Items 1-20 of 276

    • Journal Article

      The Protein‐Coding Human Genome: Annotating High‐Hanging Fruits 

      Hatje, Klas; Mühlhausen, Stefanie; Simm, Dominic; Kollmar, Martin
      BioEssays 2019; 41(11): Art. 1900066
      The major transcript variants of human protein-coding genes are annotated to a certain degree of accuracy combining manual curation, transcript data, and proteomics evidence. However, there is considerable disagreement on the annotation of about 2000 genes-they can be protein-coding, noncoding, or pseudogenes-and on the annotation of most of the predicted alternative transcripts. Pure transcriptome mapping approaches seem to be limited in discriminating functional expression from noise. These limitations have partially been overcome by dedicated algorithms to detect alternative spliced micro-exons and wobble splice variants. Recently, knowledge about splice mechanism and protein structure are incorporated into an algorithm to predict neighboring homologous exons, often spliced in a mutually exclusive manner. Predicted exons are evaluated by transcript data, structural compatibility, and evolutionary conservation, revealing hundreds of novel coding exons and splice mechanism re-assignments. The emerging human pan-genome is necessitating distinctive annotations incorporating differences between individuals and between populations.
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    • Journal Article

      Molecular contribution function in RESOLFT nanoscopy 

      Frahm, Lars; Keller-Findeisen, Jan; Alt, Philipp; Schnorrenberg, Sebastian; del Álamo Ruiz, Miguel; Aspelmeier, Timo; Munk, Axel; Jakobs, Stefan; Hell, Stefan W.
      Optics Express 2019; 27(15): Art. 21956
      The ultimate objective of a microscope of the highest resolution is to map the molecules of interest in the sample. Traditionally, linear imaging systems are characterized by their spatial frequency transfer function, which is given, in real space, by the point spread function (PSF). By extending the concept of the PSF towards the molecular contribution function (MCF), that quantifies the average contribution of a single fluorophore to the image, a straightforward concept for counting fluorophores is obtained. Using reversible saturable optical fluorescence transitions (RESOLFT), fluorophores are effectively activated only in a small, subdiffraction-sized volume before they are read out. During readout the signal exhibits an increased variance due to the stochastic nature of prior activation, which scales quadratically with the brightness of the active fluorophores while the mean of the signal scales only linearly with it. Using a two-state Markov model for the activation, showing comparable behavior to the switching kinetics of the switchable fluorescent protein rsEGFP2, we can approximate quantitatively the MCF of RESOLFT nanoscopy allowing to count the number of fluorophores within a subdiffraction-sized region of the sample. The method is validated on measurements of tubulin structures in Drosophila melagonaster larvae. Modeling and estimation of the MCF is a promising approach to quantitative microscopy.
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    • Journal Article

      THE EXPLICIT MORDELL CONJECTURE FOR FAMILIES OF CURVES 

      Checcoli Sara; Veneziano, Francesco; Viada, Evelina
      Forum of Mathematics, Sigma 2019; 7: Art. e31
      In this article we prove the explicit Mordell Conjecture for large families of curves. In addition, we introduce a method, of easy application, to compute all rational points on curves of quite general shape and increasing genus. The method bases on some explicit and sharp estimates for the height of such rational points, and the bounds are small enough to successfully implement a computer search. As an evidence of the simplicity of its application, we present a variety of explicit examples and explain how to produce many others. In the appendix our method is compared in detail to the classical method of Manin–Demjanenko and the analysis of our explicit examples is carried to conclusion.
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    • Journal Article

      Semi-supervised tri-Adaboost algorithm for network intrusion detection 

      Yuan, Yali; Huo, Liuwei; Yuan, Yachao; Wang, Zhixiao
      International Journal of Distributed Sensor Networks 2019; 15(6)
      Network intrusion detection is a relatively mature research topic, but one that remains challenging particular as technologies and threat landscape evolve. Here, a semi-supervised tri-Adaboost (STA) algorithm is proposed. In the algorithm, three different Adaboost algorithms are used as the weak classifiers (both for continuous and categorical data), constituting the decision stumps in the tri-training method. In addition, the chi-square method is used to reduce the dimension of feature and improve computational efficiency. We then conduct extensive numerical studies using different training and testing samples in the KDDcup99 dataset and discover the flows demonstrated that (1) high accuracy can be obtained using a training dataset which consists of a small number of labeled and a large number of unlabeled samples. (2) The algorithm proposed is reproducible and consistent over different runs. (3) The proposed algorithm outperforms other existing learning algorithms, even with only a small amount of labeled data in the training phase. (4) The proposed algorithm has a short execution time and a low false positive rate, while providing a desirable detection rate.
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    • Journal Article

