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See detailUNRAVELING THE COMPLEX GENETICS OF NEUROLOGICAL DISORDERS
Bobbili, Dheeraj Reddy UL

Doctoral thesis (2018)

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See detailMany-Body Perturbation Theory Approach to Raman Spectroscopy and Its Application to 2D Materials
Reichardt, Sven UL

Doctoral thesis (2018)

Raman spectroscopy has become one of the most important techniques for the characterization of materials, as it allows the simultaneous probing of several properties, such as electronic and vibrational ... [more ▼]

Raman spectroscopy has become one of the most important techniques for the characterization of materials, as it allows the simultaneous probing of several properties, such as electronic and vibrational excitations, at once. This versatility, however, makes its theoretical description very challenging and, up to now, no fully satisfactory and general way for the calculation of Raman spectra from first principles exists. In this thesis, we aim to fill this gap and present a coherent theory of Raman scattering within the framework of many-body perturbation theory. We develop a novel and general, correlation function-based approach for the calculation of Raman scattering rates that can potentially also be applied to ultra-fast Raman spectroscopy out of equilibrium. Besides these theoretical developments, we present concrete computational recipes for the calculation of Raman intensities that allow the inclusion of both excitonic effects and non-adiabatic effects of lattice vibrations. The latter has so far not been possible with state-of-the-art methods, which can only take into account one of the two effects. As a first test case, we apply our theory to graphene, for which we use it to study the laser frequency and Fermi energy dependence of the Raman G-peak intensity. The flexibility of our approach also allows us to demonstrate that non-resonant processes and quantum mechanical interference effects play a significant role in Raman scattering. This applies not only to graphene but also to other two-dimensional materials of current interest, such as MoTe2 and MoS2. In addition to the development of a consistent and comprehensive description of Raman scattering, we derive a novel approach for the calculation of phonon frequencies and the screened electron-phonon coupling. It can be applied also to strongly correlated systems, for which the currently used methods are not entirely satisfactory or insufficient. Our new method goes beyond the limitations of the methods currently in use and will permit the computation of phonon-related quantities also in systems with strong correlation effects such as Kohn anomalies (e.g., graphene) or Peierls instabilities. Lastly, we present work on the application of (magneto-)Raman spectroscopy as a probe for many-body effects in graphene. Here we focus on the description of the phenomenon of magneto-phonon resonances and how it can be used to probe electronic excitation energies and to extract electron and phonon lifetimes. [less ▲]

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See detailA Scalable and Accurate Hybrid Vulnerability Analysis Framework
Thome, Julian UL

Doctoral thesis (2018)

As the Internet has become an integral part of our everyday life for activities such as e-mail, online-banking, shopping, entertainment, etc., vulnerabilities in Web software arguably have greater impact ... [more ▼]

As the Internet has become an integral part of our everyday life for activities such as e-mail, online-banking, shopping, entertainment, etc., vulnerabilities in Web software arguably have greater impact than vulnerabilities in other types of software. Vulnerabilities in Web applications may lead to serious issues such as disclosure of confidential data, integrity violation, denial of service, loss of commercial confidence/customer trust, and threats to the continuity of business operations. For companies these issues can result in significant financial losses. The most common and serious threats for Web applications include injection vulnerabilities, where malicious input can be “injected” into the program to alter its intended behavior or the one of another system. These vulnerabilities can cause serious damage to a system and its users. For example, an attacker could compromise the systems underlying the application or gain access to a database containing sensitive information. The goal of this thesis is to provide a scalable approach, based on symbolic execution and constraint solving, which aims to effectively find injection vulnerabilities in the server-side code of Java Web applications and which generates no or few false alarms, minimizes false negatives, overcomes the path explosion problem and enables the solving of complex constraints. [less ▲]

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See detailRecent developments around the Malliavin-Stein approach (Fourth moment phenomena via exchangeable pairs)
Zheng, Guangqu UL

Doctoral thesis (2018)

Part I is a survey, part II is a collection of papers.

