TY - JOUR A1 - Risbey, James S. A1 - Lewandowsky, Stephan A1 - Cowtan, Kevin A1 - Oreskes, Naomi A1 - Rahmstorf, Stefan A1 - Jokimäki, Ari A1 - Foster, Grant T1 - A fluctuation in surface temperature in historical context BT - reassessment and retrospective on the evidence JF - Environmental research letters N2 - This work reviews the literature on an alleged global warming 'pause' in global mean surface temperature (GMST) to determine how it has been defined, what time intervals are used to characterise it, what data are used to measure it, and what methods used to assess it. We test for 'pauses', both in the normally understood meaning of the term to mean no warming trend, as well as for a 'pause' defined as a substantially slower trend in GMST. The tests are carried out with the historical versions of GMST that existed for each pause-interval tested, and with current versions of each of the GMST datasets. The tests are conducted following the common (but questionable) practice of breaking the linear fit at the start of the trend interval ('broken' trends), and also with trends that are continuous with the data bordering the trend interval. We also compare results when appropriate allowance is made for the selection bias problem. The results show that there is little or no statistical evidence for a lack of trend or slower trend in GMST using either the historical data or the current data. The perception that there was a 'pause' in GMST was bolstered by earlier biases in the data in combination with incomplete statistical testing. KW - climate variability KW - climate trends KW - temperature fluctuation KW - pause hiatus Y1 - 2018 U6 - https://doi.org/10.1088/1748-9326/aaf342 SN - 1748-9326 VL - 13 IS - 12 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Langenhan, Jennifer A1 - Jaeger, Carsten A1 - Baum, Katharina A1 - Simon, Mareike A1 - Lisec, Jan T1 - A flexible tool to correct superimposed mass isotopologue distributions in GC-APCI-MS flux experiments JF - Metabolites N2 - The investigation of metabolic fluxes and metabolite distributions within cells by means of tracer molecules is a valuable tool to unravel the complexity of biological systems. Technological advances in mass spectrometry (MS) technology such as atmospheric pressure chemical ionization (APCI) coupled with high resolution (HR), not only allows for highly sensitive analyses but also broadens the usefulness of tracer-based experiments, as interesting signals can be annotated de novo when not yet present in a compound library. However, several effects in the APCI ion source, i.e., fragmentation and rearrangement, lead to superimposed mass isotopologue distributions (MID) within the mass spectra, which need to be corrected during data evaluation as they will impair enrichment calculation otherwise. Here, we present and evaluate a novel software tool to automatically perform such corrections. We discuss the different effects, explain the implemented algorithm, and show its application on several experimental datasets. This adjustable tool is available as an R package from CRAN. KW - mass isotopologue distribution KW - enrichment calculation KW - flux KW - experiments KW - atmospheric pressure chemical ionization KW - R package KW - CorMID Y1 - 2022 U6 - https://doi.org/10.3390/metabo12050408 SN - 2218-1989 VL - 12 IS - 5 PB - MDPI CY - Basel ER - TY - JOUR A1 - Xiao, Shangbin A1 - Liu, Liu A1 - Wang, Wei A1 - Lorke, Andreas A1 - Woodhouse, Jason Nicholas A1 - Grossart, Hans-Peter T1 - A Fast-Response Automated Gas Equilibrator (FaRAGE) for continuous in situ measurement of CH4 and CO2 dissolved in water JF - Hydrology and earth system sciences : HESS N2 - Biogenic greenhouse gas emissions, e.g., of methane (CH4) and carbon dioxide (CO2) from inland waters, contribute substantially to global warming. In aquatic systems, dissolved greenhouse gases are highly heterogeneous in both space and time. To better understand the biological and physical processes that affect sources and sinks of both CH4 and CO2, their dissolved concentrations need to be measured with high spatial and temporal resolution. To achieve this goal, we developed the Fast-Response Automated Gas Equilibrator (FaRAGE) for real-time in situ measurement of dissolved CH4 and CO2 concentrations at the water surface and in the water column. FaRAGE can achieve an exceptionally short response time (t(95%) = 12 s when including the response time of the gas analyzer) while retaining an equilibration ratio of 62.6% and a measurement accuracy of 0.5% for CH4. A similar performance was observed for dissolved CO2 (t(95%) = 10 s, equilibration ratio 67.1 %). An equilibration ratio as high as 91.8% can be reached at the cost of a slightly increased response time (16 s). The FaRAGE is capable of continuously measuring dissolved CO2 and CH4 concentrations in the nM-to-submM (10(-9)-10(-3) mol L-1) range with a detection limit of subnM (10(-10) mol L-1), when coupling with a cavity ring-down greenhouse gas analyzer (Picarro GasScouter). FaRAGE allows for the possibility of mapping dissolved concentration in a "quasi" three-dimensional manner in lakes and provides an inexpensive alternative to other commercial gas equilibrators. It is simple to operate and suitable for continuous monitoring with a strong tolerance for suspended particles. While the FaRAGE is developed for inland waters, it can be also applied to ocean waters by tuning the gas-water mixing ratio. The FaRAGE is easily adapted to suit other gas analyzers expanding the range of potential applications, including nitrous oxide and isotopic composition of the gases. Y1 - 2020 U6 - https://doi.org/10.5194/hess-24-3871-2020 SN - 1027-5606 SN - 1607-7938 VL - 24 IS - 7 SP - 3871 EP - 3880 PB - European Geosciences Union (EGU) ; Copernicus CY - Munich ER - TY - JOUR A1 - Demal, Till Joscha A1 - Heise, Melina A1 - Reiz, Benedikt A1 - Dogra, Deepika A1 - Braenne, Ingrid A1 - Reichenspurner, Hermann A1 - Männer, Jörg A1 - Aherrahrou, Zouhair A1 - Schunkert, Heribert A1 - Erdmann, Jeanette A1 - Abdelilah-Seyfried, Salim T1 - A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A JF - Scientific reports N2 - The genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329.2:c.1328 G > A (p.R443H)] which encodes a predicted deleterious variant of BMPR1A. This mutation co-segregates with a linkage region on chromosome 1 that associates with the emergence of severe CHDs including Ebstein’s anomaly, atrioventricular septal defect, and others. We show that the continuous overexpression of the zebrafish homologous mutation bmpr1aap.R438H within endocardium causes a reduced AV valve area, a downregulation of Wnt/ß-catenin signalling at the AV canal, and growth of additional tissue mass in adult zebrafish hearts. This finding opens the possibility of testing genetic interactions between BMPR1A and other candidate genes within linkage region 1 which may provide a first step towards unravelling more complex genetic patterns in cardiovascular disease aetiology. Y1 - 2019 U6 - https://doi.org/10.1038/s41598-019-39648-7 SN - 2045-2322 VL - 9 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Ette, Ottmar T1 - A expulsão do Éden BT - Migração e escrita depois do paraíso JF - Literatura e autoritarismo N2 - A temática da migração está intimamente vinculada à história humana, desde a narrativa bíblica da expulsão do paraíso. O ser humano não apenas empregou técnicas cada vez mais sofisticadas para a violência, como também transmitiu, através dos séculos, técnicas de conservação e uso de seu saberconviver. Nesse sentido móvel da história, e em consonância com as literaturas do mundo, a partir de suas diversas origens, é possível dizer que existe um “Homo migrans” desde que existe o “Homo sapiens”. Assim, é possível afirmar que as ideias territoriais ou territorializantes com proveniência histórico-espacial permitem, vez ou outra, reconhecer seus esforços para filtrar e isolar a dimensão histórico-móvel e vetorial da história como narrativa, para tentar construir, com a ajuda de ideias estáticas, novos lugares da promessa ou da perda, da abundância ou da queda. KW - Migração KW - Saberconviver KW - Literaturas do mundo Y1 - 2021 U6 - https://doi.org/10.5902/1679849X65745 SN - 1679-849X IS - 25 SP - 5 EP - 42 PB - Universidade Federal de Santa Maria (UFSM) CY - Santa Maria ER - TY - JOUR A1 - Brill, Fabio Alexander A1 - Passuni Pineda, Silvia A1 - Espichan Cuya, Bruno A1 - Kreibich, Heidi T1 - A data-mining approach towards damage modelling for El Nino events in Peru JF - Geomatics, natural hazards and risk N2 - Compound natural hazards likeEl Ninoevents cause high damage to society, which to manage requires reliable risk assessments. Damage modelling is a prerequisite for quantitative risk estimations, yet many procedures still rely on expert knowledge, and empirical studies investigating damage from compound natural hazards hardly exist. A nationwide building survey in Peru after theEl Ninoevent 2017 - which caused intense rainfall, ponding water, flash floods and landslides - enables us to apply data-mining methods for statistical groundwork, using explanatory features generated from remote sensing products and open data. We separate regions of different dominant characteristics through unsupervised