      Direct characterization of cytoskeletal reorganization during blood platelet spreading 

      Paknikar, Aishwarya K.; Eltzner, Benjamin; Köster, Sarah
      Progress in Biophysics and Molecular Biology 2019; 144 p.166-176
      Blood platelets are the key cellular players in blood clotting and thus of great biomedical importance. While spreading at the site of injury, they reorganize their cytoskeleton within minutes and assume a flat appearance. As platelets possess no nucleus, many standard methods for visualizing cytoskeletal components by means of fluorescence tags fail. Here we employ silicon-rhodamine actin and tubulin probes for imaging these important proteins in a time-resolved manner. We find two distinct timescales for platelet spread area development and for cytoskeletal reorganization, indicating that although cell spreading is most likely associated with actin polymerization at the cell edges, distinct, stress-fiber-like actin structures within the cell, which may be involved in the generation of contractile forces, form on their own timescale. Following microtubule dynamics allows us to distinguish the role of myosin, microtubules and actin during early spreading.
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    • Journal Article

      An anisotropic interaction model for simulating fingerprints 

      Düring, Bertram; Gottschlich, Carsten; Huckemann, Stephan; Kreusser, Lisa Maria; Schönlieb, Carola-Bibiane
      Journal of Mathematical Biology
      Evidence suggests that both the interaction of so-called Merkel cells and the epidermal stress distribution play an important role in the formation of fingerprint patterns during pregnancy. To model the formation of fingerprint patterns in a biologically meaningful way these patterns have to become stationary. For the creation of synthetic fingerprints it is also very desirable that rescaling the model parameters leads to rescaled distances between the stationary fingerprint ridges. Based on these observations, as well as the model introduced by Kücken and Champod we propose a new model for the formation of fingerprint patterns during pregnancy. In this anisotropic interaction model the interaction forces not only depend on the distance vector between the cells and the model parameters, but additionally on an underlying tensor field, representing a stress field. This dependence on the tensor field leads to complex, anisotropic patterns. We study the resulting stationary patterns both analytically and numerically. In particular, we show that fingerprint patterns can be modeled as stationary solutions by choosing the underlying tensor field appropriately.
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    • Journal Article

      The Proximal Alternating Minimization Algorithm for Two-Block Separable Convex Optimization Problems with Linear Constraints 

      Bitterlich, Sandy; Boţ, Radu Ioan; Csetnek, Ernö Robert; Wanka, Gert
      Journal of Optimization Theory and Applications
      The Alternating Minimization Algorithm has been proposed by Paul Tseng to solve convex programming problems with two-block separable linear constraints and objectives, whereby (at least) one of the components of the latter is assumed to be strongly convex. The fact that one of the subproblems to be solved within the iteration process of this method does not usually correspond to the calculation of a proximal operator through a closed formula affects the implementability of the algorithm. In this paper, we allow in each block of the objective a further smooth convex function and propose a proximal version of the algorithm, which is achieved by equipping the algorithm with proximal terms induced by variable metrics. For suitable choices of the latter, the solving of the two subproblems in the iterative scheme can be reduced to the computation of proximal operators. We investigate the convergence of the proposed algorithm in a real Hilbert space setting and illustrate its numerical performances on two applications in image processing and machine learning.
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    • Journal Article

      Quantitative Convergence Analysis of Iterated Expansive, Set-Valued Mappings 

      Russell Luke, D.; Thao, Nguyen H.; Tam, Matthew K.
      Mathematics of Operations Research 2018; 43(4) p.1143-1176
      We develop a framework for quantitative convergence analysis of Picard iterations of expansive set-valued fixed point mappings. There are two key components of the analysis. The first is a natural generalization of single-valued averaged mappings to expansive set-valued mappings that characterizes a type of strong calmness of the fixed point mapping. The second component to this analysis is an extension of the well-established notion of metric subregularity—or inverse calmness—of the mapping at fixed points. Convergence of expansive fixed point iterations is proved using these two properties, and quantitative estimates are a natural by-product of the framework. To demonstrate the application of the theory, we prove, for the first time, a number of results showing local linear convergence of nonconvex cyclic projections for inconsistent (and consistent) feasibility problems, local linear convergence of the forward-backward algorithm for structured optimization without convexity, strong or otherwise, and local linear convergence of the Douglas-Rachford algorithm for structured nonconvex minimization. This theory includes earlier approaches for known results, convex and nonconvex, as special cases.
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    • Journal Article

