TY - JOUR A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Hege, Hans-Christian T1 - Ligand Excluded Surface: A New Type of Molecular Surface JF - IEEE Transactions on Visualization and Computer Graphics N2 - The most popular molecular surface in molecular visualization is the solvent excluded surface (SES). It provides information about the accessibility of a biomolecule for a solvent molecule that is geometrically approximated by a sphere. During a period of almost four decades, the SES has served for many purposes – including visualization, analysis of molecular interactions and the study of cavities in molecular structures. However, if one is interested in the surface that is accessible to a molecule whose shape differs significantly from a sphere, a different concept is necessary. To address this problem, we generalize the definition of the SES by replacing the probe sphere with the full geometry of the ligand defined by the arrangement of its van der Waals spheres. We call the new surface ligand excluded surface (LES) and present an efficient, grid-based algorithm for its computation. Furthermore, we show that this algorithm can also be used to compute molecular cavities that could host the ligand molecule. We provide a detailed description of its implementation on CPU and GPU. Furthermore, we present a performance and convergence analysis and compare the LES for several molecules, using as ligands either water or small organic molecules. Y1 - 2014 U6 - https://doi.org/10.1109/TVCG.2014.2346404 VL - 20 IS - 12 SP - 2486 EP - 2495 ER - TY - GEN A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Hege, Hans-Christian T1 - Ligand Excluded Surface: A New Type of Molecular Surface N2 - The most popular molecular surface in molecular visualization is the solvent excluded surface (SES). It provides information about the accessibility of a biomolecule for a solvent molecule that is geometrically approximated by a sphere. During a period of almost four decades, the SES has served for many purposes – including visualization, analysis of molecular interactions and the study of cavities in molecular structures. However, if one is interested in the surface that is accessible to a molecule whose shape differs significantly from a sphere, a different concept is necessary. To address this problem, we generalize the definition of the SES by replacing the probe sphere with the full geometry of the ligand defined by the arrangement of its van der Waals spheres. We call the new surface ligand excluded surface (LES) and present an efficient, grid-based algorithm for its computation. Furthermore, we show that this algorithm can also be used to compute molecular cavities that could host the ligand molecule. We provide a detailed description of its implementation on CPU and GPU. Furthermore, we present a performance and convergence analysis and compare the LES for several molecules, using as ligands either water or small organic molecules. T3 - ZIB-Report - 14-27 Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-51194 SN - 1438-0064 ER - TY - CHAP A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Bondar, Ana-Nicoleta A1 - Hege, Hans-Christian T1 - Dynamic Channels in Biomolecular Systems: Path Analysis and Visualization T2 - Proceedings of IEEE Symposium on Biological Data Visualization (biovis’12) Y1 - 2012 U6 - https://doi.org/10.1109/BioVis.2012.6378599 SP - 99 EP - 106 ER - TY - CHAP A1 - Kuhn, Alexander A1 - Lindow, Norbert A1 - Günther, Tobias A1 - Wiebel, Alexander A1 - Theisel, Holger A1 - Hege, Hans-Christian T1 - Trajectory Density Projection for Vector Field Visualization T2 - EuroVis 2013, short papers. M. Hlawitschka, Tino Weinkauf (eds.) Y1 - 2013 UR - http://vc.cs.ovgu.de/files/publications/2013/Kuhn_2013_EUROVIS.pdf U6 - https://doi.org/10.2312/PE.EuroVisShort.EuroVisShort2013.031-035 SP - 31 EP - 35 ER - TY - THES A1 - Lindow, Norbert T1 - Dynamische Moleküloberflächen T1 - Dynamic Molecular Surfaces Y1 - 2010 ER - TY - JOUR A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Hege, Hans-Christian T1 - Voronoi-Based Extraction and Visualization of Molecular Paths JF - IEEE Transactions on Visualization and Computer Graphics Y1 - 2011 U6 - https://doi.org/10.1109/TVCG.2011.259 VL - 17 IS - 12 SP - 2025 EP - 2034 ER - TY - JOUR A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Prohaska, Steffen A1 - Hege, Hans-Christian T1 - Accelerated Visualization of Dynamic Molecular Surfaces JF - Comput. Graph. Forum Y1 - 2010 U6 - https://doi.org/10.1111/j.1467-8659.2009.01693.x VL - 29 SP - 943 EP - 952 ER - TY - JOUR A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Bondar, Ana-Nicoleta A1 - Hege, Hans-Christian T1 - Exploring cavity dynamics in biomolecular systems JF - BMC Bioinformatics Y1 - 2013 U6 - https://doi.org/10.1186/1471-2105-14-S19-S5 VL - 14 ET - (Suppl 19):S5 ER - TY - JOUR A1 - Cournia, Zoe A1 - Allen, Toby W. A1 - Andricioaei, Ioan A1 - Antonny, Bruno A1 - Baum, Daniel A1 - Brannigan, Grace A1 - Buchete, Nicolae-Viorel A1 - Deckman, Jason T. A1 - Delemotte, Lucie A1 - del Val, Coral A1 - Friedman, Ran A1 - Gkeka, Paraskevi A1 - Hege, Hans-Christian A1 - Hénin, Jérôme A1 - Kasimova, Marina A. A1 - Kolocouris, Antonios A1 - Klein, Michael L. A1 - Khalid, Syma A1 - Lemieux, Joanne A1 - Lindow, Norbert A1 - Roy, Mahua A1 - Selent, Jana A1 - Tarek, Mounir A1 - Tofoleanu, Florentina A1 - Vanni, Stefano A1 - Urban, Sinisa A1 - Wales, David J. A1 - Smith, Jeremy C. A1 - Bondar, Ana-Nicoleta T1 - Membrane Protein Structure, Function and Dynamics: A Perspective from Experiments and Theory JF - Journal of Membrane Biology Y1 - 2015 U6 - https://doi.org/10.1007/s00232-015-9802-0 VL - 248 IS - 4 SP - 611 EP - 640 ER - TY - JOUR A1 - Mücklich, Frank A1 - Webel, Johannes A1 - Aboulfadl, Hisham A1 - Lindow, Norbert A1 - Hege, Hans-Christian T1 - Correlative Tomography – Extraction of Reliable Information with Adequate Resolution from mm Scale Down to Sub-nm Scale JF - Microsc. Microanal. Y1 - 2014 U6 - https://doi.org/10.1017/S1431927614005911 VL - 20 IS - Suppl 3 SP - 838 EP - 839 ER - TY - GEN A1 - Kozlikova, Barbora A1 - Krone, Michael A1 - Falk, Martin A1 - Lindow, Norbert A1 - Baaden, Marc A1 - Baum, Daniel A1 - Viola, Ivan A1 - Parulek, Julius A1 - Hege, Hans-Christian T1 - Visualization of Biomolecular Structures: State of the Art N2 - Structural properties of molecules are of primary concern in many fields. This report provides a comprehensive overview on techniques that have been developed in the fields of molecular graphics and visualization with a focus on applications in structural biology. The field heavily relies on computerized geometric and visual representations of three-dimensional, complex, large, and time-varying molecular structures. The report presents a taxonomy that demonstrates which areas of molecular visualization have already been extensively investigated and where the field is currently heading. It discusses visualizations for molecular structures, strategies for efficient display regarding image quality and frame rate, covers different aspects of level of detail, and reviews visualizations illustrating the dynamic aspects of molecular simulation data. The survey concludes with an outlook on promising and important research topics to foster further success in the development of tools that help to reveal molecular secrets. T3 - ZIB-Report - 15-63 Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-57217 SN - 1438-0064 ER - TY - GEN A1 - Krone, Michael A1 - Kozlikova, Barbora A1 - Lindow, Norbert A1 - Baaden, Marc A1 - Baum, Daniel A1 - Parulek, Julius A1 - Hege, Hans-Christian A1 - Viola, Ivan T1 - Visual Analysis of Biomolecular Cavities: State of the Art N2 - In this report we review and structure the branch of molecular visualization that is concerned with the visual analysis of cavities in macromolecular protein structures. First the necessary background, the domain terminology, and the goals of analytical reasoning are introduced. Based on a comprehensive collection of relevant research works, we present a novel classification for cavity detection approaches and structure them into four distinct classes: grid-based, Voronoi-based, surface-based, and probe-based methods. The subclasses are then formed by their combinations. We match these approaches with corresponding visualization technologies starting with direct 3D visualization, followed with non-spatial visualization techniques that for example abstract the interactions between structures into a relational graph, straighten the cavity of interest to see its profile in one view, or aggregate the time sequence into a single contour plot. We also discuss the current state of methods for the visual analysis of cavities in dynamic data such as molecular dynamics simulations. Finally, we give an overview of the most common tools that are actively developed and used in the structural biology and biochemistry research. Our report is concluded by an outlook on future challenges in the field. T3 - ZIB-Report - 16-42 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-60193 SN - 1438-0064 ER - TY - THES A1 - Lindow, Norbert T1 - Visual Analysis of Atomic Structures Based on the Hard-Sphere Model N2 - Visualization and Analysis of atomic compositions is essential to understand the structure and functionality of molecules. There exist versatile areas of applications, from fundamental researches in biophysics and materials science to drug development in pharmaceutics. For most applications, the hard-sphere model is the most often used molecular model. Although the model is a quite simple approximation of reality, it enables investigating important physical properties in a purely geometrical manner. Furthermore, large data sets with thousands up to millions of atoms can be visualized and analyzed. In addition to an adequate and efficient visualization of the data, the extraction of important structures plays a major role. For the investigation of biomolecules, such as proteins, especially the analysis of cavities and their dynamics is of high interest. Substrates can bind in cavities, thereby inducing changes in the function of the protein. Another example is the transport of substrates through membrane proteins by the dynamics of the cavities. For both, the visualization as well as the analysis of cavities, the following contributions will be presented in this thesis: 1. The rendering of smooth molecular surfaces for the analysis of cavities is accelerated and visually improved, which allows showing dynamic proteins. On the other hand, techniques are proposed to interactively render large static biological structures and inorganic materials up to atomic resolution for the first time. 2. A Voronoi-based method is presented to extract molecular cavities. The procedure comes with a high geometrical accuracy by a comparatively fast computation time. Additionally, new methods are presented to visualize and highlight the cavities within the molecular structure. In a further step, the techniques are extended for dynamic molecular data to trace cavities over time and visualize topological changes. 3. To further improve the accuracy of the approaches mentioned above, a new molecular surface model is presented that shows the accessibility of a substrate. For the first time, the structure and dynamics of the substrate as hard-sphere model is considered for the accessibility computation. In addition to the definition of the surface, an efficient algorithm for its computation is proposed, which additionally allows extracting cavities. The presented algorithms are demonstrated on different molecular data sets. The data sets are either the result of physical or biological experiments or molecular dynamics simulations. Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-63190 ER - TY - JOUR A1 - Redemann, Stefanie A1 - Baumgart, Johannes A1 - Lindow, Norbert A1 - Shelley, Michael A1 - Nazockdast, Ehssan A1 - Kratz, Andrea A1 - Prohaska, Steffen A1 - Brugués, Jan A1 - Fürthauer, Sebastian A1 - Müller-Reichert, Thomas T1 - C. elegans chromosomes connect to centrosomes by anchoring into the spindle network JF - Nature Communications N2 - The mitotic spindle ensures the faithful segregation of chromosomes. Here we combine the first large-scale serial electron tomography of whole mitotic spindles in early C. elegans embryos with live-cell imaging to reconstruct all microtubules in 3D and identify their plus- and minus-ends. We classify them as kinetochore (KMTs), spindle (SMTs) or astral microtubules (AMTs) according to their positions, and quantify distinct properties of each class. While our light microscopy and mutant studies show that microtubules are nucleated from the centrosomes, we find only a few KMTs directly connected to the centrosomes. Indeed, by quantitatively analysing several models of microtubule growth, we conclude that minus-ends of KMTs have selectively detached and depolymerized from the centrosome. In toto, our results show that the connection between centrosomes and chromosomes is mediated by an anchoring into the entire spindle network and that any direct connections through KMTs are few and likely very transient. Y1 - 2017 U6 - https://doi.org/10.1038/ncomms15288 VL - 8 IS - 15288 ER - TY - CHAP A1 - Arlt, Tobias A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Hilger, Andre A1 - Mahnke, Ingo A1 - Hege, Hans-Christian A1 - Lepper, Verena A1 - Siopi, Tzulia A1 - Mahnke, Heinz.Eberhard T1 - Virtual Access to Hidden Texts – Study of Ancient Papyri T2 - Eighth Joint BER II and BESSY II User Meeting, Dec 7-9, 2016, Berlin, Germany N2 - When physical unfolding/unrolling of papyri is not possible or too dangerous for preserving the precious object, tomographic approaches may be the ap- propriate alternative. Requirements are the resolution and the contrast to distinguish writing and substrate. The steps to be performed are the following: (1) Select the object of interest (archaeological arguments, cultural back- ground of the object, etc.). (2) Find the proper physical procedure, especially with respect to contrast, take the tomographic data, e.g. by absorption x-ray tomography. (3) Apply mathematical unfolding transformations to the tomographic data, in order to obtain a 2d-planar reconstruction of text. Y1 - 2016 ER - TY - GEN A1 - Lindow, Norbert A1 - Redemann, Stefanie A1 - Fabig, Gunar A1 - Müller-Reichert, Thomas A1 - Prohaska, Steffen T1 - Quantification of Three-Dimensional Spindle Architecture N2 - Mitotic and meiotic spindles are microtubule-based structures to faithfully segregate chromosomes. Electron tomography is currently the method of choice to analyze the three-dimensional architecture of both types of spindles. Over the years, we have developed methods and software for automatic segmentation and stitching of microtubules in serial sections for large-scale reconstructions. Three-dimensional reconstruction of microtubules, however, is only the first step towards biological insight. The second step is the analysis of the structural data to derive measurable spindle properties. Here, we present a comprehensive set of techniques to quantify spindle parameters. These techniques provide quantitative analyses of specific microtubule classes and are applicable to a variety of tomographic reconstructions of spindles from different organisms. T3 - ZIB-Report - 18-07 Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-66562 SN - 1438-0064 ER - TY - JOUR A1 - Baum, Daniel A1 - Lindow, Norbert A1 - Hege, Hans-Christian A1 - Lepper, Verena A1 - Siopi, Tzulia A1 - Kutz, Frank A1 - Mahlow, Kristin A1 - Mahnke, Heinz-Eberhard T1 - Revealing hidden text in rolled and folded papyri JF - Applied Physics A N2 - Ancient Egyptian papyri are often folded, rolled up or kept as small packages, sometimes even sealed. Physically unrolling or unfolding these packages might severely damage them. We demonstrate a way to get access to the hidden script without physical unfolding by employing computed tomography and mathematical algorithms for virtual unrolling and unfolding. Our algorithmic approaches are combined with manual interaction. This provides the necessary flexibility to enable the unfolding of even complicated and partly damaged papyrus packages. In addition, it allows us to cope with challenges posed by the structure of ancient papyrus, which is rather irregular, compared to other writing substrates like metallic foils or parchment. Unfolding of packages is done in two stages. In the first stage, we virtually invert the physical folding process step by step until the partially unfolded package is topologically equivalent to a scroll or a papyrus sheet folded only along one fold line. To minimize distortions at this stage, we apply the method of moving least squares. In the second stage, the papyrus is simply flattened, which requires the definition of a medial surface. We have applied our software framework to several papyri. In this work, we present the results of applying our approaches to mockup papyri that were either rolled or folded along perpendicular fold lines. In the case of the folded papyrus, our approach represents the first attempt to address the unfolding of such complicated folds. Y1 - 2017 U6 - https://doi.org/10.1007/s00339-017-0808-6 VL - 123 IS - 3 SP - 171 ER - TY - JOUR A1 - Kozlíková, Barbora A1 - Krone, Michael A1 - Falk, Martin A1 - Lindow, Norbert A1 - Baaden, Marc A1 - Baum, Daniel A1 - Viola, Ivan A1 - Parulek, Julius A1 - Hege, Hans-Christian T1 - Visualization of Biomolecular Structures: State of the Art Revisited JF - Computer Graphics Forum N2 - Structural properties of molecules are of primary concern in many fields. This report provides a comprehensive overview on techniques that have been developed in the fields of molecular graphics and visualization with a focus on applications in structural biology. The field heavily relies on computerized geometric and visual representations of three-dimensional, complex, large and time-varying molecular structures. The report presents a taxonomy that demonstrates which areas of molecular visualization have already been extensively investigated and where the field is currently heading. It discusses visualizations for molecular structures, strategies for efficient display regarding image quality and frame rate, covers different aspects of level of detail and reviews visualizations illustrating the dynamic aspects of molecular simulation data. The survey concludes with an outlook on promising and important research topics to foster further success in the development of tools