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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 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 detailExplaining free will by rational capacities
Hofmann, Frank UL

in Ethical Theory and Moral Practice (2022)

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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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See detailSpectrum of Phenotypic, Genetic, and Functional Characteristics in Epilepsy Patients With KCNC2 Pathogenic Variants 10.1212/WNL.0000000000200660
Schwarz, Niklas; Seiffert, Simone; Pendziwiat, Manuela et al

in Neurology (2022)

Background: KCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of ... [more ▼]

Background: KCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. The objective of this study was to analyse the clinical phenotype, genetic background, and biophysical function of disease-associated Kv3.2 variants.Methods: Individuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic, and functional analysis. Cases were referred through clinical and research collaborations. Selected de novo variants were examined electrophysiologically in Xenopus laevis oocytes.Results: We identified novel KCNC2 variants in 18 patients with various forms of epilepsy including genetic generalized epilepsy (GGE), developmental and epileptic encephalopathy (DEE) including early-onset absence epilepsy (EOAE), focal epilepsy (FE), and myoclonic-atonic epilepsy (MAE). 10/18 variants were de novo and 8/18 variants were classified as modifying variants. 8 drug responsive cases became seizure-free using valproic acid as monotherapy or in combination including severe DEE cases. Functional analysis of four variants demonstrated gain-of-function in three severely affected DEE cases and loss-of-function in one case with a milder phenotype (GGE) as the underlying pathomechanisms.Conclusion: These findings implicate KCNC2 as a novel causative gene for epilepsy and emphasize the critical role of KV3.2 in the regulation of brain excitability. [less ▲]

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See detailClosing Keynote: Networks, governance and design. A journey through some historical case studies
Schafer, Valerie UL

Presentation (2022, March 18)

As famous as the quotation by Lawrence Lessing “Code is law”, the sentence by David Clark at a meeting at the IETF in 1992 “We reject kings, presidents and voting, we believe in rough consensus and ... [more ▼]

As famous as the quotation by Lawrence Lessing “Code is law”, the sentence by David Clark at a meeting at the IETF in 1992 “We reject kings, presidents and voting, we believe in rough consensus and running code” became a “motto for Internet standardization” (Russell, 2006) that invites us to have a look at the past relationships and intertwinements between networks design and governance. From the 1970s topics related to distribution and openness have become key in networks infrastructures, while complementary issues related to asymmetries and multi-stakeholderism (Raymond and DeNardis 2015) have been emphasized in the 1990s and 2000s, and notably during the WSIS in Tunis and Geneva. Research related to Internet governance (Mueller and Badiei, 2020; Musiani, Schafer, 2021) has also brought to the table strong issues related to agencies, privacy, and many others that have strongly followed the development of networks and their uses as well as controversies related to net neutrality or information flows for example (DeNardis, 2020). This presentation will go through several historical case studies and rethink them through the lens of infrastructure design and governance, from Arpanet in the 1970s, XNS and then the OSI (Russell, 2014), to web archives (Schafer, Winters 2021) and research infrastructures today, through past designs and attempts, related to the Web and Xanadu, the Minitel (Schafer, Thierry, 2012; Mailland, Driscoll, 2017), platforms like Wuala (Musiani, 2022) and Wikipedia (Cardon and Levrel, 2009). This will allow us to explore some notions and approach related to closure, secret, incentives, empowerment, while finally moving from “governance” to “good governance” and its challenges. [less ▲]

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See detail"But you know you won't be back"
Scuto, Denis UL

Article for general public (2022)

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See detailWorkers rights and human rights: toward a new fundamental principle?
Yusifli, Zahra UL; Fenwick, Colin

in Elliott, Kimberly A. (Ed.) Handbook on Globalisation and Labour Standards (2022)

Detailed reference viewed: 26 (2 UL)
See detailTemporary Protection in the EU - State of Play
Mellinger, Lukas UL; Sommarribas, Adolfo UL

Report (2022)

