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See detailMännerbund, Staatsschiff, Multitude. U-Boote und Raumfahrzeuge als politische Körper
Gradinari, Irina; Pause, Johannes UL

in COLLATERAL: Online Journal for Cross-Cultural Close Reading (2022), 32

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See detailCritical Review of the ATAD Implementation: The Implementation of the ATAD in Luxembourg
Pantazatou, Aikaterini UL

in Intertax (2022), 50(1), 56-65

This article examines the implementation of the ATAD in Luxembourg. Specifically, it analyses all the additions and amendments that had to be made into Luxembourg law, due to the ATAD. It does so in an ... [more ▼]

This article examines the implementation of the ATAD in Luxembourg. Specifically, it analyses all the additions and amendments that had to be made into Luxembourg law, due to the ATAD. It does so in an analytical and critical manner by going through all ATAD anti-avoidance provisions and examining the way they were implemented into Luxembourg law and how they differentiate from the previous rules (if they existed at all). It also critically assesses whether these changes have given rise to any inconsistencies or remaining questions. [less ▲]

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See detailFostering experimental and computational synergy to modulate hyperinflammation
Del Sol Mesa, Antonio UL

in Trends in Immunology (2022), 43(1),

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See detailHow injury prevention programs are being structured and implemented worldwide: An international survey of sports physical therapists
Ley, Christophe UL; Mendonça, Luciana D.; Schuermans, Joke et al

in Physical Therapy in Sport (2022), 53

Objective To identify the role of sports physical therapists (PT) in the injury prevention process and to compare the structure of preventive programs and associated (organization) policies applied in ... [more ▼]

Objective To identify the role of sports physical therapists (PT) in the injury prevention process and to compare the structure of preventive programs and associated (organization) policies applied in athletic organizations and sports teams of varying gender and level world-wide. Design: cross-sectional study. Setting LimeSurvey platform. Participants Sports PT working with athletes invited through the International Federation of Sports Physical Therapy. Main outcome measures Sports injury prevention program (IPP) structure and implementation. Results 414 participants fully participate in this survey study. Athlete's injury history (68.84%), the most common injuries within the sport modality (67.87%) and athlete's preseason screening results (64.01%) were most frequently used to customize IPPs. Warm-up (70.04%) and individually PT-guided exercise-therapy (70.04%) were the preferred methods to organize the prevention routine. The main barrier for IPP implementation was lack of time within the athlete's weekly training schedule (66.66%). The majority of the participants (72.84%) reported to evaluate the perception of IPP's effect by comparing current and preceding seasons' injury occurrences. Conclusion These survey results are the first identifying contemporary sports injury prevention organization and implementation policies on an international level. This information might support the sports PT community in improving and standardizing IPP (implementation) strategies worldwide. [less ▲]

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See detailHow injury registration and preseason assessment are being delivered : an international survey of sports physical therapists
Ley, Christophe UL; Mendonça, Luciana D.; Schuermans, Joke et al

in Physical Therapy in Sport (2022), 53

Objective To identify the role of sports physical therapists (PT) in the organization of injury registration and preseason assessment, applied in athletic organizations and sports teams of different ... [more ▼]

Objective To identify the role of sports physical therapists (PT) in the organization of injury registration and preseason assessment, applied in athletic organizations and sports teams of different gender and level world-wide. Design cross-sectional study. Setting LimeSurvey platform. Participants Sports PTs working with athletes invited through International Federation of Sports Physical Therapy. Main outcome measures injury registration and athlete's screening. Results 414 sports PTs participated in this international survey (mean age of 37.66 (SD = 9.38) years). 340 participants indicated that the PT as the responsible for injury registration. Barriers to properly register injury throughout the season were indicated by 157 sports PT and 86 (54.77%) indicated a lack of time on their routine as the main factor. 93 participants (30.09%) indicated that they customize the prevention program based on the preseason assessment. Sports PTs who reported not performing a preseason assessment (92 participants - 22.22%) mainly indicated this to be consequence of lack of structure in the organization (44 participants – 47.82%). Conclusion The majority of the sports PTs participate on injury registration and perform preseason assessment in athletes. However, lack of time in their routine and structure in the organization were recognized as the most important barriers to organize these properly. [less ▲]

