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See detailAssessment and Improvement of the Practical Use of Mutation for Automated Software Testing
Titcheu Chekam, Thierry UL

Doctoral thesis (2019)

Software testing is the main quality assurance technique used in software engineering. In fact, companies that develop software and open-source communities alike actively integrate testing into their ... [more ▼]

Software testing is the main quality assurance technique used in software engineering. In fact, companies that develop software and open-source communities alike actively integrate testing into their software development life cycle. In order to guide and give objectives for the software testing process, researchers have designed test adequacy criteria (TAC) which, define the properties of a software that must be covered in order to constitute a thorough test suite. Many TACs have been designed in the literature, among which, the widely used statement and branch TAC, as well as the fault-based TAC named mutation. It has been shown in the literature that mutation is effective at revealing fault in software, nevertheless, mutation adoption in practice is still lagging due to its cost. Ideally, TACs that are most likely to lead to higher fault revelation are desired for testing and, the fault-revelation of test suites is expected to increase as their coverage of TACs test objectives increase. However, the question of which TAC best guides software testing towards fault revelation remains controversial and open, and, the relationship between TACs test objectives’ coverage and fault-revelation remains unknown. In order to increase knowledge and provide answers about these issues, we conducted, in this dissertation, an empirical study that evaluates the relationship between test objectives’ coverage and fault-revelation for four TACs (statement, branch coverage and, weak and strong mutation). The study showed that fault-revelation increase with coverage only beyond some coverage threshold and, strong mutation TAC has highest fault revelation. Despite the benefit of higher fault-revelation that strong mutation TAC provide for software testing, software practitioners are still reluctant to integrate strong mutation into their software testing activities. This happens mainly because of the high cost of mutation analysis, which is related to the large number of mutants and the limitation in the automation of test generation for strong mutation. Several approaches have been proposed, in the literature, to tackle the analysis’ cost issue of strong mutation. Mutant selection (reduction) approaches aim to reduce the number of mutants used for testing by selecting a small subset of mutation operator to apply during mutants generation, thus, reducing the number of analyzed mutants. Nevertheless, those approaches are not more effective, w.r.t. fault-revelation, than random mutant sampling (which leads to a high loss in fault revelation). Moreover, there is not much work in the literature that regards cost-effective automated test generation for strong mutation. This dissertation proposes two techniques, FaRM and SEMu, to reduce the cost of mutation testing. FaRM statically selects and prioritizes mutants that lead to faults (fault-revealing mutants), in order to reduce the number of mutants (fault-revealing mutants represent a very small proportion of the generated mutants). SEMu automatically generates tests that strongly kill mutants and thus, increase the mutation score and improve the test suites. First, this dissertation makes an empirical study that evaluates the fault-revelation (ability to lead to tests that have high fault-revelation) of four TACs, namely statement, branch, weak mutation and strong mutation. The outcome of the study show evidence that for all four studied TACs, the fault-revelation increases with TAC test objectives’ coverage only beyond a certain threshold of coverage. This suggests the need to attain higher coverage during testing. Moreover, the study shows that strong mutation is the only studied TAC that leads to tests that have, significantly, the highest fault-revelation. Second, in line with mutant reduction, we study the different mutant quality indicators (used to qualify "useful" mutants) proposed in the literature, including fault-revealing mutants. Our study shows that there is a large disagreement between the indicators suggesting that the fault-revealing mutant set is unique and differs from other mutant sets. Thus, given that testing aims to reveal faults, one should directly target fault-revealing mutants for mutant reduction. We also do so in this dissertation. Third, this dissertation proposes FaRM, a mutant reduction technique based on supervised machine learning. In order to automatically discriminate, before test execution, between useful (valuable) and useless mutants, FaRM build a mutants classification machine learning model. The features for the classification model are static program features of mutants categorized as mutant types and mutant context (abstract syntax tree, control flow graph and data/control dependency information). FaRM’s classification model successfully predicted fault-revealing mutants and killable mutants. Then, in order to reduce the number of analyzed mutants, FaRM selects and prioritizes fault-revealing mutants based of the aforementioned mutants classification model. An empirical evaluation shows that FaRM outperforms (w.r.t. the accuracy of fault-revealing mutant selection) random mutants sampling and existing mutation operators-based mutant selection techniques. Fourth, this dissertation proposes SEMu, an automated test input generation technique aiming to increase strong mutation coverage score of test suites. SEMu is based on symbolic execution and leverages multiple cost reduction heuristics for the symbolic execution. An empirical evaluation shows that, for limited time budget, the SEMu generates tests that successfully increase strong mutation coverage score and, kill more mutants than test generated by state-of-the-art techniques. Finally, this dissertation proposes Muteria a framework that enables the integration of FaRM and SEMu into the automated software testing process. Overall, this dissertation provides insights on how to effectively use TACs to test software, shows that strong mutation is the most effective TAC for software testing. It also provides techniques that effectively facilitate the practical use of strong mutation and, an extensive tooling to support the proposed techniques while enabling their extensions for the practical adoption of strong mutation in software testing. [less ▲]

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See detailDISSECTING GENETIC EPISTASIS IN FAMILIAL PARKINSON’S DISEASE USING A DIGENIC PATIENT-DERIVED STEM CELL MODEL
Hanss, Zoé UL

Doctoral thesis (2019)

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. 10% of PD patients present a familial form of the disease implicating genetic mutations. A variability in terms of ... [more ▼]

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. 10% of PD patients present a familial form of the disease implicating genetic mutations. A variability in terms of disease expressivity, severity and penetrance can be observed among familial cases. The idea that the classical one-gene one-trait model may not catch the full picture of genetic contribution to PD pathophysiology is increasingly recognized. Therefore, a polygenic model where multiple genes would influence the disease risk and the phenotypic traits in PD should be investigated. Mutations in PRKN, encoding the E3 ubiquitin-protein ligase Parkin, cause young onset autosomal recessive forms of PD. A variability in terms of clinical presentation and neuropathology have been observed in PD patients carrying mutations in Parkin. On the other hand, mutations in GBA were recently recognized as the most common genetic risk factor for developing PD. The incomplete penetrance of the disease in patients with GBA mutations may implicate other genetic factors. Therefore, it can be hypothesized that the interactions between common PD genes like PRKN and GBA can contribute to the phenotypic heterogeneity observed in PD cases. To explore this hypothesis, we generated patient-derived cellular models from several PD patients carrying pathogenic mutations in either both PRKN and GBA (triallelic models) or in only one of them (bi- or monoallelic models). We developed a novel strategy to gene edit the N370S mutation in GBA via CRISPR-Cas9, without interference with its respective pseudogene, which allows for the dissection of the role of GBA in the context of a PRKN mutation on an isogenic background. We identified a specific α-synuclein homeostasis in the triallelic model. The genetic and pharmacological rescue of GBA in the triallelic model modified the observed α-synuclein phenotype, proving the contribution of GBA to the observed phenotype. We then investigated whether Parkin was contributing to the phenotype. The modulation of Parkin function in the context of a GBA mutation induced a modification of the α-synuclein homeostasis. We therefore concluded that both PRKN and GBA are influencing α-synuclein homeostasis in the triallelic model. Nevertheless, the phenotypic outcome of the co-occurrence of these mutations was not additive nor synergistic. We therefore suggest the existence of an epistatic interaction between mutant GCase and Parkin that would underlie the clinical heterogeneity observed in PD patients carrying these mutations. [less ▲]

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See detailIntegrity and Confidentiality Problems of Outsourcing
Pejo, Balazs UL

Doctoral thesis (2019)

Cloud services enable companies to outsource data storage and computation. Resource-limited entities could use this pay-per-use model to outsource large-scale computational tasks to a cloud-service ... [more ▼]

Cloud services enable companies to outsource data storage and computation. Resource-limited entities could use this pay-per-use model to outsource large-scale computational tasks to a cloud-service-provider. Nonetheless, this on-demand network access raises the issues of security and privacy, which has become a primary concern of recent decades. In this dissertation, we tackle these problems from two perspectives: data confidentiality and result integrity. Concerning data confidentiality, we systematically classify the relaxations of the most widely used privacy preserving technique called Differential Privacy. We also establish a partial ordering of strength between these relaxations and enlist whether they satisfy additional desirable properties, such as composition and privacy axioms. Tackling the problem of confidentiality, we design a Collaborative Learning game, which helps the data holders to determine how to set the privacy parameter based on economic aspects. We also define the Price of Privacy to measure the overall degradation of accuracy resulting from the applied privacy protection. Moreover, we develop a procedure called Self-Division, which bridges the gap between the game and real-world scenarios. Concerning result integrity, we formulate a Stackelberg game between outsourcer and outsourcee where no absolute correctness is required. We provide the optimal strategies for the players and perform a sensitivity analysis. Furthermore, we extend the game by allowing the outsourcer no to verify and show its Nash Equilibriums. Regarding integrity verification, we analyze and compare two verification methods for Collaborative Filtering algorithms: the splitting and the auxiliary data approach. We observe that neither methods provides a full solution for the raised problem. Hence, we propose a solution, which besides outperforming these is also applicable to both stage of the algorithms. [less ▲]

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See detailIntegrative Network-Based Approaches For Modeling Human Disease
Ali, Muhammad UL

Doctoral thesis (2019)

The large-scale development of high-throughput sequencing technologies has allowed the generation of reliable omics data related to various regulatory levels. Moreover, integrative computational modeling ... [more ▼]

The large-scale development of high-throughput sequencing technologies has allowed the generation of reliable omics data related to various regulatory levels. Moreover, integrative computational modeling has enabled the disentangling of a complex interplay between these interconnected levels of regulation by interpreting concomitant large quantities of biomedical information (‘big data’) in a systematic way. In the context of human disorders, network modeling of complex gene-gene interactions has been successfully used for understanding disease-related dysregulation and for predicting novel drug targets to revert the diseased phenotype. Recent evidence suggests that changes at multiple levels of genomic regulation are responsible for the development and course of multifactorial diseases. Although existing computational approaches have been able to explain cell-type-specific and disease-associated transcriptional regulation, they so far have been unable to utilize available epigenetic data for systematically dissecting underlying disease mechanisms. In this thesis, we first provided an overview of recent advances in the field of computational modeling of cellular systems, its major strengths and limitations. Next, we highlighted various computational approaches that integrate information from different regulatory levels to understand mechanisms behind the onset and progression of multifactorial disorders. For example, we presented INTREGNET, a computational method for systematically identifying minimal sets of transcription factors (TFs) that can induce desired cellular transitions with increased efficiency. As such, INTREGNET can guide experimental attempts for achieving effective in vivo cellular transitions by overcoming epigenetic barriers restricting the cellular differentiation potential. Furthermore, we introduced an integrative network-based approach for ranking Alzheimer’s disease (AD)-associated functional genetic and epigenetic variation. The proposed approach explains how genetic and epigenetic variation can induce expression changes via gene-gene interactions, thus allowing for a systematic dissection of mechanisms underlying the onset and progression of multifactorial diseases like AD at a multi-omics level. We also showed that particular pathways, such as sphingolipids (SL) function, are significantly dysregulated in AD. In-depth integrative analysis of these SL-related genes reveals their potential as biomarkers and for SL-targeted drug development for AD. Similarly, in order to understand the functional consequences of CLN3 gene mutation in Batten disease (BD), we conducted a differential gene regulatory network (GRN)-based analysis of transcriptomic data obtained from an in vitro BD model and revealed key regulators maintaining the disease phenotype. We believe that the work conducted in this thesis provides the scientific community with a valuable resource to understand the underlying mechanism of multifactorial diseases from an integrative point of view, helping in their early diagnosis as well as in designing potential therapeutic treatments. [less ▲]

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See detailDie Entwicklung der Entfremdung vom Lernen in der unteren Sekundarstufe in Luxemburg: Der Beitrag differenzieller schulischer Lern- und Entwicklungsmilieus
Grecu, Alyssa Laureen UL

Doctoral thesis (2019)

This dissertation provides research on alienation from learning in differential learning and developmental milieus (vgl. Baumert/Stanat/Watermann 2006) within the strongly stratified educational system of ... [more ▼]

This dissertation provides research on alienation from learning in differential learning and developmental milieus (vgl. Baumert/Stanat/Watermann 2006) within the strongly stratified educational system of Luxembourg. Alienation from learning is defined as a student´s generalised negative orientation towards learning (Hascher/Hadjar 2018, S. 179) and collocates with severe consequences including school dropout (see Hascher/Hagenauer 2010, S. 220). The study focusses on the question of how the development of alienation from learning differs between the differential learning and developmental milieus within Luxembourgish secondary school tracks. The conceptual framework is based on the perspective of differential learning and developmental milieus (Baumert/Stanat/Watermann 2006), the theory of school culture (Helsper 2008; Kramer/Thiersch/Ziems 2015) and further culture sociological and resonance pedagogical approaches (Willis 1978; Beljan 2017). Combining research on school culture and research on school alienation, this works examines the interplay between school culture and individual students and its impact on alienation from learning. Conceptualized as a mixed method study, this research aims for a holistic picture on alienation from learning by combining quantitative and qualitative approaches. The quantitative part is based on a three-year panel study with students from all secondary school tracks (grade 7-9). Employing random effects models and growth curves models it investigated the degree and development of alienation from learning over time. Qualitative group discussions and interviews with classes (grade 7) and their teachers from the high-achieving and low-achieving school track (corresponding to grammar school and the lowest secondary school track) were conducted to research how schools´ specific demands contribute to alienation from learning. The method employed in the qualitative analysis was the sequence-analytical habitus reconstruction approach. Quantitative analysis reveals a moderate but increasing degree of alienation from learning in all secondary school tracks from grade 7 to 9. Therefore, alienation from learning develops similarly in all secondary school tracks. Students from the high-achieving ES-Track show the strongest degree of alienation from learning whereas students from the low-achieving Modulaire-Track show the lowest degree of alienation from learning. Qualitative analysis identifies the high-achieving and low-achieving secondary school tracks as differential learning and developmental milieus characterized by diverging educational demands and standards on the class level. Consequently, when students’ orientations conflict with the school´s demands and offers there is a high risk for them to develop alienation. Track-specific possibilities and risks were identified with regard to bonding and alienation. Strong achievement orientation, theoretical educational content and highly standardised educational settings may foster alienation from learning depending on the students´ individual competencies and orientations. [less ▲]

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See detailStudy of nanopulsed discharges for plasma-polymerization: experimental characterization and theoretical understanding of growth mechanisms in the deposition of functional polymer thin films
Loyer, François UL

Doctoral thesis (2019)

Plasma processes are highly versatile methods able to promote the formation of thin films from a vast variety of compounds thanks to the numerous energetic species they generate. Notably, plasma-enhanced ... [more ▼]

Plasma processes are highly versatile methods able to promote the formation of thin films from a vast variety of compounds thanks to the numerous energetic species they generate. Notably, plasma-enhanced chemical vapor deposition (PECVD) processes have already led to the simultaneous synthesis and deposition of a wide variety of organic functional materials. Reciprocally, the many reactive species composing the plasma induce a non-negligible number of side reactions, yielding altered chemistry compared to conventional polymerization processes. Therefore, there is a strong need for controlled methods promoting conventional polymerization pathway in plasma-based processes to increase their range of application. To this end, the atmospheric-pressure plasma-initiated chemical vapor deposition (AP-PiCVD) process was developed, differing from classical PECVD by its initiation source. AP-PiCVD relies on square-wave nanopulsed discharges with single ultra-short plasma on times (t_on ≈ 100 ns) and long plasma off-times (t_off = 0.1 – 100 ms) rather than alternative current sources yielding long and repeated discharges (t_on = 10 µs). Methacrylate monomers initiated by nanopulsed discharges highlighted a shift of growth mechanisms from classical PECVD pathways (plasma-polymerization) to conventional free-radical polymerization. Notably, the growth of polymer layers with an extremely high retention of the monomer’s chemistry and unprecedented molecular weights for an atmospheric-pressure plasma process is demonstrated at long plasma off-times. Moreover, a transition from gas phase to surface growth mechanisms is observed, allowing the deposition of conformal coatings similarly to low-pressure alternative chemical vapor deposition processes. A thorough investigation of the thin films’ chemistry confirms the conventional nature of the layers grown by AP-PiCVD and shed light upon the growth mechanisms in low-frequency nanosecond pulsed plasmas. While the on-time induces the formation of free radicals from the monomers’ fragmentation which are able to initiate and terminate the chain addition process, conventional polymerization mechanisms are strongly promoted during the off-time yielding linear polymer core. Interestingly, new insights on selective initiation mechanisms based on sacrificial functions for an enhanced control of the molecular fragmentation are put forward and discussed. The development of a model describing the kinetic of pulsed plasma was carried out and correlated with experimental observations, providing deeper understanding of the interaction between the gas phase and the surface. The extraction of important physical parameters for the description of the growth kinetics in AP-PiCVD is demonstrated and their significance discussed. Using the fundamental knowledge developed on nanosecond pulsed plasma-initiated polymerization mechanisms, thermoresponsive copolymer layers grown by AP-PiCVD are reported for the first time. The properties of the layers are evaluated and related to their chemistry, allowing the determination of an optimal co-monomers ratio to integrate both of their individual properties as a unique functional thin film. [less ▲]

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See detailAttentional bias to body- and sexually-relevant stimuli
Czeluscinska-Peczkowska, Agnieszka UL

Doctoral thesis (2019)

Sexual dysfunctions and body image dissatisfaction in women have reached significant levels, with prevalence rates being currently estimated at 50% and 38%, respectively. The potential societal and health ... [more ▼]

Sexual dysfunctions and body image dissatisfaction in women have reached significant levels, with prevalence rates being currently estimated at 50% and 38%, respectively. The potential societal and health costs are considerable, as a negative body image is considered a high risk factor for the development and maintenance of eating disorders, and sexual dysfunctions can negatively impact overall well-being. Previous research has separately examined body image dissatisfaction and sexual functioning but research linking these two areas is missing. Study 1 demonstrated the significance of contextual body image in evaluating visual sexual images. Valence ratings of sexually explicit stimuli were found to be associated with sexual functioning level mediated by contextual body image: women, who rated sexually explicit pictures less positively scored lower on sexual functioning if they reported a more self-conscious focus and avoidance of the body in the context of sexual experiences. In Study 2 we were able to prove the relevance of new sexually-explicit images in evoking sexual arousal, which was reflected by evaluative judgements and psychophysiological indicators of arousal. Study 3 aimed to compare responses to sexual stimuli and stimuli related to body image dissatisfaction (images of own body) in participants with sexual dysfunctions (SD) and a healthy control (HC) group. Contrary to our expectations, women in the SD group looked significantly longer and more frequently at self-defined most satisfying than dissatisfying body parts when compared to HC participants. There were no significant group differences in gaze duration and frequency of sexually explicit images, but the women with SDs rated these stimuli as less positive, less arousing and expressed less motivation to keep looking at them. Furthermore, by inducing a positive or negative attention bias (AB) to own body parts we aimed at changing state body image satisfaction and state sexual arousal in response to sexually explicit video-clip. The proposed AB induction was not sufficient and did not affect body image and sexual experiences. Altogether, the findings from current study suggests that it visual attention and general arousal in response to sexual stimuli in women with SD is not disturbed but rather the process of evaluation. [less ▲]

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See detailRobotic Trajectory Tracking: Position- and Force-Control
Klecker, Sophie UL

Doctoral thesis (2019)

This thesis employs a bottom-up approach to develop robust and adaptive learning algorithms for trajectory tracking: position and torque control. In a first phase, the focus is put on the following of a ... [more ▼]

This thesis employs a bottom-up approach to develop robust and adaptive learning algorithms for trajectory tracking: position and torque control. In a first phase, the focus is put on the following of a freeform surface in a discontinuous manner. Next to resulting switching constraints, disturbances and uncertainties, the case of unknown robot models is addressed. In a second phase, once contact has been established between surface and end effector and the freeform path is followed, a desired force is applied. In order to react to changing circumstances, the manipulator needs to show the features of an intelligent agent, i.e. it needs to learn and adapt its behaviour based on a combination of a constant interaction with its environment and preprogramed goals or preferences. The robotic manipulator mimics the human behaviour based on bio-inspired algorithms. In this way it is taken advantage of the know-how and experience of human operators as their knowledge is translated in robot skills. A selection of promising concepts is explored, developed and combined to extend the application areas of robotic manipulators from monotonous, basic tasks in stiff environments to complex constrained processes. Conventional concepts (Sliding Mode Control, PID) are combined with bio-inspired learning (BELBIC, reinforcement based learning) for robust and adaptive control. Independence of robot parameters is guaranteed through approximated robot functions using a Neural Network with online update laws and model-free algorithms. The performance of the concepts is evaluated through simulations and experiments. In complex freeform trajectory tracking applications, excellent absolute mean position errors (<0.3 rad) are achieved. Position and torque control are combined in a parallel concept with minimized absolute mean torque errors (<0.1 Nm). [less ▲]

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See detailCreating better ground truth to further understand Android malware: A large scale mining approach based on antivirus labels and malicious artifacts
Hurier, Médéric UL

Doctoral thesis (2019)

Mobile applications are essential for interacting with technology and other people. With more than 2 billion devices deployed all over the world, Android offers a thriving ecosystem by making accessible ... [more ▼]

Mobile applications are essential for interacting with technology and other people. With more than 2 billion devices deployed all over the world, Android offers a thriving ecosystem by making accessible the work of thousands of developers on digital marketplaces such as Google Play. Nevertheless, the success of Android also exposes millions of users to malware authors who seek to siphon private information and hijack mobile devices for their benefits. To fight against the proliferation of Android malware, the security community embraced machine learning, a branch of artificial intelligence that powers a new generation of detection systems. Machine learning algorithms, however, require a substantial number of qualified samples to learn the classification rules enforced by security experts. Unfortunately, malware ground truths are notoriously hard to construct due to the inherent complexity of Android applications and the global lack of public information about malware. In a context where both information and human resources are limited, the security community is in demand for new approaches to aid practitioners to accurately define Android malware, automate classification decisions, and improve the comprehension of Android malware. This dissertation proposes three solutions to assist with the creation of malware ground truths. The first contribution is STASE, an analytical framework that qualifies the composition of malware ground truths. STASE reviews the information shared by antivirus products with nine metrics in order to support the reproducibility of research experiments and detect potential biases. This dissertation reports the results of STASE against three typical settings and suggests additional recommendations for designing experiments based on Android malware. The second contribution is EUPHONY, a heuristic system built to unify family clusters belonging to malware ground truths. EUPHONY exploits the co-occurrence of malware labels obtained from antivirus reports to study the relationship between Android applications and proposes a single family name per sample for the sake of facilitating malware experiments. This dissertation evaluates EUPHONY on well-known malware ground truths to assess the precision of our approach and produce a large dataset of malware tags for the research community. The third contribution is AP-GRAPH, a knowledge database for dissecting the characteristics of malware ground truths. AP-GRAPH leverages the results of EUPHONY and static analysis to index artifacts that are highly correlated with malware activities and recommend the inspection of the most suspicious components. This dissertation explores the set of artifacts retrieved by AP-GRAPH from popular malware families to track down their correlation and their evolution compared to other malware populations. [less ▲]

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See detailCritical perspectives on plurilingual students' identity performance in sustainability education
Gorges, Anna UL

Doctoral thesis (2019)

The purpose of this critical video-ethnographic study is to gain new perspectives on how the open, dialogic structures in an alternative high school setting afford plurilingual adult students’ to take ... [more ▼]