clustering, and investigate feature importance rankings for classifying damage via supervised machine learning. Besides the expected effect of precipitation, the classification algorithms select the topographic wetness index as most important feature, especially in low elevation areas. The slope length and steepness factor ranks high for mountains and canyons. Partial dependence plots further hint at amplified vulnerability in rural areas. An example of an empirical damage probability map, developed with a random forest model, is provided to demonstrate the technical feasibility. KW - Natural hazard KW - damage model KW - residential buildings KW - data-mining KW - remote KW - sensing KW - open data Y1 - 2020 U6 - https://doi.org/10.1080/19475705.2020.1818636 SN - 1947-5705 SN - 1947-5713 VL - 11 IS - 1 SP - 1966 EP - 1990 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - RPRT A1 - Hajos, Yael T1 - A Critical Overview of the Public Health Emergency of International Concern Mechanism BT - The Case of Covid-19 T2 - Staat, Recht und Politik – Forschungs- und Diskussionspapiere T2 - State, Law, and Politics — Research and Discussion Papers N2 - The last years have been affected by Covid-19 and the international emergency mecha-nism to deal with health-related threats. The effects of this period manifested differ-ently worldwide, depending on matters such as international relations, national policies, power dynamics etc. Additionally, the impact of this time will likely have long-term effects which are yet to be known. This paper gives a critical overview of the Public Health Emergency of International Concern (PHEIC) mechanism in the context of Covid-19. It does so by explaining the legal framework for states of emergency, specifically in the context of a PHEIC, while considering its restrictions and limitations on human rights. It further outlines issues in the manifestation of global protections and limitations on human rights during Covid-19. Lastly, considering the likelihood of future PHEICs and the known systemic obstructions, this paper offers ways to im-prove this mechanism from a holistic, non-zero-sum perspective. N2 - Die letzten Jahre waren geprägt von Covid-19 und dem internationalen Notfallmecha-nismus zur Bewältigung gesundheitsbe-zogener Bedrohungen. Die Auswirkungen dieser Zeit zeigten sich weltweit unter-schiedlich, abhängig von den internatio-nalen Beziehungen, der nationalen Politik, der Machtdynamik usw. Außerdem werden die Auswirkungen dieser Zeit wahrschein-lich langfristige, heute noch unbekannte Folgen haben. Diese Studie gibt einen kriti-schen Überblick über den Mechanismus für internationale gesundheitliche Notfälle (Public Health Emergency of International Concern – PHEIC) im Kontext von Covid-19. Zu diesem Zweck wird der rechtliche Rahmen für Notfälle, insbesondere im Zusammenhang mit PHEIC, erläutert, und es werden die damit verbundenen Ein-schränkungen und Begrenzungen der Menschenrechte betrachtet. In Anbetracht der Wahrscheinlichkeit künftiger PHEICs und der bekannten systemischen Hin-dernisse bietet dieses Papier schließlich Möglichkeiten zur Verbesserung dieses Mechanismus aus einer ganzheitlichen Per-spektive. T3 - Staat, Recht und Politik – Forschungs- und Diskussionspapiere = State, Law, and Politics - Research and Discussion Papers - 15 Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-585238 SN - 2509-6974 IS - 15 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - RPRT A1 - Baganz, Melissa A1 - de Teresa, Aurelia Gómez A1 - Lingg, Rosana T. A1 - Montijo, Yuriditzi Pascacio T1 - A critical assessment on National Action Plans BT - Challenges and benefits for the promotion and protection of Human Rights T2 - Staat, Recht und Politik – Forschungs- und Diskussionspapiere T2 - State, Law, and Politics - Research and Discussion Papers N2 - National Action Plans (NAPs) have been increas-ingly adopted world-wide after the Vienna Dec-laration in 1993, where it was urged to consider the improvement and promotion of Human Rights. In this paper, we discuss their usefulness and success by analysing the challenges present-ed during NAP processes as well as the benefits this set of actions entails: The challenges for their implementation outweigh its actual benefits. Nevertheless, NAPs have great potential. Based on new research, we elaborate a set of recom-mendations for improving the design and imple-mentation of national action planning. In order to effectively bring NAP into practice, we consider it crucial to plan and analyse every state local circumstances in detail. The latter is important, since the implementation of a concrete