The edge-based strain smoothing method for compressible and nearly incompressible non-linear elasticity for solid mechanics

E-print/Working paper (in press)

The mod 2 cohomology rings of congruence subgroups in the Bianchi groups

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 ▲]

Critical Mineral Depletion and Recycling: From the Perspective of the Cooperation and Open-Loop Competition

E-print/Working paper (2023)

Critical minerals are essential to the success of the transition to clean and sustainable technology. However, critical minerals face supply chain disruption, resource depletion, a lack of recycling ... [more ▼]

Critical minerals are essential to the success of the transition to clean and sustainable technology. However, critical minerals face supply chain disruption, resource depletion, a lack of recycling technology and minimum demand, which may be increasing over time, at least in the short run. This paper models critical mineral extraction and recycling strategies under international cooperation and open-loop commitment competition. We show that (1) recycling technology can only partially reduce dependence on the virgin supply of critical minerals, given that recycling essentially relies on the accumulated supply from depletable resources; (2) the social planner's Markovian optimal market supply is based on either virgin or recyclable resources, with the more socially desirable being used first; (3) if the recyclable resource is exhausted, the social planner does not have an optimal choice regarding how to exploit the remaining virgin resource; but (4) under open-loop commitment, the two resources can coexist until the virgin resource is exhausted. [less ▲]

Measured foliations at infinity and constant mean curvature surfaces in quasi-Fuchsian manifolds close to the Fuchsian locus

E-print/Working paper (2023)

Recherche en histoire : les opportunités et défis du numérique

E-print/Working paper (2023)

Transferability of European-derived cardiometabolic polygenic risk scores in the South Asians and their interplay with family history 2023.03.20.23287470

E-print/Working paper (2023)

Background & Aims We aimed to investigate the effect of polygenic risk scores (PRSs) derived from individuals of European (EUR) ancestry on common diseases among individuals of South Asian (SAS) ancestry ... [more ▼]

Background & Aims We aimed to investigate the effect of polygenic risk scores (PRSs) derived from individuals of European (EUR) ancestry on common diseases among individuals of South Asian (SAS) ancestry in the UK Biobank (UKB). Additionally, we studied the interaction between PRS and family history (FH) in the same population.Methods To calculate the PRS, we used a previously published panel of SNPs derived from the EUR population and applied it to the individuals of SAS ancestry from the UKB study. We applied the PRS using summary statistics from genome-wide association studies (GWAS) for cardiometabolic and lifestyle diseases such as coronary artery disease (CAD), obesity, and type 2 diabetes (T2D). Each PRS was adjusted according to an individual\textquoterights predicted genetic ancestry to derive an adjusted PRS (aPRS). We calculated the percentiles based on aPRS and divided them according to the percentiles into three categories: low, intermediate, and high. Considering the intermediate-aPRS percentile as a reference, we compared the low and high aPRS categories and generated the odds ratio (OR) estimates.Results The risk of developing severe obesity for individuals of SAS ancestry was almost threefold higher for individuals with high aPRS than for those with intermediate aPRS, with an OR of 3.67 (95% CI = 2.47-5.48, P < 0.01). While the risk of severe obesity was lower in the low-aPRS group (OR = 0.19, CI = 0.05\textendash0.52, P < 0.01). Comparable results were found in the EUR data, where the low-PRS group had an OR of 0.26 (95% CI= 0.24-0.3, P < 0.01) and the high-PRS group had an OR of 3.2 (95% CI = 3.1-3.3, P < 0.01). We observed similar results for CAD and T2D. Further, we show that SAS individuals with a familial history of CAD and T2D with high-aPRS exhibit further higher risk to these diseases, thereby implying a greater genetic predisposition to these conditions.Conclusion Our findings suggest that using CAD, obesity, and T2D GWAS summary statistics predominantly from the EUR population have sufficient power to identify SAS individuals with higher genetic risk. With future GWAS recruiting more SAS participants and tailoring the PRSs towards SAS ancestry, we believe that the predictive power of PRS would improve. [less ▲]

Multiple Access in Constellation Domain by Non-Coherent Massive MIMO

E-print/Working paper (2023)

Multiple access is the base for increasing the capacity in multi-user communication networks. However, the growing demand for higher data rates and the number of users who requires communication services ... [more ▼]

