Modeling transcription factor binding events to DNA using a random walker/jumper representation on a 1D/2D lattice with different affinity sites

Surviving in a diverse environment requires corresponding organism responses. At the cellular level, such adjustment relies on the transcription factors (TFs) which must rapidly find their target sequences amidst a vast amount of non-relevant sequences on DNA molecules. Whether these transcription factors locate their target sites through a 1D or 3D pathway is still a matter of speculation. It has been suggested that the optimum search time is when the protein equally shares its search time between 1D and 3D diffusions. In this paper, we study the above problem using a Monte Carlo simulation by considering a very simple physical model. A 1D strip, representing a DNA, with a number of low affinity sites, corresponding to non-target sites, and high affinity sites, corresponding to target sites, is considered and later extended to a 2D strip. We study the 1D and 3D exploration pathways, and combinations of the two modes by considering three different types of molecules: a walker that randomly walks along the strip with no dissociation; a jumper that represents dissociation and then re-association of a TF with the strip at later time at a distant site; and a hopper that is similar to the jumper but it dissociates and then re-associates at a faster rate than the jumper. We analyze the final probability distribution of molecules for each case and find that TFs can locate their targets fast enough even if they spend 15% of their search time diffusing freely in the solution. This indeed agrees with recent experimental results obtained by Elf et al. 2007 and is in contrast with theoretical expectation.Comment: 24 pages, 9 figure

Selektion anbauwürdiger Saflor-Formen für den Ökologischen Landbau aus einem zweijährigen Screening-Experiment

Als alternative Ölpflanze mit hervorragender Speiseölqualität könnte Saflor für den ökologischen Landbau dort in Frage kommen, wo Raps und Sonnenblumen weniger hohe Erträge zu liefern imstande sind. In der vorliegenden Studie sollte die Anbauwürdigkeit des Saflors unter den Bedingungen des Ökologischen Landbaues mit einem Screening von 741 ausgewählten Formen dieser Art überprüft werden. Das Experiment fand 2002 an zwei Standorten statt. Eine hieraus getroffene Auswahl von 65 geeigneten Herkünften wurde 2003 in einer dreiortigen Leistungsprüfung weiter getestet. 2002 wurden sowohl bei morphologischen als auch agronomisch wichtigen Merkmalen große Unterschiede zwischen den Herkünften gefunden. Besonders in der Anfälligkeit für verschiedene Krankheiten zeigte das Material eine große Variabilität. Neben ertragslosen Formen konnten eine Reihe von Genotypen mit ausreichendem Kornansatz geerntet werden, die zusätzlich im Mittel einen Kernanteil bis zu 40% aufwiesen. Das weitergeprüfte Material zeigte 2003 eine mit den Daten aus 2002 gut übereinstimmende Krankheitsanfälligkeit. Es kann hieraus gefolgert werden, dass es bei Saflor anbauwürdige Formen gibt, die auch unter unseren eher humiden Klimabedingungen noch ausreichende Leistungen erbringen können

Validity of different algorithmic methods to identify hospital readmissions from routinely coded medical data.

BACKGROUND Hospital readmission rates are used for quality and pay-for-performance initiatives. To identify readmissions from administrative data, two commonly employed methods are focusing either on unplanned readmissions (used by the Centers for Medicare & Medicaid Services, CMS) or potentially avoidable readmissions (used by commercial vendors such as SQLape or 3 M). However, it is not known which of these methods has higher criterion validity and can more accurately identify actually avoidable readmissions. OBJECTIVES A manual record review based on data from seven hospitals was used to compare the validity of the methods by CMS and SQLape. METHODS Seven independent reviewers reviewed 738 single inpatient stays. The sensitivity, specificity, positive predictive value (PPV), and F1 score were examined to characterize the ability of an original CMS method, an adapted version of the CMS method, and the SQLape method to identify unplanned, potentially avoidable, and actually avoidable readmissions. RESULTS Both versions of the CMS method had greater sensitivity (92/86% vs. 62%) and a higher PPV (84/91% vs. 71%) than the SQLape method, in terms of identifying their outcomes of interest (unplanned vs. potentially avoidable readmissions, respectively). To distinguish actually avoidable readmissions, the two versions of the CMS method again displayed higher sensitivity (90/85% vs. 66%), although the PPV did not differ significantly between the different methods. CONCLUSIONS Thus, the CMS method has both higher criterion validity and greater sensitivity for identifying actually avoidable readmissions, compared with the SQLape method. Consequently, the CMS method should primarily be used for quality initiatives

The compendium of self-enactable techniques to change and self-manage motivation and behaviour v.1.0

Behaviour change techniques describe the content of behaviour change interventions, but do not adequately account for the actions that people must themselves undertake to successfully change or self-manage motivation or behaviour. This paper describes the development of a compendium of self-enactable techniques, combining behaviour- and motivation-regulation techniques across six existing classifications of behaviour change techniques and three scoping reviews. The compendium includes 123 techniques, each of which is labelled, defined and presented with instructive examples to facilitate self-enactment. Qualitative feedback was gathered from intervention developers and the general public to improve the utility, congruence and ease of self-enactability of the techniques. This integrative index of self-enactable techniques can assist intervention developers in selecting appropriate self-directed techniques to help people self-manage their motivation and behaviour. Future research with this compendium can expand on the number of behaviours covered by the instructive examples and link techniques with their potential impacts on factors that influence behaviours.Peer reviewe

