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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 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 detailInternship and Public History Training
Cauvin, Thomas UL

E-print/Working paper (2022)

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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 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 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 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 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 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 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 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 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 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 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 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 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 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)

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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.

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See detailGeneralising from Conventional Pipelines: A Case Study in Deep Learning-Based High-Throughput Screening
Garcia Santa Cruz, Beatriz UL; Sölter, Jan; Gomez Giro, Gemma UL et al

E-print/Working paper (2021)

The study of complex diseases relies on large amounts of data to build models toward precision medicine. Such data acquisition is feasible in the context of high-throughput screening, in which the quality ... [more ▼]

The study of complex diseases relies on large amounts of data to build models toward precision medicine. Such data acquisition is feasible in the context of high-throughput screening, in which the quality of the results relies on the accuracy of the image analysis. Although state-of-the-art solutions for image segmentation employ deep learning approaches, the high cost of manually generating ground truth labels for model training hampers the day-to-day application in experimental laboratories. Alternatively, traditional computer vision-based solutions do not need expensive labels for their implementation. Our work combines both approaches by training a deep learning network using weak training labels automatically generated with conventional computer vision methods. Our network surpasses the conventional segmentation quality by generalising beyond noisy labels, providing a 25 % increase of mean intersection over union, and simultaneously reducing the development and inference times. Our solution was embedded into an easy-to-use graphical user interface that allows researchers to assess the predictions and correct potential inaccuracies with minimal human input. To demonstrate the feasibility of training a deep learning solution on a large dataset of noisy labels automatically generated by a conventional pipeline, we compared our solution against the common approach of training a model from a small manually curated dataset by several experts. Our work suggests that humans perform better in context interpretation, such as error assessment, while computers outperform in pixel-by-pixel fine segmentation. Such pipelines are illustrated with a case study on image segmentation for autophagy events. This work aims for better translation of new technologies to real-world settings in microscopy-image analysis. [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)

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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 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 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 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 for estimating the law of an n-sample. The loss functions we have in mind are ... [more ▼]

In the Bayes paradigm and for a given loss function, we propose the construction of a new type of posterior distributions for estimating the law of an n-sample. The loss functions we have in mind are based on the total variation distance, the Hellinger distance as well as some 𝕃j-distances. 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 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 sparcity 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: 36 (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 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 detailFace-GCN: A Graph Convolutional Network for 3D Dynamic Face Identification/Recognition
Papadopoulos, Konstantinos; Kacem, Anis UL; Shabayek, Abdelrahman et al

E-print/Working paper (2021)

Face identification/recognition has significantly advanced over the past years. However, most of the proposed approaches rely on static RGB frames and on neutral facial expressions. This has two ... [more ▼]

Face identification/recognition has significantly advanced over the past years. However, most of the proposed approaches rely on static RGB frames and on neutral facial expressions. This has two disadvantages. First, important facial shape cues are ignored. Second, facial deformations due to expressions can have an impact on the performance of such a method. In this paper, we propose a novel framework for dynamic 3D face identification/recognition based on facial keypoints. Each dynamic sequence of facial expressions is represented as a spatio-temporal graph, which is constructed using 3D facial landmarks. Each graph node contains local shape and texture features that are extracted from its neighborhood. For the classification/identification of faces, a Spatio-temporal Graph Convolutional Network (ST-GCN) is used. Finally, we evaluate our approach on a challenging dynamic 3D facial expression dataset. [less ▲]

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See detailDisentangled Face Identity Representations for joint 3D Face Recognition and Expression Neutralisation
Kacem, Anis UL; cherenkova, kseniya; Aouada, Djamila UL

E-print/Working paper (2021)

In this paper, we propose a new deep learning-based approach for disentangling face identity representations from expressive 3D faces. Given a 3D face, our approach not only extracts a disentangled ... [more ▼]

In this paper, we propose a new deep learning-based approach for disentangling face identity representations from expressive 3D faces. Given a 3D face, our approach not only extracts a disentangled identity representation but also generates a realistic 3D face with a neutral expression while predicting its identity. The proposed network consists of three components; (1) a Graph Convolutional Autoencoder (GCA) to encode the 3D faces into latent representations, (2) a Generative Adversarial Network (GAN) that translates the latent representations of expressive faces into those of neutral faces, (3) and an identity recognition sub-network taking advantage of the neutralized latent representations for 3D face recognition. The whole network is trained in an end-to-end manner. Experiments are conducted on three publicly available datasets showing the effectiveness of the proposed approach. [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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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)

