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See detailThe mod 2 cohomology rings of congruence subgroups in the Bianchi groups
Berkove, Ethan; Lakeland, Grant; Rahm, Alexander UL

E-print/Working paper (in press)

We provide new tools for the calculation of the torsion in the cohomology of congruence subgroups in the Bianchi groups : An algorithm for finding particularly useful fundamental domains, and an analysis ... [more ▼]

We provide new tools for the calculation of the torsion in the cohomology of congruence subgroups in the Bianchi groups : An algorithm for finding particularly useful fundamental domains, and an analysis of the equivariant spectral sequence combined with torsion subcomplex reduction. [less ▲]

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See detailSpatio-temporal programming of lyotropic phase transition in nanoporous microfluidic confinements
Ulaganathan, Vamseekrishna UL; Ong, Irvine UL; Sengupta, Anupam UL

E-print/Working paper (2022)

Self-assembly of simple molecules into complex phases can be driven by physical constraints, for instance, due to selective molecular uptake by nanoporous surfaces. Despite the significance of surface ... [more ▼]

Self-assembly of simple molecules into complex phases can be driven by physical constraints, for instance, due to selective molecular uptake by nanoporous surfaces. Despite the significance of surface-mediated assembly in evolution of life, physical routes to molecular enrichment and assembly have remained overlooked. Here, using a lyotropic chromonic liquid crystal as model biological material, confined within nanoporous microfluidic environments, we study molecular assembly driven by nanoporous substrates. We demonstrate that nanoporous polydimethylsiloxane (PDMS) surfaces, due to selective permeation of water molecules, drive transition of disordered isotropic phase to ordered nematic, and higher order columnar phases under isothermal conditions. Synergistically, by tailoring the wettability, the surface-to-volume ratio, and surface topography of the confinements, we program the lyotropic phase transitions with a high degree of spatial and temporal control. Using a combination of timelapse polarized imaging, quantitative image processing, and a simple mathematical model, we analyze the phase transitions, and construct a master diagram capturing the role of surface wettability and channel geometry on programmable lyotropic phase transitions. Intrinsic PDMS nanoporosity and confinement cross-section, together with the imposed wettability regulate the rate of the N-M phase transition; whereas the microfluidic geometry and embedded topography enable phase transition at targeted locations. We harness the emergent long-range order during N-M transition to actuate elasto-advective transport of embedded micro-cargo, demonstrating particle manipulation concepts governed by tunable phase transitions. Our results present a programmable physical route to material assembly, and offer a new paradigm for assembling genetic components, biological cargo, and minimal synthetic cells. [less ▲]

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See detailEU acts without binding legal force producing binding legal effects at the national level: Enforcement of ESA soft law in the Czech Republic
Hubkova, Pavlina UL

E-print/Working paper (2022)

The European Supervisory Authorities (ESAs) are empowered, by their founding regulations, to adopt guidelines and recommendations “with a view to establishing consistent, efficient and effective ... [more ▼]

The European Supervisory Authorities (ESAs) are empowered, by their founding regulations, to adopt guidelines and recommendations “with a view to establishing consistent, efficient and effective supervisory practices within the ESFS, and to ensuring the common, uniform and consistent application of Union law”. These acts can be considered genuine EU soft law since they lack the binding legal force. However, they remain perfectly non-binding only at the EU level and in the relation between the ESAs and the national competent authorities (NCAs). Although the NCAs have a duty “to make every effort to comply” with such soft law, they keep a certain leeway to decide whether they eventually comply or not. Nonetheless, the situation is different in case of financial institutions under their supervision. Formally, the EU regulations attribute to them also only a duty “to make every effort to comply”. However, once the NCA decides to comply and effectively enforces the compliance from financial institutions, the latter have a very limited, or even no leeway to decide about the compliance. Within the complex regulatory system, the NCA metamorphosis from a normtaker into an effective norm-enforcer who is capable to determine what effects the ESA soft law have at the national level. This paper focuses on the life of ESA soft law in the Czech Republic. It examines the role and power of the Czech NCA (the Czech National Bank, CNB) in the light of the legislative framework and other domestic binding legal rules. It takes into consideration the real enforcement strategy and practices of the CNB to show that, in the hands of the CNB, ESA guidelines and recommendations become acts, which produce binding legal effects upon financial institutions. Based on this observation, the paper raises questions about the proper control of ESA soft law and potential remedies. [less ▲]

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See detailValue-Added Scores Show Limited Stability over Time in Primary School
Emslander, Valentin UL; Levy, Jessica; Scherer, Ronny et al

E-print/Working paper (2022)

Value-added (VA) models are used for accountability purposes and quantify the value a teacher or a school adds to their students’ achievement. If VA scores lack stability over time and vary across outcome ... [more ▼]

Value-added (VA) models are used for accountability purposes and quantify the value a teacher or a school adds to their students’ achievement. If VA scores lack stability over time and vary across outcome domains (e.g., mathematics and language learning), their use for high-stakes decision making is in question and could have detrimental real-life implications: teachers could lose their jobs, or a school might receive less funding. However, school-level stability over time and variation across domains have rarely been studied together. In the present study, we examined the stability of VA scores over time for mathematics and language learning, drawing on representative, large-scale, and longitudinal data from two cohorts of standardized achievement tests in Luxembourg (N = 7,016 students in 151 schools). We found that only 34-38% of the schools showed stable VA scores over time with moderate rank correlations of VA scores from 2017 to 2019 of r = .34 for mathematics and r = .37 for language learning. Although they showed insufficient stability over time for high- stakes decision making, school VA scores could be employed to identify teaching or school practices that are genuinely effective—especially in heterogeneous student populations. [less ▲]

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See detailIntegration of external biomass reactions into existing metabolic models
Moscardo Garcia, Maria UL; Pires Pacheco, Maria Irene UL; Sauter, Thomas UL

E-print/Working paper (2022)

Currently, seven biomass objective functions have been defined in human metabolic reconstructions. The integration of published biomass reactions into alternative models can contribute to the prediction ... [more ▼]

Currently, seven biomass objective functions have been defined in human metabolic reconstructions. The integration of published biomass reactions into alternative models can contribute to the prediction power of the model. Thus, in this work, we present a workflow to integrate reactions and biomass functions originating from several genome-scale reconstructions into models other than their home models. Additionally, a benchmark to identify the biomass that confers the highest prediction accuracy in terms of gene essentiality and growth predictions is provided. [less ▲]

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See detailAgent-based Model of Initial Token Allocations: Evaluating Wealth Concentration in Fair Launches
Delgado Fernandez, Joaquin UL; Barbereau, Tom Josua UL; Papageorgiou, Orestis UL

E-print/Working paper (2022)

With advancements in distributed ledger technologies and smart contracts, tokenized voting rights gained prominence within Decentralized Finance (DeFi). Voting rights tokens (aka. governance tokens) are ... [more ▼]

With advancements in distributed ledger technologies and smart contracts, tokenized voting rights gained prominence within Decentralized Finance (DeFi). Voting rights tokens (aka. governance tokens) are fungible tokens that grant individual holders the right to vote upon the fate of a project. The motivation behind these tokens is to achieve decentral control. Because the initial allocations of these tokens is often un-democratic, the DeFi project Yearn Finance experimented with a fair launch allocation where no tokens are pre-mined and all participants have an equal opportunity to receive them. Regardless, research on voting rights tokens highlights the formation of oligarchies over time. The hypothesis is that the tokens' tradability is the cause of concentration. To examine this proposition, this paper uses an Agent-based Model to simulate and analyze the concentration of voting rights tokens post fair launch under different trading modalities. It serves to examine three distinct token allocation scenarios considered as fair. The results show that regardless of the allocation, concentration persistently occurs. It confirms the hypothesis that the disease is endogenous: the cause of concentration is the tokens tradablility. The findings inform theoretical understandings and practical implications for on-chain governance mediated by tokens. [less ▲]

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See detailLocal Verlet buffer approach for broad-phase interaction detection in Discrete Element Method
Mainassara Chekaraou, Abdoul Wahid UL; Besseron, Xavier UL; Rousset, Alban UL et al

E-print/Working paper (2022)

The Extended Discrete Element Method (XDEM) is an innovative numerical simulation technique that extends the dynamics of granular materials known as Discrete Element Method (DEM) by additional properties ... [more ▼]

The Extended Discrete Element Method (XDEM) is an innovative numerical simulation technique that extends the dynamics of granular materials known as Discrete Element Method (DEM) by additional properties such as the thermodynamic state, stress/strain for each particle. Such DEM simulations used by industries to set up their experimental processes are complexes and heavy in computation time. At each time step, those simulations generate a list of interacting particles and this phase is one of the most computationally expensive parts of a DEM simulation. The Verlet buffer method, initially introduced in Molecular Dynamic (MD) (and also used in DEM), allows keeping the interaction list for many time steps by extending each particle neighbourhood by a certain extension range, and thus broadening the interaction list. The method relies on the temporal coherency of DEM, which guarantees that no particles move erratically from one time step to the next. In the classical approach, all the particles have their neighbourhood extended by the same value which leads to suboptimal performances in simulations where different flow regimes coexist. Additionally, and unlike in MD, there is no comprehensive study analysing the different parameters that affect the performance of the Verlet buffer method in DEM. In this work, we propose a new method for the dynamic update of the neighbour list that depends on the particles individual displacement and define a particle-specific extension range based on the local flow regime. The interaction list is analysed throughout the simulation based on the particle's displacement allowing a flexible update according to the flow regime conditions. We evaluate the influence of the Verlet extension range on the execution time through different test cases and analyse empirically the extension range value giving the best performance. [less ▲]

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See detailA generalization of Bohr-Mollerup's theorem for higher order convex functions: A tutorial
Marichal, Jean-Luc UL; Zenaïdi, Naïm

E-print/Working paper (2022)

In its additive version, Bohr-Mollerup's remarkable theorem states that the unique (up to an additive constant) convex solution $f(x)$ to the equation $\Delta f(x)=\ln x$ on the open half-line $(0,\infty ... [more ▼]

In its additive version, Bohr-Mollerup's remarkable theorem states that the unique (up to an additive constant) convex solution $f(x)$ to the equation $\Delta f(x)=\ln x$ on the open half-line $(0,\infty)$ is the log-gamma function $f(x)=\ln\Gamma(x)$, where $\Delta$ denotes the classical difference operator and $\Gamma(x)$ denotes the Euler gamma function. In a recently published open access book, the authors provided and illustrated a far-reaching generalization of Bohr-Mollerup's theorem by considering the functional equation $\Delta f(x)=g(x)$, where $g$ can be chosen in a wide and rich class of functions that have convexity or concavity properties of any order. They also showed that the solutions $f(x)$ arising from this generalization satisfy counterparts of many properties of the log-gamma function (or equivalently, the gamma function), including analogues of Bohr-Mollerup's theorem itself, Burnside's formula, Euler's infinite product, Euler's reflection formula, Gauss' limit, Gauss' multiplication formula, Gautschi's inequality, Legendre's duplication formula, Raabe's formula, Stirling's formula, Wallis's product formula, Weierstrass' infinite product, and Wendel's inequality for the gamma function. In this paper, we review the main results of this new and intriguing theory and provide an illustrative application. [less ▲]

