Publications by authors named "Wolfgang Müller"

114 Publications

Implementing FAIR data management within the German Network for Bioinformatics Infrastructure (de.NBI) exemplified by selected use cases.

Brief Bioinform 2021 Feb 16. Epub 2021 Feb 16.

Ruhr University Bochum, Faculty of Medicine, Medizinisches Proteom-Center, Bochum, Germany.

This article describes some use case studies and self-assessments of FAIR status of de.NBI services to illustrate the challenges and requirements for the definition of the needs of adhering to the FAIR (findable, accessible, interoperable and reusable) data principles in a large distributed bioinformatics infrastructure. We address the challenge of heterogeneity of wet lab technologies, data, metadata, software, computational workflows and the levels of implementation and monitoring of FAIR principles within the different bioinformatics sub-disciplines joint in de.NBI. On the one hand, this broad service landscape and the excellent network of experts are a strong basis for the development of useful research data management plans. On the other hand, the large number of tools and techniques maintained by distributed teams renders FAIR compliance challenging.
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http://dx.doi.org/10.1093/bib/bbab010DOI Listing
February 2021

Use of a quantitative data report in a hypothetical decision scenario for health policymaking: a computer-assisted laboratory study.

BMC Med Inform Decis Mak 2021 01 28;21(1):32. Epub 2021 Jan 28.

Department of General Practice and Health Services Research, Heidelberg University Hospital, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.

Background: Quantitative data reports are widely produced to inform health policy decisions. Policymakers are expected to critically assess provided information in order to incorporate the best available evidence into the decision-making process. Many other factors are known to influence this process, but little is known about how quantitative data reports are actually read. We explored the reading behavior of (future) health policy decision-makers, using innovative methods.

Methods: We conducted a computer-assisted laboratory study, involving starting and advanced students in medicine and health sciences, and professionals as participants. They read a quantitative data report to inform a decision on the use of resources for long-term care in dementia in a hypothetical decision scenario. Data were collected through eye-tracking, questionnaires, and a brief interview. Eye-tracking data were used to generate 'heatmaps' and five measures of reading behavior. The questionnaires provided participants' perceptions of understandability and helpfulness as well as individual characteristics. Interviews documented reasons for attention to specific report sections. The quantitative analysis was largely descriptive, complemented by Pearson correlations. Interviews were analyzed by qualitative content analysis.

Results: In total, 46 individuals participated [students (85%), professionals (15%)]. Eye-tracking observations showed that the participants spent equal time and attention for most parts of the presented report, but were less focused when reading the methods section. The qualitative content analysis identified 29 reasons for attention to a report section related to four topics. Eye-tracking measures were largely unrelated to participants' perceptions of understandability and helpfulness of the report.

Conclusions: Eye-tracking data added information on reading behaviors that were not captured by questionnaires or interviews with health decision-makers.
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http://dx.doi.org/10.1186/s12911-021-01401-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845041PMC
January 2021

PEtab-Interoperable specification of parameter estimation problems in systems biology.

PLoS Comput Biol 2021 01 26;17(1):e1008646. Epub 2021 Jan 26.

Institute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been-so far-no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies.
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http://dx.doi.org/10.1371/journal.pcbi.1008646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864467PMC
January 2021

Early life of Neanderthals.

Proc Natl Acad Sci U S A 2020 11 2;117(46):28719-28726. Epub 2020 Nov 2.

Department of Cultural Heritage, University of Bologna, 48121 Ravenna, Italy;

The early onset of weaning in modern humans has been linked to the high nutritional demand of brain development that is intimately connected with infant physiology and growth rate. In Neanderthals, ontogenetic patterns in early life are still debated, with some studies suggesting an accelerated development and others indicating only subtle differences vs. modern humans. Here we report the onset of weaning and rates of enamel growth using an unprecedented sample set of three late (∼70 to 50 ka) Neanderthals and one Upper Paleolithic modern human from northeastern Italy via spatially resolved chemical/isotopic analyses and histomorphometry of deciduous teeth. Our results reveal that the modern human nursing strategy, with onset of weaning at 5 to 6 mo, was present among these Neanderthals. This evidence, combined with dental development akin to modern humans, highlights their similar metabolic constraints during early life and excludes late weaning as a factor contributing to Neanderthals' demise.
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http://dx.doi.org/10.1073/pnas.2011765117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682388PMC
November 2020

Tracing human mobility in central Europe during the Upper Paleolithic using sub-seasonally resolved Sr isotope records in ornaments.

Sci Rep 2020 06 25;10(1):10386. Epub 2020 Jun 25.

Department of Palaeontology and Geology, Hungarian Natural History Museum, Ludovika tér 2-6, Budapest, 1083, Hungary.

