New sparsing approach for real-time simulations of stiff models on electronic control units - Loderer, Thomas; Heuveline, Vincent (Preprint Series of the Engineering Mathematics and Computing Lab, 2017)
For real-time simulations of stiff models on electronic control units, one important ingredient is to reduce computation time within differentiation of the right-hand side of the underlying differential equation. A sparsing method represents a powerful tool in this context. For a reliable use of a real-time simulation of a stiff model in safety-critical conditions, it is important to be able to detect, when sparsing leads to an improper influence on the considered system. In this work we propose an extension which aims at addressing this numerically challenging problem in the context of real-time simulation.

Towards an Intelligent Framework for Personalized Simulation-enhanced Surgery Assistance: Linking a Simulation Ontology to a Reinforcement Learning Algorithm for Calibration of Numerical Simulations - Schoch, Nicolai; Heuveline, Vincent (Preprint Series of the Engineering Mathematics and Computing Lab, 2017)
Evolving our previous research results in the context of cognition-guidance and patient-specifity for simulation-enhanced cardiac surgery assistance, in this work we further investigate on (1) a machine learning framework which allows to patient-individually calibrate soft tissue material parameters for subsequent simulation, and (2) a profound knowledge management framework which may enhance the ontology-driven overall setup of the cognition-guided surgery simulation in a clinic environment. Rather than being a closed research work with an in-depth theory backup and a complete evaluation, we here present a technical report and some interesting experimental works that are to serve for further research and development.

HiFlow3 – Technical Report on Release 2.0 - Gawlok, Simon; Gerstner, Philipp; Haupt, Saskia; Heuveline, Vincent; Kratzke, Jonas; Lösel, Philipp; Mang, Katrin; Schmidtobreick, Mareike; Schoch, Nicolai; Schween, Nils; Schwegler, Jonathan; Song, Chen; et al. (Preprint Series of the Engineering Mathematics and Computing Lab, 2017)

Uncertainty Quantification and High Performance Computing (Dagstuhl Seminar 16372) - Heuveline, Vincent; Schick, Michael; Webster, Clayton; Zaspel, Peter (2017)

Exploring impacts of vegetated buffer strips on nitrogen cycling using a spatially explicit hydro-biogeochemical modeling approach - Klatt, S; Kraus, D; Kraft, P; Breuer, L; Wlotzka, M; Heuveline, Vincent; Haas, E; Kiese, R; Butterbach-Bahl, Klaus (Environmental Modelling & Software, 2017)

A GPU Based Diffusion Method for Whole-Heart and Great Vessel Segmentation - Lösel, Philipp; Heuveline, Vincent (Reconstruction, Segmentation, and Analysis of Medical Images, 2017)
Segmenting the blood pool and myocardium from a 3D cardiovascular magnetic resonance (CMR) image allows to create a patient-specific heart model for surgical planning in children with complex congenital heart disease (CHD). Implementation of semi-automatic or automatic segmentation algorithms is challenging because of a high anatomical variability of the heart defects, low contrast, and intensity variations in the images. Therefore, manual segmentation is the gold standard but it is labor-intensive. In this paper we report the set-up and results of a highly scalable semi-automatic diffusion algorithm for image segmentation. The method extrapolates the information from a small number of expert manually labeled reference slices to the remaining volume. While results of most semi-automatic algorithms strongly depend on well-chosen but usually unknown parameters this approach is parameter-free. Validation is performed on twenty 3D CMR images.

Optimal Storage Operation with Model Predictive Control in the German Transmission Grid - Meyer-Hübner, Nico; Suriyah, Michael; Leibfried, Thomas; Slednev, Viktor; Bertsch, Valentin; Fichtner, Wolf; Gerstner, Philipp; Schick, Michael; Heuveline, Vincent (Advances in Energy System Optimization, 2017)

OpenGL® API-Based Analysis of Large Datasets in a Cloud Environment - Mexner, Wolfgang; Bonn, Matthias; Kopmann, Andreas; Mauch, Viktor; Ressmann, Doris; Chilingaryan, Suren A.; Jerome, Nicholas Tan; Kamp, Thomas Van De; Heuveline, Vincent; Lösel, Philipp; et al., (Advances in Computer and Electrical Engineering Design and Use of Virtualization Technology in Cloud Computing, 2018)

High Performance Computing for Cognition-Guided Cardiac Surgery: Soft Tissue Simulation for Mitral Valve Reconstruction in Knowledge-based Surgery Assistance - Schoch, N.; Engelhardt, S.; De Simone, R.; Wolf, I.; Heuveline, Vincent (Proc. 6th International Conference on High-Performance Scientific Computing 2015 (LNCS Springer), 2017)

Towards Cognition-Guided Patient-Specific FEM-based Cardiac Surgery Simulation - Schoch, Nicolai; Heuveline, Vincent (Lecture Notes in Computer Science, Proceedings of the "Functional Imaging and Modeling of the Heart (FIMH) 2017", 2017)

Regionalizing Input Data for Generation and Transmission Expansion Planning Models - Slednev, Viktor; Ruppert, Manuel; Bertsch, Valentin; Fichtner, Wolf; Meyer-Hübner, Nico; Suriyah, Michael; Leibfried, Thomas; Gerstner, Philipp; Schick, Michael; Heuveline, Vincent (Advances in Energy System Optimization, 2017)

Sparse Grids for quantifying motion uncertainties in biomechanical models of radiotherapy patients - Song, Chen; Stoll, Markus; Giske, Kristina; Bendl, Rolf; Heuveline, Vincent (Preprint Series of the Engineering Mathematics and Computing Lab, 2017)

Multilevel preconditioner of Polynomial Chaos Method for quantifying uncertainties in a blood pump - Song, Chen; Heuveline, Vincent (2017)

Energy-efficient multigrid smoothers and grid transfer operators on multi-core and GPU clusters - Wlotzka, Martin; Heuveline, Vincent (Journal of Parallel and Distributed Computing, 2017)

Energy-Aware High Performance Computing - Wlotzka, Martin; Heuveline, Vincent; Dolz, Manuel F; Heidari, M Reza; Ludwig, Thomas; Malossi, A Cristiano I; Quintana-Orti, Enrique S (2017)

Parallel multiphysics simulations using OpenPALM with application to hydrology-biogeochemistry coupling - Wlotzka, M.; Heuveline, Vincent; Klatt, S.; Kraus, D.; Haas, E.; Kiese, R.; Butterbach-Bahl, K.; Kraft, P.; Breuer, L. (2017)

An energy-efficient parallel multigrid methods for multi-core CPU platforms and HPC clusters - Wlotzka, M.; Heuveline, Vincent (EMCL Preprint Series, 2017)

New features for advanced dynamic parallel communication routines in OpenPALM: Algorithms and documentation - Wlotzka, M.; Morel, Benoit; Piacentini, A.; Heuveline, Vincent (EMCL Preprint Series, 2017)

The NOVA project: maximizing beam time efficiency through synergistic analyses of SRμCT data - Schmelzle, Sebastian; van de Kamp, Thomas; Heethoff, Michael; Heuveline, Vincent; Lösel, Philipp; Becker, Jürgen; Beckmann, Felix; Schluenzen, Frank; Hammel, Jörg U.; Kopmann, Andreas; Mexner, Wolfgang; Vogelgesang, Matthias; et al. (Developments in X-Ray Tomography XI, 2017)

Sampling Long- versus Short-Range Interactions Defines the Ability of Force Fields To Reproduce the Dynamics of Intrinsically Disordered Proteins. - Mercadante, D.; Wagner, J. A.; Aramburu, I. V.; Lemke, E. A.; Grater, F. (J Chem Theory Comput, 2017)
Molecular dynamics (MD) simulations have valuably complemented experiments describing the dynamics of intrinsically disordered proteins (IDPs), particularly since the proposal of models to solve the artificial collapse of IDPs in silico. Such models suggest redefining nonbonded interactions, by either increasing water dispersion forces or adopting the Kirkwood-Buff force field. These approaches yield extended conformers that better comply with experiments, but it is unclear if they all sample the same intrachain dynamics of IDPs. We have tested this by employing MD simulations and single-molecule Forster resonance energy transfer spectroscopy to sample the dimensions of systems with different sequence compositions, namely strong and weak polyelectrolytes. For strong polyelectrolytes in which charge effects dominate, all the proposed solutions equally reproduce the expected ensemble's dimensions. For weak polyelectrolytes, at lower cutoffs, force fields abnormally alter intrachain dynamics, overestimating excluded volume over chain flexibility or reporting no difference between the dynamics of different chains. The TIP4PD water model alone can reproduce experimentally observed changes in extensions (dimensions), but not quantitatively and with only weak statistical significance. Force field limitations are reversed with increased interaction cutoffs, showing that chain dynamics are critically defined by the presence of long-range interactions. Force field analysis aside, our study provides the first insights into how long-range interactions critically define IDP dimensions and raises the question of which length range is crucial to correctly sample the overall dimensions and internal dynamics of the large group of weakly charged yet highly polar IDPs.
Keywords: Fluorescence Resonance Energy Transfer; Humans; Intrinsically Disordered Proteins/*chemistry; Molecular Dynamics Simulation; Nuclear Pore Complex Proteins/*chemistry; Peptides/*chemistry; Polyelectrolytes/chemistry; Protein Conformation; Water/chemistry

The mechano-sensing role of the unique SH3 insertion in plakin domains revealed by Molecular Dynamics simulations. - Daday, C.; Kolsek, K.; Grater, F. (Sci Rep, 2017)
The plakin family of proteins, important actors in cross-linking force-bearing structures in the cell, contain a curious SH3 domain insertion in their chain of spectrin repeats (SRs). While SH3 domains are known to mediate protein-protein interactions, here, its canonical binding site is autoinhibited by the preceding SR. Under force, however, this SH3 domain could be released, and possibly launch a signaling cascade. We performed large-scale force-probe molecular dynamics simulations, across two orders of magnitude of loading rates, to test this hypothesis, on two prominent members of the plakin family: desmoplakin and plectin, obligate proteins at desmosomes and hemidesmosomes, respectively. Our simulations show that force unravels the SRs and abolishes the autoinhibition of the SH3 domain, an event well separated from the unfolding of this domain. The SH3 domain is free and fully functional for a significant portion of the unfolding trajectories. The rupture forces required for the two proteins significantly decrease when the SH3 domain is removed, which implies that the SH3 domain also stabilizes this junction. Our results persist across all simulations, and support a force-sensing as well as a stabilizing role of the unique SH3 insertion, putting forward this protein family as a new class of mechano-sensors.