Detailed reference viewed: 32 (11 UL)
See detailColonization and succession of the human gastrointestinal microbiome in neonates and infants at high risk of metabolic disease in adulthood
Wampach, Linda UL

Doctoral thesis (2018)

Recent studies have highlighted that the human gastrointestinal microbiome not only maintains important functions for the human host, but is also intimately linked to the development of the neonatal ... [more ▼]

Recent studies have highlighted that the human gastrointestinal microbiome not only maintains important functions for the human host, but is also intimately linked to the development of the neonatal immune system. Therefore, earliest perturbations to the initial colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. While the rate of caesarean section deliveries is increasing worldwide, it still remains unclear to what extent a caesarean section delivery (CSD) or other perturbations affect the colonization and succession of the gastrointestinal microbiome and might eventually impact the immune development of a neonate. Although much research has been performed on bacterial colonization and succession to date, far less is known about the other two domains of life, archaea and eukaryotes. Furthermore, it remains unclear whether a delivery by caesarean section causes a disruption of mother-to-infant transmission of microbiota and whether this affects human physiology early on, with potentially persistent effects in later life. Over the course of this thesis, a multitude of objectives was tackled. First of all, the description of microbial communities and trends over time within the neonatal and infant gut microbiome, and the study of the early colonization and succession by members of the three domains of life. Second, the careful application of high-throughput approaches on earliest low biomass samples, the detection of functional repertoires and strains transferred from mothers to neonates, and the analysis of the immunostimulatory potential of neonatal gut microbiomes in relation to delivery mode with likely effects on the later health status. In a first study based on 15 infants and using a combination of 16S and 18S rRNA gene amplicon sequencing and quantitative real-time PCR, earliest differences among the three domains of life according to delivery mode were detected as early as three days postpartum. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The findings complement previous observations of a delay in colonization and succession of CSD infants, which likely affects not only bacteria but also archaea and microeukaryotes. Based on the observation that the first 5 days postpartum showed significant differing trends between delivery modes and considering the fact that the very first days postpartum are generally under-studied, this highlighted the importance to perform more in-depth analyses of these microbiome samples. In a next step, based on 12 mother-neonate pairs, high-resolution, metagenomic analysis of the gut microbiomes of mothers and neonates was performed to resolve the earliest colonizing microbiome. After data curation and in accordance with the observed changes in community composition for both cohorts, differences with respect to encoded metabolic functions between the microbiomes of vaginally delivered (VD) or CSD neonates as early as day 3 were observed. Several functional pathways were over-represented in VD neonates, including lipopolysaccharide (LPS) biosynthesis. Genes encoding proteins involved in these functions were linked to specific strains, which were vertically transmitted from the respective mothers. Based on the candidate’s work, more follow-up work on LPS was done by a colleague with a background in immunology. Isolated LPS from faecal samples collected at day 3 had a higher immunostimulatory potential in VD neonates and cytokines measured in plasma collected at the same day presented an increased immune reaction in VD neonates. Collectively, these results suggest that vaginal delivery favours vertical transmission of specific gastrointestinal strains from mother to neonate, while caesarean section may impede this process and thereby decrease linked functional repertoires and immunostimulatory potential with potential effects on human physiology later in life. Taken together, the results obtained from both cohorts strongly indicate that maternal and neonatal factors, such as antibiotics intake or milk diet, but most importantly the delivery mode, have the potential to influence the initial neonatal bacterial, archaeal and microeukaryotic colonization of the gut microbiome shortly postpartum, with the potential to impact the neonatal immune development, which could thereby affect the later health status. [less ▲]

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See detailLarge-scale and Flexible Nanogenerator based on ZnO conical nanostructures by Nano-Imprint Lithography and Atomic Layer Deposition
Spirito, David Mario André UL

Doctoral thesis (2018)

The present work stands in the context of the rapid growth of portable electronics and wireless sensors. This growth drives the request for advances in materials science and technology to harvest energy ... [more ▼]