Mobility of people and goods during the Upper Paleolithic has proven difficult to reconstruct given the relative rareness of remains. Nevertheless, archaeological contexts like the Late Pleistocene horizon of Borsuka Cave (Southern Poland) represent a unique opportunity to explore patterns of objects' transportation across Central Europe. We investigated the origin of four ornaments made of European elk (Alces alces L.) incisors recovered at Borsuka Cave - the oldest known burial site in Poland, possibly a child grave. Laser-ablation plasma source mass spectrometric analyses of trace elements and Sr isotopic compositions revealed that one elk was roaming within a geologically uniform area while the others changed their pastures during their lifetimes. The non-local origin of the elk teeth is inferred from their exotic Sr isotopic compositions and the lack of evidence for the presence of elk in this territory during the Pleistocene. Instead, the elks' Sr isotopic composition show good agreement with sites near the Austria-Slovakia border region and northern Hungary, ~250 km away from the study site. We argue that the artefacts were most likely brought to Borsuka Cave by humans or by a network of exchange, so far never reported in the time range 32.5-28.8 ka cal BP for Southern Poland.
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http://dx.doi.org/10.1038/s41598-020-67017-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316840PMC
June 2020

Mechanical separation of impurities in biowaste: Comparison of four different pretreatment systems.

Waste Manag 2020 Apr 13;106:12-20. Epub 2020 Mar 13.

Unit of Environmental Engineering, Department for Infrastructure, University of Innsbruck, Technikerstraße 13, 6020 Innsbruck, Austria.

Impurities in biowaste, such as plastics, glass, metals and inert material, negatively impact the operation of anaerobic digestion plants and compost quality, and have to be removed prior to the anaerobic digestion process. Different mechanical pretreatments are available for this purpose. However, data on the removal efficiencies of pretreatment systems for different types of biowaste and for different kinds of impurities are still scarce. This study aims to determine the efficiencies for impurity removal of four biowaste pretreatment plants (BTPs) at real scale - (1) drum-screen + shredder + piston press; (2) shredder + piston press + screw press; (3) separation-mill; and (4) pulper + drum-screen. BTP 1 treats mixed food and garden wastes, while BTP 2, 3 and 4 treat mostly food waste. The efficiency of the pretreatment systems was influenced by the type of pretreated biowaste. The recovery of organics by the press was more efficient when pretreating food waste (BTP 2, 93%) than for treating mixed food and garden wastes (BTP 1, 77%). BTP 3 presented the highest recovery of biogas (up to 98%), but also the highest transfer of inert particles to the substrate. On the contrary, BTP 4 was the most efficient for the removal of inert particles; however, this system also presented 18% loss of biogas potential.
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http://dx.doi.org/10.1016/j.wasman.2020.03.006DOI Listing
April 2020

Comparison of two mechanical pre-treatment systems for impurities reduction of source-separated biowaste.

Waste Manag 2019 Dec 11;100:66-74. Epub 2019 Sep 11.

Unit of Environmental Engineering, Department for Infrastructure, University of Innsbruck, Technikerstraße 13, 6020 Innsbruck, Austria.

The treatment of source-separated biowaste is still a challenge due to its high proportion of impurities. Biowaste bins are intended exclusively for the collection of biodegradable matter, such as food, kitchen and garden waste. However, plastics, metals, glass and textiles are also found in biowaste bins. If not properly removed, these impurities cause problems to the treatment facility and depreciate the quality of the final product, when the biowaste is converted to compost. There is ongoing discussion whether the existing treatment systems are able to remove impurities, especially plastics, from biowaste thoroughly enough to ensure that the produced compost complies with state regulations. In this work, two wet mechanical pre-treatment systems were tested for their efficiency to remove impurities. The first system consisted of a screw mill, a star screen, and a food unpacking machine (process I). The second system consisted of a shredder, followed by a piston press with 12 mm pore size (process II). Both processes produced a dry output, which contained the concentrated impurities, and a wet output, which could be used as substrate for anaerobic digestion. Results showed that, although 99% of the incoming plastics were efficiently removed in process I, the impurities concentration was still too high to meet the legal standards of plastics concentration in the final product, according to the German Federal Compost Quality Association (Bundesgütegemeinschaft Kompost e.V.). The removal efficiency of glass particles was low for both processes: at least 80% of the incoming particles were transferred to the wet output.
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http://dx.doi.org/10.1016/j.wasman.2019.09.003DOI Listing
December 2019

Mechanical testing of antimicrobial biocomposite coating on metallic medical implants as drug delivery system.

Mater Sci Eng C Mater Biol Appl 2019 Nov 24;104:109757. Epub 2019 May 24.

University of Technology Sydney, School of Life Sciences, NSW 2007, Sydney, Australia; BresMedical Pty Ltd, 45 Lanacaster Street, Ingleburn, NSW 2565, Australia.

Post-operative infection often occurs following orthopedic and dental implant placement requiring systemically administered antibiotics. However, this does not provide long-term protection. Over the last few decades, alternative methods involving slow drug delivery systems based on biodegradable poly-lactic acid and antibiotic loaded hydroxyapatite microspheres were developed to prevent post-operative infection. In this study, thermally anodised and untreated Ti6Al4V discs were coated with Poly-Lactic Acid (PLA) containing Gentamicin (Gm) antibiotic-loaded coralline Hydroxyapatite (HAp) are investigated. Following chemical characterization, mechanical properties of the coated samples were measured using nanoindentation and scratch tests to determine the elastic modulus, hardness and bonding adhesion between film and substrate. It was found that PLA biocomposite multilayered films were around 400nm thick and the influence and effect of the substrate were clearly observed during the nanoindentation studies with heavier loads. Scratch tests of PLA coated samples conducted at ~160nm depth showed the minimal difference in the measured friction between Gm and non Gm containing films. It is also observed that the hardness values of PLA film coated anodised samples ranged from 0.45 to 1.9GPa (dependent on the applied loads) against untreated coated samples which ranged from 0.28 to 0.8GPa.
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http://dx.doi.org/10.1016/j.msec.2019.109757DOI Listing
November 2019

Change of entropy for the one-dimensional ballistic heat equation: Sinusoidal initial perturbation.

