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See detailInflammatory signaling in liver cells: Cross-regulation of the IL-6/JAK/STAT3 pathway and microRNAs
Servais, Florence UL

Doctoral thesis (2017)

Interleukin-6 (IL-6) plays important roles in the regulation of liver functions and promotes the development of hepatocellular carcinoma (HCC), the most common primary liver cancer. Whereas protein ... [more ▼]

Interleukin-6 (IL-6) plays important roles in the regulation of liver functions and promotes the development of hepatocellular carcinoma (HCC), the most common primary liver cancer. Whereas protein-encoding genes are well-studied, the contribution of IL-6-regulated microRNAs (miRNAs) to its effects is largely unexplored. Similarly, little is known about miRNAs regulating key molecules of the IL-6/JAK/STAT3 signaling pathway. In the main part of this thesis, cell-based high-throughput screenings systems were developed, allowing the identification of miRNAs interfering with the IL-6/JAK/STAT3 signaling. Out of 538 miRNA mimics, this dual screening approach followed by various validation steps (luciferase-3’UTR-reporter assays, western blot and flow cytometry analyses) allowed us to identify twelve miRNAs targeting STAT3, JAK1, SOCS3, IL6R and/or gp130, ten of them had not yet been reported as regulators of this pathway before. In the second part of this work, microarray analyses revealed that primary hepatocytes are considerably more responsive to IL-6 stimulation regarding changes in their miRNomes than liver-derived cell lines. Despite their weaker response, one of the top regulated miRNA found in the primary hepatocytes, miR-146b-5p, could also be induced by IL-6-type cytokines (IL-6 and Oncostatin M) in cell lines. Its functional role(s) in hepatocytes are currently investigated. A larger, comparative study included additionally Interferon gamma and IL-27, cytokines with a STAT1-dominated response, and supplementary cell lines originating not only from the liver but also from other tissues. While all cytokines had profound effects on the mRNA transcriptomes, only very small to moderate changes were observed at the miRNome level, suggesting that the regulation mediated by cytokines mainly happens through the modulation of protein-coding genes rather than by fine-tuning via miRNAs. Additionally, we analyzed expression of a broad panel of cytokines in sera of 125 patients with liver diseases (steatosis, non-alcoholic steatohepatitis, HCC) by bead-based multiplex immunoassays. We observed that, for example, serum HGF, IL-6 and IL-8 levels increased in relation with the severeness of liver pathology while PDGF-BB and RANTES decreased. When investigating the impact of the patatin-like phospholipase domain-containing protein 3 variant I148M (PNPLA3 I148M), known to be a risk factor for the development of liver diseases, on the serum levels of cytokines, no significant differences could be observed between the different genotypes. In this PhD thesis, we identified and characterized miRNAs relevant for the IL-6/JAK/STAT3 signaling pathway, including miR-146b-5p as an IL-6-inducible miRNA. Others like miR-194-5p, miR-4473 and miR-548k were demonstrated to be negative regulators of this pathway and may be of potential therapeutic significance. In addition, we showed that, while miRNAs can modulate this pathway, IL-6 seems to rather regulate the mRNA transcriptome than the miRNome. [less ▲]

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See detailAutomated and Effective Security Testing for XML-based Vulnerabilities
Jan, Sadeeq UL

Doctoral thesis (2017)

Nowadays, the External Markup Language (XML) is the most commonly used technology in web services for enabling service providers and consumers to exchange data. XML is also widely used to store data and ... [more ▼]

Nowadays, the External Markup Language (XML) is the most commonly used technology in web services for enabling service providers and consumers to exchange data. XML is also widely used to store data and configuration files that control the operation of software systems. Nevertheless, XML suffers from several well-known vulnerabilities such as XML Injections (XMLi). Any exploitation of these vulnerabilities might cause serious and undesirable consequences, e.g., denial of service and accessing or modifying highly-confidential data. Fuzz testing techniques have been investigated in the literature to detect XMLi vulnerabilities. However, their success rate tends to be very low since they cannot generate complex test inputs required for the detection of these vulnerabilities. Furthermore, these approaches are not effective for real-world complex XML-based enterprise systems, which are composed of several components including front-end web applications, XML gateway/firewall, and back-end web services. In this dissertation, we propose several automated security testing strategies for detecting XML-based vulnerabilities. In particular, we tackle the challenges of security testing in an industrial context. Our proposed strategies, target various and complementary aspects of security testing for XML-based systems, e.g., test case generation for XML gateway/firewall. The development and evaluation of these strategies have been done in close collaboration with a leading financial service provider in Luxembourg/Switzerland, namely SIX Payment Services (formerly known as CETREL S.A.). SIX Payment Services processes several thousand financial transactions daily, providing a range of financial services, e.g., online payments, issuing of credit and debit cards. The main research contributions of this dissertation are: -A large-scale and systematic experimental assessment for detecting vulnerabilities in numerous widely-used XML parsers and the underlying systems using them. In particular, we targeted two common XML parser’s vulnerabilities: (i) XML Billion Laughs (BIL), and (ii) XML External Entities (XXE). - A novel automated testing approach, that is based on constraint-solving and input mutation techniques, to detect XMLi vulnerabilities in XML gateway/firewall and back-end web services. - A black-box search-based testing approach to detect XMLi vulnerabilities in front-end web applications. Genetic algorithms are used to search for inputs that can manipulate the application to generate malicious XML messages. - An in-depth analysis of various search algorithms and fitness functions, to improve the search-based testing approach for front-end web applications. - Extensive evaluations of our proposed testing strategies on numerous real-world industrial web services, XML gateway/firewall, and web applications as well as several open-source systems. [less ▲]

