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See detailComments on Smithies
Raleigh, Thomas UL

in Asian Journal of Philosophy (2022), 1(13),

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See detailA posteriori error estimation for finite element approximations of fractional Laplacian problems and applications to poro–elasticity
Bulle, Raphaël UL

Doctoral thesis (2022)

This manuscript is concerned with a posteriori error estimation for the finite element discretization of standard and fractional partial differential equations as well as an application of fractional ... [more ▼]

This manuscript is concerned with a posteriori error estimation for the finite element discretization of standard and fractional partial differential equations as well as an application of fractional calculus to the modeling of the human meniscus by poro-elasticity equations. In the introduction, we give an overview of the literature of a posteriori error estimation in finite element methods and of adaptive refine- ment methods. We emphasize the state–of–the–art of the Bank–Weiser a posteriori error estimation method and of the adaptive refinement methods convergence results. Then, we move to fractional partial differential equations. We give some of the most common discretization methods of fractional Laplacian operator based equations. We review some results of a priori error estimation for the finite element discretization of these equations and give the state–of–the–art of a posteriori error estimation. Finally, we review the literature on the use of the Caputo’s fractional derivative in applications, focusing on anomalous diffusion and poro-elasticity applications. The rest of the manuscript is organized as follow. Chapter 1 is concerned with a proof of the reliability of the Bank–Weiser estimator for three–dimensional problems, extending a result from the literature. In Chapter 2 we present a numerical study of the Bank–Weiser estimator, provide a novel implementation of the estimator in the FEniCS finite element software and apply it to a variety of elliptic equations as well as goal-oriented error estimation. In Chapter 3 we derive a novel a posteriori estimator for the L2 error induced by the finite element discretization of fractional Laplacian operator based equations. In Chapter 4 we present new theoretical results on the convergence of a rational approximation method with consequences on the approximation of fractional norms as well as a priori error estimation results for the finite element discretization of fractional equations. Finally, in Chapter 5 we provide an application of fractional calculus to the study of the human meniscus via poro-elasticity equations. [less ▲]

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See detailThe History of Cross-Border Cooperation: some historiographical remarks
Brüll, Christoph UL

Scientific Conference (2022, March 24)

What is Cross-Border Cooperation? How to write the History of Cross-Border Cooperation? The contribution explores the historiography in the field and presents two case studies (Euregio Meuse-Rhine and ... [more ▼]

What is Cross-Border Cooperation? How to write the History of Cross-Border Cooperation? The contribution explores the historiography in the field and presents two case studies (Euregio Meuse-Rhine and Europäische Vereinigung Eifel-Ardennen). It focusses on the sources that could be used for such a history and on difficulties regarding archival research. [less ▲]

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See detailPresenter: The future of the history of cross-border cooperation
Venken, Machteld UL

Presentation (2022, March 24)

Detailed reference viewed: 81 (17 UL)
See detailScreening for Consensus: Delegation with Collective Principals
Anesi, Vincent UL; Buisseret, Peter

Presentation (2022, March 23)

A group of principals collectively and sequentially screen an agent. The principals hold heterogeneous values from the relationship that may evolve over time. At each date, the principals use a collective ... [more ▼]

A group of principals collectively and sequentially screen an agent. The principals hold heterogeneous values from the relationship that may evolve over time. At each date, the principals use a collective decision rule to propose a contract to the agent. We unearth circumstances in which every non-dictatorial decision rule yields inefficiency in the form of excessive learning: relative to a single-principal benchmark, collective principals screen the agent too aggressively. They do so in order to reduce uncertainty about the agent’s preferences, and alleviate dynamic conflicts of interest between the principals that exist regardless of their static alignment. [less ▲]

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See detailCNV-ClinViewer: Enhancing the clinical interpretation of large copy-number variants online
Macnee, Marie; Perez-Palma, Eduardo; Brünger, Tobias et al

E-print/Working paper (2022)

Purpose Large copy number variants (CNVs) can cause a heterogeneous spectrum of rare and severe disorders. However, most CNVs are benign and are part of natural variation in human genomes. CNV ... [more ▼]