Multiple access is the base for increasing the capacity in multi-user communication networks. However, the growing demand for higher data rates and the number of users who requires communication services has led to the scarcity of orthogonal resources in current wireless communications. On the other hand, integrating the satellite within terrestrial networks as an initiative of 3GPP since its Release 15 entails the need for new forms of multiple access between terrestrial and non-terrestrial users. This paper studies constellation schemes as a new domain to enhance the state-of-the-art multiple-access techniques for future communication technologies employing non-coherent communications with massive MIMO. In addition, we propose a hybrid model between the classic access methods such as Time Division Multiple Access (TDMA) or Frequency Division Multiple Access (FDMA), the emerging models of non-orthogonal multiple access (NOMA) and the proposed domain of the constellation based on non-coherent massive multiple-input multiple-output (MIMO) schemes. This model is discussed for different scenarios in satellite communications that help increase the system's capacity and avoid interference between terrestrial and non-terrestrial users. [less ▲]

The State of AI-Empowered Backscatter Communications: A Comprehensive Survey

E-print/Working paper (2023)

The Internet of Things (IoT) is undergoing significant advancements, driven by the emergence of Backscatter Communication (BC) and Artificial Intelligence (AI). BC is an energy-saving and cost-effective ... [more ▼]

The Internet of Things (IoT) is undergoing significant advancements, driven by the emergence of Backscatter Communication (BC) and Artificial Intelligence (AI). BC is an energy-saving and cost-effective communication method where passive backscatter devices communicate by modulating ambient Radio-Frequency (RF) carriers. AI has the potential to transform our way of communicating and interacting and represents a powerful tool for enabling the next generation of IoT devices and networks. By integrating AI with BC, we can create new opportunities for energy-efficient and low-cost communication and open the door to a range of innovative applications that were previously not possible. This paper brings these two technologies together to investigate the current state of AI-powered BC. We begin with an introduction to BC and an overview of the AI algorithms employed in BC. Then, we delve into the recent advances in AI-based BC, covering key areas such as backscatter signal detection, channel estimation, and jammer control to ensure security, mitigate interference, and improve throughput and latency. We also explore the exciting frontiers of AI in BC using B5G/6G technologies, including backscatter-assisted relay and cognitive communication networks, backscatter-assisted MEC networks, and BC with RIS, UAV, and vehicular networks. Finally, we highlight the challenges and present new research opportunities in AI-powered BC. This survey provides a comprehensive overview of the potential of AI-powered BC and its insightful impact on the future of IoT. [less ▲]

Multifractional Hermite processes: definition and first properties

E-print/Working paper (2023)

We define multifractional Hermite processes which generalize and extend both multifractional Brownian motion and Hermite processes. It is done by substituting the Hurst parameter in the definition of ... [more ▼]

We define multifractional Hermite processes which generalize and extend both multifractional Brownian motion and Hermite processes. It is done by substituting the Hurst parameter in the definition of Hermite processes as a multiple Wiener-Itô integral by a Hurst function. Then, we study the pointwise regularity of these processes, their local asymptotic self-similarity and some fractal dimensions of their graph. Our results show that the fundamental properties of multifractional Hermite processes are, as desired, governed by the Hurst function. Complements are given in the second order Wiener chaos, using facts from Malliavin calculus. [less ▲]

Energy-Efficient RIS-Enabled NOMA Communication for 6G LEO Satellite Networks

E-print/Working paper (2023)

Reconfigurable Intelligent surfaces (RIS) have the potential to significantly improve the performance of future 6G LEO satellite networks. In particular, RIS can improve the signal quality of ground ... [more ▼]

Reconfigurable Intelligent surfaces (RIS) have the potential to significantly improve the performance of future 6G LEO satellite networks. In particular, RIS can improve the signal quality of ground terminal, reduce power consumption of satellite and increase spectral efficiency of overall network. This paper proposes an energy-efficient RIS-enabled NOMA communication for LEO satellite networks. The proposed framework simultaneously optimizes the transmit power of ground terminals at LEO satellite and passive beamforming at RIS while ensuring the quality of services. Due to the nature of the considered system and optimization variables, the problem of energy efficiency maximization is formulated as non-convex. In practice, it is very challenging to obtain the optimal solution for such problems. Therefore, we adopt alternating optimization methods to handle the joint optimization in two steps. In step 1, for any given phase shift vector, we calculate efficient power for ground terminals at satellite using Lagrangian dual method. Then, in step 2, given the transmit power, we design passive beamforming for RIS by solving the semi-definite programming. To validate the proposed solution, numerical results are also provided to demonstrate the benefits of the proposed optimization framework. [less ▲]

The Next Generation EU (NGEU) as a catalyst for the promotion of the international role of the euro

E-print/Working paper (2023)

