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Hepcidin-25 was identified as themain iron regulator in the human body, and it by binds to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II) binding site known as the ATCUN (amino-terminal Cu(II)- and Ni(II)-binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the complex formed between hepcidin-25 and copper could reveal insight into its biological role. The present work focuses on metal-bound hepcidin-25 that can be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25 achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandemmass spectrometry (MS/MS), high-resolutionmass spectrometry (HRMS)) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a three-dimensional (3D)model of hepcidin-25with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or referencematerial comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.
A central insight from psychological studies on human eye movements is that eye movement patterns are highly individually characteristic. They can, therefore, be used as a biometric feature, that is, subjects can be identified based on their eye movements. This thesis introduces new machine learning methods to identify subjects based on their eye movements while viewing arbitrary content. The thesis focuses on probabilistic modeling of the problem, which has yielded the best results in the most recent literature. The thesis studies the problem in three phases by proposing a purely probabilistic, probabilistic deep learning, and probabilistic deep metric learning approach. In the first phase, the thesis studies models that rely on psychological concepts about eye movements. Recent literature illustrates that individual-specific distributions of gaze patterns can be used to accurately identify individuals. In these studies, models were based on a simple parametric family of distributions. Such simple parametric models can be robustly estimated from sparse data, but have limited flexibility to capture the differences between individuals. Therefore, this thesis proposes a semiparametric model of gaze patterns that is flexible yet robust for individual identification. These patterns can be understood as domain knowledge derived from psychological literature. Fixations and saccades are examples of simple gaze patterns. The proposed semiparametric densities are drawn under a Gaussian process prior centered at a simple parametric distribution. Thus, the model will stay close to the parametric class of densities if little data is available, but it can also deviate from this class if enough data is available, increasing the flexibility of the model. The proposed method is evaluated on a large-scale dataset, showing significant improvements over the state-of-the-art. Later, the thesis replaces the model based on gaze patterns derived from psychological concepts with a deep neural network that can learn more informative and complex patterns from raw eye movement data. As previous work has shown that the distribution of these patterns across a sequence is informative, a novel statistical aggregation layer called the quantile layer is introduced. It explicitly fits the distribution of deep patterns learned directly from the raw eye movement data. The proposed deep learning approach is end-to-end learnable, such that the deep model learns to extract informative, short local patterns while the quantile layer learns to approximate the distributions of these patterns. Quantile layers are a generic approach that can converge to standard pooling layers or have a more detailed description of the features being pooled, depending on the problem. The proposed model is evaluated in a large-scale study using the eye movements of subjects viewing arbitrary visual input. The model improves upon the standard pooling layers and other statistical aggregation layers proposed in the literature. It also improves upon the state-of-the-art eye movement biometrics by a wide margin. Finally, for the model to identify any subject — not just the set of subjects it is trained on — a metric learning approach is developed. Metric learning learns a distance function over instances. The metric learning model maps the instances into a metric space, where sequences of the same individual are close, and sequences of different individuals are further apart. This thesis introduces a deep metric learning approach with distributional embeddings. The approach represents sequences as a set of continuous distributions in a metric space; to achieve this, a new loss function based on Wasserstein distances is introduced. The proposed method is evaluated on multiple domains besides eye movement biometrics. This approach outperforms the state of the art in deep metric learning in several domains while also outperforming the state of the art in eye movement biometrics.
As digital media infiltrate an increasingly greater proportion of our lives, concern about the possibility of various forms of technology addictions has emerged. For technology addiction, researchers have developed a variety of self-reported scales in areas such as Internet, smartphones, videogames, social network sites (SNS) or television. However, no uniform criteria or definition exists for technology addiction. Utilized dimensions of technology addiction, to measure specific outcomes, lack a conceptual standard. Therefore, linkages between technology areas dimensions have not been examined in a broader way by the research community, in order to develop a uniform technology addiction scale.
In this regard, firstly, a theoretical model was developed in order to extract common technology dimensions. Secondly, a systematic literature review in the areas of Internet, smartphone, video games and SNS was conducted in order to extract the dimensions used. To identify relevant studies, nine databases (GoogleScholar, ScienceDirect, PubMed, EmeraldInsight, Wiley, SpringerLink, ACM, iEEE and JSTOR) were searched, producing 4698 results, and 50 studies met the inclusion criteria. Thirdly, the developed theoretical model was utilized in order to determine the dimension in each of the identified scales.
Based on analysis of the dimensional distributions, the findings suggest that there are common dimensions across areas of technology such as “compulsive use” and “negative outcomes” but also differences in dimensions across areas such as “social comfort” and “mood regulation”, which are more used in the area of SNS. Moreover, new dimensions such as “cognitive absorption” or “utility and function loss" for technology addiction were extracted, which should be considered as these have not yet been researched in a broader way. In addition, no gold standard for the conceptual criteria or definition for technology addiction has been developed yet.
Technical report
(2019)
Design and Implementation of service-oriented architectures imposes a huge number of research questions from the fields of software engineering, system analysis and modeling, adaptability, and application integration. Component orientation and web services are two approaches for design and realization of complex web-based system. Both approaches allow for dynamic application adaptation as well as integration of enterprise application.
Commonly used technologies, such as J2EE and .NET, form de facto standards for the realization of complex distributed systems. Evolution of component systems has lead to web services and service-based architectures. This has been manifested in a multitude of industry standards and initiatives such as XML, WSDL UDDI, SOAP, etc. All these achievements lead to a new and promising paradigm in IT systems engineering which proposes to design complex software solutions as collaboration of contractually defined software services.
Service-Oriented Systems Engineering represents a symbiosis of best practices in object-orientation, component-based development, distributed computing, and business process management. It provides integration of business and IT concerns.
