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'Gelegenheitsdichtung'
(2010)
Situated in an active tectonic region, Santiago de Chile, the country´s capital with more than six million inhabitants, faces tremendous earthquake hazard. Macroseismic data for the 1985 Valparaiso and the 2010 Maule events show large variations in the distribution of damage to buildings within short distances indicating strong influence of local sediments and the shape of the sediment-bedrock interface on ground motion. Therefore, a temporary seismic network was installed in the urban area for recording earthquake activity, and a study was carried out aiming to estimate site amplification derived from earthquake data and ambient noise. The analysis of earthquake data shows significant dependence on the local geological structure with regards to amplitude and duration. Moreover, the analysis of noise spectral ratios shows that they can provide a lower bound in amplitude for site amplification and, since no variability in terms of time and amplitude is observed, that it is possible to map the fundamental resonance frequency of the soil for a 26 km x 12 km area in the northern part of the Santiago de Chile basin. By inverting the noise spectral rations, local shear wave velocity profiles could be derived under the constraint of the thickness of the sedimentary cover which had previously been determined by gravimetric measurements. The resulting 3D model was derived by interpolation between the single shear wave velocity profiles and shows locally good agreement with the few existing velocity profile data, but allows the entire area, as well as deeper parts of the basin, to be represented in greater detail. The wealth of available data allowed further to check if any correlation between the shear wave velocity in the uppermost 30 m (vs30) and the slope of topography, a new technique recently proposed by Wald and Allen (2007), exists on a local scale. While one lithology might provide a greater scatter in the velocity values for the investigated area, almost no correlation between topographic gradient and calculated vs30 exists, whereas a better link is found between vs30 and the local geology. When comparing the vs30 distribution with the MSK intensities for the 1985 Valparaiso event it becomes clear that high intensities are found where the expected vs30 values are low and over a thick sedimentary cover. Although this evidence cannot be generalized for all possible earthquakes, it indicates the influence of site effects modifying the ground motion when earthquakes occur well outside of the Santiago basin. Using the attained knowledge on the basin characteristics, simulations of strong ground motion within the Santiago Metropolitan area were carried out by means of the spectral element technique. The simulation of a regional event, which has also been recorded by a dense network installed in the city of Santiago for recording aftershock activity following the 27 February 2010 Maule earthquake, shows that the model is capable to realistically calculate ground motion in terms of amplitude, duration, and frequency and, moreover, that the surface topography and the shape of the sediment bedrock interface strongly modify ground motion in the Santiago basin. An examination on the dependency of ground motion on the hypocenter location for a hypothetical event occurring along the active San Ramón fault, which is crossing the eastern outskirts of the city, shows that the unfavorable interaction between fault rupture, radiation mechanism, and complex geological conditions in the near-field may give rise to large values of peak ground velocity and therefore considerably increase the level of seismic risk for Santiago de Chile.
Companies develop process models to explicitly describe their business operations. In the same time, business operations, business processes, must adhere to various types of compliance requirements. Regulations, e.g., Sarbanes Oxley Act of 2002, internal policies, best practices are just a few sources of compliance requirements. In some cases, non-adherence to compliance requirements makes the organization subject to legal punishment. In other cases, non-adherence to compliance leads to loss of competitive advantage and thus loss of market share. Unlike the classical domain-independent behavioral correctness of business processes, compliance requirements are domain-specific. Moreover, compliance requirements change over time. New requirements might appear due to change in laws and adoption of new policies. Compliance requirements are offered or enforced by different entities that have different objectives behind these requirements. Finally, compliance requirements might affect different aspects of business processes, e.g., control flow and data flow. As a result, it is infeasible to hard-code compliance checks in tools. Rather, a repeatable process of modeling compliance rules and checking them against business processes automatically is needed. This thesis provides a formal approach to support process design-time compliance checking. Using visual patterns, it is possible to model compliance requirements concerning control flow, data flow and conditional flow rules. Each pattern is mapped into a temporal logic formula. The thesis addresses the problem of consistency checking among various compliance requirements, as they might stem from divergent sources. Also, the thesis contributes to automatically check compliance requirements against process models using model checking. We show that extra domain knowledge, other than expressed in compliance rules, is needed to reach correct decisions. In case of violations, we are able to provide a useful feedback to the user. The feedback is in the form of parts of the process model whose execution causes the violation. In some cases, our approach is capable of providing automated remedy of the violation.