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See detailEarly-to-mid idiopathic Parkinson’s disease shows a more cytotoxic but declined CD8-regulatory peripheral immune profile
Capelle, Christophe; Cire, Séverine; Hansen, Maxime UL et al

E-print/Working paper (2022)

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Brain neuroinflammation plays a role in PD pathogenesis. However, the involvement of the peripheral immune system has not been ... [more ▼]

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Brain neuroinflammation plays a role in PD pathogenesis. However, the involvement of the peripheral immune system has not been systematically investigated. Here we analyzed >700 combinatorial immunological features in fresh blood of 28 early-to-mid-stage PD patients and 24 matched controls. We found an enhanced cytotoxic immune profile in idiopathic PD patients (iPD), with a higher frequency of terminally-differentiated effector CD8 T (TEMRA), late-differentiated CD8+ natural killer T cells and neutrophils. This immune profile was intensified by elevated serum granzyme A, reduced percentages of CD8+FOXP3+ regulatory T cells and group 2 innate lymphoid cells with immunosuppressive or tolerance-inducing functions. The frequency of CD8 TEMRA was negatively correlated with disease duration, suggesting a contribution to PD pathogenesis. Our work provides a comprehensive map on disturbed peripheral adaptive and innate immune cells in early-to-mid iPD, proposing easily-accessible candidates for early diagnosis and treatments. [less ▲]

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See detailArbeitnehmer in Luxemburg wünschen sich verstärkt eine Reduktion ihrer vertraglichen Arbeitszeit
Sischka, Philipp UL; Steffgen, Georges UL

E-print/Working paper (2022)

Im Rahmen dieser Newsletter wird aufgezeigt, wie sich die gewünschte Wochenarbeitszeit von Arbeitnehmern sowie die Differenz zwischen gewünschter Wochenarbeitszeit und vertraglicher Wochenarbeitszeit in ... [more ▼]

Im Rahmen dieser Newsletter wird aufgezeigt, wie sich die gewünschte Wochenarbeitszeit von Arbeitnehmern sowie die Differenz zwischen gewünschter Wochenarbeitszeit und vertraglicher Wochenarbeitszeit in den vergangenen Jahren in Luxemburg entwickelt haben. Dabei zeigt sich, dass der Anteil an Arbeitnehmern, die gerne weniger arbeiten würden, zwischen 2018 und 2021 deutlich gestiegen ist (von 32,8% auf 43,9%). Die Arbeitnehmer, die gerne weniger pro Woche arbeiten würden, möchten im Durchschnitt etwa 8 Stunden weniger arbeiten. Diese Entwicklungen fallen jedoch differenziert nach verschiedenen Arbeitnehmer-Gruppen unterschiedlich aus. So wünschen sich Arbeitnehmer im Vergleich zu Arbeitnehmerinnen konstant eine längere Arbeitszeit. Differenziert nach Alter, sind es vor allem die ältesten Arbeitnehmer, die sich im Durchschnitt die kürzeste Wochenarbeitszeit wünschen. Arbeitnehmer, die gerne weniger arbeiten würden, berichten tendenziell auch über schlechtere Arbeitsbedingungen im Vergleich zu Arbeitnehmern, deren gewünschte Arbeitszeit mit ihrer vertraglichen Arbeitszeit übereinstimmt. Auch berichten Arbeitnehmer, die gerne weniger pro Woche arbeiten würden, über ein geringeres Wohlbefinden. [less ▲]

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See detailGenome-wide meta-analysis of over 29,000 people with epilepsy reveals 26 loci and subtype-specific genetic architecture
International League Against Epilepsy Consortium on Complex Epilepsies Krause, Roland; Landoulsi, Zied UL; May, Patrick UL et al

E-print/Working paper (2022)

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here, we report a trans-ethnic GWAS including 29,944 cases ... [more ▼]

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here, we report a trans-ethnic GWAS including 29,944 cases, stratified into three broad- and seven sub-types of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants substantially close the missing heritability gap for GGE. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analysis of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current anti-seizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment. [less ▲]

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See detailMitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1- and PRKN-linked Parkinson's disease 2022.05.17.22275087
Trinh, Joanne; Hicks, Andrew A.; Koenig, Inke R. et al

E-print/Working paper (2022)

Biallelic mutations in PINK1 and PRKN cause recessively inherited Parkinson's disease (PD). Though some studies suggest that PINK1/PRKN monoallelic mutations may not contribute to risk, deep phenotyping ... [more ▼]

Biallelic mutations in PINK1 and PRKN cause recessively inherited Parkinson's disease (PD). Though some studies suggest that PINK1/PRKN monoallelic mutations may not contribute to risk, deep phenotyping assessment showed that PINK1 or PRKN monoallelic pathogenic variants were at a significantly higher rate in PD compared to controls. Given the established role of PINK1 and Parkin in regulating mitochondrial dynamics, we explored mitochondrial DNA (mtDNA) integrity and inflammation as potential disease modifiers in carriers of mutations in these genes. MtDNA integrity, global gene expression and serum cytokine levels were investigated in a large collection of biallelic (n=84) and monoallelic (n=170) carriers of PINK1/PRKN mutations, iPD patients (n=67) and controls (n=90). Affected and unaffected PINK1/PRKN monoallelic mutation carriers can be distinguished by heteroplasmic mtDNA variant load (AUC=0.83, CI:0.74-0.93). Biallelic PINK1/PRKN mutation carriers harbor more heteroplasmic mtDNA variants in blood (p=0.0006, Z=3.63) compared to monoallelic mutation carriers. This enrichment was confirmed in iPSC-derived and postmortem midbrain neurons from biallelic PRKN-PD patients. Lastly, the heteroplasmic mtDNA variant load was found to correlate with IL6 levels in PINK1/PRKN mutation carriers (r=0.57, p=0.0074). PINK1/PRKN mutations predispose individuals to mtDNA variant accumulation in a dose- and disease-dependent manner. MtDNA variant load over time is a potential marker of disease manifestation in PINK1/PRKN mutation carriers.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe authors wish to thank the many patients and their families who volunteered, and the efforts of the many clinical teams involved. Funding has been obtained from the German Research Foundation (ProtectMove; FOR 2488, GR 3731/5-1; SE 2608/2-1; KO 2250/7-1), the Luxembourg National Research Fund in the ATTRACT (Model-IPD, FNR9631103), NCER-PD (FNR11264123) and INTER programmes (ProtectMove, FNR11250962; MiRisk-PD, C17/BM/11676395, NB 4328/2-1), the BMBF (MitoPD), the Hermann and Lilly Schilling Foundation, the European Community (SysMedPD), the Canadian Institutes of Health Research (CIHR), Peter and Traudl Engelhorn Foundation. Initial studies in Tunisia on familial parkinsonism were in collaboration with Lefkos Middleton, Rachel Gibson, and the GlaxoSmithKline PD Programme Team (2002-2005). We would like to thank Dr Helen Tuppen from the Welcome Trust Centre for Mitochondrial Research, Newcastle University, UK for providing us with the plasmid p7D1. Moreover, this project was supported by the high throughput/high content screening platform and HPC facility at the Luxembourg Centre for Systems Biomedicine, and the University of Luxembourg.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:University of Lubeck Ethics CommitteeI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors [less ▲]

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See detailErinnerungspolitik und –praxis in Luxemburg am Beispiel einer gegenwärtigen Kontroverse
Kmec, Sonja UL

E-print/Working paper (2022)

In September 2021, so-called stumbling blocks were set by a Luxembourg school class: four for Jewish people who were murdered in concentration camps and eleven for young men who were forcibly drafted into ... [more ▼]

In September 2021, so-called stumbling blocks were set by a Luxembourg school class: four for Jewish people who were murdered in concentration camps and eleven for young men who were forcibly drafted into the Wehrmacht and died in the war. The commemoration triggered a broadly received controversy, which this article aims to explain and contextualize. [less ▲]

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See detailInternship and Public History Training
Cauvin, Thomas UL

E-print/Working paper (2022)

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See detailCreating Public History Master Programs: International Guidelines
Cauvin, Thomas UL; Montt, Maria; Will, Stoutamire et al

E-print/Working paper (2022)

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See detailDoes (Re-)Entering the Labor Market at Advanced Ages Protect Against Cognitive Decline? A Panel-Matching Difference-in-differences Approach
Kim, Jung Hyun UL; Muniz-Terrera, Graciela; Leist, Anja UL

E-print/Working paper (2022)

While prolonged labor market participation becomes increasingly important in ageing societies, evidence of the impacts of entering or exiting work beyond age 65 on cognitive functioning is scarce. We ... [more ▼]

While prolonged labor market participation becomes increasingly important in ageing societies, evidence of the impacts of entering or exiting work beyond age 65 on cognitive functioning is scarce. We estimate these effects using panel-matching difference-in-differences with populationrepresentative panel datasets from South Korea and the United States. We compare countries and across socioeconomic characteristics. We find general positive effects of entering the labor market in South Korea, while only individuals with high assets in the US benefit from entering the labor market. Exiting the labor market does not result in changes in cognitive functioning in Korea but is followed by a cognitive decline in individuals with low assets in the US. Findings suggest that the benefits and disincentives from late-life labor status transitions on cognitive functioning vary between South Korea and the US and across socioeconomic groups. [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 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 detailPOTENTIAL METHOD AND PROJECTION THEOREMS FOR MACROSCOPIC HAUSDORFF DIMENSION
Daw, Lara UL; Seuret, Stephane

E-print/Working paper (2022)

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See detailtrajeR, an R package for cluster analysis of time series
Noel, Cédric UL; Schiltz, Jang UL

E-print/Working paper (2022)

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See detailRetransmission of broadcast signals by cable in hotels - An analysis of the EU CabSat-Directive in light of a pending CJEU case
Cole, Mark David UL

E-print/Working paper (2022)

It is well-known that the Court of Justice of the European Union (CJEU) has played a key role in giving the EU acquis in the area of intellectual property law the relevance it has today. Especially the ... [more ▼]