Stress Propagation through Biological Lipid Bilayers in Silico. - Aponte-Santamaria, C.; Brunken, J.; Grater, F. (J Am Chem Soc, 2017)
Membrane tension plays various critical roles in the cell. We here asked how fast and how far localized pulses of mechanical stress dynamically propagate through biological lipid bilayers. In both coarse-grained and all-atom molecular dynamics simulations of a dipalmitoylphosphatidylcholine lipid bilayer, we observed nanometer-wide stress pulses, propagating very efficiently longitudinally at a velocity of approximately 1.4 +/- 0.5 nm/ps (km/s), in close agreement with the expected speed of sound from experiments. Remarkably, the predicted characteristic attenuation time of the pulses was in the order of tens of picoseconds, implying longitudinal stress propagation over length scales up to several tens of nanometers before damping. Furthermore, the computed dispersion relation leading to such damping was consistent with proposed continuum viscoelastic models of propagation. We suggest this mode of stress propagation as a potential ultrafast mechanism of signaling that may quickly couple mechanosensitive elements in crowded biological membranes.
Keywords: 1,2-Dipalmitoylphosphatidylcholine/chemistry/metabolism; Computer Simulation; Lipid Bilayers/chemistry/*metabolism; *Molecular Dynamics Simulation; *Stress, Mechanical

Accessibility explains preferred thiol-disulfide isomerization in a protein domain. - Kolsek, K.; Aponte-Santamaria, C.; Grater, F. (Sci Rep, 2017)
Disulfide bonds are key stabilizing and yet potentially labile cross-links in proteins. While spontaneous disulfide rearrangement through thiol-disulfide exchange is increasingly recognized to play an important physiological role, its molecular determinants are still largely unknown. Here, we used a novel hybrid Monte Carlo and Molecular Dynamics scheme to elucidate the molecular principles of thiol-disulfide exchange in proteins, for a mutated immunoglobulin domain as a model system. Unexpectedly, using simple proximity as the criterion for thiol-disulfide exchange, our method correctly predicts the experimentally observed regiospecificity and selectivity of the cysteine-rich protein. While redox reactivity has been examined primarily on the level of transition states and activation barriers, our results argue for accessibility of the disulfide by the attacking thiol given the highly dynamic and sterically demanding protein as a major bottleneck of thiol-disulfide exchange. This scenario may be similarly at play in other proteins with or without an evolutionarily designed active site.
Keywords: Cysteine/chemistry; Disulfides/*chemistry; Isomerism; Molecular Dynamics Simulation; Protein Conformation; *Protein Domains; *Protein Interaction Domains and Motifs; Proteins/*chemistry; Structure-Activity Relationship; Sulfhydryl Compounds/*chemistry

Temperature dependence of protein-water interactions in a gated yeast aquaporin. - Aponte-Santamarı́a, C; Fischer, G; Båth, P; Neutze, R; de Groot, BL (Scientific Reports, 2017)

Localization and ordering of lipids around Aquaporin-0: Protein and lipid mobility effects. - Briones, B; Aponte-Santamarı́a, C; de Groot, BL (Frontiers in Physiology, 2017)

Mutation G1629E Increases von Willebrand Factor Cleavage via a Cooperative Destabilization Mechanism. - Aponte-Santamaria, C.; Lippok, S.; Mittag, J. J.; Obser, T.; Schneppenheim, R.; Baldauf, C.; Grater, F.; Budde, U.; Radler, J. O. (Biophys J, 2017)
The large multimeric glycoprotein von Willebrand Factor (VWF) plays a pivotal adhesive role during primary hemostasis. VWF is cleaved by the protease ADAMTS13 as a down-regulatory mechanism to prevent excessive VWF-mediated platelet aggregation. For each VWF monomer, the ADAMTS13 cleavage site is located deeply buried inside the VWF A2 domain. External forces in vivo or denaturants in vitro trigger the unfolding of this domain, thereby leaving the cleavage site solvent-exposed and ready for cleavage. Mutations in the VWF A2 domain, facilitating the cleavage process, cause a distinct form of von Willebrand disease (VWD), VWD type 2A. In particular, the VWD type 2A Gly1629Glu mutation drastically accelerates the proteolytic cleavage activity, even in the absence of forces or denaturants. However, the effect of this mutation has not yet been quantified, in terms of kinetics or thermodynamics, nor has the underlying molecular mechanism been revealed. In this study, we addressed these questions by using fluorescence correlation spectroscopy, molecular dynamics simulations, and free energy calculations. The measured enzyme kinetics revealed a 20-fold increase in the cleavage rate for the Gly1629Glu mutant compared with the wild-type VWF. Cleavage was found cooperative with a cooperativity coefficient n = 2.3, suggesting that the mutant VWF gives access to multiple cleavage sites of the VWF multimer at the same time. According to our simulations and free energy calculations, the Gly1629Glu mutation causes structural perturbation in the A2 domain and thereby destabilizes the domain by approximately 10 kJ/mol, promoting its unfolding. Taken together, the enhanced proteolytic activity of Gly1629Glu can be readily explained by an increased availability of the ADAMTS13 cleavage site through A2-domain-fold thermodynamic destabilization. Our study puts forward the Gly1629Glu mutant as a very efficient enzyme substrate for ADAMTS13 activity assays.
Keywords: ADAMTS13 Protein/metabolism; HEK293 Cells; Humans; Kinetics; *Molecular Dynamics Simulation; *Mutation; Protein Domains; Protein Multimerization; Protein Stability; Protein Structure, Quaternary; *Proteolysis; Thermodynamics; von Willebrand Factor/chemistry/*genetics/*metabolism

Stress-induced long-range ordering in spider silk. - Wagner, J. A.; Patil, S. P.; Greving, I.; Lammel, M.; Gkagkas, K.; Seydel, T.; Muller, M.; Markert, B.; Grater, F. (Sci Rep, 2017)
The emergence of order from disorder is a topic of vital interest. We here propose that long-range order can arise from a randomly arranged two-phase material under mechanical load. Using Small-Angle Neutron Scattering (SANS) experiments and Molecular Dynamics based finite element (FE) models we show evidence for stress-induced ordering in spider dragline silk. Both methods show striking quantitative agreement of the position, shift and intensity increase of the long period upon stretching. We demonstrate that mesoscopic ordering does not originate from silk-specific processes such as strain-induced crystallization on the atomistic scale or the alignment of tilted crystallites. It instead is a general phenomenon arising from a non-affine deformation that enhances density fluctuations of the stiff and soft phases along the direction of stress. Our results suggest long-range ordering, analogously to the coalescence of defects in materials, as a wide-spread phenomenon to be exploited for tuning the mechanical properties of many hybrid stiff and soft materials.
Keywords: Animals; *Molecular Dynamics Simulation; Silk/*chemistry; Spiders; *Stress, Mechanical; *Tensile Strength

Decoupling of size and shape fluctuations in heteropolymeric sequences reconciles discrepancies in SAXS vs. FRET measurements. - Fuertes, G.; Banterle, N.; Ruff, K. M.; Chowdhury, A.; Mercadante, D.; Koehler, C.; Kachala, M.; Estrada Girona, G.; Milles, S.; Mishra, A.; Onck, P. R.; Grater, F.; et al. (Proc Natl Acad Sci U S A, 2017)
Unfolded states of proteins and native states of intrinsically disordered proteins (IDPs) populate heterogeneous conformational ensembles in solution. The average sizes of these heterogeneous systems, quantified by the radius of gyration (R(G) ), can be measured by small-angle X-ray scattering (SAXS). Another parameter, the mean dye-to-dye distance (R(E) ) for proteins with fluorescently labeled termini, can be estimated using single-molecule Forster resonance energy transfer (smFRET). A number of studies have reported inconsistencies in inferences drawn from the two sets of measurements for the dimensions of unfolded proteins and IDPs in the absence of chemical denaturants. These differences are typically attributed to the influence of fluorescent labels used in smFRET and to the impact of high concentrations and averaging features of SAXS. By measuring the dimensions of a collection of labeled and unlabeled polypeptides using smFRET and SAXS, we directly assessed the contributions of dyes to the experimental values R(G) and R(E) For chemically denatured proteins we obtain mutual consistency in our inferences based on R(G) and R(E) , whereas for IDPs under native conditions, we find substantial deviations. Using computations, we show that discrepant inferences are neither due to methodological shortcomings of specific measurements nor due to artifacts of dyes. Instead, our analysis suggests that chemical heterogeneity in heteropolymeric systems leads to a decoupling between R(E) and R(G) that is amplified in the absence of denaturants. Therefore, joint assessments of R(G) and R(E) combined with measurements of polymer shapes should provide a consistent and complete picture of the underlying ensembles.
Keywords: Coloring Agents/chemistry; Escherichia coli/metabolism; Escherichia coli Proteins/*metabolism; Fluorescence Resonance Energy Transfer/methods; Intrinsically Disordered Proteins/*metabolism; Protein Conformation; *Protein Unfolding; *Scattering, Small Angle; X-Ray Diffraction/*methods

One-Way Allosteric Communication between the Two Disulfide Bonds in Tissue Factor. - Zhou, B.; Hogg, P. J.; Grater, F. (Biophys J, 2017)
Tissue factor (TF) is a transmembrane glycoprotein that plays distinct roles in the initiation of extrinsic coagulation cascade and thrombosis. TF contains two disulfide bonds, one each in the N-terminal and C-terminal extracellular domains. The C-domain disulfide, Cys186-Cys209, has a -RHStaple configuration in crystal structures, suggesting that this disulfide carries high pre-stress. The redox state of this disulfide has been proposed to regulate TF encryption/decryption. Ablating the N-domain Cys49-Cys57 disulfide bond was found to increase the redox potential of the Cys186-Cys209 bond, implying an allosteric communication between the domains. Using molecular dynamics simulations, we observed that the Cys186-Cys209 disulfide bond retained the -RHStaple configuration, whereas the Cys49-Cys57 disulfide bond fluctuated widely. The Cys186-Cys209 bond featured the typical -RHStaple disulfide properties, such as a longer S-S bond length, larger C-S-S angles, and higher bonded prestress, in comparison to the Cys49-Cys57 bond. Force distribution analysis was used to sense the subtle structural changes upon ablating the disulfide bonds, and allowed us to identify a one-way allosteric communication mechanism from the N-terminal to the C-terminal domain. We propose a force propagation pathway using a shortest-pathway algorithm, which we suggest is a useful method for searching allosteric signal transduction pathways in proteins. As a possible explanation for the pathway being one-way, we identified a pronounced lower degree of conformational fluctuation, or effectively higher stiffness, in the N-terminal domain. Thus, the changes of the rigid domain (N-terminal domain) can induce mechanical force propagation to the soft domain (C-terminal domain), but not vice versa.
Keywords: Allosteric Regulation; Amino Acid Sequence; Biomechanical Phenomena; Disulfides/*chemistry; *Molecular Dynamics Simulation; Mutation; Protein Domains; Thromboplastin/*chemistry/genetics/metabolism

