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The term Linked Data refers to connected information sources comprising structured data about a wide range of topics and for a multitude of applications. In recent years, the conceptional and technical foundations of Linked Data have been formalized and refined. To this end, well-known technologies have been established, such as the Resource Description Framework (RDF) as a Linked Data model or the SPARQL Protocol and RDF Query Language (SPARQL) for retrieving this information. Whereas most research has been conducted in the area of generating and publishing Linked Data, this thesis presents novel approaches for improved management. In particular, we illustrate new methods for analyzing and processing SPARQL queries. Here, we present two algorithms suitable for identifying structural relationships between these queries. Both algorithms are applied to a large number of real-world requests to evaluate the performance of the approaches and the quality of their results. Based on this, we introduce different strategies enabling optimized access of Linked Data sources. We demonstrate how the presented approach facilitates effective utilization of SPARQL endpoints by prefetching results relevant for multiple subsequent requests. Furthermore, we contribute a set of metrics for determining technical characteristics of such knowledge bases. To this end, we devise practical heuristics and validate them through thorough analysis of real-world data sources. We discuss the findings and evaluate their impact on utilizing the endpoints. Moreover, we detail the adoption of a scalable infrastructure for improving Linked Data discovery and consumption. As we outline in an exemplary use case, this platform is eligible both for processing and provisioning the corresponding information.
Organizations try to gain competitive advantages, and to increase customer satisfaction. To ensure the quality and efficiency of their business processes, they perform business process management. An important part of process management that happens on the daily operational level is process controlling. A prerequisite of controlling is process monitoring, i.e., keeping track of the performed activities in running process instances. Only by process monitoring can business analysts detect delays and react to deviations from the expected or guaranteed performance of a process instance. To enable monitoring, process events need to be collected from the process environment. When a business process is orchestrated by a process execution engine, monitoring is available for all orchestrated process activities. Many business processes, however, do not lend themselves to automatic orchestration, e.g., because of required freedom of action. This situation is often encountered in hospitals, where most business processes are manually enacted. Hence, in practice it is often inefficient or infeasible to document and monitor every process activity. Additionally, manual process execution and documentation is prone to errors, e.g., documentation of activities can be forgotten. Thus, organizations face the challenge of process events that occur, but are not observed by the monitoring environment. These unobserved process events can serve as basis for operational process decisions, even without exact knowledge of when they happened or when they will happen. An exemplary decision is whether to invest more resources to manage timely completion of a case, anticipating that the process end event will occur too late. This thesis offers means to reason about unobserved process events in a probabilistic way. We address decisive questions of process managers (e.g., "when will the case be finished?", or "when did we perform the activity that we forgot to document?") in this thesis. As main contribution, we introduce an advanced probabilistic model to business process management that is based on a stochastic variant of Petri nets. We present a holistic approach to use the model effectively along the business process lifecycle. Therefore, we provide techniques to discover such models from historical observations, to predict the termination time of processes, and to ensure quality by missing data management. We propose mechanisms to optimize configuration for monitoring and prediction, i.e., to offer guidance in selecting important activities to monitor. An implementation is provided as a proof of concept. For evaluation, we compare the accuracy of the approach with that of state-of-the-art approaches using real process data of a hospital. Additionally, we show its more general applicability in other domains by applying the approach on process data from logistics and finance.