The present work stands in the context of the rapid growth of portable electronics and wireless sensors. This growth drives the request for advances in materials science and technology to harvest energy from ambient sources. Piezoelectric nanogenerators, which convert vibrations into electrical energy, are considered as one of the promising building blocks for the design of low-cost and performant energy harvesting devices. Several demonstrations of PENGs have been reported throughout the last decade, many of them based on Zinc Oxide –ZnO– nanowires. Despite interesting performances, literature also suggests that the classical bottom-up approach of optimized ZnO-based PENGs performance approaches its limits and that top-down approaches merit further attention. This has motivated the present work, with the aim to conceptualize by models, to fabricate and to investigate a new type of piezoelectric nanogenerator based on ZnO nanostructures to overcome current limitations. To achieve this goal, we have used a top-down approach that allows an accurate control of the aspect ratio and density of tailored ZnO nanowires by using Nano-Imprint Lithography and Atomic Layer Deposition. In our work, we demonstrate that this approach enables the fabrication of large flexible piezoelectric nanogenerators with interesting properties. In the first part of this work, we have optimized the synthesis of crystalline N-doped ZnO films by ALD at a deposition temperature as low as T = 80 °C. We have particularly investigated the role of the time of purge with nitrogen as purge gas in each cycle of a ZnO monolayer of the ALD process. A thorough chemical and structural analysis illustrates that the time of purge allows tuning the N-doping-level which, despite being low, affects both the long-range and short-range structure. Raman and luminescence spectroscopy suggest a complex defect structure, characterized by nitrogen ions which substitute oxygen ions and by Zn cations on interstitial sites. Importantly, even the low level of nitrogen doping allows tuning the sheet resistivity of ZnO films by several orders of magnitude. The ability to obtain crystallized and tunable N-doped ZnO films down to 80 °C by ALD provides a critical building block to tune structural, optic and electric properties for a variety of applications. In the second part, we have designed, fabricated and characterized a new type of PENGs based on patterned nanostructures made of conical-shape ZnO pillars. First, we have used a finite element modeling to identify the optimization for the electromechanical performances of the ZnO nanowires, namely in terms of their aspect ratio and pitch. This has defined the stamps of the nano-imprint, which has then be combined with a low temperature conformal ALD to provide ZnO conical nanostructures. A thorough structural analysis of such nanostructures attests a high crystallinity, a polycrystalline growth and piezoelectric properties. This has been the necessary technological achievement for addressing in a next step functional patterned piezoelectric nanogenerators. We have produced small flexible devices with an active area of 4 x 4 mm2, using either a blocking electronic barrier with alumina, either a p-n junction with a conductive polymer (PEDOT:PSS). The different devices and architectures have then been characterized at matching impedance. The electric characterization of a device with a p-n junction exhibits a maximum output voltage of 0.2 V and a power density of 0.3 µW cm-2. An effective transverse piezoelectric coefficient value e31eff of -0.45 C m-2 is determined, which corresponds to the order of magnitude reported in literature. As a proof of concept for potential industrialization, we scaled the P-PENGs up to 20 cm² for large flexible substrates. The 3.7 billion pillars, sandwiched between electrodes, evidence the robustness of our process. The analysis of the constitutive piezoelectric equations has prompted us to pay a particular attention to an accurate setup for P-PENGs characterization, which turns out to be mandatory to compare accurately devices. For this, we setup an electromechanical actuator. Two devices with the same architecture but with different levels of N-doping are compared. Using an equivalent electrical model, the performance of the P-PENG with the higher N-doped ZnO shows a larger output voltage and power density than the device with a lower N-doping level. This comparison shows that the higher N-doping-level leads to an increase of 150 % of the power output. From this we calculate that the effective piezoelectric coefficient increases by about 60 % for a P-PENG based on higher N-doped ZnO. This latter demonstrates an energy conversion efficiency of 10 %, on top of PENG based on ZnO. [less ▲]

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See detailTuning Self-Assembly in Liquid Crystal shells: from Interfacial- to Polymer-stabilization
Noh, Junghyun UL

Doctoral thesis (2018)