See detailCRISPR/CAS9 AND PIGGYBAC MEDIATED LRRK2-G2019S IN VITRO PARKINSON’S DISEASE MODELING
Qing, Xiaobing UL

Doctoral thesis (2017)

Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by the progressive loss of dopaminergic (DA) neurons in the substantial nigra pars compacta (SNpc) area of the ... [more ▼]

Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by the progressive loss of dopaminergic (DA) neurons in the substantial nigra pars compacta (SNpc) area of the human midbrain with an unclear cause. Mutations revealed by whole genome sequencing (WGS) from familial PD cases may explain how cell loss occurs. Confirmation of this hypothesis has been hampered by the lack of available cell types from affected patients. Transgenic animal models have been used, but differences between these animals and humans have greatly impacted their usefulness for studying human diseases. Additionally, because PD is regarded to only affect humans, reliable human material-based experimental models are urgently needed. Human-induced pluripotent stem cells (hiPSCs)- derived DA neurons provide an opportunity to establish in vitro mutation-related PD models of disease-relevant cells that represent replacement alternatives to in vivo animal experiments. However, these hiPSCs-based PD models have limitations regarding the genetic background differences between patients and healthy controls. Genomic editing of hiPSCs allows for the generation of isogenic cellular models that differ only in the disease-specific mutations of interest. Currently, the biggest concern regarding nuclease-mediated genomic editing is the potentially undesirable alterations associated with remnant sequences, off-target effects and random integration, which may result in cell lines not being truly isogenic. To avoid potential confounding effects and establish a causal link between genotype and phenotype, robust isogenic cell lines free of unwanted mutagenesis are absolutely required for the study of PD. To better understand the pathogenesis of the most prevalent leucine-rich repeat kinase 2 (LRRK2) mutation, G2019S, which causes both familial and sporadic PD, patient hiPSCs have been corrected using the Cre/LoxP recombination system. However, the LoxP site inevitably remaining after excision of the selection cassette can influence gene expression. In this thesis, a “footprint-free” LRRK2-G2019S isogenic model was created using clustered regularly interspaced short palindromic repeats/Cas9-associated (CRISPR/Cas9) system and a piggyBac transposon that can remove selection cassettes without leaving remnants. In LRRK2-G2019S DA neurons, the percentage of tyrosine hydroxylase (TH)-positive neurons with a total neurite length greater than 2 cm was significantly reduced, and the average branch number was also decreased. These PD-like phenotypes could be rescued by administration of the specific LRRK2 inhibitor LRRK2-IN-1 and by the compound BRF110, which activates the Nurr1:RXRa heterodimer to replenish the DA shortage. Our data suggest that the “footprint- free” LRRK2-G2019S isogenic cell lines allow standardized, genetic background-independent, in vitro PD modeling and are suitable for screening novel drugs that have clinical applications. In addition, we have shown that in vitro TH-positive neurons with a total neurite length greater than 2 cm were positive for serine 129 phosphorylated (S129P) α-synuclein, and we hypothesize that S129P α-synuclein plays a role in the maintenance or formation of long neurites. Thus, we have also provided new insights into the roles of LRRK2-G2019S and S129P α-synuclein in PD pathogenesis. Furthermore, we have optimized CRISPR/Cas9-mediated genomic editing in hiPSCs by establishing a FACS-assisted CRISPR/Cas9 editing (FACE) strategy that uses three fluorescent proteins to isolate biallelic-edited cells with no random integration and by using Exonuclease III (ExoIII)-facilitated long single stranded DNA (ssDNA) donor to reduce random integration. [less ▲]

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See detailProjectional Editing of Software Product Lines–The PEoPL approach
Behringer, Benjamin UL

Doctoral thesis (2017)

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See detailAutomated requirements-driven testing of embedded systems based on use case specifications and timed automata
Wang, Chunhui UL

Doctoral thesis (2017)

The complexity of embedded software in safety-critical domains, such as automotive and avionics, has significantly increased over the years. For most embedded systems, standards require system testing to ... [more ▼]