Dynamic disorder can explain non-exponential kinetics of fast protein mechanical unfolding. - Costescu, B. I.; Sturm, S.; Grater, F. (J Struct Biol, 2017)
Protein unfolding often does not obey a simple two-state behavior. Previous single molecule force spectroscopy studies demonstrated stretched exponential kinetics of protein unfolding under a constant pulling force, the molecular origin of which remains subject to debate. We here set out to extensively sample the mechanical unfolding of ubiquitin and NuG2 by Molecular Dynamics (MD) simulations. Both proteins show kinetics best fit by stretched exponentials, with stretching exponents similar to those found in experiments, even though static disorder is absent in our short MD simulations. Instead, we can ascribe non-exponential kinetics to dynamic disorder, due to conformational fluctuations on the nanosecond timescale. Our study highlights the general role of dynamic disorder in protein kinetics on a broad range of time scales even including those probed in MD simulations.
Keywords: Kinetics; Microscopy, Atomic Force/methods; Molecular Conformation; Molecular Dynamics Simulation; *Protein Unfolding; Proteins/*chemistry; Single Molecule Imaging; Ubiquitin/*chemistry

In silico design of the first DNA-independent mechanism-based inhibitor of mammalian DNA methyltransferase Dnmt1 - Miletić, V; Odorčić, I; Nikolić, P; Svedružić, ŽM (PLoS ONE, 2017)

Protein conformational flexibility modulates kinetics and thermodynamics of drug binding - Amaral, M.; Kokh, Daria; Bomke, J.; Wegener, A.; Buchstaller, H. P.; Eggenweiler, H. M.; Matias, P.; Sirrenberg, C.; Wade, Rebecca C.; Frech, M. (Nature Communications, 2017)
Structure-based drug design has often been restricted by the rather static picture of protein–ligand complexes presented by crystal structures, despite the widely accepted importance of protein flexibility in biomolecular recognition. Here we report a detailed experimental and computational study of the drug target, human heat shock protein 90, to explore the contribution of protein dynamics to the binding thermodynamics and kinetics of drug-like compounds. We observe that their binding properties depend on whether the protein has a loop or a helical conformation in the binding site of the ligand-bound state. Compounds bound to the helical conformation display slow association and dissociation rates, high-affinity and high cellular efficacy, and predominantly entropically driven binding. An important entropic contribution comes from the greater flexibility of the helical relative to the loop conformation in the ligand-bound state. This unusual mechanism suggests increasing target flexibility in the bound state by ligand design as a new strategy for drug discovery.

Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity - Di Pisa, Flavio; Landi, Giacomo; Dello Iacono, Lucia; Pozzi, Cecilia; Borsari, Chiara; Ferrari, Stefania; Santucci, Matteo; Santarem, Nuno; Cordeiro-da-Silva, Anabela; Moraes, Carolina; Alcantara, Laura; Fontana, Vanessa; et al. (Molecules, 2017)

Early career researchers want Open Science - Farnham, Andrea; Kurz, Christoph; Öztürk, Mehmet Ali; Solbiati, Monica; Myllyntaus, Oona; Meekes, Jordy; Pham, Tra My; Paz, Clara; Langiewicz, Magda; Andrews, Sophie; Kanninen, Liisa; Agbemabiese, Chantal; et al. (Genome Biology, 2017)
Open Science is encouraged by the European Union and many other political and scientific institutions. However, scientific practice is proving slow to change. We propose, as early career researchers, that it is our task to change scientific research into open scientific research and commit to Open Science principles.

Application of a simple quantum chemical approach to ligand fragment scoring for Trypanosoma brucei pteridine reductase 1 inhibition - Jedwabny, Wiktoria; Panecka-Hofman, Joanna; Dyguda-Kazimierowicz, Edyta; Wade, Rebecca C.; Sokalski, W. Andrzej (Journal of Computer Aided Molecular Design, 2017)

Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit Trypanosoma brucei Pteridine Reductase in Support of Early-Stage Drug Discovery - Linciano, Pasquale; Dawson, Alice; Pöhner, Ina; Costa, David M.; Sá, Monica S.; Cordeiro-da-Silva, Anabela; Luciani, Rosaria; Gul, Sheraz; Witt, Gesa; Ellinger, Bernhard; Kuzikov, Maria; Gribbon, Philip; et al. (ACS Omega, 2017)

A unique profilin-actin interface is important for malaria parasite motility - Moreau, Catherine A.; Bhargav, Saligram P.; Kumar, Hirdesh; Quadt, Katharina A.; Piirainen, Henni; Strauss, Léanne; Kehrer, Jessica; Streichfuss, Martin; Spatz, Joachim P.; Wade, Rebecca C.; Kursula, Inari; Frischknecht, Friedrich (PLOS Pathogens, 2017)
Author summary The malaria parasite Plasmodium has two invasive forms that migrate across different tissue barriers, the ookinete and the very rapidly migrating sporozoite. Previous work has shown that the motility of these and related parasites (e.g. Toxoplasma gondii) depends on a highly dynamic actin cytoskeleton and retrograde flow of surface adhesins. These unusual actin dynamics are due to the divergent structure of protozoan actins and the actions of actin-binding proteins, which can have non-canonical functions in these parasites. Profilin is one of the most important and most investigated actin-binding proteins, which binds ADP-actin and catalyzes ADP-ATP exchange to then promote actin polymerization. Parasite profilins bind monomeric actin and contain an additional domain compared to canonical profilins. Here we show that this additional domain of profilin is critical for actin binding and rapid sporozoite motility but has little impact on the slower ookinete. Sporozoites of a parasite line carrying mutations in this domain cannot translate force production and retrograde flow into optimal parasite motility. Using molecular dynamics simulations, we find that differences between mutant parasites in their capacity to migrate can be traced back to a single hydrogen bond at the actin-profilin interface.

Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes. - Nillegoda, Nadinath B; Stank, Antonia; Malinverni, Duccio; Alberts, Niels; Szlachcic, Anna; Barducci, Alessandro; De Los Rios, Paolo; Wade, Rebecca C.; Bukau, Bernd (eLife, 2017)

Drosophila melanogaster linker histone (dH1) binding to the nucleosome. - Öztürk, Mehmet Ali; Cojocaru, Vlad; Wade, Rebecca C. (2017)

Comparative mapping of on-targets and off-targets for the discovery of anti-trypanosomatid folate pathway inhibitors - Panecka-Hofman, Joanna; Pöhner, Ina; Spyrakis, Francesca; Zeppelin, Talia; Di Pisa, Flavio; Dello Iacono, Lucia; Bonucci, Alessio; Quotadamo, Antonio; Venturelli, Alberto; Mangani, Stefano; Costi, Maria Paola; Wade, Rebecca C. (Biochimica et Biophysica Acta - General Subjects, 2017)

A novel homozygous ARL13B variant in patients with Joubert syndrome impairs its guanine nucleotide-exchange factor activity - Rafiullah, Rafiullah; Long, Alyssa B.; Ivanova, Anna A.; Ali, Hazrat; Berkel, Simone; Mustafa, Ghulam; Paramasivam, Nagarajan; Schlesner, Matthias; Wiemann, Stefan; Wade, Rebecca C.; Bolthauser, Eugen; Blum, Martin; et al. (European Journal of Human Genetics, 2017)
ARL13B encodes for the ADP-ribosylation factor-like 13B GTPase, which is required for normal cilia structure and Sonic hedgehog (Shh) signaling. Disruptions in cilia structure or function lead to a class of human disorders called ciliopathies. Joubert syndrome is characterized by a wide spectrum of symptoms, including a variable degree of intellectual disability, ataxia, and ocular abnormalities. Here we report a novel homozygous missense variant c.[223G>A] (p.(Gly75Arg) in the ARL13B gene, which was identified by whole-exome sequencing of a trio from a consanguineous family with multiple-affected individuals suffering from intellectual disability, ataxia, ocular defects, and epilepsy. The same variant was also identified in a second family. We saw a striking difference in the severity of ataxia between affected male and female individuals in both families. Both ARL13B and ARL13B-c.[223G>A] (p.(Gly75Arg) expression rescued the cilia length and Shh defects displayed by Arl13b hennin (null) cells, indicating that the variant did not disrupt either ARL13B function. In contrast, ARL13B-c.[223G>A] (p.(Gly75Arg) displayed a marked loss of ARL3 guanine nucleotide-exchange factor activity, with retention of its GTPase activities, highlighting the correlation between its loss of function as an ARL3 guanine nucleotide-exchange factor and Joubert syndrome.

Kinetics for Drug Discovery: an industry-driven effort to target drug residence time - Schuetz, Doris A.; de Witte, Wilhelmus Egbertus Arnout; Wong, Yin Cheong; Knasmueller, Bernhard; Richter, Lars; Kokh, Daria; Sadiq, Kashif; Bosma, Reggie; Nederpelt, Indira; Heitman, Laura H.; Segala, Elena; Amaral, Marta; et al. (Drug Discovery Today, 2017)
A considerable number of approved drugs show non-equilibrium binding characteristics, emphasizing the potential role of drug residence times for in vivo efficacy. Therefore, a detailed understanding of the kinetics of association and dissociation of a target–ligand complex might provide crucial insight into the molecular mechanism-of-action of a compound. This deeper understanding will help to improve decision making in drug discovery, thus leading to a better selection of interesting compounds to be profiled further. In this review, we highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium, which targets major open questions related to binding kinetics in an industry-driven public-private partnership.