Liquid crystals form a subclass of soft materials which is easily influenced and deformed by a surface, an interface and the geometry. Of particular interest, in this thesis, is the confinement of liquid ... [more ▼]

Liquid crystals form a subclass of soft materials which is easily influenced and deformed by a surface, an interface and the geometry. Of particular interest, in this thesis, is the confinement of liquid crystals in shell geometry, imposing real or virtual defects that the liquid crystal cannot avoid. With the help of microfluidics, we prepare our research platform, liquid crystal shells, which contain and are surrounded by aqueous phases. In order to maintain such a shell structure in the aqueous phases, immiscible with the liquid crystal, appropriate stabilization is required. Here we explore two different pathways of interfacial stabilization and polymer stabilization and their impact on liquid crystal self-assembly. We primarily use either a polymeric or an ionic surfactant dissolving in water to stabilize shells and tune boundary conditions of shells. Depending on symmetrically or asymmetrically imposed boundary conditions, the nematic–isotropic phase transition appears as a single transi- tion or separated into two steps. We propose that the latter phenomenon can be understood as a result of an ordering-enhancing effect by surfactants. The nematic–smectic A phase transition is also investigated under varying boundary conditions. With a precise temperature control, we explore equilibrium smectic structures and introduce a new arrangement of focal conic arrays in shell geometry. Beyond stabilizing the shell from the shell exterior, but we also incorporate a photosensitive surface agent within the shell, enabling dynamic and reversible photoswitching of the liquid crystal alignment in real time. However, shells with interfacial stabilization cannot survive more than several weeks due to their intrinsic fluid interfaces. In particular, a liquid crystal shell can serve as a permeable mem- brane which lets the constituents of aqueous phases pass through, giving a significant influence on the liquid crystalline order. To tame liquid crystal self-assembly and make the shell struc- ture permanent, we use photopolymerization to stabilize the shells. With only 5% monomer, the entire configuration of each liquid crystal shell is locked and shell lifetime extends beyond several months. The liquid crystalline order is visualized on the nanoscale via the polymer network and we further demonstrate that the shell configurations can be a unique template for creating complex polymer networks. Finally a new experimental approach is introduced to making ultrathin shells and several issues on shell instability and alignment determination are addressed. [less ▲]

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See detailDEVELOPMENT OF A COMPUTATIONAL RESOURCE FOR PERSONALIZED DIETARY RECOMMENDATIONS
Noronha, Alberto UL

Doctoral thesis (2018)

There is a global increase in the incidence of non-communicable diseases associated with unhealthy food intakes. Conditions such as diabetes, heart disease, high blood pressure, and strokes represent a ... [more ▼]

There is a global increase in the incidence of non-communicable diseases associated with unhealthy food intakes. Conditions such as diabetes, heart disease, high blood pressure, and strokes represent a high societal impact and an economic burden for health-care systems around the world. To understand these diseases, one needs to account the several factors that influence how the human body processes food, some of which are determined by the genome and patterns of gene expression that translate to the ability - or lack of - to degrade and absorb certain nutrients. Other factors, like the gut microbiota, are more volatile because its composition is highly moldable by diet and lifestyle. Multi-omics technologies can support the comprehensive collection of dietary intake data and monitoring of the health status of individuals. Also, a correct analysis of this data could lead to new insights about the complex processes involved in the digestion of dietary components and their involvement in the prevention or the appearance of health problems, but its integration and interpretation are still problematic. Thus, in this thesis, we propose the utilization of Constraint-Based Reconstruction and Analysis (COBRA) methods as a framework for the integration of this complex data. To achieve this goal, we have created a knowledge-base, the Virtual Metabolic Human (VMH), that combines information from large-scale models of metabolism from the human organism and typical gut microbes, with food composition information, and a disease compendium. VMH’s unique combination of resources leverages the exploration of metabolic pathways from different organisms, the inclusion of dietary information into in-silico experiments through its own diet designer tool, visualization and analysis of experimental and simulation data, and exploring disease mechanisms and potential treatment strategies. VMH is a step forward in providing the necessary tools to investigate the mechanisms behind the influence of diet in health and disease. Tools such as the diet designer can be used as a basis for diet optimization by predicting combinations of foods that can contribute to specific metabolic outcomes, which has the potential to be integrated and translated into treatment development and dietary recommendations in the foreseeable future. [less ▲]