The annual Ph.D. Retreat of the Research School provides each member the opportunity to present his/her current state of their research and to give an outline of a prospective Ph.D. thesis. Due to the interdisciplinary structure of the research school, this technical report covers a wide range of topics. These include but are not limited to: Human Computer Interaction and Computer Vision as Service; Service-oriented Geovisualization Systems; Algorithm Engineering for Service-oriented Systems; Modeling and Verification of Self-adaptive Service-oriented Systems; Tools and Methods for Software Engineering in Service-oriented Systems; Security Engineering of Service-based IT Systems; Service-oriented Information Systems; Evolutionary Transition of Enterprise Applications to Service Orientation; Operating System Abstractions for Service-oriented Computing; and Services Specification, Composition, and Enactment.
Sea surface temperature (SST) patterns can – as surface climate forcing – affect weather and climate at large distances. One example is El Niño-Southern Oscillation (ENSO) that causes climate anomalies around the globe via teleconnections. Although several studies identified and characterized these teleconnections, our understanding of climate processes remains incomplete, since interactions and feedbacks are typically exhibited at unique or multiple temporal and spatial scales. This study characterizes the interactions between the cells of a global SST data set at different temporal and spatial scales using climate networks. These networks are constructed using wavelet multi-scale correlation that investigate the correlation between the SST time series at a range of scales allowing instantaneously deeper insights into the correlation patterns compared to traditional methods like empirical orthogonal functions or classical correlation analysis. This allows us to identify and visualise regions of – at a certain timescale – similarly evolving SSTs and distinguish them from those with long-range teleconnections to other ocean regions. Our findings re-confirm accepted knowledge about known highly linked SST patterns like ENSO and the Pacific Decadal Oscillation, but also suggest new insights into the characteristics and origins of long-range teleconnections like the connection between ENSO and Indian Ocean Dipole.
A common feature in Answer Set Programming is the use of a second negation, stronger than default negation and sometimes called explicit, strong or classical negation. This explicit negation is normally used in front of atoms, rather than allowing its use as a regular operator. In this paper we consider the arbitrary combination of explicit negation with nested expressions, as those defined by Lifschitz, Tang and Turner. We extend the concept of reduct for this new syntax and then prove that it can be captured by an extension of Equilibrium Logic with this second negation. We study some properties of this variant and compare to the already known combination of Equilibrium Logic with Nelson's strong negation.
Sinkholes and depressions are typical landforms of karst regions. They pose a considerable natural hazard to infrastructure, agriculture, economy and human life in affected areas worldwide. The physio-chemical processes of sinkholes and depression formation are manifold, ranging from dissolution and material erosion in the subsurface to mechanical subsidence/failure of the overburden. This thesis addresses the mechanisms leading to the development of sinkholes and depressions by using complementary methods: remote sensing, distinct element modelling and near-surface geophysics.
In the first part, detailed information about the (hydro)-geological background, ground structures, morphologies and spatio-temporal development of sinkholes and depressions at a very active karst area at the Dead Sea are derived from satellite image analysis, photogrammetry and geologic field surveys. There, clusters of an increasing number of sinkholes have been developing since the 1980s within large-scale depressions and are distributed over different kinds of surface materials: clayey mud, sandy-gravel alluvium and lacustrine evaporites (salt). The morphology of sinkholes differs depending in which material they form: Sinkholes in sandy-gravel alluvium and salt are generally deeper and narrower than sinkholes in the interbedded evaporite and mud deposits. From repeated aerial surveys, collapse precursory features like small-scale subsidence, individual holes and cracks are identified in all materials. The analysis sheds light on the ongoing hazardous subsidence process, which is driven by the base-level fall of the Dead Sea and by the dynamic formation of subsurface water channels.
In the second part of this thesis, a novel, 2D distinct element geomechanical modelling approach with the software PFC2D-V5 to simulating individual and multiple cavity growth and sinkhole and large-scale depression development is presented. The approach involves a stepwise material removal technique in void spaces of arbitrarily shaped geometries and is benchmarked by analytical and boundary element method solutions for circular cavities. Simulated compression and tension tests are used to calibrate model parameters with bulk rock properties for the materials of the field site. The simulations show that cavity and sinkhole evolution is controlled by material strength of both overburden and cavity host material, the depth and relative speed of the cavity growth and the developed stress pattern in the subsurface. Major findings are: (1) A progressively deepening differential subrosion with variable growth speed yields a more fragmented stress pattern with stress interaction between the cavities. It favours multiple sinkhole collapses and nesting within large-scale depressions. (2) Low-strength materials do not support large cavities in the material removal zone, and subsidence is mainly characterised by gradual sagging into the material removal zone with synclinal bending. (3) High-strength materials support large cavity formation, leading to sinkhole formation by sudden collapse of the overburden. (4) Large-scale depression formation happens either by coalescence of collapsing holes, block-wise brittle failure, or gradual sagging and lateral widening.
The distinct element based approach is compared to results from remote sensing and geophysics at the field site. The numerical simulation outcomes are generally in good agreement with derived morphometrics, documented surface and subsurface structures as well as seismic velocities. Complementary findings on the subrosion process are provided from electric and seismic measurements in the area.
Based on the novel combination of methods in this thesis, a generic model of karst landform evolution with focus on sinkhole and depression formation is developed. A deepening subrosion system related to preferential flow paths evolves and creates void spaces and subsurface conduits. This subsequently leads to hazardous subsidence, and the formation of sinkholes within large-scale depressions. Finally, a monitoring system for shallow natural hazard phenomena consisting of geodetic and geophysical observations is proposed for similarly affected areas.
A form-function mismatch?
(2019)
Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual’s zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body’s zinc status, and its suitability as a future biomarker for an individual’s zinc status.