set of actions is intended to directly transform and improve the local living conditions of the people. In a long-term perspective, we defend the benefit of NAP’s implementation for complying obliga-tions set up by HR treaties. N2 - Nationale Aktionspläne (NAP) werden seit der Wiener Erklärung von 1993, in der die Verbesse-rung und Förderung der Menschenrechte gefor-dert wird, weltweit zunehmend angenommen. In diesem Papier diskutieren wir ihren Nutzen und Erfolg, indem wir die Herausforderungen, die sich während der NAP-Prozesse ergeben, sowie die Vorteile, die dieses Maßnahmenpaket mit sich bringt, analysieren: Die Herausforderungen bei ihrer Umsetzung überwiegen die tatsächlichen Vorteile. Dennoch haben NAPs ein großes Poten-zial. Beruhend auf neueren Forschungen erarbei-ten wir eine Reihe von Empfehlungen zur Ver-besserung der Gestaltung und Umsetzung der nationalen Aktionsplanung. Um einen NAP effek-tiv in die Praxis umzusetzen, halten wir es für entscheidend, die lokalen Gegebenheiten jedes Staates im Detail zu planen und zu analysieren. Letzteres ist wichtig, da die Umsetzung eines konkreten Maßnahmenpakets die Lebensbedin-gungen der Menschen vor Ort direkt verändern und verbessern soll. Langfristig gesehen vertei-digen wir den Nutzen der Umsetzung des NAP für die Einhaltung der in den Menschenrechts-verträgen festgelegten Verpflichtungen. T3 - Staat, Recht und Politik – Forschungs- und Diskussionspapiere = State, Law, and Politics - Research and Discussion Papers - 13 Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-576797 SN - 2509-6974 IS - 13 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Maier, Corinna Sabrina A1 - Wiljes, Jana de A1 - Hartung, Niklas A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - A continued learning approach for model-informed precision dosing BT - Updating models in clinical practice JF - CPT: pharmacometrics & systems pharmacology N2 - Model-informed precision dosing (MIPD) is a quantitative dosing framework that combines prior knowledge on the drug-disease-patient system with patient data from therapeutic drug/ biomarker monitoring (TDM) to support individualized dosing in ongoing treatment. Structural models and prior parameter distributions used in MIPD approaches typically build on prior clinical trials that involve only a limited number of patients selected according to some exclusion/inclusion criteria. Compared to the prior clinical trial population, the patient population in clinical practice can be expected to also include altered behavior and/or increased interindividual variability, the extent of which, however, is typically unknown. Here, we address the question of how to adapt and refine models on the level of the model parameters to better reflect this real-world diversity. We propose an approach for continued learning across patients during MIPD using a sequential hierarchical Bayesian framework. The approach builds on two stages to separate the update of the individual patient parameters from updating the population parameters. Consequently, it enables continued learning across hospitals or study centers, because only summary patient data (on the level of model parameters) need to be shared, but no individual TDM data. We illustrate this continued learning approach with neutrophil-guided dosing of paclitaxel. The present study constitutes an important step toward building confidence in MIPD and eventually establishing MIPD increasingly in everyday therapeutic use. Y1 - 2021 U6 - https://doi.org/10.1002/psp4.12745 SN - 2163-8306 VL - 11 IS - 2 SP - 185 EP - 198 PB - London CY - Nature Publ. Group ER - TY - JOUR A1 - Wolff, Martin A1 - Gast, Klaus A1 - Evers, Andreas A1 - Kurz, Michael A1 - Pfeiffer-Marek, Stefania A1 - Schüler, Anja A1 - Seckler, Robert A1 - Thalhammer, Anja T1 - A Conserved Hydrophobic Moiety and Helix-Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4 JF - Biomolecules N2 - Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers. KW - biophysics KW - diabetes KW - peptides KW - oligomerization KW - conformational change KW - molecular modeling KW - static and dynamic light scattering KW - spectroscopy Y1 - 2021 U6 - https://doi.org/10.3390/biom11091305 SN - 2218-273X VL - 11 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Chapman, Eric M. A1 - Lant, Benjamin A1 - Ohashi, Yota A1 - Yu, Bin A1 - Schertzberg, Michael A1 - Go, Christopher A1 - Dogra, Deepika A1 - Koskimaki, Janne A1 - Girard, Romuald A1 - Li, Yan A1 - Fraser, Andrew G. A1 - Awad, Issam A. A1 - Abdelilah-Seyfried, Salim A1 - Gingras, Anne-Claude A1 - Derry, William Brent T1 - A conserved CCM complex promotes apoptosis