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See detailDeformation Based Curved Shape Representation
Demisse, Girum UL

Doctoral thesis (2017)

Representation and modelling of an objects' shape is critical in object recognition, synthesis, tracking and many other applications in computer vision. As a result, there is a wide range of approaches in ... [more ▼]

Representation and modelling of an objects' shape is critical in object recognition, synthesis, tracking and many other applications in computer vision. As a result, there is a wide range of approaches in formulating representation space and quantifying the notion of similarity between shapes. A similarity metric between shapes is a basic building block in modelling shape categories, optimizing shape valued functionals, and designing a classifier. Consequently, any subsequent shape based computation is fundamentally dependent on the computational efficiency, robustness, and invariance to shape preserving transformations of the defined similarity metric. In this thesis, we propose a novel finite dimensional shape representation framework that leads to a computationally efficient, closed form solution, and noise tolerant similarity distance function. Several important characteristics of the proposed curved shape representation approach are discussed in relation to earlier works. Subsequently, two different solutions are proposed for optimal parameter estimation of curved shapes. Hence, providing two possible solutions for the point correspondence estimation problem between two curved shapes. Later in the thesis, we show that several statistical models can readily be adapted to the proposed shape representation framework for object category modelling. The thesis finalizes by exploring potential applications of the proposed curved shape representation in 3D facial surface and facial expression representation and modelling. [less ▲]

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See detailA Model-Based Framework for Legal Policy Simulation and Compliance Checking
Soltana, Ghanem UL

Doctoral thesis (2017)

Information systems implementing requirements from laws and regulations, such as taxes and social benefits, need to be thoroughly verified to demonstrate their compliance. Several Verification and ... [more ▼]

Information systems implementing requirements from laws and regulations, such as taxes and social benefits, need to be thoroughly verified to demonstrate their compliance. Several Verification and Validation (V&V) techniques, such as reliability testing, and modeling and simulation, can be used for assessing that such systems meet their legal. Typically, one has to model the expected (legal) behavior of the system in a form that can be executed (simulated), subject the resulting models and the system to the same input data, and then compare the observed behavior of the model simulation and system execution. Existing V&V techniques often rely on code and complex logical expressions with no intuitive appeal to legal experts for specifying the expected behavior of a given system. Subsequently, one has no practical way to validate with legal experts that the underlying legal requirements are indeed complete and constitute a faithful representation of what needs to be implemented. Further, manually defining the expected behavior of a system and its test oracles is a tedious and error-prone task. The challenge here is to find a suitable knowledge representation that can be understood by all the involved stakeholders, e.g., software engineers and legal experts, but that remains complete and precise enough to enable automated analysis such as simulation and testing. As real data is seldom accessible in highly regulated domains, V&V requires the generation of synthetic testing data that can be used to build confidence in the reliability of the system under test. In particular, such data has to be structurally and logically well-formed to raise meaningful failures that can help reasoning about the reliability of the system under test. Further, the data should exhibit as much as possible the actual or anticipated system usage to help mimic how the system would behave under realistic circumstances. Generating such data is not a trivial task as the underlying data schemas are usually large and subject to numerous complex domain-related logical constraints. In this thesis, we investigate the use of the Unified Modeling Language (UML) and model-driven technologies, e.g., model to code transformations, to facilitate V&V activities for information systems that have to conform to laws and regulations, while tackling the above challenges. All our technical solutions have been developed and empirically evaluated in close collaboration with a government administration. Concretely, the technical solutions covered by this thesis include: - A modeling notation and methodology for formalizing legal policies. We propose a modeling notation and methodology for building abstract interpretations of the law. Models built using our methodology are simple enough to be understood by the involved stakeholders and are, at the same time, detailed enough to enable automated V&V activities. - A model-based simulation framework. We develop a model-based framework and associated tool support for simulating legal policies, when formalized using the aforementioned modeling methodology. Simulation provides a comparison baseline of how a compliant system should behave. Further, simulation is a mean to support decision-making when considering legal changes. Specifically, we report on a sizable case study where we assess the anticipated economic implications of a given policy change in Luxembourg’s tax law. - A model-based generator of test cases for reliability testing. We develop a heuristic approach for generating valid and representative test cases (data). Our generator is scalable and produces high-quality test data that is suitable for testing the reliability of data-intensive systems, e.g., a tax management system. [less ▲]