that help to reveal molecular secrets. Y1 - 2016 U6 - https://doi.org/10.1111/cgf.13072 VL - 36 IS - 8 SP - 178 EP - 204 ER - TY - JOUR A1 - Krone, Michael A1 - Kozlíková, Barbora A1 - Lindow, Norbert A1 - Baaden, Marc A1 - Baum, Daniel A1 - Parulek, Julius A1 - Hege, Hans-Christian A1 - Viola, Ivan T1 - Visual Analysis of Biomolecular Cavities: State of the Art JF - Computer Graphics Forum N2 - In this report we review and structure the branch of molecular visualization that is concerned with the visual analysis of cavities in macromolecular protein structures. First the necessary background, the domain terminology, and the goals of analytical reasoning are introduced. Based on a comprehensive collection of relevant research works, we present a novel classification for cavity detection approaches and structure them into four distinct classes: grid-based, Voronoi-based, surface-based, and probe-based methods. The subclasses are then formed by their combinations. We match these approaches with corresponding visualization technologies starting with direct 3D visualization, followed with non-spatial visualization techniques that for example abstract the interactions between structures into a relational graph, straighten the cavity of interest to see its profile in one view, or aggregate the time sequence into a single contour plot. We also discuss the current state of methods for the visual analysis of cavities in dynamic data such as molecular dynamics simulations. Finally, we give an overview of the most common tools that are actively developed and used in the structural biology and biochemistry research. Our report is concluded by an outlook on future challenges in the field. Y1 - 2016 U6 - https://doi.org/10.1111/cgf.12928 SN - 1467-8659 VL - 35 IS - 3 SP - 527 EP - 551 ER - TY - CHAP A1 - Kozlikova, Barbora A1 - Krone, Michael A1 - Lindow, Norbert A1 - Falk, Martin A1 - Baaden, Marc A1 - Baum, Daniel A1 - Viola, Ivan A1 - Parulek, Julius A1 - Hege, Hans-Christian T1 - Visualization of Biomolecular Structures: State of the Art T2 - EuroVis 2015 STARS Proceedings N2 - Structural properties of molecules are of primary concern in many fields. This report provides a comprehensive overview on techniques that have been developed in the fields of molecular graphics and visualization with a focus on applications in structural biology. The field heavily relies on computerized geometric and visual representations of three-dimensional, complex, large, and time-varying molecular structures. The report presents a taxonomy that demonstrates which areas of molecular visualization have already been extensively investigated and where the field is currently heading. It discusses visualizations for molecular structures, strategies for efficient display regarding image quality and frame rate, covers different aspects of level of detail, and reviews visualizations illustrating the dynamic aspects of molecular simulation data. The report concludes with an outlook on promising and important research topics to enable further success in advancing the knowledge about interaction of molecular structures. Y1 - 2015 U6 - https://doi.org/10.2312/eurovisstar.20151112 SP - 61 EP - 81 ER - TY - JOUR A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Hege, Hans-Christian T1 - Perceptually Linear Parameter Variations JF - Computer Graphics Forum Y1 - 2012 U6 - https://doi.org/10.1111/j.1467-8659.2012.03054.x target VL - 31 IS - 2 SP - 535 EP - 544 ER - TY - JOUR A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Hege, Hans-Christian T1 - Interactive Rendering of Materials and Biological Structures on Atomic and Nanoscopic Scale JF - Computer Graphics Forum Y1 - 2012 U6 - https://doi.org/10.1111/j.1467-8659.2012.03128.x target VL - 31 IS - 3 SP - 1325 EP - 1334 ER - TY - JOUR A1 - Fabig, Gunar A1 - Kiewisz, Robert A1 - Lindow, Norbert A1 - Powers, James A. A1 - Cota, Vanessa A1 - Quintanilla, Luis J. A1 - Brugués, Jan A1 - Prohaska, Steffen A1 - Chu, Diana S. A1 - Müller-Reichert, Thomas T1 - Sperm-specific meiotic chromosome segregation in C. elegans JF - eLife Y1 - 2020 U6 - https://doi.org/10.7554/eLife.50988 VL - 9 SP - e50988 ER - TY - JOUR A1 - Lindow, Norbert A1 - Brünig, Florian A1 - Dercksen, Vincent J. A1 - Fabig, Gunar A1 - Kiewisz, Robert A1 - Redemann, Stefanie A1 - Müller-Reichert, Thomas A1 - Prohaska, Steffen A1 - Baum, Daniel T1 - Semi-automatic stitching of filamentous structures in image stacks from serial-section electron tomography JF - bioRxiv N2 - We present a software-assisted workflow for the alignment and matching of filamentous structures across a 3D stack of serial images. This is achieved by combining automatic methods, visual validation, and interactive correction. After an initial alignment, the user can continuously improve the result by interactively correcting landmarks or matches of filaments. Supported by a visual quality assessment of regions that have been already inspected, this allows a trade-off between quality and manual labor. The software tool was developed to investigate cell division by quantitative 3D analysis of microtubules (MTs) in both mitotic and meiotic spindles. For this, each spindle is cut into a series of semi-thick physical sections, of which electron tomograms are acquired. The serial tomograms are then stitched and non-rigidly aligned to allow tracing and connecting of MTs across tomogram boundaries. In practice, automatic stitching alone provides only an incomplete solution, because large physical distortions and a low signal-to-noise ratio often cause experimental difficulties. To derive 3D models of spindles despite the problems related to sample preparation and subsequent data collection, semi-automatic validation and correction is required to remove stitching mistakes. However, due to the large number of MTs in spindles (up to 30k) and their resulting dense spatial arrangement, a naive inspection of each MT is too time consuming. Furthermore, an interactive visualization of the full image stack is hampered by the size of the data (up to 100 GB). Here, we present a specialized, interactive, semi-automatic solution that considers all requirements for large-scale stitching of