Detailed reference viewed: 95 (2 UL)
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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 detailDigitalisierung von Schule und Digitalisierung im Unterricht
Harion, Dominic UL; Pause, Johannes UL

E-print/Working paper (2021)

Detailed reference viewed: 106 (9 UL)
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 detailAssange’s Extradition: Status Pending
Kafteranis, Dimitrios UL; Andreadakis, Stelios

E-print/Working paper (2021)

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

E-print/Working paper (2021)

This paper explores empirically the reasons why some banks issue Contingent Convertible Bonds while others do not. For this purpose we use a binary logistic model and control for the determinants ... [more ▼]

This paper explores empirically the reasons why some banks issue Contingent Convertible Bonds while others do not. For this purpose we use a binary logistic model and control for the determinants suggested by the literature on optimal capital structure which considers four drivers of capital structure: corporate taxes, costs of financial distress, agency costs and asymmetric information.. Our findings suggest that the banks with bigger size and those with higher Tier 1 capital, higher net loans, higher wholesale funding, lower level of leverage and lower risk weighted assets have a higher tendency to issue CoCos. Our results also suggest that banks in countries with higher annual growth rate of GDP per capita and those listed as G-SIBs are more likely to issue CoCos. [less ▲]

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

E-print/Working paper (2021)

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See detailSchool-Related Violence in Latin America and the Caribbean: Building an Evidence Base for Stronger Schools
Chávez, Cirenia; Cebotari, Victor UL; José Benítez, Maria et al

E-print/Working paper (2021)

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See detailhttps://arxiv.org/abs/2101.07083
El Emam, Christian UL; Seppi, Andrea

E-print/Working paper (2021)

We prove that any minimal Lagrangian diffeomorphism between two closed spherical surfaces with cone singularities is an isometry, without any assumption on the multiangles of the two surfaces. As an ... [more ▼]

We prove that any minimal Lagrangian diffeomorphism between two closed spherical surfaces with cone singularities is an isometry, without any assumption on the multiangles of the two surfaces. As an application, we show that every branched immersion of a closed surface of constant positive Gaussian curvature in Euclidean three-space is a branched covering onto a round sphere, thus generalizing the classical rigidity theorem of Liebmann to branched immersions. [less ▲]

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See detailPestepidemien in Luxemburg
Pauly, Michel UL

E-print/Working paper (2021)

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See detailOn the Weyl problem for complete surfaces in the hyperbolic and anti-de Sitter spaces
Schlenker, Jean-Marc UL

E-print/Working paper (2021)

The classical Weyl problem (solved by Lewy, Alexandrov, Pogorelov, and others) asks whether any metric of curvature K≥0 on the sphere is induced on the boundary of a unique convex body in $\R^3$. The ... [more ▼]

The classical Weyl problem (solved by Lewy, Alexandrov, Pogorelov, and others) asks whether any metric of curvature K≥0 on the sphere is induced on the boundary of a unique convex body in $\R^3$. The answer was extended to surfaces in hyperbolic space by Alexandrov in the 1950s, and a ``dual'' statement, describing convex bodies in terms of the third fundamental form of their boundary (e.g. their dihedral angles, for an ideal polyhedron) was later proved. We describe three conjectural generalizations of the Weyl problem in $\HH^3$ and its dual to unbounded convex subsets and convex surfaces, in ways that are relevant to contemporary geometry since a number of recent results and well-known open problems can be considered as special cases. One focus is on convex domain having a ``thin'' asymptotic boundary, for instance a quasicircle -- this part of the problem is strongly related to the theory of Kleinian groups. A second direction is towards convex subsets with a ``thick'' ideal boundary, for instance a disjoint union of disks -- here one find connections to problems in complex analysis, such as the Koebe circle domain conjecture. A third direction is towards complete, convex disks of infinite area in $\HH^3$ and surfaces in hyperbolic ends -- with connections to questions on circle packings or grafting on the hyperbolic disk. Similar statements are proposed in anti-de Sitter geometry, a Lorentzian cousin of hyperbolic geometry where interesting new phenomena can occur, and in Minkowski and Half-pipe geometry. We also collect some partial new results mostly based on recent works. [less ▲]