non-autonomously by regulating zinc homeostasis JF - Nature Communications N2 - Apoptotic death of cells damaged by genotoxic stress requires regulatory input from surrounding tissues. The C. elegans scaffold protein KRI-1, ortholog of mammalian KRIT1/CCM1, permits DNA damage-induced apoptosis of cells in the germline by an unknown cell non-autonomous mechanism. We reveal that KRI-1 exists in a complex with CCM-2 in the intestine to negatively regulate the ERK-5/MAPK pathway. This allows the KLF-3 transcription factor to facilitate expression of the SLC39 zinc transporter gene zipt-2.3, which functions to sequester zinc in the intestine. Ablation of KRI-1 results in reduced zinc sequestration in the intestine, inhibition of IR-induced MPK-1/ERK1 activation, and apoptosis in the germline. Zinc localization is also perturbed in the vasculature of krit1(-/-) zebrafish, and SLC39 zinc transporters are mis-expressed in Cerebral Cavernous Malformations (CCM) patient tissues. This study provides new insights into the regulation of apoptosis by cross-tissue communication, and suggests a link between zinc localization and CCM disease. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-09829-z SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Stauffer, Maxime A1 - Mengesha, Isaak A1 - Seifert, Konrad A1 - Krawczuk, Igor A1 - Fischer, Jens A1 - Serugendo, Giovanna Di Marzo T1 - A computational turn in policy process studies BT - coevolving network dynamics of policy change JF - Complexity N2 - The past three decades of policy process studies have seen the emergence of a clear intellectual lineage with regard to complexity. Implicitly or explicitly, scholars have employed complexity theory to examine the intricate dynamics of collective action in political contexts. However, the methodological counterparts to complexity theory, such as computational methods, are rarely used and, even if they are, they are often detached from established policy process theory. Building on a critical review of the application of complexity theory to policy process studies, we present and implement a baseline model of policy processes using the logic of coevolving networks. Our model suggests that an actor's influence depends on their environment and on exogenous events facilitating dialogue and consensus-building. Our results validate previous opinion dynamics models and generate novel patterns. Our discussion provides ground for further research and outlines the path for the field to achieve a computational turn. Y1 - 2022 U6 - https://doi.org/10.1155/2022/8210732 SN - 1076-2787 SN - 1099-0526 VL - 2022 PB - Wiley-Hindawi CY - London ER - TY - JOUR A1 - Mota, Simon A1 - Leckelt, Marius A1 - Geukes, Katharina A1 - Nestler, Steffen A1 - Humberg, Sarah A1 - Schröder-Abe, Michela A1 - Schmukle, Stefan C. A1 - Back, Mitja D. T1 - A comprehensive examination of narcissists’ self-perceived and actual socioemotional cognition ability JF - Collabra: Psychology N2 - Narcissists are assumed to lack the motivation and ability to share and understand the mental states of others. Prior empirical research, however, has yielded inconclusive findings and has differed with respect to the specific aspects of narcissism and socioemotional cognition that have been examined. Here, we propose a differentiated facet approach that can be applied across research traditions and that distinguishes between facets of narcissism (agentic vs. antagonistic) on the one hand, and facets of socioemotional cognition ability (SECA; self-perceived vs. actual) on the other. Using five nonclinical samples in two studies (total N = 602), we investigated the effect of facets of grandiose narcissism on aspects of socioemotional cognition across measures of affective and cognitive empathy, Theory of Mind, and emotional intelligence, while also controlling for general reasoning ability. Across both studies, agentic facets of narcissism were found to be positively related to perceived SECA, whereas antagonistic facets of narcissism were found to be negatively related to perceived SECA. However, both narcissism facets were negatively related to actual SECA. Exploratory condition-based regression analyses further showed that agentic narcissists had a higher directed discrepancy between perceived and actual SECA: They self-enhanced their socio-emotional capacities. Implications of these results for the multifaceted theoretical understanding of the narcissism-SECA link are discussed. KW - narcissism KW - socioemotional cognition KW - self-perceived ability KW - actual ability KW - empathy KW - emotional intelligence KW - self-enhancement Y1 - 2018 U6 - https://doi.org/10.1525/collabra.174 SN - 2474-7394 VL - 5 IS - 1 PB - University of California Press CY - Oakland ER - TY - JOUR A1 - Macdonald, Elena A1 - Otero, Noelia A1 - Butler, Tim T1 - A comparison of long-term trends in observations and emission inventories of NOx JF - Atmospheric chemistry and physics / European Geosciences Union N2 - Air pollution is a pressing issue that is associated with adverse effects on human health, ecosystems, and climate. Despite many years of effort to improve air quality, nitrogen dioxide (NO2) limit values are still regularly exceeded in Europe, particularly in cities and along streets. This study explores how concentrations of nitrogen oxides (NOx = NO + NO2) in European urban areas have changed over the last decades and how this relates to changes in emissions. To do so, the incremental approach was used, comparing urban increments (i.e. urban background minus rural concentrations) to total emissions, and roadside increments (i.e. urban roadside concentrations minus urban background concentrations) to traffic emissions. In total, nine European cities were assessed. The study revealed that potentially confounding factors like the impact of urban pollution at rural monitoring sites through atmospheric transport are generally negligible for NOx. The approach proves therefore particularly useful for this pollutant. The estimated urban increments all showed downward trends, and for the majority of the cities the trends aligned well with the total emissions. However, it was found that factors like a very densely populated surrounding or local emission sources in the rural area such as shipping traffic on inland waterways restrict the application of the approach for some cities. The roadside increments showed an overall very diverse picture in their absolute values and trends and also in their relation to traffic emissions. This variability and the discrepancies between roadside increments and emissions could be attributed to a combination of local influencing factors at the street level and different aspects introducing inaccuracies to the trends of the emis-sion inventories used, including deficient emission factors. Applying the incremental approach was evaluated as useful for long-term pan-European studies, but at the same time it was found to be restricted to certain regions and cities due to data availability issues. The results also highlight that using emission inventories for the prediction of future health impacts and compliance with limit values needs to consider the distinct variability in the concentrations not only across but also within cities. Y1 - 2021 U6 - https://doi.org/10.5194/acp-21-4007-2021 SN - 1680-7316 SN - 1680-7324 VL - 21 IS - 5 SP - 4007 EP - 4023 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Zoccarato, Luca A1 - Sher, Daniel A1 - Miki, Takeshi A1 - Segre, Daniel A1 - Grossart, Hans-Peter T1 - A comparative whole-genome approach identifies bacterial traits for marine microbial interactions JF - Communications biology N2 - Luca Zoccarato, Daniel Sher et al. leverage publicly available bacterial genomes from marine and other environments to examine traits underlying microbial interactions. Their results provide a valuable resource to investigate clusters of functional and linked traits to better understand marine bacteria community assembly and dynamics. Microbial interactions shape the structure and function of microbial communities with profound consequences for biogeochemical cycles and ecosystem health. Yet, most interaction mechanisms are studied only in model systems and their prevalence is unknown. To systematically explore the functional and interaction potential of sequenced marine bacteria, we developed a trait-based approach, and applied it to 473 complete genomes (248 genera), representing a substantial fraction of marine microbial communities. We identified genome functional clusters (GFCs) which group bacterial taxa with common ecology and life history. Most GFCs revealed unique combinations of interaction traits, including the production of siderophores (10% of genomes), phytohormones (3-8%) and different B vitamins (57-70%). Specific GFCs, comprising Alpha- and Gammaproteobacteria, displayed more interaction traits than expected by chance, and are thus predicted to preferentially interact synergistically and/or antagonistically with bacteria and phytoplankton. Linked trait clusters (LTCs) identify traits that may have evolved to act together (e.g., secretion systems, nitrogen metabolism regulation and B vitamin transporters), providing testable hypotheses for complex mechanisms of microbial