      Latency-Sensitive Data Allocation and Workload Consolidation for Cloud Storage 

      Yang, Song; Wieder, Philipp; Aziz, Muzzamil; Yahyapour, Ramin; Fu, Xiaoming; Chen, Xu
      IEEE Access 2018; 6 p.76098-76110
      Customers often suffer from the variability of data access time in (edge) cloud storage service, caused by network congestion, load dynamics, and so on. One ef cient solution to guarantee a reliable latency-sensitive service (e.g., for industrial Internet of Things application) is to issue requests with multiple download/upload sessions which access the required data (replicas) stored in one or more servers, and use the earliest response from those sessions. In order to minimize the total storage costs, how to optimally allocate data in a minimum number of servers without violating latency guarantees remains to be a crucial issue for the cloud provider to deal with. In this paper, we study the latency-sensitive data allocation problem, the latency-sensitive data reallocation problem and the latency-sensitive workload consolidation problem for cloud storage. We model the data access time as a given distribution whose cumulative density function is known, and prove that these three problems are NP-hard. To solve them, we propose an exact integer nonlinear program (INLP) and a Tabu Search-based heuristic. The simulation results reveal that the INLP can always achieve the best performance in terms of lower number of used nodes and higher storage and throughput utilization, but this comes at the expense of much higher running time. The Tabu Searchbased heuristic, on the other hand, can obtain close-to-optimal performance, but in a much lower running time.
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    • Journal Article

      Extended Object Tracking: Introduction, Overview, and Applications 

      Granström, Karl; Baum, Marcus; Reuter, Stephan
      Journal of Advances in Information Fusion 2017; 12(2)
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    • Journal Article

      Topology determines force distributions in one-dimensional random spring networks 

      Heidemann, Knut M.; Sageman-Furnas, Andrew O.; Sharma, Abhinav; Rehfeldt, Florian; Schmidt, Christoph F.; Wardetzky, Max
      Physical Review E 2018; 97(2): Art. 022306
      etworks of elastic fibers are ubiquitous in biological systems and often provide mechanical stability to cells and tissues. Fiber-reinforced materials are also common in technology. An important characteristic of such materials is their resistance to failure under load. Rupture occurs when fibers break under excessive force and when that failure propagates. Therefore, it is crucial to understand force distributions. Force distributions within such networks are typically highly inhomogeneous and are not well understood. Here we construct a simple one-dimensional model system with periodic boundary conditions by randomly placing linear springs on a circle. We consider ensembles of such networks that consist of N nodes and have an average degree of connectivity z but vary in topology. Using a graph-theoretical approach that accounts for the full topology of each network in the ensemble, we show that, surprisingly, the force distributions can be fully characterized in terms of the parameters (N,z). Despite the universal properties of such (N,z) ensembles, our analysis further reveals that a classical mean-field approach fails to capture force distributions correctly. We demonstrate that network topology is a crucial determinant of force distributions in elastic spring networks.
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    • Journal Article

      A Survey of Ant Colony Optimization Based Routing Protocols for Mobile Ad Hoc Networks 

      Zhang, Hang; Wang, Xi; Memarmoshrefi, Parisa; Hogrefe, Dieter
      IEEE Access 2017; 5 p.24139-24161
      eveloping highly efficient routing protocols for Mobile Ad hoc NETworks (MANETs) is a challenging task. In order to fulfill multiple routing requirements, such as low packet delay, high packet delivery rate, and effective adaptation to network topology changes with low control overhead, and so on, new ways to approximate solutions to the known NP-hard optimization problem of routing in MANETs have to be investigated. Swarm intelligence (SI)-inspired algorithms have attracted a lot of attention, because they can offer possible optimized solutions ensuring high robustness, flexibility, and low cost. Moreover, they can solve large-scale sophisticated problems without a centralized control entity. A successful example in the SI field is the ant colony optimization (ACO) meta-heuristic. It presents a common framework for approximating solutions to NP-hard optimization problems. ACO has been successfully applied to balance the various routing related requirements in dynamic MANETs. This paper presents a comprehensive survey and comparison of various ACO-based routing protocols in MANETs. The main contributions of this survey include: 1) introducing the ACO principles as applied in routing protocols for MANETs; 2) classifying ACO-based routing approaches reviewed in this paper into five main categories; 3) surveying and comparing the selected routing protocols from the perspective of design and simulation parameters; and 4) discussing open issues and future possible design directions of ACO-based routing protocols.
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    • Journal Article