Recent developments in the global arena such as the COVID-19 pandemic and stresses in energy markets, made it clear that it is critical for the EU to ensure its strategic autonomy in the macroeconomic ... [more ▼]

Recent developments in the global arena such as the COVID-19 pandemic and stresses in energy markets, made it clear that it is critical for the EU to ensure its strategic autonomy in the macroeconomic field. Strengthening the international role of the euro is one of the key elements in this regard. Through timely analysis of the changes stemming from the establishment of the Next Generation EU (NGEU), we seek to understand to what extent the NGEU can serve as a catalyst for the promotion of the international role of the euro. While it is implausible that the euro will overcome the primacy of the US dollar, we center our analysis around the transformation of the EU’s presence in capital markets. Following massive issuances of green bonds under the NGEU, the EU became the largest issuer of green bonds and has the potential to progress from a small supranational issuer to a sovereign size issuer. This means that the pool of highly rated euro-denominated safe assets will expand significantly. That is where we focus our analysis and where we see the opportunity of the NGEU for unlashing the potential of the euro and boosting its international role. [less ▲]

The Fundamental Value of Art NFTs

E-print/Working paper (2023)

Art-related non-fungible tokens (NFTs) took the digital art space by storm in 2021, generating massive amounts of volume and attracting a large number of users to a previously obscure part of blockchain ... [more ▼]

Art-related non-fungible tokens (NFTs) took the digital art space by storm in 2021, generating massive amounts of volume and attracting a large number of users to a previously obscure part of blockchain technology. Still, very little is known about the attributes that influence the price of these digital assets. This paper attempts to evaluate the level of speculation associated with art NFTs, comprehend the characteristics that confer value on them and design a profitable trading strategy based on our findings. We analyze 860,067 art NFTs that have been deployed on the Ethereum blockchain and have been involved in 317,950 sales using machine learning methods to forecast the probability of sale, the trade frequency and the average price. We find that NFTs are highly speculative assets and that their price and recurrence of sale are heavily determined by the floor and the last sale prices, independent of any fundamental value. [less ▲]

On the pointwise regularity of the Multifractional Brownian Motion and some extensions

E-print/Working paper (2023)

We study the pointwise regularity of the Multifractional Brownian Motion and in particular, we get the existence of slow points. It shows that a non self-similar process can still enjoy this property. We ... [more ▼]

We study the pointwise regularity of the Multifractional Brownian Motion and in particular, we get the existence of slow points. It shows that a non self-similar process can still enjoy this property. We also consider various extensions of our results in the aim of requesting a weaker regularity assumption for the Hurst function without altering the regularity of the process. [less ▲]

Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: a systematic review with meta- analyses

E-print/Working paper (2023)

Background. Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disrupters. Objective. The aim of this work was to conduct a systematic review with meta ... [more ▼]

Background. Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disrupters. Objective. The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity. Methods. The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Results. In total, 354 and 565 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 613 articles after merging duplicates. The papers included in this systematic review were 31: 18 evaluating prenatal exposure to PFASs, 11 childhood exposure, and 2 both. Overall, results were conflicting, with positive, negative, and null associations. 17 papers were included in meta-analyses (12 prenatal, 3 children, and 2 both). The method implemented for data conversion allowed a suitable comparison of different effect estimates. Meta-analyses evaluating the associations between prenatal exposure to PFOA, PFOS, PFNA, PFHxS, and the outcomes BMI, WC, and Dual-Energy X-ray Absorptiometry (DXA) showed no significant results. Meta-analyses for the associations between childhood exposure to PFASs and the outcomes BMI showed no significant results except for a negative association between PFNA and BMI (pooled estimate from a random effect model: -0.045; 95%CI: -0.087, -0.002), however, more studies are required to confirm the strength of this association. Conclusion. To increase the reliability of meta-analyses in environmental epidemiology we suggest the conversion of effect estimates to compare different studies. The pooled evidence of the meta-analyses of the present study suggests that there is no overall association between exposure to PFASs and childhood overweight/obesity. [less ▲]

A Survey on STAR-RIS: Use Cases, Recent Advances, and Future Research Challenges

E-print/Working paper (2023)

The recent development of metasurfaces, which may enable several use cases by modifying the propagation environment, is anticipated to have a substantial effect on the performance of 6G wireless ... [more ▼]