Purpose Large copy number variants (CNVs) can cause a heterogeneous spectrum of rare and severe disorders. However, most CNVs are benign and are part of natural variation in human genomes. CNV pathogenicity classification, genotype-phenotype analyses, and therapeutic target identification are challenging and time-consuming tasks that require the integration and analysis of information from multiple scattered sources by experts. Methods We developed a web-application combining >250,000 patient and population CNVs together with a large set of biomedical annotations and provide tools for CNV classification based on ACMG/ClinGen guidelines and gene-set enrichment analyses. Results Here, we introduce the CNV-ClinViewer (https://cnv-ClinViewer.broadinstitute.org), an open-source web-application for clinical evaluation and visual exploration of CNVs. The application enables real-time interactive exploration of large CNV datasets in a user-friendly designed interface. Conclusion Overall, this resource facilitates semi-automated clinical CNV interpretation and genomic loci exploration and, in combination with clinical judgment, enables clinicians and researchers to formulate novel hypotheses and guide their decision-making process. Subsequently, the CNV-ClinViewer enhances for clinical investigators patient care and for basic scientists translational genomic research. [less ▲]

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See detailINCREASING THE COMPLEXITY OF MIDBRAIN ORGANOID SYSTEMS FOR DEVELOPMENTAL STUDIES AND DISEASE MODELLING
Sabaté Soler, Sonia UL

Doctoral thesis (2022)

The discovery of iPSC technology revolutionized the biomedical field, allowing the development of translatable and complex 2D and 3D cell culture systems. Organoids are 3D models containing multiple cell ... [more ▼]

The discovery of iPSC technology revolutionized the biomedical field, allowing the development of translatable and complex 2D and 3D cell culture systems. Organoids are 3D models containing multiple cell types that mimic complex microenvironments. This is highly advantageous to understand human development, physiology and disease, especially in inaccessible areas such as the brain. Human midbrain-specific organoids have been developed to study the midbrain (abundant in dopaminergic neurons). In Parkinson’s Disease (PD), dopaminergic neurons in the substantia nigra of the midbrain degenerate, causing a broad spectrum of clinical features. Midbrain organoids (MO) are rich in dopaminergic neurons, and contain spatially organized groups of neural cells and progenitors. MO generated from PD patients’ cells recapitulate dopaminergic neuron degeneration. In this thesis, we first demonstrated that dopaminergic neuron PD phenotypes and drug rescue effects were similar between MO and mice. After, we identified different neuronal clusters, progenitor cells, radial glia and mesenchymal cells in MO by scRNA-Seq. As expected, due to the neuro-ectodermal patterning of the MO’ starting cell population, we confirmed the absence of mesoderm-derived cell types, such as microglia and endothelial cells. This represents a limitation for the system in terms of cellular and molecular complexity. Microglia in the human brain perform surveillance, defence and homeostasis functions; they phagocytose metabolic waste products and cell debris. We successfully developed a novel protocol to integrate functional microglia into our MO model. SnRNA-Seq analysis and electrophysiological results suggested a reduction of stress levels and higher maturation of neurons in the presence of microglia, respectively. We then aimed to vascularise MO, which would better recapitulate the brain environment and improve oxygen and nutrient supply into the organoid core (a common 3D culture limitation). We integrated an endothelial network into MO by fusion with vascular organoids, and observed the presence of blood vessel components like pericytes and basal lamina. Furthermore, vascularized assembloids showed decreased levels of cell death and hypoxia. Finally, by co-culturing microglia with vascularized assembloids, we modelled the neurovascular unit in 3D. Altogether, this work contributes to the development of advanced 3D region-specific organoids, which better recapitulate the complexity of the human brain. These novel MO systems represent one step further into modelling neuroinflammation and blood brain barrier disruption, typical from neurodegenerative disorders such as PD, which might lead to more reliable and personalized medical approaches. [less ▲]

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See detailConserved patterns across ion channels correlate with variant pathogenicity and clinical phenotypes 2022.03.23.485339
Brünger, Tobias; Perez-Palma, Eduardo; Montanucci, Ludovica et al

E-print/Working paper (2022)

Clinically identified genetic variants in ion channels can be benign or cause disease by increasing or decreasing the protein function. Consequently, therapeutic decision-making is challenging without ... [more ▼]