The complexity of embedded software in safety-critical domains, such as automotive and avionics, has significantly increased over the years. For most embedded systems, standards require system testing to explicitly demonstrate that the software meets its functional and safety requirements. In these domains, system test cases are often manually derived from functional requirements in natural language plus other design artefacts, like UML statecharts. The definition of system test cases is therefore time-consuming and error-prone, especially given the quickly rising complexity of embedded systems. The benefits of automatic test generation are widely acknowledged today but existing approaches often require behavioural models that tend to be complex and expensive to produce, and are thus often not part of development practice. The work proposed in this dissertation focusses on the automated generation of test cases for testing the compliance between software and its functional and timing requirements. This dissertation is inspired by contexts where functional and timing requirements are expressed by means of use case specifications and timing automata, respectively. This is the development context of our industrial partner, IEE, an automotive company located in Luxembourg, who provided the case study used to validate the approach and tool described in this dissertation. This dissertation presents five main contributions: (1) A set of guidelines for the definition of functional and timing requirements to enable the automated generation of system test cases. (2) A technique for the automated generation of functional test cases from requirements elicited in the form of use case specifications following a prescribed template and natural-language restrictions. (3) A technique that reuses the automatically generated functional test cases to generate timeliness test cases from minimal models of the timing requirements of the system. (4) A technique for the automated generation of oracles for non-deterministic systems whose specifications are expressed by means of timed automata. In the context of this dissertation, automated oracles for non-deterministic systems are necessary to evaluate the results of the generated timeliness test cases. (5) The evaluation of the applicability and effectiveness of the proposed guidelines and techniques on an industrial case study, a representative automotive embedded system developed by IEE. [less ▲]

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See detailActive Learning in Cognitive Radio Networks
Tsakmalis, Anestis UL

Doctoral thesis (2017)

In this thesis, numerous Machine Learning (ML) applications for Cognitive Radios Networks (CRNs) are developed and presented which facilitate the e cient spectral coexistence of a legacy system, the ... [more ▼]

In this thesis, numerous Machine Learning (ML) applications for Cognitive Radios Networks (CRNs) are developed and presented which facilitate the e cient spectral coexistence of a legacy system, the Primary Users (PUs), and a CRN, the Secondary Users (SUs). One way to better exploit the capacity of the legacy system frequency band is to consider a coexistence scenario using underlay Cognitive Radio (CR) techniques, where SUs may transmit in the frequency band of the PU system as long as the induced to the PU interference is under a certain limit and thus does not harmfully a ect the legacy system operability. [less ▲]

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See detailAchtsamkeit als Determinante von Glück im Alter - Theoretische und Empirische Analysen
Theisen, Marie-Paule Gaby UL

Doctoral thesis (2017)

In den späten siebziger Jahren entwickelte der Molekularbiologe und Zen-Praktiker Jon Kabat-Zinn in den USA das „Mindfulness-Based Stress Reduction Program – MBSR“ (dt.: das Programm zur Stressreduzierung ... [more ▼]

In den späten siebziger Jahren entwickelte der Molekularbiologe und Zen-Praktiker Jon Kabat-Zinn in den USA das „Mindfulness-Based Stress Reduction Program – MBSR“ (dt.: das Programm zur Stressreduzierung durch Achtsamkeit). Der Medizinprofessor begann mit Erfolg, das Programm an Schmerzpatienten der University of Massachusetts Medical School Stress Reduction Clinic zu vermitteln. Parallel dazu untersuchte der Forscher die Auswirkungen dieses Stressreduzierungsprogramms auf das psychische und physische Wohlbefinden der Patienten. Diese Forschungsergebnisse veranlassten mich dazu, das bestehende Programm MBSR an die Bedürfnisse und Wünsche von gesunden, existenziell verängstigten, gestressten Menschen im Vorrentenalter und Rentenalter anzupassen und das Programm „Achtsamkeit Entdecken – Leben im Augenblick“ (AELA) für Senioren zu entwickeln. Als theoretische Grundlage dieses Programms wurden einschlägige Theorien zu Achtsamkeit, Glück und dem Alternsprozess beschrieben und in ihrem Zusammenhang elaboriert. Anschließend daran wurden über eine Kombination von quantitativem und qualitativem Vorgehen die Nützlichkeit und die Wirkungen von Achtsamkeit auf das Glücksempfinden „betagter“ Menschen im Alltag untersucht. Im Rahmen einer quantitativ angelegten Trainingsstudie wurden über den Zeitraum von vier Wochen Achtsamkeitselemente vermittelt, die über die Selbstberichte der Teilnehmer evaluiert wurden. Insgesamt zeichneten sich dabei positive Effekte auf das Befinden der Teilnehmer ab und diese betrachteten die Achtsamkeitsübungen als nützlich, um bewusster zu leben. Im Rahmen einer qualitativen Studie wurden fünfzehn Interviews zum Leben im Alter durchgeführt und dabei unterschiedliche Aspekte – wie z.B. Wünsche und Ziele, aber auch Ängste und Befürchtungen – exploriert. In den Interviews wurde zudem erfragt, inwieweit die Personen bereits mit dem Konzept der Achtsamkeit vertraut sind und inwieweit sie dieses nutzen. Auch diese Studie belegt die Bedeutsamkeit dieses Konzeptes für das Leben im Alter. Alle Befunde sprechen somit dafür, dass der gesunde ältere Mensch durch eine regelmäßige Achtsamkeitspraxis – im Sinne eines bewussten Lebens von Augenblick zu Augenblick – Stressfreiheit und Glück erfahren kann.   [less ▲]