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See detailCorporations and Human Rights: Searching for International Norms for Corporate Conduct in Domestic Case Law
Baglayan Ceyhan, Basak UL

Doctoral thesis (2017)

Recent years have seen much debate concerning the interplay between human rights and corporations. Part of that debate has focused on corporate violations of human rights norms and possible legal ... [more ▼]

Recent years have seen much debate concerning the interplay between human rights and corporations. Part of that debate has focused on corporate violations of human rights norms and possible legal accountability mechanisms for such breaches. The present research is concerned with one such accountability mechanism, namely litigation before domestic courts seeking to enforce corporations’ international obligations and the complaints before the OECD National Contact Points (‘NCPs’). The thesis analyses how domestic courts and the OECD NCPs have conceptualised and implemented corporations’ human rights obligations. It is premised on the assumption that, through their application of international norms in their particular national context, these institutions act to crystallize and clarify the ambit of such norms. [less ▲]

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See detailContextual Integrity and Tie Strength in Online Social Networks: Social Theory, User Study, Ontology, and Validation
Ahmed, Javed UL

Doctoral thesis (2017)

Online Social Networks (OSNs) have become an important part of daily digital interactions for more than half billion users around the world. Unconstrained by physical spaces, OSNs offer to social web ... [more ▼]

Online Social Networks (OSNs) have become an important part of daily digital interactions for more than half billion users around the world. Unconstrained by physical spaces, OSNs offer to social web users new means to communicate, interact, and socialize. Online social networks exhibit many of the characteristics of human societies in terms of forming relationships and sharing personal information. However, current OSNs mainly assume binary, static, and symmetric relationship of equal value between the connected users. In human societies, social relationships are of varying tie strength, dynamic, and asymmetric in nature. The lack of an effective mechanism to represent diversity in social relationships leads to undesirable consequences of users personal information leakage to the unwanted audience and raises privacy concerns. The issue of privacy has received significant attention in both the research literature and the mainstream media. In this dissertation, we conduct a user study to analyze users' attitude towards personal information disclosure in online social networks. The study gives insight into user's information sharing behavior and interaction patterns in online social networks. The findings reveal that personal information disclosure depends on the quality of relationship among the users and it can be easily inferred from user interaction pattern in online social networks. We propose a theoretical framework that addresses the aforementioned issue from a social science perspective and exploits existing social theories of Goffman, Granovetter, and Nissenbaum to model social privacy for OSNs users. Based on this theoretical framework, we developed SOCPRI (SOCial PRIvacy) ontology to represent diversity in social relationships in online social networks. This model regulates personal information disclosure on the basis of the social role and the relationship quality between the OSNs users. The model is evaluated by translating competency questions into description logic (DL) queries to demonstrate the applicability of our approach. The results of ontology evaluation demonstrate the appropriateness of our ontology against proposed requirements. Based on this model a privacy-friendly online social networking environment can be developed to address some of the existing issues such as context collapse and user control. [less ▲]

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See detailModel-Based Specification, Deployment and Adaptation of Robot Perception Systems
Hochgeschwender, Nico UL

Doctoral thesis (2017)

As robots are becoming ubiquitous and more capable, the need for introducing solid robot software development methods is pressing to increase robots' task spectrum. This thesis is concerned with improving ... [more ▼]

As robots are becoming ubiquitous and more capable, the need for introducing solid robot software development methods is pressing to increase robots' task spectrum. This thesis is concerned with improving software engineering of robot perception systems. The presented research employs a model-based approach to provide the means to represent knowledge about robotics software. The thesis is divided into three parts, namely research on the specification, deployment and adaptation of robot perception systems. The first part contributes the design and development of two domain-specific languages, namely RPSL and DepSL. Those languages provide suitable notations and abstractions to enable domain experts to express, compose and explore functional, architectural and deployment design decisions of robot perception systems. The resulting models are interpretable, thus they can be used not only to communicate design decisions to stakeholders, but also to verify them in an early development stage. The second part contributes means for deploying perception systems on real robot systems even in the presence of varying resource conditions. To this end, functional, architectural and deployment models are composed in a graph-structure. Such a graph enables not only humans, but also robots to derive implicitly defined information about their software both at design time and run time. The second part also contributes a reference architecture for deploying robot perception systems. The architecture provides a template solution for integrating not only the models required for deployment, but also all the other means required to carry out deployment. The third part utilizes both RPSL, DepSL and the reference architecture to specify, implement and evaluate three different robot perception systems. Those are capable to satisfy changing requirements induced, for example, by the robot's tasks or environment. This is achieved by proposing algorithms which derive adaptation actions based on models and varying requirements. [less ▲]

