Difference-making grounds

We define a notion of difference-making for partial grounds of a fact in rough analogy to existing notions of difference-making for causes of an event. Using orthodox assumptions about ground, we show that it induces a non-trivial division with examples of partial grounds on both sides. We then demonstrate the theoretical fruitfulness of the notion by applying it to the analysis of a certain kind of putative counter-example to the transitivity of ground recently described by Jonathan Schaffer. First, we show that our conceptual apparatus of difference-making enables us to give a much clearer description than Schaffer does of what makes the relevant instances of transitivity appear problematic. Second, we suggest that difference-making is best seen as a mark of good grounding-based explanations rather than a necessary condition on grounding, and argue that this enables us to deal with the counter-example in a satisfactory way. Along the way, we show that Schaffer's own proposal for salvaging a form of transitivity by moving to a contrastive conception of ground is unsuccessful. We conclude by sketching some natural strategies for extending our proposal to a more comprehensive account of grounding-based explanations

LiDAR-Based Object Tracking and Shape Estimation

Umfeldwahrnehmung stellt eine Grundvoraussetzung für den sicheren und komfortablen Betrieb automatisierter Fahrzeuge dar. Insbesondere bewegte Verkehrsteilnehmer in der unmittelbaren Fahrzeugumgebung haben dabei große Auswirkungen auf die Wahl einer angemessenen Fahrstrategie. Dies macht ein System zur Objektwahrnehmung notwendig, welches eine robuste und präzise Zustandsschätzung der Fremdfahrzeugbewegung und -geometrie zur Verfügung stellt. Im Kontext des automatisierten Fahrens hat sich das Box-Geometriemodell über die Zeit als Quasistandard durchgesetzt. Allerdings stellt die Box aufgrund der ständig steigenden Anforderungen an Wahrnehmungssysteme inzwischen häufig eine unerwünscht grobe Approximation der tatsächlichen Geometrie anderer Verkehrsteilnehmer dar. Dies motiviert einen Übergang zu genaueren Formrepräsentationen. In der vorliegenden Arbeit wird daher ein probabilistisches Verfahren zur gleichzeitigen Schätzung von starrer Objektform und -bewegung mittels Messdaten eines LiDAR-Sensors vorgestellt. Der Vergleich dreier Freiform-Geometriemodelle mit verschiedenen Detaillierungsgraden (Polygonzug, Dreiecksnetz und Surfel Map) gegenüber dem einfachen Boxmodell zeigt, dass die Reduktion von Modellierungsfehlern in der Objektgeometrie eine robustere und präzisere Parameterschätzung von Objektzuständen ermöglicht. Darüber hinaus können automatisierte Fahrfunktionen, wie beispielsweise ein Park- oder Ausweichassistent, von einem genaueren Wissen über die Fremdobjektform profitieren. Es existieren zwei Einflussgrößen, welche die Auswahl einer angemessenen Formrepräsentation maßgeblich beeinflussen sollten: Beobachtbarkeit (Welchen Detaillierungsgrad lässt die Sensorspezifikation theoretisch zu?) und Modell-Adäquatheit (Wie gut bildet das gegebene Modell die tatsächlichen Beobachtungen ab?). Auf Basis dieser Einflussgrößen wird in der vorliegenden Arbeit eine Strategie zur Modellauswahl vorgestellt, die zur Laufzeit adaptiv das am besten geeignete Formmodell bestimmt. Während die Mehrzahl der Algorithmen zur LiDAR-basierten Objektverfolgung ausschließlich auf Punktmessungen zurückgreift, werden in der vorliegenden Arbeit zwei weitere Arten von Messungen vorgeschlagen: Information über den vermessenen Freiraum wird verwendet, um über Bereiche zu schlussfolgern, welche nicht von Objektgeometrie belegt sein können. Des Weiteren werden LiDAR-Intensitäten einbezogen, um markante Merkmale wie Nummernschilder und Retroreflektoren zu detektieren und über die Zeit zu verfolgen. Eine ausführliche Auswertung auf über 1,5 Stunden von aufgezeichneten Fremdfahrzeugtrajektorien im urbanen Bereich und auf der Autobahn zeigen, dass eine präzise Modellierung der Objektoberfläche die Bewegungsschätzung um bis zu 30%-40% verbessern kann. Darüber hinaus wird gezeigt, dass die vorgestellten Methoden konsistente und hochpräzise Rekonstruktionen von Objektgeometrien generieren können, welche die häufig signifikante Überapproximation durch das einfache Boxmodell vermeiden

