Methods comparison for detecting trends in herbicide monitoring time-series in streams

An inadvertent consequence of pesticide use is aquatic pesticide pollution, which has prompted the implementation of mitigation measures in many countries. Water quality monitoring programs are an important tool to evaluate the efficacy of these mitigation measures. However, large interannual variability of pesticide losses makes it challenging to detect significant improvements in water quality and to attribute these improvements to the application of specific mitigation measures. Thus, there is a gap in the literature that informs researchers and authorities regarding the number of years of aquatic pesticide monitoring or the effect size (e.g., loss reduction) that is required to detect significant trends in water quality. Our research addresses this issue by combining two exceptional empirical data sets with modelling to explore the relationships between the achieved pesticide reduction levels due to mitigation measures and the length of the observation period for establishing statistically significant trends. Our study includes both a large (Rhine at Basel, ∼36,300 km2) and small catchment (Eschibach, 1.2 km2), which represent spatial scales at either end of the spectrum that would be realistic for monitoring programs designed to assess water quality. Our results highlight several requirements in a monitoring program to allow for trend detection. Firstly, sufficient baseline monitoring is required before implementing mitigation measures. Secondly, the availability of pesticide use data helps account for the interannual variability and temporal trends, but such data are usually lacking. Finally, the timing and magnitude of hydrological events relative to pesticide application can obscure the observable effects of mitigation measures (especially in small catchments). Our results indicate that a strong reduction (i.e., 70–90 %) is needed to detect a change within 10 years of monitoring data. The trade-off in applying a more sensitive method for change detection is that it may be more prone to false-positives. Our results suggest that it is important to consider the trade-off between the sensitivity of trend detection and the risk of false positives when selecting an appropriate method and that applying more than one method can provide more confidence in trend detection

Simulation of the degradation of a concrete/clay interface:influence of temperature, unsaturated conditions and porosityvariations

For long-lived intermediate-level radioactive waste, the useof concrete as engineering barrier and Callovian-Oxfordian clay asgeological barrier at a depth of 500 m is considered in the Frenchdisposal concept (ANDRA, 2005). Upon emplacement, initially unsaturatedconcrete is expected to experience coupled processes involving heating,re-saturation with groundwater from the clay formation, gas exchanges andgeochemical reactions. After an early period of re-saturation, solutetransport is supposed to be diffusion-controlled because of the extremelylow permeability of the two media. These coupled processes may lead tochanges in the porosity of the concrete or clay barriers. In the presentpaper, a fully coupled Thermo-Hydro-Chemical (THC) response of atwo-phase (gas and solution) mass-transfer model was evaluated and testedby a sensitivity analysis. This study is an extension of a previous modelapplied to an isothermal and fully saturated concrete/clay interface(Burnol et al., 2005); it investigated the coupled effect of temperatureand unsaturated conditions assuming no production of H2(g). The systemwas simulated for a 2000-year period, which covers the most predominantthermal perturbation

Comparing FRACHEM and TOUGHREACT for reactive transport modelingof brine-rock interactions in enhanced geothermal systems (EGS)

Coupled modelling of fluid flow and reactive transport ingeothermal systems is challenging because of reservoir conditions such ashigh temperatures, elevated pressures and sometimes high salinities ofthe formation fluids. Thermal hydrological-chemical (THC) codes, such asFRACHEM and TOUGHREACT, have been developed to evaluate the long-termhydrothermal and chemical evolution of exploited reservoirs. In thisstudy, the two codes were applied to model the same geothermal reservoir,to forecast reservoir evolution using respective thermodynamic andkinetic input data. A recent (unreleased) TOUGHREACT version allows theuse of either an extended Debye-Hu?ckel or Pitzer activity model forcalculating activity coefficients, while FRACHEM was designed to use thePitzer formalism. Comparison of models results indicate that differencesin thermodynamic equilibrium constants, activity coefficients andkinetics models can result in significant differences in predictedmineral precipitation behaviour and reservoir-porosity evolution.Differences in the calculation schemes typically produce less differencein model outputs than differences in input thermodynamic and kineticdata, with model results being particularly sensitive to differences inion-interaction parameters for highsalinity systems

Can an Off-Nominal Landing by an MMRTG-Powered Spacecraft Induce a Special Region on Mars When No Ice Is Present?

