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- 1D-3D hybrid modeling-from multi-compartment models to full resolution models in space and time (2014)
- Investigation of cellular and network dynamics in the brain by means of modeling and simulation has evolved into a highly interdisciplinary field, that uses sophisticated modeling and simulation approaches to understand distinct areas of brain function. Depending on the underlying complexity, these models vary in their level of detail, in order to cope with the attached computational cost. Hence for large network simulations, single neurons are typically reduced to time-dependent signal processors, dismissing the spatial aspect of each cell. For single cell or networks with relatively small numbers of neurons, general purpose simulators allow for space and time-dependent simulations of electrical signal processing, based on the cable equation theory. An emerging field in Computational Neuroscience encompasses a new level of detail by incorporating the full three-dimensional morphology of cells and organelles into three-dimensional, space and time-dependent, simulations. While every approach has its advantages and limitations, such as computational cost, integrated and methods-spanning simulation approaches, depending on the network size could establish new ways to investigate the brain. In this paper we present a hybrid simulation approach, that makes use of reduced 1D-models using e.g., the NEURON simulator—which couples to fully resolved models for simulating cellular and sub-cellular dynamics, including the detailed three-dimensional morphology of neurons and organelles. In order to couple 1D- and 3D-simulations, we present a geometry-, membrane potential- and intracellular concentration mapping framework, with which graph- based morphologies, e.g., in the swc- or hoc-format, are mapped to full surface and volume representations of the neuron and computational data from 1D-simulations can be used as boundary conditions for full 3D simulations and vice versa. Thus, established models and data, based on general purpose 1D-simulators, can be directly coupled to the emerging field of fully resolved, highly detailed 3D-modeling approaches. We present the developed general framework for 1D/3D hybrid modeling and apply it to investigate electrically active neurons and their intracellular spatio-temporal calcium dynamics.

- Staus vermeiden, Abgase reduzieren : Simulationen optimieren Verkehrsleitstrategien (2013)
- Frankfurt, an einem gewöhnlichen Morgen gegen 8:00 Uhr: Von Osten strömen zahlreiche Pendler über die A 66 in Richtung Innenstadt. Spätestens »Am Erlenbruch« kommt es zu Staus und zäh fließendem Verkehr. Frankfurter Informatiker können diese Staus mithilfe eines Simulationssystems vorhersagen. Mehr noch: Sie berechnen den Ausstoß von Schadstoffen und deren Verteilung über das Stadtgebiet. Ziel ist die Optimierung von Verkehrsleitstrategien.

- A genome-wide longitudinal transcriptome analysis of the aging model Podospora anserina (2013)
- Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.

- Online-Self-Assessments zur Erfassung studienrelevanter Kompetenzen (2009)
- An der Universität Frankfurt entwickelte Online-Self-Assessment-Verfahren für die Studiengänge Psychologie und Informatik sollen Studieninteressierten noch vor Studienbeginn auf der Basis von Selbsterkundungsmaßnahmen und Tests eine Rückmeldung über ihre eigenen Fähigkeiten, Motive, personalen Kompetenzen und Interessen mit Blick auf den jeweiligen Studiengang geben. Sowohl die Befunde zur psychometrischen Güte der Verfahren als auch jene zur prognostischen Validität lassen ihren Einsatz zur Feststellung studienrelevanter Kompetenzen als geeignet erscheinen. Da die erfassten Kompetenzen und Merkmale substanzielle Beziehun-gen zu Studienleistungen aufweisen, könnten die Informationen über individuelle Stärken zur Wahl eines geeigneten Studienganges genutzt werden; Schwächen hingegen könnten frühzeitig Hinweise für geeignete Fördermaßnahmen liefern.

- Tree-width for first order formulae (2012)
- We introduce tree-width for first order formulae φ, fotw(φ). We show that computing fotw is fixed-parameter tractable with parameter fotw. Moreover, we show that on classes of formulae of bounded fotw, model checking is fixed parameter tractable, with parameter the length of the formula. This is done by translating a formula φ with fotw(φ)<k into a formula of the k-variable fragment Lk of first order logic. For fixed k, the question whether a given first order formula is equivalent to an Lk formula is undecidable. In contrast, the classes of first order formulae with bounded fotw are fragments of first order logic for which the equivalence is decidable. Our notion of tree-width generalises tree-width of conjunctive queries to arbitrary formulae of first order logic by taking into account the quantifier interaction in a formula. Moreover, it is more powerful than the notion of elimination-width of quantified constraint formulae, defined by Chen and Dalmau (CSL 2005): for quantified constraint formulae, both bounded elimination-width and bounded fotw allow for model checking in polynomial time. We prove that fotw of a quantified constraint formula φ is bounded by the elimination-width of φ, and we exhibit a class of quantified constraint formulae with bounded fotw, that has unbounded elimination-width. A similar comparison holds for strict tree-width of non-recursive stratified datalog as defined by Flum, Frick, and Grohe (JACM 49, 2002). Finally, we show that fotw has a characterization in terms of a cops and robbers game without monotonicity cost.