Poly(A) Polymerase 1 (PAPS1) influences organ size and pathogen response in Arabidopsis thaliana
(2014)
Polyadenylation of pre-mRNAs is critical for efficient nuclear export, stability, and translation of the mature mRNAs, and thus for gene expression. The bulk of pre-mRNAs are processed by canonical nuclear poly(A) polymerase (PAPS). Both vertebrate and higher-plant genomes encode more than one isoform of this enzyme, and these are coexpressed in different tissues. However, in neither case is it known whether the isoforms fulfill different functions or polyadenylate distinct subsets of pre-mRNAs. This thesis shows that the three canonical nuclear PAPS isoforms in Arabidopsis are functionally specialized owing to their evolutionarily divergent C-terminal domains. A moderate loss-of-function mutant in PAPS1 leads to increase in floral organ size, whereas leaf size is reduced. A strong loss-of-function mutation causes a male gametophytic defect, whereas a weak allele leads to reduced leaf growth. By contrast, plants lacking both PAPS2 and PAPS4 function are viable with wild-type leaf growth. Polyadenylation of SMALL AUXIN UP RNA (SAUR) mRNAs depends specifically on PAPS1 function. The resulting reduction in SAUR activity in paps1 mutants contributes to their reduced leaf growth, providing a causal link between polyadenylation of specific pre-mRNAs by a particular PAPS isoform and plant growth. Additionally, opposite effects of PAPS1 on leaf and flower growth reflect the different identities of these organs. The overgrowth of paps1 mutant petals is due to increased recruitment of founder cells into early organ primordia whereas the reduced leaf size is due to an ectopic pathogen response. This constitutive immune response leads to increased resistance to the biotrophic oomycete Hyaloperonospora arabidopsidis and reflects activation of the salicylic acid-independent signalling pathway downstream of ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)/PHYTOALEXIN DEFICIENT4 (PAD4). Immune responses are accompanied by intracellular redox changes. Consistent with this, the redox-status of the chloroplast is altered in paps1-1 mutants. The molecular effects of the paps1-1 mutation were analysed using an RNA sequencing approach that distinguishes between long- and short tailed mRNA. The results shown here suggest the existence of an additional layer of regulation in plants and possibly vertebrate gene expression, whereby the relative activities of canonical nuclear PAPS isoforms control de novo synthesized poly(A) tail length and hence expression of specific subsets of mRNAs.
Planetary research is often user-based and requires considerable skill, time, and effort. Unfortunately, self-defined boundary conditions, definitions, and rules are often not documented or not easy to comprehend due to the complexity of research. This makes a comparison to other studies, or an extension of the already existing research, complicated. Comparisons are often distorted, because results rely on different, not well defined, or even unknown boundary conditions. The purpose of this research is to develop a standardized analysis method for planetary surfaces, which is adaptable to several research topics. The method provides a consistent quality of results. This also includes achieving reliable and comparable results and reducing the time and effort of conducting such studies. A standardized analysis method is provided by automated analysis tools that focus on statistical parameters. Specific key parameters and boundary conditions are defined for the tool application. The analysis relies on a database in which all key parameters are stored. These databases can be easily updated and adapted to various research questions. This increases the flexibility, reproducibility, and comparability of the research. However, the quality of the database and reliability of definitions directly influence the results. To ensure a high quality of results, the rules and definitions need to be well defined and based on previously conducted case studies. The tools then produce parameters, which are obtained by defined geostatistical techniques (measurements, calculations, classifications). The idea of an automated statistical analysis is tested to proof benefits but also potential problems of this method. In this study, I adapt automated tools for floor-fractured craters (FFCs) on Mars. These impact craters show a variety of surface features, occurring in different Martian environments, and having different fracturing origins. They provide a complex morphological and geological field of application. 433 FFCs are classified by the analysis tools due to their fracturing process. Spatial data, environmental context, and crater interior data are analyzed to distinguish between the processes involved in floor fracturing. Related geologic processes, such as glacial and fluvial activity, are too similar to be separately classified by the automated tools. Glacial and fluvial fracturing processes are merged together for the classification. The automated tools provide probability values for each origin model. To guarantee the quality and reliability of the results, classification tools need to achieve an origin probability above 50 %. This analysis method shows that 15 % of the FFCs are fractured by intrusive volcanism, 20 % by tectonic activity, and 43 % by water & ice related processes. In total, 75 % of the FFCs are classified to an origin type. This can be explained by a combination of origin models, superposition or erosion of key parameters, or an unknown fracturing model. Those features have to be manually analyzed in detail. Another possibility would be the improvement of key parameters and rules for the classification. This research shows that it is possible to conduct an automated statistical analysis of morphologic and geologic features based on analysis tools. Analysis tools provide additional information to the user and are therefore considered assistance systems.