The purpose of this critical video-ethnographic study is to gain new perspectives on how the open, dialogic structures in an alternative high school setting afford plurilingual adult students’ to take agency and the development of a positive student identity. With this goal, the study seeks to contribute to the research literature on plurilingual adult students and on nontraditional students learning about sustainability. The overarching question that guides this study is how does the figured world of multilingual sustainability education based on socioscientific issues mediate plurilingual adult students identities as competent science students? This study is multi-theoretical, multi-method, and multi-level, and as such, the manuscriptstyle dissertation presents several case studies of students as they participate in an interdisciplinary unit on sustainability. Situated in a superdiverse context, the data collection took place at an alternative high school, where students who dropped out of the traditional school system have the chance to get a leaving certificate. Data resources include video data, audio data, student artefacts, fieldnotes and photographs. Multimodal discourse analysis based on Gee (1996) was used to reveal the structures at the micro, meso and macro level that mediate learning for students in the alternative educational setting and afford them to make connections to their everyday lives. Three individual manuscripts examine three separate case studies regarding students’ use of transmodalling, students’ engagement in socio-scientific issues, and students’ perspectives on the holistic teaching and learning approaches in their school. Drawing on dialectic understandings of learning, the three case studies each illuminate holistic approaches to learning focusing on students’ multimodal means of expression, emotions and identity development that afford them with opportunities to take agency and create solidarity in the class and school community. This study concludes that dialogic pedagogy as space of possibilities mediates student’ development of identities as competent science learners, which has implications for their identities as agents positioned for transformative actions. [less ▲]

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See detailFichte und der Skeptizismus
Motz, Oliver Tobias UL

Doctoral thesis (2019)

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See detailAutomated optimisation of stem cell-derived neuronal cell culture in three dimensional microfluidic device
Kane, Khalid Ibnou Walid UL

Doctoral thesis (2019)

This dissertation is a compilation of publications and manuscripts that aim 1) to integrate an automated platform optimised for long term in vitro cell culture maintenance for Parkinson’s disease, long ... [more ▼]

This dissertation is a compilation of publications and manuscripts that aim 1) to integrate an automated platform optimised for long term in vitro cell culture maintenance for Parkinson’s disease, long term live cell imaging and the handling of many cell lines, 2) to combine physics principles with imaging techniques to optimise the seeding of Matrigel embedded human neuroepithelial stem cells into a three-dimensional microfluidic device, and 3) to combine engineering principles with cell biology to optimise the design of a three-dimensional microfluidic system based on phaseguide technology. In the first publication manuscript, we investigated Matrigel as a surrogate extracellular matrix in three-dimensional cell culture systems, including microfluidic cell culture. The study aimed at understanding and characterising the properties of Matrigel. Using classical rheological measurements of Matrigel (viscosity versus shear rate) in combination with fluorescence microscopy and fluorescent beads for particle image velocimetry measurements (velocity profiles), the shear rates experienced by cells in a microfluidic device for three-dimensional cell culture was characterised. We discussed how the result of which helped to mechanically optimise the use of Matrigel in microfluidic systems to minimise the shear stress experienced by cells during seeding in a microchannel. The second manuscript proposes a methodology to passively control the flow of media in a three-dimensional microfluidic channel. We used the fluid dynamic concept of similitude to dynamically replicate cerebral blood flow in a rectangular cross-sectional microchannel. This similarity model of a target cell type and a simple fluid flow mathematical prediction model was used to iterate the most optimum dimensions within some manufacturing constraints to adapt the design of the OrganoPlate, a cell culture plate fully compatible with laboratory automation, which allowed its re-dimension to achieve over 24h of flow for the culture of human neuroepithelial stem cells into midbrain specific dopaminergic neurons. In the third publication manuscript, we propose an automated cell culture platform optimised for long-term maintenance and monitoring of different cells in three-dimensional microfluidic cell culture devices. The system uses Standard in Laboratory Automation or SiLA, an open source standardisation which allows rapid software integration of laboratory automation hardware. The automation platform can be flexibly adapted to various experimental protocols and features time-lapse imaging microscopy for quality control and electrophysiology monitoring to assess cellular activity. It was biologically validated by differentiating Parkinson’s disease patient derived human neuroepithelial stem cells into midbrain specific dopaminergic neurons. This system is the first example of an automated Organ-on-a-Chip culture and has the potential to enable a versatile array of in vitro experiments for patient-specific disease modelling. Finally, the fourth manuscript initiates the assessment of the neuronal activity of induced pluripotent stem cell derived neurons from Parkinson’s Disease patients with LRRK2-G2019S mutations and isogenic controls. A novel image analysis pipeline that combined semi-automated neuronal segmentation and quantification of calcium transient properties was developed and used to analyse neuronal firing activity. It was found that LRRK2-G2019S mutants have shortened inter-spike intervals and an increased rate of spontaneous calcium transient induction than control cell lines. [less ▲]

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See detailShear Transfer in Heavy Steel-Concrete Composite Columns with Multiple Encased Steel Profiles
Chrzanowski, Maciej UL

Doctoral thesis (2019)

The PhD Thesis is dealing with the shear transfer in heavy steel-concrete composite columns with multiple encased steel profiles. In the conducted research, a focus was placed on two aspects of shear ... [more ▼]

The PhD Thesis is dealing with the shear transfer in heavy steel-concrete composite columns with multiple encased steel profiles. In the conducted research, a focus was placed on two aspects of shear transfer: (1) local shear transfer at the steel-concrete interface and (2) global shear transfer between the embedded steel profiles. With reference to the current practice, gaps in the knowledge and in the available solutions have been identified. The development of a novel, easy-applicable and efficient type of shear connectors for an application in composite columns with one or multiple-encased steel profiles satisfies the improvement need to assure local shear transfer between steel and concrete materials. The novel type of flat shear connectors has a form of reinforcement bars welded to the flanges of steel profiles. Three main orientations, in accordance to the steel beam longitudinal axis, were investigated: 1) transversal, 2) longitudinal and 3) angled under 45° - V-shaped. The force transfer mechanism of the proposed shear connectors considers the usage of the external stirrups to anchorage the compression struts and bear the tensile forces. In parallel, the steel-concrete bond phenomenon was examined and analysed. In the consideration of the global shear transfer and in respect to the mechanical engineering model and behaviour of large composite columns with more than one embedded steel profile, the common practice so far is to assume a homogenous system with one stiffness and analyse it based on the Bernoulli beam theory. However, the results of the recent tests caused some doubts whether this approach is correct. The derivation away from the Bernoulli beam behaviour leads to a changed stiffness of the column and hence changed critical buckling load. An innovative hybrid conception has been proposed, where a transition towards the Vierendeel truss model embedded into the Timoshenko beam model is considered in order to govern the identified significant effects of shear deformation. Within this objective, big-scale beam/column members with two embedded steel profiles were examined in order to investigate an internal forces distribution and its bending and shear stiffness. A complex interaction between the materials and lack of knowledge regarding composite behaviour in columns with multiple encased steel profiles opens opportunities to develop novel systems and design methods. The described objectives are investigated experimentally and by the FE numerical simulations. As an outcome, an analytical model for the resistance of the developed novel shear connectors and innovative mechanical engineering model for the description of the structural behaviour, as well as effective stiffness, of a composite member with more than one embedded steel profile are given. [less ▲]

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See detailMultiscale modeling of mitochondria
Garcia, Guadalupe Clara UL

Doctoral thesis (2019)

Life is based on energy conversion by which cells and organisms can adapt to the environment. The involved biological processes are intrinsically multiscale phenomena since they are based on molecular ... [more ▼]

Life is based on energy conversion by which cells and organisms can adapt to the environment. The involved biological processes are intrinsically multiscale phenomena since they are based on molecular interactions on a small scale leading to the emerging behavior of cells, organs and organisms. To understand the underlying regulation and to dissect the mechanisms that control system behavior, appropriate mathematical multiscale models are needed. Such models do not only offer the opportunity to test different hypothesized mechanisms but can also address current experimental technology gaps by zooming in and out of the dynamics, changing scales, coarse-graining the dynamics and giving us distinct views of the phenomena. In this dissertation substantial efforts were done to combine different computational modeling strategies based on different assumptions and implications to model an essential system of eukaryotic life -- the energy providing mitochondria -- where the spatiotemporal domain is suspected to have a substantial influence on its function. Mitochondria are highly dynamic organelles that fuse, divide, and are transported along the cytoskeleton to ensure cellular energy homeostasis. These processes cover different scales, in space and time, where on the more global scale mitochondria exhibit changes in their molecular content in response to their physiological context including circadian modulation. On the smaller scales, mitochondria show also faster adaptation by changing their morphology within minutes. For both processes, the relation between the underlying structure of either their regulating network or the spatial morphology and the functional consequences are essential to understand principles of energy homeostasis and their link to health and disease conditions. This thesis focuses on different scales of mitochondrial adaptation. On the small scales, fission and fusion of mitochondria are rather well established but substantial evidence indicates that the internal structure is also highly variable in dependence on metabolic condition. However, a quantitative mechanistic understanding how mitochondrial morphology affects energetic states is still elusive. In the first part of this dissertation I address this question by developing an agent-based dynamic model based on three-dimensional morphologies from electron microscopy tomography, which considers the molecular dynamics of the main ATP production components. This multiscale approach allows for investigating the emergent behavior of the energy generating mechanism in dependence on spatial properties and molecular orchestration. Interestingly, comparing spatiotemporal simulations with a corresponding space-independent approach, I found only minor space dependence in equilibrium conditions but qualitative difference in fluctuating environments and in particular indicate that the morphology provides a mechanism to buffer energy at synapses. On the more global scale of the regulation of mitochondrial protein composition, I applied a data driven approach to explore how mitochondrial activity is changing during the day and how food intake restrictions can effect the structure of the underlying adaptation process. To address the question if at different times of the day, the mitochondrial composition might adapt and have potential implications for function, I analyzed temporal patterns of hepatic transcripts of mice that had either unlimited access to food or were hold under temporal food restrictions. My analysis showed that mitochondrial activity exhibits a temporal activity modulation where different subgroups of elements are active at different time points and that food restriction increases temporal regulation. Overall, this thesis provides new insights into mitochondrial biology at different scales by providing an innovative computational modeling framework to investigate the relation between morphology and energy production as well as by characterizing temporal modulation of the regulatory network structure under different conditions. [less ▲]

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See detailNonlinear Observation and Control of a Lightweight Robotic Manipulator Actuated by Shape Memory Alloy (SMA) Wires
Quintanar Guzman, Serket UL

Doctoral thesis (2019)

In the last decade, the industry of Unmanned Aerial Vehicles (UAV) has gone through immense growth and diversification. Nowadays, we find drone based applications in a wide range of industries, such as ... [more ▼]

In the last decade, the industry of Unmanned Aerial Vehicles (UAV) has gone through immense growth and diversification. Nowadays, we find drone based applications in a wide range of industries, such as infrastructure, agriculture, transport, among others. This phenomenon has generated an increasing interest in the field of aerial manipulation. The implementation of aerial manipulators in the UAV industry could generate a significant increase in possible applications. However, the restriction on the available payload is one of the main setbacks of this approach. The impossibility to equip UAVs with heavy dexterous industrial robotic arms has driven the interest in the development of lightweight manipulators suitable for these applications. In the pursuit of providing an alternative lightweight solution for the aerial manipulators, this thesis proposes a lightweight robotic arm actuated by Shape Memory Alloy (SMA) wires. Although SMA wires represent a great alternative to conventional actuators for lightweight applications, they also imply highly nonlinear dynamics, which makes them difficult to control. Seeking to present a solution for the challenging task of controlling SMA wires, this work investigates the implications and advantages of the implementation of state feedback control techniques. The final aim of this study is the experimental implementation of a state feedback control for position regulation of the proposed lightweight robotic arm. Firstly, a mathematical model based on a constitutive model of the SMA wire is developed and experimentally validated. This model describes the dynamics of the proposed lightweight robotic arm from a mechatronics perspective. The proposed robotic arm is tested with three output feedback controllers for angular position control, namely a PID, a Sliding Mode and an Adaptive Controller. The controllers are tested in a MATLAB simulation and finally implemented and experimentally tested in various different scenarios. Following, in order to perform the experimental implementation of a state feedback control technique, a state and unknown input observer is developed. First, a non-switching observable model with unknown input of the proposed robotic arm is derived from the model previously presented. This model takes the martensite fraction rate of the original model as an unknown input, making it possible to eliminate the switching terms in the model. Then, a state and unknown input observer is proposed. This observer is based on the Extended Kalman Filter (EKF) for state estimation and sliding mode approach for unknown input estimation. Sufficient conditions for stability and convergence are established. The observer is tested in a MATLAB simulation and experimentally validated in various different scenarios. Finally, a state feedback control technique is tested in simulation and experimentally implemented for angular position control of the proposed lightweight robotic arm. Specifically, continuous and discrete-time State-Dependent Riccati Equation (SDRE) control laws are derived and implemented. To conclude, a quantitative and qualitative comparative analysis between an output feedback control approach and the implemented state feedback control is carried out under multiple scenarios, including position regulation, position tracking and tracking with changing payloads. [less ▲]

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See detailNumerical Modeling of air-gap membrane distillation
Cramer, Kerstin Julia UL

Doctoral thesis (2019)

Fresh water supply is a problem in large parts of the world and present on every continent. Many countries facing physical water scarcity, however, have access to the sea and lie in arid zones of the ... [more ▼]

Fresh water supply is a problem in large parts of the world and present on every continent. Many countries facing physical water scarcity, however, have access to the sea and lie in arid zones of the earth where solar energy is plentiful available. Membrane distillation (MD) describes an emerging desalination technology which has advantages when driven by solar energy or waste heat. In MD, seawater is thermally desalinated by generating a temperature gradient between hot salt water and produced fresh water which are separated by a membrane. In air-gap membrane distillation (AGMD) an insulating air-gap is introduced between membrane and distillate in order to minimize conductive losses. Despite its advantages, the permeate stream needs to be increased for large-scale application. To improve performance and energy efficiency, a detailed understanding of the highly coupled heat and mass transfer is crucial. However, for AGMD not many models exist and the existing models simplify the heat and mass transfer processes. The goal of this thesis is therefore to increase the understanding of the AGMD process and the predictive power of numerical models. A three-dimensional (3D) macro-scale model is developed with emphasis on the heat and mass transfer. It integrates aspects from multiphase flow modeling namely energy conservation over phase-change interfaces and the thermodynamic concept of moist air in the air-gap. Thereby, it computes the condensation mass flow independently from the evaporation mass flow, allowing to study the influence of convection on the heat and mass transfer in the air-gap. The model is accelerated for computation on graphical processing units (GPU). Employing the macro-scale model, a comparative analysis of the effects of module orientation on module performance and efficiency is performed. Vortexes in the air-gap are observed when using a module configuration where the hot feed flows below air-gap and membrane and the temperature gradient is opposing gravity. These vortexes lead to a significantly increased energy utilization also at low feed velocities. As the main advantage of AGMD is the reduction of heat losses, this configuration could bring further improvement. Furthermore, membrane transport properties are determined from high-resolution 3D membrane imaging combined with Lattice-Boltzmann simulation. Thereby, the 3D structure of membrane samples is obtained and porosity, tortuosity and permeability values are computed for the investigated membranes. Following the findings in the papers, further studies are suggested employing the modeling approaches developed in this thesis. [less ▲]

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See detailGeneration of midbrain organoids as a model to study Parkinson's disease
Smits, Lisa UL

Doctoral thesis (2019)

The study of 3D cell culture models not only bridges the gap between traditional 2D in vitro experiments and in vivo animal models, it also addresses processes that cannot be recapitulated by these ... [more ▼]

The study of 3D cell culture models not only bridges the gap between traditional 2D in vitro experiments and in vivo animal models, it also addresses processes that cannot be recapitulated by these traditional models. Therefore, it offers an opportunity to better understand complex biology, for instance brain development, where conventional models have not proven successful. The so{called brain organoid technology provides a physiologically relevant context, which holds great potential for its application in modelling neurological diseases. To obtain these highly specialised structures, resembling specifically key features of the human midbrain, we derived a human midbrain-specific organoid (hMO) system from regionally patterned neural stem cells (NSCs). The resulting neural tissue exhibited abundant neurons with midbrain dopaminergic neuron (mDAN) identity, as well as astroglia and oligodendrocyte di erentiation. Within the hMOs, we could observe neurite myelination and the formation of synaptic connections. Regular fire patterning and neural network synchronicity were determined by multielectrode array (MEA) recordings. In addition to electrophysiologically functional mDANs producing and secreting dopamine (DA), we also detected responsive neuronal subtypes, like GABAergic and glutamatergic neurons. To investigate Parkinson's disease (PD)-relevant pathomechanisms, we derived hMOs from PD patients carrying the LRRK2-G2019S mutation and compared them to healthy control hMOs. In addition to a reduced number and complexity of mDANs, we determined a signi cant increase of the stem cell marker FOXA2 in the patient-derived hMOs. This suggests a neurodevelopmental defect induced by a PD-specific mutation and emphasises the importance of advanced three-dimensional (3D) stem cell-based in vitro models. The in this thesis described hMOs are suitable to reveal PD{relevant phenotypes, thus constitute as a powerful tool for human-specific in vitro disease modelling of neurological disorders with a great potential to be utilised in advanced therapy development. [less ▲]

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See detailIl "Tieste" di Ugo Foscolo e l'estetica teatrale di Melchiorre Cesarotti. Per la storia e le implicazioni di un'inconciliabilità ideologica e filosofica
Scagnetti, Matteo Martino UL

Doctoral thesis (2019)

This work analyzes the tragedy written by Ugo Foscolo (1778-1827) at the end of his adolescence : Tieste. The drama has not been sufficiently studied yet, but presents various and important elements of ... [more ▼]

This work analyzes the tragedy written by Ugo Foscolo (1778-1827) at the end of his adolescence : Tieste. The drama has not been sufficiently studied yet, but presents various and important elements of interest. The idea of literature emerging from it is definitely new, and Tieste tries untrodden ways, incompatible with the dominant idea of tragedy at its epoch. Most of all, Tieste marks a rebellion against the aesthetic canons of Melchiorre Cesarotti (1730-1808), a well-known philosopher who had a deep influence in the theatrical field and who had established the standards of a good tragedy. Cesarotti’s parameters were still those of the Enlightenment, and imposed a moral message to every tragedy, whose characters should be rewarded or punished on the basis of their goodness or their wickedness. For Cesarotti, a character would have encountered an unfavourable fate only as a consequence of a moral crime. His virtue, instead, would have avoided any danger. In Foscolo, on the contrary, there is no providence, and the destiny of human beings doesn’t depend on their behaviour. Virtuous characters are powerless and succumb without even understanding why, while the evil tyrant triumphs, moved only by his sadism. The evil is ineffable and inexplicable, and Reason, which solves every problem in Cesarotti’s Weltanschauung, is now helpless and meaningless. Foscolo’s first tragedy therefore represents the transition from an Ancien Régime world view to the phantoms and the nightmares of the contemporary age, when no certitude is possible anymore. [less ▲]

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See detailComputational and symbolic analysis of distance-bounding protocols
Toro Pozo, Jorge Luis UL

Doctoral thesis (2019)

Contactless technologies are gaining more popularity everyday. Credit cards enabled with contactless payment, smart cards for transport ticketing, NFC-enabled mobile phones, and e-passports are just a few ... [more ▼]

Contactless technologies are gaining more popularity everyday. Credit cards enabled with contactless payment, smart cards for transport ticketing, NFC-enabled mobile phones, and e-passports are just a few examples of contactless devices we are familiar with nowadays. Most secure systems meant for these devices presume physical proximity between the device and the reader terminal, due to their short communication range. In theory, a credit card should not be charged of an on-site purchase if the card is not up to a few centimeters away from the payment terminal. In practice, this is not always true. Indeed, some contactless payment protocols, such as Visa's payWave, have been shown vulnerable to relay attacks. In a relay attack, a man-in-the-middle uses one or more relay devices in order to make two distant devices believe they are close. Relay attacks have been implemented also to bypass keyless entry and start systems in various modern cars. Relay attacks can be defended against with distance-bounding protocols, which are security protocols that measure the round-trip times of a series of challenge/response rounds in order to guarantee physical proximity. A large number of these protocols have been proposed and more sophisticated attacks against them have been discovered. Thus, frameworks for systematic security analysis of these protocols have become of high interest. As traditional security models, distance-bounding security models sit within the two classical approaches: the computational and the symbolic models. In this thesis we propose frameworks for security analysis of distance-bounding protocols, within the two aforementioned models. First, we develop an automata-based computational framework that allows us to generically analyze a large class of distance-bounding protocols. Not only does the proposed framework allow us to straightforwardly deliver computational (in)security proofs but it also permits us to study problems such as optimal trade-offs between security and space complexity. Indeed, we solve this problem for a prominent class of protocols, and propose a protocol solution that is optimally secure amongst space-constrained protocols within the considered class. Second, by building up on an existing symbolic framework, we develop a causality-based characterization of distance-bounding security. This constitutes the first symbolic property that guarantees physical proximity without modeling continuous time or physical location. We extend further our formalism in order to capture a non-standard attack known as terrorist fraud. By using our definitions and the verification tool Tamarin, we conduct a security survey of over 25 protocols, which include industrial protocols based on the ISO/IEC 14443 standard such as NXP's MIFARE Plus with proximity check and Mastercard's PayPass payment protocol. For the industrial protocols we find attacks, propose fixes and deliver security proofs of the repaired versions. [less ▲]

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See detailPROVABLE SECURITY ANALYSIS FOR THE PASSWORD AUTHENTICATED KEY EXCHANGE PROBLEM
Lopez Becerra, José Miguel UL

Doctoral thesis (2019)

Password-based Authenticated Key-Exchange (PAKE) protocols allow the establishment of secure communications despite a human-memorable password being the only secret that is previously shared between the ... [more ▼]

Password-based Authenticated Key-Exchange (PAKE) protocols allow the establishment of secure communications despite a human-memorable password being the only secret that is previously shared between the participants. After more than 25 years since the initial proposal, the PAKE problem remains an active area of research, probably due to the vast amount of passwords deployed on the internet as password-based still constitutes the most extensively used method for user authentication. In this thesis, we consider the computational complexity approach to improve the current understanding of the security provided by previously proposed PAKE protocols and their corresponding security models. We expect that this work contributes to the standardization, adoption and more efficient implementation of the considered protocols. Our first contribution is concerning forward secrecy for the SPAKE2 protocol of Abdalla and Pointcheval (CT-RSA 2005). We prove that the SPAKE2 protocol satisfies the so-called notion of weak forward secrecy. Furthermore, we demonstrate that the incorporation of key-confirmation codes in the original SPAKE2 results in a protocol that provably satisfies the stronger notion of perfect forward secrecy. As forward secrecy is an explicit requirement for cipher suites supported in the TLS handshake, we believe our results fill the gap in the literature and facilitate the adoption of SPAKE2 in the recently approved TLS 1.3. Our second contribution is regarding tight security reductions for EKE-based protocols. We present a security reduction for the PAK protocol instantiated over Gap Diffie-Hellman groups that is tighter than previously known reductions. We discuss the implications of our results for concrete security. Our proof is the first to show that the PAK protocol can provide meaningful security guarantees for values of the parameters typical in today's world. Finally, we study the relation between two well-known security models for PAKE protocols. Security models for PAKEs aim to capture the desired security properties that such protocols must satisfy when executed in the presence of an adversary. They are usually classified into i) indistinguishability-based (IND-based) or ii) simulation-based (SIM-based), however, controversy remains within the research community regarding what is the most appropriate security model that better reflects the capabilities that an adversary is supposed to have in real-world scenarios. Furthermore, the relation between these two security notions is unclear and mentioned as a gap in the literature. We prove that SIM-BMP security from Boyko et al. (EUROCRYPT 2000) implies IND-RoR security from Abdalla et al. (PKC 2005) and that IND-RoR security is equivalent to a slightly modified version of SIM-BMP security. We also investigate whether IND-RoR security implies (unmodified) SIM-BMP security. [less ▲]

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See detailEffective Testing Of Advanced Driver Assistance Systems Using Evolutionary Algorithms And Machine Learning
Ben Abdessalem (helali), Raja UL

Doctoral thesis (2019)

Improving road safety is a major concern for most car manufacturers. In recent years, the development of Advanced Driver Assistance Systems (ADAS) has subsequently seen a tremendous boost. The development ... [more ▼]