Phys Rev E 2019 Apr;99(4-1):042107

Theoretical and Applied Mechanics, Peter the Great Saint Petersburg Polytechnic University, Politekhnicheskaja 29, 195251 Saint Petersburg, Russia.

This work presents a thermodynamic analysis of the ballistic heat equation from two viewpoints: classical irreversible thermodynamics (CIT) and extended irreversible thermodynamics (EIT). A formula for calculating the entropy within the framework of EIT for the ballistic heat equation is derived. The entropy is calculated for a sinusoidal initial temperature perturbation by using both approaches. The results obtained from CIT show that the entropy is a non-monotonic function and that the entropy production can be negative. The results obtained for EIT show that the entropy is a monotonic function and that the entropy production is nonnegative. A comparison between the entropy behaviors predicted for the ballistic, for the ordinary Fourier-based, and for the hyperbolic heat equation is made. A crucial difference of the asymptotic behavior of the entropy for the ballistic heat equation is shown. It is argued that mathematical time reversibility of the partial differential ballistic heat equation is not consistent with its physical irreversibility. The processes described by the ballistic heat equation are irreversible because of the entropy increase.
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http://dx.doi.org/10.1103/PhysRevE.99.042107DOI Listing
April 2019

Developments in the MPI-M Earth System Model version 1.2 (MPI-ESM1.2) and Its Response to Increasing CO.

J Adv Model Earth Syst 2019 Apr 16;11(4):998-1038. Epub 2019 Apr 16.

Max Planck Institute for Meteorology Hamburg Germany.

A new release of the Max Planck Institute for Meteorology Earth System Model version 1.2 (MPI-ESM1.2) is presented. The development focused on correcting errors in and improving the physical processes representation, as well as improving the computational performance, versatility, and overall user friendliness. In addition to new radiation and aerosol parameterizations of the atmosphere, several relatively large, but partly compensating, coding errors in the model's cloud, convection, and turbulence parameterizations were corrected. The representation of land processes was refined by introducing a multilayer soil hydrology scheme, extending the land biogeochemistry to include the nitrogen cycle, replacing the soil and litter decomposition model and improving the representation of wildfires. The ocean biogeochemistry now represents cyanobacteria prognostically in order to capture the response of nitrogen fixation to changing climate conditions and further includes improved detritus settling and numerous other refinements. As something new, in addition to limiting drift and minimizing certain biases, the instrumental record warming was explicitly taken into account during the tuning process. To this end, a very high climate sensitivity of around 7 K caused by low-level clouds in the tropics as found in an intermediate model version was addressed, as it was not deemed possible to match observed warming otherwise. As a result, the model has a climate sensitivity to a doubling of CO over preindustrial conditions of 2.77 K, maintaining the previously identified highly nonlinear global mean response to increasing CO forcing, which nonetheless can be represented by a simple two-layer model.
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http://dx.doi.org/10.1029/2018MS001400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386935PMC
April 2019

Enhancement of Benzothiazoles as Pteridine Reductase-1 Inhibitors for the Treatment of Trypanosomatidic Infections.

J Med Chem 2019 04 9;62(8):3989-4012. Epub 2019 Apr 9.

Dipartimento di Scienze della Vita , University of Modena and Reggio Emilia , Via Campi 103 , 41125 Modena , Italy.

2-Amino-benzo[ d]thiazole was identified as a new scaffold for the development of improved pteridine reductase-1 (PTR1) inhibitors and anti-trypanosomatidic agents. Molecular docking and crystallography guided the design and synthesis of 42 new benzothiazoles. The compounds were assessed for Trypanosoma brucei and Leishmania major PTR1 inhibition and in vitro activity against T. brucei and amastigote Leishmania infantum. We identified several 2-amino-benzo[ d]thiazoles with improved enzymatic activity ( TbPTR1 IC = 0.35 μM; LmPTR1 IC = 1.9 μM) and low μM antiparasitic activity against T. brucei. The ten most active compounds against TbPTR1 were able to potentiate the antiparasitic activity of methotrexate when evaluated in combination against T. brucei, with a potentiating index between 1.2 and 2.7. The compound library was profiled for early ADME toxicity, and 2-amino- N-benzylbenzo[ d]thiazole-6-carboxamide (4c) was finally identified as a novel potent, safe, and selective anti-trypanocydal agent (EC = 7.0 μM). Formulation of 4c with hydroxypropyl-β-cyclodextrin yielded good oral bioavailability, encouraging progression to in vivo studies.
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http://dx.doi.org/10.1021/acs.jmedchem.8b02021DOI Listing
April 2019

Drug Delivery From Polymer-Based Nanopharmaceuticals-An Experimental Study Complemented by Simulations of Selected Diffusion Processes.

Front Bioeng Biotechnol 2019 8;7:37. Epub 2019 Mar 8.

Institute of Mechanics, Faculty V of Mechanical Engineering and Transport Systems, Berlin University of Technology, LKM, Berlin, Germany.