filamentous structures in serial-section image stacks. The key to our solution is a careful design of the visualization and interaction tools for each processing step to guarantee real-time response, and an optimized workflow that efficiently guides the user through datasets. Y1 - 2020 U6 - https://doi.org/10.1101/2020.05.28.120899 ER - TY - GEN A1 - Lindow, Norbert A1 - Brünig, Florian A1 - Dercksen, Vincent J. A1 - Fabig, Gunar A1 - Kiewisz, Robert A1 - Redemann, Stefanie A1 - Müller-Reichert, Thomas A1 - Prohaska, Steffen T1 - Semi-automatic Stitching of Serial Section Image Stacks with Filamentous Structures N2 - In this paper, we present a software-assisted workflow for the alignment and matching of filamentous structures across a stack of 3D serial image sections. This is achieved by a combination of automatic methods, visual validation, and interactive correction. After an initial alignment, the user can continuously improve the result by interactively correcting landmarks or matches of filaments. This is supported by a quality assessment that visualizes regions that have been already inspected and, thus, allows a trade-off between quality and manual labor. The software tool was developed in collaboration with biologists who investigate microtubule-based spindles during cell division. To quantitatively understand the structural organization of such spindles, a 3D reconstruction of the numerous microtubules is essential. Each spindle is cut into a series of semi-thick physical sections, of which electron tomograms are acquired. The sections then need to be stitched, i.e. non-rigidly aligned; and the microtubules need to be traced in each section and connected across section boundaries. Experiments led to the conclusion that automatic methods for stitching alone provide only an incomplete solution to practical analysis needs. Automatic methods may fail due to large physical distortions, a low signal-to-noise ratio of the images, or other unexpected experimental difficulties. In such situations, semi-automatic validation and correction is required to rescue as much information as possible to derive biologically meaningful results despite of some errors related to data collection. Since the correct stitching is visually not obvious due to the number of microtubules (up to 30k) and their dense spatial arrangement, these are difficult tasks. Furthermore, a naive inspection of each microtubule is too time consuming. In addition, interactive visualization is hampered by the size of the image data (up to 100 GB). Based on the requirements of our collaborators, we present a practical solution for the semi-automatic stitching of serial section image stacks with filamentous structures. T3 - ZIB-Report - 19-30 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-73739 SN - 1438-0064 ER - TY - GEN A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Hege, Hans-Christian T1 - Atomic Accessibility Radii for Molecular Dynamics Analysis N2 - In molecular structure analysis and visualization, the molecule’s atoms are often modeled as hard spheres parametrized by their positions and radii. While the atom positions result from experiments or molecular simulations, for the radii typically values are taken from literature. Most often, van der Waals (vdW) radii are used, for which diverse values exist. As a consequence, different visualization and analysis tools use different atomic radii, and the analyses are less objective than often believed. Furthermore, for the geometric accessibility analysis of molecular structures, vdW radii are not well suited. The reason is that during the molecular dynamics simulation, depending on the force field and the kinetic energy in the system, non-bonded atoms can come so close to each other that their vdW spheres intersect. In this paper, we introduce a new kind of atomic radius, called atomic accessibility radius’, that better characterizes the accessibility of an atom in a given molecular trajectory. The new radii reflect the movement possibilities of atoms in the simulated physical system. They are computed by solving a linear program that maximizes the radii of the atoms under the constraint that non-bonded spheres do not intersect in the considered molecular trajectory. Using this data-driven approach, the actual accessibility of atoms can be visualized more precisely. T3 - ZIB-Report - 18-18 KW - molecular dynamics KW - atomic radii KW - cavity analysis Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-68468 SN - 1438-0064 ER - TY - CHAP A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Hege, Hans-Christian T1 - Atomic Accessibility Radii for Molecular Dynamics Analysis T2 - Workshop on Molecular Graphics and Visual Analysis of Molecular Data N2 - In molecular structure analysis and visualization, the molecule’s atoms are often modeled as hard spheres parametrized by their positions and radii. While the atom positions result from experiments or molecular simulations, for the radii typically values are taken from literature. Most often, van der Waals (vdW) radii are used, for which diverse values exist. As a consequence, different visualization and analysis tools use different atomic radii, and the analyses are less objective than often believed. Furthermore, for the geometric accessibility analysis of molecular structures, vdW radii are not well suited. The reason is that during the molecular dynamics simulation, depending on the force field and the kinetic energy in the system, non-bonded atoms can come so close to each other that their vdW spheres intersect. In this paper, we introduce a new kind of atomic radius, called atomic accessibility radius’, that better characterizes the accessibility of an atom in a given molecular trajectory. The new radii reflect the movement possibilities of atoms in the simulated physical system. They are computed by solving a linear program that maximizes the radii of the atoms under the constraint that non-bonded spheres do not intersect in the considered molecular trajectory. Using this data-driven approach, the actual accessibility of atoms can be visualized more precisely. Y1 - 2018 SN - 978-3-03868-061-1 U6 - https://doi.org/10.2312/molva.20181101 PB - The Eurographics Association ER - TY - CHAP A1 - Lindow, Norbert A1 - Redemann, Stefanie A1 - Brünig, Florian A1 - Fabig, Gunar A1 - Müller-Reichert, Thomas A1 - Prohaska, Steffen T1 - Quantification of three-dimensional spindle architecture T2 - Methods in Cell Biology Part B N2 - Mitotic and meiotic spindles are microtubule-based structures to faithfully segregate chromosomes. Electron tomography is currently the method of choice to analyze the three-dimensional (3D) architecture of both types of spindles. Over the years, we have developed methods and software for automatic segmentation and stitching of microtubules in serial sections for large-scale reconstructions. 