TY - JOUR A1 - Zirkel, J. A1 - Cecil, A. A1 - Schäfer, F. A1 - Rahlfs, S. A1 - Ouedraogo, A. A1 - Xiao, K. A1 - Sawadogo, S. A1 - Coulibaly, B. A1 - Becker, K. A1 - Dandekar, T. T1 - Analyzing Thiol-Dependent Redox Networks in the Presence of Methylene Blue and Other Antimalarial Agents with RT-PCR-Supported in silico Modeling JF - Bioinformatics and Biology Insights N2 - BACKGROUND: In the face of growing resistance in malaria parasites to drugs, pharmacological combination therapies are important. There is accumulating evidence that methylene blue (MB) is an effective drug against malaria. Here we explore the biological effects of both MB alone and in combination therapy using modeling and experimental data. RESULTS: We built a model of the central metabolic pathways in P. falciparum. Metabolic flux modes and their changes under MB were calculated by integrating experimental data (RT-PCR data on mRNAs for redox enzymes) as constraints and results from the YANA software package for metabolic pathway calculations. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, chloroquine resistance based on pfmdr/and pfcrt transporters, as well as pyrimethamine/sulfadoxine resistance (by mutations in DHF/DHPS), were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs. CONCLUSIONS: Theoretical and experimental results support that methylene blue should, because of its resistance-breaking potential, be further tested as a key component in drug combination therapy efforts in holoendemic areas. KW - methylene blue KW - malaria KW - elementary mode analysis KW - drug KW - resistance KW - combination therapy KW - pathway KW - metabolic flux Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123751 N1 - This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited. VL - 6 ER - TY - THES A1 - Zinner, Thomas T1 - Performance Modeling of QoE-Aware Multipath Video Transmission in the Future Internet T1 - Leistungsmodellierung einer Mehrpfad Video Übertragung im zukünftigen Internet unter Berücksichtigung der QoE N2 - Internet applications are becoming more and more flexible to support diverge user demands and network conditions. This is reflected by technical concepts, which provide new adaptation mechanisms to allow fine grained adjustment of the application quality and the corresponding bandwidth requirements. For the case of video streaming, the scalable video codec H.264/SVC allows the flexible adaptation of frame rate, video resolution and image quality with respect to the available network resources. In order to guarantee a good user-perceived quality (Quality of Experience, QoE) it is necessary to adjust and optimize the video quality accurately. But not only have the applications of the current Internet changed. Within network and transport, new technologies evolved during the last years providing a more flexible and efficient usage of data transport and network resources. One of the most promising technologies is Network Virtualization (NV) which is seen as an enabler to overcome the ossification of the Internet stack. It provides means to simultaneously operate multiple logical networks which allow for example application-specific addressing, naming and routing, or their individual resource management. New transport mechanisms like multipath transmission on the network and transport layer aim at an efficient usage of available transport resources. However, the simultaneous transmission of data via heterogeneous transport paths and communication technologies inevitably introduces packet reordering. Additional mechanisms and buffers are required to restore the correct packet order and thus to prevent a disturbance of the data transport. A proper buffer dimensioning as well as the classification of the impact of varying path characteristics like bandwidth and delay require appropriate evaluation methods. Additionally, for a path selection mechanism real time evaluation mechanisms are needed. A better application-network interaction and the corresponding exchange of information enable an efficient adaptation of the application to the network conditions and vice versa. This PhD thesis analyzes a video streaming architecture utilizing multipath transmission and scalable video coding and develops the following optimization possibilities and results: Analysis and dimensioning methods for multipath transmission, quantification of the adaptation possibilities to the current network conditions with respect to the QoE for H.264/SVC, and evaluation and optimization of a future video streaming architecture, which allows a better interaction of application and network. N2 - Die Applikationen im Internet passen sich immer besser an unterschiedliche Anforderungen der Nutzer und variierende Netzwerkbedingungen an. Neue Mechanismen ermöglichen die zielgerichtete Anpassung der Anwendungsqualität und damit der benötigten Bandbreite. Im Falle von Videostreaming ermöglicht der skalierbare Videocodec