Background: Cysteine is a component in organic compounds including glutathione that have been implicated in the adaptation of plants to stresses. O-acetylserine (thiol) lyase (OAS-TL) catalyses the final step of cysteine biosynthesis. OAS-TL enzyme isoforms are localised in the cytoplasm, the plastids and mitochondria but the contribution of individual OAS-TL isoforms to plant sulphur metabolism has not yet been fully clarified.
Results: The seedling lethal phenotype of the Arabidopsis onset of leaf death3-1 (old3-1) mutant is due to a point mutation in the OAS-A1 gene, encoding the cytosolic OAS-TL. The mutation causes a single amino acid substitution from Gly(162) to Glu(162), abolishing old3-1 OAS-TL activity in vitro. The old3-1 mutation segregates as a monogenic semidominant trait when backcrossed to its wild type accession Landsberg erecta (Ler-0) and the Di-2 accession. Consistent with its semi-dominant behaviour, wild type Ler-0 plants transformed with the mutated old3-1 gene, displayed the early leaf death phenotype. However, the old3-1 mutation segregates in an 11: 4: 1 (wild type: semi-dominant: mutant) ratio when backcrossed to the Colombia-0 and Wassilewskija accessions. Thus, the early leaf death phenotype depends on two semi-dominant loci. The second locus that determines the old3-1 early leaf death phenotype is referred to as odd-ler (for old3 determinant in the Ler accession) and is located on chromosome 3. The early leaf death phenotype is temperature dependent and is associated with increased expression of defence-response and oxidative-stress marker genes. Independent of the presence of the odd-ler gene, OAS-A1 is involved in maintaining sulphur and thiol levels and is required for resistance against cadmium stress.
Conclusions: The cytosolic OAS-TL is involved in maintaining organic sulphur levels. The old3-1 mutation causes genome-dependent and independent phenotypes and uncovers a novel function for the mutated OAS-TL in cell death regulation.
This thesis is focused on the electronic, spin-dependent and dynamical properties of thin magnetic systems. Photoemission-related techniques are combined with synchrotron radiation to study the spin-dependent properties of these systems in the energy and time domains. In the first part of this thesis, the strength of electron correlation effects in the spin-dependent electronic structure of ferromagnetic bcc Fe(110) and hcp Co(0001) is investigated by means of spin- and angle-resolved photoemission spectroscopy. The experimental results are compared to theoretical calculations within the three-body scattering approximation and within the dynamical mean-field theory, together with one-step model calculations of the photoemission process. From this comparison it is demonstrated that the present state of the art many-body calculations, although improving the description of correlation effects in Fe and Co, give too small mass renormalizations and scattering rates thus demanding more refined many-body theories including nonlocal fluctuations. In the second part, it is shown in detail monitoring by photoelectron spectroscopy how graphene can be grown by chemical vapour deposition on the transition-metal surfaces Ni(111) and Co(0001) and intercalated by a monoatomic layer of Au. For both systems, a linear E(k) dispersion of massless Dirac fermions is observed in the graphene pi-band in the vicinity of the Fermi energy. Spin-resolved photoemission from the graphene pi-band shows that the ferromagnetic polarization of graphene/Ni(111) and graphene/Co(0001) is negligible and that graphene on Ni(111) is after intercalation of Au spin-orbit split by the Rashba effect. In the last part, a time-resolved x-ray magnetic circular dichroic-photoelectron emission microscopy study of a permalloy platelet comprising three cross-tie domain walls is presented. It is shown how a fast picosecond magnetic response in the precessional motion of the magnetization can be induced by means of a laser-excited photoswitch. From a comparision to micromagnetic calculations it is demonstrated that the relatively high precessional frequency observed in the experiments is directly linked to the nature of the vortex/antivortex dynamics and its response to the magnetic perturbation. This includes the time-dependent reversal of the vortex core polarization, a process which is beyond the limit of detection in the present experiments.