It is well-known that the Court of Justice of the European Union (CJEU) has played a key role in giving the EU acquis in the area of intellectual property law the relevance it has today. Especially the series of judgments clarifying the broad notion of “communication to the public” as laid down in form of an exclusive right in the so-called InfoSoc Directive 2001/29/EC with which the position of authors was significantly reinforced is an extensively debated and commented outcome. Until the recent addition of the DSM Copyright-Directive (EU) 2019/790 to the EU acquis with its inclusion of a press publisher’s right and increased obligations of platforms when they allow users to upload potentially copyrighted material, the InfoSoc Directive of 2001 has always been in the centre of attention. In the shadow of that Directive stands the so-called CabSat Directive 93/83/EEC , originally created in 1993 as supplementary action in order to ensure the realization of an EU-wide single market for television broadcasting which was initiated by the Television without Frontiers-Directive (TwFD) 89/552/EEC . The aim of the CabSat Directive was and remains the goal of ensuring that in the use of satellite distribution of broadcast programmes as well as retransmission by cable, rightholders’ positions are safeguarded and procedures respected that allow for a smooth realization of such use of broadcast signals. This Directive has only rarely been subject of preliminary reference requests by national courts. This makes a currently pending case highly relevant and gives the Court a unique opportunity to complement its case law on communication to the public for the specific aspect of retransmission of broadcasting signals: It has already in the ground-breaking decision of SGAE in 2006 clarified very firmly that the forwarding of broadcast signals – television programmes, notabene – by hotel operators to the individual rooms of a hotel and thereby offering the guests the possibility of individual access to the broadcast programmes constitutes a communication to the public. For such communication an authorization by the author(s) is needed and without such authorization it violates the exclusive right as laid down in Art. 3(1) InfoSoc Directive. While this has been settled concerning authors, the pending case of C-716/20 concerns exactly the same setup – a hotel operator picking up a satellite signal and disseminating it via cable to the hotel rooms – except that this time the questions to the court are asked through the lens of the CabSat Directive and the legal position of broadcasters vis-à-vis the hotel operators as provided for by the specific national law which transposed EU law. This contribution will therefore first explain the notion of ‘cable retransmission’ and in which parts of EU law it is laid down or referred to (II.). It will then give a more detailed look at the relevant provisions of the CabSat Directive and other related secondary law which establishes the framework for questions of cable retransmission and communication to the public (III.). Further, the case law of the CJEU will be analysed in order to identify those judgments that contribute to the clarification of the open question whether a retransmission by cable of a broadcast programme by hotel operators falls under the notion of cable retransmission as presented (IV.). As the actual question has not been answered by the Court in its jurisprudence so far, the main aspects of the pending preliminary proceedings will be explained without going into the details of the national proceedings of the previous instances, before the Portuguese Supremo Tribunal de Justiça (Supreme Court) decided to stay the proceedings and request from the CJEU a clarification of the EU law-related aspects. The criteria as developed will show – when applied to the case at hand – that the hotel operator needs to be qualified as an operator of a cable network conducting a cable retransmission (V.). Finally, in a concluding section the relevance of the outcome of this case will be discussed (VI.). [less ▲]

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See detailThe European Guarantee Fund and COVID-19: Agile But in Need of Greater Accountability
Howarth, David UL; Hodson, Dermot

E-print/Working paper (2022)

The European Guarantee Fund formed an important part of the EU’s first response to the COVID-19 pandemic. Despite delays from some member states and the European Commission over the creation of this ... [more ▼]

The European Guarantee Fund formed an important part of the EU’s first response to the COVID-19 pandemic. Despite delays from some member states and the European Commission over the creation of this instrument, the European Investment Bank (EIB) moved at high speed to support SMEs and mid-caps. The European Guarantee Fund was vertically accountable to national governments, but it needed stronger horizontal accountability to the European Parliament and diagonal accountability to NGOs. The EIB should commit to an independent ex-post evaluation of the European Guarantee Fund’s design, operation and impact. [less ▲]

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See detailNimmt die Beschäftigungsqualität in Luxemburg ab?
Sischka, Philipp UL; Steffgen, Georges UL

E-print/Working paper (2022)

Im Rahmen dieser Newsletter wird aufgezeigt wie sich die verschiedenen Dimensionen der Beschäftigungsqualität in den vergangenen 6 Jahren in Luxemburg entwickelt haben. Dabei zeigt sich, dass die ... [more ▼]

Im Rahmen dieser Newsletter wird aufgezeigt wie sich die verschiedenen Dimensionen der Beschäftigungsqualität in den vergangenen 6 Jahren in Luxemburg entwickelt haben. Dabei zeigt sich, dass die Einkommenszufriedenheit und die wahrgenommenen Ausbildungsmöglichkeiten über die Zeit insgesamt eher abgenommen, und die Work-Life-Konflikte zugenommen haben. Diese Entwicklungen fallen differenziert nach verschiedenen Arbeitnehmer-Gruppen unterschiedlich aus. Beispielsweise haben Work-Life-Konflikte bei Arbeitnehmerinnen stärker zugenommen als bei Arbeitnehmern. Arbeitnehmer mit Kindern wiederum berichten im Vergleich zu Arbeitnehmer ohne Kinder über einen Rückgang der Beförderungsmöglichkeiten. Arbeitnehmer in staatlichen Organisationen weisen über die Zeit konstant höhere Werte bei Einkommenszufriedenheit, Ausbildungsmöglichkeiten und Arbeitsplatzsicherheit auf, im Vergleich zu Arbeitnehmern in privaten Unternehmen oder sonstigen Organisationen. Ergänzend zeigt sich, dass die Dimensionen der Beschäftigungsqualität mit verschiedenen Wohlbefindens-Dimensionen assoziiert sind. Insbesondere weisen höhere Work-Life-Konflikte Zusammenhänge mit geringerer Arbeitsmotivation, geringerer Arbeitszufriedenheit und geringerem generellem Well-Being, sowie erhöhtem Burnoutniveau und verstärkten Gesundheitsproblemen auf. [less ▲]

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See detailClinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence 2022.01.20.22269585
Hassanin, Emadeldin; Spier, Isabel; Bobbili, Dheeraj Reddy UL et al

E-print/Working paper (2022)

Background and aims: Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification.Methods To ... [more ▼]

Background and aims: Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification.Methods To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (<20%), intermediate (20-80%), or high PRS (>80\%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios (OR) and to compute the lifetime incidence, respectively. Results: Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22\%, compared to 40 and 74 for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26 for non-carriers and 98 for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve (AUC) in risk prediction (0.704). Conclusion: The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups. [less ▲]

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See detailAn a posteriori error estimator for the spectral fractional power of the Laplacian
Bulle, Raphaël UL; Barrera, Olga; Bordas, Stéphane UL et al

E-print/Working paper (2022)

We develop a novel a posteriori error estimator for the L2 error committed by the finite ele- ment discretization of the solution of the fractional Laplacian. Our a posteriori error estimator takes ... [more ▼]

We develop a novel a posteriori error estimator for the L2 error committed by the finite ele- ment discretization of the solution of the fractional Laplacian. Our a posteriori error estimator takes advantage of the semi–discretization scheme using a rational approximation which allows to reformulate the fractional problem into a family of non–fractional parametric problems. The estimator involves applying the implicit Bank–Weiser error estimation strategy to each parametric non–fractional problem and reconstructing the fractional error through the same rational approximation used to compute the solution to the original fractional problem. We provide several numerical examples in both two and three-dimensions demonstrating the effectivity of our estimator for varying fractional powers and its ability to drive an adaptive mesh refinement strategy. [less ▲]

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See detailFiefs des comtes de Luxembourg au 13e siècle (Grande Région SaarLorLux)
Moulin, Philippe; Helfer, Malte UL; Pauly, Michel UL et al

E-print/Working paper (2022)

This map is an attempt at a cartographic representation of the active fiefs of the Counts of Luxembourg between 1200 and 1310. The map is intended to visualise the presence, frequency and type of feudal ... [more ▼]

This map is an attempt at a cartographic representation of the active fiefs of the Counts of Luxembourg between 1200 and 1310. The map is intended to visualise the presence, frequency and type of feudal estates of the Counts of Luxembourg. [less ▲]

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See detailHomological projective duality for the Segre cubic
Beckmann, Thorsten; Belmans, Pieter UL

E-print/Working paper (2022)

The Segre cubic and Castelnuovo-Richmond quartic are two projectively dual hypersurfaces in P^4, with a long and rich history starting in the 19th century. We will explain how Kuznetsov's theory of ... [more ▼]

The Segre cubic and Castelnuovo-Richmond quartic are two projectively dual hypersurfaces in P^4, with a long and rich history starting in the 19th century. We will explain how Kuznetsov's theory of homological projective duality lifts this projective duality to a relationship between the derived category of a small resolution of the Segre cubic and a small resolution of the Coble fourfold, the double cover of P^4 ramified along the Castelnuovo-Richmond quartic. Homological projective duality then provides a description of the derived categories of linear sections, which we will describe to illustrate the theory. The case of the Segre cubic and Coble fourfold is non-trivial enough to exhibit interesting behavior, whilst being easy enough to explain the general machinery in this special and very classical case. [less ▲]

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See detailFrom gravity to string topology
Merkoulov (merkulov), Serguei UL

E-print/Working paper (2022)

The chain gravity properad introduced earlier by the author acts on the cyclic Hochschild of any cyclic A∞ algebra equipped with a scalar product of degree −d. In particular, it acts on the cyclic ... [more ▼]

The chain gravity properad introduced earlier by the author acts on the cyclic Hochschild of any cyclic A∞ algebra equipped with a scalar product of degree −d. In particular, it acts on the cyclic Hochschild complex of any Poincare duality algebra of degree d, and that action factors through a quotient dg properad ST3−d of ribbon graphs which is in focus of this paper. We show that its cohomology properad H∙(ST3−d) is highly non-trivial and that it acts canonically on the reduced equivariant homology H¯S1∙(LM) of the loop space LM of any simply connected d-dimensional closed manifold M. By its very construction, the string topology properad H∙(ST3−d) comes equipped with a morphism from the gravity properad which is fully determined by the compactly supported cohomology of the moduli spaces Mg,n of stable algebraic curves of genus g with marked points. This result gives rise to new universal operations in string topology as well as reproduces in a unified way several known constructions: we show that (i) H∙(ST3−d) is also a properad under the properad of involutive Lie bialgebras in degree 3−d whose induced action on H¯S1∙(LM) agrees precisely with the famous purely geometric construction of M. Chas and D. Sullivan, (ii) H∙(ST3−d) is a properad under the properad of homotopy involutive Lie bialgebras in degree 2−d; (iii) E. Getzler's gravity operad injects into H∙(ST3−d) implying a purely algebraic counterpart of the geometric construction of C. Westerland establishing an action of the gravity operad on H¯S1∙(LM). [less ▲]

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See detailRobust density estimation with the L1-loss. Applications to the estimation of a density on the line satisfying a shape constraint
Baraud, Yannick UL; Halconruy, Hélène UL; Maillard, Guillaume UL

E-print/Working paper (2022)

We solve the problem of estimating the distribution of presumed i.i.d.\ observations for the total variation loss. Our approach is based on density models and is versatile enough to cope with many ... [more ▼]

We solve the problem of estimating the distribution of presumed i.i.d.\ observations for the total variation loss. Our approach is based on density models and is versatile enough to cope with many different ones, including some density models for which the Maximum Likelihood Estimator (MLE for short) does not exist. We mainly illustrate the properties of our estimator on models of densities on the line that satisfy a shape constraint. We show that it possesses some similar optimality properties, with regard to some global rates of convergence, as the MLE does when it exists. It also enjoys some adaptation properties with respect to some specific target densities in the model for which our estimator is proven to converge at parametric rate. More important is the fact that our estimator is robust, not only with respect to model misspecification, but also to contamination, the presence of outliers among the dataset and the equidistribution assumption. This means that the estimator performs almost as well as if the data were i.i.d.\ with density $p$ in a situation where these data are only independent and most of their marginals are close enough in total variation to a distribution with density $p$. {We also show that our estimator converges to the average density of the data, when this density belongs to the model, even when none of the marginal densities belongs to it}. Our main result on the risk of the estimator takes the form of an exponential deviation inequality which is non-asymptotic and involves explicit numerical constants. We deduce from it several global rates of convergence, including some bounds for the minimax L1-risks over the sets of concave and log-concave densities. These bounds derive from some specific results on the approximation of densities which are monotone, convex, concave and log-concave. Such results may be of independent interest. [less ▲]