Clinically identified genetic variants in ion channels can be benign or cause disease by increasing or decreasing the protein function. Consequently, therapeutic decision-making is challenging without molecular testing of each variant. Our biophysical knowledge of ion channel structures and function is just emerging, and it is currently not well understood which amino acid residues cause disease when mutated.We sought to systematically identify biological properties associated with variant pathogenicity across all major voltage and ligand-gated ion channel families. We collected and curated 3,049 pathogenic variants from hundreds of neurodevelopmental and other disorders and 12,546 population variants for 30 ion channel or channel subunits for which a high-quality protein structure was available. Using a wide range of bioinformatics approaches, we computed 163 structural features and tested them for pathogenic variant enrichment. We developed a novel 3D spatial distance scoring approach that enables comparisons of pathogenic and population variant distribution across protein structures.We discovered and independently replicated that several pore residue properties and proximity to the pore axis were most significantly enriched for pathogenic variants compared to population variants. Using our novel 3D scoring approach, we showed that the strongest pathogenic variant enrichment was observed for pore-lining residues and alpha-helix residues within 5 A distance from the pore axis center and not involved in gating. Within the subset of residues located at the pore, the hydrophobicity of the pore was the feature most strongly associated with variant pathogenicity. We also found an association between the identified properties and both clinical phenotypes and fucntional in vitro assays for voltage-gated sodium channels (SCN1A, SCN2A, SCN8A) and N-methyl-D-aspartate (NMDA) receptor (GRIN1, GRIN2A, GRIN2B) encoding genes. In an independent expert-curated dataset of 1,422 neurodevelopmental disorder pathogenic patient variants, and 679 electrophysiological experiments that pore axis distance is associated with seizure age of onset and cognitive performance as well as differential gain vs. loss-of-channel function.In summary, we identified biological properties associated with ion-channel malfunction and show that these are correlated with in vitro functional read-outs and clinical phenotypes in patients with neurodevelopmental disorders. Our results suggest that clinical decision support algorithms that predict variant pathogenicity and function are feasible in the future.Competing Interest StatementThe authors have declared no competing interest.DSSPDictionary of Protein Secondary StructuregnomADGenome aggregation DatabaseGoFGain of functionGRIN genesGRIN1, GRIN2A. GRIN2BHGMDHuman Gene Mutation DatabaseNMDA receptorN-methyl-D-aspartate receptorGABA receptorGamma-aminobutyric acid receptorLoFLoss of functionSCN genesSCN1A, SCN2A, SCN8AVCFVariant Call Format [less ▲]

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See detailSystematic Identification of High "Value-Added" in Educational Contexts (SIVA)
Emslander, Valentin UL; Levy, Jessica; Fischbach, Antoine UL

Report (2022)

The aim of the SIVA project is to investigate differences between schools with stable high value-added (VA) scores to those with low or medium VA scores to learn about their effective pedagogical ... [more ▼]

The aim of the SIVA project is to investigate differences between schools with stable high value-added (VA) scores to those with low or medium VA scores to learn about their effective pedagogical strategies. We attempt to achieve this goal through classroom observations and questionnaires for students in grade 2, their parents, their teachers, as well as school presidents. More specifically, with the present study we want to learn from target schools with stable positive VA scores – a statistical method usually used to estimate schools' effectiveness. We will use VA modelling constructively to compare those schools identified as highly effective (i.e., with high VA scores) to schools with medium or low VA scores on variables such as pedagogical strategies, student background, and school climate. To this end, a mixed-methods design based on questionnaires, observations, and results from the Luxembourg School Monitoring Programme ÉpStan (LUCET, 2021) will be applied. The content of the investigation is based on a synthesis of models of school learning and quality, focusing on aspects such as school organization or classroom management (e.g., Hattie, 2008; Helmke et al., 2008; Klieme et al., 2001) and is extended by specificities about the Luxembourgish school system, which are not represented in international school learning models (such as the division into two-year learning cycles, the multilingual school setting, and the diverse student population). With the aim to obtain a preferably broad picture, students, parents, teachers, school presidents and regional directors will be investigated. While parents, teachers, school presidents and regional directors can—as adults—fill out questionnaires individually, obtaining the opinion from children at such a young age can be challenging. The SIVA project tackles this issue by choosing item formats that are appealing and understandable for young children (see, e.g.,Lehnert, 2019), as well as by including classroom observations conducted by neutral educational experts (please, find both the questionnaires and observation sheets in the attachments). [less ▲]