Improving road safety is a major concern for most car manufacturers. In recent years, the development of Advanced Driver Assistance Systems (ADAS) has subsequently seen a tremendous boost. The development of such systems requires complex testing to ensure vehicle’s safety and reliability. Performing road tests tends to be dangerous, time-consuming, and costly. Hence, a large part of testing for ADAS has to be carried out using physics-based simulation platforms, which are able to emulate a wide range of virtual traffic scenarios and road environments. The main difficulties with simulation-based testing of ADAS are: (1) the test input space is large and multidimensional, (2) simulation platforms provide no guidance to engineers as to which scenarios should be selected for testing, and hence, simulation is limited to a small number of scenarios hand-picked by engineers, and (3) test executions are computationally expensive because they often involve executing high-fidelity mathematical models capturing continuous dynamic behaviors of vehicles and their environment. The complexity of testing ADAS is further exacerbated when many ADAS are employed together in a self-driving system. In particular, when self-driving systems include many ADAS (i.e., features), they tend to interact and impact one another’s behavior in an unknown way and may lead to conflicting situations. The main challenge here is to detect and manage feature interactions, in particular, those that violate system safety requirements, hence leading to critical failures. In practice, once feature interaction failures are detected, engineers need to devise resolution strategies to resolve potential conflicts between features. Developing resolution strategies is a complex task and despite the extensive domain expertise, these resolution strategies can be erroneous and are too complex to be manually repaired. In this dissertation, in addition to testing individual ADAS, we focus on testing self-driving systems that include several ADAS. In this dissertation, we propose a set of approaches based on meta-heuristic search and machine learning techniques to automate ADAS testing and to repair feature interaction failures in self-driving systems. The work presented in this dissertation is motivated by ADAS testing needs at IEE, a world-leading part supplier to the automotive industry. In this dissertation, we focus on the problem of design time testing of ADAS in a simulated environment, relying on Simulink models. The main research contributions in this dissertation are: - A testing approach for ADAS that combines multi-objective search with surrogate models to guide testing towards the most critical behaviors of ADAS, and to explore a larger part of the input search space with less computational resources. - An automated testing algorithm that builds on learnable evolution models and uses classification decision trees to guide the generation of new test scenarios within complex and multidimensional input spaces and help engineers interpret test results. - An automated technique that detects feature interaction failures in the context of self-driving systems based on analyzing executable function models typically developed to specify system behaviors at early development stages. - An automated technique that uses a new many-objective search algorithm to localize and repair errors in the feature interaction resolution rules for self-driving systems. [less ▲]

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See detailALIGNED MULTI-WALL CARBON NANOTUBE SHEETS FOR LIQUID CRYSTAL DISPLAYS
Rahman, Md Asiqur UL

Doctoral thesis (2019)

The great interest in carbon nanotubes (CNTs) was triggered by their discovery by Iijima and has led to significant research efforts finding exceptional electrical and mechanical properties. The ... [more ▼]

The great interest in carbon nanotubes (CNTs) was triggered by their discovery by Iijima and has led to significant research efforts finding exceptional electrical and mechanical properties. The extraordinarily high anisotropy is not just limited to the shape of CNTs, but it is also reflected in their properties that show strong orientational dependence. However, a crucial step involves the incorporation of CNTs into macro-size devices while keeping the nanotubes perfectly aligned in a single direction with a high degree of nanotube straightness. It has been an additional challenge to produce CNT assemblies that meet all these requirements until Kaili Jiang et al introduced a solid state method to produce highly aligned multi-wall CNTs pulled from a forest. They reported that it is possible to pull continuous strings of nanotubes from vertically-aligned CNT forests, forming parallel arrays aligned along the pulling direction. Due to their high alignment, transparency, flexibility, conductivity and optical anisotropy, sheets formed by aligned CNTs are promising as optical polarizer, heaters, sensors, energy devices and aligning and electrodes layers in displays. The alignment of a liquid crystal (LC) on a CNT surface was first realized by Giusy Scalia et al. Later, Russel et al. showed that surfaces with aligned CNTs align LCs unidirectionally, followed by Fu et al. demonstrating that coated CNT sheets can also act as transparent electrodes for switching LC. Thus, aligned CNT sheets show promise as attractive multifunctional systems for LC displays, being able to simultaneously serve diverse functions by replacing both polyimide (PI) and indium tin oxide (ITO) layers, thus, minimizing costs and simplifying the fabrication process. The mechanical properties of CNTs offer also better performance than ITO when used on flexible substrates. However, the optical anisotropy of MWCNT sheets in the range of visible wavelengths remains almost unexplored. There is thus an urgent need to investigate and fundamentally understand the interaction of light with CNT sheets in order to accurately realize CNT-based liquid crystal optical devices. In LC displays, the modulation of light is based on the use of polarized light, and the introduction of an optically anisotropic layer can affect the modulation; thus, it is important to acquire fundamental knowledge on the interaction between aligned MWCNT sheets and light. We followed the technique reported by Kaili Jiang and Ray Baughman to produce highly aligned CNT sheets by pulling CNTs from a spinnable CNT forest. We further deposited the aligned CNT sheets on a glass substrate and characterized them in the visible wavelength range, finding that the aligned CNT sheets anisotropically absorb light. Furthermore, the linearly polarized light travelling through the CNT sheets is rotated and the polarization of the light is affected by the presence of even a single layer of CNTs. Moreover, the magnitude of rotation of polarization increases as the layer thickness increases. We performed theoretical investigations which closely fit the experimental data, suggests that the origin of the rotation is mainly due to the anisotropic absorption. However, other contributions, such as from birefringence, cannot be ruled out. By optical investigations, the dependence of the optical behavior on the thickness of CNTs was also established. Moreover, the average orientational order parameter of the CNT sheets was evaluated from the anisotropic absorption of aligned CNT sheets. A high value of orientational order parameter in CNT sheets is needed since the alignment of the CNT sheets translates to LC alignment. The order parameter of free-standing CNT sheets was found to be ~0.6; however, it decreases once deposited on a substrate. The adhesion between the CNT sheets and the substrate is an additional problem and was studied using different strategies correlating the adhesion to the final alignment of the CNTs on a substrate. Parts of this research effort were devoted to investigating CNT sheets on various polymer surfaces, leaving the surface of CNTs almost free from polymer, for a direct investigation of the LC alignment on the CNT graphitic surface. The general goal was to improve the adhesion while keeping the alignment of the CNTs intact as pulled from the forest. We found a tradeoff between the adhesion of the CNTs and their alignment on a substrate; however, achieving highly-ordered CNTs and perfect adhesion on the surface is an issue. A second approach was based on complete coverage of CNTs by coating the nanotube films with inorganic dielectric layers (SiO_2 or Al_2 O_3). We found that SiO_2 coating preserved the freely-suspended CNT alignment while improving the film flatness. These inorganic coatings help to obtain good electrical performance of LC in cells made with the CNT-based substrates. The alignment of the liquid crystal 4-cyano-4'-pentylbiphenyl (5CB) in the cells was generally planar and unidirectional, with differences in the quality depending on the type of coating layer and on the value of the order parameter of the CNT sheets. We investigated both the uniformity of the LC alignment as well as the switching voltages and times and compared this to the performance of the LC in commercial cells. Integration of aligned CNTs with LC requires the understanding of the interactions of CNT layers with light to realize CNT devices. Aligned CNTs from forests can be obtained easily; sequentially depositing CNT layers, however, while maintaining control of the degree of alignment when integrating them into devices is an open issue. This work shows the occurrence of unexpected interactions with polarized light due to the intrinsic properties of CNTs and due to their alignment. By exploring and optimizing the optical performance of CNT sheets, through their orientational order, it can be possible to use them as optical films for producing, among other optical devices, variable rotation of polarization, polarizers and transparent electrodes that also can align LCs integrated into LCDs. [less ▲]

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See detailOptical investigation of voltage losses in high-efficiency Cu(In,Ga)Se2 thin-film solar cells
Wolter, Max UL

Doctoral thesis (2019)

The increases in power conversion efficiencies up to 23.35 % in thin-film Cu(In,Ga)Se2 (CIGS) solar cells in recent years can mainly be ascribed to the alkali post-deposition treatment (PDT). The latter ... [more ▼]

The increases in power conversion efficiencies up to 23.35 % in thin-film Cu(In,Ga)Se2 (CIGS) solar cells in recent years can mainly be ascribed to the alkali post-deposition treatment (PDT). The latter consists of an additional treatment step after absorber growth where alkali elements, such as sodium (Na) or rubidium (Rb), are injected into the absorber. While the beneficial effects of the alkali PDT, attributed partly to a reduction of voltage losses, are undeniable, it is not yet entirely clear what underlying mechanisms are responsible. To clarify the specific influence of the alkali PDT on the voltage of the CIGS solar cells, photoluminescence (PL) spectroscopy experiments were conducted on state-of-the-art CIGS absorbers having undergone different alkali PDTs. Photoluminescence allows the investigation of possible voltage losses on the absorbers through the analysis of optoelectronic quantities such as the absorption coefficient, the quasi-Fermi level splitting (QFLS), electronic defects, and potential fluctuations. Mainly due to a smooth surface and a band gap minimum inside the bulk, the PL spectra of state-of-the-art CIGS absorbers are distorted by interference fringes. To remove the interference fringes at room temperature, an experimental method, which revolves around the measurement of PL under varying angles, is developed in this thesis. In addition, to enable PL experiments even at low temperatures, an auxiliary polystyrene-based scattering layer is conceptualized and deposited on the surface of the absorbers. With the influence of the interference fringes under control, the quasi-Fermi level splitting can be measured on bare and CdS-covered absorbers. The results reveal an improvement of the QFLS in absorbers that contain Na with an additional increase being recorded in absorbers that also contain Rb. The improvement of the QFLS is present in both bare and CdS-covered absorbers, indicating that the beneficial effect of the alkali PDT is not only occurring on the surface but also inside the bulk. To identify possible origins of the QFLS increase, various PL-based experiments were performed. At room temperature, spatially-resolved PL measurements on the microscopic scale do not reveal any optoelectronic inhomogeneities in state-of-the-art CIGS absorbers. Defect spectroscopy at low temperatures also does not reveal the presence of deep-level trap states. Through temperature- and excitation-dependent PL experiments, a reduction of electrostatic potential fluctuations is observed in absorbers that contain Na with a stronger reduction witnessed in absorbers that contain Rb as well. The extraction of the absorption coefficient through PL measurements at room temperature reveals a reduction of band tails with alkali PDT that empirically correlates to the measured increase in the QFLS. This correlation might indicate that the band tails, through non-radiative recombination, may be the origin of the performance-limiting voltage losses. In combination with reports from literature, it is suggested that the beneficial effect of the light alkali PDT (Na) is mainly a doping effect i.e. an increase in the QFLS through an increase in the hole carrier concentration. The beneficial effect of the heavier alkali PDT (Rb) is attributed partly to a surface effect but mainly to a grain boundary effect, either through a reduction in band bending or a reduction of non-radiative recombination through tail states. Finally, the various voltage losses in state-of-the-art CIGS solar cells are compared to the best crystalline silicon device, revealing almost identical losses. This shows that the alkali PDT enables the fabrication of high-efficiency CIGS solar cells that show, in terms of voltage, identical performance. To bridge the gap between CIGS and the even better performing GaAs, the results of this thesis suggest that grain boundaries are crucial in this endeavour. [less ▲]

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See detailOptimization of logical networks for the modelling of cancer signalling pathways
De Landtsheer, Sébastien UL

Doctoral thesis (2019)

Cancer is one of the main causes of death throughout the world. The survival of patients diagnosed with various cancer types remains low despite the numerous progresses of the last decades. Some of the ... [more ▼]

Cancer is one of the main causes of death throughout the world. The survival of patients diagnosed with various cancer types remains low despite the numerous progresses of the last decades. Some of the reasons for this unmet clinical need are the high heterogeneity between patients, the differentiation of cancer cells within a single tumor, the persistence of cancer stem cells, and the high number of possible clinical phenotypes arising from the combination of the genetic and epigenetic insults that confer to cells the functional characteristics enabling them to proliferate, evade the immune system and programmed cell death, and give rise to neoplasms. To identify new therapeutic options, a better understanding of the mechanisms that generate and maintain these functional characteristics is needed. As many of the alterations that characterize cancerous lesions relate to the signaling pathways that ensure the adequacy of cellular behavior in a specific micro-environment and in response to molecular cues, it is likely that increased knowledge about these signaling pathways will result in the identification of new pharmacological targets towards which new drugs can be designed. As such, the modeling of the cellular regulatory networks can play a prominent role in this understanding, as computational modeling allows the integration of large quantities of data and the simulation of large systems. Logical modeling is well adapted to the large-scale modeling of regulatory networks. Different types of logical network modeling have been used successfully to study cancer signaling pathways and investigate specific hypotheses. In this work we propose a Dynamic Bayesian Network framework to contextualize network models of signaling pathways. We implemented FALCON, a Matlab toolbox to formulate the parametrization of a prior-knowledge interaction network given a set of biological measurements under different experimental conditions. The FALCON toolbox allows a systems-level analysis of the model with the aim of identifying the most sensitive nodes and interactions of the inferred regulatory network and point to possible ways to modify its functional properties. The resulting hypotheses can be tested in the form of virtual knock-out experiments. We also propose a series of regularization schemes, materializing biological assumptions, to incorporate relevant research questions in the optimization procedure. These questions include the detection of the active signaling pathways in a specific context, the identification of the most important differences within a group of cell lines, or the time-frame of network rewiring. We used the toolbox and its extensions on a series of toy models and biological examples. We showed that our pipeline is able to identify cell type-specific parameters that are predictive of drug sensitivity, using a regularization scheme based on local parameter densities in the parameter space. We applied FALCON to the analysis of the resistance mechanism in A375 melanoma cells adapted to low doses of a TNFR agonist, and we accurately predict the re-sensitization and successful induction of apoptosis in the adapted cells via the silencing of XIAP and the down-regulation of NFkB. We further point to specific drug combinations that could be applied in the clinics. Overall, we demonstrate that our approach is able to identify the most relevant changes between sensitive and resistant cancer clones. [less ▲]

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See detailSelf-Organizing Cellulose Nanorods: From the fundamental physical chemistry of self-assembly to the preparation of functional films
Honorato Rios, Camila UL

Doctoral thesis (2019)

Cellulose nanocrystals (CNCs), nanorods isolated by acid hydrolysis from cellulose sources, be- long to a selective type of functional biomaterials. The intriguing ability of these nanoparticles to self ... [more ▼]

Cellulose nanocrystals (CNCs), nanorods isolated by acid hydrolysis from cellulose sources, be- long to a selective type of functional biomaterials. The intriguing ability of these nanoparticles to self-organize and develop a chiral nematic liquid crystal phase when suspended in aqueous suspensions, is increasing interest regardless of the diverse range of research fields. Unfortu- nately (or fortunately, for this thesis), pristine CNCs are always disperse, with great variations in rod length within a single sample. Of particular interest is the fractionation of CNC rods by separation of the coexisting phases: isotropic phase from the liquid crystalline (LC) part. Since the aspect ratio is considered to be the critical parameter that dictates the particle fraction at which cholesteric-isotropic phase separation starts, it is expected that the high aspect ratio rods will separate from low aspect ratio rods, and this is indeed what I found in this thesis. By a systematic repetition of separation of phases, I could reach a quality of separation of long from short rods that is remarkable. The fractionation procedure was then improved by varying the equilibrium phase volume fraction at which the phases were separated, reducing with this new procedure the multiple separations from five cycles to only one. The onset of liquid crystallinity was drastically reduced in the long rod fraction and the decrease in the threshold for complete liquid crystallinity was even stronger. The mass fraction threshold at which gelation of the CNC suspension is triggered is not at all affected by the fractionation. Since gelation is a percolation phenomenon, the expectation was that also the onset of gelation would move to lower mass fractions, but this remained at about the same value. Together with the shift to lower mass fractions of the cholesteric liquid crystal phase formation we have thus opened access to a whole new range of the equilibrium phase diagram, where the full sample is cholesteric yet not gelled. I demonstrate that the critical parameter for inducing gelation is in fact not the fraction of CNC, but the concentration of counterions in the solution. This suggests that the gelation is more complex than direct percolation between individual CNC rods, and instead is related to loss of colloidal stability due to reduced electrostatic screening. I also show that the behavior of key parameters, such as the period of the helical modulation, so-called pitch, that is characteristic of the cholesteric phase, is very different in the range of phase coexistence compared to the range of complete liquid crystallinity. In addition, I found that the dependence of the pitch on CNC mass fraction has less to do with the size of the nanorods but rather than with the variation of effective volume fraction as a result of more rods in the suspension or higher counterion concentration. I corroborate this hypothesis by adding different amounts of salt to CNC suspensions of varying mass fraction such that the ion concentration is held constant, thereby tuning the pitch to the same value throughout the suspensions. In films prepared by drying CNC suspensions, the pitch can go down to a few hundred nanome- ters, resulting in circularly polarized colorful Bragg re ection of visible light. By working with the long-rod fraction we can absolutely obtain a highly-ordered monodomain structure that results in uniform color of films, with only one circular polarization re ected, as should be the case. While the study is carried out on CNCs, the implications go far beyond this particular nanoma- terial, revealing new challenges and opportunities in general liquid crystal and colloid physics, as well as in strategic research where fractionation and the drying of initially disperse populations of nanorods is desirable. [less ▲]

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See detailSecond-principles methods for large-scale simulations of realistic functional oxides
Escorihuela Sayalero, Carlos UL

Doctoral thesis (2019)

The application of Condensed Matter theory via simulation has been over the last decades a solid approach to research in Materials Science. In particular for the case of Perovskite materials the research ... [more ▼]

The application of Condensed Matter theory via simulation has been over the last decades a solid approach to research in Materials Science. In particular for the case of Perovskite materials the research has been extensive, and customarily (but not only) performed using Density Functional Theory. The collective effort to develop lighter simulation techniques and exploring different theoretical approaches to computationally study materials has provided the scientific community with the possibility to strengthen the interaction between experimental and theoretical research. However, the access to large-scale simulations is still nowadays limited due to the high computational cost of such simulations. In 2013 J. C. Wojdel et al. presented a theory of modelization of crystals known as second-principles models, and which are the central point of the development of my work. In this Thesis I develop in depth a novel methodology to produce second-principles models efficiently and in a quasi-automatic way from Density Functional Theory data. The scheme presented here identifies, given a set of reliable data to be fit, the most relevant atomic couplings of a system. The fitting process that I present is also analytical, which translates into a fast and accurate model production. I also explore the modelization of chemically inhomogeneous or nanostructured systems using second-principles models. Moreover, I present a heuristic procedure to produce models of the inhomogeneous material which is efficient and sound. Finally, I also show examples of complex problems that can be tackled thanks to the second-principles models, such as the character of 180º anti-phase domain walls in SrTiO3, thermodynamical studies of heat transport across 180º domain walls in PbTiO3 and the reproduction of experimentally-observed polarization vortices in (PbTiO3)n/(SrTiO3)n superlattices. [less ▲]

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See detailMathematical Histopathology and Systems Pharmacology of Melanoma
Albrecht, Marco UL

Doctoral thesis (2019)

Treated metastatic melanoma often becomes resistant and relapses whereby resistance mechanisms can be found at the level of biochemical, histological, and pharmacological data. By using this data in a ... [more ▼]

Treated metastatic melanoma often becomes resistant and relapses whereby resistance mechanisms can be found at the level of biochemical, histological, and pharmacological data. By using this data in a mathematical form, an integrative understanding of tumour progression can be gained that reveal the functionality of more complex and hidden recurrence mechanisms. The aims of this thesis were - to investigate how a new engineering concept on tumour growth, based on porous media theory, can be leveraged to support medicine and cancer biology research, - to identify suitable tests for cancer growth model validation, - to study how elements of biochemical cancer pathways are linked to the elements of physical growth, and - to establish a pharmacokinetics module for the melanoma cancer drug dabrafenib. The studied engineering concept is qualitatively suitable to represent late-stage metastatic melanoma in irregular fibrous tissue types, whereby all equations are tested for biological relevance and parametrisation. The framework allows modelling of tissue-specific growth, and the thesis shows that the simulated tumour can shift between compact growth with ECM displacement and invasive growth with ECM circumvention as a consequence of cell plasticity/viscosity change. This is unique among continuous models of tumour growth. However, the investigation also shows that the pressure-saturation relationships are not biologically motivated and can be replaced by a swelling polymer model which captures the water absorbing effect of glycans. The thesis addresses a biologically and computationally reasonable strategy to validate the tumour growth model as complete as possible. A suitable way to validate a part of the tumour growth model is using time course data of spheroid growth in hydrogels of different stiffness values. Spheroids generated from the LU451 melanoma cell line mainly grow due to ECM degradation, have a time-variant growth rate increasing with gel rigidity, and the confined environment renders the melanoma cell line drug-resistant upon dabrafenib dose escalation. This setting reveals the interplay between mechanical and biochemical development over time. The dependency between biological elements of cancer pathways and the mechanical elements of the engineering concept on tumour growth were clarified. Therefore, the literature on mechanoregulation has been reviewed and serves as a computational link between systems biology and physical oncology. Finally, the thesis provides preliminary steps and a concept toward a serious interdisciplinary methodology to understand tumour growth, although this cannot be considered a final model for any of the known melanoma growth settings. Additionally, the thesis provides a novel quantitative systems pharmacology approach to consider liver-enzyme-induction and drug-drug-interaction. The finding is that the potent dabrafenib metabolite desmethyl-dabrafenib accumulates with consequential efficacy loss in a confined tumour environment. [less ▲]

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See detailTrading Zones of Digital History
Kemman, Max Jonathan UL

Doctoral thesis (2019)

As long as there have been computers, there have been scholars pulling at historians, challenging them to use these computers for historical research. Yet what role computers can have in historical ... [more ▼]

As long as there have been computers, there have been scholars pulling at historians, challenging them to use these computers for historical research. Yet what role computers can have in historical research is a matter of continuous debate. Under the signifier of “digital history”, historians have experimented with tools, concepts, and methods from other disciplines, mostly computer science and computational linguistics, to benefit the historical discipline. The collaborations that emerge through these experiments can be characterised as a two-sided uncertainty: historians uncertain how they as historians should use digital methods, and computational experts uncertain how digital methods should work with historical data sets. The opportunity that arises from these uncertainties is that historians and computational experts need to negotiate the methods and concepts under development. In this thesis, I investigate these negotiations as trading zones, as local spaces of negotiation. These negotiations are characterised as a duality of boundary practices. First, boundary crossing, the crossing of boundaries of disciplines, discourses, and institutions to collaborate. Second, boundary construction, the establishment of boundaries of groups and communities to preserve disciplinary values and remain recognisable as part of a community of practice. How boundary crossing and construction are balanced, whether disciplinary boundaries are shifted, and to what extent historians’ practices are transformed by continued interaction with computational experts, are open questions demanding closer scrutiny. These considerations lead to the research question underlying this thesis: how are historians affected by interactions with computational experts in the context of digital history collaborations? I investigate this question through a mixed-methods, multi-sited ethnographic approach, consisting of an open online survey which received 173 responses, 4.5 years of observations at the University of Luxembourg, 37 interviews, and an LDA topic modelling analysis of 10,918 blog posts from 73 historians between 2008-2017. Through these approaches, I examine trading zones as configured by three different dimensions. First, connectedness, the extent to which collaborators connect with one another through physical proximity, communication, and the sharing of practices. Second, power asymmetry, the extent to which participants shape their own field of action as well as the fields of action of their collaborators. Third, cultural maintenance, the extent to which collaborators become more alike or stay apart by adopting new practices or displacing previous practices. On a macro level, referring to the global historical discipline, I conclude that methodological approaches developed in local trading zones have hardly diffused to macro solutions. Insofar digital infrastructures were appropriated in the macro community, these were aligned with traditional practices. Rather than transforming historical scholarship, the challenge was to provide infrastructures congruent with existing values and practices. On a meso level, referring to the historians engaged in digital history trading zones, I conclude that the effect of interactions was dependent on individual decisions and incentives. Some historians experimented with or adopted computational practices and concepts. Yet other historians detached their work from the shared objective of a collaboration in order to reduce risks, as well as to maintain disciplinary practices. The majority of participants in trading zones were scholars from the humanities, physically distant from collaborators, communicating more often with disciplinary peers than with cross-disciplinary collaborators. As such, even when participating in trading zones of digital history, a significant number of historians remained aligned with traditional practices. Changing practices were regularly not in the direction of computational practices, but to incentives of politics or funding. While historians that participated in digital history trading zones therefore did learn new practices, this did not entail a computational transformation of their scholarship. Finally, on a micro level, some historians chose to engage intensively with computational experts. I call these individuals digital history brokers, who exemplified significant shifts in practices. Brokers conducted project management; coordinated practices from archival and library domains such as data collection, transformation, and description; learned about the potential and limitations of computational technologies and where to apply these; employed inter-languages to translate between the different collaborating domains; and finally transformed historical questions into infrastructural problems. Digital history brokers thereby not only developed interactional expertise to collaborate with computational experts. They furthermore developed political proficiency to negotiate the socio- economic potential of digital history strategies with politics, university administrators, and funding agencies. I therefore describe the practices of brokers as infrastructuring, covering a duality of negotiations. First, cross-disciplinary socio-technical negotiations with computational experts how to support scholarly practices with digital technology. Second, intra-disciplinary socio-political negotiations how to diffuse those practices within the community of practice. Digital history brokers therefore transform their own practices, so that other historians do not have to on meso or macro levels, but can employ digitised sources and digital methodology through infrastructures in a fashion that naturally fits into their practices as historians. I thereby provide a critical view on digital history grounded in how it is conducted and negotiated. This thesis is therefore aimed mainly at scholars interested in digital history and its relation to the historical discipline and to digital humanities, as well as scholars interested in studying digital history as a specific case of cross-disciplinarity. [less ▲]