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See detailAUTOMATED DEBUGGING AND FAULT LOCALIZATION OF MATLAB/SIMULINK MODELS
Liu, Bing UL

Doctoral thesis (2017)

Matlab/Simulink is an advanced environment for modeling and simulating multidomain dynamic systems. It has been widely used to model advanced Cyber-Physical Systems, e.g. in the automotive or avionics ... [more ▼]

Matlab/Simulink is an advanced environment for modeling and simulating multidomain dynamic systems. It has been widely used to model advanced Cyber-Physical Systems, e.g. in the automotive or avionics industry. To ensure the reliability of Simulink models (i.e., ensuring that they are free of faults), these models are subject to extensive testing to verify the logic and behavior of software modules developed in the models. Due to the complex structure of Simulink models, finding root causes of failures (i.e., faults) is an expensive and time-consuming task. Therefore, there is a high demand for automatic fault localization techniques that can help en- gineers to locate faults in Simulink models with less human intervention. This demand leads to the proposal and development of various approaches and techniques that are able to automatically locate faults in Simulink models. Fault localization has been an active research area that focuses on developing automated tech- niques to support software debugging. Although there have been many techniques proposed to localize faults in programs, there has not been much research on fault localization for Simulink models. In this dissertation, we investigate and develop a lightweight fault localization approach to automatically and accurately locate faults in Simulink models. To enhance the usability of our approach, we also develop a stand-alone desktop application that provides engineers with a usable interface to facilitate localization of faults in their models. [less ▲]

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See detailParkinson's disease: Evaluation of a neuroprotective target and identification of candidate biomarker signatures using murine models
Ashrafi, Amer UL

Doctoral thesis (2017)

Parkinson's disease (PD) is one of the most common age-related neurologic diseases. While existing therapeutic approaches, focusing on dopamine replacement, can alleviate some of the cardinal symptoms ... [more ▼]

Parkinson's disease (PD) is one of the most common age-related neurologic diseases. While existing therapeutic approaches, focusing on dopamine replacement, can alleviate some of the cardinal symptoms, they are associated with severe adverse effects in the long-term. Therefore, identification of new therapeutic interventions to reverse, stop or slow down the progression of Parkinson’s disease is a major focus of PD research. Similarly, identifying reliable biomarkers that would enable early therapeutic intervention is another key area of current research. Here, we evaluated a recently proposed non-dopaminergic protein drug target for PD, Regulator of G-Protein Signaling 4 (RGS4), and performed preliminary studies aimed at the identification of novel biomarker signatures using two murine models of Parkinson’s disease. Recent research on new non-dopaminergic PD drug targets has indicated that inhibition of RGS4, a member of the RGS family of proteins that inactivate G-proteins, could be an effective adjuvant treatment option. However, the effectiveness of RGS4 inhibition for an array of PDlinked functional and structural neuroprotection endpoints had not yet been demonstrated. Here, we used the 6-Hydroxydopamine (6-OHDA) lesioning mouse model to address this question. We observed, using a battery of behavioral and pathological measures, that mice deficient for RGS4 are not protected from 6-OHDA induced injury, and showed enhanced susceptibility in some measures of motor function. Our results suggest that inhibition of RGS4 as a non-dopaminergic target for PD should be approached with caution. In the second part of this study, two alpha-synuclein based PD mouse models, human E46K mutated overexpressed alpha-synuclein and alpha-synuclein fibril spreading models, were used to investigate early pathological events in PD and identify novel candidate biomarker signatures for subsequent validation. Two different time points, before disease onset, and at peak disease manifestation, were analyzed in the two models. Using multiple histopathology and molecular biology techniques, we were able to identify complex changes in patterns of gene expression at early stages of the disease, well before neurodegeneration is detectable. These findings might open venues for new therapeutic strategies and provide insights on the molecular perturbations occurring during the earliest stages of the disease, paving the way for the development of a biomarker signatures for early diagnosis of Parkinson’s disease. [less ▲]