The objective and motivation behind this research is to provide applications with easy-to-use interfaces to communities of deaf and functionally illiterate users, which enables them to work without any human assistance. Although recent years have witnessed technological advancements, the availability of technology does not ensure accessibility to information and communication technologies (ICT). Extensive use of text from menus to document contents means that deaf or functionally illiterate can not access services implemented on most computer software. Consequently, most existing computer applications pose an accessibility barrier to those who are unable to read fluently. Online technologies intended for such groups should be developed in continuous partnership with primary users and include a thorough investigation into their limitations, requirements and usability barriers. In this research, I investigated existing tools in voice, web and other multimedia technologies to identify learning gaps and explored ways to enhance the information literacy for deaf and functionally illiterate users. I worked on the development of user-centered interfaces to increase the capabilities of deaf and low literacy users by enhancing lexical resources and by evaluating several multimedia interfaces for them. The interface of the platform-independent Italian Sign Language (LIS) Dictionary has been developed to enhance the lexical resources for deaf users. The Sign Language Dictionary accepts Italian lemmas as input and provides their representation in the Italian Sign Language as output. The Sign Language dictionary has 3082 signs as set of Avatar animations in which each sign is linked to a corresponding Italian lemma. I integrated the LIS lexical resources with MultiWordNet (MWN) database to form the first LIS MultiWordNet(LMWN). LMWN contains information about lexical relations between words, semantic relations between lexical concepts (synsets), correspondences between Italian and sign language lexical concepts and semantic fields (domains). The approach enhances the deaf users’ understanding of written Italian language and shows that a relatively small set of lexicon can cover a significant portion of MWN. Integration of LIS signs with MWN made it useful tool for computational linguistics and natural language processing. The rule-based translation process from written Italian text to LIS has been transformed into service-oriented system. The translation process is composed of various modules including parser, semantic interpreter, generator, and spatial allocation planner. This translation procedure has been implemented in the Java Application Building Center (jABC), which is a framework for extreme model driven design (XMDD). The XMDD approach focuses on bringing software development closer to conceptual design, so that the functionality of a software solution could be understood by someone who is unfamiliar with programming concepts. The transformation addresses the heterogeneity challenge and enhances the re-usability of the system. For enhancing the e-participation of functionally illiterate users, two detailed studies were conducted in the Republic of Rwanda. In the first study, the traditional (textual) interface was compared with the virtual character-based interactive interface. The study helped to identify usability barriers and users evaluated these interfaces according to three fundamental areas of usability, i.e. effectiveness, efficiency and satisfaction. In another study, we developed four different interfaces to analyze the usability and effects of online assistance (consistent help) for functionally illiterate users and compared different help modes including textual, vocal and virtual character on the performance of semi-literate users. In our newly designed interfaces the instructions were automatically translated in Swahili language. All the interfaces were evaluated on the basis of task accomplishment, time consumption, System Usability Scale (SUS) rating and number of times the help was acquired. The results show that the performance of semi-literate users improved significantly when using the online assistance. The dissertation thus introduces a new development approach in which virtual characters are used as additional support for barely literate or naturally challenged users. Such components enhanced the application utility by offering a variety of services like translating contents in local language, providing additional vocal information, and performing automatic translation from text to sign language. Obviously, there is no such thing as one design solution that fits for all in the underlying domain. Context sensitivity, literacy and mental abilities are key factors on which I concentrated and the results emphasize that computer interfaces must be based on a thoughtful definition of target groups, purposes and objectives.