The success of medical therapy depends on the correct amount and the appropriate delivery of the required drugs for treatment. By using biodegradable polymers a drug delivery over a time span of weeks or even months is made possible. This opens up a variety of strategies for better medication. The drug is embedded in a biodegradable polymer (the "carrier") and injected in a particular position of the human body. As a consequence of the interplay between the diffusion process and the degrading polymer the drug is released in a controlled manner. In this work we study the controlled release of medication experimentally by measuring the delivered amount of drug within a cylindrical shell over a long time interval into the body fluid. Moreover, a simple continuum model of the Fickean type is initially proposed and solved in closed-form. It is used for simulating some of the observed release processes for this type of carrier and takes the geometry of the drug container explicitly into account. By comparing the measurement data and the model predictions diffusion coefficients are obtained. It turns out that within this simple model the coefficients change over time. This contradicts the idea that diffusion coefficients are constants independent of the considered geometry. The model is therefore extended by taking an additional absorption term into account leading to a concentration dependent diffusion coefficient. This could now be used for further predictions of drug release in carriers of different shape. For a better understanding of the complex diffusion and degradation phenomena the underlying physics is discussed in detail and even more sophisticated models involving different degradation and mass transport phenomena are proposed for future work and study.
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http://dx.doi.org/10.3389/fbioe.2019.00037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418005PMC
March 2019

Accelerating Drug Discovery Efforts for Trypanosomatidic Infections Using an Integrated Transnational Academic Drug Discovery Platform.

SLAS Discov 2019 03;24(3):346-361

14 Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.

According to the World Health Organization, more than 1 billion people are at risk of or are affected by neglected tropical diseases. Examples of such diseases include trypanosomiasis, which causes sleeping sickness; leishmaniasis; and Chagas disease, all of which are prevalent in Africa, South America, and India. Our aim within the New Medicines for Trypanosomatidic Infections project was to use (1) synthetic and natural product libraries, (2) screening, and (3) a preclinical absorption, distribution, metabolism, and excretion-toxicity (ADME-Tox) profiling platform to identify compounds that can enter the trypanosomatidic drug discovery value chain. The synthetic compound libraries originated from multiple scaffolds with known antiparasitic activity and natural products from the Hypha Discovery MycoDiverse natural products library. Our focus was first to employ target-based screening to identify inhibitors of the protozoan Trypanosoma brucei pteridine reductase 1 ( TbPTR1) and second to use a Trypanosoma brucei phenotypic assay that made use of the T. brucei brucei parasite to identify compounds that inhibited cell growth and caused death. Some of the compounds underwent structure-activity relationship expansion and, when appropriate, were evaluated in a preclinical ADME-Tox assay panel. This preclinical platform has led to the identification of lead-like compounds as well as validated hits in the trypanosomatidic drug discovery value chain.
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http://dx.doi.org/10.1177/2472555218823171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484532PMC
March 2019

Focused ultrasound transiently increases membrane conductance in isolated crayfish axon.

J Neurophysiol 2019 02 19;121(2):480-489. Epub 2018 Dec 19.

Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School , Boston, Massachusetts.

We report a novel phenomenon produced by focused ultrasound (US) that may be important for understanding its effects on cell membranes. When a US burst (2.1 MHz, 1-mm focal diameter, 0.1-1 MPa) was focused on a motor axon of the crayfish neuromuscular junction, it consistently produced a fast hyperpolarization, which was followed or superseded by subthreshold depolarizations or action potentials in a stochastic manner. The depolarization persisted in the presence of voltage-gated channel blockers [1 µM TTX ( I), 50 µM ZD7288 ( I), and 200 µM 4-aminopyridine ( I)] and typically started shortly after the onset of a 5-ms US burst, with a mean latency of 3.35 ± 0.53 ms (SE). The duration and amplitude of depolarizations averaged 2.13 ± 0.87 s and 10.1 ± 2.09 mV, with a maximum of 200 s and 60 mV, respectively. The US-induced depolarization was always associated with a decrease in membrane resistance. By measuring membrane potential and resistance during the US-induced depolarization, the reversal potential of US-induced conductance ( g) was estimated to be -8.4 ± 2.3 mV, suggesting a nonselective conductance. The increase in g was 10-100 times larger than the leak conductance; thus it could significantly influence neuronal activity. This change in conductance may be due to stimulation of mechanoreceptors. Alternatively, US may perturb the lateral motion of phospholipids and produce nanopores, which then increase g. These results may be important for understanding mechanisms underlying US-mediated modulation of neuronal activity and brain function. NEW & NOTEWORTHY We report a specific increase in membrane conductance produced by ultrasound (US) on neuronal membrane. When a 5-ms US tone burst was focused on a crayfish motor axon, it stochastically triggered either depolarization or a spike train. The depolarization was up to 60 mV in amplitude and 200 s in duration and therefore could significantly influence neuronal activity. Depolarization was still evoked by US burst in the presence of Na and Ca channel blockers and had a reversal potential of -8.4 ± 2.3 mV, suggesting a nonselective permeability. US can be applied noninvasively in the form of a focused beam to deep brain areas through the skull and has been shown to modulate brain activity. Understanding the depolarization reported here should be helpful for improving the use of US for noninvasive modulation and stimulation in brain-related disease.
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http://dx.doi.org/10.1152/jn.00541.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842880PMC
February 2019

Veto player theory and reform making in Western Europe.

Eur J Polit Res 2018 May 26;57(2):282-307. Epub 2017 Jul 26.