3D reconstruction of microtubules, however, is only the first step toward biological insight. The second step is the analysis of the structural data to derive measurable spindle properties. Here, we present a comprehensive set of techniques to quantify spindle parameters. These techniques provide quantitative analyses of specific microtubule classes and are applicable to a variety of tomographic reconstructions of spindles from different organisms. Y1 - 2018 U6 - https://doi.org/10.1016/bs.mcb.2018.03.012 SN - 0091-679X VL - 145 SP - 45 EP - 64 PB - Academic Press ER - TY - GEN A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Leborgne, Morgan A1 - Hege, Hans-Christian T1 - Interactive Visualization of RNA and DNA Structures N2 - The analysis and visualization of nucleic acids (RNA and DNA) play an increasingly important role due to the growing number of known 3-dimensional structures of such molecules. The great complexity of these structures, in particular, those of RNA, demands interactive visualization to get deeper insights into the relationship between the 2D secondary structure motifs and their 3D tertiary structures. Over the last decades, a lot of research in molecular visualization has focused on the visual exploration of protein structures while nucleic acids have only been marginally addressed. In contrast to proteins, which are composed of amino acids, the ingredients of nucleic acids are nucleotides. They form structuring patterns that differ from those of proteins and, hence, also require different visualization and exploration techniques. In order to support interactive exploration of nucleic acids, the computation of secondary structure motifs as well as their visualization in 2D and 3D must be fast. Therefore, in this paper, we focus on the performance of both the computation and visualization of nucleic acid structure. For the first time, we present a ray casting-based visualization of RNA and DNA secondary and tertiary structures, which enables real-time visualization of even large molecular dynamics trajectories. Furthermore, we provide a detailed description of all important aspects to visualize nucleic acid secondary and tertiary structures. With this, we close an important gap in molecular visualization. T3 - ZIB-Report - 18-33 KW - ribonucleic acids KW - DNA KW - RNA KW - secondary & tertiary structures KW - interactive rendering KW - ray casting KW - brushing & linking Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-69704 SN - 1438-0064 ER - TY - JOUR A1 - Lindow, Norbert A1 - Baum, Daniel A1 - Leborgne, Morgan A1 - Hege, Hans-Christian T1 - Interactive Visualization of RNA and DNA Structures JF - IEEE Transactions on Visualization and Computer Graphics N2 - The analysis and visualization of nucleic acids (RNA and DNA) is playing an increasingly important role due to their fundamental importance for all forms of life and the growing number of known 3D structures of such molecules. The great complexity of these structures, in particular, those of RNA, demands interactive visualization to get deeper insights into the relationship between the 2D secondary structure motifs and their 3D tertiary structures. Over the last decades, a lot of research in molecular visualization has focused on the visual exploration of protein structures while nucleic acids have only been marginally addressed. In contrast to proteins, which are composed of amino acids, the ingredients of nucleic acids are nucleotides. They form structuring patterns that differ from those of proteins and, hence, also require different visualization and exploration techniques. In order to support interactive exploration of nucleic acids, the computation of secondary structure motifs as well as their visualization in 2D and 3D must be fast. Therefore, in this paper, we focus on the performance of both the computation and visualization of nucleic acid structure. We present a ray casting-based visualization of RNA and DNA secondary and tertiary structures, which enables for the first time real-time visualization of even large molecular dynamics trajectories. Furthermore, we provide a detailed description of all important aspects to visualize nucleic acid secondary and tertiary structures. With this, we close an important gap in molecular visualization. Y1 - 2019 U6 - https://doi.org/10.1109/TVCG.2018.2864507 VL - 25 IS - 1 SP - 967 EP - 976 ER - TY - GEN A1 - Redemann, Stefanie A1 - Lantzsch, Ina A1 - Lindow, Norbert A1 - Prohaska, Steffen A1 - Srayko, Martin A1 - Müller-Reichert, Thomas T1 - A switch in microtubule orientation during C. elegans meiosis N2 - In oocytes of many organisms, meiotic spindles form in the absence of centrosomes [1–5]. Such female meiotic spindles have a pointed appearance in metaphase with microtubules focused at acentrosomal spindle poles. At anaphase, the microtubules of acentrosomal spindles then transition to an inter- chromosomal array, while the spindle poles disappear. This transition is currently not understood. Previous studies have focused on this inter- chromosomal microtubule array and proposed a pushing model to drive chromosome segregation [6, 7]. This model includes an end-on orientation of microtubules with chromosomes. Alternatively, chromosomes were thought to associate along bundles of microtubules [8, 9]. Starting with metaphase, this second model proposed a pure lateral chromosome-to-microtubule association up to the final meiotic stages of anaphase. Here we applied large-scale electron tomography [10] of staged