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See detailAn archaeal compound as a driver of Parkinson’s disease pathogenesis
Trezzi, Jean-Pierre; Aho, Velma UL; Jäger, Christian UL et al

E-print/Working paper (2022)

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial ... [more ▼]

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial taxa, changes to viral and archaeal populations have also been observed. Mechanistic links between gut microbes and PD pathogenesis remain elusive but could involve molecules that promote α-synuclein aggregation. Here, we show that 2-hydroxypyridine (2-HP) represents a key molecule for the pathogenesis of PD. We observe significantly elevated 2-HP levels in faecal samples from patients with PD or its prodrome, idiopathic REM sleep behaviour disorder (iRBD), compared to healthy controls. 2-HP is correlated with the archaeal species Methanobrevibacter smithii and with genes involved in methane metabolism, and it is detectable in isolate cultures of M. smithii. We demonstrate that 2-HP is selectively toxic to transgenic α-synuclein overexpressing yeast and increases α-synuclein aggregation in a yeast model as well as in human induced pluripotent stem cell derived enteric neurons. It also exacerbates PD-related motor symptoms, α-synuclein aggregation, and striatal degeneration when injected intrastriatally in transgenic mice overexpressing human α-synuclein. Our results highlight the effect of an archaeal molecule in relation to the gut-brain axis, which is critical for the diagnosis, prognosis, and treatment of PD. [less ▲]

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See detailSplitting fields of X^n-X-1 (particularly for n=5), prime decomposition and modular forms
Khare, Chandrashekhar; La Rosa, Alfio Fabio UL; Wiese, Gabor UL

E-print/Working paper (2022)

We study the splitting fields of the family of polynomials $f_n(X)= X^n-X-1$. This family of polynomials has been much studied in the literature and has some remarkable properties. Serre related the ... [more ▼]

We study the splitting fields of the family of polynomials $f_n(X)= X^n-X-1$. This family of polynomials has been much studied in the literature and has some remarkable properties. Serre related the function on primes $N_p(f_n)$, for a fixed $n \leq 4$ and $p$ a varying prime, which counts the number of roots of $f_n(X)$ in $\mathbb F_p$ to coefficients of modular forms. We study the case $n=5$, and relate $N_p(f_5)$ to mod $5$ modular forms over $\mathbb Q$, and to characteristic 0, parallel weight 1 Hilbert modular forms over $\mathbb Q(\sqrt{19 \cdot 151})$. [less ▲]

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See detailOn Leopoldt's and Gross's defects for Artin representations
Maksoud, Alexandre UL

E-print/Working paper (2022)

We generalize Waldschmidt's bound for Leopoldt's defect and prove a similar bound for Gross's defect for an arbitrary extension of number fields. As an application, we prove new cases of the generalized ... [more ▼]

We generalize Waldschmidt's bound for Leopoldt's defect and prove a similar bound for Gross's defect for an arbitrary extension of number fields. As an application, we prove new cases of the generalized Gross conjecture (also known as the Gross-Kuz'min conjecture) beyond the classical abelian case, and we show that Gross's p-adic regulator has at least half of the conjectured rank. We also describe and compute non-cyclotomic analogues of Gross's defect. [less ▲]

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See detailA Conjecture of Coleman on the Eisenstein Family
Advocaat, Bryan UL; Kiming, Ian; Wiese, Gabor UL

E-print/Working paper (2022)

We prove for primes $p\ge 5$ a conjecture of Coleman on the analytic continuation of the family of modular functions $\frac{\Es_\k}{V(\Es_\k)}$ derived from the family of Eisenstein series $\Es_\k$. The ... [more ▼]

We prove for primes $p\ge 5$ a conjecture of Coleman on the analytic continuation of the family of modular functions $\frac{\Es_\k}{V(\Es_\k)}$ derived from the family of Eisenstein series $\Es_\k$. The precise, quantitative formulation of the conjecture involved a certain on $p$ depending constant. We show by an example that the conjecture with the constant that Coleman conjectured cannot hold in general for all primes. On the other hand, the constant that we give is also shown not to be optimal in all cases. The conjecture is motivated by its connection to certain central statements in works by Buzzard and Kilford, and by Roe, concerning the ``halo'' conjecture for the primes $2$ and $3$, respectively. We show how our results generalize those statements and comment on possible future developments. [less ▲]

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See detailbinny: an automated binning algorithm to recover high-quality genomes from complex metagenomic datasets 2021.12.22.473795
Hickl, Oskar UL; Teixeira Queiros, Pedro UL; Wilmes, Paul UL et al

E-print/Working paper (2021)

The reconstruction of genomes is a critical step in genome-resolved metagenomics as well as for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces ... [more ▼]

The reconstruction of genomes is a critical step in genome-resolved metagenomics as well as for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces high-quality metagenome-assembled genomes from both contiguous and highly fragmented genomes. Based on established metrics, binny outperforms existing state-of-the-art binning methods and finds unique genomes that could not be detected by other methods.binny uses k-mer-composition and coverage by metagenomic reads for iterative, non-linear dimension reduction of genomic signatures as well as subsequent automated contig clustering with cluster assessment using lineage-specific marker gene sets.When compared to five widely used binning algorithms, binny recovers the most near-complete (\>95 pure, \>90 complete) and high-quality (\>90 pure, \>70 complete) genomes from simulated data sets from the Critical Assessment of Metagenome Interpretation (CAMI) initiative, as well as from a real-world benchmark comprised of metagenomes from various environments. binny is implemented as Snakemake workflow and available from https://github.com/a-h-b/binny.Competing Interest StatementThe authors have declared no competing interest. [less ▲]

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See detailZwischen Denkmalschutz und kanonischem Recht. Die Debatte über die Umnutzung entweihter Kirchen
Pauly, Michel UL

E-print/Working paper (2021)

Beim Denkmalschutz von Kirchen wird das Mobiliar in den Kirchen, vom Gestühl bis zum liturgischen Gerät, leider nicht mitgeschützt. Ein ausführlichres Inventar und eine Vereinfachung der Rechtspraxis ... [more ▼]

Beim Denkmalschutz von Kirchen wird das Mobiliar in den Kirchen, vom Gestühl bis zum liturgischen Gerät, leider nicht mitgeschützt. Ein ausführlichres Inventar und eine Vereinfachung der Rechtspraxis drängen sich auf. [less ▲]

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See detailThe precautionary principle and the authorisation of Covid-19 vaccines under EU
Donati, Alessandra UL

E-print/Working paper (2021)

The decision of the EU Commission, based on positive advice from the European Medicines Agency, to grant conditional marketing authorisation to Covid-19 vaccines should be qualified as a precautionary ... [more ▼]

The decision of the EU Commission, based on positive advice from the European Medicines Agency, to grant conditional marketing authorisation to Covid-19 vaccines should be qualified as a precautionary measure. Under the established case law of the CJEU, the conditions for the application of this principle are met. Such conditions are the existence of a risk to the environment and public health and uncertainty. Given this qualification as a precautionary measure, whether the Commission had complied with the procedural obligations that surround the implementation of this principle under EU law was assessed. Some shortcomings are identified concerning the risk assessment conducted by the European Medicines Agency and the risk management carried out by the Commission. [less ▲]

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See detailEntre force et diplomatie spatiale : le missile russe Nudol s'invite à la table des négociations
Zarkan, Laetitia UL; Degrange, Valentin; Peter, Hugo

E-print/Working paper (2021)

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See detailRevisiting conceptual tools at the crossroad of postcolonial and sociolinguistic studies
Tavares, Bernardino UL; Tavares Vieira, Aleida Evandra UL

E-print/Working paper (2021)

This is the first research brief in the DisPOSEG Project. DisPOSEG stands for “Disentangling postcolonial encounters in globalisation: a sociolinguistic-ethnographic study of Lusophone migrant workers’ ... [more ▼]

This is the first research brief in the DisPOSEG Project. DisPOSEG stands for “Disentangling postcolonial encounters in globalisation: a sociolinguistic-ethnographic study of Lusophone migrant workers’ positioning in third space,” a three-year CORE project funded by the FNR, Luxembourg. This multi-sited project contributes to the fields of postcolonialism, migration studies, sociolinguistics and workplace studies by investigating language, history and migration from Portuguese-speaking countries (Portugal and its former colonies) into Luxembourg, with a focus on migrants’ work, social and linguistic interactions. It problematises interactions of/between concomitant populations of those countries that form this dichotomic colonial matrix of former coloniser and former colonised, and their descendants in Luxembourg, a geographical spaces traditionally perceived as non-colonial. In this first research brief we outline and revisit four interlinked key concepts guiding the project. [less ▲]

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See detailHow relaxing develops and affects well-being throughout childhood
Cunsolo, Sabbiana; Cebotari, Victor UL; Richardson, Dominic et al

E-print/Working paper (2021)

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See detailHow inquiring develops and affects well-being throughout childhood
Vrolijk, Marloes; Cebotari, Victor UL; Richardson, Dominic et al

E-print/Working paper (2021)

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See detailHow enriching sensory awareness develops and affects well-being throughout childhood
Linzarini, Adriano; Cebotari, Victor UL; Richardson, Dominic et al

E-print/Working paper (2021)

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See detailQuantum Skyrmion Lattices in Heisenberg Ferromagnets
Haller, Andreas UL; Groenendijk, Solofo; Habibi, Alireza et al

E-print/Working paper (2021)

Skyrmions are topological magnetic textures which can arise in non-centrosymmetric ferromagnetic materials. In most systems experimentally investigated to date, skyrmions emerge as classical objects ... [more ▼]

Skyrmions are topological magnetic textures which can arise in non-centrosymmetric ferromagnetic materials. In most systems experimentally investigated to date, skyrmions emerge as classical objects. However, the discovery of skyrmions with nanometer length scales has sparked interest in their quantum properties. Quantum corrections to the classical magnetic textures have already been considered in the semiclassical regime. Here, we go beyond this limit by investigating quantum skyrmions in the deep quantum regime. We use density matrix renormalization group techniques to study two-dimensional spin-1/2 Heisenberg ferromagnets with Dzyaloshinskii-Moriya interactions and discover a broad region in the zero temperature phase diagram which hosts quantum skyrmion lattice ground states. We argue that this novel quantum skyrmion phase can be detected experimentally in the magnetization profile via local magnetic polarization measurements as well as in the spin structure factor measurable via neutron scattering experiments. Finally, we explore the resulting quantum skyrmion state, analyze its real space polarization profile and show that it is a non-classical state featuring entanglement between quasiparticle and environment mainly localized near the boundary spins of the skyrmion. [less ▲]

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See detailNeurotoxic Amyloidogenic Peptides Identified in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19
Islam, Saba; Charnley, Mirren; Bindra, Guneet et al

E-print/Working paper (2021)

COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe ... [more ▼]

COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe headaches, and even stroke are reported in as many as 30% of cases and can persist even after the infection is over (so-called ‘long COVID’). These neurological symptoms are thought to be caused by brain inflammation, triggered by the virus infecting the central nervous system of COVID-19 patients, however we still don’t fully understand the mechanisms for these symptoms. The neurological effects of COVID-19 share many similarities to neurodegenerative diseases such as Alzheimer’s and Parkinson’s in which the presence of cytotoxic protein-based amyloid aggregates is a common etiological feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we performed a bioinformatic scan of the SARS-CoV-2 proteome, detecting peptide fragments that were predicted to be highly amyloidogenic. We selected two of these peptides and discovered that they do rapidly self-assemble into amyloid. Furthermore, these amyloid assemblies were shown to be highly toxic to a neuronal cell line. We introduce and support the idea that cytotoxic amyloid aggregates of SARS-CoV-2 proteins are causing some of the neurological symptoms commonly found in COVID-19 and contributing to long COVID, especially those symptoms which are novel to long COVID in contrast to other post-viral syndromes. [less ▲]

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See detailNon-Standard Errors
Wolff, Christian UL; Zhang, Lu UL; Holzmeister, Felix

E-print/Working paper (2021)

Detailed reference viewed: 49 (13 UL)
See detailPublic support for tax policies in COVID-19 times: Evidence from Luxembourg
Olivera, Javier; van Kerm, Philippe UL

E-print/Working paper (2021)

We study attitudes towards the introduction of hypothetical new taxes to finance the cost of the COVID-19 pandemic. We rely on survey data collected in Luxembourg in 2020. The survey asks for the ... [more ▼]

We study attitudes towards the introduction of hypothetical new taxes to finance the cost of the COVID-19 pandemic. We rely on survey data collected in Luxembourg in 2020. The survey asks for the agreement of respondents over: a one-time net wealth tax, an inheritance tax, a temporary solidarity income tax, and a temporary increase in VAT. All questions include different and randomly assigned tax attributes (tax rates and exemption amounts). We find a clear divide with relativelyhigh support for new wealth and inheritance taxes on the one hand and a low support for increases in VAT and income taxes on the other hand. While 58% of respondents agree or strongly agree with a one-time tax levied on net worth, only24% are in favor of a small increase in VAT. Support for any tax is however negatively associated with the size of the tax as measured by the predicted revenues. Our results indicate that a one-time wealth tax could raise substantial revenues andstill garner public support. [less ▲]

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See detailZur Entwicklung des TSG unter Berücksichtigung der aktuellen politischen Debatte
de Silva, Adrian UL

E-print/Working paper (2021)

The article deals with developments regarding the Transsexual Act and the current political debate on trans law in the Federal Republic of Germany.

Detailed reference viewed: 78 (5 UL)
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See detailAt the Edge of a Seamless Cloud Experience
Rac, Samuel UL; Brorsson, Mats Hakan UL

E-print/Working paper (2021)

There is a growing need for low latency for many devices and users. The traditional cloud computing paradigm can not meet this requirement, legitimizing the need for a new paradigm. Edge computing ... [more ▼]

There is a growing need for low latency for many devices and users. The traditional cloud computing paradigm can not meet this requirement, legitimizing the need for a new paradigm. Edge computing proposes to move computing capacities to the edge of the network, closer to where data is produced and consumed. However, edge computing raises new challenges. At the edge, devices are more heterogeneous than in the data centre, where everything is optimized to achieve economies of scale. Edge devices can be mobile, like a car, which complicates architecture with dynamic topologies. IoT devices produce a considerable amount of data that can be processed at the Edge. In this paper, we discuss the main challenges to be met in edge computing and solutions to achieve a seamless cloud experience. We propose to use technologies like containers and WebAssembly to manage applications' execution on heterogeneous devices. [less ▲]

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See detailJudicial Education and Judicial Independence: Paper given at the 2021 Commonwealth Law Conference
Happold, Matthew UL

E-print/Working paper (2021)

The link between judicial education and an efficient judiciary is, one hopes, obvious. But in order to ensure judicial independence, contemporary wisdom has it, judicial education should also be in the ... [more ▼]

The link between judicial education and an efficient judiciary is, one hopes, obvious. But in order to ensure judicial independence, contemporary wisdom has it, judicial education should also be in the hands of the judiciary. Absent such control, there is a risk that judges may be indoctrinated by interested actors and their independence compromised. Some critics, however, have been sceptical about judicial control of judicial education. Judicial control of education often justified on basis of expertise as well as need to protect independence. But judges are not pedagogues (and their view of what judging does, or should, entail are often untheorized). Nor are they particularly representative of society. In addition, a danger unmitigated by judicial control of judicial education is regulatory capture, defined as ‘the result or process by which regulation, in law or application, is consistently or repeatedly directed away from the public interest and toward the interests of the regulated industry, by the intent and action of the industry itself'. Even if other voices are integrated into discussions, the danger exists that they might seek to subvert the process to privilege their interests over the general interest. Such concerns have recently been raised in England and Wales with regard to the Equal Treatment Bench Book. The paper examines the relationship between judicial education and judicial independence through the lens of this controversy. It concludes that when judicial education trespass on the independence of the individual judge is not an easy question to answer (not least because education is always about socialization) but, crucially, it is not one answered by putting judicial education in the hands of the judiciary. [less ▲]

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See detailParental migration and psychological well-being of children. Longitudinal evidence from Ghana
Raturi, Radhika; Cebotari, Victor UL

E-print/Working paper (2021)

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See detailFrom SLAM to Situational Awareness: Challenges and Survey
Bavle, Hriday UL; Sanchez Lopez, Jose Luis UL; Schmidt F, Eduardo et al

E-print/Working paper (2021)

Detailed reference viewed: 56 (1 UL)
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See detailA Formalisation of Abstract Argumentation in Higher-Order Logic
Steen, Alexander UL; Fuenmayor Pelaez, David UL

E-print/Working paper (2021)

We present an approach for representing abstract argumentation frameworks based on an encoding into classical higher-order logic. This provides a uniform framework for computer-assisted assessment of ... [more ▼]

We present an approach for representing abstract argumentation frameworks based on an encoding into classical higher-order logic. This provides a uniform framework for computer-assisted assessment of abstract argumentation frameworks using interactive and automated reasoning tools. This enables the formal analysis and verification of meta-theoretical properties as well as the flexible generation of extensions and labellings with respect to well-known argumentation semantics. [less ▲]

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See detailActive reconfiguration of cytoplasmic lipid droplets governs migration of nutrient-limited phytoplankton
Sengupta, Anupam UL; Dhar, Jayabrata UL; Danza, Francesco et al

E-print/Working paper (2021)

As open oceans continue to warm, modified currents and enhanced stratification exacerbate nitrogen and phosphorus limitation, constraining primary production. The ability to migrate vertically bestows ... [more ▼]

As open oceans continue to warm, modified currents and enhanced stratification exacerbate nitrogen and phosphorus limitation, constraining primary production. The ability to migrate vertically bestows motile phytoplankton a crucial–albeit energetically expensive–advantage toward vertically redistributing for optimal growth, uptake and resource storage in nutrient-limited water columns. However, this traditional view discounts the possibility that the phytoplankton migration strategy may be actively selected by the storage dynamics when nutrients turn limiting. Here we report that storage and migration in phytoplankton are coupled traits, whereby motile species harness energy storing lipid droplets (LDs) to biomechanically regulate migration in nutrient limited settings. LDs grow and translocate–directionally–within the cytoplasm to accumulate below the cell nucleus, tuning the speed, trajectory and stability of swimming cells. Nutrient reincorporation reverses the LD translocation, restoring the homeostatic migratory traits measured in population-scale millifluidic experiments. Combining intracellular LD tracking and quantitative morphological analysis of red-tide forming alga, Heterosigma akashiwo, along with a model of cell mechanics, we discover that the size and spatial localization of growing LDs govern the ballisticity and orientational stability of migration. The strain-specific shifts in migration which we identify here are amenable to a selective emergence of mixotrophy in nutrient-limited phytoplankton. We rationalize these distinct behavioral acclimatization in an ecological context, relying on concomitant tracking of the photophysiology and reactive oxygen species (ROS) levels, and propose a dissipative energy budget for motile phytoplankton alleviating nutrient limitation. The emergent resource acquisition strategies, enabled by distinct strain-specific migratory acclimatizing mechanisms, highlight the active role of the reconfigurable cytoplasmic LDs in guiding vertical movement. By uncovering the mechanistic coupling between dynamics of intracellular changes to physiologically-governed migration strategies, this work offers a tractable framework to delineate diverse strategies which phytoplankton may harness to maximize fitness and resource pool in nutrient-limited open oceans of the future. [less ▲]

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See detailAnalysis and Probing of Parallel Channels in the Lightning Network
Biryukov, Alexei UL; Naumenko, Gleb; Tikhomirov, Sergei UL

E-print/Working paper (2021)

Bitcoin can process only a few transactions per second, which is insufficient for a global payment network. The Lightning Network (LN) aims to address this challenge. The LN allows for low-latency bitcoin ... [more ▼]

Bitcoin can process only a few transactions per second, which is insufficient for a global payment network. The Lightning Network (LN) aims to address this challenge. The LN allows for low-latency bitcoin transfers through a network of payment channels. In contrast to regular Bitcoin transactions, payments in the LN are not globally broadcast. Thus it may improve not only Bitcoin's scalability but also privacy. However, the probing attack allows an adversary to discover channel balances, threatening users' privacy. Prior work on probing did not account for the possibility of multiple (parallel) channels between two nodes. Naive probing algorithms yield false results for parallel channels. In this work, we develop a new probing model that accurately accounts for parallel channels. We describe jamming-enhanced probing that allows for full balance information extraction in multi-channel hops, which was impossible with earlier probing methods. We quantify the attacker's information gain and propose an optimized algorithm for choosing probe amounts for N-channel hops. We demonstrate its efficiency based on real-world data using our own probing-focused LN simulator. Finally, we discuss countermeasures such as new forwarding strategies, intra-hop payment split, rebalancing, and unannounced channels. [less ▲]

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See detailEconomic development, weather shocks and child marriage in South Asia: A machine learning approach
Dietrich, Stephan; Meysonnat, Aline; Rosales, Francisco et al

E-print/Working paper (2021)

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See detailInwieweit weisen organisationale Schutzmaßnahmen gegen COVID-19 einen Zusammenhang mit dem Wohlbefinden von Arbeitnehmerinnen und Arbeitnehmer auf?
Sischka, Philipp UL; Steffgen, Georges UL