University of Vienna Austria.

Veto player theory generates predictions about governments' capacity for policy change. Due to the difficulty of identifying significant laws needed to change the policy status quo, evidence about governments' ability to change policy has been mostly provided for a limited number of reforms and single-country studies. To evaluate the predictive power of veto player theory for policy making across time, policy areas and countries, a dataset was gathered that incorporates about 5,600 important government reform measures in the areas of social, labour, economic and taxation policy undertaken in 13 Western European countries from the mid-1980s until the mid-2000s. Veto player theory is applied in a combined model with other central theoretical expectations on policy change derived from political economy (crisis-driven policy change) and partisan theory (ideology-driven policy change). Robust support is found that governments introduce more reform measures when economic conditions are poor and when the government is positioned further away from the policy status quo. No empirical support is found for predictions of veto player theory in its pure form, where no differentiation between government types is made. However, the findings provide support for the veto player theory in the special case of minimal winning cabinets, where the support of all government parties is sufficient (in contrast to minority cabinets) and necessary (in contrast to oversized cabinets) for policy change. In particular, it is found that in minimal winning cabinets the ideological distance between the extreme government parties significantly decreases the government's ability to introduce reforms. These findings improve our understanding of reform making in parliamentary democracies and highlight important issues and open questions for future applications and tests of the veto player theory.
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http://dx.doi.org/10.1111/1475-6765.12226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900944PMC
May 2018

Eocene greenhouse climate revealed by coupled clumped isotope-Mg/Ca thermometry.

Proc Natl Acad Sci U S A 2018 02 22;115(6):1174-1179. Epub 2018 Jan 22.

Department of Geology & Geophysics, Yale University, New Haven, CT 06511.

Past greenhouse periods with elevated atmospheric CO were characterized by globally warmer sea-surface temperatures (SST). However, the extent to which the high latitudes warmed to a greater degree than the tropics (polar amplification) remains poorly constrained, in particular because there are only a few temperature reconstructions from the tropics. Consequently, the relationship between increased CO, the degree of tropical warming, and the resulting latitudinal SST gradient is not well known. Here, we present coupled clumped isotope (Δ)-Mg/Ca measurements of foraminifera from a set of globally distributed sites in the tropics and midlatitudes. Δ is insensitive to seawater chemistry and therefore provides a robust constraint on tropical SST. Crucially, coupling these data with Mg/Ca measurements allows the precise reconstruction of Mg/Ca throughout the Eocene, enabling the reinterpretation of all planktonic foraminifera Mg/Ca data. The combined dataset constrains the range in Eocene tropical SST to 30-36 °C (from sites in all basins). We compare these accurate tropical SST to deep-ocean temperatures, serving as a minimum constraint on high-latitude SST. This results in a robust conservative reconstruction of the early Eocene latitudinal gradient, which was reduced by at least 32 ± 10% compared with present day, demonstrating greater polar amplification than captured by most climate models.
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http://dx.doi.org/10.1073/pnas.1714744115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819407PMC
February 2018

SABIO-RK: an updated resource for manually curated biochemical reaction kinetics.

Nucleic Acids Res 2018 01;46(D1):D656-D660

Scientific Databases and Visualization Group, Heidelberg Institute for Theoretical Studies (HITS gGmbH), Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany.

SABIO-RK (http://sabiork.h-its.org/) is a manually curated database containing data about biochemical reactions and their reaction kinetics. The data are primarily extracted from scientific literature and stored in a relational database. The content comprises both naturally occurring and alternatively measured biochemical reactions and is not restricted to any organism class. The data are made available to the public by a web-based search interface and by web services for programmatic access. In this update we describe major improvements and extensions of SABIO-RK since our last publication in the database issue of Nucleic Acid Research (2012). (i) The website has been completely revised and (ii) allows now also free text search for kinetics data. (iii) Additional interlinkages with other databases in our field have been established; this enables users to gain directly comprehensive knowledge about the properties of enzymes and kinetics beyond SABIO-RK. (iv) Vice versa, direct access to SABIO-RK data has been implemented in several systems biology tools and workflows. (v) On request of our experimental users, the data can be exported now additionally in spreadsheet formats. (vi) The newly established SABIO-RK Curation Service allows to respond to specific data requirements.
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http://dx.doi.org/10.1093/nar/gkx1065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753344PMC
January 2018

A generally applicable lightweight method for calculating a value structure for tools and services in bioinformatics infrastructure projects.

Brief Bioinform 2019 07;20(4):1215-1221

Sustainable noncommercial bioinformatics infrastructures are a prerequisite to use and take advantage of the potential of big data analysis for research and economy. Consequently, funders, universities and institutes as well as users ask for a transparent value model for the tools and services offered. In this article, a generally applicable lightweight method is described by which bioinformatics infrastructure projects can estimate the value of tools and services offered without determining exactly the total costs of ownership. Five representative scenarios for value estimation from a rough estimation to a detailed breakdown of costs are presented. To account for the diversity in bioinformatics applications and services, the notion of service-specific 'service provision units' is introduced together with the factors influencing them and the main underlying assumptions for these 'value influencing factors'. Special attention is given on how to handle personnel costs and indirect costs such as electricity. Four examples are presented for the calculation of the value of tools and services provided by the German Network for Bioinformatics Infrastructure (de.NBI): one for tool usage, one for (Web-based) database analyses, one for consulting services and one for bioinformatics training events. Finally, from the discussed values, the costs of direct funding and the costs of payment of services by funded projects are calculated and compared.
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http://dx.doi.org/10.1093/bib/bbx140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781588PMC
July 2019

Who will attack the competitors? How political parties resolve strategic and collective action dilemmas in negative campaigning.