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See detailForm und Funktion des Diminutivs im luxemburgisch-moselfränkischen Übergangsgebiet
Edelhoff, Maike UL

Doctoral thesis (2017)

Diminutive formation is a common word formation process of the Luxembourgish (Lux.) lan-guage and the neighbouring Moselle-Franconian (MsFrc) dialects. The aim of this thesis is to collect and to analyse ... [more ▼]

Diminutive formation is a common word formation process of the Luxembourgish (Lux.) lan-guage and the neighbouring Moselle-Franconian (MsFrc) dialects. The aim of this thesis is to collect and to analyse the characteristics of this process, integrate them into common morpho-logical theories and to establish their geolinguistic properties. On a functional level, the diminutives show the same characteristics in both varieties although the loss of the evaluative meaning is further developed in Lux. than in MsFrc. How-ever, the most apparent differences can be seen on the level of the fomal execution of the di-minutive rule: While the diminutives in MsFrc share many similarities, such as grammatical gender, the singular suffix and to an extent also the plural marking with Standard German, the Lux. language differs greatly from the others. In Lux. the singular formation is quite similar to the one in the other varieties, however, the plural suffix is triggered by the syllabic and prosodic properties of the base noun. Additionally, the grammatical gender of the diminutive is in con-cordance with the gender of the base noun and hence, not influenced by the suffix. The reasons for these peculiar attributes are to be found both in the historical development of the language and its current structural form as well as in its sociolinguistic context. The consequences of the differing structural properties are clearly displayed on a geo-linguistic level. Although the varieties are historically closely related the differing formal ex-pressions of the diminutive meaning lead to the emergence of groups of isoglosses coinciding with the state border. In brief, the history and the present situation of the diminutive serve as evidence that the dialect continuum that once crossed the state border has been falling apart and that it has been replaced by a solid linguistic border that separates the closely related varieties from each other. [less ▲]

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See detailLe mouvement-liberté. Généalogie philosophique et littéraire d'un imaginaire politique
Jeusette, Julien UL

Doctoral thesis (2017)

Cette thèse, qui se situe au croisement de trois champs de recherche (la littérature, la philosophie, l’histoire des idées), a pour ambition de retracer la manière dont le déracinement, le nomadisme et ... [more ▼]

Cette thèse, qui se situe au croisement de trois champs de recherche (la littérature, la philosophie, l’histoire des idées), a pour ambition de retracer la manière dont le déracinement, le nomadisme et l’errance ont été investis, à un moment donné de notre Histoire, d’une appréciation positive, au moment même où la sédentarité et l’enracinement se sont vus taxés de conservatisme ennuyeux. Nous postulons que cet imaginaire politique, que nous appelons « mouvement-liberté » (tout discours axiologique valorisant le mouvement libre et infini, et dévalorisant toute forme d’immobilité), émerge dans Les Nourritures terrestres d’André Gide et dans Ainsi parlait Zarathoustra de Nietzsche à la fin du XIXe siècle. Nous montrons ensuite que ce discours s’amplifie au cours des années 1920-1930, notamment au sein des textes que nous avons qualifiés de « romans de fuite » ; la troisième partie de la thèse porte sur les années 1960-1970 et met en évidence la redondance discursive du « mouvement-liberté » au sein de la « French theory ». La dernière partie met en lumière la façon dont le « mouvement-liberté », qui était politiquement critique et explicitement de l’ordre du contre-pouvoir de la fin du XIXe siècle jusqu’aux années 1970, est aujourd’hui récupéré par le néolibéralisme, qui le revendique pour son propre compte et le travestit en « idéologie nomade ». [less ▲]

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See detailAb initio approaches to Resonant Raman Spectroscopy of Transition Metal Dichalcogenides
Pereira Coutada Miranda, Henrique UL