C. elegans oocytes in meiosis to analyze the orientation of microtubules in respect to chromosomes. We show that microtubules at metaphase I are primarily oriented laterally to the chromosomes and that microtubules switch to an end-on orientation during progression through anaphase. We further show that this switch in microtubule orientation involves a kinesin-13 microtubule depolymerase, KLP-7, which removes laterally associated microtubules around chromosomes. From this we conclude that both lateral and end-on modes of microtubule-to-chromosome orientations are successively used in C. elegans oocytes to segregate meiotic chromosomes. T3 - ZIB-Report - 18-34 Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-69855 SN - 1438-0064 ER - TY - JOUR A1 - Redemann, Stefanie A1 - Lantzsch, Ina A1 - Lindow, Norbert A1 - Prohaska, Steffen A1 - Srayko, Martin A1 - Müller-Reichert, Thomas T1 - A switch in microtubule orientation during C. elegans meiosis JF - Current Biology N2 - In oocytes of many organisms, meiotic spindles form in the absence of centrosomes [1–5]. Such female meiotic spindles have a pointed appearance in metaphase with microtubules focused at acentrosomal spindle poles. At anaphase, the microtubules of acentrosomal spindles then transition to an inter- chromosomal array, while the spindle poles disappear. This transition is currently not understood. Previous studies have focused on this inter- chromosomal microtubule array and proposed a pushing model to drive chromosome segregation [6, 7]. This model includes an end-on orientation of microtubules with chromosomes. Alternatively, chromosomes were thought to associate along bundles of microtubules [8, 9]. Starting with metaphase, this second model proposed a pure lateral chromosome-to-microtubule association up to the final meiotic stages of anaphase. Here we applied large-scale electron tomography [10] of staged C. elegans oocytes in meiosis to analyze the orientation of microtubules in respect to chromosomes. We show that microtubules at metaphase I are primarily oriented laterally to the chromosomes and that microtubules switch to an end-on orientation during progression through anaphase. We further show that this switch in microtubule orientation involves a kinesin-13 microtubule depolymerase, KLP-7, which removes laterally associated microtubules around chromosomes. From this we conclude that both lateral and end-on modes of microtubule-to-chromosome orientations are successively used in C. elegans oocytes to segregate meiotic chromosomes. Y1 - 2018 U6 - https://doi.org/10.1016/j.cub.2018.07.012 SN - 0960-9822 ER - TY - JOUR A1 - Lantzsch, Ina A1 - Yu, Che-Hang A1 - Chen, Yu-Zen A1 - Zimyanin, Vitaly A1 - Yazdkhasti, Hossein A1 - Lindow, Norbert A1 - Szentgyoergyi, Erik A1 - Pani, Ariel M A1 - Prohaska, Steffen A1 - Srayko, Martin A1 - Fürthauer, Sebastian A1 - Redemann, Stefanie T1 - Microtubule reorganization during female meiosis in C. elegans JF - eLife N2 - Most female meiotic spindles undergo striking morphological changes while transitioning from metaphase to anaphase. The ultra-structure of meiotic spindles, and how changes to this structure correlate with such dramatic spindle rearrangements remains largely unknown. To address this, we applied light microscopy, large-scale electron tomography and mathematical modeling of female meiotic \textit{Caenorhabditis elegans} spindles. Combining these approaches, we find that meiotic spindles are dynamic arrays of short microtubules that turn over within seconds. The results show that the metaphase to anaphase transition correlates with an increase in microtubule numbers and a decrease in their average length. Detailed analysis of the tomographic data revealed that the microtubule length changes significantly during the metaphase-to-anaphase transition. This effect is most pronounced for microtubules located within 150 nm of the chromosome surface. To understand the mechanisms that drive this transition, we developed a mathematical model for the microtubule length distribution that considers microtubule growth, catastrophe, and severing. Using Bayesian inference to compare model predictions and data, we find that microtubule turn-over is the major driver of the spindle reorganizations. Our data suggest that in metaphase only a minor fraction of microtubules, those closest to the chromosomes, are severed. The large majority of microtubules, which are not in close contact with chromosomes, do not undergo severing. Instead, their length distribution is fully explained by growth and catastrophe. This suggests that the most prominent drivers of spindle rearrangements are changes in nucleation and catastrophe rate. In addition, we provide evidence that microtubule severing is dependent on katanin. Y1 - 2021 U6 - https://doi.org/10.7554/eLife.58903 VL - 10 SP - e58903 ER - TY - GEN A1 - Baum, Daniel A1 - Lindow, Norbert A1 - Hege, Hans-Christian A1 - Lepper, Verena A1 - Siopi, Tzulia A1 - Kutz, Frank A1 - Mahlow, Kristin A1 - Mahnke, Heinz-Eberhard T1 - Revealing hidden text in rolled and folded papyri N2 - Ancient Egyptian papyri are often folded, rolled up or kept as small packages, sometimes even sealed. Physically unrolling or unfolding these packages might severely damage them. We demonstrate a way to get access to the hidden script without physical unfolding by employing computed tomography and mathematical algorithms for virtual unrolling and unfolding. Our algorithmic approaches are combined with manual interaction. This provides the necessary flexibility to enable the unfolding of even complicated and partly damaged papyrus packages. In addition, it allows us to cope with challenges posed by the structure of ancient papyrus, which is rather irregular, compared to other writing substrates like metallic foils or parchment. Unfolding of packages is done in two stages. In the first stage, we virtually invert the physical folding process step by step until the partially unfolded package is topologically equivalent to a scroll or a papyrus sheet folded only along one fold line. To minimize distortions at this stage, we apply the method of moving least squares. In the second stage, the papyrus is simply