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See detailNOMA-Enabled Backscatter Communications for Green Transportation in Automotive-Industry 5.0
Khan, Wali Ullah UL; Ihsan, Asim; Nguyen, Tu N. et al

in IEEE Transactions on Industrial Informatics (2022)

Automotive-Industry 5.0 will use emerging 6G communications to provide robust, computationally intelligent, and energy-efficient data sharing among various onboard sensors, vehicles, and other intelligent ... [more ▼]

Automotive-Industry 5.0 will use emerging 6G communications to provide robust, computationally intelligent, and energy-efficient data sharing among various onboard sensors, vehicles, and other intelligent transportation system entities. Nonorthogonal multiple access (NOMA) and backscatter communications are two key techniques of 6G communications for enhanced spectrum and energy efficiency. In this article, we provide an introduction to green transportation and also discuss the advantages of using backscatter communications and NOMA in Automotive Industry 5.0. We also briefly review the recent work in the area of NOMA empowered backscatter communications. We discuss different use cases of backscatter communications in NOMA-enabled 6G vehicular networks. We also propose a multicell optimization framework to maximize the energy efficiency of the backscatter-enabled NOMA vehicular network. In particular, we jointly optimize the transmit power of the roadside unit and the reflection coefficient of the backscatter device in each cell, where several practical constraints are also taken into account. The problem of energy efficiency is formulated as nonconvex, which is hard to solve directly. Thus, first, we adopt the Dinkelbach method to transform the objective function into a subtractive one, then we decouple the problem into two subproblems. Second, we employ dual theory and KKT conditions to obtain efficient solutions. Finally, we highlight some open issues and future research opportunities related to NOMA-enabled backscatter communications in 6G vehicular networks. [less ▲]

See detailÜble Gerüchte versetzen ukrainische Frauen in Angst - so wollen sie sich schützen
Ganschow, Inna UL; Becker, Jessica

Article for general public (2022)

Die Angst unter den Geflüchteten, dass sie an Menschen- oder Organhändler geraten könnten, ist groß. Diese Gerüchte hätten sich schnell verbreitet. Daher sei in den Lagern an der polnisch-ukrainischen ... [more ▼]

Die Angst unter den Geflüchteten, dass sie an Menschen- oder Organhändler geraten könnten, ist groß. Diese Gerüchte hätten sich schnell verbreitet. Daher sei in den Lagern an der polnisch-ukrainischen Grenze auch Überzeugungsarbeit notwendig. Den Geflüchteten werde erklärt, was sie in Deutschland erwartet. "Da ist so viel Vertrauen gefragt", sagt Inna Ganschow. Die Russin ist mit dem Verein MMS Humanitas an die polnisch-ukrainische Grenze gefahren, um Flüchtlinge nach Deutschland zu bringen. Trotz all der traumatischen Erlebnisse glaubten die Geflüchteten aber noch immer an das Gute im Menschen. "Sie steigen in den Bus, weil sie hoffen, dass es ihnen besser gehen wird als im Lager oder Keller zu Hause", erklärt Ganschow. [less ▲]

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See detailPresentation in Computational Sciences PhD Presentation Day
Shang, Lan UL

Presentation (2022, March 22)

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See detailDigital twinning for enhancing breast cancer surgery
Mazier, Arnaud UL

Presentation (2022, March 22)

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See detailDevelopment of data integration tools within functional genomics
Teixeira Queiros, Pedro UL

Doctoral thesis (2022)

Due to technological advances across all scientific domains, data is generated at an extremely fast pace. This is especially true in biology, where advances in computational and sequencing technologies ... [more ▼]

Due to technological advances across all scientific domains, data is generated at an extremely fast pace. This is especially true in biology, where advances in computational and sequencing technologies led to the necessity to develop automated methods for data analysis; thus the field of bioinformatics was born. This thesis focuses on one specific field within bioinformatics - functional genomics. To be precise, in the development of techniques and software for the integration of data to generate novel insights. Indeed, as the amount of knowledge increases, so does the need to integrate it systematically. In this context, the work described herein relates to the integration of multiple resources to improve the functional annotation of proteins, which led to the development of two bioinformatic tools - Mantis and UniFunc. For the downstream integration and analysis of functional predictions, a network annotation tool was developed - UniFuncNet, which, together with the previous tools, enables the efficient functional characterisation of individual organisms or communities. [less ▲]