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See detailFrom communities to protein complexes: A local community detection algorithm on PPI networks
Dilmaghani, Saharnaz; Brust, Mathias UL; Ribeiro, Carlos H. et al

in PLoS ONE (2022), 17(1), 1-17

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See detailThe Myth of Beirut’s Resilience: Introduction to the Thematic Issue
Buccianti-Barakat, Liliane; Hesse, Markus UL

in Urban Planning (2022), 7(1), 82-86

This editorial introduces a thematic issue of Urban Planning on recent developments in Beirut, Lebanon. It emphasises the multiple crises the city has been undergoing for some time, which include an ... [more ▼]

This editorial introduces a thematic issue of Urban Planning on recent developments in Beirut, Lebanon. It emphasises the multiple crises the city has been undergoing for some time, which include an enduring political and economic crisis, the impact of the Covid‐19 pandemic, and most recently the devastating impact of the blast that happened in the port of Beirut on 4th August 2020. The editorial outlines the specific challenges resulting from these crises and addresses the concept of resilience, which is taken up by the articles included in this issue. [less ▲]

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See detailOpinion Statement ECJ-TF 2/2021 on the ECJ Decision of 25 February 2021 in Société Générale (Case C-403/19) on the Calculation of the Maximum Amount of a Foreign Direct Tax Credit
Kofler, Georg; Garcia Prats, Alfredo; Haslehner, Werner UL et al

in European Taxation (2022)

The Court’s decision in Société Générale reinforces established case law that EU law neither prohibits juridical double taxation nor does it impose an obligation on the residence Member State to prevent ... [more ▼]

The Court’s decision in Société Générale reinforces established case law that EU law neither prohibits juridical double taxation nor does it impose an obligation on the residence Member State to prevent the disadvantages that could arise from the exercise of competence thus attributed by the two Member States. The parallel existence of taxing jurisdiction, however, must be distinguished from the exercise of such jurisdiction by each Member State. While Member States are free to determine the connecting factors for the allocation of taxing jurisdiction in tax treaties, in exercising the “power of taxation, so allocated by bilateral conventions for the avoidance of double taxation, the Member States must comply with EU rules and, more particularly, observe the principle of equal treatment”. It is generally accepted in the Court’s case law that both the ordinary credit and exemption (including exemption with progression) methods are permissible to avoid double taxation. In Société Générale, this position was confirmed, specifically as regards the “maximum deduction” under the ordinary credit method in tax treaties, even though this treatment can result in a disadvantage for cross-border income as compared with domestic income. As the disadvantage in Société Générale was due to the difference between gross-basis taxation of dividends in the source Member States (Italy, the Netherlands and the United Kingdom) and net-basis taxation of those foreign-sourced dividends in the residence state (France), it remains to be seen whether or not future cases will bring clarity in light of the Seabrokers decision of the EFTA Court, which examined how expenses can be lawfully allocated to foreign income from the perspective of the residence Member State. [less ▲]

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See detailUncertainty-driven symmetry-breaking and stochastic stability in a generic differential game of lobbying
Boucekkine, Raouf; Fabien, Prieur; Ruan, Weihua et al

in Economic Theory (2022)

We study a 2-players stochastic differential game of lobbying. Players invest in lobbying activities to alter the legislation in her own benefit. The payoffs are quadratic and uncertainty is driven by a ... [more ▼]

We study a 2-players stochastic differential game of lobbying. Players invest in lobbying activities to alter the legislation in her own benefit. The payoffs are quadratic and uncertainty is driven by a Wiener process. We consider the Nash symmetric game where players face the same cost and extract symmetric payoffs, and we solve for Markov Perfect Equilibria (MPE) in the class of affine functions. First, we prove a general sufficient (catching up) optimality condition for two-players stochastic games with uncertainty driven by Wiener processes. Second, we prove that the number and nature of MPE depend on the extent of uncertainty (i.e the variance of the Wiener processes). In particular, we prove that while a symmetric MPE always exists, two asymmetric MPE emerge if and only if uncertainty is large enough. Third, we study the stochastic stability of all the equilibria. We notably find, that the state converges to a stationary invariant distribution under asymmetric MPE. Fourth, we study the implications for rent dissipation asymptotically and compare the outcomes of symmetric vs asymmetric MPE in this respect, ultimately enhancing again the role of uncertainty. [less ▲]