E-print/Working paper (2021)

m Rahmen dieser Newsletter werden ArbeitnehmerInnen in Luxemburg in fünf Gruppen aufgeteilt, die auf ihrer Arbeit in unterschiedlichem Umfang Corona-Schutzmaßnahmen ausgesetzt sind. Neben ... [more ▼]

m Rahmen dieser Newsletter werden ArbeitnehmerInnen in Luxemburg in fünf Gruppen aufgeteilt, die auf ihrer Arbeit in unterschiedlichem Umfang Corona-Schutzmaßnahmen ausgesetzt sind. Neben ArbeitnehmerInnen mit 1) „einem geringen Umfang an Schutzmaßnahmen“, 2) „einem mittleren Umfang an Schutzmaßnahmen“, sowie 3) „einem hohen Umfang an Schutzmaßnahmen“, lassen sich auch noch Personen 4) „mit einem hohen Umfang an Schutzmaßnahmen, bei jedoch geringer körperlicher Distanz“, sowie Personen 5) „mit permanentem Homeoffice“ unterscheiden. Die Analysen zeigen, dass Frauen, jüngere ArbeitnehmerInnen und ArbeitnehmerInnen in Teilzeit häufiger in der Gruppe „Hohes Maß an Schutzmaßnahmen, geringe Distanz“ zu finden sind. Darüber hinaus sind Männer, ArbeitnehmerInnen mit Wohnsitz in Luxemburg und ArbeitnehmerInnen in einer Vorgesetztenposition häufiger in der Gruppe derjenigen zu finden, die permanent im Homeoffice arbeiten. ArbeitnehmerInnen der Gruppe „Geringes Maß an Schutzmaßnahmen“ oder „Hohes Maß an Schutzmaßnahmen, geringe Distanz“ weisen insgesamt schlechtere Arbeitsbedingungen auf und haben die höchste Angst vor einer Ansteckung durch COVID-19. Im Gegensatz dazu weisen ArbeitnehmerInnen der Gruppe „Hohes Maß an Schutzmaßnahmen“ und der Gruppe „permanentes Homeoffice“, bessere Arbeitsbedingungen auf. Es zeigt sich, dass Arbeitnehmer, die in einem Umfeld mit einem geringen Maß an Schutzmaßnahmen arbeiten müssen, ein deutlich geringeres Wohlbefinden haben. [less ▲]

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See detailHessian heat kernel estimates and Calderón-Zygmund inequalities on complete Riemannian manifolds
Cao, Jun; Cheng, Li-Juan; Thalmaier, Anton UL

E-print/Working paper (2021)

We address some fundamental questions about geometric analysis on Riemannian manifolds. The L^p-Calderón-Zygmund inequality is one of the cornerstones in the regularity theory of elliptic equations, and ... [more ▼]

We address some fundamental questions about geometric analysis on Riemannian manifolds. The L^p-Calderón-Zygmund inequality is one of the cornerstones in the regularity theory of elliptic equations, and it has been asked under which geometric conditions it holds for a reasonable class of non-compact Riemannian manifolds, and to what extent assumptions on the derivative of curvature and on the injectivity radius of the manifold are necessary. In the present paper, for 1<p<2, we give a positive answer for the validity of the L^p-Calderón-Zygmund inequality on a Riemannian manifold assuming only a lower bound on the Ricci curvature. It is well known that this alone is not sufficient for p>2. In this case we complement the study of Güneysu-Pigola (2015) and derive sufficient geometric criteria for the validity of the Calderón-Zygmund inequality under additional Kato class bounds on the Riemann curvature tensor and the covariant derivative of Ricci curvature. Bounds in the Kato class are integral conditions and much weaker than pointwise bounds. Throughout the proofs, probabilistic tools, like Hessian formulas and Bismut type representations for heat semigroups, play a significant role. [less ▲]

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See detailSome inequalities on Riemannian manifolds linking Entropy, Fisher information, Stein discrepancy and Wasserstein distance
Cheng, Li-Juan; Thalmaier, Anton UL; Wang, Feng-Yu

E-print/Working paper (2021)

For a complete connected Riemannian manifold M let V∊ C^2(M) be such that µ(dx)=exp(-V(x))vol(dx) is a probability measure on M. Taking µ as reference measure, we derive inequalities for probability ... [more ▼]

For a complete connected Riemannian manifold M let V∊ C^2(M) be such that µ(dx)=exp(-V(x))vol(dx) is a probability measure on M. Taking µ as reference measure, we derive inequalities for probability measures on M linking relative entropy, Fisher information, Stein discrepancy and Wasserstein distance. These inequalities strengthen in particular the famous log-Sobolev and transportation-cost inequality and extend the so-called Entropy/Stein-discrepancy/Information (HSI) inequality established by Ledoux, Nourdin and Peccati (2015) for the standard Gaussian measure on Euclidean space to the setting of Riemannian manifolds. [less ▲]

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See detailGravity prop and moduli spaces Mg,n
Merkoulov (merkulov), Serguei UL

E-print/Working paper (2021)

Let Mg,n be the moduli space of algebraic curves of genus g with m+n marked points decomposed into the disjoint union of two sets of cardinalities m and n, and H∙c(Mm+n) its compactly supported cohomology ... [more ▼]

Let Mg,n be the moduli space of algebraic curves of genus g with m+n marked points decomposed into the disjoint union of two sets of cardinalities m and n, and H∙c(Mm+n) its compactly supported cohomology group. We prove that the collection of S-bimodules {H∙−mc(Mg,m+n)} has the structure of a properad (called the gravity properad) such that it contains the (degree shifted) E. Getzler's gravity operad as the sub-collection {H∙−1c(M0,1+n)}n≥2. Moreover, we prove that the generators of the 1-dimensional cohomology groups H∙−1c(M0,1+2), H∙−2c(M0,2+1) and H∙−3c(M0,3+0) satisfy with respect to this properadic structure the relations of the (degree shifted) quasi-Lie bialgebra, a fact making the totality of cohomology groups ∏g,m,nH∙c(Mg,m+n)⊗Sopm×Sn(sgnm⊗Idn) into a complex with the differential fully determined by the just mentioned three cohomology classes . It is proven that this complex contains infinitely many cohomology classes, all coming from M. Kontsevich's odd graph complex. The gravity prop structure is established with the help of T. Willwacher's twisting endofunctor (in the category of properads under the operad of Lie algebras) and K. Costello's theory of moduli spaces of nodal disks with marked boundaries and internal marked points (such that each disk contains at most one internal marked point). [less ▲]

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See detailFrom robust tests to Bayes-like posterior distributions
Baraud, Yannick UL

E-print/Working paper (2021)

In the Bayes paradigm and for a given loss function, we propose the construction of a new type of posterior distributions, that extends the classical Bayes one, for estimating the law of an $n$-sample ... [more ▼]

In the Bayes paradigm and for a given loss function, we propose the construction of a new type of posterior distributions, that extends the classical Bayes one, for estimating the law of an $n$-sample. The loss functions we have in mind are based on the total variation and Hellinger distances as well as some L_j-ones. We prove that, with a probability close to one, this new posterior distribution concentrates its mass in a neighbourhood of the law of the data, for the chosen loss function, provided that this law belongs to the support of the prior or, at least, lies close enough to it. We therefore establish that the new posterior distribution enjoys some robustness properties with respect to a possible misspecification of the prior, or more precisely, its support. For the total variation and squared Hellinger losses, we also show that the posterior distribution keeps its concentration properties when the data are only independent, hence not necessarily i.i.d., provided that most of their marginals or the average of these are close enough to some probability distribution around which the prior puts enough mass. The posterior distribution is therefore also stable with respect to the equidistribution assumption. We illustrate these results by several applications. We consider the problems of estimating a location parameter or both the location and the scale of a density in a nonparametric framework. Finally, we also tackle the problem of estimating a density, with the squared Hellinger loss, in a high-dimensional parametric model under some sparsity conditions. The results established in this paper are non-asymptotic and provide, as much as possible, explicit constants. [less ▲]

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See detailNo more Piecemeal Tactics
Kafteranis, Dimitrios UL; Robert, Brochhaus

E-print/Working paper (2021)

Detailed reference viewed: 39 (0 UL)
See detailHolonomic approximation through convex integration
Massot, Patrick; Theilliere, Mélanie UL

E-print/Working paper (2021)

Convex integration and the holonomic approximation theorem are two well-known pillars of flexibility in differential topology and geometry. They may each seem to have their own flavor and scope. The goal ... [more ▼]

Convex integration and the holonomic approximation theorem are two well-known pillars of flexibility in differential topology and geometry. They may each seem to have their own flavor and scope. The goal of this paper is to bring some new perspective on this topic. We explain how to prove the holonomic approximation theorem for first order jets using convex integration. More precisely we first prove that this theorem can easily be reduced to proving flexibility of some specific relation. Then we prove this relation is open and ample, hence its flexibility follows from off-the-shelf convex integration. [less ▲]

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See detailAssessing the role of polygenic background on the penetrance of monogenic forms in Parkinson\textquoterights disease. 2021.06.06.21253270
Hassanin, Emadeldin; May, Patrick UL; Aldisi, Rana et al

E-print/Working paper (2021)

Background: Several rare and common variants are associated with Parkinson's disease. However, there is still an incomplete penetrance in the carriers of rare variants associated with Parkinson's disease ... [more ▼]

Background: Several rare and common variants are associated with Parkinson's disease. However, there is still an incomplete penetrance in the carriers of rare variants associated with Parkinson's disease. To address this issue, we investigated whether a PRS calculated from significant GWAS SNPs affects the penetrance of Parkinson's disease among carriers of rare monogenic variants in known Parkinson's disease genes and those with a family history. Methods: We calculated the PRS based on common variants and selected the carriers of rare monogenic variants by using the exome data from UK Biobank. Individuals were divided into three risk categories based on PRS: low (<10%), intermediate (10%-90%), and high (>90%) risk groups. We then compared how PRS affects Parkinson\textquoterights disease risk among carriers of rare monogenic variants and those with family-history. Results: We observed a two-fold higher odds ratio for a carrier of a monogenic variant that had a high PRS (OR 4.07,95\% CI, 1.72-8.08) compared to carriers with a low PRS (OR 1.91, 95\% CI, 0.31-6.05). In the same line, carriers with a first-degree family history and with \>90\% PRS have even a higher risk of developing PD (OR 23.53, 95\%CI 5.39-71.54) compared to those with \<90\% PRS (OR 9.54, 95\% CI 3.32-21.65). Conclusions: Our results show that PRS, carrier status, and family history contribute independently and additively to the Parkinson's disease risk. [less ▲]

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See detailBreast and prostate cancer risk: the interplay of polygenic risk, high-impact monogenic variants, and family history 2021.06.04.21258277
Hassanin, Emadeldin; May, Patrick UL; Aldisi, Rana et al

E-print/Working paper (2021)

Purpose: Investigate to which extent polygenic risk scores (PRS), high-impact monogenic variants, and family history affect breast and prostate cancer risk by assessing cancer prevalence and cancer ... [more ▼]

Purpose: Investigate to which extent polygenic risk scores (PRS), high-impact monogenic variants, and family history affect breast and prostate cancer risk by assessing cancer prevalence and cancer cumulative lifetime incidence. Methods 200,643 individuals from the UK Biobank were stratified as follows: 1. carriers or non-carriers of high impact constitutive, monogenic variants in cancer susceptibility genes, 2. high or non-high PRS (90th percentile threshold), 3. with or without a family history of cancer. Multivariable logistic regression was used to compare the odds ratio (OR) across the different groups while Cox proportional hazards models were used to compute the cumulative incidence through life. Results Breast and prostate cancer cumulative incidence by age 70 is 7 and 5 for non-carriers with non-high PRS and reaches 37 and 32 among carriers of high-impact variants in cancer susceptibility genes with high PRS. The additional presence of family history is associated with a further increase of the risk of developing cancer reaching an OR of 14 and 21 for breast and prostate cancer, respectively. Conclusion: High PRS confers a cancer risk comparable to high-impact monogenic variants. Family history, monogenic variants, and PRS contribute additively to breast and prostate cancer risk. [less ▲]