About the relation between implicit Theory of Mind & the comprehension of complement sentences
(2010)
Previous studies on the relation between language and social cognition have shown that children’s mastery of embedded sentential complements plays a causal role for the development of a Theory of Mind (ToM). Children start to succeed on complementation tasks in which they are required to report the content of an embedded clause in the second half of the fourth year. Traditional ToM tasks test the child’s ability to predict that a person who is holding a false belief (FB) about a situation will act "falsely". In these task, children do not represent FBs until the age of 4 years. According the linguistic determinism hypothesis, only the unique syntax of complement sentences provides the format for representing FBs. However, experiments measuring children’s looking behavior instead of their explicit predictions provided evidence that already 2-year olds possess an implicit ToM. This dissertation examined the question of whether there is an interrelation also between implicit ToM and the comprehension of complement sentences in typically developing German preschoolers. Two studies were conducted. In a correlational study (Study 1 ), 3-year-old children’s performance on a traditional (explicit) FB task, on an implicit FB task and on language tasks measuring children’s comprehension of tensed sentential complements were collected and tested for their interdependence. Eye-tracking methodology was used to assess implicit ToM by measuring participants’ spontaneous anticipatory eye movements while they were watching FB movies. Two central findings emerged. First, predictive looking (implicit ToM) was not correlated with complement mastery, although both measures were associated with explicit FB task performance. This pattern of results suggests that explicit, but not implicit ToM is language dependent. Second, as a group, 3-year-olds did not display implicit FB understanding. That is, previous findings on a precocious reasoning ability could not be replicated. This indicates that the characteristics of predictive looking tasks play a role for the elicitation of implicit FB understanding as the current task was completely nonverbal and as complex as traditional FB tasks. Study 2 took a methodological approach by investigating whether children display an earlier comprehension of sentential complements when using the same means of measurement as used in experimental tasks tapping implicit ToM, namely anticipatory looking. Two experiments were conducted. 3-year-olds were confronted either with a complement sentence expressing the protagonist’s FB (Exp. 1) or with a complex sentence expressing the protagonist’s belief without giving any information about the truth/ falsity of the belief (Exp. 2). Afterwards, their expectations about the protagonist’s future behavior were measured. Overall, implicit measures reveal no considerably earlier understanding of sentential complementation. Whereas 3-year-olds did not display a comprehension of complex sentences if these embedded a false proposition, children from 3;9 years on were proficient in processing complement sentences if the truth value of the embedded proposition could not be evaluated. This pattern of results suggests that (1) the linguistic expression of a person’s FB does not elicit implicit FB understanding and that (2) the assessment of the purely syntactic understanding of complement sentences is affected by competing reality information. In conclusion, this dissertation found no evidence that the implicit ToM is related to the comprehension of sentential complementation. The findings suggest that implicit ToM might be based on nonlinguistic processes. Results are discussed in the light of recently proposed dual-process models that assume two cognitive mechanisms that account for different levels of ToM task performance.
We establish elements of a new approach to ellipticity and parametrices within operator algebras on manifolds with higher singularities, only based on some general axiomatic requirements on parameter-dependent operators in suitable scales of spaes. The idea is to model an iterative process with new generations of parameter-dependent operator theories, together with new scales of spaces that satisfy analogous requirements as the original ones, now on a corresponding higher level. The "full" calculus involves two separate theories, one near the tip of the corner and another one at the conical exit to infinity. However, concerning the conical exit to infinity, we establish here a new concrete calculus of edge-degenerate operators which can be iterated to higher singularities.
This thesis presents methods for automated synthesis of flexible chip multiprocessor systems from parallel programs targeted at FPGAs to exploit both task-level parallelism and architecture customization. Automated synthesis is necessitated by the complexity of the design space. A detailed description of the design space is provided in order to determine which parameters should be modeled to facilitate automated synthesis by optimizing a cost function, the emphasis being placed on inclusive modeling of parameters from application, architectural and physical subspaces, as well as their joint coverage in order to avoid pre-constraining the design space. Given a parallel program and a set of an IP library, the automated synthesis problem is to simultaneously (i) select processors (ii) map and schedule tasks to them, and (iii) select one or several networks for inter-task communications such that design constraints and optimization objectives are met. The research objective in this thesis is to find a suitable model for automated synthesis, and to evaluate methods of using the model for architectural optimizations. Our contributions are a holistic approach for the design of such systems, corresponding models to facilitate automated synthesis, evaluation of optimization methods using state of the art integer linear and answer set programming, as well as the development of synthesis heuristics to solve runtime challenges.