On 24 February 2022, the armed forces of the Russian Federation launched an unprovoked full-scale invasion of Ukraine. This was an unprecedented act of aggression against a sovereign and independent ... [more ▼]

On 24 February 2022, the armed forces of the Russian Federation launched an unprovoked full-scale invasion of Ukraine. This was an unprecedented act of aggression against a sovereign and independent country and goes against fundamental principles of international law. It has been strongly condemned by the international community, including the European Union. As of mid-March, over three million Ukrainian and international refugees are fleeing the war to neighbouring EU and third countries (including Moldova). This massive inflow of Ukrainian refugees into the EU resulted in the Council adopting the implementing Decision 2022/382 of 4 March 2022, introducing temporary protection as a means of dealing with the crisis. [less ▲]

Detailed reference viewed: 61 (4 UL)
See detailA Workshop on War Letters (in the Digital Age)
Janz, Nina UL; van der Lange, Milan

Report (2022)

Impressions of building a community around people working on the digitization of historical ‘egodocuments’ using Transkribus.

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See detailLa relecture entre pairs : un levier de motivation de la pratique de l’écrit
Lejot, Eve UL

Scientific Conference (2022, March 17)

Les enseignants corrigent et donnent des conseils d’amélioration à leurs apprenants, mais les commentaires des enseignants sont parfois mal compris (Cole, Coats, Lentell 1986 ; Smith 1997), alors que la ... [more ▼]

Les enseignants corrigent et donnent des conseils d’amélioration à leurs apprenants, mais les commentaires des enseignants sont parfois mal compris (Cole, Coats, Lentell 1986 ; Smith 1997), alors que la relecture entre pairs apporte un échange avec moins de pression (Lejot 2017). Cet échange se fait à un niveau de hiérarchie égal et facilite la négociation de sens des éléments du texte. Néanmoins, certains élèves pointent le manque de qualification des pairs pour remplacer les commentaires des professeurs dans l’enseignement supérieur (Rollinson 2005). Cette démarche trouve toute sa force pour les doctorants. Mis en place sur un semestre, ce système fermé de relecture et de commentaires reçus en boucle est bénéfique et motivant pour ces derniers. Dans les ateliers interdisciplinaires sur les compétences transversales et en l'occurrence celle de l'écrit académique, les doctorants soulignent l’énergie, la réflexion commune et le soutien que leur a apporté la relecture de texte d'un pair et d'être eux-mêmes relus (Lejot 2017). Relire est formateur et être compris par des chercheurs pairs fait faire un grand pas en termes de cohérence d'écriture et d'argumentation bien articulée à ces groupes des écoles doctorales. [less ▲]

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See detailActive Homework: an underresearched element of the active schools concept
Bailey, Richard; Heck, Sandra UL; Scheuer, Claude UL

in German Journal of Exercise and Sport Research (2022)

Background Most physical activity (PA) interventions targeting children focus on the school setting. However, children and young people are often less active at home. The purpose of this article is to ... [more ▼]

Background Most physical activity (PA) interventions targeting children focus on the school setting. However, children and young people are often less active at home. The purpose of this article is to review evidence from the last ten years of the contribution of physically Active Homework (AH) to the promotion of PA. Methods Using a rapid review methodology, the article reports on evidence contribution of AH and considers conditions for its effective implementation. Results Although research literature on the effects of AH is limited and missing a theoretical base, studies reporting small positive associations between AH and PA levels were identified. Increases in PA were, however, of low intensity; moderate and vigorous intensities remained relatively unchanged. Conclusions Strategies to increase PA extending beyond the school gym are needed. Further and better research is needed to understand the conditions of effective implementation of AH. Nevertheless, there is a plausibility in providing students regular opportunities to further promote PA in students’ lives by practicing movement and sports skills, and offering a flexible way of finding and pursuing meaningful activities. The fact that AH may encourage the engagement of families and communities, multiplies its potential benefits. [less ▲]

Detailed reference viewed: 45 (1 UL)