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See detailDevelopment and analysis of individual-based gut microbiome metabolic models
Magnusdottir, Stefania UL

Doctoral thesis (2017)

The human gut microbiota plays a large role in the metabolism of our diet. These microorganisms can break down indigestible materials such as polysaccharides and convert them into metabolites that the ... [more ▼]

The human gut microbiota plays a large role in the metabolism of our diet. These microorganisms can break down indigestible materials such as polysaccharides and convert them into metabolites that the human body can take up and utilize (e.g., vitamins, essential amino acids, and short-chain fatty acids). Disbalances in the gut microbiome have been associated with several diseases, including diabetes and obesity. However, little is known about the detailed metabolic crosstalk that occurs between individual organisms within the microbiome and between the microbiome and the human intestinal cells. Because of the complexity of the intestinal ecosystem, these interactions are difficult to determine using existing experimental methods. Constraint-based reconstruction and analysis (COBRA) can help identify the possible metabolic mechanisms at play in the human gut. By combining mathematical, computational, and experimental methods, we can generate hypotheses and design targeted experiments to elucidate the metabolic mechanisms in the gut microbiome. In this thesis, I first applied comparative genomics to analyze the biosynthesis pathways of eight B-vitamins in hundreds of human gut microbial species. The results suggested that many gut microbes do not synthesize any B-vitamins, that is, they depend on the host’s diet and neighboring bacteria for these essential nutrients. Second, I developed a semi-automatic reconstruction refinement pipeline that quickly generates biologically relevant genome-scale metabolic reconstructions (GENREs) of human gut microbes based on automatically generated metabolic reconstructions, comparative genomics data, and data extracted from biochemical experiments on the relevant organisms. The pipeline generated metabolically diverse reconstructions that maintain high accuracy with known biochemical data. Finally, the refined GENREs were combined with metagenomic data from individual stool samples to build personalized human gut microbiome metabolic reconstructions. The resulting large-scale microbiome models were both taxonomically and functionally diverse. The work presented in this thesis has enabled the generation of biologically relevant human gut microbiome metabolic reconstructions. Metabolic models resulting from such reconstructions can be applied to study metabolism within the human gut microbiome and between the gut microbiome and the human host. Additionally, they can be used to study the effects of different dietary components on the metabolic exchanges in the gut microbiome and the metabolic differences between healthy and diseased microbiomes. [less ▲]

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See detailThe politics of knowledge that govern the European Union lifelong learning policy space – A Foucauldian reading
Rizzo, Stephen UL

Doctoral thesis (2017)

This contemporary historical research calls into question the mentalities that construct the EU lifelong learning policy space in specific ways. By drawing on the Foucauldian concepts of governmentality ... [more ▼]

This contemporary historical research calls into question the mentalities that construct the EU lifelong learning policy space in specific ways. By drawing on the Foucauldian concepts of governmentality and genealogy, this thesis analyses selected main EU lifelong learning policy literature by focusing on how this space has been articulated in governable forms. In line with a Foucauldian interpretation of power, the EU as a subject is decentred and considered as an epistemological form of assumption so that power and knowledge are analysed according to how they operate in this space. The governmentalist approach explores the technologies of the self and the technologies of government that construct and govern the conduct of conduct of the subject through the recurrent narratives in this space. In combination with this approach, the genealogical analysis of the episteme lifelong learning traces the different terminological interpretations which have been systematically reconfigured throughout the years to attain new connotations. These different connotations are problematised not only because the distinctiveness of the definition influenced the trajectory lifelong learning took throughout the years, but also because lifelong learning can, at one and the same time, control or liberate people. The distinctive contribution to academic literature that this thesis achieves is that it problematises the unquestionable truths that construct the EU lifelong learning policy space from a non-normative point of view. The overriding idea is for the actors in this space to make visible the taken-for granted principles and to create the possibility to challenge prevailing power relations and challenge what is uncritically taken as natural. [less ▲]

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See detailComputational Aspects of Classical and Hilbert Modular Forms
van Hirtum, Jasper UL

Doctoral thesis (2017)

The main topic of this thesis is the study of classical and Hilbert modular forms and computational aspects of their q-expansions. The coefficients of q-expansions of eigenforms are particularly ... [more ▼]