The recent development of metasurfaces, which may enable several use cases by modifying the propagation environment, is anticipated to have a substantial effect on the performance of 6G wireless communications. Metasurface elements can produce essentially passive sub-wavelength scattering to enable a smart radio environment. STAR-RIS, which refers to reconfigurable intelligent surfaces (RIS) that can transmit and reflect concurrently (STAR), is gaining popularity. In contrast to the widely studied RIS, which can only reflect the wireless signal and serve users on the same side as the transmitter, the STAR-RIS can both reflect and refract (transmit), enabling 360-degree wireless coverage, thus serving users on both sides of the transmitter. This paper presents a comprehensive review of the STAR-RIS, with a focus on the most recent schemes for diverse use cases in 6G networks, resource allocation, and performance evaluation. We begin by laying the foundation for RIS (passive, active, STARRIS), and then discuss the STAR-RIS protocols, advantages, and applications. In addition, we categorize the approaches within the domain of use scenarios, which includes increasing coverage, enhancing physical layer security (PLS), maximizing sum rate, improving energy efficiency (EE), and reducing interference. Next, we will discuss the various strategies for resource allocation and measures for performance evaluation. We aimed to elaborate, compare, and evaluate the literature in terms of setup, channel characteristics, methodology, and objectives. In conclusion, we examine the open research problems and potential future prospects in this field. [less ▲]

Interaction of mitochondrial polygenic score and environmental factors in LRRK2 p.Gly2019Ser parkinsonism 2023.01.02.23284113

E-print/Working paper (2023)

The objective of our study was to investigate the impact of the mitochondrial polygenic score (MGS) and lifestyle/environmental data on age at onset in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and ... [more ▼]

The objective of our study was to investigate the impact of the mitochondrial polygenic score (MGS) and lifestyle/environmental data on age at onset in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic Parkinson\textquoterights disease (iPD).In this study, we included N=486 patients with LRRK2-PD and N=9259 patients with iPD from AMP-PD, Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data was utilized to perform the MGS analysis, using 14 Single Nucleotide Polymorphisms (SNPs) from genes causally associated with mitochondrial function and PD risk. Additionally, lifestyle and environmental data were obtained from the PD risk factor questionnaire (PD-RFQ). Correlation analyses and linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO.We observed that higher MGS was associated with earlier AAO in patients with LRRK2-PD (p=4.0\texttimes10-4, β=-0.18) but not in patients with iPD. A correlation between MGS and AAO was visibly stronger in European ancestry LRRK2-PD patients (p=0.01, r=-0.16) than in Tunisian Arab-Berber patients (p=0.44, r=-0.05). We found that the MGS interacted with coffee (p=0.03, β=-0.38) and caffeinated soda consumption (p=0.03, β=-0.37) in LRRK2-PD and with caffeine soda consumption (p=0.047, β=-0.22) and pesticide exposure (p=0.02, β=-0.37) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeine or were exposed to pesticides.The MGS related to mitochondrial function was associated with AAO in LRRK2-PD but not iPD with an ethnic-specific effect. Caffeine consumption or pesticide exposure interacted with MGS to predict PD AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD.Competing Interest StatementCK serves as a medical advisor to Centogene and Retromer Therapeutics and received speaking honoraria from Desitin. The remaining authors declare no conflict of interest.Funding StatementThis project was supported by the DFG RU ProtectMove (DFG FOR2488), the Michael J. Fox Foundation (MJFF-021227 \& MJFF-019271), and the Else Kroener-Fresenius-Stiftung.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethical permission was given by the Ethical Committee of the Institut National de Neurologie and certified by the Ministry of Health, Tunisia.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData sharing is not applicable to this article as no new data were created or analysed in this study. Data used in the preparation of this manuscript were obtained from the Fox Insight database (https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp) on 18/10/2020. For up-to-date information on the study, visit https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp. Data used in the preparation of this article were obtained from the Accelerating Medicine Partnership (AMP) Parkinson\textquoterights Disease (AMP PD) Knowledge Platform. For up-to-date information on the study, visit https://www.amp-pd.org. [less ▲]

From methylation to myelination: epigenomic and transcriptomic profiling of chronic inactive demyelinated multiple sclerosis lesions 2023.01.12.523740

E-print/Working paper (2023)

Introduction In the progressive phase of multiple sclerosis (MS), the hampered differentiation capacity of oligodendrocyte precursor cells (OPCs) eventually results in remyelination failure. We have ... [more ▼]