Party Politics 2017 Nov 29;23(6):666-679. Epub 2015 Nov 29.

Department of Government, University of Vienna, Vienna, Austria.

Negative campaigning presents parties with a collective action problem. While parties would prefer to have their competitors attacked, potential backlash effects from negative messages mean that individual politicians typically lack the incentives to carry out such attacks. We theorize that parties solve this problem by implementing a division of labour that takes into account the incentives of individual office holders, their availability for campaign activity, and media relevance. Drawing on these arguments we expect that holders of high public office and party leaders are less likely to issue attacks, leaving the bulk of the 'dirty work' to be carried out by party floor leaders and general secretaries. Examining almost 8000 press releases issued by over 600 individual politicians during four election campaigns in Austria, we find strong support for our theoretical expectations.
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http://dx.doi.org/10.1177/1354068815619832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624298PMC
November 2017

Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit Pteridine Reductase in Support of Early-Stage Drug Discovery.

ACS Omega 2017 Sep 11;2(9):5666-5683. Epub 2017 Sep 11.

Laboratório Nacional de Biociências CNPEM, Centro Nacional de Pesquisa em Energia e Materials, Rua Giuseppe Máximo Scolfaro, 10.000, CEP 13083-970 Campinas/SP, Brasil.

Pteridine reductase-1 (PTR1) is a promising drug target for the treatment of trypanosomiasis. We investigated the potential of a previously identified class of thiadiazole inhibitors of PTR1 for activity against (). We solved crystal structures of several PTR1-inhibitor complexes to guide the structure-based design of new thiadiazole derivatives. Subsequent synthesis and enzyme- and cell-based assays confirm new, mid-micromolar inhibitors of PTR1 with low toxicity. In particular, compound , a biphenyl-thiadiazole-2,5-diamine with IC = 16 μM, was able to potentiate the antitrypanosomal activity of the dihydrofolate reductase inhibitor methotrexate (MTX) with a 4.1-fold decrease of the EC value. In addition, the antiparasitic activity of the combination of and MTX was reversed by addition of folic acid. By adopting an efficient hit discovery platform, we demonstrate, using the 2-amino-1,3,4-thiadiazole scaffold, how a promising tool for the development of anti- agents can be obtained.
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http://dx.doi.org/10.1021/acsomega.7b00473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623949PMC
September 2017

Methods to estimate the transfer of contaminants into recycling products - A case study from Austria.

Waste Manag 2017 Nov 31;69:88-100. Epub 2017 Aug 31.

Universität Innsbruck, Unit for Environmental Engineering, Section of Waste Treatment and Resource Management, Austria.

Recycling of waste materials is desirable to reduce the consumption of limited primary resources, but also includes the risk of recycling unwanted, hazardous substances. In Austria, the legal framework demands secondary products must not present a higher risk than comparable products derived from primary resources. However, the act provides no definition on how to assess this risk potential. This paper describes the development of different quantitative and qualitative methods to estimate the transfer of contaminants in recycling processes. The quantitative methods comprise the comparison of concentrations of harmful substances in recycling products to corresponding primary products and to existing limit values. The developed evaluation matrix, which considers further aspects, allows for the assessment of the qualitative risk potential. The results show that, depending on the assessed waste fraction, particular contaminants can be critical. Their concentrations were higher than in comparable primary materials and did not comply with existing limit values. On the other hand, the results show that a long-term, well-established quality control system can assure compliance with the limit values. The results of the qualitative assessment obtained with the evaluation matrix support the results of the quantitative assessment. Therefore, the evaluation matrix can be suitable to quickly screen waste streams used for recycling to estimate their potential environmental and health risks. To prevent the transfer of contaminants into product cycles, improved data of relevant substances in secondary resources are necessary. In addition, regulations for material recycling are required to assure adequate quality control measures, including limit values.
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http://dx.doi.org/10.1016/j.wasman.2017.08.035DOI Listing
November 2017

Identifiers for the 21st century: How to design, provision, and reuse persistent identifiers to maximize utility and impact of life science data.

PLoS Biol 2017 Jun 29;15(6):e2001414. Epub 2017 Jun 29.

Oxford e-Research Centre, University of Oxford, Oxford, United Kingdom.

In many disciplines, data are highly decentralized across thousands of online databases (repositories, registries, and knowledgebases). Wringing value from such databases depends on the discipline of data science and on the humble bricks and mortar that make integration possible; identifiers are a core component of this integration infrastructure. Drawing on our experience and on work by other groups, we outline 10 lessons we have learned about the identifier qualities and best practices that facilitate large-scale data integration. Specifically, we propose actions that identifier practitioners (database providers) should take in the design, provision and reuse of identifiers. We also outline the important considerations for those referencing identifiers in various circumstances, including by authors and data generators. While the importance and relevance of each lesson will vary by context, there is a need for increased awareness about how to avoid and manage common identifier problems, especially those related to persistence and web-accessibility/resolvability. We focus strongly on web-based identifiers in the life sciences; however, the principles are broadly relevant to other disciplines.
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http://dx.doi.org/10.1371/journal.pbio.2001414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490878PMC
June 2017

Data management and data enrichment for systems biology projects.