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See detailDynamical hybrid modeling of human metabolism
Ben Guebila, Marouen UL

Doctoral thesis (2018)

Human metabolism plays a key role in disease pathogenesis and drug action. Half a century of biochemical literature leveraged by the advent of genomics allowed the emergence of computational modeling ... [more ▼]

Human metabolism plays a key role in disease pathogenesis and drug action. Half a century of biochemical literature leveraged by the advent of genomics allowed the emergence of computational modeling techniques and the in silico analysis of complex biological systems. In particular, Constraint-Based Reconstruction and Analysis (COBRA) methods address the complexity of metabolism through building tissue-specific networks in their steady state. It is known that biological systems respond to perturbations induced by pathogens, drugs or malignant processes by shifting their activity to safeguard key metabolic functions. Extending the modeling framework to consider the dynamics of these complex systems will bring simulations closer to observable human phenotypes. In this thesis, I combined physiologically-based pharmacokinetic (PBPK) models with genome-scale metabolic models (GSMMs) to form hybrid genome-scale dynamical models that provide a hypothesis-free framework to study the perturbations induced by one or more perturbagen on human tissues. On a first stage, these methodologies were applied to decipher the absorption of levodopa and amino acids by the intestinal epithelium and allowed to derive a model-based diet for Parkinson's Disease patients. In the next phase, we extended the study to 605 drugs in order to predict the occurrence of gastrointestinal side effects through a machine learning classifier, using a combination of gene expression and metabolic reactions set as features. Finally, the approach upscaled to several tissues, specifically to investigate the genesis of metabolic symptoms in type 1 diabetes and to suggest key metabolic players underlying within and between-individual variability to insulin action. Taken as whole, the integration of two modeling techniques constrained by expert biological knowledge and heterogeneous data types will be a step forward in achieving convergence in human biology. [less ▲]

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See detailModelling the Extensionally Driven Transitions of DNA
Taghavi, Amirhossein UL

Doctoral thesis (2018)

Empirical measurements on DNA under tension show a jump by a factor of ≈ 1.5 − 1.7 in the relative extension at applied force of ≈ 65 − 70 pN, indi- cating a structural transition. The still ambiguously ... [more ▼]

Empirical measurements on DNA under tension show a jump by a factor of ≈ 1.5 − 1.7 in the relative extension at applied force of ≈ 65 − 70 pN, indi- cating a structural transition. The still ambiguously characterised stretched ‘phase’ is known as S-DNA. Using atomistic and coarse-grained Monte Carlo simulations we study DNA over-stretching in the presence of organic salts Ethidium Bromide (EtBr) and Arginine (an amino acid present in the RecA binding cleft). We present planar-stacked triplet disproportionated DNA as a solution phase of the double helix under tension, and dub it ‘Σ DNA’, with the three right-facing points of the Σ character serving as a mnemonic for the three grouped bases. Like unstretched Watson-Crick base paired DNA structures, the structure of the Σ phase is linked to function: the partitioning of bases into codons of three base-pairs each is the first stage of operation of recombinase enzymes such as RecA, facilitating alignment of homologous or near-homologous sequences for genetic exchange or repair. By showing that this process does not require any very sophisticated manipulation of the DNA, we position it as potentially appearing as an early step in the de- velopment of life, and correlate the postulated sequence of incorporation of amino acids (GADV then GADVESPLIT and then the full 20 residue set of canonical amino acids) into molecular biology with the ease of Σ-formation for sequences including the associated codons. To further investigate the de- pendence of stretching behaviour on the concentration of intercalating salt molecules, we present a physically motivated coarse-grained force-field for DNA under tension and use it to qualitatively reproduce regimes of force- extension behaviour which are not atomistically accessible. [less ▲]