interactions. Our approach translates multidimensional genomic information into an atlas of marine bacteria and their putative functions, relevant for understanding the fundamental rules that govern community assembly and dynamics. Y1 - 2022 U6 - https://doi.org/10.1038/s42003-022-03184-4 SN - 2399-3642 VL - 5 IS - 1 PB - Springer Nature CY - Berlin ER - TY - JOUR A1 - Mbebi, Alain J. A1 - Breitler, Jean-Christophe A1 - Bordeaux, M'elanie A1 - Sulpice, Ronan A1 - McHale, Marcus A1 - Tong, Hao A1 - Toniutti, Lucile A1 - Castillo, Jonny Alonso A1 - Bertrand, Benoit A1 - Nikoloski, Zoran T1 - A comparative analysis of genomic and phenomic predictions of growth-related traits in 3-way coffee hybrids JF - G3: Genes, genomes, genetics N2 - Genomic prediction has revolutionized crop breeding despite remaining issues of transferability of models to unseen environmental conditions and environments. Usage of endophenotypes rather than genomic markers leads to the possibility of building phenomic prediction models that can account, in part, for this challenge. Here, we compare and contrast genomic prediction and phenomic prediction models for 3 growth-related traits, namely, leaf count, tree height, and trunk diameter, from 2 coffee 3-way hybrid populations exposed to a series of treatment-inducing environmental conditions. The models are based on 7 different statistical methods built with genomic markers and ChlF data used as predictors. This comparative analysis demonstrates that the best-performing phenomic prediction models show higher predictability than the best genomic prediction models for the considered traits and environments in the vast majority of comparisons within 3-way hybrid populations. In addition, we show that phenomic prediction models are transferrable between conditions but to a lower extent between populations and we conclude that chlorophyll a fluorescence data can serve as alternative predictors in statistical models of coffee hybrid performance. Future directions will explore their combination with other endophenotypes to further improve the prediction of growth-related traits for crops. KW - genomic prediction KW - phenomic prediction KW - 3-way coffee hybrids KW - chlorophyll a fluorescence KW - GenPred KW - Shared Data Resource Y1 - 2022 U6 - https://doi.org/10.1093/g3journal/jkac170 SN - 2160-1836 VL - 12 IS - 9 PB - Genetics Soc. of America CY - Pittsburgh, PA ER - TY - JOUR A1 - Baumgart, Lene A1 - Boos, Pauline A1 - Braunsmann, Katharina T1 - A circulatory loop BT - the reciprocal relationship of organizations, digitalization, and gender JF - Social inclusion N2 - In the digitalization debate, gender biases in digital technologies play a significant role because of their potential for social exclusion and inequality. It is therefore remarkable that organizations as drivers of digitalization and as places for social integration have been widely overlooked so far. Simultaneously, gender biases and digitalization have structurally immanent connections to organizations. Therefore, a look at the reciprocal relationship between organizations, digitalization, and gender is needed. The article provides answers to the question of whether and how organizations (re)produce, reinforce, or diminish gender‐specific inequalities during their digital transformations. On the one hand, gender inequalities emerge when organizations use post‐bureaucratic concepts through digitalization. On the other hand, gender inequalities are reproduced when organizations either program or implement digital technologies and fail to establish control structures that prevent gender biases. This article shows that digitalization can act as a catalyst for inequality‐producing mechanisms, but also has the potential to mitigate inequalities. We argue that organizations must be considered when discussing the potential of exclusion through digitalization. KW - digitalization KW - gender bias KW - gender inequalities KW - organizations Y1 - 2023 U6 - https://doi.org/10.17645/si.v11i4.7056 SN - 2183-2803 VL - 11 IS - 4 SP - 160 EP - 171 PB - Cogitatio Press CY - Lisbon ER - TY - JOUR A1 - Krebs, Simon K. A1 - Rakotoarinoro, Nathanael A1 - Stech, Marlitt A1 - Zemella, Anne A1 - Kubick, Stefan T1 - A CHO-based cell-free dual fluorescence reporter system for the straightforward assessment of amber suppression and scFv functionality JF - Frontiers in Bioengineering and Biotechnology N2 - Incorporation of noncanonical amino acids (ncAAs) with bioorthogonal reactive groups by amber suppression allows the generation of synthetic proteins with desired novel properties. Such modified molecules are in high