Mathematical modeling of biological systems is a powerful tool to systematically investigate the functions of biological processes and their relationship with the environment. To obtain accurate and biologically interpretable predictions, a modeling framework has to be devised whose assumptions best approximate the examined scenario and which copes with the trade-off of complexity of the underlying mathematical description: with attention to detail or high coverage. Correspondingly, the system can be examined in detail on a smaller scale or in a simplified manner on a larger scale. In this thesis, the role of photosynthesis and its related biochemical processes in the context of plant metabolism was dissected by employing modeling approaches ranging from kinetic to stoichiometric models. The Calvin-Benson cycle, as primary pathway of carbon fixation in C3 plants, is the initial step for producing starch and sucrose, necessary for plant growth. Based on an integrative analysis for model ranking applied on the largest compendium of (kinetic) models for the Calvin-Benson cycle, those suitable for development of metabolic engineering strategies were identified. Driven by the question why starch rather than sucrose is the predominant transitory carbon storage in higher plants, the metabolic costs for their synthesis were examined. The incorporation of the maintenance costs for the involved enzymes provided a model-based support for the preference of starch as transitory carbon storage, by only exploiting the stoichiometry of synthesis pathways. Many photosynthetic organisms have to cope with processes which compete with carbon fixation, such as photorespiration whose impact on plant metabolism is still controversial. A systematic model-oriented review provided a detailed assessment for the role of this pathway in inhibiting the rate of carbon fixation, bridging carbon and nitrogen metabolism, shaping the C1 metabolism, and influencing redox signal transduction. The demand of understanding photosynthesis in its metabolic context calls for the examination of the related processes of the primary carbon metabolism. To this end, the Arabidopsis core model was assembled via a bottom-up approach. This large-scale model can be used to simulate photoautotrophic biomass production, as an indicator for plant growth, under so-called optimal, carbon-limiting and nitrogen-limiting growth conditions. Finally, the introduced model was employed to investigate the effects of the environment, in particular, nitrogen, carbon and energy sources, on the metabolic behavior. This resulted in a purely stoichiometry-based explanation for the experimental evidence for preferred simultaneous acquisition of nitrogen in both forms, as nitrate and ammonium, for optimal growth in various plant species. The findings presented in this thesis provide new insights into plant system's behavior, further support existing opinions for which mounting experimental evidences arise, and posit novel hypotheses for further directed large-scale experiments.
Mars is one of the best candidates among planetary bodies for supporting life. The presence of water in the form of ice and atmospheric vapour together with the availability of biogenic elements and energy are indicators of the possibility of hosting life as we know it. The occurrence of permanently frozen ground – permafrost, is a common phenomenon on Mars and it shows multiple morphological analogies with terrestrial permafrost. Despite the extreme inhospitable conditions, highly diverse microbial communities inhabit terrestrial permafrost in large numbers. Among these are methanogenic archaea, which are anaerobic chemotrophic microorganisms that meet many of the metabolic and physiological requirements for survival on the martian subsurface. Moreover, methanogens from Siberian permafrost are extremely resistant against different types of physiological stresses as well as simulated martian thermo-physical and subsurface conditions, making them promising model organisms for potential life on Mars. The main aims of this investigation are to assess the survival of methanogenic archaea under Mars conditions, focusing on methanogens from Siberian permafrost, and to characterize their biosignatures by means of Raman spectroscopy, a powerful technology for microbial identification that will be used in the ExoMars mission. For this purpose, methanogens from Siberian permafrost and non-permafrost habitats were subjected to simulated martian desiccation by exposure to an ultra-low subfreezing temperature (-80ºC) and to Mars regolith (S-MRS and P-MRS) and atmospheric analogues. They were also exposed to different concentrations of perchlorate, a strong oxidant found in martian soils. Moreover, the biosignatures of methanogens were characterized at the single-cell level using confocal Raman microspectroscopy (CRM). The results showed survival and methane production in all methanogenic strains under simulated martian desiccation. After exposure to subfreezing temperatures, Siberian permafrost strains had a faster metabolic recovery, whereas the membranes of non-permafrost methanogens remained intact to a greater extent. The strain Methanosarcina soligelidi SMA-21 from Siberian permafrost showed significantly higher methane production rates than all other strains after the exposure to martian soil and atmospheric analogues, and all strains survived the presence of perchlorate at the concentration on Mars. Furthermore, CRM analyses revealed remarkable differences in the overall chemical composition of permafrost and non-permafrost strains of methanogens, regardless of their phylogenetic relationship. The convergence of the chemical composition in non-sister permafrost strains may be the consequence of adaptations to the environment, and could explain their greater resistance compared to the non-permafrost strains. As part of this study, Raman spectroscopy was evaluated as an analytical technique for remote detection of methanogens embedded in a mineral matrix. This thesis contributes to the understanding of the survival limits of methanogenic archaea under simulated martian conditions to further assess the hypothetical existence of life similar to methanogens on the martian subsurface. In addition, the overall chemical composition of methanogens was characterized for the first time by means of confocal Raman microspectroscopy, with potential implications for astrobiological research.