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See detailThe Effect of ATP INDUCED CALCIUM DYNAMICS ON EPITHELIAL TO MESENCHYMAL TRANSITIONS
Grzyb, Kamil UL

Doctoral thesis (2019)

Cells respond to a multitude of external triggers by a limited number of signaling pathways activated by receptors on plasma membrane, such as receptor tyrosine kinases (RTKs) or G protein-coupled ... [more ▼]

Cells respond to a multitude of external triggers by a limited number of signaling pathways activated by receptors on plasma membrane, such as receptor tyrosine kinases (RTKs) or G protein-coupled receptors (GPCRs). These pathways do not simply convey the downstream signal, but instead the signal is very often processed by encoding and integrated with the current state of the cell. A traditional transcriptional analysis tends to provide an averaged output measured in a population, what often masks the behavior of individual cells. However, with recent single cell techniques developments, it is possible to investigate transcription in individual living cells. This contributed tremendously to the understanding of development and progression of many diseases including cancer. The more we understand about this high complexity of signaling mechanisms and multitude of cellular safety countermeasures, the more we see cancer as a microevolution state of “rebellious cells” (cells entering the fate opposite to the one intended) following a patch through a discreet system. This thesis specifically focused on the temporal aspect of signaling in the context of the epithelia-to-mensenchymal transition (EMT) by combining single cell experiments and bioinformatics analysis. We investigated cellular signaling changes in response to different dynamical profiles of the stimuli. In particular, we used the HMLER cell line, which is a metastatic breast cancer model for the epithelial to mesenchymal transition. By applying stochastic or oscillatory pulses of extracellular ATP-induced Ca2+ signals with different interspike intervals, we were investigating different transcription states from those evoked by constant ATP-induced Ca2+ dose responses. In order to precisely apply those stimulation profiles, we have developed and established a perfusion system. This device allows to treat population of cells simultaneously with the exact same dynamical profiles. Cells treated by these well controlled signals were subsequently processed by the single cell RNA-seq technique Drop-seq for transcriptional analysis. The resulting high dimensional digital gene expression matrices were analyzed by a developed high-throughput computational analysis pipeline. This analysis includes the identification of differentially expressed genes and cellular clusters (states) by dimensionality reduction methods (PCA, t-SNE) and pathway analysis. We evaluated changes and trends of genes from difference dynamical profiles by investigating their involvement in stress, stemness and regulation of motility. First, we confirmed that oscillatory stimulation with extracellular ATP (eATP) tends to lower the burden of cellular stress and apoptosis related pathways while maintaining its other effector functions compared to constant eATP stimulation. Interestingly, stochastic spiking of extracellular ATP in our setup led to a massive (~80%) increase in overall differential gene expression compared to deterministic oscillatory stimulation with the same period. Consequentially, stochastic signaling seems to activate a much wider range of biological pathways, which indicates the much higher complexity in information processing capability of producing rebellious cells during cancer progression and metastasis. On the other hand, our findings suggests that oscillatory eATP stimulation could contribute to EMT by lowering ID3 expression compared to stochastic stimulation where we observed a stronger upregulation of IRS2. Finally, we integrated the DEGs into biological processes involved in each conditions and put these new insights into the context of the eATP-induced Ca2+ induced epithelial to mesenchymal transition. Overall, this thesis has applied recent single cell technologies to characterize underlying principles of cellular heterogeneity induced by cell signaling and specifically investigated the complex mechanisms of cell fate in the context of EMT [less ▲]

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See detailModeling CLN3 and ATP13A2 deficiency in yeast and zebrafish and use of the ATP13A2 models for drug repurposing
Heins Marroquin, Ursula UL

Doctoral thesis (2019)

Neuronal ceroid lipofuscinoses (NCL) are a heterogeneous group of inherited recessive neurodegenerative disorders that appear during childhood and result in premature death. Nowadays, mutations in 14 ... [more ▼]

Neuronal ceroid lipofuscinoses (NCL) are a heterogeneous group of inherited recessive neurodegenerative disorders that appear during childhood and result in premature death. Nowadays, mutations in 14 genes are known to cause NCL and this project focused on CLN3 and ATP13A2 (CLN12), two genes linked to a juvenile form of NCL (JNCL). Mutations in CLN12 are known to cause two additional rare neurodegenerative disorders called Kufor-Rakeb syndrome and spastic paraplegia- 78. Since the number of people affected with a rare disease is relatively small and the cost of the drug development process is high, the chance for a patient to get therapeutic treatment is very low. Therefore, the aim of this PhD project was to develop a new drug screening pipeline for the identification of drug candidates that could be used for the treatment of some of these rare diseases. In this work, we successfully developed a phenotypic high-throughput assay based on a decreased zinc resistance phenotype in an ATP13A2-deficient yeast model and we screened more than 2500 compounds, resulting in the identification of 11 hits. Subsequently, we created a stable ATP13A2 knockout line in zebrafish and developed a validation platform based on decreased manganese resistance in this line. Using this approach, N-acetylcysteine and furaltadone emerged as promising compounds for follow-up studies. A similar strategy could not be implemented for CLN3, due to failure, despite extensive efforts, to find a suitable phenotype in yeast for a drug screening. Nevertheless, we successfully created two stable cln3 mutant lines in zebrafish. No overt phenotype was initially observed, but behavioral tests suggested that cln3 mutants display subtle neurological dysfunction, making them more susceptible to treatment with picrotoxin, a pro-convulsive drug. Further investigation is needed, but our preliminary data indicate that cln3 mutant larvae may recapitulate certain aspects of JNCL pathology. On the whole, this work provides a time- and cost-efficient pipeline for the discovery of drugs against ATP13A2 deficiencies, which can be applied for the screening of larger compound libraries in the future. In addition, we generated a new CLN3 disease model in zebrafish that will be instrumental for the development of drug screens and also may help to elucidate the molecular disease mechanism of JNCL. [less ▲]

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See detailNumerical analysis of gait load distribution in the human pelvis and design of a biomechanical testing device: experimental assessment of two implants for anterior fragility fractures
Ricci, Pierre-Louis UL

Doctoral thesis (2019)

The current project research was conducted at the University of Luxembourg in cooperation with orthopaedic surgeons from the Centre Hospitalier de Luxembourg and the Universitätsklinikum des Saarlandes ... [more ▼]

The current project research was conducted at the University of Luxembourg in cooperation with orthopaedic surgeons from the Centre Hospitalier de Luxembourg and the Universitätsklinikum des Saarlandes. The main objective was to investigate the gait load distribution in the human pelvis and the influence of the stiffness of the pubic symphysis and the sacroiliac joints on this force transmission in order to numerically and experimentally assess the stability provided by two reconstruction systems for anterior fragility fractures. To begin with, the global approach consisted in combining inverse dynamics and finite element methods to investigate physiological loadings applied to the pelvis during the gait cycle. Then, an experimental test bench was designed to reproduce those gait conditions on artificial pelvises for biomechanical assessment of different systems used for fragility fractures of the pelvis. At first, muscles forces and joint contact forces from the gait applied to the pelvis were calculated by inverse dynamics with an experimentally validated musculoskeletal model. Implementation in a finite element model including bones and joints of the pelvis highlighted that superior rami experience the highest stresses. Fracture of a superior ramus changed the initial load distribution by increasing the stresses at the inferior ramus and on the posterior structures. Combination of superior and inferior rami fractures on the same side redirected the forces backwards and showed high stresses on the sacral alae where compression fractures are commonly seen clinically. Reconstruction devices showed differences in stability at early stage of healing with benefits provided by the iliopubic subcutaneous plate. No noticeable differences compared to the Supra-Acetabular External Fixator were seen during later healing. Regarding the influence of the joint stiffness on the load distribution in a healthy pelvis, an increase of PS stiffness redirected loads to the anterior pelvis whereas an increase of PS laxity redirected loads to the posterior structures. A fusion of the sacroiliac joints did not show noticeable changes in the normal load distribution. Following the computational investigation, an experimental test bench was designed with numerical engineering tools. The biomechanical setup aimed at reproducing loadings observed during previously studied moments of the gait on artificial pelvises with fused joints. Static loadings and cyclic loadings were performed on artificial pelvises with and without reconstruction devices: first with a superior ramus fracture only and then with superior and inferior rami fractures. The Supra-Acetabular External Fixator and the iliopubic subcutaneous plate did not show any significant stability difference when a superior ramus fracture is considered. When including the inferior ramus fracture on the same side, the iliopubic subcutaneous plate significantly improved the stability of the reconstructed pelvis by reducing IV the displacement of the superior fracture, contrary to the Supra-Acetabular External Fixator that did not show any improvement. For both configurations, no fatigue phenomenon was observed during cyclic loadings simulating four days of walking for a patient (5 000 cycles). There is no conflict of interest related to this work. [less ▲]

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See detailDesign and Cryptanalysis of Symmetric-Key Algorithms in Black and White-box Models
Udovenko, Aleksei Nikolaevich UL

Doctoral thesis (2019)

Cryptography studies secure communications. In symmetric-key cryptography, the communicating parties have a shared secret key which allows both to encrypt and decrypt messages. The encryption schemes used ... [more ▼]

Cryptography studies secure communications. In symmetric-key cryptography, the communicating parties have a shared secret key which allows both to encrypt and decrypt messages. The encryption schemes used are very efficient but have no rigorous security proof. In order to design a symmetric-key primitive, one has to ensure that the primitive is secure at least against known attacks. During 4 years of my doctoral studies at the University of Luxembourg under the supervision of Prof. Alex Biryukov, I studied symmetric-key cryptography and contributed to several of its topics. Part I is about the structural and decomposition cryptanalysis. This type of cryptanalysis aims to exploit properties of the algorithmic structure of a cryptographic function. The first goal is to distinguish a function with a particular structure from random, structure-less functions. The second goal is to recover components of the structure in order to obtain a decomposition of the function. Decomposition attacks are also used to uncover secret structures of S-Boxes, cryptographic functions over small domains. In this part, I describe structural and decomposition cryptanalysis of the Feistel Network structure, decompositions of the S-Box used in the recent Russian cryptographic standard, and a decomposition of the only known APN permutation in even dimension. Part II is about the invariant-based cryptanalysis. This method became recently an active research topic. It happened mainly due to recent extreme cryptographic designs, which turned out to be vulnerable to this cryptanalysis method. In this part, I describe an invariant-based analysis of NORX, an authenticated cipher. Further, I show a theoretical study of linear layers that preserve low-degree invariants of a particular form used in the recent attacks on block ciphers. Part III is about the white-box cryptography. In the white-box model, an adversary has full access to the cryptographic implementation, which in particular may contain a secret key. The possibility of creating implementations of symmetric-key primitives secure in this model is a long-standing open question. Such implementations have many applications in industry; in particular, in mobile payment systems. In this part, I study the possibility of applying masking, a side-channel countermeasure, to protect white-box implementations. I describe several attacks on direct application of masking and provide a provably-secure countermeasure against a strong class of the attacks. Part IV is about the design of symmetric-key primitives. I contributed to design of the block cipher family SPARX and to the design of a suite of cryptographic algorithms, which includes the cryptographic permutation family SPARKLE, the cryptographic hash function family ESCH, and the authenticated encryption family SCHWAEMM. In this part, I describe the security analysis that I made for these designs. [less ▲]

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See detailLe Droit de la Coopération Décentralisée au Mali: Une Approche Juridique du Droit Administratif International
Diallo, Mory UL

Doctoral thesis (2019)

Le droit des collectivités territoriales autorise un grand nombre de types de coopération allant du jumelage à la forme contractuelle ou conventionnelle. Parmi ceux-ci, la coopération décentralisée occupe ... [more ▼]

Le droit des collectivités territoriales autorise un grand nombre de types de coopération allant du jumelage à la forme contractuelle ou conventionnelle. Parmi ceux-ci, la coopération décentralisée occupe une place déterminante. Elle concerne toutes les actions extérieures effectuées par les collectivités territoriales. Cependant, cette coopération décentralisée des collectivités territoriales maliennes demeure toujours subtile .Le concept manque encore de précision, ce qui provoque une confusion dans sa compréhension par les élus et les agents des collectivités territoriales à la recherche de solution aux multiples questionnements sur le régime juridique de ces conventions. Si le législateur a tenté de règlementer la compétence, il reste muet toujours sur le régime juridique. Ces accords de coopération décentralisée semblent n’appartenir à aucune catégorie juridique précise. Dans l’optique de la détermination d’un droit, nous avons tenté de prendre les considérations des exigences du droit interne et du droit international. Dans un premier temps, l’étude s’intéresse aux questions relatives à l’élaboration du régime de la coopération décentralisée. Elle fait ressortir les fondements légaux nationaux et internationaux ainsi que la qualification de ces accords. Dans un second temps, l’étude s’intéresse aux problèmes de la mise en œuvre des conventions de coopération décentralisée dont l’objectif est de démontrer le caractère exécutoire des conventions de coopération ainsi que les différentes alternatives de résolution du contentieux. Enfin, l’objet de cette thèse tente de préciser le régime juridique des conventions conclues entre les collectivités territoriales maliennes et leurs partenaires étrangers dans la perspective de privilégier le droit administratif local à caractère international [less ▲]

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See detailEntwicklung eines intelligenten, robotergestützten Assistenzsystems für die Demontage industrieller Produkte
Jungbluth, Jan UL

Doctoral thesis (2019)

Technical assistance systems are used in many aspects of our private environment to simplify our daily lives. Such assistance would also be desirable in our working environment, especially in physically ... [more ▼]

Technical assistance systems are used in many aspects of our private environment to simplify our daily lives. Such assistance would also be desirable in our working environment, especially in physically demanding activities such as dismantling products for maintenance, corrective maintenance, or remanufacturing. However, the use of robot-supported assistance systems is prevented by the imponderabilities in the dismantling process of different products due to the lack of autonomy of the technical systems. In the course of this dissertation, the development of intelligent, robot-supported assistance systems that can support people in such complex processes in a target-oriented manner are considered, and the following research question is posed: What are the technical requirements for such assistance systems and how can they be implemented? In the reviewed scientific literature, no holistic approach has been identified for the development of these systems, but many approaches to partial aspects of such a system have been collected across several research disciplines. In order to address the research question, this dissertation discusses the theoretical fields of technical assistance systems, human-robot systems, and the field of application in order to define technical requirements. A demonstrator for experimental validation is implemented in the form of a multi-agent system in which various technical systems are integrated and interconnected by software. The function of the developed robot-based assistance system could be verified in concrete dismantling processes in conjunction with suitable man-machine communication interfaces. Finally, this dissertation identifies further research questions that must be addressed before such systems can be introduced in the industrial environment. [less ▲]

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See detailLegal Design for the General Data Protection Regulation. A Methodology for the Visualization and Communication of Legal Concepts
Rossi, Arianna UL

Doctoral thesis (2019)

Privacy policies are known to be impenetrable, lengthy, tedious texts that are hardly read and poorly understood. Therefore, the General Data Protection Regulation (GDPR) introduces provisions to enhance ... [more ▼]

Privacy policies are known to be impenetrable, lengthy, tedious texts that are hardly read and poorly understood. Therefore, the General Data Protection Regulation (GDPR) introduces provisions to enhance the transparency of such documents and suggests icons as visual elements to provide “in an easily visible, intelligible and clearly legible manner a meaningful overview of the intended processing.” The present dissertation discusses how design, and in particular legal design, can support the concrete implementation of the GDPR’s transparency obligation. Notwithstanding the many benefits that visual communication demonstrably provides, graphical elements do not improve comprehension per se. Research on graphical symbols for legal concepts is still scarce, while both the creation and consequent evaluation of icons depicting abstract or unfamiliar concepts represent a challenge. More- over, precision of representation can support the individuals’ sense-making of the meaning of graphical symbols, but at the expense of simplicity and us- ability. Hence, this research proposed a methodology that combines semantic web technologies with principles of semiotics and ergonomics, and empirical methods drawn from the emerging discipline of legal design, that was used to create and evaluate DaPIS, the Data Protection Icon Set meant to support the data subjects’ navigation of privacy policies. The icon set is modeled on PrOnto, an ontological representation of the GDPR, and is organized around its core modules: personal data, roles and agents, processing operations, processing purposes, legal bases, and data subjects’ rights. In combination with the description of a privacy policy in the legal standard XML Akoma Ntoso, such an approach makes the icons machine-readable and semi-automatically retrievable. Icons can thus serve as information markers in lengthy privacy statements and support the navigation of the text by the data subject. [less ▲]

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See detailThe Phenomenon of Online Live-Streaming of Child Sexual Abuse: Challenges and Legal Responses
Dushi, Desara UL

Doctoral thesis (2019)

In the recent years, the importance of Internet in the education of children all over the world has grown enormously. But as every other phenomenon, the easy access to the Internet creates a great number ... [more ▼]

In the recent years, the importance of Internet in the education of children all over the world has grown enormously. But as every other phenomenon, the easy access to the Internet creates a great number of concerns that should not be neglected. Over the past two decades, the internet has become a new medium through which child exploitation and sexual abuse happens. Technology is being used not only as a means of committing old forms of sexual abuse and exploitation of children, but also for creating new ones. This variety of crime types ranges from child pornography, sexting and sextortion to online grooming, and live- streaming of child abuse. This dissertation focuses on a very current, fast developing, and not very explored topic, the phenomenon of live-streaming of child abuse. The research includes a perspective of (public) international law, the situation in Europe due to the activities of the Council of Europe and the EU and also a “reality” test with two legal system approaches, Italy and England & Wales, on how to handle online child sexual abuse material and more specifically live-streaming of such abuses. On the basis of this observation, the main objective is to critically analyze the status quo of existing framework in the area of online child sexual abuse and exploitation in order to find out how flexible it is to be applied to this specific crime, if it can be applied, and how can it be improved in order to better respond to this new global reality. Based on all of this I draw conclusions over the insufficiency of existing framework to cover the crime of live-streaming of child abuse and plead for filling the legal lacunae by extending specific criminal provisions -ideally harmonized on an international level- specially made to tackle this crime. [less ▲]

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See detailStress - modulated bulk photovoltaic effect in polar oxide crystals
Nadupalli, Shankari UL

Doctoral thesis (2019)

Light-induced phenomena in ferroelectric materials have been exploited for decades for optoelectronic applications. Homogeneous illumination of a non-centrosymmetric ferroelectric material creates ... [more ▼]

Light-induced phenomena in ferroelectric materials have been exploited for decades for optoelectronic applications. Homogeneous illumination of a non-centrosymmetric ferroelectric material creates anomalously high voltages exceeding a value which is usually limited by its band gap. This phenomenon is called the bulk-photovoltaic effect (BPVE). Lithium niobate is a prototypical material for BPVE. The only limiting factor in lithium niobate is its low photo-current values, which can be improved by doping the crystal with donor metals. This study focuses primarily on light induced processes in mono-domain lithium niobate single crystals doped with transition metal ions, particularly the influence of stress on the BPVE. The effect of stress on BPVE is termed the piezo-photovoltaic effect (PPVE). This thesis report is framed to systemically introduce topics which cause, influence and aid in understanding the PPVE. Topics such as the symmetry in crystals, their physical properties, the intrinsic bulk photovoltaic effect (BPVE) are introduced and the structure, defects, light-induced charge transport in donor doped lithium niobate and the reason behind the appearance of BPVE are discussed in this report. The techniques and experimental arrangements used in this work are detailed in this thesis. A direct evidence of BPVE and the influence of stress is shown in the results. Transition metal doped lithium niobate crystals are oriented via x-ray diffraction (XRD) and a basic chemical characterization is undertaken using secondary ion mass spectrometry (SIMS) to identify dopant elements. Absorption spectroscopy in the UV/VIS/NIR range revealed windows in the spectra indicating photo-excitation of the donor doped ions. The absorption lines show that a shift in the fundamental band-edge occurs in lithium niobate for different dopant elements. Electron paramagnetic resonance (EPR) spectrometry is performed on the samples to confirm the location of the dopant ion in the crystal matrix by indicating its symmetry. The difference in the dopant concentration and the change in the oxidation state of the dopant ion under light illumination is obtained from EPR study. Direct measurements to obtain bulk photovoltaic current density in iron doped- lithium niobate single crystals are performed at increasing intensities at different wavelengths to determine the BPV coefficients. This study provides a quantitative analysis of different components of the BPV tensor values. The highest BPV component measured along the polar axis with extraordinary light polarisation is observed when iron doped lithium niobate is illuminated with light wavelength 450 nm. Obtained BPV tensor components are corroborated by the influence of the structural environment and the dipole interactions on charge transport mechanism of BPVE. The charge transport mechanism and the obtained values of the BPV tensor components are justified and discussed on the basis of the polaronic charge transport phenomena existing in the literature. The influence of stress on BPVE is measured using a custom-designed set-up. The PPV components in lithium niobate are experimentally investigated for stress levels in the 1MPa - 10MPa range. A detailed discussion on the experimental observations are given in this report. The prime discovery of this thesis is the intrinsic character of the piezo-photovoltaic effect (PPVE), where increase in the light induced current is observed when the crystal is subjected to uniaxial compressive stress. The Young's modulus of lithium niobate is 202 GPa. Applying 10 MPa compressive stress translates to strain levels of just 50 ppm. 10 MPa of compressive stress along the polar axis of the crystal increased the short-circuit photo-current by 73%. When stress is applied perpendicular to the polar axis, about 370% increase in short-circuit photocurrent was observed with just 50 ppm of strain, which is a drastic for such moderate amounts of stress levels. This study proves the vitality of strain tuning to increase the PV properties in crystalline solar cells. Extrapolating the observed effect, PPVE is envisioned as a phenomenon which could be exploited in other polar oxide ceramics and thin-films where large photovoltaic energy generation can be made possible beating the existing limits. [less ▲]

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See detailTiming-aware Model Based Design with Application to Automotive Embedded Systems
Sundharam, Sakthivel Manikandan UL

Doctoral thesis (2019)

Cyber-Physical System (CPS) are systems piloting physical processes which have become an integral part of our daily life. We use them for many purposes: transportation (cars, planes, trains), space ... [more ▼]