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See detailLeveraging stretching directions for stationkeeping in Earth-Moon halo orbits
Muralidharan, Vivek UL; Howell, Kathleen C.

in Advances in Space Research (2022), 69(1), 620-646

Near Rectilinear Halo Orbits (NRHOs) are stable or nearly stable orbits that are defined as part of the L1 and L2 halo orbit families in the circular restricted three-body problem. Within the Earth-Moon ... [more ▼]

Near Rectilinear Halo Orbits (NRHOs) are stable or nearly stable orbits that are defined as part of the L1 and L2 halo orbit families in the circular restricted three-body problem. Within the Earth-Moon regime, the L1 and L2 NRHOs are proposed as long horizon trajectories for cislunar exploration missions, including NASA’s upcoming Gateway mission. The spacecraft, however, incurs continuous deviations due to unmodeled forces and orbit determination errors in this dynamically sensitive region. The current investigation focuses on an impulsive stationkeeping technique to maintain the spacecraft near a virtual reference orbit despite these uncertainties. The flow dynamics in the region are utilized to identify appropriate maneuver and target locations. The investigation reflects the impact of various factors on maneuver cost and efficacy. For orbits where position and velocity states are particularly sensitive to epoch time, an additional feedback control strategy is applied for phasing constraints. [less ▲]

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See detailRepresentaciones (ficticias) de un pequeño medio literario: el caso de la literatura luxemburguesa
Glesener, Jeanne UL

in Theory Now: journal of literature, critique, and thought (2022), 5(1), 77-96

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See detailComparison of high-performance and conventional internal insulation materials based on hygrothermal analysis using in situ measurements and simulation
Latz, Sebastian UL; Maas, Stefan UL; Scholzen, Frank UL et al

in Bauphysik (2022), 1

Following the European directive to reduce CO2 emissions of existing buildings by improving energy efficiency, internal insulation systems play a central role in the renovation of historically valuable ... [more ▼]

Following the European directive to reduce CO2 emissions of existing buildings by improving energy efficiency, internal insulation systems play a central role in the renovation of historically valuable buildings which cannot be insulated from the outside for reasons of monumental protection, or in cases where no additional exterior space is available. However, besides the thermal property of insulation systems, there are other relevant properties to be considered before choosing an internal insulation system, such as the hygrothermal behavior which plays a particularly important role in diffusion-open interior insulation systems. As the internal insulation layer reduces the temperature of the existing wall during the heating season, its drying potential after rain events is considerably reduced. In addition to the effects of moisture from the outside (mainly wind driven rain), the entry of humidity from the inside through diffusion plays an important role. In the presented study, high performance insulation materials with nanostructure based on silicon dioxide and polyurethane are compared to conventional material based on wood fiber from a hygrothermal point of view by analyzing in situ measurements and simulations. [less ▲]

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See detailSupply chain design for industrial additive manufacturing
Friedich, Anne; Lange, Anne UL; Elbert, Ralf

in International Journal of Operations and Production Management (2022)

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See detailKibble-Zurek mechanism for nonequilibrium phase transitions in driven systems with quenched disorder
Reichhardt, C. J. O.; Del Campo Echevarria, Adolfo UL; Reichhardt, C.

in Communications Physics (2022)

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See detailProject-based learning course on metabolic network modelling in computational systems biology.
Sauter, Thomas UL; Bintener, Tamara; Kishk, Ali UL et al

in PLoS computational biology (2022), 18(1), 1009711

Project-based learning (PBL) is a dynamic student-centred teaching method that encourages students to solve real-life problems while fostering engagement and critical thinking. Here, we report on a PBL ... [more ▼]

Project-based learning (PBL) is a dynamic student-centred teaching method that encourages students to solve real-life problems while fostering engagement and critical thinking. Here, we report on a PBL course on metabolic network modelling that has been running for several years within the Master in Integrated Systems Biology (MISB) at the University of Luxembourg. This 2-week full-time block course comprises an introduction into the core concepts and methods of constraint-based modelling (CBM), applied to toy models and large-scale networks alongside the preparation of individual student projects in week 1 and, in week 2, the presentation and execution of these projects. We describe in detail the schedule and content of the course, exemplary student projects, and reflect on outcomes and lessons learned. PBL requires the full engagement of students and teachers and gives a rewarding teaching experience. The presented course can serve as a role model and inspiration for other similar courses. [less ▲]