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See detailOptimal convergence rates for the invariant density estimation of jump-diffusion processes
Amorino, Chiara UL; Nualart, Eulalia

E-print/Working paper (2021)

We aim at estimating the invariant density associated to a stochastic differential equation with jumps in low dimension, which is for d = 1 and d = 2. We consider a class of jump diffusion processes whose ... [more ▼]

We aim at estimating the invariant density associated to a stochastic differential equation with jumps in low dimension, which is for d = 1 and d = 2. We consider a class of jump diffusion processes whose invariant density belongs to some Hölder space. Firstly, in dimension one, we show that the kernel density estimator achieves the convergence rate 1/T, which is the optimal rate in the absence of jumps. This improves the convergence rate obtained in [Amorino, Gloter (2021)], which depends on the Blumenthal-Getoor index for d = 1 and is equal to log T/T for d = 2. Secondly, we show that is not possible to find an estimator with faster rates of estimation. Indeed, we get some lower bounds with the same rates { 1/T , log T/T } in the mono and bi-dimensional cases, respectively. Finally, we obtain the asymptotic normality of the estimator in the one-dimensional case. [less ▲]

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See detailConstitutional engineering of State of exception regimes within the European Union
Gerkrath, Jörg UL

E-print/Working paper (2021)

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See detailTHE EU SUSTAINABLE FINANCE FRAMEWORK IN LIGHT OF INTERNATIONAL STANDARDS
Bodellini, Marco UL

E-print/Working paper (2021)

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See detailThe Seventh International Olympiad in Cryptography NSUCRYPTO: problems and solutions
Gorodilova, Anastasiya; Tokareva, Natalia N.; Agievich, Sergey et al

E-print/Working paper (2021)

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See detailDivision in modules and Kummer theory
Tronto, Sebastiano UL

E-print/Working paper (2021)

In this work we generalize the concept of injective module and develop a theory of divisibility for modules over a general ring, which provides a general and unified framework to study Kummer-like field ... [more ▼]

In this work we generalize the concept of injective module and develop a theory of divisibility for modules over a general ring, which provides a general and unified framework to study Kummer-like field extensions arising from commutative algebraic groups. With these tools we provide an effective bound for the degree of the field extensions arising from division points of elliptic curves, extending previous results of Javan Peykar for CM curves and of Lombardo and the author for the non-CM case. [less ▲]

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See detailSome uniform bounds for elliptic curves over Q
Lombardo, Davide; Tronto, Sebastiano UL

E-print/Working paper (2021)

We give explicit uniform bounds for several quantities relevant to the study of Galois representations attached to elliptic curves E/Q. We consider in particular the subgroup of scalars in the image of ... [more ▼]

We give explicit uniform bounds for several quantities relevant to the study of Galois representations attached to elliptic curves E/Q. We consider in particular the subgroup of scalars in the image of Galois, the first Galois cohomology group with values in the torsion of E, and the Kummer extensions generated by points of infinite order in E(Q). [less ▲]

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See detailDynamic Universal Accumulator with Batch Update over Bilinear Groups
Vitto, Giuseppe UL; Biryukov, Alexei UL

E-print/Working paper (2021)

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See detailCentral limit theorem for a birth-growth model with Poisson arrivals and random growth speed.
Bhattacharjee, Chinmoy UL; Molchanov, Ilya; Turin, Riccardo

E-print/Working paper (2021)

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See detailEfficient and Transferable Adversarial Examples from Bayesian Neural Networks
Gubri, Martin UL; Cordy, Maxime UL; Papadakis, Mike UL et al

E-print/Working paper (2021)

An established way to improve the transferability of black-box evasion attacks is to craft the adversarial examples on a surrogate ensemble model to increase diversity. We argue that transferability is ... [more ▼]