demand for basic research and therapeutic applications such as cancer treatment and in vivo imaging. The positioning of the ncAA-responsive codon within the protein's coding sequence is critical in order to maintain protein function, achieve high yields of ncAA-containing protein, and allow effective conjugation. Cell-free ncAA incorporation is of particular interest due to the open nature of cell-free systems and their concurrent ease of manipulation. In this study, we report a straightforward workflow to inquire ncAA positions in regard to incorporation efficiency and protein functionality in a Chinese hamster ovary (CHO) cell-free system. As a model, the well-established orthogonal translation components Escherichia coli tyrosyl-tRNA synthetase (TyrRS) and tRNATyr(CUA) were used to site-specifically incorporate the ncAA p-azido-l-phenylalanine (AzF) in response to UAG codons. A total of seven ncAA sites within an anti-epidermal growth factor receptor (EGFR) single-chain variable fragment (scFv) N-terminally fused to the red fluorescent protein mRFP1 and C-terminally fused to the green fluorescent protein sfGFP were investigated for ncAA incorporation efficiency and impact on antigen binding. The characterized cell-free dual fluorescence reporter system allows screening for ncAA incorporation sites with high incorporation efficiency that maintain protein activity. It is parallelizable, scalable, and easy to operate. We propose that the established CHO-based cell-free dual fluorescence reporter system can be of particular interest for the development of antibody-drug conjugates (ADCs). KW - expanded genetic code KW - orthogonal system KW - noncanonical amino acid KW - unnatural amino acid KW - antibody KW - cell-free protein synthesis KW - mRFP1 KW - sfGFP Y1 - 2022 U6 - https://doi.org/10.3389/fbioe.2022.873906 SN - 2296-4185 VL - 10 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Haueis, Lisa A1 - Stech, Marlitt A1 - Kubick, Stefan T1 - A Cell-free Expression Pipeline for the Generation and Functional Characterization of Nanobodies JF - Frontiers in Bioengineering and Biotechnology N2 - Cell-free systems are well-established platforms for the rapid synthesis, screening, engineering and modification of all kinds of recombinant proteins ranging from membrane proteins to soluble proteins, enzymes and even toxins. Also within the antibody field the cell-free technology has gained considerable attention with respect to the clinical research pipeline including antibody discovery and production. Besides the classical full-length monoclonal antibodies (mAbs), so-called "nanobodies" (Nbs) have come into focus. A Nb is the smallest naturally-derived functional antibody fragment known and represents the variable domain (VHH, similar to 15 kDa) of a camelid heavy-chain-only antibody (HCAb). Based on their nanoscale and their special structure, Nbs display striking advantages concerning their production, but also their characteristics as binders, such as high stability, diversity, improved tissue penetration and reaching of cavity-like epitopes. The classical way to produce Nbs depends on the use of living cells as production host. Though cell-based production is well-established, it is still time-consuming, laborious and hardly amenable for high-throughput applications. Here, we present for the first time to our knowledge the synthesis of functional Nbs in a standardized mammalian cell-free system based on Chinese hamster ovary (CHO) cell lysates. Cell-free reactions were shown to be time-efficient and easy-to-handle allowing for the "on demand" synthesis of Nbs. Taken together, we complement available methods and demonstrate a promising new system for Nb selection and validation. KW - cell-free protein synthesis KW - In vitro transcription KW - translation KW - nanobody KW - VHH KW - camelid KW - CHO cell lysate Y1 - 2022 U6 - https://doi.org/10.3389/fbioe.2022.896763 SN - 2296-4185 VL - 10 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Christakoudi, Sofa A1 - Tsilidis, Konstantinos K. A1 - Muller, David C. A1 - Freisling, Heinz A1 - Weiderpass, Elisabete A1 - Overvad, Kim A1 - Söderberg, Stefan A1 - Häggström, Christel A1 - Pischon, Tobias A1 - Dahm, Christina C. A1 - Zhang, Jie A1 - Tjønneland, Anne A1 - Schulze, Matthias Bernd T1 - A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort JF - Scientific Reports N2 - Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring. KW - all-cause mortality KW - anthropometric measures KW - mass index KW - overweight KW - cancer KW - prediction KW - adiposity KW - size Y1 - 2020 VL - 10 IS - 1 PB - Springer Nature CY - Berlin ER -