The main topic of this thesis is the study of classical and Hilbert modular forms and computational aspects of their q-expansions. The coefficients of q-expansions of eigenforms are particularly interesting because of their arithmetic significance. Most notably, modular forms are an essential ingredient in Andrew Wiles’s proof of Fermat’s last theorem. This thesis consists of two parts: the first part concerns the distribution of the coefficients of a given classical eigenform; the second part studies computational aspects of the adelic q-expansion of Hilbert modular forms of weight 1. Part I of this thesis is an adapted version of the article On the Distribution of Frobenius of Weight 2 Eigenforms with Quadratic Coefficient Field published in Experimental Mathematics [38]. It presents a heuristic model that settles the following question related to the Sato-Tate and Lang-Trotter conjectures: given a normalised eigenform of weight 2 with quadratic coefficient field, what is the asymptotic behaviour of the number of primes p such that the p-th coefficient of this eigenform is a rational integer? Our work contributes to this problem in two ways. First, we provide an explicit heuristic model that describes the asymptotic behaviour in terms of the associated Galois representation. Secondly, we show that this model holds under reasonable assumptions and present numerical evidence that supports these assumptions. Part II concerns the study of (adelic) q-expansions of Hilbert modular forms. Our main achievements are the design, proof and implementation of several algorithms that compute the adelic q-expansions of Hilbert modular forms of weight 1 over C and over finite fields. One reason we are studying such q-expansions is that their coefficients (conjecturally) describe the arithmetic of Galois extensions of a totally real number field with Galois group in GL 2 (F p ) that are unramified at p. Using the adelic q-expansions of Hilbert modular forms of higher weight, these algorithms enable the explicit computation of Hilbert modular forms of any weight over C and the computation of Hilbert modular forms of parallel weight both over C and in positive characteristics. The main improvement to existing methods is that this algorithm can be applied in (partial) weight 1, which fills the gap left by standard computational methods. Moreover, the algorithm computes in all characteristics simultaneously. More precisely, we prove that, under certain conditions in higher weight, the output of the algorithm for given level N and quadratic character E includes a finite set of primes L such that all Hilbert modular forms of given parallel weight, level N and quadratic character E over F p are liftable for all primes p outside the set L. In particular, testing primes in the set L enabled the computation of examples of non-liftable Hilbert modular forms of weight 1. [less ▲]

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See detailStudent-driven Inquiry-based Science Education in Luxembourg Primary School Contexts
Dombkowski-Wilmes, Sara Elizabeth UL

Doctoral thesis (2017)

This study examined the use of a student-driven inquiry-based science education instructional approach designed specifically to meet the contextualized needs of Luxembourg primary schools. The key issues ... [more ▼]

This study examined the use of a student-driven inquiry-based science education instructional approach designed specifically to meet the contextualized needs of Luxembourg primary schools. The key issues, namely an increasing linguistically diverse student population and limited instructional time for science, were considered in the design of the instructional approach. Drawing on theories of dialogic inquiry, the instructional approach engages students in asking questions and designing investigations to build their science understanding. This interpretive qualitative study utilized a multi-perspective approach to analyse how teachers used the instructional approach in their classrooms and explored two overarching research questions, first, what instructional opportunities does Science Workshop, an inquiry-based student-driven science instructional approach, afford when used in Luxembourg primary classrooms? And second, what does analysis of interactions in these contexts reveal about inquiry-based science instruction in multilingual classrooms? Qualitative methodologies, specifically case studies of classroom implementation, were used to examine the use of the program teachers’ adaptations of the program in their classrooms. Bakhtinian notions of heteroglossia and dialogic pedagogies were used as lenses to examine the instructional opportunities afforded. Interaction analysis was used to examine instruction in a focal classroom when the inquiry-based approach was used. Analyses rooted in sociocultural theoretical frameworks of science and language learning revealed three key contributions toward the use of IBSE in Luxembourg primary schools. First, the key characteristics of teacher professional learning opportunities that supported teachers’ use of the program in Luxembourg, which included workshops, material support, and opportunities to share implementation cases were identified. Second, the ways in which ritualized instructional components afford students spaces to engage on micro-scales in building synchronous interactions during science investigations were revealed. Third, that the science notebooks can position students to engage in dialogic discussions surrounding science investigations was shown through detailed analysis. Taken together, these interrelated points contribute to an understanding of the use of student-driven instructional approaches in multilingual science classrooms in general, while revealing implications for the use of inquiry-based science instructional approaches in Luxembourg primary schools specifically. [less ▲]

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See detailDynamic Career Attitudes And Life Satisfaction Among CEDIES' Postgraduates From Luxembourg
Karavdic, Senad UL

Doctoral thesis (2017)

Introduction: With an ever increasing number of university students and the employment shift from an opportunity to insecure development, new postgraduate generations have to be amenable to continuous ... [more ▼]