TRAPP webserver: predicting protein binding site flexibility and detecting transient binding pockets. - Stank, Antonia; Kokh, Daria; Horn, Max; Sizikova, Elena; Neil, Rebecca; Panecka, Joanna; Richter, Stefan; Wade, Rebecca C. (Nucleic Acids Research, 2017)

Using a graph-based coherence model in document-Level machine translation - Born, Leo; Mesgar, Mohsen; Strube, Michael (2017)

Trust, but verify! Better entity linking through automatic verification - Heinzerling, Benjamin; Strube, Michael; Lin, Chin-Yew (2017)

Revisiting selectional preferences for coreference resolution - Heinzerling, Benjamin; Moosavi, Nafise Sadat; Strube, Michael (2017)

Proceedings of the First ACL Workshop on Ethics in Natural Language Processing, Valencia, Spain, 4 April 2017 - Hovy, Dirk; Spruit, Shannon; Mitchell, Margaret; Bender, Emily M.; Strube, Michael; Wallach, Hanna (Proceedings of the First ACL Workshop on Ethics in Natural Language Processing, Valencia, Spain, 4 April 2017, 2017)

Event argument identification on dependency graphs with bidirectional LSTMs - Judea, Alex; Strube, Michael (2017)

Proceedings of the IJCNLP 2017, Tutorial Abstracts, Taipei, Taiwan, 27 November 2017 - Kurohashi, Sadao; Strube, Michael (Proceedings of the IJCNLP 2017, Tutorial Abstracts, Taipei, Taiwan, 27 November 2017, 2017)

Use generalized representations, but do not forget surface features - Moosavi, Nafise Sadat; Strube, Michael (2017)

Lexical features in coreference resolution: To be used with caution - Moosavi, Nafise Sadat; Strube, Michael (2017)

Data sets for author name disambiguation: An empirical analysis and a new resource - Müller, Mark-Christoph; Reitz, Florian; Roy, Nicolas (Scientometrics, 2017)

Semantic author name disambiguation with word embeddings - Müller, Mark-Christoph (Research and Advanced Technology for Digital Libraries, 2017)

Idealized hydrodynamic simulations of turbulent oxygen-burning shell convection in 4π geometry - Jones, S.; Andrássy, Róbert; Sandalski, S.; Davis, A.; Woodward, P.; Herwig, F. (Monthly Notices of the Royal Astronomical Society, 2016)

i-process Nucleosynthesis and Mass Retention Efficiency in He-shell Flash Evolution of Rapidly Accreting White Dwarfs - Denissenkov, Pavel A.; Herwig, Falk; Battino, Umberto; Ritter, Christian; Pignatari, Marco; Jones, Samuel; Paxton, Bill (The Astrophysical Journal Letters, 2017)

Uncertainty in Explosive Yields of Core-Collapse Supernovae - Andrews, S.; Fryer, C.; Even, W. P.; Jones, S.; Pignatari, M.; NuGrid Collaboration, (2017)

A metric space for Type Ia supernova spectra: a new method to assess explosion scenarios - Sasdelli, Michele; Hillebrandt, W.; Kromer, M.; Ishida, E. E. O.; Röpke, Friedrich; Sim, S. A.; Pakmor, R.; Seitenzahl, I. R.; Fink, M. (Monthly Notices of the Royal Astronomical Society, 2017)

Constructing stable 3D hydrodynamical models of giant stars - Ohlmann, Sebastian T.; Röpke, Friedrich; Pakmor, Rüdiger; Springel, Volker (Astronomy & Astrophysics, 2017)

Neutrinos from type Ia supernovae: The gravitationally confined detonation scenario - Wright, Warren P.; Kneller, James P.; Ohlmann, Sebastian T.; Röpke, Friedrich; Scholberg, Kate; Seitenzahl, Ivo R. (Physical Review D, 2017)

A Numerical Scheme for the Compressible Low-Mach Number Regime of Ideal Fluid Dynamics - Barsukow, Wasilij; Edelmann, Philipp V. F.; Klingenberg, Christian; Miczek, Fabian; Röpke, Friedrich (Journal of Scientific Computing, 2017)

A low-Mach Roe-type solver for the Euler equations allowing for gravity source terms - Barsukow, Wasilij; Edelmann, Philipp V.F.; Klingenberg, Christian; Röpke, Friedrich (ESAIM: ProcS, 2017)

Testing a one-dimensional prescription of dynamical shear mixing with a two-dimensional hydrodynamic simulation - Edelmann, P. V. F.; Röpke, Friedrich; Hirschi, R.; Georgy, C.; Jones, S. (Astronomy & Astrophysics, 2017)

Combustion in thermonuclear supernova explosions - Röpke, Friedrich (2017)

Type Ia supernovae with and without blueshifted narrow Na I D lines - how different is their structure? - Hachinger, S.; Röpke, Friedrich; Mazzali, P. A.; Gal-Yam, A.; Maguire, K.; Sullivan, M.; Taubenberger, S.; Ashall, C.; Campbell, H.; Elias-Rosa, N.; Feindt, U.; Greggio, L.; et al. (Monthly Notices of the Royal Astronomical Society, 2017)

Soft Gamma-ray Observation of SN2014J with Suzaku - Terada, Yukikatsu; Maeda, Keiich; Fukazawa, Yasushi; Bamba, Aya; Ueda, Yoshihiro; Katsuda, Satoru; Enoto, Teruaki; Takahashi, Tadayuki; Tamagawa, Toru; Röpke, Friedrich; Summa, Alexander; Diehl, Roland (Proceedings of the 14th International Symposium on Nuclei in the Cosmos (NIC2016), 2017)

Simulating the observed diversity of Type Ia supernovae . Introducing a model data base - Kromer, M.; Ohlmann, S.; Röpke, Friedrich (Mem. Societa Astronomica Italiana, 2017)

Spitzer observations of SN 2014J and properties of mid-IR emission in Type Ia supernovae - Johansson, J.; Goobar, A.; Kasliwal, M. M.; Helou, G.; Masci, F.; Tinyanont, S.; Jencson, J.; Cao, Y.; Fox, O. D.; Kromer, M.; Amanullah, R.; Banerjee, D. P. K.; et al. (Monthly Notices of the Royal Astronomical Society, 2017)

Testing for redshift evolution of Type Ia supernovae using the strongly lensed PS1-10afx at z = 1.4 - Petrushevska, T.; Amanullah, R.; Bulla, M.; Kromer, M.; Ferretti, R.; Goobar, A.; Papadogiannakis, S. (Astronomy & Astrophysics, 2017)

Abundance tomography of Type Iax SN 2011ay with tardis - Barna, Barnabás; Szalai, Tamás; Kromer, Markus; Kerzendorf, Wolfgang E.; Vinkó, József; Silverman, Jeffrey M.; Marion, G. H.; Wheeler, J. Craig (Monthly Notices of the Royal Astronomical Society, 2017)

Multi-messenger Observations of a Binary Neutron Star Merger - Abbott, B. P.; Abbott, R.; Abbott, T. D.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; et al., (The Astrophysical Journal Letters, 2017)

A kilonova as the electromagnetic counterpart to a gravitational-wave source - Smartt, S. J.; Chen, T.-W.; Jerkstrand, A.; Coughlin, M.; Kankare, E.; Sim, S. A.; Fraser, M.; Inserra, C.; Maguire, K.; Chambers, K. C.; Huber, M. E.; Krühler, T.; et al. (Nature, 2017)

Early light curves for Type Ia supernova explosion models - Noebauer, U. M.; Kromer, M.; Taubenberger, S.; Baklanov, P.; Blinnikov, S.; Sorokina, E.; Hillebrandt, W. (Monthly Notices of the Royal Astronomical Society, 2017)

Semi-analytic derivation of the threshold mass for prompt collapse in binary neutron-star mergers - Bauswein, Andreas; Stergioulas, Nikolaos (Monthly Notices of the Royal Astronomical Society, 2017)

Neutron-star Mergers and Nuclear Physics - Bauswein, A.; Ardevol Pulpillo, R.; Clark, J.A.; Just, O.; Goriely, S.; Janka, H.-T.; Stergioulas, N. (Acta Physica Polonica B, 2017)

Dynamics of compact object mergers - Bauswein, A. (2017)

Neutron-star Radius Constraints from GW170817 and Future Detections - Bauswein, Andreas; Just, Oliver; Janka, Hans-Thomas; Stergioulas, Nikolaos (The Astrophysical Journal Letters, 2017)

Magnetorotational instability in neutron star mergers: impact of neutrinos - Guilet, Jérôme; Bauswein, Andreas; Just, Oliver; Janka, Hans-Thomas (Monthly Notices of the Royal Astronomical Society, 2017)

Impact of Neutrino Interactions on Outflows of Neutron-Star Mergers - Just, Oliver; Goriely, Stephane; Bauswein, Andreas; Obergaulinger, Martin; Pulpillo, Ricard Ardevol; Janka, Hans-Thomas (Proceedings of the 14th International Symposium on Nuclei in the Cosmos (NIC2016), 2017)

Inferring the post-merger gravitational wave emission from binary neutron star coalescences - Chatziioannou, Katerina; Clark, James Alexander; Bauswein, Andreas; Millhouse, Margaret; Littenberg, Tyson B.; Cornish, Neil (Physical Review D, 2017)

Return of the features - Efficient feature selection and interpretation for photometric redshifts - D'Isanto, Antonio; Cavuoti, S.; Gieseke, F.; Polsterer, Kai (Astronomy & Astrophysics, 2018)

Generalised model-independent characterisation of strong gravitational lenses. III. Perturbed axisymmetric lenses - Wagner, J. (Astronomy & Astrophysics, 2018)

Generalised model-independent characterisation of strong gravitational lenses. II. Transformation matrix between multiple images - Wagner, J.; Tessore, N. (Astronomy & Astrophysics, 2018)

Model-independent and model-based local lensing properties of CL0024+1654 from multiply imaged galaxies - Wagner, Jenny; Liesenborgs, Jori; Tessore, Nicolas (Astronomy & Astrophysics, 2018)

Design and Implementation of I/O-Efficient Taxa Quartets Counting in the Context of Phylogenetic Analysis - Rülicke, Linda (2018)

Inferring Species Trees by Minimizing Quartet-based Uncertainty - Giesse, Sebastian (2018)

Models, Optimizations, and Tools for Large-Scale Phylogenetic Inference, Handling Sequence Uncertainty, and Taxonomic Validation - Kozlov, Alexey (2018)

The state of software for evolutionary biology - Darriba, Diego; Flouri, Tomáš; Stamatakis, Alexandros (Molecular Biology and Evolution, 2018)

MPBoot: fast phylogenetic maximum parsimony tree inference and bootstrap approximation - Hoang, Diep Thi; Vinh, Le Sy; Flouri, Tomáš; Stamatakis, Alexandros; von Häseler, Arndt; Minh, Bui Quang (BMC Evolutionary Biology, 2018)

Resolving complex phylogeographic patterns in the Balkan Peninsula using closely related wall-lizard species as a model system - Psonis, Nikolaos; Antoniou, Aglaia; Karameta, Emmanouela; Leaché, Adam D; Kotsakiozi, Panayiota; Darriba, Diego; Kozlov, Alexey; Stamatakis, Alexandros; Poursanidis, Dimitris; Kukushkin, Oleg; others, (Molecular Phylogenetics and Evolution, 2018)

EPA-ng: Massively Parallel Evolutionary Placement of Genetic Sequences - Barbera, Pierre; Kozlov, Alexey; Czech, Lucas; Morel, Benoit; Darriba, Diego; Flouri, Tomáš; Stamatakis, Alexandros (Systematic Biology, 2018)
Next generation sequencing (NGS) technologies have led to a ubiquity of molecular sequence data. This data avalanche is particularly challenging in metagenetics, which focuses on taxonomic identification of sequences obtained from diverse microbial environments. Phylogenetic placement methods determine how these sequences fit into an evolutionary context. Previous implementations of phylogenetic placement algorithms, such as the evolutionary placement algorithm (EPA) included in RAxML, or PPLACER, are being increasingly used for this purpose. However, due to the steady progress in NGS technologies, the current implementations face substantial scalability limitations. Herein, we present EPA-NG, a complete reimplementation of the EPA that is substantially faster, offers a distributed memory parallelization, and integrates concepts from both, RAxML-EPA and PPLACER. EPA-NG can be executed on standard shared memory, as well as on distributed memory systems (e.g., computing clusters). To demonstrate the scalability of EPA-NG, we placed 1 billion metagenetic reads from the Tara Oceans Project onto a reference tree with 3748 taxa in just under 7 h, using 2048 cores. Our performance assessment shows that EPA-NG outperforms RAxML-EPA and PPLACER by up to a factor of 30 in sequential execution mode, while attaining comparable parallel efficiency on shared memory systems. We further show that the distributed memory parallelization of EPA-NG scales well up to 2048 cores. EPA-NG is available under the AGPLv3 license: https://github.com/Pbdas/epa-ng.