J Biotechnol 2017 Nov 10;261:229-237. Epub 2017 Jun 10.

Scientific Databases and Visualization Group, Heidelberg Institute for Theoretical Studies (HITS gGmbH), Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany. Electronic address:

Collecting, curating, interlinking, and sharing high quality data are central to de.NBI-SysBio, the systems biology data management service center within the de.NBI network (German Network for Bioinformatics Infrastructure). The work of the center is guided by the FAIR principles for scientific data management and stewardship. FAIR stands for the four foundational principles Findability, Accessibility, Interoperability, and Reusability which were established to enhance the ability of machines to automatically find, access, exchange and use data. Within this overview paper we describe three tools (SABIO-RK, Excemplify, SEEK) that exemplify the contribution of de.NBI-SysBio services to FAIR data, models, and experimental methods storage and exchange. The interconnectivity of the tools and the data workflow within systems biology projects will be explained. For many years we are the German partner in the FAIRDOM initiative (http://fair-dom.org) to establish a European data and model management service facility for systems biology.
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http://dx.doi.org/10.1016/j.jbiotec.2017.06.007DOI Listing
November 2017

Hydrocyclones for the separation of impurities in pretreated biowaste.

Waste Manag 2017 Jun 13;64:12-19. Epub 2017 Mar 13.

Unit of Environmental Engineering, Section of Waste Treatment and Resource Management, Universität Innsbruck, Technikerstraβe 13, 6020 Innsbruck, Austria.

The aim of the mechanical pretreatment in case of anaerobic digestion of biowaste is to produce a substrate without impurities. To facilitate a failure free operation of the anaerobic digestion process even small impurities like stones or sand should be separated. As a result of an insufficient pretreatment or impurities separation, plant malfunctions, increased equipment wear or pipe clogging are reported. Apart from grit chambers or pulper systems, a hydrocyclone is a cost-efficient and space-saving option to remove impurities. The aim of this work was to investigate the efficiency of hydrocyclones for the separation of impurities. Two hydrocyclones at two different plants were investigated regarding their capability to separate the small inert impurities from pretreated source separated biowaste. In plant A, the hydrocyclone is part of the digester system. In plant B, the hydrocyclone is part of the biowaste pretreatment line (after milling and sieving the biowaste) before digestion. Separation rates of inert impurities such as stones, glass and sand were determined as well as the composition of the concentrated solids separated by the hydrocyclone. Due to the heterogeneity of the biowaste the impurity separation rates showed variations, therefore the following mean results were obtained in average: the investigated hydrocyclones of plant B, part of the biowaste treatment, separated more than 80% of the inert impurities in the waste stream before anaerobic digestion. These impurities had a size range of 0.5-4mm. The hydrocyclone integrated in the digester system of plant A showed separation rates up to 80% only in the size range of 2-4mm.
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http://dx.doi.org/10.1016/j.wasman.2017.03.001DOI Listing
June 2017

Negative Campaigning and the Logic of Retaliation in Multiparty Competition.

Int J Press Polit 2016 Apr 29;21(2):253-272. Epub 2016 Jan 29.

University of Vienna, Vienna, Austria.

The extant literature has demonstrated that the is a core feature of negative campaigning. Attacks by one side induce counterattacks by the other. Yet most research on the interactive nature of negative campaigning is limited to two-party competition and provides little theoretical justification for why political actors should respond to attacks with counterattacks. The present paper addresses these research gaps. We argue that the negativity bias in human information processing and the zero-sum nature of elections make retaliation a rational strategy. Importantly, these arguments also imply that retaliation may not be the only plausible response to attacks in multiparty systems. Rather, parties may prefer to react to attacks from one competitor by attacking another. To grasp empirically how being attacked and attacking are related, we conduct a highly disaggregated time series analysis of such instances while controlling for other factors that may influence actor behavior. Our analyses draw on several thousand party press releases issued during three national election campaigns in Austria, a typical European multiparty system. They show that retaliation is an important strategy also in multiparty politics. Yet in such context, parties do not exclusively follow a tit-for-tat approach but rather display more complex patterns of attack behavior.
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http://dx.doi.org/10.1177/1940161215626566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111739PMC
April 2016

FAIRDOMHub: a repository and collaboration environment for sharing systems biology research.

Nucleic Acids Res 2017 01 28;45(D1):D404-D407. Epub 2016 Nov 28.

School of Computer Science, The University of Manchester, Kilburn Building, Oxford Road, Manchester, M13 9PL, UK

The FAIRDOMHub is a repository for publishing FAIR (Findable, Accessible, Interoperable and Reusable) Data, Operating procedures and Models (https://fairdomhub.org/) for the Systems Biology community. It is a web-accessible repository for storing and sharing systems biology research assets. It enables researchers to organize, share and publish data, models and protocols, interlink them in the context of the systems biology investigations that produced them, and to interrogate them via API interfaces. By using the FAIRDOMHub, researchers can achieve more effective exchange with geographically distributed collaborators during projects, ensure results are sustained and preserved and generate reproducible publications that adhere to the FAIR guiding principles of data stewardship.
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http://dx.doi.org/10.1093/nar/gkw1032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210530PMC
January 2017

The distribution of individual cabinet positions in coalition governments: A sequential approach.