Introduction: With an ever increasing number of university students and the employment shift from an opportunity to insecure development, new postgraduate generations have to be amenable to continuous upgrading, complete with a wide range of skills in the promotion of their career development. Keeping in mind that the job market and work environment are variables that are mostly changing, the possession of an active career attitude may be a guarantee for postgraduates’ employability and their career outcome. Giving importance to the adjustment during the transitional period, life satisfaction (LS) may be altered based on the discrepancy between career aspiration and career achievement. Among university postgraduates, the main objectives of our doctoral work are to (1) measure the associations between dynamic career attitudes (DCA), generic employment capabilities and socioeconomic factors (2) determine the underlying structure of DCA, protean career orientation and career goal (3) analyze relations between DCA dimensions and career factors such as career goals, protean career orientation and LS (4) evaluate the effects of DCA dimensions on LS for native and non-native Luxembourgish postgraduates. Method: A survey was conducted among 2800 participants registered at the Centre for Documentation and Information on Higher Education (CEDIES). Data collection was realized via an information flyer that was sent to the home addresses of the postgraduates and that contained instructions about the aims of the study and a link to the survey. The postgraduates could directly access the anonymous online questionnaire in either French or English. To explore the associations and relations between variables student t-tests and bivariate correlations were used. Exploratory factor analysis was conducted to identify the underlying relationships between measured DCA dimensions, protean career orientation and career goals. In order to determine the statistical significance of the indirect effect for the mediation analysis, the bootstrapped confidence interval on 1000 bootstrap samples was used. A multiple logistic regression was applied to each group, but only significant variables (p<0.05) were introduced into the regression models. Results: A total of 644 volunteers completed the self-assessment questionnaire online. Majority of the participants were female, students and not employed. Postgraduates with high employment capabilities tend to present a higher dynamic career score that has been identified as a construct of four career dimensions (career adaptability, career optimism, career related knowledge and career planning). Each dimension was mediated from self-directed career dimension of protean career orientation by intrinsic career goal. Career adaptability and career optimism predicted both, happiness and LS. However, this relationship seems only to be presented for ‘postgraduates that are still studying. In the same vein, the DCA dimension of career optimism has been associated to LS by native Luxembourgers, whereas perceived financial situation intervenes in explanation of LS by non-native postgraduates. Discussion and Conclusion: The Dynamic Career Attitudes scale appears to be a relevant instrument in evaluating disparities in employment capabilities among postgraduates. Our findings indicated the application of intrinsic career goal in the development of career attitudes, where career adaptability and career optimism explained the highest proportion of the variance related to LS. The acquisition of qualitative information on DCA from a comparable population at different stages (from career goals aspirations and the process toward career goal accomplishments), could be rendered more straightforward for future research. Finally, it could be interesting to assess the DCA of university graduates during and after their Master’s degrees; before they start work and in the early years of their careers. Contextualizing our findings, the differences of native Luxembourgish and non-native postgraduates don't differ in LS, however, it seems to be influenced by different variables such as financial situation suggesting the introduction of the social grant of CEDIES for the most disadvantaged students. Practical implications are also suggested. Promoting programs proposed by University services towards counseling and an accompaniment to their career attitudes may enhance postgraduates’ LS which are major indicators for a successful mobility. [less ▲]

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See detailAspekte der luxemburgischen Syntax
Döhmer, Caroline Elisabeth UL

Doctoral thesis (2017)

Das Ziel dieser Arbeit ist eine empirische und systematische Beschreibung ausgewählter syntaktischer Phänomene im Luxemburgischen. Im Vordergrund der deskriptiven Analyse stehen vier Themenbereiche ... [more ▼]

Das Ziel dieser Arbeit ist eine empirische und systematische Beschreibung ausgewählter syntaktischer Phänomene im Luxemburgischen. Im Vordergrund der deskriptiven Analyse stehen vier Themenbereiche: Kasussyntax und -funktionen (Genitiv, Possession, Partitiv), Pronominalsyntax (Syntax und Semantik von Personalpronomen), Verbcluster (2-, 3- und 4-gliedrige Cluster im Nebensatz) sowie die syntaktischen Eigenschaften von Nebensatzeinleitungen (Kongruenz und Verdopplungen). Die Arbeit soll einerseits dazu beitragen, die luxemburgische Sprache in ihren strukturellen Eigenschaften besser verstehen zu können und andererseits die (syntaktische) Erschließung des Kontinentalwestgermanischen weiter voranbringen. Somit liefert diese Dissertation einen wichtigen Beitrag in der derzeit aufblühenden Forschungsrichtung der linguistischen Luxemburgistik und ordnet sich gleichzeitig in die allgemeine westgermanische Syntaxforschung ein. [less ▲]

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See detailVERHALTEN AUSGEWÄHLTER NANOPARTIKEL IN KOMMUNALEN KLÄRANLAGEN UNTER BESONDERER BERÜCKSICHTIGUNG DER ANAEROBEN SCHLAMMBEHANDLUNG
Rahimi, Anahita Bahareh UL

Doctoral thesis (2017)

The increasing use of nanoparticles and the market to commercialize this innovative technology requires a deeper understanding of the behavior of nanoparticles (NPs) and the resulting consequences in an ... [more ▼]