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See detailThe formal moment map geometry of the space of symplectic connections
La Fuente-Gravy, Laurent UL

E-print/Working paper (2021)

We deform the moment map picture on the space of symplectic connections on a symplectic manifold. To do that, we study a vector bundle of Fedosov star product algebras on the space of symplectic ... [more ▼]

We deform the moment map picture on the space of symplectic connections on a symplectic manifold. To do that, we study a vector bundle of Fedosov star product algebras on the space of symplectic connections. We describe a natural formal connection on this bundle adapted to the star product algebras on the fibers. We study its curvature and show the star product trace of the curvature is a formal symplectic form on the space of symplectic connections. The action of Hamiltonian diffeomorphisms on symplectic connections preserves the formal symplectic structure and we show the star product trace can be interpreted as a formal moment map for this action. Finally, we apply this picture to study automorphisms of star products and Hamiltonian diffeomorphisms. [less ▲]

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See detailHeterozygous variants in KCNC2 cause a broad spectrum of epilepsy phenotypes associated with characteristic functional alterations 2021.05.21.21257099
Schwarz, Niklas; Seiffert, Simone; Pendziwiat, Manuela et al

E-print/Working paper (2021)

Background KCNC2 encodes a member of the shaw-related voltage-gated potassium channel family (KV3.2), which are important for sustained high-frequency firing and optimized energy efficiency of action ... [more ▼]

Background KCNC2 encodes a member of the shaw-related voltage-gated potassium channel family (KV3.2), which are important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain.Methods Individuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic and functional analysis. The cases were referred through clinical and research collaborations in our study. Four de novo variants were examined electrophysiologically in Xenopus laevis oocytes.Results We identified novel KCNC2 variants in 27 patients with various forms of epilepsy. Functional analysis demonstrated gain-of-function in severe and loss-of-function in milder phenotypes as the underlying pathomechanisms with specific response to valproic acid.Conclusion These findings implicate KCNC2 as a novel causative gene for epilepsy emphasizing the critical role of KV3.2 in the regulation of brain excitability with an interesting genotype-phenotype correlation and a potential concept for precision medicine. [less ▲]

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See detailWie belastend erleben (Alleinerziehende) Eltern ihre Arbeit?
Sischka, Philipp UL; Steffgen, Georges UL

E-print/Working paper (2021)

Im Rahmen dieser Newsletter wird analysiert, wie sich verschiedene Arbeitnehmergruppen hinsichtlich ihrer familiären Situation unterscheiden, und in welchem Maße die familiäre Situation der Arbeitnehmer ... [more ▼]

Im Rahmen dieser Newsletter wird analysiert, wie sich verschiedene Arbeitnehmergruppen hinsichtlich ihrer familiären Situation unterscheiden, und in welchem Maße die familiäre Situation der Arbeitnehmer mit verschiedenen Quality of Work, Quality of Employment und Well-Being Dimensionen zusammenhängt. Die familiäre Situation wird dabei überwiegend vom Alter der Arbeitnehmer bestimmt. Alleinerziehende Eltern, d.h. Arbeitnehmer ohne Partner und mit minderjährigen Kindern, weisen zwischen 2016 und 2020 den höchsten Anstieg bei mentalen und emotionalen Anforderungen auf. Gleichzeitig zeigt sich für diese Gruppe ein Rückgang der Arbeitszufriedenheit und des generellen Well-Being, sowie ein Anstieg des Burnoutniveaus und der Gesundheitsprobleme. [less ▲]

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See detailAggregated hold-out for sparse linear regression with a robust loss function
Maillard, Guillaume UL

E-print/Working paper (2021)

Sparse linear regression methods generally have a free hyperparameter which controls the amount of sparsity, and is subject to a bias-variance tradeoff. This article considers the use of Aggregated hold ... [more ▼]

Sparse linear regression methods generally have a free hyperparameter which controls the amount of sparsity, and is subject to a bias-variance tradeoff. This article considers the use of Aggregated hold-out to aggregate over values of this hyperparameter, in the context of linear regression with the Huber loss function. Aggregated hold-out (Agghoo) is a procedure which averages estimators selected by hold-out (cross-validation with a single split). In the theoretical part of the article, it is proved that Agghoo satisfies a non-asymptotic oracle inequality when it is applied to sparse estimators which are parametrized by their zero-norm. In particular, this includes a variant of the Lasso introduced by Zou, Hastié and Tibshirani \cite{Zou_Has_Tib:2007}. Simulations are used to compare Agghoo with cross-validation. They show that Agghoo performs better than CV when the intrinsic dimension is high and when there are confounders correlated with the predictive covariates. [less ▲]

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See detailTrade-offs in phenotypic noise synchronize emergent topology to actively enhance transport in microbial environments
Dhar, Jayabrata UL; Thai, Le Phuong Anh UL; Ghoshal, Arkajyoti UL et al

E-print/Working paper (2021)

Phenotypic noise underpins homeostasis and fitness of individual cells. Yet, the extent to which noise shapes cell-to-population properties in microbial active matter remains poorly understood. By ... [more ▼]

Phenotypic noise underpins homeostasis and fitness of individual cells. Yet, the extent to which noise shapes cell-to-population properties in microbial active matter remains poorly understood. By quantifying variability in confluent \textit{E.coli} strains, we catalogue noise across different phenotypic traits. The noise, measured over different temperatures serving as proxy for cellular activity, spanned more than two orders of magnitude. The maximum noise was associated with the cell geometry and the critical colony area at the onset of mono-to-multilayer transition (MTMT), while the lower bound was set by the critical time of the MTMT. Our results, supported by a hydrodynamic model, suggest that a trade-off between the noise in the cell geometry and the growth rate can lead to the self-regulation of the MTMT timing. The MTMT cascades synchronous emergence of hydrodynamic fields, actively enhancing the micro-environmental transport. Our results highlight how interplay of phenotypic noise triggers emergent deterministic properties, and reveal the role of multifield topology--of the colony structure and hydrodynamics--to insulate confluent systems from the inherent noise associated with natural cell-environment settings. [less ▲]

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See detailLoss of function variants in the KCNQ5 gene are associated with genetic generalized epilepsies
Krueger, Johanna; Schubert, Julian; Kegele, Josua et al

E-print/Working paper (2021)

Objective: De novo missense variants in KCNQ5, encoding the voltage gated K+ channel KV7.5, have been described as a cause of developmental and epileptic encephalopathy (DEE) or intellectual disability ... [more ▼]

Objective: De novo missense variants in KCNQ5, encoding the voltage gated K+ channel KV7.5, have been described as a cause of developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease-related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms. Methods: 1292 families with GGE were studied by next-generation sequencing. Whole-cell patch-clamp recordings, biotinylation and phospholipid overlay assays were performed in mammalian cells combined with docking and homology modeling. Results: We identified three deleterious heterozygous missense variants, one truncation and one splice site alteration in five independent families with GGE with predominant absence seizures, two variants were also associated with mild to moderate ID. All three missense variants displayed a strongly decreased current density indicating a loss-of-function (LOF). When mutant channels were co-expressed with wild-type (WT) KV7.5 or KV7.5 and KV7.3 channels, three variants also revealed a significant dominant-negative effect on WT channels. Other gating parameters were unchanged. Biotinylation assays indicated a normal surface expression of the variants. The p.Arg359Cys variant altered PI(4,5)P2-interaction, presumably in the non-conducting preopen-closed state. Interpretation: Our study indicates that specific deleterious KCNQ5 variants are associated with GGE, partially combined with mild to moderate ID. The disease mechanism is a LOF partially with dominant-negative effects through functional, rather than trafficking deficits. LOF of KV7.5 channels will reduce the M-current, likely resulting in increased excitability of KV7.5-expressing neurons. Further studies on a network level are necessary to understand which circuits are affected and how the variants induce generalized seizures. [less ▲]

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See detailUltra-rare constrained missense variants in the epilepsies: Shared and specific enrichment patterns in neuronal gene-sets 2021.04.18.440264
Koko, Mahmoud; Krause, Roland UL; Sander, Thomas et al

E-print/Working paper (2021)

Background: Burden analysis in epilepsy has shown an excess of deleterious ultra-rare variants (URVs) in few gene-sets, such as known epilepsy genes, constrained genes, ion channel or GABAA receptor genes ... [more ▼]

Background: Burden analysis in epilepsy has shown an excess of deleterious ultra-rare variants (URVs) in few gene-sets, such as known epilepsy genes, constrained genes, ion channel or GABAA receptor genes. We set out to investigate the burden of URVs in a comprehensive range of gene-sets presumed to be implicated in epileptogenesis. Methods: We investigated several constraint and conservation-based strategies to study whole exome sequencing data from European individuals with developmental and epileptic encephalopathies (DEE, n = 1,003), genetic generalized epilepsy (GGE, n = 3,064), and non-acquired focal epilepsy (NAFE, n = 3,522), collected by the Epi25 Collaborative, compared to 3,962 ancestry-matched controls. The burden of 12 URVs types in 92 gene-sets was compared between epilepsy cases (DDE, GGE, NAFE) and controls using logistic regression analysis. Results: Burden analysis of brain-expressed genes revealed an excess of different URVs types in all three epilepsy categories which was largest for constrained missense variants. The URVs burden was prominent in neuron-specific, synaptic and developmental genes as well as genes encoding ion channels and receptors, and it was generally higher for DEE and GGE compared to NAFE. The patterns of URVs burden in gene-sets expressed in inhibitory vs. excitatory neurons or receptors suggested a high burden in both in DEE but a differential involvement of inhibitory genes in GGE, while excitatory genes were predominantly affected in NAFE. Top ranking susceptibility genes from a recent genome-wide association study (GWAS) of generalized and focal epilepsies displayed a higher URVs burden in constrained coding regions in GGE and NAFE, respectively. Conclusions: Using exome-based gene-set burden analysis, we demonstrate that missense URVs affecting mainly constrained sites are enriched in neuronal genes in both common and rare severe epilepsy syndromes. Our results indicate a differential impact of these URVs in genes expressed in inhibitory vs. excitatory neurons and receptors in generalized vs. focal epilepsies. The excess of URVs in top-ranking GWAS risk-genes suggests a convergence of rare deleterious and common risk-variants in the pathogenesis of generalized and focal epilepsies. [less ▲]

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Peer Reviewed
See detailMalliavin calculus for marked binomial processes: portfolio optimisation in the trinomial model and compound Poisson approximation
Halconruy, Hélène UL

E-print/Working paper (2021)

In this paper we develop a stochastic analysis for marked binomial processes, that can be viewed as the discrete analogues of marked Poisson processes. The starting point is the statement of a chaotic ... [more ▼]