Introduction In the progressive phase of multiple sclerosis (MS), the hampered differentiation capacity of oligodendrocyte precursor cells (OPCs) eventually results in remyelination failure. We have previously shown that DNA methylation of Id2/Id4 is highly involved in OPC differentiation and remyelination. In this study, we took an unbiased approach by determining genome-wide DNA methylation patterns within chronically demyelinated MS lesions and investigated how certain epigenetic signatures relate to OPC differentiation capacity.Methods We compared genome-wide DNA methylation and transcriptional profiles between chronically demyelinated MS lesions and matched normal-appearing white matter (NAWM), making use of post-mortem brain tissue (n=9/group). DNA methylation differences that inversely correlated with mRNA expression of their corresponding genes were validated for their cell-type specificity in laser-captured OPCs using pyrosequencing. The CRISPR-dCas9-DNMT3a/TET1 system was used to epigenetically edit human-iPSC-derived oligodendrocytes to assess the effect on cellular differentiation.Results Our data show hypermethylation of CpGs within genes that cluster in gene ontologies related to myelination and axon ensheathment. Cell type-specific validation indicates a region-dependent hypermethylation of MBP, encoding for myelin basic protein, in OPCs obtained from white matter lesions compared to NAWM-derived OPCs. By altering the DNA methylation state of specific CpGs within the promotor region of MBP, using epigenetic editing, we show that cellular differentiation can be bidirectionally manipulated using the CRISPR-dCas9-DNMT3a/TET1 system in vitro.Conclusion Our data indicate that OPCs within chronically demyelinated MS lesions acquire an inhibitory phenotype, which translates into hypermethylation of crucial myelination related genes. Altering the epigenetic status of MBP can restore the differentiation capacity of OPCs and possibly boost (re)myelination.Competing Interest StatementThe authors have declared no competing interest. [less ▲]

Cardiovascular risk prediction - a systems medicine approach

E-print/Working paper (2023)

Background Guidelines for the prevention of cardiovascular disease (CVD) have recommended the assessment of the total CVD risk by risk scores. Current risk algorithms are low in sensitivity and ... [more ▼]

Background Guidelines for the prevention of cardiovascular disease (CVD) have recommended the assessment of the total CVD risk by risk scores. Current risk algorithms are low in sensitivity and specificity and they have not incorporated emerging risk markers for CVD. We suggest that CVD risk assessment can be still improved. We have developed a long-term risk prediction model of cardiovascular mortality in patients with stable coronary artery disease (CAD) based on newly available machine learning and on an extended dataset of new biomarkers.Methods 2953 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study were included. 184 laboratory and 21 demographic markers were ranked according to their contribution to risk of cardiovascular (CV) mortality using different data mining approaches. A self-learning bioinformatics workflow, including seven different machine learning algorithms, was developed for CV risk prediction. The study population was stratified into patients with and without significant CAD. Thereby, significant CAD was defined as a lumen narrowing of 50 or more in at least one of the coronary segments or a history of definite myocardial infarction. The machine learning models in both subpopulations were compared with established CV risk assessment tools.Results After a follow-up of 10 years, 603 (20.4%) patients died of cardiovascular causes. 95% patients without CAD deceased within ten years and 247 (13.2 %) patients with CAD within 5 years. Overall and in patients without CAD, NT-proBNP (N-terminal pro B-type natriuretic peptide), TnT (Troponin T), estimated cystatin c based GFR (glomerular filtration rate) and age were the highest ranked predictors, while in patients with CAD, NT-proBNP, GFR, CT-proAVP (C-terminal pro arginine vasopressin) and TNT were highest predictive. In the comparison with the FRS, PROCAM and ESC risk scores, the machine learning workflow produced more accurate and robust CV mortality prediction in patients without CAD. Equivalent CV risk prediction was obtained in the CAD subpopulation in comparison with the Marschner risk score. Overall, the existing algorithms in general tend to assign more patients into the medium risk groups, while the machine learning algorithms tend to have a clearer risk/no risk assignment. The framework is available upon request.Conclusion We have developed a fully automated and self-validating computational framework of machine learning techniques using an extensive database of clinical, routinely and non-routinely measured laboratory data. Our framework predicts long-term CV mortality at least as accurate as existing CVD risk scores. A combination of four highly ranked biomarkers and the random forest approach showed the best predictive results. Moreover, a dynamic computational model has several advantages over static CVD risk prediction tools: it is freeware, transparent, variable, transferable and expandable to any population, types of events and time frames. [less ▲]

Self-Supervised Learning for Place Representation Generalization across Appearance Changes

E-print/Working paper (2023)

What can inform us about the arrival of daily extreme stock market events?