Doctoral thesis (2017)

This thesis deals with the theory and simulation of resonant Raman spectroscopy in two-dimensional transition metal dichalcogenides. We present two different ab initio approaches. In the first, we ... [more ▼]

This thesis deals with the theory and simulation of resonant Raman spectroscopy in two-dimensional transition metal dichalcogenides. We present two different ab initio approaches. In the first, we calculate the Raman susceptibility tensor as a function of laser energy from the change of the dielectric susceptibility with atomic displacements. In the second, we formulate the Raman tensor in terms of time-dependent perturbation theory and calculate it using electron-light and electron-phonon coupling matrix elements obtained from density functional theory. We investigate the role of resonance, quantum interference and excitonic effects in the Raman spectra of single and triple-layer MoTe2. We compare our simulations with experimental results, explaining the dependence of the Raman intensities on the excitation energy. We demonstrate that the two approaches are formally and numerically equivalent in the adiabatic limit. In addition, the second approach allows to include the dynamical effects and captures a shift of the intensities with respect to the adiabatic case. This method is also more computationally efficient and is extended to include temperature effects using many-body perturbation theory. We have implemented both of these methods in a software package with interfaces to open source ab initio codes. Furthermore, we have developed web based tools to visualize excitonic states and phonon modes. [less ▲]

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See detailTESTING 21ST CENTURY SKILLS IN A CHANGING NATURE OF WORK: THE CONSTRUCT VALIDITY OF COMPLEX PROBLEM SOLVING AND ORGANIZATIONAL LEARNING
Mainert, Jakob Simon UL

Doctoral thesis (2017)

This thesis investigates the empirical assessment and construct validity of complex problem-solving (CPS) skills and organizational learning (OL) in a changing nature of work. Technological and ... [more ▼]

This thesis investigates the empirical assessment and construct validity of complex problem-solving (CPS) skills and organizational learning (OL) in a changing nature of work. Technological and organizational change enlarge the gap between the type of employee required by the market and the employees who are actually being provided by higher education as human capital to the market. Two constructs, CPS and OL, might strengthen human capital to close the emerging gap in a changing nature of work. [less ▲]

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See detailL'intégration des élèves nouvellement arrivés en France dans l'espace scolaire français. Langues, représentations, identités en contexte.
Kadas, Timea UL

Doctoral thesis (2017)

Our thesis focuses on newcomer students in France and aims at understanding how these students integrate into French schools and exploring the educational paths they tread. Thus, this study is based ... [more ▼]

Our thesis focuses on newcomer students in France and aims at understanding how these students integrate into French schools and exploring the educational paths they tread. Thus, this study is based mainly on the analysis of the discourse of thirteen students concerning their learning and their school experiences. It is also based on the representations that these students have of themselves, others (French students, teachers), their learning in general, their learning of the French language in particular and the context in which this learning takes place. Our thesis also focuses on the students’ first languages and their role in the learning process. The link between language and identity has long been established by researchers from different disciplines. Therefore, we have tried to understand, through an autobiographical project based on the notions of multiliteracy and multimodality, how the first languages of the students can be taken into consideration in order to help them progress in both the learning of French and learning in general. We also considered the significance of such an approach in the reconstruction of these students' identities. Furthermore, in response to our initial question regarding how these students integrate into the French education system, we investigated two complementary perspectives: that of the institution through interviews with three teachers, three heads of school and two inspectors and that of the students’ families through questioning nine parents. The aim of this study is to contribute to the body of research on the role of migration in the French educational context and to provide a better understanding of the current educational challenges facing our globalized society. [less ▲]

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See detailStem cells for modeling Parkinson's disease
Nickels, Sarah Louise UL

Doctoral thesis (2017)

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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 detailKusuoka-Stroock type bounds for densities related to low-dimensional projections of high-dimensional SDE
Ledent, Antoine Patrick Isabelle Eric UL

Doctoral thesis (2017)

One of the purposes of this thesis is to use Malliavin calculus and Stochastic Taylor expansions to study the densities of interacting systems of stochastic differential equations (SDE), seen as ... [more ▼]