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See detailDynamic Network Reconstruction in Systems Biology: Methods and Algorithms
Yue, Zuogong UL

Doctoral thesis (2018)

Dynamic network reconstruction refers to a class of problems that explore causal interactions between variables operating in dynamical systems. This dissertation focuses on methods and algorithms that ... [more ▼]

Dynamic network reconstruction refers to a class of problems that explore causal interactions between variables operating in dynamical systems. This dissertation focuses on methods and algorithms that reconstruct/infer network topology or dynamics from observations of an unknown system. The essential challenges, compared to system identification, are imposing sparsity on network topology and ensuring network identifiability. This work studies the following cases: multiple experiments with heterogeneity, low sampling frequency and nonlinearity, which are generic in biology that make reconstruction problems particularly challenging. The heterogeneous data sets are measurements in multiple experiments from the underlying dynamical systems that are different in parameters, whereas the network topology is assumed to be consistent. It is particularly common in biological applications. This dissertation proposes a way to deal with multiple data sets together to increase computational robustness. Furthermore, it can also be used to enforce network identifiability by multiple experiments with input perturbations. The necessity to study low-sampling-frequency data is due to the mismatch of network topology of discrete-time and continuous-time models. It is generally assumed that the underlying physical systems are evolving over time continuously. An important concept system aliasing is introduced to manifest whether the continuous system can be uniquely determined from its associated discrete-time model with the specified sampling frequency. A Nyquist-Shannon-like sampling theorem is provided to determine the critical sampling frequency for system aliasing. The reconstruction method integrates the Expectation Maximization (EM) method with a modified Sparse Bayesian Learning (SBL) to deal with reconstruction from output measurements. A tentative study on nonlinear Boolean network reconstruction is provided. The nonlinear Boolean network is considered as a union of local networks of linearized dynamical systems. The reconstruction method extends the algorithm used for heterogeneous data sets to provide an approximated inference but improve computational robustness significantly. The reconstruction algorithms are implemented in MATLAB and wrapped as a package. With considerations on generic signal features in practice, this work contributes to practically useful network reconstruction methods in biological applications. [less ▲]

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See detailThe institution of linguistic dissidence in the Balearic Islands: ideological dynamics of Catalan standardisation
Duane Bernedo, Lucas John UL

Doctoral thesis (2018)

This thesis describes ethnographically the recent institution of linguistic dissidence in the Balearic Islands, understood as the establishment of a belief in the archipelago’s socio-political field that ... [more ▼]

This thesis describes ethnographically the recent institution of linguistic dissidence in the Balearic Islands, understood as the establishment of a belief in the archipelago’s socio-political field that claims ‘Balearic’, and not the current Catalan, must share official status with Castilian as its authentic autochthonous language. Three associations of language activists created in 2013 are responsible for this development. This thesis analyses two years of social media activity of the three language activist associations, together with other materials. Findings show how activists engaged in a struggle for the legitimisation of an alternative standard that revolved around authenticity ideologies, while they simultaneously secured and advanced the anonymity value of Castilian. Social media was instrumental for these purposes, as it provided activists representational control to articulate discourses about language and to police language practices. This thesis also examines the implications that this development represented for Catalan standardisation. I interviewed 11 language planners working at different institutions in the Balearic Islands and two Catalan language advocates. The interviews provided accounts on the ways institutional actors police the standard variety. After finding a vertical distribution of standard practices among institutional actors, the analysis focuses on a local planner’s social media practices. In all, this thesis advances three arguments about the activists’ strategic adoption of the standard language regime, the existence of an identification need in the Balearic linguistic market, and the role of minoritisation on standardisation. [less ▲]

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See detailComputational Integrative Models for Cellular Conversion: Application to Cellular Reprogramming and Disease Modeling
Zickenrott, Sascha UL

Doctoral thesis (2018)

The groundbreaking identification of only four transcription factors that are able to induce pluripotency in any somatic cell upon perturbation stimulated the discovery of copious amounts of instructive ... [more ▼]