Phylogenomics and the evolution of hemipteroid insects - Johnson, Kevin P; Dietrich, Christopher H; Friedrich, Frank; Beutel, Rolf G; Wipfler, Benjamin; Peters, Ralph S; Allen, Julie M; Petersen, Malte; Donath, Alexander; Walden, Kimberly KO; others, (Proceedings of the National Academy of Sciences, 2018)

A roadmap for global synthesis of the plant tree of life - Eiserhardt, Wolf L; Antonelli, Alexandre; Bennett, Dominic J; Botigué, Laura R; Burleigh, J Gordon; Dodsworth, Steven; Enquist, Brian J; Forest, Félix; Kim, Jan T; Kozlov, Alexey; others, (American Journal of Botany, 2018)

Clarifying the Relationships between Microsporidia and Cryptomycota - Bass, David; Czech, Lucas; Williams, Bryony AP; Berney, Cédric; Dunthorn, Micah; Mahé, Frederic; Torruella, Guifré; Stentiford, Grant D; Williams, Tom A (Journal of Eukaryotic Microbiology, 2018)

New data, same story: phylogenomics does not support Syrphoidea (Diptera: Syrphidae, Pipunculidae) - Pauli, Thomas; Burt, Trevor O; Meusemann, Karen; Bayless, Keith; Donath, Alexander; Podsiadlowski, Lars; Mayer, Christoph; Kozlov, Alexey; Vasilikopoulos, Alexandros; Liu, Shanlin; others, (Systematic Entomology, 2018)

Phylogenomic analysis of Apoidea sheds new light on the sister group of bees - Sann, Manuela; Niehuis, Oliver; Peters, Ralph S; Mayer, Christoph; Kozlov, Alexey; Podsiadlowski, Lars; Bank, Sarah; Meusemann, Karen; Misof, Bernhard; Bleidorn, Christoph; others, (BMC Evolutionary Biology, 2018)

Transcriptome sequence-based phylogeny of chalcidoid wasps (Hymenoptera: Chalcidoidea) reveals a history of rapid radiations, convergence, and evolutionary success - Peters, Ralph S; Niehuis, Oliver; Gunkel, Simon; Bläser, Marcel; Mayer, Christoph; Podsiadlowski, Lars; Kozlov, Alexey; Donath, Alexander; van Noort, Simon; Liu, Shanlin; others, (Molecular Phylogenetics and Evolution, 2018)

Methods for Automatic Reference Trees and Multilevel Phylogenetic Placement - Czech, Lucas; Stamatakis, Alexandros (Bioinformatics, 2018)

Scalable Methods for Post-Processing, Visualizing, and Analyzing Phylogenetic Placements - Czech, Lucas; Stamatakis, Alexandros (bioRxiv, 2018)

ParGenes: a tool for massively parallel model selection and phylogenetic tree inference on thousands of genes. - Morel, Benoit; Kozlov, Alexey; Stamatakis, Alexandros (Bioinformatics, 2018)

Population and Evolutionary Genetic Inferences in the Whole-Genome Era: Software Challenges - Stamatakis, Alexandros (2018)

Compressing Streams of Phylogenetic Trees - Trefzer, Axel; Stamatakis, Alexandros (bioRxiv, 2018)

RAxML-NG: A fast, scalable, and user-friendly tool for maximum likelihood phylogenetic inference - Kozlov, Alexey; Darriba, Diego; Flouri, Tomas; Morel, Benoit; Stamatakis, Alexandros (bioRxiv, 2018)

Precipitation sensitivity to the uncertainty of terrestrial water flow in WRF-Hydro: An ensemble analysis for Central Europe - Arnault, J.; Rummler, T.; Baur, F.; Lerch, Sebastian; Wagner, S.; Fersch, B.; Zhang, Z.; Kerandi, N.; Keil, C.; Kunstmann, H. (Journal of Hydrometeorology, 2018)

Combining predictive distributions for the statistical post-processing of ensemble forecasts - Baran, S.; Lerch, Sebastian (International Journal of Forecasting, 2018)

Forecast dominance testing via sign randomization - Ehm, W.; Krüger, F. (Electronic Journal of Statistics, 2018)

Special section in memory of Stephen E. Fienberg (1942–2016) AOAS Editor-in-Chief 2013–2015 - Gneiting, Tilmann; Asher, J.; Carriquiry, A.; Davis, R.; Dawid, A. P.; Efron, B.; Haberman, S.; Kou, S.; Newton, M.; Paddock, S.; Prewitt, K.; Raftery, A.; et al. (The Annals of Applied Statistics, 2018)

Forecasting wind gusts in winter storms using a calibrated convection‐permitting ensemble - Pantillon, F.; Lerch, Sebastian; Knippertz, P.; Corsmeier, U. (Quarterly Journal of the Royal Meteorological Society, 2018)

Neural networks for postprocessing ensemble weather forecasts - Rasp, S.; Lerch, Sebastian (Monthly Weather Review, 2018)

Skill of global raw and postprocessed ensemble predictions of rainfall over northern tropical Africa - Vogel, P.; Knippertz, P.; Fink, A. H.; Schlueter, A.; Gneiting, Tilmann (Weather and Forecasting, 2018)

Uncertainty quantification for a blood pump device with generalized polynomial chaos expansion - Song, Chen (2018)

Extraction of Spatial-Temporal Features of Bus Loads in Electric Grids through Clustering in a Dynamic Model Space - Zhang, Wei; Mu, Gang; Song, Chen; Yan, Gangui; Heuveline, Vincent (IEEE Transactions on Sustainable Energy, 2019)

Uncertainty quantification for fluid-structure interaction, application to aortic biomechanics - Kratzke, Jonas (2018)

Dielectrophoretic force-driven convection in annular geometry under Earth’s gravity - Seelig, Torsten; Meyer, Antoine; Gerstner, Philipp; Meier, Martin; Jongmanns, Marcel; Baumann, Martin; Heuveline, Vincent; Egbers, Christoph (arXiv preprint arXiv:1812.05460, 2018)

OpenGL@API-Based Analysis of Large Datasets in a Cloud Environment - Mexner, Wolfgang; Bonn, Matthias; Kopmann, Andreas; Mauch, Viktor; Ressmann, Doris; Chilingaryan, Suren A; Jerome, Nicholas Tan; van de Kamp, Thomas; Heuveline, Vincent; Lösel, Philipp (2018)

Nested Schur-Complement Solver for a Low-Mach Number Model: Application to a Cyclone-Cyclone Interaction - Gawlok, Simon; Heuveline, Vincent (Preprint Series of the Engineering Mathematics and Computing Lab, 2018)

Learning model discrepancy of an electric motor with Bayesian inference - John, David; Schick, Michael; Heuveline, Vincent (Preprint Series of the Engineering Mathematics and Computing Lab, 2018)

Bayesian inference for estimating model discrepancy of an electric motor - John, David; Schick, Michael; Heuveline, Vincent (PAMM, 2018)

Parasitoid biology preserved in mineralized fossils - van de Kamp, Thomas; Schwermann, Achim H.; dos Santos Rolo, Tomy; Lösel, Philipp; Engler, Thomas; Etter, Walter; Faragó, Tomáš; Göttlicher, Jörg; Heuveline, Vincent; Kopmann, Andreas; Mähler, Bastian; Mörs, Thomas; et al. (Nature Communications, 2018)

Toric Varieties vs. Horofunction Compactifications of Polyhedral Norms - Ji, Lizhen; Schilling, Anna (L’Enseignement Mathèmatique, 2018)

Autoregulation of von Willebrand factor function by a disulfide bond switch. - Butera, D.; Passam, F.; Ju, L.; Cook, K. M.; Woon, H.; Aponte-Santamaria, C.; Gardiner, E.; Davis, A. K.; Murphy, D. A.; Bronowska, A.; Luken, B. M.; Baldauf, C.; et al. (Sci Adv, 2018)
Force-dependent binding of platelet glycoprotein Ib (GPIb) receptors to plasma von Willebrand factor (VWF) plays a key role in hemostasis and thrombosis. Previous studies have suggested that VWF activation requires force-induced exposure of the GPIb binding site in the A1 domain that is autoinhibited by the neighboring A2 domain. However, the biochemical basis of this "mechanopresentation" remains elusive. From a combination of protein chemical, biophysical, and functional studies, we find that the autoinhibition is controlled by the redox state of an unusual disulfide bond near the carboxyl terminus of the A2 domain that links adjacent cysteine residues to form an eight-membered ring. Only when the bond is cleaved does the A2 domain bind to the A1 domain and block platelet GPIb binding. Molecular dynamics simulations indicate that cleavage of the disulfide bond modifies the structure and molecular stresses of the A2 domain in a long-range allosteric manner, which provides a structural explanation for redox control of the autoinhibition. Significantly, the A2 disulfide bond is cleaved in ~75% of VWF subunits in healthy human donor plasma but in just ~25% of plasma VWF subunits from heart failure patients who have received extracorporeal membrane oxygenation support. This suggests that the majority of plasma VWF binding sites for platelet GPIb are autoinhibited in healthy donors but are mostly available in heart failure patients. These findings demonstrate that a disulfide bond switch regulates mechanopresentation of VWF.