Computationally Linking Chemical Exposure to Molecular Effects with Complex Data: Comparing Methods to Disentangle Chemical Drivers in Environmental Mixtures and Knowledge-based Deep Learning for Predictions in Environmental Toxicology

Chemical exposures affect the environment and may lead to adverse outcomes in its organisms. Omics-based approaches, like standardised microarray experiments, have expanded the toolbox to monitor the distribution of chemicals and assess the risk to organisms in the environment. The resulting complex data have extended the scope of toxicological knowledge bases and published literature. A plethora of computational approaches have been applied in environmental toxicology considering systems biology and data integration. Still, the complexity of environmental and biological systems given in data challenges investigations of exposure-related effects. This thesis aimed at computationally linking chemical exposure to biological effects on the molecular level considering sources of complex environmental data. The first study employed data of an omics-based exposure study considering mixture effects in a freshwater environment. We compared three data-driven analyses in their suitability to disentangle mixture effects of chemical exposures to biological effects and their reliability in attributing potentially adverse outcomes to chemical drivers with toxicological databases on gene and pathway levels. Differential gene expression analysis and a network inference approach resulted in toxicologically meaningful outcomes and uncovered individual chemical effects — stand-alone and in combination. We developed an integrative computational strategy to harvest exposure-related gene associations from environmental samples considering mixtures of lowly concentrated compounds. The applied approaches allowed assessing the hazard of chemicals more systematically with correlation-based compound groups. This dissertation presents another achievement toward a data-driven hypothesis generation for molecular exposure effects. The approach combined text-mining and deep learning. The study was entirely data-driven and involved state-of-the-art computational methods of artificial intelligence. We employed literature-based relational data and curated toxicological knowledge to predict chemical-biomolecule interactions. A word embedding neural network with a subsequent feed-forward network was implemented. Data augmentation and recurrent neural networks were beneficial for training with curated toxicological knowledge. The trained models reached accuracies of up to 94% for unseen test data of the employed knowledge base. However, we could not reliably confirm known chemical-gene interactions across selected data sources. Still, the predictive models might derive unknown information from toxicological knowledge sources, like literature, databases or omics-based exposure studies. Thus, the deep learning models might allow predicting hypotheses of exposure-related molecular effects. Both achievements of this dissertation might support the prioritisation of chemicals for testing and an intelligent selection of chemicals for monitoring in future exposure studies.:Table of Contents ... I Abstract ... V Acknowledgements ... VII Prelude ... IX 1 Introduction 1.1 An overview of environmental toxicology ... 2 1.1.1 Environmental toxicology ... 2 1.1.2 Chemicals in the environment ... 4 1.1.3 Systems biological perspectives in environmental toxicology ... 7 Computational toxicology ... 11 1.2.1 Omics-based approaches ... 12 1.2.2 Linking chemical exposure to transcriptional effects ... 14 1.2.3 Up-scaling from the gene level to higher biological organisation levels ... 19 1.2.4 Biomedical literature-based discovery ... 24 1.2.5 Deep learning with knowledge representation ... 27 1.3 Research question and approaches ... 29 2 Methods and Data ... 33 2.1 Linking environmental relevant mixture exposures to transcriptional effects ... 34 2.1.1 Exposure and microarray data ... 34 2.1.2 Preprocessing ... 35 2.1.3 Differential gene expression ... 37 2.1.4 Association rule mining ... 38 2.1.5 Weighted gene correlation network analysis ... 39 2.1.6 Method comparison ... 41 Predicting exposure-related effects on a molecular level ... 44 2.2.1 Input ... 44 2.2.2 Input preparation ... 47 2.2.3 Deep learning models ... 49 2.2.4 Toxicogenomic application ... 54 3 Method comparison to link complex stream water exposures to effects on the transcriptional level ... 57 3.1 Background and motivation ... 58 3.1.1 Workflow ... 61 3.2 Results ... 62 3.2.1 Data preprocessing ... 62 3.2.2 Differential gene expression analysis ... 67 3.2.3 Association rule mining ... 71 3.2.4 Network inference ... 78 3.2.5 Method comparison ... 84 3.2.6 Application case of method integration ... 87 3.3 Discussion ... 91 3.4 Conclusion ... 99 4 Deep learning prediction of chemical-biomolecule interactions ... 101 4.1 Motivation ... 102 4.1.1Workflow ...105 4.2 Results ... 107 4.2.1 Input preparation ... 107 4.2.2 Model selection ... 110 4.2.3 Model comparison ... 118 4.2.4 Toxicogenomic application ... 121 4.2.5 Horizontal augmentation without tail-padding ...123 4.2.6 Four-class problem formulation ... 124 4.2.7 Training with CTD data ... 125 4.3 Discussion ... 129 4.3.1 Transferring biomedical knowledge towards toxicology ... 129 4.3.2 Deep learning with biomedical knowledge representation ...133 4.3.3 Data integration ...136 4.4 Conclusion ... 141 5 Conclusion and Future perspectives ... 143 5.1 Conclusion ... 143 5.1.1 Investigating complex mixtures in the environment ... 144 5.1.2 Complex knowledge from literature and curated databases predict chemical- biomolecule interactions ... 145 5.1.3 Linking chemical exposure to biological effects by integrating CTD ... 146 5.2 Future perspectives ... 147 S1 Supplement Chapter 1 ... 153 S1.1 Example of an estrogen bioassay ... 154 S1.2 Types of mode of action ... 154 S1.3 The dogma of molecular biology ... 157 S1.4 Transcriptomics ... 159 S2 Supplement Chapter 3 ... 161 S3 Supplement Chapter 4 ... 175 S3.1 Hyperparameter tuning results ... 176 S3.2 Functional enrichment with predicted chemical-gene interactions and CTD reference pathway genesets ... 179 S3.3 Reduction of learning rate in a model with large word embedding vectors ... 183 S3.4 Horizontal augmentation without tail-padding ... 183 S3.5 Four-relationship classification ... 185 S3.6 Interpreting loss observations for SemMedDB trained models ... 187 List of Abbreviations ... i List of Figures ... vi List of Tables ... x Bibliography ... xii Curriculum scientiae ... xxxix Selbständigkeitserklärung ... xlii