- On functional module detection in metabolic networks (2013)
- Functional modules of metabolic networks are essential for understanding the metabolism of an organism as a whole. With the vast amount of experimental data and the construction of complex and large-scale, often genome-wide, models, the computer-aided identification of functional modules becomes more and more important. Since steady states play a key role in biology, many methods have been developed in that context, for example, elementary flux modes, extreme pathways, transition invariants and place invariants. Metabolic networks can be studied also from the point of view of graph theory, and algorithms for graph decomposition have been applied for the identification of functional modules. A prominent and currently intensively discussed field of methods in graph theory addresses the Q-modularity. In this paper, we recall known concepts of module detection based on the steady-state assumption, focusing on transition-invariants (elementary modes) and their computation as minimal solutions of systems of Diophantine equations. We present the Fourier-Motzkin algorithm in detail. Afterwards, we introduce the Q-modularity as an example for a useful non-steady-state method and its application to metabolic networks. To illustrate and discuss the concepts of invariants and Q-modularity, we apply a part of the central carbon metabolism in potato tubers (Solanum tuberosum) as running example. The intention of the paper is to give a compact presentation of known steady-state concepts from a graph-theoretical viewpoint in the context of network decomposition and reduction and to introduce the application of Q-modularity to metabolic Petri net models.

- QuateXelero : an accelerated exact network motif detection algorithm (2013)
- Finding motifs in biological, social, technological, and other types of networks has become a widespread method to gain more knowledge about these networks’ structure and function. However, this task is very computationally demanding, because it is highly associated with the graph isomorphism which is an NP problem (not known to belong to P or NP-complete subsets yet). Accordingly, this research is endeavoring to decrease the need to call NAUTY isomorphism detection method, which is the most time-consuming step in many existing algorithms. The work provides an extremely fast motif detection algorithm called QuateXelero, which has a Quaternary Tree data structure in the heart. The proposed algorithm is based on the well-known ESU (FANMOD) motif detection algorithm. The results of experiments on some standard model networks approve the overal superiority of the proposed algorithm, namely QuateXelero, compared with two of the fastest existing algorithms, G-Tries and Kavosh. QuateXelero is especially fastest in constructing the central data structure of the algorithm from scratch based on the input network.

- A note on the expressive power of linear orders (2011)
- This article shows that there exist two particular linear orders such that first-order logic with these two linear orders has the same expressive power as first-order logic with the Bit-predicate FO(Bit). As a corollary we obtain that there also exists a built-in permutation such that first-order logic with a linear order and this permutation is as expressive as FO(Bit).

- The succinctness of first-order logic on linear orders (2005)
- Succinctness is a natural measure for comparing the strength of different logics. Intuitively, a logic L_1 is more succinct than another logic L_2 if all properties that can be expressed in L_2 can be expressed in L_1 by formulas of (approximately) the same size, but some properties can be expressed in L_1 by (significantly) smaller formulas. We study the succinctness of logics on linear orders. Our first theorem is concerned with the finite variable fragments of first-order logic. We prove that: (i) Up to a polynomial factor, the 2- and the 3-variable fragments of first-order logic on linear orders have the same succinctness. (ii) The 4-variable fragment is exponentially more succinct than the 3-variable fragment. Our second main result compares the succinctness of first-order logic on linear orders with that of monadic second-order logic. We prove that the fragment of monadic second-order logic that has the same expressiveness as first-order logic on linear orders is non-elementarily more succinct than first-order logic.

- Effect sizes in experimental pain produced by gender, genetic variants and sensitization procedures (2011)
- Background: Various effects on pain have been reported with respect to their statistical significance, but a standardized measure of effect size has been rarely added. Such a measure would ease comparison of the magnitude of the effects across studies, for example the effect of gender on heat pain with the effect of a genetic variant on pressure pain. Methodology/Principal Findings: Effect sizes on pain thresholds to stimuli consisting of heat, cold, blunt pressure, punctuate pressure and electrical current, administered to 125 subjects, were analyzed for 29 common variants in eight human genes reportedly modulating pain, gender and sensitization procedures using capsaicin or menthol. The genotype explained 0–5.9% of the total interindividual variance in pain thresholds to various stimuli and produced mainly small effects (Cohen's d 0–1.8). The largest effect had the TRPA1 rs13255063T/rs11988795G haplotype explaining >5% of the variance in electrical pain thresholds and conferring lower pain sensitivity to homozygous carriers. Gender produced larger effect sizes than most variant alleles (1–14.8% explained variance, Cohen's d 0.2–0.8), with higher pain sensitivity in women than in men. Sensitization by capsaicin or menthol explained up to 63% of the total variance (4.7–62.8%) and produced largest effects according to Cohen's d (0.4–2.6), especially heat sensitization by capsaicin (Cohen's d = 2.6). Conclusions: Sensitization, gender and genetic variants produce effects on pain in the mentioned order of effect sizes. The present report may provide a basis for comparative discussions of factors influencing pain.