Stability of Biological Membranes upon Mechanical Indentation. - Franz, F.; Aponte-Santamaria, C.; Daday, C.; Miletic, V.; Grater, F. (J Phys Chem B, 2018)
Mechanical perturbations are ubiquitous in living cells, and many biological functions are dependent on the mechanical response of lipid membranes. Recent force-spectroscopy studies have captured the stepwise fracture of stacks of bilayers, avoiding substrate effects. However, the effect of stacking bilayers, as well as the exact molecular mechanism of the fracture process, is unknown. Here, we use atomistic and coarse-grained force-clamp molecular dynamics simulation to assess the effects of mechanical indentation on stacked and single bilayers. Our simulations show that the rupture process obeys the laws of force-activated barrier crossing, and stacking multiple membranes stabilizes them. The rupture times follow a log-normal distribution which allows the interpretation of membrane rupture as a pore-growth process. Indenter hydrophobicity determines the type of pore formation, the preferred dwelling region, and the resistance of the bilayer against rupture. Our results provide a better understanding of the nanomechanics underlying the plastic rupture of lipid membranes.
Keywords: Hydrophobic and Hydrophilic Interactions; Lipid Bilayers/*chemistry; Microscopy, Atomic Force; Molecular Dynamics Simulation; *Stress, Mechanical

Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology. - Friedman, R.; Khalid, S.; Aponte-Santamaria, C.; Arutyunova, E.; Becker, M.; Boyd, K. J.; Christensen, M.; Coimbra, J. T. S.; Concilio, S.; Daday, C.; van Eerden, F. J.; Fernandes, P. A.; et al. (J Membr Biol, 2018)
This is a perspective article entitled "Frontiers in computational biophysics: understanding conformational dynamics of complex lipid mixtures relevant to biology" which is following a CECAM meeting with the same name.
Keywords: Cell Membrane/*chemistry/*metabolism; Computational Biology/*methods; Lipid Bilayers/*chemistry; Molecular Dynamics Simulation; Protein Binding; Thermodynamics

CONAN: A Tool to Decode Dynamical Information from Molecular Interaction Maps. - Mercadante, D.; Grater, F.; Daday, C. (Biophys J, 2018)
The analysis of contacts is a powerful tool to understand biomolecular function in a series of contexts, from the investigation of dynamical behavior at equilibrium to the study of nonequilibrium dynamics in which the system moves between multiple states. We thus propose a tool called CONtact ANalysis (CONAN) that, from molecular dynamics (MD) trajectories, analyzes interresidue contacts, creates videos of time-resolved contact maps, and performs correlation, principal component, and cluster analysis, revealing how specific contacts relate to functionally relevant states sampled by MD. We present how CONAN can identify features describing the dynamics of ubiquitin both at equilibrium and during mechanical unfolding. Additionally, we show the analysis of MD trajectories of an alpha-synuclein mutant peptide that undergoes an alpha-beta conformational transition that can be easily monitored using CONAN, which identifies the multiple states that the peptide explores along its conformational dynamics. The high versatility and ease of use of the software make CONAN a tool that can significantly facilitate the understanding of the complex dynamical behavior of proteins or other biomolecules. CONAN and its documentation are freely available for download on GitHub.
Keywords: Molecular Dynamics Simulation; Mutation; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Mapping/*methods; Ubiquitin/chemistry/metabolism; alpha-Synuclein/chemistry/genetics/metabolism

Mechano-redox control of integrin de-adhesion. - Passam, F.; Chiu, J.; Ju, L.; Pijning, A.; Jahan, Z.; Mor-Cohen, R.; Yeheskel, A.; Kolsek, K.; Tharichen, L.; Aponte-Santamaria, C.; Grater, F.; Hogg, P. J. (Elife, 2018)
How proteins harness mechanical force to control function is a significant biological question. Here we describe a human cell surface receptor that couples ligand binding and force to trigger a chemical event which controls the adhesive properties of the receptor. Our studies of the secreted platelet oxidoreductase, ERp5, have revealed that it mediates release of fibrinogen from activated platelet alphaIIbbeta3 integrin. Protein chemical studies show that ligand binding to extended alphaIIbbeta3 integrin renders the betaI-domain Cys177-Cys184 disulfide bond cleavable by ERp5. Fluid shear and force spectroscopy assays indicate that disulfide cleavage is enhanced by mechanical force. Cell adhesion assays and molecular dynamics simulations demonstrate that cleavage of the disulfide induces long-range allosteric effects within the betaI-domain, mainly affecting the metal-binding sites, that results in release of fibrinogen. This coupling of ligand binding, force and redox events to control cell adhesion may be employed to regulate other protein-protein interactions.
Keywords: Allosteric Regulation; Binding Sites; Blood Platelets/chemistry/cytology/*metabolism; Cloning, Molecular; Crystallography, X-Ray; Escherichia coli/genetics/metabolism; Fibrinogen/*chemistry/genetics/metabolism; Gene Expression; Genetic Vectors/chemistry/metabolism; Humans; Kinetics; *Mechanotransduction, Cellular; Molecular Dynamics Simulation; Oxidation-Reduction; Platelet Adhesiveness; Platelet Glycoprotein GPIIb-IIIa Complex/*chemistry/genetics/metabolism; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Disulfide-Isomerases/chemistry/genetics/metabolism; Protein Interaction Domains and Motifs; Proteolysis; Recombinant Proteins/chemistry/genetics/metabolism; Substrate Specificity

On the mechanism of spontaneous thiol-disulfide exchange in proteins. - Putzu, M.; Grater, F.; Elstner, M.; Kubar, T. (Phys Chem Chem Phys, 2018)
The thiol-disulfide exchange reaction in model systems and small peptides was investigated by means of a combined QM/MM metadynamics scheme. The free energy landscapes of these systems were generated, providing the structures of reactants and products with atomic detail, as well as the heights of free energy barriers (or, activation energies) opposing the spontaneous exchange. A QM/MM scheme with purely classical water turned out to be an efficient and accurate compromise solution. The calculations yielded the expected symmetric trisulfide transition state at S-S distances of 2.7 A, interestingly, with a slight deviation from linearity at an S-S-S angle of 165 degrees . The structure of the transition state as well as the free energy barrier were very similar for the intramolecular thiol-disulfide reactions in model peptides. While CXC disulfide bonds were found sterically unfavorable, CXXC were favored over longer-range disulfide bonds along the peptide backbone, in line with the high abundance of CXXC motifs in redox proteins.
Keywords: Amino Acid Motifs; Disulfides/*chemistry; Molecular Structure; Peptides/chemistry; Proteins/*chemistry; Sulfhydryl Compounds/*chemistry; Water/chemistry

Probing molecular forces in multi-component physiological membranes. - Ray, A.; Grater, F.; Thukral, L. (Phys Chem Chem Phys, 2018)
Biological membranes are remarkably heterogeneous, composed of diverse lipid mixtures with distinct chemical structure and composition. By combining molecular dynamics simulations and the newly developed Lipid-Force Distribution Analysis (L-FDA), we explore force transmission in complex multi-component membrane models mimicking eukaryotic organelles. We found that the chemical-moiety based segmentation at membrane interfaces revealed a distinctive distribution of bonded and non-bonded forces in diverse membrane environment. Our molecular stress analysis could have far-reaching implications in describing the relationship between membrane mechanical properties and functional states of chemically distinct lipids.
Keywords: Algorithms; Cluster Analysis; Endoplasmic Reticulum/chemistry; Golgi Apparatus/chemistry; Lipid Bilayers/*chemistry/metabolism; Mitochondria/chemistry; Molecular Dynamics Simulation; Phosphatidylcholines/chemistry; Phosphatidylethanolamines/chemistry

Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors. - Tan, P. S.; Aramburu, I. V.; Mercadante, D.; Tyagi, S.; Chowdhury, A.; Spitz, D.; Shammas, S. L.; Grater, F.; Lemke, E. A. (Cell Rep, 2018)
Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC). Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs. Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1. Association and dissociation rate constants are more than an order of magnitude lower than in the archetypal-fuzzy complex between FG-Nup153 and NTRs. Unexpectedly, this behavior appears not to be encoded selectively into CRM1 but rather into the FG-Nup214 sequence. The same distinct binding mechanisms are unperturbed in O-linked beta-N-acetylglucosamine-modified FG-Nups. Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell.
Keywords: Escherichia coli/genetics/metabolism; Fluorescence Resonance Energy Transfer; Glycine/metabolism; Humans; Models, Molecular; Nuclear Pore/chemistry/*metabolism; Nuclear Pore Complex Proteins/chemistry/*metabolism; Phenylalanine/metabolism; Protein Binding; Protein Conformation

The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing - Begolo, Daniela; Vincent, Isabel M.; Giordani, Federica; Pöhner, Ina; Witty, Michael J.; Rowan, Timothy G.; Bengaly, Zakaria; Gillingwater, Kirsten; Freund, Yvonne; Wade, Rebecca C.; Barrett, Michael P.; Clayton, Christine (PLoS Pathogens, 2018)

MCMap - A Computational Tool for Mapping Energy Landscapes of Transient Protein-Protein Interactions - Foerster, Johannes M.; Pöhner, Ina; Ullmann, G. Matthias (ACS Omega, 2018)

Estimation of Drug-Target Residence Times by τ-Random Acceleration Molecular Dynamics Simulations - Kokh, Daria; Amaral, Marta; Bomke, Joerg; Grädler, Ulrich; Musil, Djordje; Buchstaller, Hans-Peter; Dreyer, Matthias K.; Frech, Matthias; Lowinski, Maryse; Vallee, Francois; Bianciotto, Marc; Rak, Alexey; et al. (Journal of Chemical Theory and Computation, 2018)

Dependence of Chromatosome Structure on Linker Histone Sequence and Posttranslational Modification - Öztürk, Mehmet Ali; Cojocaru, Vlad; Wade, Rebecca C. (Biophysical Journal, 2018)

Toward an Ensemble View of Chromatosome Structure: A Paradigm Shift from One to Many - Öztürk, Mehmet Ali; Cojocaru, Vlad; Wade, Rebecca C. (Structure, 2018)

Prediction of Drug–Target Binding Kinetics by Comparative Binding Energy Analysis - Ganotra, Gaurav K.; Wade, Rebecca C. (ACS Medicinal Chemistry Letters, 2018)

New approaches for computing ligand–receptor binding kinetics - Bruce, Neil J; Ganotra, Gaurav K; Kokh, Daria; Sadiq, Kashif; Wade, Rebecca C. (Current Opinion in Structural Biology, 2018)

Halogen–Aromatic π Interactions Modulate Inhibitor Residence Times - Heroven, Christina; Georgi, Victoria; Ganotra, Gaurav K.; Brennan, Paul; Wolfreys, Finn; Wade, Rebecca C.; Fernández-Montalván, Amaury E.; Chaikuad, Apirat; Knapp, Stefan (Angewandte Chemie International Edition, 2018)