The groundbreaking identification of only four transcription factors that are able to induce pluripotency in any somatic cell upon perturbation stimulated the discovery of copious amounts of instructive factors triggering different cellular conversions. Such conversions are highly significant to regenerative medicine with its ultimate goal of replacing or regenerating damaged and lost cells. Precise directed conversion of damaged cells into healthy cells offers the tantalizing prospect of promoting regeneration in situ. In the advent of high-throughput sequencing technologies, the distinct transcriptional and accessible chromatin landscapes of several cell types have been characterized. This characterization provided clear evidences for the existence of cell type specific gene regulatory networks determined by their distinct epigenetic landscapes that control cellular phenotypes. Further, these networks are known to dynamically change during the ectopic expression of genes initiating cellular conversions and stabilize again to represent the desired phenotype. Over the years, several computational approaches have been developed to leverage the large amounts of high-throughput datasets for a systematic prediction of instructive factors that can potentially induce desired cellular conversions. To date, the most promising approaches rely on the reconstruction of gene regulatory networks for a panel of well-studied cell types relying predominantly on transcriptional data alone. Though useful, these methods are not designed for newly identified cell types as their frameworks are restricted only to the panel of cell types originally incorporated. More importantly, these approaches rely majorly on gene expression data and cannot account for the cell type specific regulations modulated by the interplay of the transcriptional and epigenetic landscape. In this thesis, a computational method for reconstructing cell type specific gene regulatory networks is proposed that aims at addressing the aforementioned limitations of current approaches. This method integrates transcriptomics, chromatin accessibility assays and available prior knowledge about gene regulatory interactions for predicting instructive factors that can potentially induce desired cellular conversions. Its application to the prioritization of drugs for reverting pathologic phenotypes and the identification of instructive factors for inducing the cellular conversion of adipocytes into osteoblasts underlines the potential to assist in the discovery of novel therapeutic interventions. [less ▲]

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See detailComputational Integrative Models for Cellular Conversion: Application to Cellular Reprogramming and Disease Modeling
Jung Geb. Zickenrott, Sascha UL

Doctoral thesis (2018)

The groundbreaking identification of only four transcription factors that are able to induce pluripotency in any somatic cell upon perturbation stimulated the discovery of copious amounts of instructive ... [more ▼]

The groundbreaking identification of only four transcription factors that are able to induce pluripotency in any somatic cell upon perturbation stimulated the discovery of copious amounts of instructive factors triggering different cellular conversions. Such conversions are highly significant to regenerative medicine with its ultimate goal of replacing or regenerating damaged and lost cells. Precise directed conversion of damaged cells into healthy cells offers the tantalizing prospect of promoting regeneration in situ. In the advent of high-throughput sequencing technologies, the distinct transcriptional and accessible chromatin landscapes of several cell types have been characterized. This characterization provided clear evidences for the existence of cell type specific gene regulatory networks determined by their distinct epigenetic landscapes that control cellular phenotypes. Further, these networks are known to dynamically change during the ectopic expression of genes initiating cellular conversions and stabilize again to represent the desired phenotype. Over the years, several computational approaches have been developed to leverage the large amounts of high-throughput datasets for a systematic prediction of instructive factors that can potentially induce desired cellular conversions. To date, the most promising approaches rely on the reconstruction of gene regulatory networks for a panel of well-studied cell types relying predominantly on transcriptional data alone. Though useful, these methods are not designed for newly identified cell types as their frameworks are restricted only to the panel of cell types originally incorporated. More importantly, these approaches rely majorly on gene expression data and cannot account for the cell type specific regulations modulated by the interplay of the transcriptional and epigenetic landscape. In this thesis, a computational method for reconstructing cell type specific gene regulatory networks is proposed that aims at addressing the aforementioned limitations of current approaches. This method integrates transcriptomics, chromatin accessibility assays and available prior knowledge about gene regulatory interactions for predicting instructive factors that can potentially induce desired cellular conversions. Its application to the prioritization of drugs for reverting pathologic phenotypes and the identification of instructive factors for inducing the cellular conversion of adipocytes into osteoblasts underlines the potential to assist in the discovery of novel therapeutic interventions. [less ▲]