flattened, which requires the definition of a medial surface. We have applied our software framework to several papyri. In this work, we present the results of applying our approaches to mockup papyri that were either rolled or folded along perpendicular fold lines. In the case of the folded papyrus, our approach represents the first attempt to address the unfolding of such complicated folds. T3 - ZIB-Report - 17-02 KW - unfolding, papyri, computed tomography Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-61826 SN - 1438-0064 ER - TY - JOUR A1 - Mahnke, Heinz-Eberhard A1 - Arlt, Tobias A1 - Baum, Daniel A1 - Hege, Hans-Christian A1 - Herter, Felix A1 - Lindow, Norbert A1 - Manke, Ingo A1 - Siopi, Tzulia A1 - Menei, Eve A1 - Etienne, Marc A1 - Lepper, Verena T1 - Virtual unfolding of folded papyri JF - Journal of Cultural Heritage N2 - The historical importance of ancient manuscripts is unique since they provide information about the heritage of ancient cultures. Often texts are hidden in rolled or folded documents. Due to recent impro- vements in sensitivity and resolution, spectacular disclosures of rolled hidden texts were possible by X-ray tomography. However, revealing text on folded manuscripts is even more challenging. Manual unfolding is often too risky in view of the fragile condition of fragments, as it can lead to the total loss of the document. X-ray tomography allows for virtual unfolding and enables non-destructive access to hid- den texts. We have recently demonstrated the procedure and tested unfolding algorithms on a mockup sample. Here, we present results on unfolding ancient papyrus packages from the papyrus collection of the Musée du Louvre, among them objects folded along approximately orthogonal folding lines. In one of the packages, the first identification of a word was achieved, the Coptic word for “Lord”. Y1 - 2020 U6 - https://doi.org/10.1016/j.culher.2019.07.007 VL - 41 SP - 264 EP - 269 PB - Elsevier ER - TY - GEN A1 - Mahnke, Heinz-Eberhard A1 - Arlt, Tobias A1 - Baum, Daniel A1 - Hege, Hans-Christian A1 - Herter, Felix A1 - Lindow, Norbert A1 - Manke, Ingo A1 - Siopi, Tzulia A1 - Menei, Eve A1 - Etienne, Marc A1 - Lepper, Verena T1 - Virtual unfolding of folded papyri N2 - The historical importance of ancient manuscripts is unique since they provide information about the heritage of ancient cultures. Often texts are hidden in rolled or folded documents. Due to recent impro- vements in sensitivity and resolution, spectacular disclosures of rolled hidden texts were possible by X-ray tomography. However, revealing text on folded manuscripts is even more challenging. Manual unfolding is often too risky in view of the fragile condition of fragments, as it can lead to the total loss of the document. X-ray tomography allows for virtual unfolding and enables non-destructive access to hid- den texts. We have recently demonstrated the procedure and tested unfolding algorithms on a mockup sample. Here, we present results on unfolding ancient papyrus packages from the papyrus collection of the Musée du Louvre, among them objects folded along approximately orthogonal folding lines. In one of the packages, the first identification of a word was achieved, the Coptic word for “Lord”. T3 - ZIB-Report - 19-44 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-74338 SN - 1438-0064 ER - TY - JOUR A1 - Lindow, Norbert A1 - Brünig, Florian A1 - Dercksen, Vincent J. A1 - Fabig, Gunar A1 - Kiewisz, Robert A1 - Redemann, Stefanie A1 - Müller-Reichert, Thomas A1 - Prohaska, Steffen A1 - Baum, Daniel T1 - Semi-automatic stitching of filamentous structures in image stacks from serial-section electron tomography JF - Journal of Microscopy N2 - We present a software-assisted workflow for the alignment and matching of filamentous structures across a three-dimensional (3D) stack of serial images. This is achieved by combining automatic methods, visual validation, and interactive correction. After the computation of an initial automatic matching, the user can continuously improve the result by interactively correcting landmarks or matches of filaments. Supported by a visual quality assessment of regions that have been already inspected, this allows a trade-off between quality and manual labor. The software tool was developed in an interdisciplinary collaboration between computer scientists and cell biologists to investigate cell division by quantitative 3D analysis of microtubules (MTs) in both mitotic and meiotic spindles. For this, each spindle is cut into a series of semi-thick physical sections, of which electron tomograms are acquired. The serial tomograms are then stitched and non-rigidly aligned to allow tracing and connecting of MTs across tomogram boundaries. In practice, automatic stitching alone provides only an incomplete solution, because large physical distortions and a low signal-to-noise ratio often cause experimental difficulties. To derive 3D models of spindles despite dealing with imperfect data related to sample preparation and subsequent data collection, semi-automatic validation and correction is required to remove stitching mistakes. However, due to the large number of MTs in spindles (up to 30k) and their resulting dense spatial arrangement, a naive inspection of each MT is too time-consuming. Furthermore, an interactive visualization of the full image stack is hampered by the size of the data (up to 100 GB). Here, we present a specialized, interactive, semi-automatic solution that considers all requirements for large-scale stitching of filamentous structures in serial-section image stacks. To the best of our knowledge, it is the only currently available tool which is able to process data of the type and size presented here. The key to our solution is a careful design of the visualization and interaction tools for each processing step to guarantee real-time response, and an optimized workflow that efficiently guides the user through datasets. The final solution presented here is the result of an iterative process with tight feedback loops between the involved computer scientists and cell biologists. Y1 - 2021 U6 - https://doi.org/10.1111/jmi.13039 VL - 284 IS - 1 SP - 25 EP - 44 ER -