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See detailA Longitudinal Study of the Effects of Well-being and Perceived Control on Preparations for Old Age: Moderation Effects of Contexts
Park, Jeongsoo; Hess, Thomas M.; Fung, Helene H. et al

in European Journal of Ageing (2022)

Extending research on determinants of preparations for old age across adulthood, we examined the relationship between well-being, perceived control, and preparations for old age over time, along with ... [more ▼]

Extending research on determinants of preparations for old age across adulthood, we examined the relationship between well-being, perceived control, and preparations for old age over time, along with variation in the strength of these relationships depending on domains of functioning, cultures, and age. We analyzed longitudinal data from the Ageing as Future study assessing changes in well-being, perceived control, and preparations in four different life domains (social relations, finances, work, and health) across a five-year period collected from adults aged from 30 – 85 years in Germany (N= 623), Hong Kong (N= 317), and the United States (N= 315). Positive feelings about one’s current situation predicted greater perceived control five-years later, and vice versa. Also, perceived control and preparations were positively associated over time, with only a few exceptions within each domain. For example, high control beliefs were related to subsequent greater preparations and well-being within the domain of social relations and finances, with weak effects of culture. These results suggest that current well-being may promote adaptive behaviors in later life, with the accumulated effects over time. Thus, focusing on how to improve our well-being may promote engagement in preparations for old age. Our results also indicate that these relations in our model vary by contexts, highlighting the importance of variability in age-related processes. [less ▲]

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See detailInsights from an information thermodynamics analysis of a synthetic molecular motor
Amano, Shuntaro; Esposito, Massimiliano UL; Kreidt, Elisabeth et al

in Nature Chemistry (2022), 14(5), 530-537

Information is physical, a realization that has transformed the physics of measurement and communication. However, the flow between information, energy and mechanics in chemical systems remains largely ... [more ▼]

Information is physical, a realization that has transformed the physics of measurement and communication. However, the flow between information, energy and mechanics in chemical systems remains largely unexplored. Here we analyse a minimalist autonomous chemically driven molecular motor in terms of information thermodynamics, a framework that quantitatively relates information to other thermodynamic parameters. The treatment reveals how directional motion is generated by free energy transfer from chemical to mechanical (conformational and/or co-conformational) processes by `energy flow' and `information flow'. It provides a thermodynamic level of understanding of molecular motors that is general, complements previous analyses based on kinetics and has practical implications for machine design. In line with kinetic analysis, we find that power strokes do not affect the directionality of chemically driven machines. However, we find that power strokes can modulate motor velocity, the efficiency of free energy transfer and the number of fuel molecules consumed per cycle. This may help explain the role of such (co-)conformational changes in biomachines and illustrates the interplay between energy and information in chemical systems. [less ▲]

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See detailIntercorrelated random fields with bounds and the Bayesian identification of their parameters: Application to linear elastic struts and fibers
Rappel, Hussein; Girolami, Mark; Beex, Lars UL

in International Journal for Numerical Methods in Engineering (2022), 123(15), 3418-3463

Many materials and structures consist of numerous slender struts or fibers. Due to the manufacturing processes of different types of struts and the growth processes of natural fibers, their mechanical ... [more ▼]

Many materials and structures consist of numerous slender struts or fibers. Due to the manufacturing processes of different types of struts and the growth processes of natural fibers, their mechanical response frequently fluctuates from strut to strut, as well as locally within each strut. In associated mechanical models each strut is often represented by a string of beam elements, since the use of conventional three-dimensional finite elements renders the simulations computationally inefficient. The parameter input fields of each string of beam elements are ideally such that the local fluctuations and fluctuations between individual strings of beam elements are accurately captured. The goal of this study is to capture these fluctuations in several intercorrelated bounded random fields. Two formulations to describe the intercorrelations between each random field, as well as the case without any intercorrelation, are investigated. As only a few sets of input fields are available (due to time constraints of the supposed experimental techniques), the identification of the random fields’ parameters involves substantial uncertainties. A probabilistic identification approach based on Bayes’ theorem is employed to treat the involved uncertainties. [less ▲]