E-print/Working paper (2023)

Estimator selection for regression functions in exponential families with application to changepoint detection

E-print/Working paper (2023)

Covariant Riesz transform on differential forms for 1<p\leq2

E-print/Working paper (2022)

Distributionally robust optimal allocation with costly verification

E-print/Working paper (2022)

Is Bitcoin a better safe-haven asset for individual investors than Gold? – Evidence from sanctioned Russia

E-print/Working paper (2022)

Extensive research on safe-haven assets has been conducted in the literature. An important finding is that safe-haven assets are frequently used by institutional investors, such as pension funds and ... [more ▼]

Extensive research on safe-haven assets has been conducted in the literature. An important finding is that safe-haven assets are frequently used by institutional investors, such as pension funds and investment banks, to ride out high volatility. However, the issue of whether individual investors can benefit from it during a financial crisis has not been adequately addressed. Using the case of sanctioned Russia, we attempt to study whether Bitcoin as a decentralized asset can play a more useful role than gold to protect individual investors when the majority of safe-haven assets are restricted from transactions. Our main results show that both assets exhibit intraday weak safe-haven properties against the ruble. However, gold saw a waning trend compared with its historical performance, whereas Bitcoin’s capability increased during this period. Further sentiment analysis demonstrates Russian investors’ positive attitudes regarding Bitcoin boosting its price in response to the ruble’s depreciation. The return on gold is more likely to be impacted by international investors who are concerned about global uncertainties. [less ▲]

The Zoom City: Working From Home, Urban Productivity and Land Use

E-print/Working paper (2022)

Who will benefit and who will lose from a permanent increase in working from home (WFH)? This paper investigates the impact of WFH on cities of different sizes, highlights the dangers of too much WFH, and ... [more ▼]

Who will benefit and who will lose from a permanent increase in working from home (WFH)? This paper investigates the impact of WFH on cities of different sizes, highlights the dangers of too much WFH, and discusses aspects of the disagreement between workers and firms. Our results suggest that WFH raises urban productivity and average wages only in large cities. We also study the optimal fraction of WFH and show that workers-residents have incentives to adopt an inefficiently high WFH scheme. The implementation of remote work in the short run---at fixed rents and wages---implies higher benefits for long-distance commuters and lower benefits or even losses for short-distance ones. It also implies benefits for some firms and losses for others, which potentially explains the low prevalence of WFH before the pandemic. Finally, we show that advances in digital technology, which increase the productivity of remote workers, lead to increased welfare benefits. A calibration exercise for the average and the largest European capital cities sheds more light on the impact of WFH on cities of different sizes. [less ▲]

FastCycle: A Message Sharing Framework for Modular Automated Driving Systems

E-print/Working paper (2022)

Automated Driving Systems (ADS) have rapidly evolved in recent years and their architecture becomes sophisticated. Ensuring robustness, reliability and safety of performance is particularly important. The ... [more ▼]

Automated Driving Systems (ADS) have rapidly evolved in recent years and their architecture becomes sophisticated. Ensuring robustness, reliability and safety of performance is particularly important. The main challenge in building an ADS is the ability to meet certain stringent performance requirements in terms of both making safe operational decisions and finishing processing in real-time. Middlewares play a crucial role to handle these requirements in ADS. The way middlewares share data between the different system components has a direct impact on the overall performance, particularly the latency overhead. To this end, this paper presents FastCycle as a lightweight multi-threaded zero-copy messaging broker to meet the requirements of a high fidelity ADS in terms of modularity, real-time performance and security. We discuss the architecture and the main features of the proposed framework. Evaluation of the proposed framework based on standard metrics in comparison with popular middlewares used in robotics and automated driving shows the improved performance of our framework. The implementation of FastCycle and the associated comparisons with other frameworks are open sourced. [less ▲]

#Involution - Didaktischer Kommentar

E-print/Working paper (2022)

Forecasting of a complex microbial community using meta-omics

E-print/Working paper (2022)

Microbial communities are complex assemblages whose dynamics are shaped by abiotic and biotic factors. A major challenge concerns correctly forecasting the community behaviour in the future. In this ... [more ▼]