      An evolutionarily conserved glycine-tyrosine motif forms a folding core in outer membrane proteins. 

      Michalik, Marcin; Orwick-Rydmark, Marcella; Habeck, Michael; Alva, Vikram; Arnold, Thomas; Linke, Dirk
      PloS one 2017; 12(8): Art. e0182016
      An intimate interaction between a pair of amino acids, a tyrosine and glycine on neighboring β-strands, has been previously reported to be important for the structural stability of autotransporters. Here, we show that the conservation of this interacting pair extends to nearly all major families of outer membrane β-barrel proteins, which are thought to have originated through duplication events involving an ancestral ββ hairpin. We analyzed the function of this motif using the prototypical outer membrane protein OmpX. Stopped-flow fluorescence shows that two folding processes occur in the millisecond time regime, the rates of which are reduced in the tyrosine mutant. Folding assays further demonstrate a reduction in the yield of folded protein for the mutant compared to the wild-type, as well as a reduction in thermal stability. Taken together, our data support the idea of an evolutionarily conserved 'folding core' that affects the folding, membrane insertion, and thermal stability of outer membrane protein β-barrels.
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    • Journal Article

      ESTIMATION OF PARAMETERS IN A PLANAR SEGMENT PROCESS WITH A BIOLOGICAL APPLICATION 

      Beneš, Viktor; Večeřa, Jakub; Eltzner, Benjamin; Wollnik, Carina; Rehfeldt, Florian; Králová, Veronika; Huckemann, Stephan
      Image Analysis & Stereology 2017; 36(1) p.25-33
      The paper deals with modeling of segment systems in a bounded planar set (a cell) by means of random segment processes. Two models with a density with respect to the Poisson process are presented. In model I interactions are given by the number of intersections, model II includes the length distribution and takes into account distances from the centre of the cell. The estimation of parameters of the models is suggested based on Takacz-Fiksel method. The method is tested first using simulated data. Further the real data from fluorescence imaging of stress fibres in mesenchymal human stem cells are evaluated. We apply model II which is inhomogeneous. The degree-of-fit testing of the model using various characteristics yields quite satisfactory results.
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    • Journal Article

      Double Lie algebroids and representations up to homotopy 

      Gracia-Saz, A.; Jotz Lean, M.; Mackenzie, K. C. H.; Mehta, R. A.
      Journal of Homotopy and Related Structures
      We showthat a double Lie algebroid, together with a chosen decomposition, is equivalent to a pair of 2-term representations up to homotopy satisfying compatibility conditions which extend the notion of matched pair of Lie algebroids. We discuss in detail the double Lie algebroids arising from the tangent bundle of a Lie algebroid and the cotangent bundle of a Lie bialgebroid.
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    • Journal Article

      The Quantum Sine-Gordon Model in Perturbative AQFT 

      Bahns, Dorothea; Rejzner, Kasia
      Communications in Mathematical Physics
      We study the Sine-Gordon model with Minkowski signature in the framework of perturbative algebraic quantum field theory.We calculate the vertex operator algebra braiding property.We prove that in the finite regime of themodel, the expectation value— with respect to the vacuum or a Hadamard state—of the Epstein Glaser S-matrix and the interacting current or the field respectively converge, both given as formal power series.
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    • Journal Article

      Data-driven coarse graining of large biomolecular structures. 