Die Neue Ökonomische Geographie (NEG) erklärt Agglomerationen aus einem mikroökonomischen Totalmodell heraus. Zur Vereinfachung werden verschiedene Symmetrieannahmen getätigt. So wird davon ausgegangen, dass die betrachteten Regionen die gleiche Größe haben, die Ausgabenanteile für verschiedene Gütergruppen identisch sind und die Transportkosten für alle Industrieprodukte die selben sind. Eine Folge dieser Annahmen ist es, dass zwar erklärt werden kann, unter welchen Bedingungen es zur Agglomerationsbildung kommt, nicht aber wo dies geschieht. In dieser Arbeit werden drei Standardmodelle der NEG um verschiedene Asymmetrien erweitert und die Veränderung der Ergebnisse im Vergleich zum jeweiligen Basismodell dargestellt. Dabei wird neben der Theorie auf die Methoden der Simulation eingegangen, die sich grundsätzlich auf andere Modelle übertragen lassen. Darauf aufbauend wird eine asymmetrische Modellvariante auf die wirtschaftliche Entwicklung Deutschlands angewandt. So lässt sich das Ausbleiben eines flächendeckenden Aufschwungs in den neuen Ländern, die starken Wanderungsbewegungen in die alten Länder und das dauerhafte Lohnsatzgefälle in einem Totalmodell erklären.
Based on technological advances made within the past decades, ground-penetrating radar (GPR) has become a well-established, non-destructive subsurface imaging technique. Catalyzed by recent demands for high-resolution, near-surface imaging (e.g., the detection of unexploded ordnances and subsurface utilities, or hydrological investigations), the quality of today's GPR-based, near-surface images has significantly matured. At the same time, the analysis of oil and gas related reflection seismic data sets has experienced significant advances. Considering the sensitivity of attribute analysis with respect to data positioning in general, and multi-trace attributes in particular, trace positioning accuracy is of major importance for the success of attribute-based analysis flows. Therefore, to study the feasibility of GPR-based attribute analyses, I first developed and evaluated a real-time GPR surveying setup based on a modern tracking total station (TTS). The combination of current GPR systems capability of fusing global positioning system (GPS) and geophysical data in real-time, the ability of modern TTS systems to generate a GPS-like positional output and wireless data transmission using radio modems results in a flexible and robust surveying setup. To elaborate the feasibility of this setup, I studied the major limitations of such an approach: system cross-talk and data delays known as latencies. Experimental studies have shown that when a minimal distance of ~5 m between the GPR and the TTS system is considered, the signal-to-noise ratio of the acquired GPR data using radio communication equals the one without radio communication. To address the limitations imposed by system latencies, inherent to all real-time data fusion approaches, I developed a novel correction (calibration) strategy to assess the gross system latency and to correct for it. This resulted in the centimeter trace accuracy required by high-frequency and/or three-dimensional (3D) GPR surveys. Having introduced this flexible high-precision surveying setup, I successfully demonstrated the application of attribute-based processing to GPR specific problems, which may differ significantly from the geological ones typically addressed by the oil and gas industry using seismic data. In this thesis, I concentrated on archaeological and subsurface utility problems, as they represent typical near-surface geophysical targets. Enhancing 3D archaeological GPR data sets using a dip-steered filtering approach, followed by calculation of coherency and similarity, allowed me to conduct subsurface interpretations far beyond those obtained by classical time-slice analyses. I could show that the incorporation of additional data sets (magnetic and topographic) and attributes derived from these data sets can further improve the interpretation. In a case study, such an approach revealed the complementary nature of the individual data sets and, for example, allowed conclusions about the source location of magnetic anomalies by concurrently analyzing GPR time/depth slices to be made. In addition to archaeological targets, subsurface utility detection and characterization is a steadily growing field of application for GPR. I developed a novel attribute called depolarization. Incorporation of geometrical and physical feature characteristics into the depolarization attribute allowed me to display the observed polarization phenomena efficiently. Geometrical enhancement makes use of an improved symmetry extraction algorithm based on Laplacian high-boosting, followed by a phase-based symmetry calculation using a two-dimensional (2D) log-Gabor filterbank decomposition of the data volume. To extract the physical information from the dual-component data set, I employed a sliding-window principle component analysis. The combination of the geometrically derived feature angle and the physically derived polarization angle allowed me to enhance the polarization characteristics of subsurface features. Ground-truth information obtained by excavations confirmed this interpretation. In the future, inclusion of cross-polarized antennae configurations into the processing scheme may further improve the quality of the depolarization attribute. In addition to polarization phenomena, the time-dependent frequency evolution of GPR signals might hold further information on the subsurface architecture and/or material properties. High-resolution, sparsity promoting decomposition approaches have recently had a significant impact on the image and signal processing community. In this thesis, I introduced a modified tree-based matching pursuit approach. Based on different synthetic examples, I showed that the modified tree-based pursuit approach clearly outperforms other commonly used time-frequency decomposition approaches with respect to both time and frequency resolutions. Apart from the investigation of tuning effects in GPR data, I also demonstrated the potential of high-resolution sparse decompositions for advanced data processing. Frequency modulation of individual atoms themselves allows to efficiently correct frequency attenuation effects and improve resolution based on shifting the average frequency level. GPR-based attribute analysis is still in its infancy. Considering the growing widespread realization of 3D GPR studies there will certainly be an increasing demand towards improved subsurface interpretations in the future. Similar to the assessment of quantitative reservoir properties through the combination of 3D seismic attribute volumes with sparse well-log information, parameter estimation in a combined manner represents another step in emphasizing the potential of attribute-driven GPR data analyses.