NLO QCD corrections to graviton production at hadron colliders

Models with large extra dimensions predict the existence of Kaluza-Klein graviton resonances. We compute the next-to-leading order QCD corrections to graviton plus jet hadro-production, which is an important channel for graviton searches at the Tevatron and the LHC. The QCD corrections are sizable and lead to a significant reduction of the scale dependence. We present numerical results for cross sections and distributions, and discuss the uncertainty from parton distribution functions and the ultraviolet sensitivity of the theoretical prediction.Comment: 19 pages, 9 eps figures, v2: additional references and comments, new Fig. 9. Matches published version in Physical Review

Numerical calculation of automorphic functions for finite index subgroups of triangle groups

We present a new method to calculate automorphic functions for finite index subgroups of triangle groups. Since automorphic functions are holomorphic, it is well known that the real and the imaginary part are both harmonic. The central idea of my advisor Monien was to look at the two parts separately. We solve the Laplace equation to find the real and imaginary part of an automorphic function. This solution can be calculated using numerical methods. To each finite index subgroup of a triangle group we can associate a Belyi function and a dessin d'enfant. The zeros of this Belyi function are the values of the automorphic function we calculated at elliptic points. Hence, we can find an approximation for the coefficients of the Belyi function. The precision of this approximation is increased by the use of Newton's method. Once we have an approximation with high accuracy, we find the correct algebraic number using the LLL algorithm. From the exact Belyi function we can reconstruct the exact automorphic function. In order to handle finite index subgroups of triangle groups, we introduce the notion of generalized Farey symbols. These symbols are a generalization of the classical Farey symbols for the modular group. They are used to do efficient calculations with subgroups of Hecke groups

Communications Regulation in the Age of Digital Convergence : Legal and Economic Perspectives

This book brings together contributions of a distinguished panel of regulators as well as lawyers and economists from both academia and industry to present their insights on the digital convergence phenomenon in the telecommunications industry. The contributions cover a great deal of the relevant topics in communications regulation, such as technological and network neutrality, distribution of the digital dividend, and incentives for investment and innovation

Constraints on leptophilic dark matter from the AMS-02 experiment

The annihilation of dark matter particles in the galactic halo of the Milky Way may lead to cosmic ray signatures that can be probed by the AMS-02 experiment, which has measured the composition and fluxes of charged cosmic rays with unprecedented precision. Given the absence of characteristic spectral features in the electron and positron fluxes measured by AMS-02, we derive upper limits on the dark matter annihilation cross section for leptophilic dark matter models. Our limits are based on a new background model that describes all recent measurements of the energy spectra of cosmic ray positrons and electrons. For thermal dark matter relics, we can exclude dark matter masses below about 100 GeV. We include the radiation of electroweak gauge bosons in the dark matter annihilation process and compute the antiproton signal that can be expected within leptophilic dark matter models.Comment: 7 pages, 3 figures, 1 table. Matches the published version apart from typo corrected in Eq.