Microbial communities are complex assemblages whose dynamics are shaped by abiotic and biotic factors. A major challenge concerns correctly forecasting the community behaviour in the future. In this context, communities in biological wastewater treatment plants (BWWTPs) represent excellent model systems, because forecasting them is required to ultimately control and operate the plants in a sustainable manner. Here, we forecast the microbial community from the water-air interface of the anaerobic tank of a BWWTP via longitudinal meta-omics (metagenomics, metatranscriptomics and metaproteomics) data covering 14 months at weekly intervals. We extracted all the available time-dependent information, summarised it in 17 temporal signals (explaining 91.1 of the temporal variance) and linked them over time to rebuild the sequence of ecological phenomena behind the community dynamics. We forecasted the signals over the following five years and tested the predictions with 21 extra samples. We were able to correctly forecast five signals accounting for 22.5 of the time-dependent information in the system and generate mechanistic predictions on the ecological events in the community (e.g. a predation cycle involving bacteria, viruses and amoebas). Through the forecasting of the 17 signals and the environmental variables readings we reconstructed the gene abundance and expression for the following 5 years, showing a nearly perfect trend prediction (coefficient of determination >= 0.97) for the first 2 years. The study demonstrates the maturity of microbial ecology to forecast composition and gene expression of open microbial ecosystems using year-spanning interactions between community cycles and environmental parameters. [less ▲]

Second Order Bismut formulae and applications to Neumann semigroups on manifolds

E-print/Working paper (2022)

Equivariant elliptic cohomology, toric varieties, and derived equivalences

E-print/Working paper (2022)

Optimal coalition splitting with heterogenous strategies

E-print/Working paper (2022)

We consider a group of players initially members of a coalition managing cooperatively a public bad, in this case, the stock of pollution. Countries are technologically heterogeneous but the pollution ... [more ▼]

We consider a group of players initially members of a coalition managing cooperatively a public bad, in this case, the stock of pollution. Countries are technologically heterogeneous but the pollution damage is uniform. We essentially attempt to characterize the conditions under which a country may eventually split and when it splits within an infinite horizon multi-stage differential game. In contrast to the existing literature, we do not assume that after splitting, the splitting player and the remaining coalition will adopt Markovian strategies. Instead, we assume that the latter will remain committed to the collective control of pollution and play open-loop, while the splitting player plays Markovian. Within a full linear-quadratic model, we characterize the optimal strategies. We later compare with the outcomes of the case where the splitting player and the remaining coalition play both Markovian. We highlight several interesting results in terms of the implications for long- term pollution levels and the duration of coalitions with heterogeneous strategies. [less ▲]

EU acts without binding legal force producing binding legal effects at the national level: Enforcement of ESA soft law in the Czech Republic

E-print/Working paper (2022)

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

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

Optimal Timing of Carbon Capture and Storage Policies - a Social Planner's View

E-print/Working paper (2022)

Carbon capture and storage (CCS) is considered one of the most realistic and plausible options for reducing greenhouse gas (GHG) emissions from large pollution sources. However, CCS deployment is costly ... [more ▼]

Carbon capture and storage (CCS) is considered one of the most realistic and plausible options for reducing greenhouse gas (GHG) emissions from large pollution sources. However, CCS deployment is costly. This paper considers the social cost of CCS projects and GHG damage from a central planer's point of view, providing clear information about when each player should deploy CCS. The findings are twofold: (1) given the heterogeneity of players, it is not socially optimal for all players to start CCS projects at the same time; instead, the player that has a cost advantage should start first; (2) it may be socially desirable for the player with a cost disadvantage never starts CCS. We show the conditions that support both possibilities. The second finding provides a clear policy guideline for the decision-maker: reduce the costs of the high-cost player in order to reduce global GHG emissions, provided that is the aim of the supranational institute. [less ▲]

Integration of external biomass reactions into existing metabolic models

E-print/Working paper (2022)

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

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

Agent-based Model of Initial Token Allocations: Evaluating Wealth Concentration in Fair Launches

E-print/Working paper (2022)

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

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

How to make users adopt more sustainable cryptocurrencies: Evidence from Nigeria

E-print/Working paper (2022)

Some of the most popular decentralised cryptocurrency networks have drawn widespread criticism for consuming vast amounts of electricity and have thus become targets of regulatory interest. Attempts to ... [more ▼]

Some of the most popular decentralised cryptocurrency networks have drawn widespread criticism for consuming vast amounts of electricity and have thus become targets of regulatory interest. Attempts to influence cryptocurrency network operations via policy in the pursuit of sustainability in the past, however, have been widely unsuccessful. Some were abandoned out of fear of jeopardising innovation while others failed due to the highly globalised nature of decentralised systems. Considering Bitcoin as an archetype for cryptocurrencies with high energy demand, this study takes a bottom-up approach by analysing statements made by Nigerian cryptocurrency users (N = 158) concerning their perception of sustainability issues. Three main findings emerged: 1) Despite self-reporting as highly knowledgeable, most participants significantly underestimate the energy demand of Bitcoin. 2) Those who accurately assess the energy demand of Bitcoin are more likely to support measures targeting its energy demand than those who misestimate it. 3) Those who support measures predominantly hold private actors responsible. In light of these findings, it is concluded that the primary task of policy makers in the context of cryptocurrency sustainability is to enforce consumer education. [less ▲]