Cyber-Physical System (CPS) are systems piloting physical processes which have become an integral part of our daily life. We use them for many purposes: transportation (cars, planes, trains), space (satellite, spacecrafts), medical application, robotics, energy management, home appliance, manufacturing, and so many other applications. Model-Driven Engineering (MDE) is widely applied in the industry to develop new software functions and integrate them into the existing run-time environment of a Cyber-Physical System (CPS), for instance, the control software for automotive engines, which are deployed on modern multi-core hardware architectures. Such an engine control system consists of different sub-systems, ranging from an air system to the exhaust system. Each of these sub-systems, again, consists of software functions which are necessary to read from the sensors and write to the actuators. In this setting, MBD provides indispensable means to model and implement the desired functionality, and to validate the functional, the non-functional, and in particular the real-time behavior against the requirements. Current industrial practice in model-based development completely relies on generative MBD, i.e., on code generation to bridge the gap between model and implementation. An alternative approach, although not yet used in the automotive domain is model interpretation. In this thesis, in the place of code generation, we investigate the applicability of model interpretation to automotive software development with a help of a control function design. We present the benefits compared to the existing code-generation practice. The control laws of these software functions typically assume deterministic sampling rates and constant delays from input to output. However, on the target processors, the execution times of the software will depend on many factors such as the amount of interferences from other tasks, resulting in varying delays from sensing to actuating. The literature approaches support the simulation of control algorithms, but not their actual implementation. Further in the thesis, we present the CPAL model interpretation engine running in a co-simulation environment to study control performances while taking the run-time delays into account. The main advantage is that the model developed for simulation can be re-used on the target processors. Additionally, the simulations performed at design phase can be made realistic in the timing dimension through the use of timing annotations inserted in the models to capture the delays on the actual hardware. Introspection features natively available facilitate the implementation of self-adaptive and fault-tolerance strategies to mitigate and compensate the run-time latencies. Experiments on controller tasks with injected delays show that our approach is on-par with the existing techniques with respect to simulation. We then discuss the main benefits of our development approach which are the support for rapid-prototyping and the re-use of the simulation model at run-time, resulting in productivity and quality gains. As the processing power is increasingly available with today's hardware, other concerns than execution performance such as simplicity and predictability become important factors towards functional safety objective. The motivation towards predictable execution behavior, we revisited FIFO scheduling with o set and strictly periodic task activations. The execution order in this case is uniquely and statically determined. This means that whatever the execution platform and the task execution times, be it in simulation mode in a design environment or at run-time on the actual target, the task execution order will remain identical. Beyond the task execution order, the reading and writing events that can be observed outside the tasks occur in the same order. This property, leveraged by our MBD environment CPAL design flow provides a form of timing equivalent behavior between development phase and run-time phase which eases the implementation of the application and the verification of its timing correctness. Thus, the proposed development environment facilitates where also the non-experts are able to quickly model and deploy complex embedded systems without having to master real-time scheduling and resource-sharing protocols. In practice, the design of a software component involves designers from various viewpoints such as control theory, software engineering, safety, etc. In practice, while a designer from one discipline focuses on the core aspects of the field, he / she neglects or considers less importantly the other engineering aspects (for instance, real-time software engineering or energy efficiency). This may cause some of the functional and non-functional requirements not to be met satisfactorily. In the thesis, we present a model-driven co-design framework based on the timing tolerance contract to address such design gaps between control and real-time software engineering. The framework consists of three steps: controller design, verified by jitter margin analysis along with co-simulation, software design veri fied by a novel schedulability analysis, and the run-time verification by monitoring the execution of the models on target. This framework builds on earlier mentioned CPAL design environment, which enforces a timing-realistic behavior in simulation through timing and scheduling annotations. Through various case studies, we show that our tool enables not only to automate the analysis process at design time but also to enhance the design process by systematically combining models and analyses. [less ▲]

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See detailThe cause of interface recombination in Cu-rich CIS thin film solar cells
Elanzeery, Hossam UL

Doctoral thesis (2019)

Cu(In,Ga)Se2 (CIGS) thin film solar cells are considered one of the most promising thin film technologies reaching efficiencies beyond 22 %. The record efficiencies for CIGS thin film solar cells are ... [more ▼]

Cu(In,Ga)Se2 (CIGS) thin film solar cells are considered one of the most promising thin film technologies reaching efficiencies beyond 22 %. The record efficiencies for CIGS thin film solar cells are based on CIGS absorbers grown under Cu-deficiency conditions. CIGS absorbers grown under Cu-excess (Cu-rich) show larger grains and better transport properties compared to CIGS absorbers grown under Cu-deficiency (Cu-poor) conditions. However, solar cells based on Cu-rich CIGS absorbers suffer from significantly lower efficiencies compared to Cu-poor CIGS solar cells. The lower efficiency of Cu-rich CIGS solar cells compared to Cu-poor CIGS cells is attributed to lower open circuit voltage (VOC) in Cu-rich CIGS cells compared to Cu-poor CIGS cells. The reason behind the lower VOC values was investigated and was attributed to recombination losses at the absorber/buffer interface and higher doping of Cu-rich CIGS cells compared to Cu-poor CIGS cells but the complete picture behind the origin of these interface recombination losses and high doping in Cu-rich CIGS cells was not fully understood. The work of this thesis explains why Cu-rich CIGS cells suffer from interface recombination losses, higher doping and lower efficiencies. This explanation is divided into three parts: The first part characterizes Cu-rich and Cu-poor solar cells of the ternary CIS and the quaternary CIGS. This part confirms that Cu-rich CI(G)S solar cells suffer from lower efficiencies, lower VOC, interface recombination losses and higher doping compared to Cu-poor CI(G)S solar cells. Moreover, a 200±20 meV defect was observed for Cu-rich CIS cells. The second part introduces different post-deposition treatments (PDTs) to Cu-rich CI(G)S cells. An ex-situ KF, in-situ KF and a Se-only PDT were introduced to Cu-rich CIS cells. All the three treatments succeeded in improving the VOC, improving the interface recombination losses, decreasing the doping and passivating the 200±20 meV defect that has been identified as a Se-related defect in Cu-rich CIS solar cells. A Ga-Se PDT was introduced to Cu-rich CIGS solar cells and successfully improved the VOC, improved the interface recombination losses and decreased the doping of Cu-rich CIGS solar cells. The third part analyses the changes observed on Cu-rich CI(G)S cells before and after the PDTs. Based on these observations, it was concluded that the origin behind both the interface recombination losses and the high doping of Cu-rich CI(G)S cells is a Se-related acceptor defect (detected by admittance measurements for Cu-rich CIS and speculated for Cu-rich CIGS). The passivation of this defect reduces the recombination losses at the absorber/buffer interface, decreases the doping, improves the VOC and consequently leads to an increase in the efficiency of Cu-rich CI(G)S solar cells. Moreover, this part shows that the Se-related defect is formed as a result of the strong etching step that is mandatory for Cu-rich CI(G)S absorbers to remove conductive copper selenide secondary phases. Applying the same strong etching conditions to Cu-poor CIS absorbers leads to the formation of the Se-related defect. After understanding that the Se-related defect is formed as a result of the strong etching conditions and that the Se-related defect can be passivated with PDTs that are rich in Se, an alternative mean of passivating this defect without PDTs was proposed. The Se-related defect was shown to be passivated using buffer layers of high enough thiourea (source of Sulphur) and without any PDTs leading to the reduction of interface recombination losses, decrease of the doping, increase of the VOC and increase of the efficiency of Cu-rich CIS cells. To conclude, the reason behind the interface recombination losses and high doping in Cu-rich CI(G)S solar cells is a Se-related acceptor defect originating after etching the absorbers with strong etching conditions. This defect can be passivated with high enough chalcogen either with PDTs (high enough Selenium) or buffer layers (high enough Sulphur). [less ▲]

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See detailPOST-PROCESS AND IN-PROCESS ANALYSIS METHODS FOR LASER WELDING OF ALUMINUM-COPPER
Schmalen, Pascal Guy UL

Doctoral thesis (2019)

Copper is well-known for excellent conductivity and corrosion resistance, whereas aluminium is known for low density and great formability. The laser joining of Al and Cu combines those properties, e.g ... [more ▼]

Copper is well-known for excellent conductivity and corrosion resistance, whereas aluminium is known for low density and great formability. The laser joining of Al and Cu combines those properties, e.g. in manufacturing of solar absorbers and wiring harnesses. Furthermore, the joining of Al and Cu is an enabler of new products, e.g. the manufacturing of battery modules, where a reliable joining process for numerous Al-Cu connections, the tabs of the Li-ion batteries, is needed. The joining of Al and Cu is considered as complex due to the formation of intermetallic compounds inside the joint, which are causing a brittle joint with increased resistance. The focus of this work is the improvement and extension of the laser welding process of Al and Cu. It was found that the determination of suitable process parameters is one of the major restrictions in the application of the process. Hence, this work deals with the analysis of methods to determine process parameters, which was performed in three main parts: o The comprehensive process understanding is one essential part to improve the joint quality. The formation of the intermetallics inside the joint is a process, which takes place in a short time frame of a few μs and a scale of few hundreds of μm. Metallographic studies were performed to gain insights into the local formation of specific intermetallic compounds. Furthermore, intensive research on etchants was combined with the information gained from a micro-XRD analysis in order to identify and localize the most critical phases. o The post–process quality measurements are the essential part to quantify and evaluate the properties of the joint and thus to adapt process parameters. Yet, the quality measurements are varying in recent literature. In this work, the mechanical, electrical and optical methods were combined with hardness measurements and metallographic studies. The methods were enhanced and it was found that especially electrical methods have a great potential to assist the determination of process parameters. o In-process analysis methods were studied to identify the potential of process monitoring of Al-Cu weld seams. It was found that the optical analysis of the vapour plume, which is formed during the keyhole welding, can be used to estimate the joint quality. Chromatic filters were used to analyse specific process radiation of Al and Cu, which contains information about the current intermixture of the joint. The investigations were carried out with a spectroscope. Concluding, it will be shown that the present work assists the choice of suitable process parameters, and thus supports the future implementation of laser technology to join Al and Cu. [less ▲]

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See detailMixed Frequency Single Receiver Architectures and Calibration Procedures for Linear and Non-Linear Vector Network Analysis
Harzheim, Thomas UL

Doctoral thesis (2019)

In this thesis several new advancements in the field of linear and non-linear vector network analysis are presented. Three distinct but interconnected topics are addressed in this work: First the concept ... [more ▼]

In this thesis several new advancements in the field of linear and non-linear vector network analysis are presented. Three distinct but interconnected topics are addressed in this work: First the concept and feasibility of the single receiver vector network analyzer (VNA) architecture and the implications for existing error models are analyzed, starting with the one-port reflectometer, through two-port unidirectional 5-term, bidirectional 10-term and finally 7-term error models. New VNA error models, which are able to capture the effects of the leaky RF receiver input wave selector switch, are derived, along with new calibration and correction procedures for this architecture. Modifications to the existing test-set architectures are introduced to reduce the effects of the leaky RF receiver input wave selector switch and shorten the required measurement time in this VNA architecture. A purpose built 275 MHz to 6000 MHz single receiver VNA system based upon commercial-of-the-shelf components is presented and analyzed. Measurements carried out with this VNA system are used in conjunction with numerical test-set and VNA simulations to verify the efficacy of the new calibration and correction methods as well as different VNA test-set architectures according to EURAMET standards and procedures. The second main topic of this thesis is the introduction of phase repeatable synthesizers as a new calibration and correction phase reference standard for non-linear VNA measurements. Due to the high output power capability of this new phase reference standard, new non-linear test-set and measurement scenarios such as the full non-linear two port characterization of high power solid-state amplifiers become possible, which were out of reach before due to low system signal-to-noise ratios provided by comb-generator based sources in this setup. The third and final topic of this thesis integrates the contents and achievements of the two previous topics to prove and verify the feasibility of VNA based harmonic, i.e. non-linear, transponder-based stepped-FMCW radar systems operating directly in the frequency domain. A new stepped-FMCW theory based on mixed-frequency S-parameters is presented in conjunction with a phase-slope based ranging procedure which avoids time-domain transformation. A complete system-analysis and modeling of the harmonic radar system including the passive transponder tag is provided. Numerous high-resolution measurements are presented and analyzed to verify the validity and accuracy of the non-linear harmonic radar equation, to evaluate illumination and harmonic return signal polarization based propagation effects in a multi-path indoor measurement scenario and to demonstrate the performance of the harmonic radar system in severe clutter situations. [less ▲]

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See detailOPTICAL ANALYSIS OF EFFICIENCY LIMITATIONS OF CU(IN,GA)SE2 GROWN UNDER COPPER EXCESS
Babbe, Finn UL

Doctoral thesis (2019)

Solar cells made from the compound semiconductor Cu(In,Ga)Se2 reach efficiencies of 22:9 % and are thus even better than multi crystalline silicon solar cells. All world records are achieved using ... [more ▼]

Solar cells made from the compound semiconductor Cu(In,Ga)Se2 reach efficiencies of 22:9 % and are thus even better than multi crystalline silicon solar cells. All world records are achieved using absorber layers with an overall copper deficient composition, but Cu-rich grown samples have multiple favourable properties. However, especially losses in the open circuit voltage limit the device performance. Within this work these efficiency limitations of chalcopyrites grown with copper excess are investigated. The work has been divided into four chapters addressing different scientific questions. (i) Do alkali treatments improve Cu-rich absorber layers? The alkali treatment, which lead to the recent improvements of the efficiency world record, is adapted to CuInSe2 samples with Cu-rich composition. The treatment leads to an improvement of the VOC which originates roughly equally from an improvement of the bulk and the removal of a defect close to the interface. The treatment also improves the VOC of Cu-poor samples. In both cases, the treatment increases the fill factor (FF) and leads to a reduction of copper content at the surface. (ii) Is the VOC limited by deep defects in Cu-rich Cu(In,Ga)Se2? A deep defect, which likely limits the VOC, is observed in photoluminescence measurements (PL) independent of a surface treatment. The defect level is proposed to originate from the second charge transition of the CuIn antisite defect (CuIn(-1/-2)). During the investigation also a peak at 0:9 eV is detected and attributed to a DA-transition involving a third acceptor situated (135 ± 10) meV above the valence band. The A3 proposed to originate from the indium vacancy (VIn). Furthermore the defect was detected in admittance measurements and in Cu(In,Ga)Se2 samples with low gallium content. (iii) Is the diode factor intrinsically higher in Cu-rich chalcopyrites? Cu-rich solar cells exhibit larger diode ideality factors which reduce the FF. A direct link between the power law exponent from intensity dependent PL measurements of absorbers and the diode factor of devices is derived and verified using Cu-poor Cu(In,Ga)Se2 samples. This optical diode factor is the same in Cu-rich and Cu-poor samples. (iv) Is the quasi Fermi level splitting (qFLs) of Cu-rich Cu(In,Ga)Se2 absorber layers comparable to Cu-poor samples? Measuring the qFLs of passivated Cu-rich and Cu-poor Cu(In,Ga)Se2 samples, on average a 120 meV lower splitting is determined for Cu-rich samples. This difference increases with gallium content and is likely linked to a defect moving deeper into the bandgap, possibly related to the second charge transition of the CuIn antisite defect. Overall, samples with Cu-rich composition are not limited by the diode factor. However, a deep defect band causes recombination lowering the qFLs and thus the VOC. This defect is not removed by alkali treatments. A key component to improve Cu-rich solar cells in the future, especially Cu(In,Ga)Se2, will be to remove or passivate this defect level. [less ▲]

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See detailConfined in a Fiber: Realizing Flexible Gas Sensors by Electrospinning Liquid Crystals
Reyes, Catherine UL

Doctoral thesis (2019)

Liquid crystalline phases (LCs) readily exhibit optical responsivity to small fluctuations in their immediate environment. By encapsulating LC phase forming compounds within polymer fibers through the ... [more ▼]

Liquid crystalline phases (LCs) readily exhibit optical responsivity to small fluctuations in their immediate environment. By encapsulating LC phase forming compounds within polymer fibers through the electrospinning process (a fiber spinning method known for being a fast way of forming chemically diverse non-woven mats), it is possible to create functionalized LC-polymer fiber mats that are responsive as well. As these fiber mats can be handled macroscopically, a usercan observe the responses of the mats macroscopically without the need for bulky electronics. This thesis presents several non-woven fiber mats that were coaxially electrospun to contain LC within their individual polymer fibers cores for use as novel volatile organic compound (VOC) sensors. The mats are flexible, lightweight, and shown to both macroscopically and microscopically respond to toluene gas. Such gas responsive mats may be incorporated into garments for visually alerting the wearer when they are exposed to harmful levels of VOCs for example. Additionally, the interaction and re-prioritization of several electrospinning variables (from the chemistry based to the processing based) for forming the LC-mats are also discussed. The balance of these variables determines whether a wide range of phenomena occur during fiber formation. For instance, unexpected phase separation between the polymer sheath solution and the LC core can mean the difference between forming fully dried fibrous mats and wet/meshed films. A chapter is devoted to discussing the impact that solvent miscibility with an LC can have on fiber production, including also the effect that water can have when condensed into the electrospinning coaxial jet. The fiber shapes that the polymer fiber sheaths adopt (beaded versus non-beaded), as well as the continuity of the LC core, will influence the visual app earance of the mats. These optical properties, in turn, influence the mats’ responsivity to gases and whether the responses can be macroscopically observed with or without additional polarizers. During two types of gas sensing experiments --mats exposed to gas when contained in a cell, and mats exposed to gas diffused in ambient air without containment, we see that not all fibers within a mat respond at the same time. Moreover, different segments of the fibers within the same non-woven mat also show slightly different rates of response due to variations in fiber thickness, LC content, and whether the fiber cores had variations in LC filling (i.e. LC director twists, and gaps). [less ▲]

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See detailDEUTSCHE SOLDATENGRÄBER DES ZWEITEN WELTKRIEGES ZWISCHEN HELDENVERHERRLICHUNG UND ZEICHEN DER VERSÖHNUNG – KULTURWISSENSCHAFTLICH-HISTORISCHE FALLSTUDIEN ZUR ENTWICKLUNG DES UMGANGES MIT DEM KRIEGSTOD
Janz, Nina UL

Doctoral thesis (2019)

Ten cultural-historical case studies investigate how deaths in war were dealt with based on soldier graves of the Second World War. In this dissertation, the resting places of the fallen German soldiers ... [more ▼]

Ten cultural-historical case studies investigate how deaths in war were dealt with based on soldier graves of the Second World War. In this dissertation, the resting places of the fallen German soldiers offer a unique perspective in the evaluation of death during a violent conflict and in the post-war period. The examination frame extends from 1939 to the present and follows the reception and importance of the graves and the fallen in military, politics and society. Some single chapters of this thesis have been already published or are intended for publication. Methodologically, the study consists of empirical work, such as the analysis of unpublished archival sources, as well as hermeneutical tools in the form of interviews, surveys, local documentation, and field studies of burial sites and exhumations. Two terms – hero glorification and signs of reconciliation – illustrate the differences in how the meaning of the graves and their dead soldiers was perceived. This difference highlights the change in values and meaning that the graves had to face. In the Second World War, the Wehrmacht responded to the nearly five million German casualties with mythical hero stories, propaganda and parades, but also with an elaborate administration system and rules concerning the dead and their graves. The instructions for the soldier’s death included details about the material and inscription of the gravestone to the identification of unknown dead. The graves sustained a structure and organization in accordance with a modern military grave system. The claim to a single grave and the registration and notification of the relatives was included in the Wehrmacht. The denotation of the dead as heroes and their resting places as heroes' graves (Heldengräber) and heroes' groves (Heldenhaine) shows the attempt to integrate them into the ideology and propaganda of the National Socialist regime. However, the management of graves, as well as the cult of heroes, had to fail due to the reality of war – i.e., the number of casualties, the chaotic conditions at the front and the defeat of the Germans. The hero's glorification could not be maintained after the end of the war. In post-war society, an attempt was made to defuse the symbolism of military death and put it into a neutral and harmless context other than National Socialism. The continuation of the graves’ management, the search for unknown resting places and the construction of cemeteries could no longer be operated by the military. Under the slogan of reconciliation and the expression of peace and understanding instead, access to the Wehrmacht graves was reached first in Western Europe, after 1989 in Eastern Europe by the Volksbund Deutsche Kriegsgräberfürsorge e.V. The Volksbund builds and cares for cemeteries and exhumes the remains until the present. This effort is still being made by the Germans today and illustrates the importance of war graves care in modern international context. The studies show how mutable and dependent are the meaning and symbolism of the death of a soldier within different political and social constructs and epochs. In these studies, the range of soldiers' graves as a research topic is clarified and further perspectives for questions and investigation contexts are shown. The investigation of German soldiers' graves of the Second World War in terms of their relevance is of particular importance. The fact that great efforts are still being made to find and maintain the resting places of dead soldiers more than 70 years after the war demonstrates the political dimension of the war dead and their graves. Above all, the distinctiveness of these objects as resting places for German soldiers makes an interesting and even controversial topic for science, politics and society not only in Germany but also in other European countries. [less ▲]

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See detailNovel Insight into the Role of the S100A8/A9 Protein Complex in the Regulation of Neutrophil Functions
Jung, Nicolas UL

Doctoral thesis (2019)

S100A8 and S100A9 are members of the S100 family of cytoplasmic EF-hand calcium-binding proteins and are abundantly expressed in the cytosol of neutrophils. Mostly found under heterodimeric form, S100A8 ... [more ▼]

S100A8 and S100A9 are members of the S100 family of cytoplasmic EF-hand calcium-binding proteins and are abundantly expressed in the cytosol of neutrophils. Mostly found under heterodimeric form, S100A8/A9 have various intracellular and extracellular functions; they act as alarmins, amplifying the host inflammatory response. Our previous study showed that the intracellular activity of S100A8/A9 is carried by the phosphorylation of S100A9. Based on these results, we further investigated the importance of this post-translational modification on the extracellular activity of the protein complex and its impact on the inflammatory functions of neutrophils. First, we analyzed the phosphorylation state of secreted S100A8/A9 and the mechanism by which the protein complex is released into the extracellular space. Our results show that S100A9 is secreted under a phosphorylated form within the S100A8/A9 protein complex and this release is highly correlated to the process of NETosis. Next, we investigated the inflammatory response of neutrophil-like dHL-60 cells when stimulated with the phosphorylated and non-phosphorylated form of S100A8/A9. Our results indicate that only the phosphorylated form of S100A8/A9 increases the expression and secretion of various cytokines (e.g. TNFa, CCL4, CXCL8). Using receptor-neutralizing antibodies, we then determined the receptor and signaling pathways associated to S100A8/A9-P-induced cytokine secretion. The reduction of expression levels of the previously mentioned cytokines, after TLR4 blocking, point out that S100A8/A9-P-induced signaling is mediated in part by TLR4. Finally, we investigated the post-transcriptional response induced by S100A8/A9-P stimulation. Using miRNA-sequencing of S100A8/A9-P stimulated dHL-60 cells, we identified an upregulation of miR-146a-5p, miR-146b-5p and miR-155-5p expression. Since these three microRNAs have previously been described to regulate TLR4 signaling at various levels, we investigated their influence on the inflammatory response mediated by S100A8/A9-P. Stable overexpression of miR-146a-5p and miR-155-5p in dHL-60 cells resulted in the reduced S100A8/A9-P-mediated secretion of cytokines through the inhibition of key players in the TLR4 signaling pathways. To summarize, our results give new insight into the pro-inflammatory functions induced by S100A8/A9-P in neutrophils and reveal the potential of the phosphorylated protein complex as a major regulator of inflammation in chronic inflammatory diseases. [less ▲]

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See detailInvestigating trust in a multilingual theatre project: Potentialities for a humanising pedagogy
Weyer, Dany UL

Doctoral thesis (2019)

Education plays a vital role in shaping social realities by promoting dialogue, solidarity, mutual understanding, and positive social interactions. However, some pedagogical approaches are believed to not ... [more ▼]