An established way to improve the transferability of black-box evasion attacks is to craft the adversarial examples on a surrogate ensemble model to increase diversity. We argue that transferability is fundamentally related to epistemic uncertainty. Based on a state-of-the-art Bayesian Deep Learning technique, we propose a new method to efficiently build a surrogate by sampling approximately from the posterior distribution of neural network weights, which represents the belief about the value of each parameter. Our extensive experiments on ImageNet and CIFAR-10 show that our approach improves the transfer rates of four state-of-the-art attacks significantly (up to 62.1 percentage points), in both intra-architecture and inter-architecture cases. On ImageNet, our approach can reach 94% of transfer rate while reducing training computations from 11.6 to 2.4 exaflops, compared to an ensemble of independently trained DNNs. Our vanilla surrogate achieves 87.5% of the time higher transferability than 3 test-time techniques designed for this purpose. Our work demonstrates that the way to train a surrogate has been overlooked although it is an important element of transfer-based attacks. We are, therefore, the first to review the effectiveness of several training methods in increasing transferability. We provide new directions to better understand the transferability phenomenon and offer a simple but strong baseline for future work. [less ▲]

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See detailObserving Many Researchers Using the Same Data and Hypothesis Reveals a Hidden Universe of Uncertainty
Breznau, Nate; Rinke, Eike Mark; Wuttke, Alexander et al

E-print/Working paper (2021)

How does noise generated by researcher decisions undermine the credibility of science? We test this by observing all decisions made among 73 research teams as they independently conduct studies on the ... [more ▼]

How does noise generated by researcher decisions undermine the credibility of science? We test this by observing all decisions made among 73 research teams as they independently conduct studies on the same hypothesis with identical starting data. We find excessive variation of outcomes. When combined, the 107 observed research decisions taken across teams explained at most 2.6 of the total variance in effect sizes and 10 of the deviance in subjective conclusions. Expertise, prior beliefs and attitudes of the researchers explain even less. Each model deployed to test the hypothesis was unique, which highlights a vast universe of research design variability that is normally hidden from view and suggests humility when presenting and interpreting scientific findings. [less ▲]

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See detailBatch Learning in Stochastic Dual Dynamic Programming
Avila, Daniel; Papavasiliou, Anthona; Löhndorf, Nils UL

E-print/Working paper (2021)

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See detailRapid Artificial Intelligence Solutions in a Pandemic - The COVID-19-20 Lung CT Lesion Segmentation Challenge.
Roth, Holger; Xu, Ziyue; Diez, Carlos Tor et al

E-print/Working paper (2021)

Artificial intelligence (AI) methods for the automatic detection and quantification of COVID-19 lesions in chest computed tomography (CT) might play an important role in the monitoring and management of ... [more ▼]

Artificial intelligence (AI) methods for the automatic detection and quantification of COVID-19 lesions in chest computed tomography (CT) might play an important role in the monitoring and management of the disease. We organized an international challenge and competition for the development and comparison of AI algorithms for this task, which we supported with public data and state-of-the-art benchmark methods. Board Certified Radiologists annotated 295 public images from two sources (A and B) for algorithms training (n=199, source A), validation (n=50, source A) and testing (n=23, source A; n=23, source B). There were 1,096 registered teams of which 225 and 98 completed the validation and testing phases, respectively. The challenge showed that AI models could be rapidly designed by diverse teams with the potential to measure disease or facilitate timely and patient-specific interventions. This paper provides an overview and the major outcomes of the COVID-19 Lung CT Lesion Segmentation Challenge - 2020. [less ▲]

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See detailBorder or bordering practice? Changing perspectives on borders and challenges of praxeological approaches
Connor, Ulla UL

E-print/Working paper (2021)

In Border Studies, the ongoing discussions on methodological and theoretical questions have led to the development of transformed approaches and vocabulary for border research. This contribution ... [more ▼]

In Border Studies, the ongoing discussions on methodological and theoretical questions have led to the development of transformed approaches and vocabulary for border research. This contribution highlights the shift from ‘border’ to ‘bordering practice’ and questions its sources in the scientific context, such as the cultural turn and the related practice turn. Despite the popular use of the term ‘practice’ in Border Studies, sociological practice theories are not at the center of the development of dynamic concepts for studying borders. The article emphasizes the compatibility of sociological practice theories with the practice and process orientation in Border Studies. It gives a short overview of praxeological thinking in sociology and identifies methodological challenges for Border Studies targeting the development of praxeological re-search perspectives for borders. [less ▲]

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See detailGlacier-fed stream biofilms harbour diverse resistomes and biosynthetic gene clusters 2021.11.18.469141
Busi, Susheel Bhanu UL; de Nies, Laura UL; Pramateftaki, Paraskevi et al

E-print/Working paper (2021)