Halogenaromatische π-Wechselwirkungen modulieren die Verweilzeit von Inhibitoren - Heroven, Christina; Georgi, Victoria; Ganotra, Gaurav K.; Brennan, Paul; Wolfreys, Finn; Wade, Rebecca C.; Fernández-Montalván, Amaury E.; Chaikuad, Apirat; Knapp, Stefan (Angewandte Chemie, 2018)

Equilibrium model of drug-modulated GagPol-embedded HIV-1 reverse transcriptase dimerization to enhance premature protease activation - Sadiq, Kashif; Mirambeau, Gilles; Meyerhans, Andreas (AIDS Research and Human Retroviruses, 2018)

Inter-subunit interactions drive divergent dynamics in mammalian and \textitPlasmodium actin filaments - Douglas, Ross G.; Nandekar, Prajwal; Aktories, Julia-Elisabeth; Kumar, Hirdesh; Weber, Rebekka; Sattler, Julia M.; Singer, Mirko; Lepper, Simone; Sadiq, Kashif; Wade, Rebecca C.; Frischknecht, Friedrich (PLoS biology, 2018)

Impact of carbonylation on glutathione peroxidase-1 activity in human hyperglycemic endothelial cells - Sultan, Cheryl S.; Saackel, Andrea; Stank, Antonia; Fleming, Thomas; Fedorova, Maria; Hoffmann, Ralf; Wade, Rebecca C.; Hecker, Markus; Wagner, Andreas H. (Redox Biology, 2018)

On the road to MSC 2020 (Editorial) - Bannister, Adam; Müller, Fabian G.; Müller, Mark-Christoph; Teschke, Olaf (Newsletter of the European Mathematical Society, 2018)

BPEmb: Tokenization-free pre-trained subword embeddings in 275 languages - Heinzerling, Benjamin; Strube, Michael (2018)

Unrestricted bridging resolution - Hou, Yufang; Markert, Katja; Strube, Michael (Computational Linguistics, 2018)

Exploiting a speaker’s credibility to detect fake news - Kirilin, Angelika; Strube, Michael (2018)

A neural local coherence model for text quality assessment - Mesgar, Mohsen; Strube, Michael (2018)

Title generation and keyphrase extraction from Persian scientific texts - Mohseni, Mahdi; Faili, Hashaam (2018)

On the contribution of word-level semantics to practical author name disambiguation - Müller, Mark-Christoph (2018)

Transparent, efficient, and robust word embedding access with WOMBAT - Müller, Mark-Christoph; Strube, Michael (2018)

Using linguistic features to improve generalization in neural coreference resolvers - Moosavi, Nafise Sadat; Strube, Michael (2018)

Not just depressed: Bipolar disorder prediction on Reddit - Sekulić, Ivan; Gjurković, Matej; Šnajder, Jan (2018)

Extending and exploiting the entity graph for analysis, classification and visualization of German texts - Suter, Julia; Strube, Michael (2018)

What’s important in a text? An extensive evaluation of linguistic annotations for summarization - Zopf, Markus; Botschen, Teresa; Falke, Tobias; Heinzerling, Benjamin; Marasovic, Ana; Mihaylov, Todor; P.V.S., Avinesh; Loza Mencía, Eneldo; Fürnkranz, Johannes; Frank, Anette (2018)

Proceedings of the 2nd ACL Workshop on Ethics in Natural Language Processing, New Orleans, Louis., 5 June 2018 - Alfano, Mark; Hovy, Dirk; Mitchell, Margaret; Strube, Michael (Proceedings of the 2nd ACL Workshop on Ethics in Natural Language Processing, New Orleans, Louis., 5 June 2018, 2018)

Three Hypervelocity White Dwarfs in Gaia DR2: Evidence for Dynamically Driven Double-degenerate Double-detonation Type Ia Supernovae - Shen, Ken J.; Boubert, Douglas; Gänsicke, Boris T.; Jha, Saurabh W.; Andrews, Jennifer E.; Chomiuk, Laura; Foley, Ryan J.; Fraser, Morgan; Gromadzki, Mariusz; Guillochon, James; Kotze, Marissa M.; Maguire, Kate; et al. (The Astrophysical Journal, 2018)

Type Iax supernovae as a few-parameter family - Barna, Barnabás; Szalai, Tamás; Kerzendorf, Wolfgang E; Kromer, Markus; Sim, Stuart A; Magee, Mark R; Leibundgut, Bruno (Monthly Notices of the Royal Astronomical Society, 2018)

The r-process nucleosynthesis and related challenges - Goriely, Stephane; Bauswein, Andreas; Janka, Hans-Thomas; Just, Oliver; Pllumbi, Else (EPJ Web Conf., 2017)

The Progenitor Systems of Thermonuclear Supernovae - Hillebrandt, W.; Bulla, M.; Kromer, M.; Pakmor, R.; Röpke, Friedrich; Schrauth, M.; Sim, S. A. (2018)
Despite the importance of Type Ia supernovae for modern astrophysics, their detailed explosion mechanism is still not fully understood. In this article, we present recent findings from numerical models in the context of their observed diversity and we discuss how these models can help to shed light on the explosion mechanism and to identify their progenitor systems. It is shown that the models have considerable predictive power and they can aid the identification of sources of systematic errors when used as distance indicators for cosmology.

Towards Multidimensional Hydrodynamic Simulations of Stars - Röpke, Friedrich; Berberich, J.; Edelmann, P. F. V.; Horst, Leonhard; Jones, S. W.; Michel, A.; Botto Poala, A. (2018)
With the Seven-League Hydro (SLH) code, designed to model hydrodynamic flows in stellar interiors, simulations of dynamical processes in multidimensional hydrodynamic simulations are carried out. After a description of the features of SLH, we present several examples of its applications to problems in stellar astrophysics.

Nucleosynthesis during a Thermonuclear Supernova Explosion - Panov, I. V.; Glazyrin, S. I.; Röpke, Friedrich; Blinnikov, S. I. (Astronomy Letters, 2018)

Universal relations for differentially rotating relativistic stars at the threshold to collapse - Bozzola, Gabriele; Stergioulas, Nikolaos; Bauswein, Andreas (Monthly Notices of the Royal Astronomical Society, 2018)

An updated Type II supernova Hubble diagram - Gall, E. E. E.; Kotak, R.; Leibundgut, B.; Taubenberger, S.; Hillebrandt, W.; Kromer, M.; Burgett, W. S.; Chambers, K.; Flewelling, H.; Huber, M. E.; Kaiser, N.; Kudritzki, R. P.; et al. (Astronomy & Astrophysics, 2018)

Models for Type Ia Supernovae and Related Astrophysical Transients - Röpke, Friedrich; Sim, Stuart A. (Space Science Reviews, 2018)

OGLE14-073 - a promising pair-instability supernova candidate - Kozyreva, Alexandra; Kromer, Markus; Noebauer, Ulrich M; Hirschi, Raphael (Monthly Notices of the Royal Astronomical Society, 2018)

Thermonuclear explosions of rapidly differentially rotating white dwarfs: Candidates for superluminous Type Ia supernovae? - Fink, M.; Kromer, M.; Hillebrandt, W.; Röpke, Friedrich; Pakmor, R.; Seitenzahl, I.R.; Sim, S.A. (Astronomy & Astrophysics, 2018)

Monte-Carlo methods for NLTE spectral synthesis of supernovae - Ergon, M.; Fransson, C.; Jerkstrand, A.; Kozma, C.; Kromer, M.; Spricer, K. (Astronomy & Astrophysics, 2018)

Improving the convergence properties of the moving-mesh code AREPO - Pakmor, Rüdiger; Springel, Volker; Bauer, Andreas; Mocz, Philip; Munoz, Diego J.; Ohlmann, Sebastian T.; Schaal, Kevin; Zhu, Chenchong (Monthly Notices of the Royal Astronomical Society, 2016)

Hydrodynamic moving-mesh simulations of the common envelope phase in binary stellar systems - Ohlmann, Sebastian T.; Röpke, Friedrich; Pakmor, Rüdiger; Springel, Volker (Astrophysical Journal Letters, 2016)

Type Ia supernovae from violent mergers of carbon-oxygen white dwarfs: polarization signatures - Bulla, M.; Sim, S. A.; Pakmor, R.; Kromer, M.; Taubenberger, S.; Röpke, Friedrich; Hillebrandt, W.; Seitenzahl, I. R. (Monthly Notices of the Royal Astronomical Society, 2016)

Quantitative spectral analysis of the sdB star HD 188112: A helium-core white dwarf progenitor - Latour, M.; Heber, U.; Irrgang, A.; Schaffenroth, V.; Geier, S.; Hillebrandt, W.; Röpke, Friedrich; Taubenberger, S.; Kromer, M.; Fink, M. (Astronomy & Astrophysics, 2016)

H ingestion into He-burning convection zones in super-AGB stellar models as a potential site for intermediate neutron-density nucleosynthesis - Jones, S.; Ritter, C.; Herwig, F.; Fryer, C.; Pignatari, M.; Bertolli, M. G.; Paxton, B. (Monthly Notices of the Royal Astronomical Society, 2015)

Neutron-star Merger Ejecta as Obstacles to Neutrino-powered Jets of Gamma-Ray Bursts - Just, O.; Obergaulinger, M.; Janka, H.-T.; Bauswein, A.; Schwarz, N. (Astrophysical Journal Letters, 2016)

The Origin of the Cosmic Gamma-ray Background in the MeV Range - Ruiz-Lapuente, Pilar; The, Lih-Sin; Hartmann, Dieter H.; Ajello, Marco; Canal, Ramon; Röpke, Friedrich; Ohlmann, Sebastian T.; Hillebrandt, Wolfgang (The Astrophysical Journal, 2016)

Three-dimensional simulations of gravitationally confined detonations compared to observations of SN 1991T - Seitenzahl, Ivo R.; Kromer, Markus; Ohlmann, Sebastian T.; Ciaraldi-Schoolmann, Franco; Marquardt, Kai; Fink, Michael; Hillebrandt, Wolfgang; Pakmor, Rüdiger; Röpke, Friedrich; Ruiter, Ashley J.; Sim, Stuart A.; Taubenberger, Stefan (Astronomy & Astrophysics, 2016)

Neutron excess number and nucleosynthesis of heavy elements in a type Ia supernova explosion - Panov, I. V.; Korneev, I. Y.; Blinnikov, S. I.; Röpke, Friedrich (Soviet Journal of Experimental and Theoretical Physics Letters, 2016)