H.264/SVC, die flexible Veränderung der Bildwiederholungsrate, der Auflösung des Videos und der Bildqualität an die vorhandenen Ressourcen im Netzwerk. Um eine gute vom Nutzer erfahrene Dienstgüte (Quality of Experience, QoE) zu garantieren, muss die Videoqualität richtig angepasst und optimiert werden. Aber nicht nur die Anwendungen des heutigen Internets haben sich verändert. Gerade in den letzten Jahren entstanden neue Netzwerk- und Transporttechnologien, welche eine flexiblere und effizientere Nutzung der Kommunikationsnetze erlauben. Eine dieser Techniken ist die Virtualisierung von Netzwerken. Sie erlaubt es auf einem gemeinsamen physikalischen Netz verschiedene logische Netze zu betreiben, die zum Beispiel Anwendungs-abhängige Adressierung unterstützen, eigene Namensgebung erlauben oder ein individuelles Ressourcen Management ermöglichen. Neuartige Transportmechanismen wie Mehrpfadübertragung auf Netzwerk- und Transportebene des ISO/OSI Stacks streben eine effiziente Ausnutzung der zur Verfügung stehenden Übertragungsmöglichkeiten an. Doch die simultane Übertragung von Daten über heterogene Kommunikationspfade und –technologien führt unausweichlich zu einer Veränderung der Reihenfolge, in der die Pakete ankommen. Es werden zusätzliche Mechanismen und Puffer benötigt, um die ursprüngliche Paketreihenfolge wieder herzustellen und so einen störenden Einfluss auf den Datentransport zu verhindern. Die richtige Dimensionierung dieser Puffer sowie die Klassifizierung des Einflusses von variierenden Pfadparametern wie Bandbreite und Verzögerungen setzen passende Evaluierungsmethoden voraus. Darüber hinaus werden für die Auswahl von geeigneten Pfaden aus einer Menge vorhandener Pfade echtzeitfähige Bewertungsmechanismen benötigt. Eine bessere Interaktion zwischen Applikationen und Netzwerk und der damit verbundene Informationsaustausch ermöglicht die effiziente Anpassung der Applikationsqualität an das Netzwerk und umgekehrt. Diese Doktorarbeit analysiert eine auf Mehrpfadübertragung und skalierbarer Videokodierung basierende Videostreaming Architektur und erarbeitet die folgenden Optimierungsmöglichkeiten und Auswertungen: Analyse- und Dimensionierungsmethoden für Mehrpfadübertragung, Quantifizierung der Anpassungsmöglichkeiten von SVC an das Netzwerk unter Berücksichtigung der QoE und Evaluierung und Optimierung einer zukünftigen Videostreaming Architektur, welche eine stärkere Interaktion zwischen Applikation und Netzwerk ermöglicht. T3 - Würzburger Beiträge zur Leistungsbewertung Verteilter Systeme - 03/12 KW - Videoübertragung KW - H.264 SVC KW - Modellierung KW - Quality-of-Experience KW - Mehrpfadübertragung KW - Multipath Transmission KW - Video Streaming KW - H.264/SVC KW - QoE KW - Performance Modeling Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72324 ER - TY - JOUR A1 - Wolff, Alexander A1 - Rutter, Iganz T1 - Augmenting the Connectivity of Planar and Geometric Graphs JF - Journal of Graph Algorithms and Applications N2 - In this paper we study connectivity augmentation problems. Given a connected graph G with some desirable property, we want to make G 2-vertex connected (or 2-edge connected) by adding edges such that the resulting graph keeps the property. The aim is to add as few edges as possible. The property that we consider is planarity, both in an abstract graph-theoretic and in a geometric setting, where vertices correspond to points in the plane and edges to straight-line segments. We show that it is NP-hard to � nd a minimum-cardinality augmentation that makes a planar graph 2-edge connected. For making a planar graph 2-vertex connected this was known. We further show that both problems are hard in the geometric setting, even when restricted to trees. The problems remain hard for higher degrees of connectivity. On the other hand we give polynomial-time algorithms for the special case of convex geometric graphs. We also study the following related problem. Given a planar (plane geometric) graph G, two vertices s and t of G, and an integer c, how many edges have to be added to G such that G is still planar (plane geometric) and contains c edge- (or vertex-) disjoint s{t paths? For the planar case we give a linear-time algorithm for c = 2. For the plane geometric case we give optimal worst-case bounds for c = 2; for c = 3 we characterize the cases that have a solution. Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97587 ER - TY - JOUR A1 - Staiger, Christine A1 - Cadot, Sidney A1 - Kooter, Raul A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Klau, Gunnar W. A1 - Wessels, Lodewyk F. A. T1 - A Critical Evaluation of Network and Pathway-Based Classifiers for Outcome Prediction in Breast Cancer JF - PLoS One N2 - Recently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically constructed by aggregating the expression levels of several genes. The secondary data sources are employed to guide this aggregation. Although many studies claim that these approaches improve classification performance over single genes classifiers, the gain in performance is difficult to assess. This stems mainly from the fact that different breast cancer data sets and validation procedures are employed to assess the performance. Here we address these issues by employing a large cohort of six breast cancer data sets as benchmark set and by performing an unbiased evaluation of the classification accuracies of the different approaches. Contrary to previous claims, we find that composite feature classifiers do not outperform simple single genes classifiers. We investigate the effect of (1) the number of selected features; (2) the specific gene set from which features are selected; (3) the size of the training set and (4) the heterogeneity of the data set on the performance of composite feature and single genes classifiers. Strikingly, we find that randomization of secondary data sources, which destroys all biological information in these sources, does not result in a deterioration in performance of composite feature classifiers. Finally, we show that when a proper correction for gene set size is performed, the stability of single genes sets is similar to the stability of composite feature sets. Based on these results there is currently no reason to prefer prognostic classifiers based on composite features over single genes classifiers for predicting outcome in breast cancer. KW - modules KW - protein-interaction networks KW - expression signature KW - classification KW - set KW - metastasis KW - stability KW - survival KW - database KW - markers Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131323 VL - 7 IS - 4 ER - TY - THES A1 - Schröter, Martin T1 - Newton Methods for Image Registration T1 - Newton-Methoden zur Bildregistrierung N2 - Consider the situation where two or more images are taken from the same object. After taking the first image, the object is moved or rotated so that the second recording depicts it in a different manner. Additionally, take heed of the possibility that the imaging techniques may have also been changed. One of the main problems in image processing is to determine the spatial relation between such images. The corresponding process of finding the spatial alignment is called “registration”. In this work, we study the optimization problem which corresponds to the registration task. Especially, we exploit the Lie group structure of the set of transformations to construct efficient, intrinsic algorithms. We also apply the algorithms to medical registration tasks. However, the methods developed are not restricted to the field of medical image processing. We also have a closer look at more general forms of optimization problems and show connections to related tasks. N2 - Wir betrachten Problemstellungen, in denen zwei Bilder von ein und demselben Objekt aufgenommen wurden. Nach der ersten Aufnahme hat sich allerdings das Objekt bewegt oder deformiert, so dass es sich in den nächsten Bildern auf eine andere Weise darstellt. Zudem kann sich die Aufnahmetechnik geändert haben. Eine der Hauptprobleme in der Bildverarbeitung ist es, die räumliche Korrespondenz zwischen solchen Bildern zu bestimmen. Die zugehörige Aufgabe, eine solche räumliche Übereinstimmung zu finden, nennt man "Registrierung". In dieser Arbeit untersuchen wir das mit der Registrierung verbundene Optimierungsproblem. Insbesondere nutzen wir die Lie-Gruppen-Struktur der Menge der zulässigen Transformationen aus, um effiziente, intrinsische Argorithmen zu entwickeln. Wir wenden diese dann auf Probleme der medizinischen Bildregistrierung an, jedoch sind unsere Methoden nicht auf dieses Feld beschränkt. Wir werfen auch einen genaueren Blick auf eine allgemeinere Form von Optimierungsproblemen und zeigen Verknüpfungen zu verwandten Fragestellungen auf. KW - Newton-Verfahren KW - Registrierung KW - Stochastische Optimierung KW - Newton Methods KW - Image Registration KW - Stochastic Algorithms KW - Optimization on Lie Groups Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-71490 ER - TY - JOUR A1 - Schokraie, Elham A1 - Warnken, Uwe A1 - Hotz-Wagenblatt, Agnes A1 - Grohme, Markus A. A1 - Hengherr, Steffen A1 - Förster, Frank A1 - Schill, Ralph O. A1 - Frohme, Marcus A1 - Dandekar, Thomas A1 - Schnölzer, Martina T1 - Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state JF - PLoS One N2 - Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state. KW - life-span regulation KW - genes KW - Yolk protein KW - water stress KW - expression KW - tolerance KW - richtersius coronifer KW - superoxide-dismutase KW - caenorhabditis elegans KW - arabidopsis thaliana KW - vitellogenin Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134447 VL - 7 IS - 9 ER - TY - INPR A1 - Nassourou, Mohamadou T1 - Towards a Knowledge-Based Learning System for The Quranic Text N2 - In this research, an attempt to create a knowledge-based learning system for the Quranic text has