Education plays a vital role in shaping social realities by promoting dialogue, solidarity, mutual understanding, and positive social interactions. However, some pedagogical approaches are believed to not shoulder the responsibility to counter current social, economic, and political forces in Europe and beyond that present challenges in terms of social cohesion and ways of living together. This study contributes to recent debates concerning a change of dominant school practices by recognising learning and teaching as collaborative processes between teachers and students and trust as a central element in education. Despite the interest in and positive appraisal of trust in education, little attention has been paid to concrete teaching practices and strategies on how to implement trust in learning and teaching. A case study of a multilingual theatre project of a primary school class and a video ethnographic approach allowed to explore details of classroom practices, (inter-)actions, and activities. This research set out to explore four questions: (a) What are “signs of trust” in an educational context?; (b) How and in what ways can a teacher build, maintain, or strengthen trust?; (c) How and in what ways can “signs of trust” shape interactions in the classroom?; (d) How can “sings of trust” be analysed? As a result of more than 80 hours of video-recorded participant observations and interview data, the results of this investigation show that the classroom teacher continuously and consistently maintained a work environment based on six attributes of trust identified in the literature: vulnerability, benevolence, reliability, competence, honesty, and openness. Most importantly, she valued and promoted responsibility, autonomy, collaboration, and peer support. The teacher’s verbal and non-verbal trustworthy and trusting behaviour is then interpreted as the driving force behind the pupils’ engagement as active, competent, and reliable partners in all aspects of the theatre project. In fact, the pupils signalled ownership of their learning, proactively and independently engaged with the curriculum, and positively oriented towards each other’s relationships and competences. Despite the exploratory nature and small sample of participants, the findings of this study highlight that education imbued with trust offers opportunities of growth for both teachers and students. Moreover, the data suggests that the achievement and maintenance of trust can be seen as a collaborative effort involving all members of the classroom community and facilitated by a myriad of meaning-making resources (verbal, non-verbal, with objects, even a simple look in the eye or a smile). If the debate about the value of trust for all learners is to be moved forward, a better understanding of the wider impacts on personal and social lives needs to be gained. [less ▲]

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See detailADAPTIVE WAVEFORM DESIGN FRAMEWORK FOR MIMO RADAR UNDER PRACTICAL CONSTRAINTS
Hammes, Christian UL

Doctoral thesis (2019)

The recent developments in radar technology - powerful signal processors, increased modulation bandwidth and access to higher carrier frequencies - offers enhanced flexi- bility in waveform design and ... [more ▼]

The recent developments in radar technology - powerful signal processors, increased modulation bandwidth and access to higher carrier frequencies - offers enhanced flexi- bility in waveform design and receiver processing. This provides additional degrees of freedom in the signal design and processing, thereby offering additional avenues to im- plement interference mitigation. The radar environment is dynamic in general, with the inhomogeneous interference sources changing rapidly both in space and time. In this context, an adaptive waveform and adaptive receiver design for Multiple-Input-Multiple- Output (MIMO) radar system is a promising way forward towards dynamic interference mitigation. Even-though the technology offers flexibility, the need to commercialize radar elements imposes certain constraints on the platform to ensure commercial viability. In this context, the transmitted waveform has to satisfy practical design constraints imposed by the hardware including discrete phase modulation and limited number of processing chains. These coupled with the dynamic scenarios warrants a rapid signal adaptation with enhanced performance while satisfying the design constraints. Motivated by the aforementioned requirements, the thesis proposes a general framework for MIMO radar signal adaptation under practical design constraints. The transmit antennas are restricted to operate in a multiplex mode, where a fewer number of pro- cessing chains are multiplexed across an arbitrary number of transmit antennas. Each of these chains, also referred to as channels, have the capability to modulate the phase of a traditional radar pulse in discrete steps. Further, the modulation is assumed to be in the slow time domain (inter-pulse); such a phase modulation results in benign requirements on the platform. Furthermore, the antennas are assumed to be mounted uniformly in a way that the virtual MIMO paradigm for maximum angular resolution is satisfied. The slow time modulation naturally results in in an angle-Doppler coupling; this issue is addressed by phase center motion (PCM) techniques, where nonlinear and random PCM techniques for mitigating angle-Doppler coupling are proposed. While the PCM techniques provide orthogonal signals, a transmit beamforming approach is also consid- ered to exploit the salient features of MIMO and phased array radars. Towards this, an approach based on block circulant decomposition for the slow-time modulation is proposed to generate a particular beam shape while minimizing the cross-correlation between transmitted signals, such that the virtual MIMO paradigm is satisfied. The thesis formulates the radiation pattern design as a dictionary based convex optimization and proposes closed-form signal design solutions for particular configuration of channels, discrete phase stages and transmit antenna elements. The beampattern design is then elegantly combined with the PCM approach to reduce Doppler ambiguity while sup- pressing angle-Doppler coupling. The proposed waveform design methodology is shown to be amenable to fast adaptation. Further, the adaptive waveform design is fused with state of the art adaptive receiver techniques to conceive a novel adaptive MIMO radar system under practical constraints in this thesis. [less ▲]

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See detailMODELING HUMAN METABOLISM: A DYNAMIC MULTI-TISSUE APPROACH
Martins Conde, Patricia UL

Doctoral thesis (2019)

Despite significant advances in constraint-based modelling, a methodology for modelling dynamic multi-tissue models of human metabolism is still missing. Additionally, prior to analysing diseased models ... [more ▼]

Despite significant advances in constraint-based modelling, a methodology for modelling dynamic multi-tissue models of human metabolism is still missing. Additionally, prior to analysing diseased models, it is important to develop a good methodology, as it would not only enable us to capture the effects of metabolism-associated diseases, but it would also allow us to recapitulate known physiological healthy properties of human metabolism. Therefore, a dynamic multi-tissue model using a new methodology was developed. The objective function comprises a set of complex functions that the multi-tissue model needs to perform. To demonstrate the capabilities of this new approach, different healthy, and unhealthy conditions were simulated. In a first step, the effect of different healthy conditions was analysed (i.e. the fasting, the ingestion of different meals, and exercising at various intensities, and conditions), demonstrating the model’s capability to correctly predict metabolic changes occurring on energy-associated pathways. In the second step, biomarkers for a range of inborn errors of metabolism were predicted, and the predictions were shown to be in good agreement with previous data. Finally, after verifying the capability of the dynamic multi-tissue model to review known physiological aspects of human metabolism, this model was further integrated with a physiologically- based pharmacokinetic model of glucose metabolism, previously developed by Schaller et al. (2013). Contrasting conditions, such as healthy and diabetic, were simulated using the multi-scale model during fasting and after an oral glucose tolerance test and candidate drugs to treat type 2 diabetes mellitus were predicted. Five out of the 80 simulated drug targets were predicted as candidate anti-diabetic targets, and the majority of drugs known to inhibit the predicted drug targets, have already been shown to have anti-diabetic effects. The developed approach can be applied to any metabolic disease and to any system where homeostasis plays an important role, or where a simple biomass optimization function is not applicable. Furthermore, the large amount of data collected for the multi-tissue model generation is of significant value for tissue constraint-based metabolic modellers who need data to constrain their models. [less ▲]

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See detailFUNCTIONAL CHARACTERISATION OF THE A30P MUTATION IN ALPHA-SYNUCLEIN GENE IN A PATIENT-DERIVED CELLULAR MODEL OF PARKINSON’S DISEASE
Rodrigues Dos Santos, Bruno Filipe UL

Doctoral thesis (2019)

Our study aims to perform detailed phenotyping of the A30P alpha-synuclein familial case of PD, allowing to identify underlying mechanisms of the disease that may translate into novel therapies ... [more ▼]

Our study aims to perform detailed phenotyping of the A30P alpha-synuclein familial case of PD, allowing to identify underlying mechanisms of the disease that may translate into novel therapies. Parkinson’s disease (PD) is the second most common neurodegenerative disease. Approximately 20% of PD cases are known to have a genetic cause. From these, mutations in SNCA, the gene encoding alpha-synuclein, are linked to an autosomal dominant inheritance of the disease. In 1998, our group discovered the second known point mutation within the SNCA gene, causing an A30P exchange of the peptide sequence. We generated first patient-derived cellular model of the A30P alpha-synuclein mutation carrier, by obtaining fibroblasts from an affected sibling of the index patient, an unaffected sibling of the patient, and an age-matched gender-matched non-PD control. We reprogrammed these fibroblasts into induced pluripotent stem cells (iPSCs), and differentiated them into midbrain dopaminergic neurons. We obtained enriched cultures of 80% midbrain neurons (FoxA2+/Tuj1+), with approximately 12 % dopaminergic (TH+), for which we observed electrophysiological activity and dopamine release. We detected a significant reduction of the protein level of mitochondria complexes II, IV, and V in the patient lines compared with the controls, additionally we found a significant impairment of mitochondrial respiration and an increased susceptibility of the cells to oxidative stress. Gene-edited isogenic controls were generated to dissect mutation-specific effects. Furthermore, we investigated mitochondrial morphology and dynamics, and how these processes contribute to the dopaminergic neurodegeneration. Additionally, we were implementing previously established readouts on our high-throughput automated screening platform that will allow us to identify FDA approved compounds with potential to be re-purposed and used as PD treatment. We believe that detailed phenotyping of the A30P alpha-synuclein monogenic case may help to identify underlying mechanisms of the disease that may translate into novel therapies, which would also apply to the more common sporadic forms of PD. [less ▲]

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See detailFrom Information Theory Puzzles in Deletion Channels to Deniability in Quantum Cryptography
Atashpendar, Arash UL

Doctoral thesis (2019)

Research questions, originally rooted in quantum key exchange (QKE), have branched off into independent lines of inquiry ranging from information theory to fundamental physics. In a similar vein, the ... [more ▼]

Research questions, originally rooted in quantum key exchange (QKE), have branched off into independent lines of inquiry ranging from information theory to fundamental physics. In a similar vein, the first part of this thesis is dedicated to information theory problems in deletion channels that arose in the context of QKE. From the output produced by a memoryless deletion channel with a uniformly random input of known length n, one obtains a posterior distribution on the channel input. The difference between the Shannon entropy of this distribution and that of the uniform prior measures the amount of information about the channel input which is conveyed by the output of length m. We first conjecture on the basis of experimental data that the entropy of the posterior is minimized by the constant strings 000..., 111... and maximized by the alternating strings 0101..., 1010.... Among other things, we derive analytic expressions for minimal entropy and propose alternative approaches for tackling the entropy extremization problem. We address a series of closely related combinatorial problems involving binary (sub/super)-sequences and prove the original minimal entropy conjecture for the special cases of single and double deletions using clustering techniques and a run-length encoding of strings. The entropy analysis culminates in a fundamental characterization of the extremal entropic cases in terms of the distribution of embeddings. We confirm the minimization conjecture in the asymptotic limit using results from hidden word statistics by showing how the analytic-combinatorial methods of Flajolet, Szpankowski and Vallée, relying on generating functions, can be applied to resolve the case of fixed output length and n → ∞. In the second part, we revisit the notion of deniability in QKE, a topic that remains largely unexplored. In a work by Donald Beaver it is argued that QKE protocols are not necessarily deniable due to an eavesdropping attack that limits key equivocation. We provide more insight into the nature of this attack and discuss how it extends to other prepare-and-measure QKE schemes such as QKE obtained from uncloneable encryption. We adopt the framework for quantum authenticated key exchange developed by Mosca et al. and extend it to introduce the notion of coercer-deniable QKE, formalized in terms of the indistinguishability of real and fake coercer views. We also elaborate on the differences between our model and the standard simulation-based definition of deniable key exchange in the classical setting. We establish a connection between the concept of covert communication and deniability by applying results from a work by Arrazola and Scarani on obtaining covert quantum communication and covert QKE to propose a simple construction for coercer-deniable QKE. We prove the deniability of this scheme via a reduction to the security of covert QKE. We relate deniability to fundamental concepts in quantum information theory and suggest a generic approach based on entanglement distillation for achieving information-theoretic deniability, followed by an analysis of other closely related results such as the relation between the impossibility of unconditionally secure quantum bit commitment and deniability. Finally, we present an efficient coercion-resistant and quantum-secure voting scheme, based on fully homomorphic encryption (FHE) and recent advances in various FHE primitives such as hashing, zero-knowledge proofs of correct decryption, verifiable shuffles and threshold FHE. [less ▲]

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See detailDynamiques de (dés)appartenance au cours de la vie : le cas des Portugais de "seconde génération" au Grand-Duché de Luxembourg
Martins, Heidi Rodrigues UL

Doctoral thesis (2019)

Cette étude s’intéresse aux sentiments de (dés)appartenances et à leur (re)construction au cours de la vie des Portugais de « seconde génération » au Luxembourg. Sur le plan théorique, notre recherche se ... [more ▼]

Cette étude s’intéresse aux sentiments de (dés)appartenances et à leur (re)construction au cours de la vie des Portugais de « seconde génération » au Luxembourg. Sur le plan théorique, notre recherche se fonde essentiellement sur trois approches : le transnationalisme, la théorie des dynamiques relationnelles et la théorie du parcours de vie. Les enfants d’é(im)migrés, a-t-on suggéré, sont élevés dans un champ social transnational qui implique des contacts transfrontaliers et des visites (au sens réel et/ou symbolique) dans le pays d’origine. Ainsi, dans un premier temps, nous commençons par investiguer de manière compréhensive leurs pratiques (trans)nationales (notamment leur variation en portée, intensité et fréquence au cours du parcours de vie) ; puis, dans un deuxième temps, nous demandons : comment les Portugais de « seconde génération » au Luxembourg (re)construisent-ils, négocient-ils et accomplissent-ils leurs (dés)appartenances au cours du parcours de vie et quelle est le rôle joué par le pays d’origine ?. Pour répondre à ce questionnement, nous avons adopté comme méthodologie principale l’entretien compréhensif. Les données empiriques pour cette étude qualitative proviennent de 25 entretiens compréhensifs (incluant la réalisation d’une Carte de (dés)appartenance) réalisés auprès de membres de la « seconde génération » issue de l’é(im)migration portugaise au Luxembourg. Les participants avaient entre 19 et 55 ans au moment de l’entretien. Le corpus a fait l’objet d’une analyse par théorisation ancrée. En plus de montrer le poids de la « donne résidentielle » et de la « donne technologique », qui a fortement infléchi/ et infléchit encore les parcours des enfants d’é(im)migrés Portugais au Luxembourg (en fonction de la cohorte), nous mettons en exergue les deux sources de tensions majeures quant à leurs sentiments de (dés)appartenance et mettons en avant l’agentivité de nos participants qui, à partir de deux stratégies de (dés)appartenance (déportugalisation et/ou luxembourgisation), mobilisent les clés de résolution de ces mêmes tensions. Nous soulignons également le rôle qu’y jouent les sentiments de fierté et de reconnaissance (liés de près à la question de la mobilité sociale). Nous concluons par, l’intégration de notre modèle de (re)construction des (dés)appartenance dans un processus plus large que nous nommons processus de (re)configuration identitaire. [less ▲]

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See detailCo-evolutionary Hybrid Bi-level Optimization
Kieffer, Emmanuel UL

Doctoral thesis (2019)

Multi-level optimization stems from the need to tackle complex problems involving multiple decision makers. Two-level optimization, referred as ``Bi-level optimization'', occurs when two decision makers ... [more ▼]

Multi-level optimization stems from the need to tackle complex problems involving multiple decision makers. Two-level optimization, referred as ``Bi-level optimization'', occurs when two decision makers only control part of the decision variables but impact each other (e.g., objective value, feasibility). Bi-level problems are sequential by nature and can be represented as nested optimization problems in which one problem (the ``upper-level'') is constrained by another one (the ``lower-level''). The nested structure is a real obstacle that can be highly time consuming when the lower-level is $\mathcal{NP}-hard$. Consequently, classical nested optimization should be avoided. Some surrogate-based approaches have been proposed to approximate the lower-level objective value function (or variables) to reduce the number of times the lower-level is globally optimized. Unfortunately, such a methodology is not applicable for large-scale and combinatorial bi-level problems. After a deep study of theoretical properties and a survey of the existing applications being bi-level by nature, problems which can benefit from a bi-level reformulation are investigated. A first contribution of this work has been to propose a novel bi-level clustering approach. Extending the well-know ``uncapacitated k-median problem'', it has been shown that clustering can be easily modeled as a two-level optimization problem using decomposition techniques. The resulting two-level problem is then turned into a bi-level problem offering the possibility to combine distance metrics in a hierarchical manner. The novel bi-level clustering problem has a very interesting property that enable us to tackle it with classical nested approaches. Indeed, its lower-level problem can be solved in polynomial time. In cooperation with the Luxembourg Centre for Systems Biomedicine (LCSB), this new clustering model has been applied on real datasets such as disease maps (e.g. Parkinson, Alzheimer). Using a novel hybrid and parallel genetic algorithm as optimization approach, the results obtained after a campaign of experiments have the ability to produce new knowledge compared to classical clustering techniques combining distance metrics in a classical manner. The previous bi-level clustering model has the advantage that the lower-level can be solved in polynomial time although the global problem is by definition $\mathcal{NP}$-hard. Therefore, next investigations have been undertaken to tackle more general bi-level problems in which the lower-level problem does not present any specific advantageous properties. Since the lower-level problem can be very expensive to solve, the focus has been turned to surrogate-based approaches and hyper-parameter optimization techniques with the aim of approximating the lower-level problem and reduce the number of global lower-level optimizations. Adapting the well-know bayesian optimization algorithm to solve general bi-level problems, the expensive lower-level optimizations have been dramatically reduced while obtaining very accurate solutions. The resulting solutions and the number of spared lower-level optimizations have been compared to the bi-level evolutionary algorithm based on quadratic approximations (BLEAQ) results after a campaign of experiments on official bi-level benchmarks. Although both approaches are very accurate, the bi-level bayesian version required less lower-level objective function calls. Surrogate-based approaches are restricted to small-scale and continuous bi-level problems although many real applications are combinatorial by nature. As for continuous problems, a study has been performed to apply some machine learning strategies. Instead of approximating the lower-level solution value, new approximation algorithms for the discrete/combinatorial case have been designed. Using the principle employed in GP hyper-heuristics, heuristics are trained in order to tackle efficiently the $\mathcal{NP}-hard$ lower-level of bi-level problems. This automatic generation of heuristics permits to break the nested structure into two separated phases: \emph{training lower-level heuristics} and \emph{solving the upper-level problem with the new heuristics}. At this occasion, a second modeling contribution has been introduced through a novel large-scale and mixed-integer bi-level problem dealing with pricing in the cloud, i.e., the Bi-level Cloud Pricing Optimization Problem (BCPOP). After a series of experiments that consisted in training heuristics on various lower-level instances of the BCPOP and using them to tackle the bi-level problem itself, the obtained results are compared to the ``cooperative coevolutionary algorithm for bi-level optimization'' (COBRA). Although training heuristics enables to \emph{break the nested structure}, a two phase optimization is still required. Therefore, the emphasis has been put on training heuristics while optimizing the upper-level problem using competitive co-evolution. Instead of adopting the classical decomposition scheme as done by COBRA which suffers from the strong epistatic links between lower-level and upper-level variables, co-evolving the solution and the mean to get to it can cope with these epistatic link issues. The ``CARBON'' algorithm developed in this thesis is a competitive and hybrid co-evolutionary algorithm designed for this purpose. In order to validate the potential of CARBON, numerical experiments have been designed and results have been compared to state-of-the-art algorithms. These results demonstrate that ``CARBON'' makes possible to address nested optimization efficiently. [less ▲]

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See detailArtificial Intelligence for the Detection of Electricity Theft and Irregular Power Usage in Emerging Markets
Glauner, Patrick Oliver UL

Doctoral thesis (2019)

Power grids are critical infrastructure assets that face non-technical losses (NTL), which include, but are not limited to, electricity theft, broken or malfunctioning meters and arranged false meter ... [more ▼]

Power grids are critical infrastructure assets that face non-technical losses (NTL), which include, but are not limited to, electricity theft, broken or malfunctioning meters and arranged false meter readings. In emerging markets, NTL are a prime concern and often range up to 40% of the total electricity distributed. The annual world-wide costs for utilities due to NTL are estimated to be around USD 100 billion. Reducing NTL in order to increase revenue, profit and reliability of the grid is therefore of vital interest to utilities and authorities. In the beginning of this thesis, we provide an in-depth discussion of the causes of NTL and the economic effects thereof. Industrial NTL detection systems are still largely based on expert knowledge when deciding whether to carry out costly on-site inspections of customers. Electric utilities are reluctant to move to large-scale deployments of automated systems that learn NTL profiles from data. This is due to the latter's propensity to suggest a large number of unnecessary inspections. In this thesis, we compare expert knowledge-based decision making systems to automated statistical decision making. We then branch out our research into different directions: First, in order to allow human experts to feed their knowledge in the decision process, we propose a method for visualizing prediction results at various granularity levels in a spatial hologram. Our approach allows domain experts to put the classification results into the context of the data and to incorporate their knowledge for making the final decisions of which customers to inspect. Second, we propose a machine learning framework that classifies customers into NTL or non-NTL using a variety of features derived from the customers' consumption data as well as a selection of master data. The methodology used is specifically tailored to the level of noise in the data. Last, we discuss the issue of biases in data sets. A bias occurs whenever training sets are not representative of the test data, which results in unreliable models. We show how quantifying and reducing these biases leads to an increased accuracy of the trained NTL detectors. This thesis has resulted in appreciable results on real-world big data sets of millions customers. Our systems are being deployed in a commercial NTL detection software. We also provide suggestions on how to further reduce NTL by not only carrying out inspections, but by implementing market reforms, increasing efficiency in the organization of utilities and improving communication between utilities, authorities and customers. [less ▲]

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See detailSociographie des associations islamiques au Luxembourg, à l'aune de l'institutionnalisation
Pirenne, Elsa

Doctoral thesis (2019)

Detailed reference viewed: 62 (24 UL)
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See detailA Transaction’s Journey: Transactional Enhancements for Public Blockchain-based Distributed Ledgers
Fiz Pontiveros, Beltran UL

Doctoral thesis (2019)

Interest in the decentralised nature of blockchain-based distributed ledgers has rapidly grown over the past few years. While a portion of this interest is fuelled by the price surge in Bitcoin towards ... [more ▼]

Interest in the decentralised nature of blockchain-based distributed ledgers has rapidly grown over the past few years. While a portion of this interest is fuelled by the price surge in Bitcoin towards the end of 2017, numerous companies across industries such as healthcare and finance have shown a keen interest in this technology and begun investing in diverse research projects. The work presented in this dissertation proposes a series of enhancements to blockchain-based distributed ledger technologies by focusing on a key element in the system: the transaction. By investigating the life cycle of a transaction in popular blockchain systems like bitcoin and ethereum, several enhancements were identified to tackle some of the challenges under active research today by the blockchain community. [less ▲]

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See detailSupporting Change in Product Lines Within the Context of Use Case-driven Development and Testing
Hajri, Ines UL

Doctoral thesis (2019)

Product Line Engineering (PLE) is a crucial practice in many software development environments where systems are complex and developed for multiple customers with varying needs. At the same time, many ... [more ▼]

Product Line Engineering (PLE) is a crucial practice in many software development environments where systems are complex and developed for multiple customers with varying needs. At the same time, many business contexts are use case-driven where use cases are the main artifacts driving requirements elicitation and many other development activities. In these contexts, variability information is often not explicitly represented, which leads to ad-hoc change management for use cases, domain models and test cases in product families. In this thesis, we address the problems of modeling variability in requirements with additional traceability to feature models and the manual and error prone requirements configuration and regression testing in product families. We provide the following contributions: - A modeling method for capturing variability information in product line use case and domain models by relying exclusively on commonly used artifacts in use-case driven development, thus avoiding unnecessary modeling overhead. - An approach for automated configuration of product specific use case and domain models that guides customers in making configuration decisions and automatically generates use case diagrams, use case specifications, and domain models for configured products. - A change impact analysis approach for evolving configuration decisions in product line use case models that automatically identifies the impact of decision changes on other decisions, and incrementally reconfigures product specific use case diagrams and specifications for evolving decisions. - An approach for automated classification and prioritization of system test cases in a family of products that automatically classifies and prioritizes, for each new product, system test cases of previous product(s) in a product line, and provides guidance in modifying existing system test cases to cover new use case scenarios that have not been tested in the product line before. All our approaches have been developed and evaluated in close collaboration with our industry partner IEE. [less ▲]