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See detailActive Harmonics Compensation in Smart Grids
Kobou Ngani, Patrick UL

Doctoral thesis (2018)

The quality of electric power is a key factor for the electricity supply service. It defines how good the characteristics of the supplied power meet the standard ones. Among several other power quality ... [more ▼]

The quality of electric power is a key factor for the electricity supply service. It defines how good the characteristics of the supplied power meet the standard ones. Among several other power quality issues, the harmonics are of more and more concern over the last decades. This is essentially due to the widespread use of electronic components. This thesis focuses on the development of a voltage active power filter implementing a new selective harmonics compensation algorithm. The first design is described as following: band-pass filters decompose the measured voltage signal as a sum of different harmonics voltages; PLLs (frequency-tuned) transform of the oscillating signals into two orthogonal and rotating components (dq-transform). The dq-components of each harmonic are controlled to zero using standard PI-controllers and the compensating harmonics waves are generated via the inverse PLL. All the harmonics compensating waves are superimposed and added to the fundamental reference signal. This represents the final control signal of the inverter. Implemented in the MATLAB-SIMULINK simulation environment, this foreseen methodology depicted as major issue the control stability especially when the system frequency differs from the rated 50-Hertz frequency. This is the reason why a second design has been proposed. The major improvement is done on the harmonics detection stability by replacing the PLLs frames by the well-known internal frame of the fundamental voltage of the controlled inverter. After the convincing theoretical results from the simulations, the method is implemented and validated experimentally on a test rig in the lab. The two key features of the developed active power filter (APF) are: 1)Its ability to be used as a standalone power unit that compensates by itself the harmonics that could appear in the system while generating the fundamental voltage necessary to build up the micro-grid. 2)Its ability to serve as a full grid-tied power element that not only mitigates the voltages harmonics on the coupled grid but also supports the grid by controlling the exchanged active and reactive powers between the inverter and the grid. In addition to the developed harmonic mitigation technique, a new grid synchronization method has been proposed along with a new power control algorithm combined with a grid impedance estimator for grid-tied inverter. Further investigations and development are required for three-phase unbalance voltage systems as well as for single-phase voltage power system for low power grids. [less ▲]

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See detailContributions to the asymptotic study of Hermite driven processes
Tran, Thi Thanh Diu UL

Doctoral thesis (2018)

This thesis consists of two parts. Part I is an introduction to Hermite processes, Hermite random fields, Fisher information and to the papers constituting the thesis. More precisely, in Section 1 we ... [more ▼]

This thesis consists of two parts. Part I is an introduction to Hermite processes, Hermite random fields, Fisher information and to the papers constituting the thesis. More precisely, in Section 1 we introduce Hermite processes in a nutshell, as well as some of its basic properties. It is the necessary background for the articles [a] and [c]. In Section 2 we consider briefly the multiparameter Hermite random fields and we study some less elementary facts which are used in the article [b]. In section 3, we recall some terminology about Fisher information related to the article [d]. Finally, our articles [a] to [d] are summarised in Section 4. Part II consists of the articles themselves: [a] T.T. Diu Tran (2017): Non-central limit theorem for quadratic functionals of Hermite-driven long memory moving average processes. Stochastic and Dynamics, 18, no. 4. [b] T.T. Diu Tran (2016): Asymptotic behavior for quadratic variations of nonGaussian multiparameter Hermite random fields. Under revision for Probability and Mathematical Statistics. [c] I. Nourdin, T.T. Diu Tran (2017): Statistical inference for Vasicek-type model driven by Hermite processes. Submitted to Stochastic Process and their Applications. [d] T.T. Diu Tran (2017+): Fisher information and multivariate Fouth Moment Theorem. Main results have already been obtained. It should be submitted soon. [less ▲]

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See detailAdaptive capacities of cancer cells in Glioblastoma
Dirkse, Anne Marie Elisabeth UL

Doctoral thesis (2018)

Detailed reference viewed: 15 (3 UL)