Sprachverständnisuntersuchungen sind sowohl für die Forschung zum Spracherwerb und zu dessen Störungen als auch für die Diagnostik in der klinischen Praxis von essentieller Bedeutung. Zwei der verbreitetesten Methoden zur Erfassung des Verständnisses von syntaktischen Strukturen sind das Ausagieren von Sätzen (AS) und die Satz-Bild-Zuordnung (SBZ). Beide Methoden sind mit unterschiedlichen Anforderungen an die Probanden sowie mit spezifischen Vor- und Nachteilen verbunden (vgl. z.B. Goodluck 1996, Gerken & Shady 1996), woraus sich die Frage ergibt, inwiefern die Wahl der Methode das Testergebnis und die damit verbundenen Schlussfolgerungen beeinflusst. In der hier beschriebenen empirischen Untersuchung wurden die AS- und die SBZ-Methode anhand des Verstehens semantisch reversibler Sätze mit Objektvoranstellung direkt miteinander verglichen: Jeweils 24 monolingual mit Deutsch als Muttersprache aufwachsenden, sprachunauffälligen Kindern im Alter von 3;0 bis 3;5 bzw. 5;0 bis 5;5 Jahren wurden insgesamt zwölf Items, von denen neun aus semantisch reversiblen Sätzen mit Objektvoranstellung und drei aus entsprechenden subjektinitialen Kontrastsätzen bestanden, sowohl mittels der AS-Methode als auch mittels der SBZ-Methode präsentiert. Zum Ausagieren der Testsätze (AS-Test) wurden Spielzeugfiguren verwendet, für die Satz-Bild-Zuordnung (SBZ-Test) wurden pro Item ein Ziel- und zwei Ablenkerbilder erstellt. Die kindlichen Reaktionen wurden nach syntaktischen Kriterien als korrekt bzw. inkorrekt bewertet, Abweichungen wurden hinsichtlich der Fehlerart klassifiziert. Zusätzlich wurde bei den einzelnen Kindern der Erwerbsstand der untersuchten Struktur beurteilt und es wurden, sofern möglich, die eingesetzten Sprachverständnisstrategien ermittelt. Der Vergleich der Methoden ergab für die einzelnen Altersgruppen sehr unterschiedliche Befunde: Bei den 3;0- bis 3;5-jährigen Kindern zeigten sich im SBZ-Test teilweise starke Rateeffekte, die zu verfälschten Ergebnissen und kaum interpretierbaren Reaktionsmustern führten, während dies im AS-Test nicht der Fall war. Für diese Altersgruppe ist demnach die AS-Methode als die geeignetere anzusehen. Bei den 5;0- bis 5;5-jährigen Kindern konnte indes keine derartige Diskrepanz zwischen den beiden Tests festgestellt werden. Vielmehr waren die Leistungen hier insgesamt vergleichbar, so dass für diese Altersgruppe die AS- und die SBZ-Methode als für die Untersuchung des Syntaxverständnisses gleichwertig gelten können. Darüber hinaus bestätigte die Untersuchung viele der in der Literatur beschriebenen Vor- und Nachteile der beiden Methoden, darunter der geringere Materialbeschaffungsaufwand bei der AS-Methode, die größere Durchführungspraktikabilität der SBZ-Methode, die höhere Attraktivität und das geringere Risiko für Antwort-biases bei der AS-Methode, die leichtere Bewertbarkeit der kindlichen Reaktionen bei der SBZ-Methode. Im Vergleich der Altersgruppen zeigte sich, dass die 5;0- bis 5;5-jährigen Kinder Testsätze mit Objektvoranstellung deutlich besser verstanden als die 3;0- bis 3;5-jährigen: Die meisten der jüngeren Kinder hatten die untersuchte Struktur offenbar noch nicht erworben – sie interpretierten die Sätze mit Objektvoranstellung stattdessen am häufigsten nach der Wortreihenfolgestrategie, verstanden sie also wie subjektinitiale Strukturen. Von den 5;0- bis 5;5-jährigen Kindern dagegen hatten 75% die untersuchte Struktur rezeptiv erworben, interpretierten die Testsätze also primär korrekt nach der grammatischen Strategie. Aus diesen Ergebnissen wurde geschlossen, dass die Struktur semantisch reversibler Sätze mit Objektvoranstellung frühestens ab einem Alter von 5;0 bis 5;5 Jahren als in der ungestörten Sprachentwicklung rezeptiv erworben gelten kann. Da sich jedoch in beiden Altersgruppen trotz allem eine erhebliche interindividuelle Variation hinsichtlich der Verständnisfähigkeiten zeigte, muss insgesamt von einem relativ langen Zeitfenster für den ungestörten Erwerb dieser Struktur ausgegangen werden.