Arbeitnehmer in Luxemburg wünschen sich verstärkt eine Reduktion ihrer vertraglichen Arbeitszeit

E-print/Working paper (2022)

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

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

Genome-wide meta-analysis of over 29,000 people with epilepsy reveals 26 loci and subtype-specific genetic architecture

E-print/Working paper (2022)

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

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

Job Location Decisions and the Effect of Children on the Employment Gender Gap

E-print/Working paper (2022)

A model-based approach to density estimation in sup-norm

E-print/Working paper (2022)

Building on the l−estimators of Baraud, we define a general method for finding a quasi-best approximant in sup-norm to a target density p⋆ belonging to a given model m, based on independent samples drawn ... [more ▼]

Building on the l−estimators of Baraud, we define a general method for finding a quasi-best approximant in sup-norm to a target density p⋆ belonging to a given model m, based on independent samples drawn from distributions p⋆i which average to p⋆ (which does not necessarily belong to m). We also provide a general method for selecting among a countable family of such models. Both of these esti- mators satisfy oracle inequalities in the general setting. The quality of the bounds depends on the volume of sets C on which |f| is close to its maximum, where f = p − q for some p, q ∈ m (or p ∈ m and q ∈ m′, in the case of model selection). In particular, using piecewise polynomials on dyadic partitions of Rd, we recover optimal rates of convergence for classes of functions with anisotropic smoothness, with optimal depen- dence on semi-norms measuring the smoothness of p⋆ in the coordinate directions. Moreover, our method adapts to the anisotropic smoothness, as long as it is smaller than 1 plus the degree of the polynomials. [less ▲]

Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1- and PRKN-linked Parkinson's disease 2022.05.17.22275087

E-print/Working paper (2022)

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

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

Erinnerungspolitik und –praxis in Luxemburg am Beispiel einer gegenwärtigen Kontroverse

E-print/Working paper (2022)

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

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

Internship and Public History Training

E-print/Working paper (2022)

Findings from the ÉpStan National Education Monitoring against the Background of the COVID-19 Pandemic

E-print/Working paper (2022)

Federated Geometric Monte Carlo Clustering to Counter Non-IID Datasets

E-print/Working paper (2022)

Federated learning allows clients to collaboratively train models on datasets that are acquired in different locations and that cannot be exchanged because of their size or regulations. Such collected ... [more ▼]

Federated learning allows clients to collaboratively train models on datasets that are acquired in different locations and that cannot be exchanged because of their size or regulations. Such collected data is increasingly non-independent and non- identically distributed (non-IID), negatively affecting training accuracy. Previous works tried to mitigate the effects of non- IID datasets on training accuracy, focusing mainly on non-IID labels, however practical datasets often also contain non-IID features. To address both non-IID labels and features, we propose FedGMCC1, a novel framework where a central server aggregates client models that it can cluster together. FedGMCC clustering relies on a Monte Carlo procedure that samples the output space of client models, infers their position in the weight space on a loss manifold and computes their geometric connection via an affine curve parametrization. FedGMCC aggregates connected models along their path connectivity to produce a richer global model, incorporating knowledge of all connected client models. FedGMCC outperforms FedAvg and FedProx in terms of convergence rates on the EMNIST62 and a genomic sequence classification datasets (by up to +63%). FedGMCC yields an improved accuracy (+4%) on the genomic dataset with respect to CFL, in high non-IID feature space settings and label incongruency. [less ▲]

Finite Mixture Models for an underlying Beta distribution with an application to COVID-19 data

E-print/Working paper (2022)

Does (Re-)Entering the Labor Market at Advanced Ages Protect Against Cognitive Decline? A Panel-Matching Difference-in-differences Approach

E-print/Working paper (2022)

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

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

Die Vielfalt der Sozialen Arbeit in Luxemburg und die Arbeitsmarktzahlen 2021

E-print/Working paper (2022)

Dieser Newsletter beschreibt den Arbeitsmarkt der Sozialen Arbeit in Luxemburg 2021, gibt einen Überblick über die Berufsqualifikationen und die Vielfalt der Praxisfelder und spezifischen Arbeitsbereiche.

CNV-ClinViewer: Enhancing the clinical interpretation of large copy-number variants online

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 ▲]

‘Entropy in Differing Constitutional Traditions? Standing in Climate Actions across the EU before the Court of Justice and National Courts

E-print/Working paper (2022)