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See detailHyperideal polyhedra in the 3-dimensional anti-de Sitter space
Chen, Qiyu UL; Schlenker, Jean-Marc UL

in Advances in Mathematics (2022), 404(Paper No. 108441, 61 pp),

We study hyperideal polyhedra in the 3-dimensional anti-de Sitter space AdS3, which are defined as the intersection of the projective model of AdS3 with a convex polyhedron in RP3 whose vertices are all ... [more ▼]

We study hyperideal polyhedra in the 3-dimensional anti-de Sitter space AdS3, which are defined as the intersection of the projective model of AdS3 with a convex polyhedron in RP3 whose vertices are all outside of AdS3 and whose edges all meet AdS3. We show that hyperideal polyhedra in AdS3 are uniquely determined by their combinatorics and dihedral angles, as well as by the induced metric on their boundary together with an additional combinatorial data, and describe the possible dihedral angles and the possible induced metrics on the boundary. [less ▲]

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See detailWoran forschen Sie?
Uhrmacher, Martin UL

in Forum für Politik, Gesellschaft und Kultur in Luxemburg (2022), 423

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See detailMechanistically Coupled PK (MCPK) Model to Describe Enzyme Induction and Occupancy Dependent DDI of Dabrafenib Metabolism.
Albrecht, Marco; Kogan, Yuri; Kulms, Dagmar et al

in Pharmaceutics (2022), 14(2),

Dabrafenib inhibits the cell proliferation of metastatic melanoma with the oncogenic BRAF(V600)-mutation. However, dabrafenib monotherapy is associated with pERK reactivation, drug resistance, and ... [more ▼]

Dabrafenib inhibits the cell proliferation of metastatic melanoma with the oncogenic BRAF(V600)-mutation. However, dabrafenib monotherapy is associated with pERK reactivation, drug resistance, and consequential relapse. A clinical drug-dose determination study shows increased pERK levels upon daily administration of more than 300 mg dabrafenib. To clarify whether such elevated drug concentrations could be reached by long-term drug accumulation, we mechanistically coupled the pharmacokinetics (MCPK) of dabrafenib and its metabolites. The MCPK model is qualitatively based on in vitro and quantitatively on clinical data to describe occupancy-dependent CYP3A4 enzyme induction, accumulation, and drug-drug interaction mechanisms. The prediction suggests an eight-fold increase in the steady-state concentration of potent desmethyl-dabrafenib and its inactive precursor carboxy-dabrafenib within four weeks upon 150 mg b.d. dabrafenib. While it is generally assumed that a higher dose is not critical, we found experimentally that a high physiological dabrafenib concentration fails to induce cell death in embedded 451LU melanoma spheroids. [less ▲]

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See detailInterrogating the effect of enzyme kinetics on metabolism using differentiable constraint-based models
Wilken, St Elmo; Besançon, Mathieu; Kratochvil, Miroslav UL et al

in Metabolic Engineering (2022)

Metabolic models are typically characterized by a large number of parameters. Traditionally, metabolic control analysis is applied to differential equation-based models to investigate the sensitivity of ... [more ▼]

Metabolic models are typically characterized by a large number of parameters. Traditionally, metabolic control analysis is applied to differential equation-based models to investigate the sensitivity of predictions to parameters. A corresponding theory for constraint-based models is lacking, due to their formulation as optimization problems. Here, we show that optimal solutions of optimization problems can be efficiently differentiated using constrained optimization duality and implicit differentiation. We use this to calculate the sensitivities of predicted reaction fluxes and enzyme concentrations to turnover numbers in an enzyme-constrained metabolic model of Escherichia coli. The sensitivities quantitatively identify rate limiting enzymes and are mathematically precise, unlike current finite difference based approaches used for sensitivity analysis. Further, efficient differentiation of constraint-based models unlocks the ability to use gradient information for parameter estimation. We demonstrate this by improving, genome-wide, the state-of-the-art turnover number estimates for E. coli. Finally, we show that this technique can be generalized to arbitrarily complex models. By differentiating the optimal solution of a model incorporating both thermodynamic and kinetic rate equations, the effect of metabolite concentrations on biomass growth can be elucidated. We benchmark these metabolite sensitivities against a large experimental gene knockdown study, and find good alignment between the predicted sensitivities and in vivo metabolome changes. In sum, we demonstrate several applications of differentiating optimal solutions of constraint-based metabolic models, and show how it connects to classic metabolic control analysis. [less ▲]