Within our research group Bayesian Risk Solutions we have coined the idea of a Bayesian Risk Management (BRM). It claims (1) a more transparent and diligent data analysis as well as (2)an open-minded incorporation of human expertise in risk management. In this dissertation we formulize a framework for BRM based on the two pillars Hardcore-Bayesianism (HCB) and Softcore-Bayesianism (SCB) providing solutions for the claims above. For data analysis we favor Bayesian statistics with its Markov Chain Monte Carlo (MCMC) simulation algorithm. It provides a full illustration of data-induced uncertainty beyond classical point-estimates. We calibrate twelve different stochastic processes to four years of CO2 price data. Besides, we calculate derived risk measures (ex ante/ post value-at-risks, capital charges, option prices) and compare them to their classical counterparts. When statistics fails because of a lack of reliable data we propose our integrated Bayesian Risk Analysis (iBRA) concept. It is a basic guideline for an expertise-driven quantification of critical risks. We additionally review elicitation techniques and tools supporting experts to express their uncertainty. Unfortunately, Bayesian thinking is often blamed for its arbitrariness. Therefore, we introduce the idea of a Bayesian due diligence judging expert assessments according to their information content and their inter-subjectivity.
Der vorliegende erste Band der Reihe „Schriften zum deutschen und russischen Strafrecht“ beschäftigt sich mit der für die Rechtsordnungen Deutschlands und Russlands gleichermaßen aktuellen Frage nach der zutreffenden Bestimmung des Subjekts bei den Sonderdelikten im Wirtschaftsstrafrecht. Da das russische Strafrecht keine allgemeine Vorschrift zur „Überwälzung“ besonderer persönlicher Merkmale enthält, muss der Adressatenkreis von Sonderdelikten durch – im Einzelnen strittige – dogmatische Konstruktionen bestimmt werden; besondere Schwierigkeiten bereitet die Einordnung des Insolvenzverwalters. Für das deutsche Strafrecht sind dagegen die Probleme bei der Anwendung des § 14 StGB, der eine für alle Sonderdelikte geltende Vorschrift darstellt, zu erörtern; ein Schwerpunkt liegt ebenfalls bei der Untersuchung der Stellung des Insolvenzverwalters. Der Band enthält eine deutsch- und eine russischsprachige Fassung des Beitrages.