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See detailEarly literacy development in a multilingual educational context: a quasi-experimental intervention and longitudinal study
Wealer, Cyril UL

Doctoral thesis (2019)

Based on concerns about literacy difficulties experienced by children learning to read and write in a second language, repeated calls have been made for more research on literacy development in ... [more ▼]

Based on concerns about literacy difficulties experienced by children learning to read and write in a second language, repeated calls have been made for more research on literacy development in multilingual educational settings. Enhanced understanding of literacy development in a second language is essential to optimize support structures for children learning to read and write in a language they have yet to fully acquire. The current thesis presents two longitudinal studies contributing towards this aim. Both studies were conducted with young children growing up in Luxembourg, a linguistically and culturally diverse country where the language spoken in preschool is Luxembourgish, but children learn to read and write in German in Grade 1. Study 1 was a quasi-experimental intervention study exploring the efficacy of a classroom-based early literacy intervention. Children from 28 preschool classes (age 5-6) were allocated to either the intervention (n = 89) or a standard curriculum (control) group (n = 100). Classroom teachers delivered four intervention sessions (20 minutes each) per week over 12 weeks (48 sessions in total) to their whole classes. The intervention programme targeted phonological awareness, letter-sound knowledge and print awareness embedded in a language and literacy-rich context. All children were assessed before and immediately after the intervention in preschool, and at a nine months follow-up in Grade 1 (age 6-7) after having started formal literacy instruction in German for five months. The intervention group significantly outperformed the control group on early literacy measures immediately postintervention in preschool and the results generalised to measure of reading comprehension and spelling in Grade 1. The study provides clear evidence for the efficacy of the early literacy intervention, particularly for a subpopulation of children with low oral language skills in Luxembourgish, many of whom were second language learners. Study 2 was a correlational study on a subsample of the children from Study 1 (from untrained control group). The aim was to identify preschool predictors in Luxembourgish of literacy skills in German in Grade 1 for multilingual children learning German as a second language. Ninety-eight children completed measures of potential predictors in preschool (age 5-6), including phonological awareness, letter-sound knowledge, rapid automatized naming, verbal short-term memory and vocabulary knowledge in Luxembourgish, along with measures of word reading, reading comprehension and spelling in German in Grade 1 (age 6-7). While moderate to strong correlations were found between all individual preschool predictors and later literacy measures, only phonological awareness, and letter-sound knowledge emerged as unique predictors of all literacy measures. These findings suggest that, despite individual differences, learning to read in a second language may be in many aspects similar to learning to read in a first language. Taken together, the findings of this thesis represent important steps in extending the theoretical knowledge base on second language literacy acquisition and in strengthening the evidence base for identification and prevention strategies of literacy difficulties in linguistically diverse children in Luxembourg. [less ▲]

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See detailAutomated Identification of National Implementations of European Union Directives With Multilingual Information Retrieval Based On Semantic Textual Similarity
Nanda, Rohan UL

Doctoral thesis (2019)

The effective transposition of European Union (EU) directives into Member States is important to achieve the policy goals defined in the Treaties and secondary legislation. National Implementing Measures ... [more ▼]

The effective transposition of European Union (EU) directives into Member States is important to achieve the policy goals defined in the Treaties and secondary legislation. National Implementing Measures (NIMs) are the legal texts officially adopted by the Member States to transpose the provisions of an EU directive. The measures undertaken by the Commission to monitor NIMs are time-consuming and expensive, as they resort to manual conformity checking studies and legal analysis. In this thesis, we developed a legal information retrieval system using semantic textual similarity techniques to automatically identify the transposition of EU directives into the national law at a fine-grained provision level. We modeled and developed various text similarity approaches such as lexical, semantic, knowledge-based, embeddings-based and concept-based methods. The text similarity systems utilized both textual features (tokens, N-grams, topic models, word and paragraph embeddings) and semantic knowledge from external knowledge bases (EuroVoc, IATE and Babelfy) to identify transpositions. This thesis work also involved the development of a multilingual corpus of 43 directives and their corresponding NIMs from Ireland (English legislation), Italy (Italian legislation) and Luxembourg (French legislation) to validate the text similarity based information retrieval system. A gold standard mapping (prepared by two legal researchers) between directive articles and NIM provisions was prepared to evaluate the various text similarity models. The results show that the lexical and semantic text similarity techniques were more effective in identifying transpositions as compared to the embeddings-based techniques. We also observed that the unsupervised text similarity techniques had the best performance in case of the Luxembourg Directive-NIM corpus. We also developed a concept recognition system based on conditional random fields (CRFs) to identify concepts in European directives and national legislation. The results indicate that the concept recognitions system improved over the dictionary lookup program by tagging the concepts which were missed by dictionary lookup. The concept recognition system was extended to develop a concept-based text similarity system using word-sense disambiguation and dictionary concepts. The performance of the concept-based text similarity measure was competitive with the best performing text similarity measure. The labeled corpus of 43 directives and their corresponding NIMs was utilized to develop supervised text similarity systems by using machine learning classifiers. We modeled three machine learning classifiers with different textual features to identify transpositions. The results show that support vector machines (SVMs) with term frequency-inverse document frequency (TF-IDF) features had the best overall performance over the multilingual corpus. Among the unsupervised models, the best performance was achieved by TF-IDF Cosine similarity model with macro average F-score of 0.8817, 0.7771 and 0.6997 for the Luxembourg, Italian and Irish corpus respectively. These results demonstrate that the system was able to identify transpositions in different national jurisdictions with a good performance. Thus, it has the potential to be useful as a support tool for legal practitioners and Commission officials involved in the transposition monitoring process. [less ▲]

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See detailThe EU Dimension in Education for Democratic Citizenship: a Legal Analysis
Grimonprez, Kris Johanna UL

Doctoral thesis (2018)

Education for democratic citizenship equips learners with knowledge, skills and understanding and develops their attitudes and behaviour, with the aim of empowering them to exercise and defend their ... [more ▼]

Education for democratic citizenship equips learners with knowledge, skills and understanding and develops their attitudes and behaviour, with the aim of empowering them to exercise and defend their democratic rights and responsibilities in society, to value diversity and to play an active part in democratic life (the consensual definition in the Charter on Education for Democratic Citizenship and Human Rights Education of the Council of Europe, 2010). What does this mean for EU citizens? The dissertation reads this Charter in combination with EU law and argues that an EU dimension must be incorporated in national citizenship education. A method for objective, critical and pluralistic EU learning is proposed, a method based on the Treaties and on case teaching (stories for critical thinking). Starting from EU law, suitable content for the EU dimension in mainstream education is then explored on the basis of four criteria: (i) additional content for national education for democratic citizenship, (ii) significant content, i.e. relating to foundational (EU primary law) values, objectives and principles, (iii) inviting critical thinking, (iv) affecting the large majority of EU citizens, including static citizens (who live at home in their own country). A broader view of EU citizenship is developed, beyond that resulting from classic citizenship rights. Finally, it is argued that the EU has the legal competence to support the EU dimension in education. Member States are invited to take more action to ensure quality education, which must now include education for democratic citizenship and its EU dimension. Democracy in the EU needs an educational substratum. [less ▲]

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See detailA study of the molecular mechanisms underlying the response of human colorectal adenomacarcinoma enterocytes to prebiotics and probiotics
Greenhalgh, Kacy UL

Doctoral thesis (2018)

The human gastrointestinal tract (GIT) microbiome plays essential roles in maintaining human health. A variety of diseases including colorectal cancer (CRC) are associated with microbial dysbiosis ... [more ▼]

The human gastrointestinal tract (GIT) microbiome plays essential roles in maintaining human health. A variety of diseases including colorectal cancer (CRC) are associated with microbial dysbiosis. Administration of microbial isolates associated with health benefits (e.g. prebiotics) together with specific dietary components (e.g., probiotics) may find application as supportive therapeutic options in the treatment and management of CRC. Although microbiome-modulating therapeutics hold great promise, such approaches are presently not formally integrated into treatment plans. To obtain better understanding of combined pre- and probiotic regimens in relation to CRC, the present study was dedicated to investigate the effects of selected prebiotics on the proliferation of CRC primary cells and conventional CRC-cell lines, the effects of prebiotics on the growth and metabolism of selected probiotic strains, and the combinatorial/synbiotic effects of selected pre- and probiotics on CRC proliferation. In addition, this work established the in vitro gut-on-a chip HuMiX model with a simulated high-fibre medium for co-culturing human and microbial cells in HuMiX. Furthermore, the anti-carcinogenic combinatorial effects of dietary fiber (e.g., prebiotics), and GIT bacteria (e.g., probiotics) were evaluated using human GIT transcriptomes and metabolomes in HuMiX. An integrated in vitro and in silico modeling approach was finally established to decipher the complex cross-talk between gut bacteria, dietary components and human host cells. My results demonstrate that in stark contrast to the individual pre- or probiotic treatments, the synbiotic regimen of the probiotic Lactobacillus rhamnosus GG and dietary fiber results in the down-regulation of genes involved in pro-carcinogenic pathways and drug resistance (e.g., ABC transporters) and reduced levels of the oncometabolite lactate. Distinct ratios of organic and short-chain fatty acids are produced during the simulated regimens. Treatment of primary CRC-derived cells with a molecular cocktail reflecting the synbiotic regimen attenuated self-renewal capacity. The developped integrated in vitro and in silico modelling approach provides mechanistic insights into the interplay between pre- and probiotics and elucidation of the microbiota-host relationship. In summary, my dissertation work illustrates the potential of HuMiX to be used for nutritional studies and more precisely for studying the underlying mechanisms of the effects that dietary components (e.g., dietary fiber) and probiotics have on CRC-derived cells. Thereby, this dissertation work highlights the potential for formulating efficacious dietary supplements including synbiotics in the context of therapeutic regimens for microbiome-linked diseases in the future. [less ▲]

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See detailTopology and interaction effects in one-dimensional systems
Calzona, Alessio UL

Doctoral thesis (2018)

With the discovery of the integer quantum Hall effect by von Klitzing and collaborators in 1980, the mathematical field of topology entered the world of condensed matter physics. Almost three decades ... [more ▼]

With the discovery of the integer quantum Hall effect by von Klitzing and collaborators in 1980, the mathematical field of topology entered the world of condensed matter physics. Almost three decades later, this eventually led to the theoretical prediction and the experimental realization of many intriguing topological materials and topology-based devices. In this Ph.D. thesis, we will study the interplay between topology and another key topic in condensed matter physics, namely the study of inter-particle interactions in many-body systems. This interplay is analyzed from two different perspectives. Firstly, we studied how the presence of electron-electron interactions affects single-electron injection into a couple of counter-propagating one-dimensional edge channels. The latter appear at the edges of topologically non-trivial systems in the quantum spin Hall regime and they can also be engineered by exploiting the integer quantum Hall effect. Because of inter-channel interactions, the injected electron splits up into a couple of counter-propagating fractional excitations. Here, we carefully study and discuss their properties by means of an analytical approach based on the Luttinger liquid theory and the bosonization method. Our results are quite relevant in the context of the so-called electron quantum optics, a fast developing field which deeply exploits the topological protection of one-dimensional edge states to study the coherent propagation of electrons in solid-state devices. As an aside, we also showed that similar analytical techniques can also be used to study the time-resolved dynamics of a Luttinger liquid subject to a sudden change of the interaction strength, a protocol known as quantum quench which is gaining more and more attention, especially within the cold-atoms community. Secondly, we study how inter-particle interactions can enhance the topological properties of strictly one-dimensional fermionic systems. More precisely, the starting point is the seminal Kitaev chain, a free-fermionic lattice model which hosts exotic Majorana zero-energy modes at its ends. The latter are extremely relevant in the context of topological quantum computation because of their non-Abelian anyonic exchange statistics. Here we show that, by properly adding electron-electron interactions to the Kitaev chain, it is possible to obtain lattice models which feature zero-energy parafermionic modes, an even more intriguing generalization of Majoranas. To this end, we develop at first an exact mapping between Z4 parafermions and ordinary fermions on a lattice. We subsequently exploit this mapping to analytically obtain an exactly solvable fermionic model hosting zero-energy parafermions. We study their properties and numerically investigate their signatures and robustness even when parameters are tuned away from the exactly solvable point. [less ▲]

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See detailBioactive nanotopographies for the control of mesenchymal stem cell differentiation for applications in bone tissue engineering
Realista Coelho Dos Santos Pedrosa, Catarina UL

Doctoral thesis (2018)

Nanotopography with length scales of the order of extracellular matrix elements offers the possibility of regulating cell behavior. Investigation of the impact of nanotopography on cell response has been ... [more ▼]

Nanotopography with length scales of the order of extracellular matrix elements offers the possibility of regulating cell behavior. Investigation of the impact of nanotopography on cell response has been limited by inability to precisely control geometries, especially at high spatial resolutions, and across practically large areas. This work allowed the fabrication of well-controlled and periodic nanopillar arrays of silicon to investigate their impact on osteogenic differentiation of human mesenchymal stem cells (hMSCs). Silicon nanopillar arrays with critical dimensions in the range of 40-200 nm, exhibiting standard deviations below 15% across full wafers were realized using self-assembly of block copolymer colloids. To investigate if modifications of surface chemistry could further improve the modulation of hMSC differentiation, mimetic peptides were grafted on the fabricated nanoarrays. A peptide known for its ability to ameliorate cell adhesion (RGD peptide), a synthetic peptide able to enhance osteogenesis (BMP-2 mimetic peptide), and a combination or both molecules were covalently grafted on the nanostructures. Immunofluorescence and quantitative polymerase chain reaction (RT-qPCR) measurements reveal clear dependence of osteogenic differentiation of hMSCs on the diameter and periodicity of the arrays. Moreover, the differentiation of hMSCs was found to be dependent on the age of the donor. Surface functionalization allowed additional enhancement of the expression of osteogenic markers, in particular when RGD peptide and BMP-2 mimetic peptide were co-immobilized. These findings can contribute for the development of personalized treatments of bone diseases, namely novel implant nanostructuring depending on patient age. [less ▲]

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See detailDefining, Measuring, and Enabling Transparency for Electronic Medical Systems
Pierina Brustolin Spagnuelo, Dayana UL

Doctoral thesis (2018)

Transparency is a novel concept in the context of Information and Communication Technology (ICT). It has arisen from regulations as a data protection principle, and it is now being studied to encompass ... [more ▼]

Transparency is a novel concept in the context of Information and Communication Technology (ICT). It has arisen from regulations as a data protection principle, and it is now being studied to encompass the peculiarities of digital information. Transparency, however, is not the first security concept to be borrowed from regulations; privacy once emerged from discussions on individual’s rights. Privacy began to be vigorously debated in 1890, when Warren and Brandeis analysed legal cases for which penalties were applied on the basis of defamation, infringement of copyrights, and violation of confidence. The authors defended that those cases were, in fact, built upon a broader principle called privacy. But privacy was only given a structured definition almost one century later, in 1960, when Prosser examined cases produced after Warren and Brandeis’ work, classifying violation of privacy into four different torts; it took twenty years more before the concept was thoroughly studied for its functions in ICT. Guidelines by the OECD outlined principles to support the discussion of privacy as a technical requirement. Proceeded by international standards for a privacy framework (ISO/IEC 29100), which translated the former legal concepts into information security terms, such as data minimisation, accuracy, and accountability. Transparency has a younger, but comparable history; the current General Data Protection Regulation (GDPR) defines it as a principle which requires “that any information and communication relating to the processing of those personal data be easily accessible and easy to understand [..]". However, other related and more abstract concepts preceded it. In the Health Insurance Portability and Accountability Act (HIPAA) of 1996, the Privacy Rule demands to document privacy policies and procedures and to notify individuals of uses of their health information. Former European Directives, i.e., 95/46/EC and 2011/24/EU, establish “the right for individuals to have access to their personal data concerning their health [..] also in the context of cross-border healthcare”. The same did the Freedom of Information Act (FOIA) of 1966, instituting that any person has a right to obtain from agencies information regarding their records. These and other similar requests refer to the transversal quality called transparency. Similarly to what happened with privacy, transparency was also the subject of guidelines that clarify its interpretation in ICT. However, no framework or standard has been defined yet that translates transparency into a technical property. This translation is the goal of our work. This thesis is dedicated to debate existing interpretations for transparency, to establish requirements and measurement procedures for it, and to study solutions that can help systems adhere to the transparency principle from a technical perspective. Our work constitutes an initial step towards the definition of a framework that helps accomplish meaningful transparency in the context of Electronic Medical Systems. [less ▲]

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See detailIntegration of omics data for biotechnology-relevant microbial communities
Herold, Malte UL

Doctoral thesis (2018)

Naturally occurring and artificial bacterial communities play an import role in many biotechnological processes. To elucidate bacterial interactions that are important for potential optimized ... [more ▼]

Naturally occurring and artificial bacterial communities play an import role in many biotechnological processes. To elucidate bacterial interactions that are important for potential optimized biotechnological applications, high-throughput measurements of biomolecules, metagenomics, metratranscriptomics,metaproteomics, and meta-metabolomics provide a detailed snapshot of mixed microbial consortia. Integration of multiple layers of omics data allows to reconstruct structure and function of complex microbial communities and is demonstrated for two different model systems. The first chapter focuses on synthetic communities consisting of strains representing key species found in biomining operations and acid mine drainage and that are of economical interest for copper production. A high-quality closed reference genome for L. ferriphilum was obtained by DNA sequencing and was subsequently used to integrate functional omics data, i.e. transcriptomic and proteomic profiling. The combination of genomics, genome annotation, and functional omics data allowed an in-depth characterization of L. ferriphilum in culture medium and in the presence of the iron sulfide mineral chalcopyrite, an economically relevant copper ore. Subsequently, analyses were performed for co-cultures of up to three organisms highlighting specific interaction mechanisms. The cultures without L. ferriphilum showed higher copper solubilisation rates, as the highly efficient iron oxidiser might raise the redox potential above the optimal range. For in situ studies, reference-based analyses are of limited use, e.g. due to a lack in reference genomes of culturable isolates. Hence, the second chapter focuses on an approach to study mixed microbial communities independent of prior knowledge and available reference genomes. A timeseries of oleaginous floating sludge samples that spans over one and a half years was analysed by integrating metagenomic, metatranscriptomic, metaproteomic, and meta-metabolomic data. This allowed the reconstruction of population level genomes and the characterization of the niches of the respective populations. The functional potential was assessed, as well as expression profiles over time, yielding a detailed view on lifestyle strategies and the potential impact of abiotic factors. Understanding the niche ecology of the predominant lipid accumulators in the system could lead towards optimized biofuel production. [less ▲]

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See detailFirst-Principles Modeling of Molecular Crystals: Crystal Structure Prediction and Vibrational Properties
Hoja, Johannes UL

Doctoral thesis (2018)

Understanding the structure and stability, as well as response properties of molecular crystals at certain thermodynamic conditions is crucial for the engineering of new molecular materials and the design ... [more ▼]

Understanding the structure and stability, as well as response properties of molecular crystals at certain thermodynamic conditions is crucial for the engineering of new molecular materials and the design of pharmaceuticals. A reliable description of the polymorphic energy landscape of a molecular crystal would provide an extensive insight into the development of drugs in terms of the existence and the likelihood of late-appearing polymorphs. Furthermore, accurate modeling of low-frequency vibrational spectra would be important for the characterization of molecular crystal polymorphs. However, an accurate description of molecular crystals is very challenging since many properties highly depend on the crystal-packing arrangement of the involved molecules and the temperature. The difficulties for computational predictions of molecular crystal polymorphs lie in the high dimensionality of crystallographic and conformational space, and the need for very accurate relative free energies. It was shown that accurate lattice energies can be obtained by using density-functional theory (DFT) calculations supplemented by a high-level model for long-range van der Waals (vdW) dispersion interactions, such as the many-body dispersion (MBD) model. Therefore, this thesis utilizes throughout vdW-inclusive DFT using the MBD and the related pairwise Tkatchenko-Scheffler (TS) dispersion model and the importance of dispersion interactions is highlighted for several properties. A hierarchical stability-ranking approach based on the DFT+MBD framework for the final stage of a molecular crystal structure prediction procedure is presented and analyzed. This approach provides excellent stability rankings over the diverse set of molecular crystals studied in the latest blind test of the Cambridge Crystallographic Data Centre. The results suggest that accounting for many-body dispersion effects and vibrational free energies can be crucial for the description of relative stabilities, especially for highly polymorphic systems. The presented approach enables the calculation of reliable structures and thermodynamic stabilities for pharmaceutically relevant systems, contributing to a better understanding of complex polymorphic energy landscapes. Furthermore, many first-principles calculations are performed by using fully optimized structures and free energies obtained within the harmonic approximation, neglecting the thermal expansion of the studied molecular crystal and further anharmonic effects. Therefore, this thesis illustrates that the majority of the thermal expansion of molecular crystals can be captured with the used methods by applying the quasi-harmonic approximation. In addition, we estimate further anharmonic effects on the vibrational frequencies by utilizing Morse oscillators. [less ▲]

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See detailEntrepreneurial Teams, New Venture Direction and Growth: Evidence from Luxembourg
Tryba Geb. Fricke, Anne Karin UL

Doctoral thesis (2018)

New ventures can be an important driver of economic growth and technological progress. Yet, many new ventures fail and do not overcome the challenges of the early entrepreneurial phase. Extant research ... [more ▼]

New ventures can be an important driver of economic growth and technological progress. Yet, many new ventures fail and do not overcome the challenges of the early entrepreneurial phase. Extant research has acknowledged that the people who jointly start and manage a new venture have a key impact on its subsequent success and development. However, a discrepancy exists in how the interplay of their characteristics, cognition, and actions ultimately shape the way a new venture evolves. Therefore the primary purpose of this thesis is to contribute to this research stream by exploring the multifaceted role of entrepreneurial teams for new venture direction and growth. This is done with the aid of three research papers relying on a multiple case study and a specifically designed dataset from Luxembourg. The first paper illuminates how the shared pre-start-up transition moments of entrepreneurial team members influence the joint decision logic in the initial venture phase. Focusing on the composition of entrepreneurial teams, the second paper illustrates early activities that allow new ventures to leverage the diverse educational backgrounds of their team members to achieve financial growth. Lastly, the third paper explores aspects of leadership in new ventures and uncovers how agreement on an early shared vision affects subsequent changes in the entrepreneurial team, taking into account members’ relational ties. This thesis makes important contributions to research in entrepreneurship and strategic management, adding to a more fine-grained view on the micro-foundations and outcomes of entrepreneurial action. Also, it has practical implications for entrepreneurs, their mentors and investors, entrepreneurship education and policymakers. [less ▲]

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See detailZebrafish models of Dravet syndrome: discovery of antiseizure drug leads and analysis of behavioural comorbidities
Jacmin, Maxime UL

Doctoral thesis (2018)

Dravet syndrome (DS) is one of the most frequent genetic epilepsies, with an incidence of 1/30,000. Most DS patients are pharmacoresistant, in that they do not respond adequately to currently available ... [more ▼]