This work aims at addressing whether a catastrophic failure of an entry, descent, and landing event of a Multimission Radioisotope Thermoelectric Generator-based lander could embed the heat sources into the martian subsurface and create a local environment that (1) would temporarily satisfy the conditions for a martian Special Region and (2) could establish a transport mechanism through which introduced terrestrial organisms could be mobilized to naturally occurring Special Regions elsewhere on Mars. Two models were run, a primary model by researchers at the Lawrence Berkeley National Laboratory and a secondary model by researchers at the Jet Propulsion Laboratory, both of which were based on selected starting conditions for various surface composition cases that establish the worst-case scenario, including geological data collected by the Mars Science Laboratory at Gale Crater. The summary outputs of both modeling efforts showed similar results: that the introduction of the modeled heat source could temporarily create the conditions established for a Special Region, but that there would be no transport mechanism by which an introduced terrestrial microbe, even if it was active during the temporarily induced Special Region conditions, could be transported to a naturally occurring Special Region of Mars

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo

This is the final published versionAvailable from Ivyspring International Publisher via the DOI in this recordInvasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy and bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [64Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus. To enable translation of the tracer to the clinical setting, we report here the development of a humanised version of the antibody (hJF5), and pre-clinical imaging of lung infection using a [64Cu]NODAGA-hJF5 tracer. The humanised antibody tracer shows a significant increase in in vivo biodistribution in A. fumigatus infected lungs compared to its radiolabeled murine counterpart [64Cu]NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds to the antigenic determinant 1,5-galactofuranose (Galf) present in a diagnostic mannoprotein antigen released by the pathogen during invasive growth in the lung. The absence of the epitope Galf in mammalian carbohydrates, coupled with the enhanced imaging capabilities of the hJF5 antibody, means that the [64Cu]NODAGA-hJF5 tracer developed here represents an ideal candidate for the diagnosis of IPA and translation to the clinical setting.This work was supported by the European Union Seventh Framework Programme FP7/2007-2013 under Grant 602820, the Deutsche Forschungsgemeinschaft (Grant WI3777/1-2 to SW), and the Werner Siemens Foundation. We thank Sven Krappman for use of the A. fumigatustdTomato strain, and acknowledge the Imaging Centre Essen (IMCES) for assistance with optical imaging of lungs

The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator

Mdc1 is a large modular phosphoprotein scaffold that maintains signaling and repair complexes at double-stranded DNA break sites. Mdc1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with the tail of γH2AX following DNA damage, but the role of the N-terminal forkhead-associated (FHA) domain remains unclear. We show that a major binding target of the Mdc1 FHA domain is a previously unidentified DNA damage and ATM-dependent phosphorylation site near the N-terminus of Mdc1 itself. Binding to this motif stabilizes a weak self-association of the FHA domain to form a tight dimer. X-ray structures of free and complexed Mdc1 FHA domain reveal a ‘head-to-tail' dimerization mechanism that is closely related to that seen in pre-activated forms of the Chk2 DNA damage kinase, and which both positively and negatively influences Mdc1 FHA domain-mediated interactions in human cells prior to and following DNA damag

The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM

The activation of ATR-ATRIP in response to double-stranded DNA breaks (DSBs) depends upon ATM in human cells and Xenopus egg extracts. One important aspect of this dependency involves regulation of TopBP1 by ATM. In Xenopus egg extracts, ATM associates with TopBP1 and thereupon phosphorylates it on S1131. This phosphorylation enhances the capacity of TopBP1 to activate the ATR-ATRIP complex. We show that TopBP1 also interacts with the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. This interaction involves the Nbs1 subunit of the complex. ATM can no longer interact with TopBP1 in Nbs1-depleted egg extracts, which suggests that the MRN complex helps to bridge ATM and TopBP1 together. The association between TopBP1 and Nbs1 involves the first pair of BRCT repeats in TopBP1. In addition, the two tandem BRCT repeats of Nbs1 are required for this binding. Functional studies with mutated forms of TopBP1 and Nbs1 suggested that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. These findings suggest that the MRN complex is a crucial mediator in the process whereby ATM promotes the TopBP1-dependent activation of ATR-ATRIP in response to DSBs