The type Iax supernova, SN 2015H. A white dwarf deflagration candidate - Magee, M. R.; Kotak, R.; Sim, S. A.; Kromer, M.; Rabinowitz, D.; Smartt, S. J.; Baltay, C.; Campbell, H. C.; Chen, T.-W.; Fink, M.; Gal-Yam, A.; Galbany, L.; et al. (Astronomy & Astrophysics, 2016)

Measurements of the Soft Gamma-Ray Emission from SN2014J with Suzaku - Terada, Y.; Maeda, K.; Fukazawa, Y.; Bamba, A.; Ueda, Y.; Katsuda, S.; Enoto, T.; Takahashi, T.; Tamagawa, T.; Röpke, Friedrich; Summa, A.; Diehl, R. (The Astrophysical Journal, 2016)

The peculiar Type Ia supernova iPTF14atg: Chandrasekhar-mass explosion or violent merger? - Kromer, M.; Fremling, C.; Pakmor, R.; Taubenberger, S.; Amanullah, R.; Cenko, S. B.; Fransson, C.; Goobar, A.; Leloudas, G.; Taddia, F.; Röpke, Friedrich; Seitenzahl, I. R.; et al. (Monthly Notices of the Royal Astronomical Society, 2016)

Magnetic Field Amplification During the Common Envelope Phase - Ohlmann, Sebastian T.; Röpke, Friedrich; Pakmor, Rüdiger; Springel, Volker; Müller, Ewald (Monthly Notices of the Royal Astronomical Society, 2016)

Predicting polarization signatures for double-detonation and delayed-detonation models of Type Ia supernovae - Bulla, M.; Sim, S. A.; Kromer, M.; Seitenzahl, I. R.; Fink, M.; Ciaraldi-Schoolmann, F.; Röpke, Friedrich; Hillebrandt, W.; Pakmor, R.; Ruiter, A. J.; Taubenberger, S. (Monthly Notices of the Royal Astronomical Society, 2016)

Do electron-capture supernovae make neutron stars?. First multidimensional hydrodynamic simulations of the oxygen deflagration - Jones, S.; Röpke, Friedrich; Pakmor, R.; Seitenzahl, I. R.; Ohlmann, S. T.; Edelmann, P. V. F. (Astronomy & Astrophysics, 2016)

The r-process nucleosynthesis during the decompression of neutron star crust material - Goriely, S; Bauswein, A; Janka, H-T; Panebianco, S; Sida, J-L; Lemaître, J-F; Hilaire, S; Dubray, N (Journal of Physics Conference Series, 2016)

Exploring properties of high-density matter through remnants of neutron-star mergers - Bauswein, Andreas; Stergioulas, Nikolaos; Janka, Hans-Thomas (European Physical Journal A, 2016)

On the robustness of the r-process in neutron-star mergers against variations of nuclear masses - Mendoza-Temis, J J; Wu, M R; Martínez-Pinedo, G; Langanke, K; Bauswein, A; Janka, H-T; Frank, A (Journal of Physics Conference Series, 2016)

Observing gravitational waves from the post-merger phase of binary neutron star coalescence - Clark, J A; Bauswein, A; Stergioulas, N; Shoemaker, D (Classical and Quantum Gravity, 2016)

NuGrid Stellar Data Set. I.Stellar Yields from H to Bi for Stars with Metallicities Z = 0.02 and Z = 0.01 - Pignatari, M.; Herwig, F.; Hirschi, R.; Bennett, M.; Rockefeller, G.; Fryer, C.; Timmes, F. X.; Ritter, C.; Heger, A.; Jones, S.; Battino, U.; Dotter, A.; et al. (The Astrophysical Journal Supplement Series, 2016)

Uncertainties in Galactic Chemical Evolution Models - Côté, Benoit; Ritter, Christian; O’Shea, Brian W.; Herwig, Falk; Pignatari, Marco; Jones, Samuel; Fryer, Chris L. (The Astrophysical Journal, 2016)

Parallel Computing: On the Road to Exascale, Proceedings of the International Conference on Parallel Computing, ParCo 2015, 1-4 September 2015, Edinburgh, Scotland, UK - Joubert, Gerhard R.; Leather, Hugh; Parsons, Mark; Peters, Frans J.; Sawyer, Mark (Parallel Computing: On the Road to Exascale, Proceedings of the International Conference on Parallel Computing, ParCo 2015, 1-4 September 2015, Edinburgh, Scotland, UK, 2016)

Hydrodynamics of the Common Envelope Phase in Binary Stellar Evolution - Ohlmann, Sebastian T. (2016)

Low Mach Number Simulations of Convective Boundary Mixing in Classical Novae - Bolaños Rosales, Alejandro (2016)

Extreme Scale-out SuperMUC Phase 2 - lessons learned - Hammer, Nicolay; Jamitzky, Ferdinand; Satzger, Helmut; Allalen, Momme; Block, Alexander; Karmakar, Anupam; Brehm, Matthias; Bader, Reinhold; Iapichino, Luigi; Ragagnin, Antonio; Karakasis, Vasilios; Kranzlmueller, Dieter; et al. (2016)

Photometric redshift estimations - Polsterer, Kai L. (2017)

Properties of optically selected BL Lacertae candidates from the SDSS - Kügler, S. D.; Nilsson, K.; Heidt, J.; Esser, J.; Schultz, T. (A&A, 2014)
Context. Deep optical surveys open the avenue for finding large numbers of BL Lac objects that are hard to identify because they lack the unique properties classifying them as such. While radio or X-ray surveys typically reveal dozens of sources, recent compilations based on optical criteria alone have increased the number of BL Lac candidates considerably. However, these compilations are subject to biases and may contain a substantial number of contaminating sources.

Speedy Greedy Feature Selection: Better Redshift Estimation via Massive Parallelism - Gieseke, F.; Polsterer, Kai; Oancea, Cosmin Eugen; Igel, Christian (European Symposium on Artificial Neural Networks, Computational Intelligence And Machine Learning, 2014)
Nearest neighbor models are among the most basic tools in machine learning, and recent work has demonstrated their effectiveness in the field of astronomy. The performance of these models crucially depends on the underlying metric, and in particular on the selection of a meaningful subset of informative features. The feature selection is task-dependent and usually very time-consuming. In this work, we propose an efficient parallel implementation of incremental feature selection for nearest neighbor models utilizing nowadays graphics processing units. Our framework provides significant computational speed-ups over its sequential single-core competitor of up to two orders of magnitude. We demonstrate the applicability of the overall scheme on one of the most challenging tasks in astronomy: redshift estimation for distant galaxies.

Improving the performance of photometric regression models via massive parallel feature selection - Polsterer, Kai; Gieseke, F.; Igel, Christian; Goto, Tomotsugu (2014)
Regression tasks are common in astronomy, for instance, the estimation of the redshift or the metallicity of galaxies. Generating regression models, however, is often hindered by the heterogeneity of the available input catalogs, which leads to missing data and/or features of differing explanatory power. In this work, we show how simple but effective feature selection schemes from data mining can be used to significantly improve the performance of regression models for photometric redshift and metallicity estimation (even without any particular knowledge of the input parameters' physical properties). Our framework tests huge amounts of possible feature combinations. Since corresponding (single-core) implementations are computationally very demanding, we make use of the massive computational resources provided by nowadays graphics processing units to significantly reduce the overall runtime. This renders an exhaustive search possible, as we demonstrate in our experimental evaluation. We conclude the work by discussing further applications of our approach in the context of large-scale astronomical learning settings.

On GPU-Based Nearest Neighbor Queries for Large-Scale Photometric Catalogs in Astronomy - Heinermann, Justin; Kramer, Manuel; Polsterer, Kai; Gieseke, Fabian (2013)
Nowadays astronomical catalogs contain patterns of hundreds of millions of objects with data volumes in the terabyte range. Upcoming projects will gather such patterns for several billions of objects with peta- and exabytes of data. From a machine learning point of view, these settings often yield unsupervised, semi-supervised, or fully supervised tasks, with large training and huge test sets. Recent studies have demonstrated the effectiveness of prototype-based learning schemes such as simple nearest neighbor models. However, although being among the most computationally efficient methods for such settings (if implemented via spatial data structures), applying these models on all remaining patterns in a given catalog can easily take hours or even days. In this work, we investigate the practical effectiveness of GPU-based approaches to accelerate such nearest neighbor queries in this context. Our experiments indicate that carefully tuned implementations of spatial search structures for such multi-core devices can significantly reduce the practical runtime. This renders the resulting frameworks an important algorithmic tool for current and upcoming data analyses in astronomy.

Learning morphological maps of galaxies with unsupervised regression - Kramer, Oliver; Gieseke, Fabian; Polsterer, Kai Lars (Expert Systems with Applications, 2013)

Finding new high-redshift quasars by asking the neighbours - Polsterer, Kai Lars; Zinn, Peter-Christian; Gieseke, Fabian (2013)

Linear Dimensionality Reduction for Time Series - Gianniotis, Nikos (Neural Information Processing, 2017)
Visualisation by dimensionality reduction is an important tool for data exploration. In this work we are interested in visualising time series. To that end we formulate a latent variable model that mirrors probabilistic principal component analysis (PPCA). However, as opposed to PPCA which maps the latent variables directly to the data space, we first map the latent variables to the parameter space of a recurrent neural network, i.e. each latent projection instantiates a recurrent network. Each instantiated recurrent network in turn is responsible for modelling a time series in the dataset. Hence, each latent variable is indirectly mapped to a time series. Incorporating the recurrent network in the latent variable model helps us account for the temporal nature of the time series and capture their underlying dynamics. The proposed algorithm is demonstrated on two benchmark problems and a real world dataset.

Detecting Quasars in Large-Scale Astronomical Surveys - Gieseke, Fabian; Polsterer, Kai Lars; Thom, Andreas; Zinn, Peter; Bomanns, Dominik; Dettmar, Ralf-Jurgen; Kramer, Oliver; Vahrenhold, Jan (2010 Ninth International Conference on Machine Learning and Applications, 2010)

Black Hole Mass Estimates Based on C IV are Consistent with Those Based on the Balmer Lines - Assef, R. J.; Denney, K. D.; Kochanek, C. S.; Peterson, B. M.; Kozłowski, S.; Ageorges, N.; Barrows, R. S.; Buschkamp, P.; Dietrich, M.; Falco, E.; Feiz, C.; Gemperlein, H.; et al. (ApJ, 2011)

Infrared Narrowband Tomography of the Local Starburst NGC 1569 with the Large Binocular Telescope/LUCIFER. - Pasquali, A.; Bik, A.; Zibetti, S.; Ageorges, N.; Seifert, W.; Brandner, W.; Rix, H.-W.; Jütte, M.; Knierim, V.; Buschkamp, P.; Feiz, C.; Gemperlein, H.; et al. (The Astronomical Journal, 2011)