The genome can be considered the blueprint for an organism. Composed of DNA, it harbours all organism-specific instructions for the synthesis of all structural components and their associated functions. The role of carriers of actual molecular structure and functions was believed to be exclusively assumed by proteins encoded in particular segments of the genome, the genes. In the process of converting the information stored genes into functional proteins, RNA – a third major molecule class – was discovered early on to act a messenger by copying the genomic information and relaying it to the protein-synthesizing machinery. Furthermore, RNA molecules were identified to assist in the assembly of amino acids into native proteins. For a long time, these - rather passive - roles were thought to be the sole purpose of RNA. However, in recent years, new discoveries have led to a radical revision of this view. First, RNA molecules with catalytic functions - thought to be the exclusive domain of proteins - were discovered. Then, scientists realized that much more of the genomic sequence is transcribed into RNA molecules than there are proteins in cells begging the question what the function of all these molecules are. Furthermore, very short and altogether new types of RNA molecules seemingly playing a critical role in orchestrating cellular processes were discovered. Thus, RNA has become a central research topic in molecular biology, even to the extent that some researcher dub cells as “RNA machines”. This thesis aims to contribute towards our understanding of RNA-related phenomena by applying Bioinformatics means. First, we performed a genome-wide screen to identify sites at which the chemical composition of DNA (the genotype) critically influences phenotypic traits (the phenotype) of the model plant Arabidopsis thaliana. Whole genome hybridisation arrays were used and an informatics strategy developed, to identify polymorphic sites from hybridisation to genomic DNA. Following this approach, not only were genotype-phenotype associations discovered across the entire Arabidopsis genome, but also regions not currently known to encode proteins, thus representing candidate sites for novel RNA functional molecules. By statistically associating them with phenotypic traits, clues as to their particular functions were obtained. Furthermore, these candidate regions were subjected to a novel RNA-function classification prediction method developed as part of this thesis. While determining the chemical structure (the sequence) of candidate RNA molecules is relatively straightforward, the elucidation of its structure-function relationship is much more challenging. Towards this end, we devised and implemented a novel algorithmic approach to predict the structural and, thereby, functional class of RNA molecules. In this algorithm, the concept of treating RNA molecule structures as graphs was introduced. We demonstrate that this abstraction of the actual structure leads to meaningful results that may greatly assist in the characterization of novel RNA molecules. Furthermore, by using graph-theoretic properties as descriptors of structure, we indentified particular structural features of RNA molecules that may determine their function, thus providing new insights into the structure-function relationships of RNA. The method (termed Grapple) has been made available to the scientific community as a web-based service. RNA has taken centre stage in molecular biology research and novel discoveries can be expected to further solidify the central role of RNA in the origin and support of life on earth. As illustrated by this thesis, Bioinformatics methods will continue to play an essential role in these discoveries.
Background: For heterogeneous tissues, such as blood, measurements of gene expression are confounded by relative proportions of cell types involved. Conclusions have to rely on estimation of gene expression signals for homogeneous cell populations, e.g. by applying micro-dissection, fluorescence activated cell sorting, or in-silico deconfounding. We studied feasibility and validity of a non-negative matrix decomposition algorithm using experimental gene expression data for blood and sorted cells from the same donor samples. Our objective was to optimize the algorithm regarding detection of differentially expressed genes and to enable its use for classification in the difficult scenario of reversely regulated genes. This would be of importance for the identification of candidate biomarkers in heterogeneous tissues.
Results: Experimental data and simulation studies involving noise parameters estimated from these data revealed that for valid detection of differential gene expression, quantile normalization and use of non-log data are optimal. We demonstrate the feasibility of predicting proportions of constituting cell types from gene expression data of single samples, as a prerequisite for a deconfounding-based classification approach. Classification cross-validation errors with and without using deconfounding results are reported as well as sample-size dependencies. Implementation of the algorithm, simulation and analysis scripts are available.
Conclusions: The deconfounding algorithm without decorrelation using quantile normalization on non-log data is proposed for biomarkers that are difficult to detect, and for cases where confounding by varying proportions of cell types is the suspected reason. In this case, a deconfounding ranking approach can be used as a powerful alternative to, or complement of, other statistical learning approaches to define candidate biomarkers for molecular diagnosis and prediction in biomedicine, in realistically noisy conditions and with moderate sample sizes.
Multi-color fluorescence imaging experiments of wave forming Dictyostelium cells have revealed that actin waves separate two domains of the cell cortex that differ in their actin structure and phosphoinositide composition. We propose a bistable model of actin dynamics to account for these experimental observation. The model is based on the simplifying assumption that the actin cytoskeleton is composed of two distinct network types, a dendritic and a bundled network. The two structurally different states that were observed in experiments correspond to the stable fixed points in the bistable regime of this model. Each fixed point is dominated by one of the two network types. The experimentally observed actin waves can be considered as trigger waves that propagate transitions between the two stable fixed points.
