretical method also provide the sensitivity pattern to the initial condition uncertainty, allowing for targeted measurements to improve the skill of the prediction. It is suggested that a relatively small fleet of several autonomous underwater vehicles can reduce the uncertainty in AMOC strength prediction by 70% for 1–5 years lead times

Membership duration in a Spanish Union : a survival analysis

This article presents an analysis of the characteristics that are associated with union membership duration using data from the membership registers of the largest Spanish trade union: Comisiones Obreras (CCOO, Workers' Commissions). Making use of survival analysis techniques, the results indicate that the shortest membership durations and the highest risks of leaving are associated with workers with poor employment conditions, mainly youth and foreigners, as well as those in firms, economic sectors, and territories where the union has a rather weak presence. As workers in these situations represent the majority of both current joining and leaving rates, the article concludes that retention policies should focus on the early stages of union membership

Thiophene antibacterials that allosterically stabilize DNA-cleavage complexes with DNA gyrase

A paucity of novel acting antibacterials is in development to treat the rising threat of antimicrobial resistance, particularly in Gram-negative hospital pathogens, which has led to renewed efforts in antibiotic drug discovery. Fluoroquinolones are broad-spectrum antibacterials that target DNA gyrase by stabilizing DNA-cleavage complexes, but their clinical utility has been compromised by resistance. We have identified a class of antibacterial thiophenes that target DNA gyrase with a unique mechanism of action and have activity against a range of bacterial pathogens, including strains resistant to fluoroquinolones. Although fluoroquinolones stabilize double-stranded DNA breaks, the antibacterial thiophenes stabilize gyrase-mediated DNA-cleavage complexes in either one DNA strand or both DNA strands. X-ray crystallography of DNA gyrase–DNA complexes shows the compounds binding to a protein pocket between the winged helix domain and topoisomerase-primase domain, remote from the DNA. Mutations of conserved residues around this pocket affect activity of the thiophene inhibitors, consistent with allosteric inhibition of DNA gyrase. This druggable pocket provides potentially complementary opportunities for targeting bacterial topoisomerases for antibiotic development

Interplay of DNA supercoiling and catenation during the segregation of sister duplexes

The discrete regulation of supercoiling, catenation and knotting by DNA topoisomerases is well documented both in vivo and in vitro, but the interplay between them is still poorly understood. Here we studied DNA catenanes of bacterial plasmids arising as a result of DNA replication in Escherichia coli cells whose topoisomerase IV activity was inhibited. We combined high-resolution two-dimensional agarose gel electrophoresis with numerical simulations in order to better understand the relationship between the negative supercoiling of DNA generated by DNA gyrase and the DNA interlinking resulting from replication of circular DNA molecules. We showed that in those replication intermediates formed in vivo, catenation and negative supercoiling compete with each other. In interlinked molecules with high catenation numbers negative supercoiling is greatly limited. However, when interlinking decreases, as required for the segregation of newly replicated sister duplexes, their negative supercoiling increases. This observation indicates that negative supercoiling plays an active role during progressive decatenation of newly replicated DNA molecules in vivo

Explaining Extreme Events of 2012 from a Climate Perspective

Attribution of extreme events is a challenging science and one that is currently undergoing considerable evolution. In this paper are 19 analyses by 18 different research groups, often using quite different methodologies, of 12 extreme events that occurred in 2012. In addition to investigating the causes of these extreme events, the multiple analyses of four of the events, the high temperatures in the United States, the record low levels of Arctic sea ice, and the heavy rain in northern Europe and eastern Australia, provide an opportunity to compare and contrast the strengths and weaknesses of the various methodologies. The differences also provide insights into the structural uncertainty of event attribution, that is, the uncertainty that arises directly from the differences in analysis methodology. In these cases, there was considerable agreement between the different assessments of the same event. However, different events had very different causes. Approximately half the analyses found some evidence that anthropogenically caused climate change was a contributing factor to the extreme event examined, though the effects of natural fluctuations of weather and climate on the evolution of many of the extreme events played key roles as well.Peer Reviewe

The extreme European summer 2012

The European summer of 2012 was marked by strongly contrasting rainfall anomalies, which led to flooding in northern Europe and droughts and wildfires in southern Europe. This season was not an isolated event, rather the latest in a string of summers characterized by a southward shifted Atlantic storm track as described by the negative phase of the SNAO. The degree of decadal variability in these features suggests a role for forcing from outside the dynamical atmosphere, and preliminary numerical experiments suggest that the global SST and low Arctic sea ice extent anomalies are likely to have played a role and that warm North Atlantic SSTs were a particular contributing factor. The direct effects of changes in radiative forcing from greenhouse gas and aerosol forcing are not included in these experiments, but both anthropogenic forcing and natural variability may have influenced the SST and sea ice changes