      Chen, Yi-Ling; Habeck, Michael
      PloS one 2017; 12(8): Art. e0183057
      Advances in experimental and computational techniques allow us to study the structure and dynamics of large biomolecular assemblies at increasingly higher resolution. However, with increasing structural detail it can be challenging to unravel the mechanism underlying the function of molecular machines. One reason is that atomistic simulations become computationally prohibitive. Moreover it is difficult to rationalize the functional mechanism of systems composed of tens of thousands to millions of atoms by following each atom's movements. Coarse graining (CG) allows us to understand biological structures from a hierarchical perspective and to gradually zoom into the adequate level of structural detail. This article introduces a Bayesian approach for coarse graining biomolecular structures. We develop a probabilistic model that aims to represent the shape of an experimental structure as a cloud of bead particles. The particles interact via a pairwise potential whose parameters are estimated along with the bead positions and the CG mapping between atoms and beads. Our model can also be applied to density maps obtained by cryo-electron microscopy. We illustrate our approach on various test systems.
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    • Journal Article

      Distribution and evolution of stable single α-helices (SAH domains) in myosin motor proteins 

      Simm, Dominic; Hatje, Klas; Kollmar, Martin
      PLOS ONE 2017; 12(4): Art. e0174639
      Stable single-alpha helices (SAHs) are versatile structural elements in many prokaryotic and eukaryotic proteins acting as semi-flexible linkers and constant force springs. This way SAH-domains function as part of the lever of many different myosins. Canonical myosin levers consist of one or several IQ-motifs to which light chains such as calmodulin bind. SAH-domains provide flexibility in length and stiffness to the myosin levers, and may be particularly suited for myosins working in crowded cellular environments. Although the function of the SAH-domains in human class-6 and class-10 myosins has well been characterised, the distribution of the SAH-domain in all myosin subfamilies and across the eukaryotic tree of life remained elusive. Here, we analysed the largest available myosin sequence dataset consisting of 7919 manually annotated myosin sequences from 938 species representing all major eukaryotic branches using the SAH-prediction algorithm of Waggawagga, a recently developed tool for the identification of SAH-domains. With this approach we identified SAH-domains in more than one third of the supposed 79 myosin subfamilies. Depending on the myosin class, the presence of SAH-domains can range from a few to almost all class members indicating complex patterns of independent and taxon-specific SAH-domain gain and loss.
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    • Journal Article

      Model-based testing as a service 

      Herbold, Steffen; Hoffmann, Andreas
      International Journal on Software Tools for Technology Transfer
      The quality ofWeb services is an important factor for businesses that advertise or sell their services in the Internet. Failures can directly lead to fewer costumers or security problems. However, the testing of complexWeb services that are organized in service-oriented architectures is a difficult and complex problem. Model-based testing (MBT) is one solution to deal with the complexity of the testing. With MBT, testers do not define the tests directly, but rather specify the structure and behavior of the System Under Test using models. Then, a test strategy is used to derive test cases automatically from the models. However, MBT yields a large amount of tests for complex systems which require lots of resources for their execution, thereby limiting its potential. Within this article, we discuss how cloud computing can be used to provide the required resources for scaling up test campaigns with large amounts of test cases derived using MBT.
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    • Journal Article

      Directional global three-part image decomposition 

      Thai, D. H.; Gottschlich, C.
      EURASIP Journal on Image and Video Processing 2016; 2016(1): Art. 12
      We consider the task of image decomposition, and we introduce a new model coined directional global three-part decomposition (DG3PD) for solving it. As key ingredients of the DG3PD model, we introduce a discrete multi-directional total variation norm and a discrete multi-directional G-norm. Using these novel norms, the proposed discrete DG3PD model can decompose an image into two or three parts. Existing models for image decomposition by Vese and Osher (J. Sci. Comput. 19(1–3):553–572, 2003), by Aujol and Chambolle (Int. J. Comput. Vis. 63(1):85–104, 2005), by Starck et al. (IEEE Trans. Image Process. 14(10):1570–1582, 2005), and by Thai and Gottschlich are included as special cases in the new model. Decomposition of an image by DG3PD results in a cartoon image, a texture image, and a residual image. Advantages of the DG3PD model over existing ones lie in the properties enforced on the cartoon and texture images. The geometric objects in the cartoon image have a very smooth surface and sharp edges. The texture image yields oscillating patterns on a defined scale which are both smooth and sparse. Moreover, the DG3PD method achieves the goal of perfect reconstruction by summation of all components better than the other considered methods. Relevant applications of DG3PD are a novel way of image compression as well as feature extraction for applications such as latent fingerprint processing and optical character recognition.
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