Die Aussicht auf hohe Bonuszahlungen im Erfolgsfall war ein Grund neben mehreren, der Bankmanager im Vorfeld der Finanzkrise dazu verleitet hat, risikoreiche Unternehmensstrategien zu verfolgen und die langfristige Stabilität der Institute zu gefährden. Vor allem im Kreditwesen wurden falsche Anreize in der leistungs- und erfolgsabhängigen Vergütung gesetzt. Die Vergütungssysteme belohnten Manager und Mitarbeiter für die Erreichung kurzfristiger Gewinnziele – ungeachtet der eingegangenen Risiken. Boni wurden meist in bar ausgezahlt und orientierten sich primär an nicht risikoadjustierten Kennzahlen. Inzwischen hat sich in Anbetracht der Dramatik der Finanz- und Wirtschaftskrise eine deutliche Änderung in der Gestaltung der Bonussysteme angekündigt. Wie die Geschäftsberichte einzelner Institute des Jahres 2009 andeuten, werden mit der Erholung des Bankensektors mittelfristig auch die Bonuszahlungen wieder ansteigen.
In reading, word frequency is commonly regarded as the major bottom-up determinant for the speed of lexical access. Moreover, language processing depends on top-down information, such as the predictability of a word from a previous context. Yet, however, the exact role of top-down predictions in visual word recognition is poorly understood: They may rapidly affect lexical processes, or alternatively, influence only late post-lexical stages. To add evidence about the nature of top-down processes and their relation to bottom-up information in the timeline of word recognition, we examined influences of frequency and predictability on event-related potentials (ERPs) in several sentence reading studies. The results were related to eye movements from natural reading as well as to models of word recognition. As a first and major finding, interactions of frequency and predictability on ERP amplitudes consistently revealed top-down influences on lexical levels of word processing (Chapters 2 and 4). Second, frequency and predictability mediated relations between N400 amplitudes and fixation durations, pointing to their sensitivity to a common stage of word recognition; further, larger N400 amplitudes entailed longer fixation durations on the next word, a result providing evidence for ongoing processing beyond a fixation (Chapter 3). Third, influences of presentation rate on ERP frequency and predictability effects demonstrated that the time available for word processing critically co-determines the course of bottom-up and top-down influences (Chapter 4). Fourth, at a near-normal reading speed, an early predictability effect suggested the rapid comparison of top-down hypotheses with the actual visual input (Chapter 5). The present results are compatible with interactive models of word recognition assuming that early lexical processes depend on the concerted impact of bottom-up and top-down information. We offered a framework that reconciles the findings on a timeline of word recognition taking into account influences of frequency, predictability, and presentation rate (Chapter 4).
Die Analyse vergleicht Installationen von Bruce Nauman und Olafur Eliasson ausgehend von der Fragestellung, wie sich die künstlerischen Performativitätsstrategien der 1960er/70er Jahren und die der zeitgenössischen Kunst in ihren Wirkungen und Effekten unterscheiden lassen. Dabei werden die Positionen der beiden Künstler als paradigmatisch für eine Ästhetik des Performativen angesehen. Neben dem Vergleich der Künstler steht die theoretische Auseinandersetzung mit der Diskursfigur der Performativität sowie deren methodischen Anwendbarkeit in der Kunstwissenschaft im Vordergrund. Während sich Installationen der 1960er/70er Jahre besonders durch die psycho-physische Einwirkung auf die Sinneswahrnehmung des Betrachters auszeichnen und durchaus Schockeffekte beim Betrachter hervorrufen, befasst sich die zeitgenössische Kunstpraxis vornehmlich mit visuellen und poetischen Effekten, die eine kontemplative Rezeptionshaltung des Betrachters einfordern. Bruce Nauman war es ein Anliegen, den tradierten Status des Kunstwerks als ein zu Betrachtendes, das sich durch Begriffe wie Form, Ursprung und Originalität fassen ließ, in Frage zu stellen und stattdessen eine reale leibliche Erfahrung für den Betrachter nachvollziehbar werden zu lassen. Künstlern wie Olafur Eliasson geht es in den künstlerischen Produktionen vor allem um die Wahrnehmung der Wahrnehmung sowie der Erzeugung von Präsenzeffekten. Mit dem Aufkommen solcher Verfahren wurde deutlich, dass performative Installationen nach anderen Beschreibungsformen verlangten und, dass diese durch eine Ästhetik des Performativen gefasst werden können. Wie genau vollzieht sich der Wandel von den performativen Strategien der 1960er/70er Jahre zu denen der zeitgenössischen Installationskünstlern? Verläuft dieser vom Schock zur Poesie?
Brüche und Umbrüche
(2010)