Species mixing reduces drought susceptibility of Scots pine (Pinus sylvestris L.) and oak (Quercus robur L., Quercus petraea (Matt.) Liebl.) – Site water supply and fertility modify the mixing effect

Tree species mixing has been widely promoted as a promising silvicultural tool for reducing drought stress. However, so far only a limited number of species combinations have been studied in detail, revealing inconsistent results. In this study, we analysed the effect of mixing Scots pine and oak (pedunculate oak and sessile oak) trees on their drought response along a comprehensive ecological gradient across Europe. The objective was to improve our knowledge of general drought response patterns of two fundamental European tree species in mixed versus monospecific stands. We focused on three null hypotheses: () tree drought response does not differ between Scots pine and oak, () tree drought response of Scots pine and oak is not affected by stand composition (mixture versus monoculture) and () tree drought response of Scots pine and oak in mixtures and monocultures is not modified by tree size or site conditions. To test the hypotheses, we analysed increment cores of Scots pine and oak, sampled in mixed and monospecific stands, covering a wide range of site conditions. We investigated resistance (the ability to maintain growth levels during drought), recovery (the ability to restore a level of growth after drought) and resilience (the capacity to recover to pre-drought growth levels), involving site-specific drought events that occurred between 1976 and 2015. In monocultures, oak showed a higher resistance and resilience than Scots pine, while recovery was lower. Scots pine in mixed stands exhibited a higher resistance, but also a lower recovery compared with Scots pine in monocultures. Mixing increased the resistance and resilience of oak. Ecological factors such as tree size, site water supply and site fertility were found to have significant effects on the drought response. In the case of Scots pine, resistance was increased by tree size, while recovery was lowered. Resistance of oak increased with site water supply. The observed mixing effect on the tree drought response of Scots pine and oak was in some cases modified by the site conditions studied. Positive mixing effects in terms of resistance and resilience of oak increased with site water supply, while the opposite was found regarding recovery. In contrast, site fertility lessened the positive mixing effect on the resistance of Scots pine. We hypothesise that the observed positive mixing effects under drought mainly result from water- and/or light-related species interactions that improve resource availability and uptake according to temporal and spatial variations in environmental conditions.This work was supported by the European Union as part of the ERA-Net SUMFOREST project REFORM – Mixed species forest management. Lowering risk, increasing resilience (2816ERA02S, PCIN2017-026) and the Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 778322. All contributors thank their national funding institutions for supporting the establishment, mensuration and analysis of the studied triplets. The first author wants to thank the German Federal Ministry of Food and Agriculture (BMEL) for financial support through the Federal Office for Agriculture and Food (BLE) (grant number 2816ERA02S), as well as the Bayerische Staatsforsten (BaySF) and Landesbetrieb Forst Brandenburg for providing suitable research sites. Research on the Lithuanian triplets (LT 1, LT 2) was made possible by the national funding institution Research Council of Lithuania (LMTLT) (agreement number S-SUMFOREST-17-1). The French site FR 1 belongs to the OPTMix experimental site (https://optmix.irstea.fr), which is supported annually by Ecofor, Allenvi, and the French national research infrastructure ANAEE-F. A special thank is due to Peter Biber for supporting the statistical analysis

Earth System Model Evaluation Tool (ESMValTool) v2.0 - An extended set of large-scale diagnostics for quasi-operational and comprehensive evaluation of Earth system models in CMIP

The Earth System Model Evaluation Tool (ESMValTool) is a community diagnostics and performance metrics tool designed to improve comprehensive and routine evaluation of Earth system models (ESMs) participating in the Coupled Model Intercomparison Project (CMIP). It has undergone rapid development since the first release in 2016 and is now a well-tested tool that provides end-to-end provenance tracking to ensure reproducibility. It consists of (1) an easy-to-install, well-documented Python package providing the core functionalities (ESMValCore) that performs common preprocessing operations and (2) a diagnostic part that includes tailored diagnostics and performance metrics for specific scientific applications. Here we describe large-scale diagnostics of the second major release of the tool that supports the evaluation of ESMs participating in CMIP Phase 6 (CMIP6). ESMValTool v2.0 includes a large collection of diagnostics and performance metrics for atmospheric, oceanic, and terrestrial variables for the mean state, trends, and variability. ESMValTool v2.0 also successfully reproduces figures from the evaluation and projections chapters of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5) and incorporates updates from targeted analysis packages, such as the NCAR Climate Variability Diagnostics Package for the evaluation of modes of variability, the Thermodynamic Diagnostic Tool (TheDiaTo) to evaluate the energetics of the climate system, as well as parts of AutoAssess that contains a mix of top-down performance metrics. The tool has been fully integrated into the Earth System Grid Federation (ESGF) infrastructure at the Deutsches Klimarechenzentrum (DKRZ) to provide evaluation results from CMIP6 model simulations shortly after the output is published to the CMIP archive. A result browser has been implemented that enables advanced monitoring of the evaluation results by a broad user community at much faster timescales than what was possible in CMIP5