Background Antimicrobial resistance (AMR) is a universal phenomenon whose origins lay in natural ecological interactions such as competition within niches, within and between micro- to higher-order ... [more ▼]

Background Antimicrobial resistance (AMR) is a universal phenomenon whose origins lay in natural ecological interactions such as competition within niches, within and between micro- to higher-order organisms. However, the ecological and evolutionary processes shaping AMR need to be better understood in view of better antimicrobial stewardship. Resolving antibiotic biosynthetic pathways, including biosynthetic gene clusters (BGCs), and corresponding antimicrobial resistance genes (ARGs) may therefore help in understanding the inherent mechanisms. However, to study these phenomena, it is crucial to examine the origins of AMR in pristine environments with limited anthropogenic influences. In this context, epilithic biofilms residing in glacier-fed streams (GFSs) are an excellent model system to study diverse, intra- and inter-domain, ecological crosstalk.Results We assessed the resistomes of epilithic biofilms from GFSs across the Southern Alps (New Zealand) and the Caucasus (Russia) and observed that both bacteria and eukaryotes encoded twenty-nine distinct AMR categories. Of these, beta-lactam, aminoglycoside, and multidrug resistance were both abundant and taxonomically distributed in most of the bacterial and eukaryotic phyla. AMR-encoding phyla included Bacteroidota and Proteobacteria among the bacteria, alongside Ochrophyta (algae) among the eukaryotes. Additionally, BGCs involved in the production of antibacterial compounds were identified across all phyla in the epilithic biofilms. Furthermore, we found that several bacterial genera (Flavobacterium, Polaromonas, etc.) including representatives of the superphylum Patescibacteria encode both ARGs and BGCs within close proximity of each other, thereby demonstrating their capacity to simultaneously influence and compete within the microbial community.Conclusions Our findings highlight the presence and abundance of AMR in epilithic biofilms within GFSs. Additionally, we identify their role in the complex intra- and inter-domain competition and the underlying mechanisms influencing microbial survival in GFS epilithic biofilms. We demonstrate that eukaryotes may serve as AMR reservoirs owing to their potential for encoding ARGs. We also find that the taxonomic affiliation of the AMR and the BGCs are congruent. Importantly, our findings allow for understanding how naturally occurring BGCs and AMR contribute to the epilithic biofilms mode of life in GFSs. Importantly, these observations may be generalizable and potentially extended to other environments which may be more or less impacted by human activity.Competing Interest StatementThe authors have declared no competing interest.AMRAntimicrobial resistanceARGsAntimicrobial resistance gene(s)BGCBiosynthetic gene clustersCACaucasusCPRCandidate Phyla radiationGFSsGlacier-fed stream(s)GLGlacierIRS-RSisoleucyl-tRNA synthetase - high resistanceIMPIntegrate Meta-Omics PipelineKEGGKyoto Encyclopedia of Genes and GenomesMAGsMetagenome-assembled genome(s)NRPSNon-ribosomal peptide synthetasesPKSPolyketide synthases (type I and type II)RiPPsPost-translationally modified peptide(s)SASouthern Alps [less ▲]

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See detailAll in one stroke? Intervention Spaces for Dark Patterns
Rossi, Arianna UL; Bongard, Kerstin UL

E-print/Working paper (2021)

This position paper draws from the complexity of dark patterns to develop arguments for differentiated interventions. We propose a matrix of interventions with a \textit{measure axis} (from user-directed ... [more ▼]

This position paper draws from the complexity of dark patterns to develop arguments for differentiated interventions. We propose a matrix of interventions with a \textit{measure axis} (from user-directed to environment-directed) and a \textit{scope axis} (from general to specific). We furthermore discuss a set of interventions situated in different fields of the intervention spaces. The discussions at the 2021 CHI workshop "What can CHI do about dark patterns?" should help hone the matrix structure and fill its fields with specific intervention proposals. [less ▲]

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See detailInnovation in Malmö after the Öresund Bridge
Ejermo, Olof; Hussinger, Katrin UL; Kalash, Basheer et al

E-print/Working paper (2021)

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See detailPhase transitions and noise sensitivity on the Poisson space via stopping sets and decision trees
Last, Guenter; Peccati, Giovanni UL; Yogeshwaran, Dhandapani

E-print/Working paper (2021)

Detailed reference viewed: 53 (5 UL)