Eur J Polit Res 2015 Nov 24;54(4):802-818. Epub 2015 Aug 24.

University of Vienna Austria.

Multiparty government in parliamentary democracies entails bargaining over the payoffs of government participation, in particular the allocation of cabinet positions. While most of the literature deals with the numerical distribution of cabinet seats among government parties, this article explores the distribution of individual portfolios. It argues that coalition negotiations are sequential choice processes that begin with the allocation of those portfolios most important to the bargaining parties. This induces conditionality in the bargaining process as choices of individual cabinet positions are not independent of each other. Linking this sequential logic with party preferences for individual cabinet positions, the authors of the article study the allocation of individual portfolios for 146 coalition governments in Western and Central Eastern Europe. The results suggest that a sequential logic in the bargaining process results in better predictions than assuming mutual independence in the distribution of individual portfolios.
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http://dx.doi.org/10.1111/1475-6765.12108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973820PMC
November 2015

Impurities in pretreated biowaste for co-digestion: A determination approach.

Waste Manag 2016 Jun 4;52:96-103. Epub 2016 Apr 4.

Unit of Environmental Engineering, Section of Waste Treatment and Resource Management, Universität Innsbruck, Technikerstraße 13, 6020 Innsbruck, Austria.

Although the mechanical treatment of source separated organic waste typically includes processing steps to remove impurities like plastic bags, smaller particles like glass, stones or sand are often not sufficiently removed. These particles lead to plant malfunctions, increased equipment abrasion and accumulation in the digester. It is possible to remove these small impurities before or during the fermentation process but this requires additional equipment at the waste treatment facilities. For pretreated biowaste with fairly low concentrations of impurities and small particle sizes no appropriate method was found in literature to determine these particles. Therefore various approaches to develop an appropriate method were tested and finally one method was selected. Sample mass calculation showed that for the determination of impurities >2mm a sample mass of about 6kg is required to receive statistically sound result. Firstly an elutriation step is used to concentrate the impurities in a sinking fraction, still containing some organic material. The elutriated material is then dried. After drying the elutriated material, impurities can be fairly easily sorted manually. The elutriation process is applicable for the determination of impurities >1mm. Due to the difficult manual sorting of particles <2mm and the reduced sample mass required for the determination of particles <2mm, these particles are determined by a different procedure: A sample mass of about 1kg is dried and combusted in a muffle furnace. The remaining ashes are sieved from 2 to 0.06mm. Particles <0.06mm were not considered as impurities. The data regarding the impurities content and particle size distribution in food- and biowaste are required for assessing separation options as well as the behavior of stones or sand in the digester. This allows describing the quality of the pretreated biowaste. Furthermore the need to adopt or improve the existing pretreatment can be identified and the impact to the fermentation process (impurities accumulated in the digester, etc.) can be evaluated.
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http://dx.doi.org/10.1016/j.wasman.2016.03.055DOI Listing
June 2016

The Human Physiome: how standards, software and innovative service infrastructures are providing the building blocks to make it achievable.

Interface Focus 2016 Apr;6(2):20150103

Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.

Reconstructing and understanding the Human Physiome virtually is a complex mathematical problem, and a highly demanding computational challenge. Mathematical models spanning from the molecular level through to whole populations of individuals must be integrated, then personalized. This requires interoperability with multiple disparate and geographically separated data sources, and myriad computational software tools. Extracting and producing knowledge from such sources, even when the databases and software are readily available, is a challenging task. Despite the difficulties, researchers must frequently perform these tasks so that available knowledge can be continually integrated into the common framework required to realize the Human Physiome. Software and infrastructures that support the communities that generate these, together with their underlying standards to format, describe and interlink the corresponding data and computer models, are pivotal to the Human Physiome being realized. They provide the foundations for integrating, exchanging and re-using data and models efficiently, and correctly, while also supporting the dissemination of growing knowledge in these forms. In this paper, we explore the standards, software tooling, repositories and infrastructures that support this work, and detail what makes them vital to realizing the Human Physiome.
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http://dx.doi.org/10.1098/rsfs.2015.0103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759754PMC
April 2016

Decadal predictions of the North Atlantic CO2 uptake.

Nat Commun 2016 Mar 30;7:11076. Epub 2016 Mar 30.

Max Planck Institute for Meteorology, Bundesstraße 53, 20146 Hamburg, Germany.

As a major CO2 sink, the North Atlantic, especially its subpolar gyre region, is essential for the global carbon cycle. Decadal fluctuations of CO2 uptake in the North Atlantic subpolar gyre region are associated with the evolution of the North Atlantic Oscillation, the Atlantic meridional overturning circulation, ocean mixing and sea surface temperature anomalies. While variations in the physical state of the ocean can be predicted several years in advance by initialization of Earth system models, predictability of CO2 uptake has remained unexplored. Here we investigate the predictability of CO2 uptake variations by initialization of the MPI-ESM decadal prediction system. We find large multi-year variability in oceanic CO2 uptake and demonstrate that its potential predictive skill in the western subpolar gyre region is up to 4-7 years. The predictive skill is mainly maintained in winter and is attributed to the improved physical state of the ocean.
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http://dx.doi.org/10.1038/ncomms11076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820896PMC
March 2016