In this paper we develop a stochastic analysis for marked binomial processes, that can be viewed as the discrete analogues of marked Poisson processes. The starting point is the statement of a chaotic expansion for square-integrable (marked binomial) functionals, prior to the elaboration of a Markov-Malliavin structure within this framework. We take advantage of the new formalism to deal with two main applications. First, we revisit the Chen-Stein method for the (compound) Poisson approximation which we perform in the paradigm of the built Markov-Malliavin structure, before studying in the second one the problem of portfolio optimisation in the trinomial model. [less ▲]

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See detailGenotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications
Johannesen, Katrine M.; Liu, Yuanyuan; Gjerulfsen, Cathrine E. et al

E-print/Working paper (2021)

We report detailed functional analyses and genotype-phenotype correlations in 433 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6. Five different ... [more ▼]

We report detailed functional analyses and genotype-phenotype correlations in 433 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6. Five different clinical subgroups could be identified: 1) Benign familial infantile epilepsy (BFIE) (n=17, normal cognition, treatable seizures), 2) intermediate epilepsy (n=36, mild ID, partially pharmacoresponsive), 3) developmental and epileptic encephalopathy (DEE, n=191, severe ID, majority pharmacoresistant), 4) generalized epilepsy (n=21, mild to moderate ID, frequently with absence seizures), and 5) affected individuals without epilepsy (n=25, mild to moderate ID). Groups 1-3 presented with early-onset (median: four months) focal or multifocal seizures and epileptic discharges, whereas the onset of seizures in group 4 was later (median: 39 months) with generalized epileptic discharges. The epilepsy was not classifiable in 143 individuals. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin insensitive human NaV1.6 channels and whole-cell patch clamping. Two variants causing DEE showed a strong gain-of-function (GOF, hyperpolarising shift of steady-state activation, strongly increased neuronal firing rate), and one variant causing BFIE or intermediate epilepsy showed a mild GOF (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (LOF, reduced current amplitudes, depolarising shift of steady-state activation, reduced neuronal firing). Including previous studies, functional effects were known for 165 individuals. All 133 individuals carrying GOF variants had either focal (76, groups 1-3), or unclassifiable epilepsy (37), whereas 32 with LOF variants had either generalized (14), no (11) or unclassifiable (5) epilepsy; only two had DEE. Computational modeling in the GOF group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. GOF variant carriers responded significantly better to sodium channel blockers (SCBs) than to other anti-seizure medications, and the same applied for all individuals of groups 1-3.In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of LOF variant carriers and the extent of the electrophysiological dysfunction of the GOF variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that SCBs present a therapeutic treatment option in early onset SCN8A-related focal epilepsy. [less ▲]

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See detailSustainable Finance Law: The EU Paradigm and the Way Forward
Alexandraki, Chrysa UL

E-print/Working paper (2021)

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See detailEmbedding Intelligence in Materials for Responsive Built Environment using Liquid Crystal Elastomer Actuators and Sensors
Schwartz, Mathew; Lagerwall, Jan UL

E-print/Working paper (2021)

Liquid Crystal Elastomers (LCEs) are an exciting category of material that has tremendous application potential across a variety of fields, owing to their unique properties that enable both sensing and ... [more ▼]

Liquid Crystal Elastomers (LCEs) are an exciting category of material that has tremendous application potential across a variety of fields, owing to their unique properties that enable both sensing and actuation. To some, LCEs are simply another type of Shape Memory Polymer, while to others they are an interesting on-going scientific experiment. In this visionary article, we bring an interdisciplinary discussion around creative and impactful ways that LCEs can be applied in the Built Environment to support kinematic and kinetic buildings and situational awareness. We focus particularly on the autonomy made possible by using LCEs, potentially removing needs for motors, wiring and tubing, and even enabling fully independent operation in response to natural environment variations, requiring no power sources. To illustrate the potential, we propose a number of concrete application scenarios where LCEs could offer innovative solutions to problems of great societal importance, such as autonomous active ventilation, heliotropic solar panels systems which can also remove snow or sand autonomously, and invisible coatings with strain mapping functionality, alerting residents in case of dangerous (static or dynamic) loads on roofs or windows, as well as assisting building safety inspection teams after earthquakes. [less ▲]

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See detailAus dem Arbeitsalltag einer Sozialforscherin: Unterwegs mit „Chercheurs à l’école“
Höpner, Moritz UL

E-print/Working paper (2021)

In mid-March, our team member Caroline Residori visited a senior class of the Lycée Technique in Lallange. As part of the Chercheurs à l’école initiative, she told the young people between the ages of 17 ... [more ▼]

In mid-March, our team member Caroline Residori visited a senior class of the Lycée Technique in Lallange. As part of the Chercheurs à l’école initiative, she told the young people between the ages of 17 and 21 many new things about the everyday work of a social researcher. Just like her colleague Céline Dujardin, who visited the Athénée de Luxembourg, she created an interesting orientation afternoon as part of this FNR projects. “The everyday life of researchers is much more than hours of reading and concentrated pipetting in the lab,” Caroline emphasizes. “In every research discipline, it pays off to have a closer look,” Céline adds. [less ▲]

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See detailDemocratic Legitimacy of the Single Resolution Board: Is Legality the Right Question?
Mendes, Joana UL

E-print/Working paper (2021)

The choice to entrust EU banking resolution to an independent body opened the familiar democratic legitimacy conundrum that besets independent institutions in national and in EU law. This paper examines ... [more ▼]

The choice to entrust EU banking resolution to an independent body opened the familiar democratic legitimacy conundrum that besets independent institutions in national and in EU law. This paper examines both the conventional view on the relationship between legality control and democratic legitimacy, that the German Federal Constitutional Court endorsed in its SSM/SRM judgment, and the limits of such conception. Conceived as a “compensatory measure”, legal protection through judicial review and internal administrative review enables the Court to bring independent institutions within the (national) constitutional framework that they strain. Law’s binding character becomes a matter of ensuring not only the rule of law but also democracy. Yet, even detailed legal mandates cannot preclude administrative bodies to define the way law is completed and concretised. While the Court does not adhere to a ‘transmission-belt model’ of administrations, not surprisingly – as a court deciding on democratic legitimacy – it falls short of recognising that legality can do very little to ground the democratic legitimacy of fundamental political choices, such as those entrusted to the Single Resolution Board. [less ▲]

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See detailDigitalisierung von Schule und Digitalisierung im Unterricht
Harion, Dominic UL; Pause, Johannes UL

E-print/Working paper (2021)

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See detailAssange’s Extradition: Status Pending
Kafteranis, Dimitrios UL; Andreadakis, Stelios

E-print/Working paper (2021)

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See detailAddressing Hate Speech with Data Science: An Overview from Computer Science Perspective
Lenzini, Gabriele UL; Srba; Pikuliak, Matus et al

E-print/Working paper (2021)

From a computer science perspective, addressing on-line hate speech is a challenging task that is attracting the attention of both industry (mainly social media platform owners) and academia. In this ... [more ▼]

From a computer science perspective, addressing on-line hate speech is a challenging task that is attracting the attention of both industry (mainly social media platform owners) and academia. In this chapter, we provide an overview of state-of-the-art data-science approaches - how they define hate speech, which tasks they solve to mitigate the phenomenon, and how they address these tasks. We limit our investigation mostly to (semi-)automatic detection of hate speech, which is the task that the majority of existing computer science works focus on. Finally, we summarize the challenges and the open problems in the current data-science research and the future directions in this field. Our aim is to prepare an easily understandable report, capable to promote the multidisciplinary character of hate speech research. Researchers from other domains (e.g., psychology and sociology) can thus take advantage of the knowledge achieved in the computer science domain but also contribute back and help improve how computer science is addressing that urgent an d socially relevant issue which is the prevalence of hate speech in social media. [less ▲]

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See detailPanic? Probing Angst over Immigration and Crime
Mahe, Clotilde UL; Parra-Cely, Sergio

E-print/Working paper (2021)

We examine empirically whether immigration affects crime in an emerging country, Ecuador. We exploit the fact that immigration flows of Venezuelans suddenly evolved from voluntary to forced, and occurred ... [more ▼]

We examine empirically whether immigration affects crime in an emerging country, Ecuador. We exploit the fact that immigration flows of Venezuelans suddenly evolved from voluntary to forced, and occurred disproportionately along land borders. We use nationally representative administrative and survey data to precisely estimate an economically null effect of Venezuelan immigration on property and violent crime. We also show that natives are more likely to believe that immigration worsens the economy, despite clear evidence of negative labour market impact due to recent Venezuelan inflows. Results confirm that fears over immigration and crime are not necessarily supported by facts. [less ▲]

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See detailHierarchical a posteriori error estimation of Bank-Weiser type in the FEniCS Project
Bulle, Raphaël UL; Hale, Jack UL; Lozinski, Alexei et al

E-print/Working paper (2021)

In the seminal paper of Bank and Weiser [Math. Comp., 44 (1985), pp.283-301] a new a posteriori estimator was introduced. This estimator requires the solution of a local Neumann problem on every cell of ... [more ▼]

In the seminal paper of Bank and Weiser [Math. Comp., 44 (1985), pp.283-301] a new a posteriori estimator was introduced. This estimator requires the solution of a local Neumann problem on every cell of the finite element mesh. Despite the promise of Bank-Weiser type estimators, namely locality, computational efficiency, and asymptotic sharpness, they have seen little use in practical computational problems. The focus of this contribution is to describe a novel implementation of hierarchical estimators of the Bank-Weiser type in a modern high-level finite element software with automatic code generation capabilities. We show how to use the estimator to drive (goal-oriented) adaptive mesh refinement and to mixed approximations of the nearly-incompressible elasticity problems. We provide comparisons with various other used estimators. An open-source implementation based on the FEniCS Project finite element software is provided as supplementary material. [less ▲]

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See detailIntroducing the COVID-19 crisis Special Education Needs Coping Survey
Dukes, Daniel; Van Herwegen, Jo; Alessandri, Michael et al

E-print/Working paper (2021)

Individuals with special education needs have been particularly affected by the COVID-19 pandemic as they have been shown to be at high risk of losing medical and institutional support at a time when ... [more ▼]

Individuals with special education needs have been particularly affected by the COVID-19 pandemic as they have been shown to be at high risk of losing medical and institutional support at a time when people are being asked to stay isolated, suffering increased anxiety and depression as a consequence. Their families have often found themselves under tremendous pressure to provide support, engendering financial hardship, and physical and emotional strains. In such times, it is vital that international collaborations assess the impact on the individuals and their families, affording the opportunity to make national and international comparisons of how people have coped and what needs to be done to optimize the measures taken by families, associations and governments. This paper introduces one such collaboration. [less ▲]

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See detailWhich Factors Play a Role in Coco Issuance? Evidence from European Banks.
Wolff, Christian UL

E-print/Working paper (2021)

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See detailA Robustness Check to Multiple Overlapping Deprivation Analysis (MODA) Methodology: The Case of Nigeria
Fagbeja, Teju; Cebotari, Victor UL

E-print/Working paper (2021)

Detailed reference viewed: 26 (0 UL)