Anorexia nervosa und unipolare Affektive Störungen stellen häufige und schwerwiegende kinder- und jugendpsychiatrische Störungsbilder dar, deren Pathogenese bislang nicht vollständig entschlüsselt ist. Verschiedene Studien zeigen bei erwachsenen Patienten gravierende Auffälligkeiten in den kognitiven Funktionen. Dahingegen scheinen bei adoleszenten Patienten lediglich leichtere Einschränkungen in den kognitiven Funktionen vorzuliegen. Die Prävalenz der Anorexia nervosa und unipolaren Affektiven Störung ist mit Beginn der Adoleszenz deutlich erhöht. Es ist anzunehmen, dass kognitive Dysfunktionen, die sich bereits in diesem Alter abzeichnen, den weiteren Krankheitsverlauf bis in das Erwachsenenalter, die Behandlungsergebnisse und die Prognose maßgeblich beeinträchtigen könnten. Zudem ist von einem höheren Chronifizierungsrisiko auszugehen. In der vorliegenden Arbeit wurden daher kognitive Funktionen bei adoleszenten Patientinnen mit Anorexia nervosa sowie Patienten mit unipolaren Affektiven Störungen untersucht. Die Überprüfung der kognitiven Funktionen bei Patientinnen mit Anorexia nervosa erfolgte vor und nach Gewichtszunahme. Weiterhin wurden zugrundeliegende biologische Mechanismen überprüft. Zudem wurde die Spezifität kognitiver Dysfunktionen für beide Störungsbilder untersucht und bei Patienten mit unipolaren Affektiven Störungen geschlechtsbezogene Unterschiede exploriert. Insgesamt gingen 47 Patientinnen mit Anorexia nervosa (mittleres Alter 16,3 + 1,6 Jahre), 39 Patienten mit unipolaren Affektiven Störungen (mittleres Alter 15,5 + 1,3 Jahre) sowie 78 Kontrollprobanden (mittleres Alter 16,5 + 1,3 Jahre) in die Untersuchung ein. Sämtliche Studienteilnehmer durchliefen eine neuropsychologische Testbatterie, bestehend aus Verfahren zur Überprüfung der kognitiven Flexibilität sowie visuellen und psychomotorischen Verarbeitungsgeschwindigkeit. Neben einem Intelligenzscreening wurden zudem das Ausmaß der depressiven Symptomatik sowie die allgemeine psychische Belastung erfasst. Die Ergebnisse legen nahe, dass bei adoleszenten Patientinnen mit Anorexia nervosa, sowohl im akut untergewichtigen Zustand als auch nach Gewichtszunahme, lediglich milde Beeinträchtigungen in den kognitiven Funktionen vorliegen. Im akut untergewichtigen Zustand offenbarten sich deutliche Zusammenhänge zwischen dem appetitregulierenden Peptid Agouti-related Protein und kognitiver Flexibilität, nicht jedoch zwischen Agouti-related Protein und visueller oder psychomotorischer Verarbeitungsgeschwindigkeit. Bei dem Vergleich von Anorexia nervosa und unipolaren Affektiven Störungen prädizierte die Zugehörigkeit zu der Patientengruppe Anorexia nervosa ein Risiko für das Vorliegen kognitiver Dysfunktionen. Es zeigte sich zudem, dass adoleszente Patienten mit unipolaren Affektiven Störungen lediglich in der psychomotorischen Verarbeitungsgeschwindigkeit tendenziell schwächere Leistungen offenbarten als gesunde Kontrollprobanden. Es ergab sich jedoch ein genereller geschlechtsbezogener Vorteil für weibliche Probanden in der visuellen und psychomotorischen Verarbeitungsgeschwindigkeit. Die vorliegenden Befunde unterstreichen die Notwendigkeit der Überprüfung kognitiver Funktionen bei adoleszenten Patienten mit Anorexia nervosa sowie unipolaren Affektiven Störungen in der klinischen Routinediagnostik. Die Patienten könnten von spezifischen Therapieprogrammen profitieren, die Beeinträchtigungen in den kognitiven Funktionen mildern bzw. präventiv behandeln.