Dravet syndrome (DS) is one of the most frequent genetic epilepsies, with an incidence of 1/30,000. Most DS patients are pharmacoresistant, in that they do not respond adequately to currently available anticonvulsant drugs (ASDs). Beside the seizure occurrence in these patients, many DS patients also suffer from cognitive impairment that can be aggravated by some of the seizure medications prescribed. Preclinical models such as mouse models of Dravet syndrome have been developed and described to exhibit cognitive deficits similar to those of DS patients, but are only suitable for the evaluation of small number of compounds, thereby limiting their utility for drug discovery. An animal model with higher screening throughput would therefore be of value for drug discovery efforts focused on seizure reduction and decrease of the comorbidities associated with DS. Recent studies on zebrafish have demonstrated its ability to be a promising in vivo model for DS. Two different zebrafish DS models - one based on a loss-of-function mutation in the zebrafish ortholog of SCN1A, the other based on an antisense knockdown of this gene - exhibit seizure-like behaviour and epileptiform discharges that are exacerbated by hyperthermia. The mutant line was also described to display greater anxiety levels. In this Doctoral thesis project, we are investigating these zebrafish DS models with regard to (1) their seizure occurrence and potential reduction following exposure to several anticonvulsant drug candidates, and (2), their cognitive functions in order to determine possible similarities with cognitive impairment in human DS patients. Our results indicate these zebrafish DS models to exhibit memory impairment and higher anxiety levels. These findings provide an initial insight into the resemblance between human patients and zebrafish in terms of comorbidities. Finally, we also identified several novel anticonvulsant compounds and drug candidates with antiseizure activity in these zebrafish DS models. [less ▲]

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See detailLink Optimization in Future Generation Satellite Systems
Mengali, Alberto UL

Doctoral thesis (2018)

In recent years, communication networks have seen a huge growth in the amount of requested throughput, pushed from the combination of two main drivers: the introduction of new services and the improvement ... [more ▼]

In recent years, communication networks have seen a huge growth in the amount of requested throughput, pushed from the combination of two main drivers: the introduction of new services and the improvement of existing ones, requiring increased amount of traffic (e.g. higher quality of video content). These effects mandate the constant evolution of current systems in order to cope with the growing user demand and should be tackled from multiple angles. On the one hand, better utilization of available resources might help in the short term to keep up with the market and has always been an important priority for operators of terrestrial and satellite networks alike. On the other hand, acquisition and exploitation of currently unused resources might fuel the growth for a significantly longer period of time, ensuring longevity and thus enabling future-proofing of current systems. Both these topics are addressed in this thesis with specific applications relevant to satellite communication networks. In the first part, this thesis focuses on maximization of the user capacity by better exploiting the available radio resources. Motivated by the substantial capacity gains enabled by a higher bandwidth allocation, we investigate the optimization of satellite systems employing full-frequency reuse on the user downlink. Unlike most of the literature on the subject, usually resorting to precoding techniques to mitigate the interference, we propose a combination of predistortion and precoding to jointly counteract on-board non-linear distortions and multi-user interference. First, a flexible framework for the optimization of transmit processing schemes in communication chains is presented. This framework expands on the application of the well known gradient descent technique by applying it to the maximization of the received Signal to Noise plus Interference ratio in complex communication systems. To do so, it identifies a suitable mathematical representation of various key blocks of the system and exploits the chain rule of the derivative to compute the overall gradient as a cascade of the single components. Afterwards, this framework is validated by optimizating the coefficients of the proposed predistortion architecture for the satellite system in analysis. The obtained results highlight the flexibility of the developed optimization framework and the benefits of the suggested predistortion strategy compared to existing state of the art solutions. In the second part of the thesis, the focus is shifted towards investigating the exploitation of novel resources by looking at the use of optical frequencies for ground-to-space feeder links. The topic is introduced by a survey of existing benefits and limitations of free space optical communications. Subsequently, the implications of employing optical frequencies in long distance ground-to-space feeder links with transparent satellites are addressed. Furthermore, a powerful and flexible simulation tool was developed and exploited during the course of this thesis to model and assess the Physical (PHY) layer performance of hybrid optical/Radio Frequencies (RF) satellite networks. This tool is presented together with the scenarios and results obtained as part of the project ONSET (Optical Feeder Links Study for Satellite Networks - ESA Contract No. 40000113462/15/NL/NDe). Finally, the thesis investigates a scenario that combines the transmit processing techniques analyzed in the first part and the context of optical feeder links evaluated in the second part. A hybrid optical/RF system is considered with an electrical predistorter in place to counteract the impairments induced by the combined effects of electrical and optical non-linearities encountered along the end-to-end chain. The developed mathematical framework is exploited to jointly optimize the predistortion coefficients and the working point for the electro-optical modulator. The performance results obtained after the optimization procedure demonstrate the efficacy of the proposed approach for hybrid optical/RF systems with analog modulations. [less ▲]

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See detailPrivacy-preserving Recommender Systems Facilitated By The Machine Learning Approach
Wang, Jun UL

Doctoral thesis (2018)

Recommender systems, which play a critical role in e-business services, are closely linked to our daily life. For example, companies such as Youtube and Amazon are always trying to secure their profit by ... [more ▼]

Recommender systems, which play a critical role in e-business services, are closely linked to our daily life. For example, companies such as Youtube and Amazon are always trying to secure their profit by estimating personalized user preferences and recommending the most relevant items (e.g., products, news, etc.) to each user from a large number of candidates. State-of-the-art recommender systems are often built on top of collaborative filtering techniques, of which the accuracy performance relies on precisely modeling user-item interactions by analyzing massive user historical data, such as browsing history, purchasing records, locations and so on. Generally, more data can lead to more accurate estimations and more commercial strategies, as such, service providers have incentives to collect and use more user data. On the one hand, recommender systems bring more income to service providers and more convenience to users; on the other hand, the user data can be abused, arising immediate privacy risks to the public. Therefore, how to preserve privacy while enjoying recommendation services becomes an increasingly important topic to both the research community and commercial practitioners. The privacy concerns can be disparate when constructing recommender systems or providing recommendation services under different scenarios. One scenario is that, a service provider wishes to protect its data privacy from the inference attack, a technique aims to infer more information (e.g., whether a record is in or not) about a database, by analyzing statistical outputs; the other scenario is that, multiple users agree to jointly perform a recommendation task, but none of them is willing to share their private data with any other users. Security primitives, such as homomorphic encryption, secure multiparty computation, and differential privacy, are immediate candidates to address privacy concerns. A typical approach to build efficient and accurate privacy-preserving solutions is to improve the security primitives, and then apply them to existing recommendation algorithms. However, this approach often yields a solution far from the satisfactory-of-practice, as most users have a low tolerance to the latency-increase or accuracy-drop, regarding recommendation services. The PhD program explores machine learning aided approaches to build efficient privacy-preserving solutions for recommender systems. The results of each proposed solution demonstrate that machine learning can be a strong assistant for privacy-preserving, rather than only a troublemaker. [less ▲]

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See detailWine as an Investment
Sun, Huizhu UL

Doctoral thesis (2018)

During the last two decades, the wine auction market experienced non-monotonic dynamics and provided abnormal returns. When fine wine prices started to rise in the mid-1980s, wine investing transcended ... [more ▼]

During the last two decades, the wine auction market experienced non-monotonic dynamics and provided abnormal returns. When fine wine prices started to rise in the mid-1980s, wine investing transcended from a pastime into a serious investment transforming wine into a widespread investment activity. As an alternative asset, fine wine attracts increased attention among individual and institutional investors in recent years, particularly during the financial crisis due to its diversification potential. Economists also began evaluating wine as a new alternative asset class. In this thesis, we review the wine auction markets, study the price dynamics, and answer some fundamental questions. To build solid conclusions, we developed the largest French wine auction database encompassing the last 20 years. We summary our main contributions as follows. First, we review and explain the growth in recent global wine auction markets. Second, we construct price indices with hedonic regression models to observe market movements. Third, we investigate wine investment’s diversification potential. Wine in an optimal portfolio can improve the risk-return characteristics; however, the augmentation depends significantly on the market segmentation to which the investor applies it. Fourth, we analyze the wine price bubbles and collapses detection using a newly developed econometric approach. We elucidate strong evidence of two bubbles in the Bordeaux and Burgundy wine auction markets, whereas Rhône wine price behaved in a similar, but less significant, trend as Bordeaux and Burgundy wine markets. Finally, we examine the price determinants with a particular focus on the expert effect on this experienced good. We illuminate expert influence remains economically and statistically significant throughout the sample period. Using event study methodology, we disentangle the expert effect from other price variations and assert the market significantly reflects expert’s big re-ratings in the short term, yet the effect diminishes over time. However, this re-rating effect holds insignificant for modest changes. [less ▲]

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See detailTransport and thermodynamics in driven quantum systems
Haughian, Patrick UL

Doctoral thesis (2018)

This thesis studies the nonequilibrium properties of quantum dots with regard to electrical conduction as well as thermodynamics. The work documented here shows how these properties behave under the ... [more ▼]

This thesis studies the nonequilibrium properties of quantum dots with regard to electrical conduction as well as thermodynamics. The work documented here shows how these properties behave under the influence of time-dependent drive protocols, pursuing two main lines of inquiry. The first concerns the interplay between nanomechanics and drive: In nanomechanical systems with strong coupling between the charge and vibrational sectors, conductance is strongly suppressed, an effect known as Franck-Condon blockade. Using a model Hamiltonian for a molecular quantum dot coupled to a pair of leads, it is shown here that this blockade can be exponentially lifted by resonantly driving the dot. Moreover, a multi-drive protocol is proposed for such a system to facilitate charge pumping that enjoys the same exponential amplification. The second line of inquiry moves beyond charge transport, examining the thermodynamics of a driven quantum dot coupled to a lead. Taking a Green's function approach, it is found that the laws of thermodynamics can be formulated for arbitrary dot-lead coupling strength in the presence of dot and coupling drive, as long as the drive protocol only exhibits mild non-adiabaticity. Finally, the effects of initial states are studied in this situation, proving that the integrated work production in the long-time limit conforms to the second law of thermodynamics for a wide class of initial states and arbitrary drive and coupling strength. [less ▲]

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See detailLegitimate expectations in Luxembourg tax law - A study of administrative circulars and tax rulings issued by the Luxembourg tax authorities
Chaouche, Fatima UL

Doctoral thesis (2018)

This thesis analyzes the status of tax circulars and tax rulings in domestic law. More precisely, by first studying the status of each of these administrative interpretative acts, I then investigate their ... [more ▼]

This thesis analyzes the status of tax circulars and tax rulings in domestic law. More precisely, by first studying the status of each of these administrative interpretative acts, I then investigate their enforceability before domestic courts and enquire to what extent unlawful circulars and contra legem rulings can be relied upon by virtue of the principle of legitimate expectations. After extracting a series of shortcomings in the protection of taxpayers who rely on such administrative interpretative acts, I then, articulate from a normative perspective, what I claim to be the appropriate level of protection for contra legem circulars and advance decisions in the Luxembourg legal order. [less ▲]

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See detailBildungswerte und Schulentfremdung: Institutions- und Kompositionseffekte in den Bildungskontexten Luxemburgs und der Schweiz
Scharf, Jan UL

Doctoral thesis (2018)

Values and attitudes towards schooling – as the core concepts of this research – are increasingly recognized as important factors affecting educational achievement and attainment. Values of Education (VoE ... [more ▼]

Values and attitudes towards schooling – as the core concepts of this research – are increasingly recognized as important factors affecting educational achievement and attainment. Values of Education (VoE) are conceptualised along the five instrumental goals outlined in the social production function theory by Lindenberg (1991; Ormel et al., 1999). School alienation (SAL) is defined as negative attitudes towards academic domains of schooling, namely teachers and learning (Hascher & Hadjar, 2018: 179). Based on the assumption that SAL depicts a process intensified over the course of secondary education (Finn, 1989), this dissertation finds evidence for developmental trends between grade seven and grade eight comparatively across country settings and to show how educational contexts and the perceived VoE affect SAL. This sociological study provides an in-depth comparison of the stratified school systems of Luxembourg and of the Canton of Berne (Switzerland) based upon newly-collected panel data of the international research project School Alienation in Switzerland and Luxembourg (SASAL) (N = 465/508). Following the distinction of primary and secondary effects of social origin by Boudon (1974), these core concepts are discussed in the frames of Bourdieu’s (1982 [1979], 1992) habitus theory, emphasizing the transmission of cultural capital in families, and of rational choice approaches (e.g. Esser, 1999). Moreover, theoretical approaches on disparities structured by gender (e.g. Breen et al., 2010) and migration background (Kristen & Dollmann, 2010) as well as further axes of educational inequalities are considered to explain found differences in students’ educational values and attitudes towards schooling. The validation of the measurement instrument of VoE by means of factor analysis indicates four dimensions of VoE among school students in these contexts: stimulation as an intrinsic value, comfort and status related to standards of living and future career goals, behavioural confirmation in terms of expectations of significant others, and the social goal affection. Structural equation models demonstrate that the lower value of stimulation through education among boys mediates their higher level of SAL across country contexts. Yet, a higher value of comfort/status among students increases the development of negative attitudes. Whereas immigrant students’ higher behavioural confirmation in the Canton of Bern backs the immigrant optimism thesis (Kao & Tienda, 1995), immigrant students in Luxembourg reveal a general lower VoE and are more alienated from teachers. Contextual effects estimated in multilevel models explain the higher prevalence of alienation from learning in Luxembourgish classrooms. Within the stratified and segregated secondary schooling, students in the academic track are more alienated compared to students in technical secondary education. This result contradicts the differentiation–polarization theory (Van Houtte, 2006) in the context of Luxembourg. On the other hand, in Berne, alienation from learning does not differ between school tracks, but is overall lower in the less segregated, more permeable schools. Classroom composition effects, however, show no clear pattern. In line with prior research, alienation from learning is lower in Luxembourgish classrooms with a higher percentage of immigrant students. With regard to the consequences of SAL, the results show a negative impact of alienation from learning on school achievement in both country settings. Deriving implications, the findings provide some arguments in favour of comprehensive school models. [less ▲]

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See detailConservation Laws in Nonequilibrium Thermodynamics: Stochastic Processes, Chemical Reaction Networks, and Information Processing
Rao, Riccardo UL

Doctoral thesis (2018)

Thermodynamics has a long history. It was established during the 19th century as a phenomenological theory grasping the principles underlying heat engines. In the 20th and 21st centuries its range of ... [more ▼]

Thermodynamics has a long history. It was established during the 19th century as a phenomenological theory grasping the principles underlying heat engines. In the 20th and 21st centuries its range of applicability was extended to nonequilibrium stochastic and chemical processes. However a systematic procedure to identify the thermodynamic forces at work in these systems was lacking. In this thesis, we provide one by making use of conservation laws. Of particular importance are the conservation laws which are broken when putting the system in contact with different reservoirs (thermostats or chemostats). These laws depend on the internal structure of the system and are specific to each system. We introduce a systematic procedure to identify them and show how they shape the entropy production (i.e. the dissipation) into fundamental contributions. Each of these provides precious insight on how to drive and control the system out of equilibrium. We first present our results at the level of phenomenological thermodynamics. We then show that they can be systematically derived for various dynamics: Markov jump processes used in stochastic thermodynamics, also including the chemical master equation, and deterministic chemical rate equations with and without diffusion, which are used to describe chemical reaction networks. Generalized nonequilibrium Landauer principles ensue form our theory. They predict that the minimal thermodynamic cost necessary to transform the system from an arbitrary nonequilibrium state to another can be expressed in terms of information metrics such as relative entropies between the equilibrium and nonequilibrium states of the system. [less ▲]

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See detailThe Significance of the Place of Performance in Commercial Contracts under the European Union Choice of Law Rules
Okoli, Chukwuma Samuel Adesina UL

Doctoral thesis (2018)

The central theme of this thesis is that the place of performance is of considerable significance as a connecting factor in international commercial contracts. This thesis challenges and questions the ... [more ▼]

The central theme of this thesis is that the place of performance is of considerable significance as a connecting factor in international commercial contracts. This thesis challenges and questions the approach of the European legislator, which does not explicitly give the place of performance special significance in the determination of the applicable law in the absence of choice for commercial contracts. This thesis proposes that the place of performance should be explicitly given special significance under a revised Article 4 of Rome I Regulation. Second, it is argued that the absolute significance given to the place of performance in determining foreign country overriding mandatory rules is a good reason why the place of performance should be explicitly given special significance under a revised Article 4 of Rome I Regulation. Third, inspired by the coherence between matters of European Union jurisdiction and choice of law in civil and commercial matters, it is argued that the place of performance which is given special significance under the European Union rules on the allocation of jurisdiction for commercial contracts is a good reason why the place of performance should be explicitly given special significance under a revised Article 4 of Rome I Regulation. This thesis then concludes by proposing a model revised Article 4 of Rome I Regulation that could be used as an international solution by legislators, judges, arbitrators, and other decision makers who wish to reform their choice of law rules in determining the applicable law in the absence of choice for international commercial contracts. [less ▲]

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See detailEvaluating Vulnerability Prediction Models
Jimenez, Matthieu UL

Doctoral thesis (2018)

Today almost every device depends on a piece of software. As a result, our life increasingly depends on some software form such as smartphone apps, laundry machines, web applications, computers ... [more ▼]

Today almost every device depends on a piece of software. As a result, our life increasingly depends on some software form such as smartphone apps, laundry machines, web applications, computers, transportation and many others, all of which rely on software. Inevitably, this dependence raises the issue of software vulnerabilities and their possible impact on our lifestyle. Over the years, researchers and industrialists suggested several approaches to detect such issues and vulnerabilities. A particular popular branch of such approaches, usually called Vulnerability Prediction Modelling (VPM) techniques, leverage prediction modelling techniques that flag suspicious (likely vulnerable) code components. These techniques rely on source code features as indicators of vulnerabilities to build the prediction models. However, the emerging question is how effective such methods are and how they can be used in practice. The present dissertation studies vulnerability prediction models and evaluates them on real and reliable playground. To this end, it suggests a toolset that automatically collects real vulnerable code instances, from major open source systems, suitable for applying VPM. These code instances are then used to analyze, replicate, compare and develop new VPMs. Specifically, the dissertation has 3 main axes: The first regards the analysis of vulnerabilities. Indeed, to build VPMs accurately, numerous data are required. However, by their nature, vulnerabilities are scarce and the information about them is spread over different sources (NVD, Git, Bug Trackers). Thus, the suggested toolset (develops an automatic way to build a large dataset) enables the reliable and relevant analysis of VPMs. The second axis focuses on the empirical comparison and analysis of existing Vulnerability Prediction Models. It thus develops and replicates existing VPMs. To this end, the thesis introduces a framework that builds, analyse and compares existing prediction models (using the already proposed sets of features) using the dataset developed on the first axis. The third axis explores the use of cross-entropy (metric used by natural language processing) as a potential feature for developing new VPMs. Cross-entropy, usually referred to as the naturalness of code, is a recent approach that measures the repetitiveness of code (relying on statistical models). Using cross-entropy, the thesis investigates different ways of building and using VPMs. Overall, this thesis provides a fully-fledge study on Vulnerability Prediction Models aiming at assessing and improving their performance. [less ▲]

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See detailImpact of floating bodies on buildings and structures during flooding
Liao, Yu-Chung UL

Doctoral thesis (2018)

Flood is one of the most serious natural disasters that affect human beings, so how to effectively reduce flood damage to human beings is of vital im- portance. One of the keys to reducing flood damage is ... [more ▼]

Flood is one of the most serious natural disasters that affect human beings, so how to effectively reduce flood damage to human beings is of vital im- portance. One of the keys to reducing flood damage is to design buildings effectively enough to withstand flooding and the impact of floating debris on the structures. Although, many studies exist to address the impact of floods on structures, the impact of floating debris on the buildings and structures, i.e. wall or bridge during flooding have not been fully addressed yet. Thus, the objec- tive of this dissertation is to predict the trajectory of floating debris of rivers during flooding and analyze its impact on the structures. For achieving this goal, a numerical tool based on the mesh-less method of Smoothed Particle Hydrodynamics (SPH), Discrete Element Method (DEM) and Finite Element Method (FEM) is proposed in this dissertation. Where SPH is employed to describe the fluid flow and DEM is employed to ob- tain the contact force between the floating debris and structures. And a coupling model of SPH and DEM is presented and implemented based on the OpenFPM, a scalable and open C++ framework for particles and mesh simulation in parallel. Buildings and structures are represented by Finite Element Method (FEM) mesh, for which impact with floating debris is de- termined. These contacts of floating debris cause forces at the positions of impact, e.g. mechanical load and are evaluated by using commercial Finite Element Analysis (FEA) software Abaqus. As a result, a numerical tool combing the SPH-DEM and FEA is presented in this dissertation It is worth to notice, that treating the inlet/outlet con- dition in SPH is a challenging issue due to its Lagrangian nature. A suitable boundary treatment for the inlet / outlet condition in SPH for river flooding problem in 3D is unavailable in literatures. Thus, this dissertation extended the open boundary treatment for SPH using semi-analytical conditions and Riemann solver in 2D (Ferrand et al., 2017) to 3D. Which in results, a new open boundary treatment that is suitable for describing the inlet/outlet condition of SPH in 3D is presented and applied to describe the inlet/outlet condition in this dissertation. The numerical tool is applied to study the scenario of floating trees, trans- porting in the Mosel river and hitting the flood control wall at Kesten town in the west Germany during flooding. As the result of simulation shows, the floating trees are driven by the river and heading to the downstream and eventually collide with the flood control wall. This impact causes the flood control wall crack from the position of impact. Which means that the flood control wall is not capable of standing the impact of floating trees that transported in the river. [less ▲]

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See detailREPRESENTING THE SOCIAL CHARACTER OF PLACES: ONTOLOGY MODELS OF THE URBAN ENVIRONMENT
Calafiore, Alessia UL

Doctoral thesis (2018)

The thesis aimed at rendering machine understandable the social dimension of urban places to provide a new generation of urban analytics based on peoples’ socio- spatial behaviour. The main outcome has ... [more ▼]

The thesis aimed at rendering machine understandable the social dimension of urban places to provide a new generation of urban analytics based on peoples’ socio- spatial behaviour. The main outcome has been a formal framework, encoded in the form of Ontology Design Patterns, to represent the interaction between the architectural aspects of the city, its form, and the behaviour of city dwellers. Ontology models are based on place theories discussed by social and cultural geographers - such as Henri Lefevbre, Edward Soja and Doreen Massey - and experimented in a knowledge discovery pipeline by exploring geographic crowdsourced data coming from the TripAdvisor platform. [less ▲]

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See detailCollision-Free Navigation of Small UAVs in Complex Urban Environment
Annaiyan, Arun UL

Doctoral thesis (2018)

Small unmanned aerial vehicles (UAVs) are expected to become highly innovative solutions for all kind of tasks such as transport, surveillance, inspection or guidance, and many commercial ideas already ... [more ▼]

Small unmanned aerial vehicles (UAVs) are expected to become highly innovative solutions for all kind of tasks such as transport, surveillance, inspection or guidance, and many commercial ideas already exist. Herein, small multi rotor UAVs are preferred since they are easy to construct and to fly, at least in wide open spaces. However, many UAV business cases are foreseen in complex urban environments which are very challenging from the perspective of UAV flight. Our work focuses on the autonomous flight and collision-free navigation in an urban environment, where GPS is still considered for localization but where variations in the accuracy or temporary unavailability of GPS position data is explicitly considered. Herein, urban environments are challenging because they require flight nearby large structures and also nearby moving obstacles such as humans and other moving objects, at low altitudes or in very narrow spaces and thus also in areas where GPS (global positioning system) position data might temporarily be very inaccurate or even not available. Therefore we designed a custom stereo camera with adjustable base length for the perception of the possible potential obstacles in the unknown outdoor environment. In this context the optimal design and sensitivity parameters are investigated in outdoor experiments. Using the stereo images, graph based SLAM approach is used for online three dimensional mapping of the static and dynamic environment. For the memory efficiency incremental online loop closure detection using bag of words method is implemented here. By having the three dimensional map, the cost of the cell and its transition calculated in real time by the modified D* lite which will search and generate three dimensional collision free path planning. Experiments of the 3D mapping and collision free path planning are conducted using small UAV in outdoor scenario. The combined experimental results of real time mapping and path planning demonstrated that the three dimensional collision free path planning is able to handle the real time computational constraints while maintaining safety distance. [less ▲]

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