been performed. The knowledge base is made up of the Quranic text along with detailed information about each chapter and verse, and some rules. The system offers the possibility to study the Quran through web-based interfaces, implementing novel visualization techniques for browsing, querying, consulting, and testing the acquired knowledge. Additionally the system possesses knowledge acquisition facilities for maintaining the knowledge base. KW - Wissensbanksystem KW - Wissensmanagement KW - Text Mining KW - Visualisierung KW - Koran KW - Knowledge-based System KW - Knowledge Management System KW - Text Mining KW - Visualization KW - Quran Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-70003 ER - TY - JOUR A1 - Naseem, Muhammad A1 - Dandekar, Thomas T1 - The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions JF - PLOS Pathogens N2 - No abstract available. KW - disease KW - pseudomas-syringae KW - arabidpsis thaliana KW - immunity KW - organogenesis KW - transcription KW - resistance KW - crosstalk Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131901 VL - 8 IS - 11 ER - TY - JOUR A1 - Merget, Benjamin A1 - Koetschan, Christian A1 - Hackl, Thomas A1 - Förster, Frank A1 - Dandekar, Thomas A1 - Müller, Tobias A1 - Schultz, Jörg A1 - Wolf, Matthias T1 - The ITS2 Database JF - Journal of Visual Expression N2 - The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable ITS2 sequence, it confined this marker to low-level phylogenetics only. However, the combination of the ITS2 sequence and its highly conserved secondary structure improves the phylogenetic resolution1 and allows phylogenetic inference at multiple taxonomic ranks, including species delimitation. The ITS2 Database presents an exhaustive dataset of internal transcribed spacer 2 sequences from NCBI GenBank accurately reannotated. Following an annotation by profile Hidden Markov Models (HMMs), the secondary structure of each sequence is predicted. First, it is tested whether a minimum energy based fold (direct fold) results in a correct, four helix conformation. If this is not the case, the structure is predicted by homology modeling. In homology modeling, an already known secondary structure is transferred to another ITS2 sequence, whose secondary structure was not able to fold correctly in a direct fold. The ITS2 Database is not only a database for storage and retrieval of ITS2 sequence-structures. It also provides several tools to process your own ITS2 sequences, including annotation, structural prediction, motif detection and BLAST search on the combined sequence-structure information. Moreover, it integrates trimmed versions of 4SALE and ProfDistS for multiple sequence-structure alignment calculation and Neighbor Joining tree reconstruction. Together they form a coherent analysis pipeline from an initial set of sequences to a phylogeny based on sequence and secondary structure. In a nutshell, this workbench simplifies first phylogenetic analyses to only a few mouse-clicks, while additionally providing tools and data for comprehensive large-scale analyses. KW - homology modeling KW - molecular systematics KW - internal transcribed spacer 2 KW - alignment KW - genetics KW - secondary structure KW - ribosomal RNA KW - phylogenetic tree KW - phylogeny Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124600 VL - 61 IS - e3806 ER - TY - JOUR A1 - Krueger, Beate A1 - Friedrich, Torben A1 - Förster, Frank A1 - Bernhardt, Jörg A1 - Gross, Roy A1 - Dandekar, Thomas T1 - Different evolutionary modifications as a guide to rewire two-component systems JF - Bioinformatics and Biology Insights N2 - Two-component systems (TCS) are short signalling pathways generally occurring in prokaryotes. They frequently regulate prokaryotic stimulus responses and thus are also of interest for engineering in biotechnology and synthetic biology. The aim of this study is to better understand and describe rewiring of TCS while investigating different evolutionary scenarios. Based on large-scale screens of TCS in different organisms, this study gives detailed data, concrete alignments, and structure analysis on three general modification scenarios, where TCS were rewired for new responses and functions: (i) exchanges in the sequence within single TCS domains, (ii) exchange of whole TCS domains; (iii) addition of new components modulating TCS function. As a result, the replacement of stimulus and promotor cassettes to rewire TCS is well defined exploiting the alignments given here. The diverged TCS examples are non-trivial and the design is challenging. Designed connector proteins may also be useful to modify TCS in selected cases. KW - histidine kinase KW - connector KW - Mycoplasma KW - engineering KW - promoter KW - sensor KW - response regulator KW - synthetic biology KW - sequence alignment Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123647 N1 - This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited. VL - 6 ER -