The Adana Basin of southern Turkey, situated at the SE margin of the Central Anatolian Plateau is ideally located to record Neogene topographic and tectonic changes in the easternmost Mediterranean realm. Using industry seismic reflection data we correlate 34 seismic profiles with corresponding exposed units in the Adana Basin. The time-depth conversion of the interpreted seismic profiles allows us to reconstruct the subsidence curve of the Adana Basin and to outline the occurrence of a major increase in both subsidence and sedimentation rates at 5.45 – 5.33 Ma, leading to the deposition of almost 1500 km3 of conglomerates and marls. Our provenance analysis of the conglomerates reveals that most of the sediment is derived from and north of the SE margin of the Central Anatolian Plateau. A comparison of these results with the composition of recent conglomerates and the present drainage basins indicates major changes between late Messinian and present-day source areas. We suggest that these changes in source areas result of uplift and ensuing erosion of the SE margin of the plateau. This hypothesis is supported by the comparison of the Adana Basin subsidence curve with the subsidence curve of the Mut Basin, a mainly Neogene basin located on top of the Central Anatolian Plateau southern margin, showing that the Adana Basin subsidence event is coeval with an uplift episode of the plateau southern margin. The collection of several fault measurements in the Adana region show different deformation styles for the NW and SE margins of the Adana Basin. The weakly seismic NW portion of the basin is characterized by extensional and transtensional structures cutting Neogene deposits, likely accomodating the differential uplift occurring between the basin and the SE margin of the plateau. We interpret the tectonic evolution of the southern flank of the Central Anatolian Plateau and the coeval subsidence and sedimentation in the Adana Basin to be related to deep lithospheric processes, particularly lithospheric delamination and slab break-off.
Transcription factors (TFs) are ubiquitous gene expression regulators and play essential roles in almost all biological processes. This Ph.D. project is primarily focused on the functional characterisation of MYB112 - a member of the R2R3-MYB TF family from the model plant Arabidopsis thaliana. This gene was selected due to its increased expression during senescence based on previous qRT-PCR expression profiling experiments of 1880 TFs in Arabidopsis leaves at three developmental stages (15 mm leaf, 30 mm leaf and 20% yellowing leaf). MYB112 promoter GUS fusion lines were generated to further investigate the expression pattern of MYB112. Employing transgenic approaches in combination with metabolomics and transcriptomics we demonstrate that MYB112 exerts a major role in regulation of plant flavonoid metabolism. We report enhanced and impaired anthocyanin accumulation in MYB112 overexpressors and MYB112-deficient mutants, respectively. Expression profiling reveals that MYB112 acts as a positive regulator of the transcription factor PAP1 leading to increased anthocyanin biosynthesis, and as a negative regulator of MYB12 and MYB111, which both control flavonol biosynthesis. We also identify MYB112 early responsive genes using a combination of several approaches. These include gene expression profiling (Affymetrix ATH1 micro-arrays and qRT-PCR) and transactivation assays in leaf mesophyll cell protoplasts. We show that MYB112 binds to an 8-bp DNA fragment containing the core sequence (A/T/G)(A/C)CC(A/T)(A/G/T)(A/C)(T/C). By electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation coupled to qPCR (ChIP-qPCR) we demonstrate that MYB112 binds in vitro and in vivo to MYB7 and MYB32 promoters revealing them as direct downstream target genes. MYB TFs were previously reported to play an important role in controlling flavonoid biosynthesis in plants. Many factors acting upstream of the anthocyanin biosynthesis pathway show enhanced expression levels during nitrogen limitation, or elevated sucrose content. In addition to the mentioned conditions, other environmental parameters including salinity or high light stress may trigger anthocyanin accumulation. In contrast to several other MYB TFs affecting anthocyanin biosynthesis pathway genes, MYB112 expression is not controlled by nitrogen limitation, or carbon excess, but rather is stimulated by salinity and high light stress. Thus, MYB112 constitutes a previously uncharacterised regulatory factor that modifies anthocyanin accumulation under conditions of abiotic stress.