The increasing use of nanoparticles and the market to commercialize this innovative technology requires a deeper understanding of the behavior of nanoparticles (NPs) and the resulting consequences in an environmentally The increasing use of nanoparticles and the market to commercialize this innovative technology requires a deeper understanding of the behavior of nanoparticles (NPs) and the resulting consequences in an environmentally relevant matrix. However, since the fate and behavior of nanoparticles is largely unknown to the environment, this study was done to investigate the key properties of nanoparticles, parameters to describe them and to discuss how these parameters can influence their fate and behavior in the natural environment. The core goal of this discussion is to relate sludge treatment to relevant properties of the nanoparticle, which may interact with a range of substances naturally present in wastewater treatment plants (WWTPs) and activated sludge. Understanding these properties is necessary for interpreting the fate of nanoparticles and predicting their effects in the actual environment. Environmentally matrix are challenging to investigate, for instance as in sludge and anaerobic sludge stabilization. According to the literature, it will be assumed that about 95% of the NPs entering the WWTP end up in the sludge. This work reports on the investigation and observation of NPs behavior in the different stages, using different experiments and metering devices. The different experiments include (i) characterization of NPs before their application (NanoSight), (ii) behavior analysis in terms of kinetic transformations (Turbiscan), (iii) long- and short-term analysis of NPs effects on anaerobic sludge stabilization (laboratory fermentation plants). The characterization represents the current size distribution of the NPs in a controlled environment (H2O). Size is one of the defining properties of NPs, which causes changes in physical and chemical properties of NPs compared to their original materials. The results show that the distribution of NPs depends on the type of particle, surface coating and dispersion concentration. These parameters are subject to permanent changes in sludge. That is why an exact allocation to the effects seems almost impossible. Characterization is indispensable for the subsequent comprehension of the effects, and for the understanding of findings, which may result from the behavioral analysis, as well as from the effect analysis. The behavioral analysis was carried out by Turbiscan technology to consider relevant sludge parameters and substances (Chemical Oxygen Demand COD, Polymers, Humic acids, digestion process) to the behavior of NPs in sludge. The initial aim was to progressively add of representative substances to approximate the experiment to natural conditions. The phase separation detection identified a clear sedimentation behavior in all samples. To explain this and the kinetic modification as well as the resultant kinetic instability, the NPs’ diameter (particle size detection) were studied. The more instable samples had often smaller diameters. The substances within the sludge seem to influence the kinetic stability of NPs. This could be caused by the dynamic corona (active interaction with environment) and hard corona (strongly bound and restrained interaction with environment) formation, as well as agglomeration or modification of surface charges. Changes in kinetic stability means changes in the behavior and fate of NPs in such an environmental media like sludge. However, since the sludge is filtered for the behavioral analysis, the microorganism’s role is neglected. In order to complete the behavioral analysis considering the microorganism’s contribution, the consequences of the NP-behavior are measured as effects under various realistic conditions. The effects of NPs’ behavior on the anaerobic microorganisms were investigated based on their potential and efficiency in anaerobic sludge stabilization for gaining additional insights. The long-term effects of NPs in sludge treatment plants (STP) were investigated using four parallel pilot reactors operated under identical conditions, with daily feeding (substrate and two different NP-concentration). There was a temporary decrease of Biogas especially at the third phase (second concentration) except for the ZnO-reactor while the proportion of methane remained stable. Based on the knowledge obtained from the characterization and behavioral analysis, this might be due to the kinetic transformation of NPs. When the particle size for instability is exceeded as a consequence of surface changes and agglomerations, rapid sedimentation occurs. After eliminating the NP-reactivity and obtaining NP-agglomerations, NPs are extracted from the digestion system (sedimentation). Due to that, the microorganisms are able to operate to their full potential and efficiency, which is an indication of extracellular inhibition and preclude probably the intracellular inhibition caused by ions release. The short-term effects of ENPs in batch experiments were investigated under identical conditions. Furthermore, oxygen was used as an inhibitor to intensify the NP’s effects on the anaerobic microorganisms and digestion process. Oxygen is toxic for anaerobic microorganisms and enhance the release of ions. NP-effects were evaluated for methane yield. It will be assumed that the corona formations created by the sludge substances, reduce the release of ions and the NP-toxicity, even after decreasing the biomass. In addition, the NPs are able to eliminate O2 as an inhibitor, as well as positively influence the production dynamics and methane yield. To sum up, the growing interest in nanoparticles and their potential has presented many challenges for science, in toxicology and innovative technologies. These challenges bring new questions related to understanding NPs and their interplay with certain circumstances. A considerable contribution has been made for understanding the behavior of nanoparticles in the environmentally relevant media. However, a partial understanding for the fate of nanoparticles in complex matrices has been gained. As the nanoparticles themselves are such a complex matter, they require more research in developing a more complete understanding of the way they function. Having this knowledge would enable to explore progressively their behavior and fate in complex matrices.. [less ▲]

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