One of the purposes of this thesis is to use Malliavin calculus and Stochastic Taylor expansions to study the densities of interacting systems of stochastic differential equations (SDE), seen as projections of SDE onto a low-dimensional space, and to control the dependence of the constants on the dimension of the background space. The setting includes time-dependent SDE and a relatively large class of path-dependent SDE. Several results also shed light on the classical theory of SDE, independently of the control on the constants. In Part 1, assuming the system satisfies suitably defined projected equivalents of the classic ellipticity or weak Hörmander conditions, we prove Gaussian estimates in terms of the Euclidean distance where, provided natural assumptions, for a fixed target-space dimension, the constants depend polynomially on the background dimension, and, in the elliptic case, on the number of driving Brownian motions. In Part 2, we first define suitable generalisations of (time-dependent) control distances and prove Kusuoka-Stroock type results without control on the constants. In particular, we obtain a time-dependent extension of a result of Léandre about SDE with non-trivial drifts, i.e., drifts which are not uniformly contained in the span of the other vector fields. Then, we introduce a condition which we call the `Progressive Hörmander condition' and prove similar control-type estimates valid under this assumption, with polynomial control on the growth of the constants with background space dimension. The condition is of independent interest in the study of SDE, and shows the connection between the classic works of Ben Arous, Kusuoka, Léandre and Stroock, and the more recent works of Bally, Caramellino, Delarue, Menozzi and Pigato. To main technique required is the study of density and scaling properties of some careful choice of linear combinations of terms of the signature of the driving path. In Part 3, we introduce a stricter condition called the `separated progressive Hörmander condition', and prove lower bounds and local strict positivity under this assumption. (By `local' we mean local around the solution of the deterministic ODE driven by a null control, rather than local round the initial point.) The main technical difficulty is the identification of points contained in the interior of the support of the log-signature of the path in the d dimensional Euclidean space composed of d Brownian motions and a deterministic linear component. The purpose of Part 4 is to use some results and techniques of the rest of the thesis to prove extensions of a theorem of Löcherbach about uniformly elliptic interacting branching diffusions. [less ▲]

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See detailMolecular mechanisms of kinase inhibitor resistance in melanoma
Cesi, Giulia UL

Doctoral thesis (2017)

In my thesis, I elucidated several aspects of melanoma biology, all related to the influence of targeted therapies in both responding and resistant melanoma cells. To better understand the MAPK signalling ... [more ▼]

In my thesis, I elucidated several aspects of melanoma biology, all related to the influence of targeted therapies in both responding and resistant melanoma cells. To better understand the MAPK signalling pathway, the impact of BRAF inhibitors on metabolic alterations as well as the connection between BRAF inhibitors and the onset of drug resistance was investigated. This introduction is focused on four topics: i) melanoma, ii) cancer metabolism, iii) miRNAs and iv) extracellular vesicles. First, melanoma biology including incidence rates, etiology, canonical and altered signalling pathways, therapies and resistance mechanisms will be introduced. The second part of the introduction will concentrate on metabolic alterations in the context of cancer and their implication on proliferation and survival. Thirdly, miRNAs and extracellular vesicles will be illustrated providing insights into their role in cancer development and especially drug resistance [less ▲]

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See detailCHARACTERIZATION OF PARKINSON’S DISEASE GENE DJ-1/PARK7 IN CD4+CD25+FOXP3+ REGULATORY T-CELLS
Danileviciute, Egle UL

Doctoral thesis (2017)

DJ-1, also known as PARK7, as its name suggests, is one of the familial Parkinson’s disease (PD) genes. Defects in human DJ-1 are the cause of autosomal recessive early-onset PD. DJ-1 is a redox ... [more ▼]

DJ-1, also known as PARK7, as its name suggests, is one of the familial Parkinson’s disease (PD) genes. Defects in human DJ-1 are the cause of autosomal recessive early-onset PD. DJ-1 is a redox-responsive protein and is long thought to mainly play an essential protective role in neurons. DJ-1 is ubiquitously expressed throughout the body rather than only in brain and is involved in several biological functions. We here seek to characterize a novel role of DJ-1 in regulatory T cells, currently recognized as CD4+CD25+FOXP3+ regulatory T-cells (Tregs), which are well-known immune suppressor cells in many peripheral diseases and emerging to play a role in several neurodegenerative diseases. [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 ▲]

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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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