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Peer Reviewed
See detailExplaining free will by rational capacities
Hofmann, Frank UL

in Ethical Theory and Moral Practice (2022), 25

Detailed reference viewed: 39 (3 UL)
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See detailVerifiable, Secure and Privacy-Preserving Computation
Soroush, Najmeh UL

Doctoral thesis (2022)

In this thesis, I present the research I conducted with my co-authors on numerous areas of verifiable, secure, and privacy-preserving computation during my doctoral studies at the University of Luxembourg ... [more ▼]

In this thesis, I present the research I conducted with my co-authors on numerous areas of verifiable, secure, and privacy-preserving computation during my doctoral studies at the University of Luxembourg, where Professor Peter Ryan advised me. In the first part, I study the functional encryption scheme. In the standard setting of functional encryption, it is assumed both the Central Authority (CA) and the encryptors to run their respective algorithms faithfully. However, in the case of dishonest parties, the security of the cryptosystem may be violated. It means that dishonest parties can cause inconsistent results which may not be detected. In the first part, we improve on this situation by considering Inner-Product Encryption (IPE), a special case of functional encryption and a primitive that has attracted wide interest from practitioners and researchers in the last decade. Specifically, we construct the first efficient verifiable Inner Product Encryption (VIPE) scheme according to the inner-product functionality. As the next step, we construct a verifiable IPE that satisfies unconditional verifiability, whereas privacy relies on the standard assumption. The second part of this thesis presents my research on e-voting protocols. I revisit the coercion-resistant e-voting protocol by Juels, Catalano and Jakobsson (JCJ) and, particularly, the attempts to make it usable and practical. In JCJ the user needs to handle cryptographic credentials and fake these in case of coercion. We present a hardware-independent protocol that can be implemented using a combination of a digitally stored cryptographic length key and a PIN only known by the voter. The long credential could be stored in several places or hidden via steganography. At the ballot casting phase, the software will input the digital key and the password to form the credential submitted with the vote. Depending on the level of coercion, the coerced voter can either fake the long credential or, for stronger levels of coercion, the voter can reveal the digitally stored credential to the coercer but fake the PIN. Due to our improved tally, the coercer will not know if he got faked credentials or PINs. On the other hand, since the voter memories the PIN is a high chance of users making a PIN typo error which will invalidate the vote and remain undetected. Note that naively giving feedback on the correctness of the PIN is not possible for coercion-resistance as it would allow the coercer to check whether he got a fake PIN or not. Instead, we will define a set of allowed PIN errors (e.g., chosen by the election administrator). We will consider a ballot valid if it has a correct PIN or an allowed PIN error but invalid for other PINs. At the tally phase, we construct protocols that secretly check whether a given PIN is in the set of allowed PINs and will sort out invalid ballots. We also design another End-to-End verifiable e-voting scheme achieving coercion-resistance via deniable vote updating. We propose a new e-voting system that enables voters with an intuitive mechanism to update their possibly coerced vote in a deniable way. What is more, our e-voting system does not introduce any additional trust assumptions for end-to-end verifiability and vote privacy besides the standards. Moreover, we demonstrate that our e-voting system can be instantiated efficiently for practical elections. With these properties, our e-voting system has the potential to close the gap between theory and practice in coercion-resistant e-voting. [less ▲]

Detailed reference viewed: 123 (17 UL)
See detailScreening for Consensus : Delegation with Collective Principals
Anesi, Vincent UL; Buisseret, Peter

Presentation (2022, March 21)

A group of principals collectively and sequentially screen an agent. The principals hold heterogeneous values from the relationship that may evolve over time. At each date, the principals use a collective ... [more ▼]

A group of principals collectively and sequentially screen an agent. The principals hold heterogeneous values from the relationship that may evolve over time. At each date, the principals use a collective decision rule to propose a contract to the agent. We unearth circumstances in which every non-dictatorial decision rule yields inefficiency in the form of excessive learning: relative to a single-principal benchmark, collective principals screen the agent too aggressively. They do so in order to reduce uncertainty about the agent’s preferences, and alleviate dynamic conflicts of interest between the principals that exist regardless of their static alignment. [less ▲]

Detailed reference viewed: 27 (4 UL)