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See detailDie 22. Legion, der Rhein und die Binnenschifffahrt bei den Legionen des Imperium Romanum
Groff, Thierry UL

in Mainzer Zeitschrift. Mittelrheinisches Jahrbuch für Archäologie, Kunst und Geschichte (2022), 117

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See detailA new approach to model categorical homotopy fiber sequences
Govzmann, Alisa UL; Pistalo, Damjan UL; Poncin, Norbert UL

in Dissertationes Mathematicae (2022), doi: 10.4064/dm858-5-2022

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See detailNeurodegeneration and neuroinflammation are linked, but independent of a-synuclein inclusions, in a seeding/spreading mouse model of Parkinson's disease
Garcia, Pierre UL; Wemheuer, W.; Uriarte, O. et al

in Glia (2022)

A key pathological process in Parkinson's disease (PD) is the transneuronal spreading of α-synuclein. Alpha-synuclein (α-syn) is a presynaptic protein that, in PD, forms pathological inclusions. Other ... [more ▼]

A key pathological process in Parkinson's disease (PD) is the transneuronal spreading of α-synuclein. Alpha-synuclein (α-syn) is a presynaptic protein that, in PD, forms pathological inclusions. Other hallmarks of PD include neurodegeneration and microgliosis in susceptible brain regions. Whether it is primarily transneuronal spreading of α-syn particles, inclusion formation, or other mechanisms, such as inflammation, that cause neurodegeneration in PD is unclear. We used a model of spreading of α-syn induced by striatal injection of α-syn preformed fibrils into the mouse striatum to address this question. We performed quantitative analysis for α-syn inclusions, neurodegeneration, and microgliosis in different brain regions, and generated gene expression profiles of the ventral midbrain, at two different timepoints after disease induction. We observed significant neurodegeneration and microgliosis in brain regions not only with, but also without α-syn inclusions. We also observed prominent microgliosis in injured brain regions that did not correlate with neurodegeneration nor with inclusion load. Using longitudinal gene expression profiling, we observed early gene expression changes, linked to neuroinflammation, that preceded neurodegeneration, indicating an active role of microglia in this process. Altered gene pathways overlapped with those typical of PD. Our observations indicate that α-syn inclusion formation is not the major driver in the early phases of PD-like neurodegeneration, but that microglia, activated by diffusible, oligomeric α-syn, may play a key role in this process. Our findings uncover new features of α-syn induced pathologies, in particular microgliosis, and point to the necessity for a broader view of the process of α-syn spreading. [less ▲]

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See detailLeveraging the Potential of Digital Technology for Better Individualized Treatment of Parkinson's Disease.
Fröhlich, Holger; Bontridder, Noémi; Petrovska-Delacréta, Dijana et al

in Frontiers in neurology (2022), 13

Recent years have witnessed a strongly increasing interest in digital technology within medicine (sensor devices, specific smartphone apps) and specifically also neurology. Quantitative measures derived ... [more ▼]

Recent years have witnessed a strongly increasing interest in digital technology within medicine (sensor devices, specific smartphone apps) and specifically also neurology. Quantitative measures derived from digital technology could provide Digital Biomarkers (DMs) enabling a quantitative and continuous monitoring of disease symptoms, also outside clinics. This includes the possibility to continuously and sensitively monitor the response to treatment, hence opening the opportunity to adapt medication pathways quickly. In addition, DMs may in the future allow early diagnosis, stratification of patient subgroups and prediction of clinical outcomes. Thus, DMs could complement or in certain cases even replace classical examiner-based outcome measures and molecular biomarkers measured in cerebral spinal fluid, blood, urine, saliva, or other body liquids. Altogether, DMs could play a prominent role in the emerging field of precision medicine. However, realizing this vision requires dedicated research. First, advanced data analytical methods need to be developed and applied, which extract candidate DMs from raw signals. Second, these candidate DMs need to be validated by (a) showing their correlation to established clinical outcome measures, and (b) demonstrating their diagnostic and/or prognostic value compared to established biomarkers. These points again require the use of advanced data analytical methods, including machine learning. In addition, the arising ethical, legal and social questions associated with the collection and processing of sensitive patient data and the use of machine learning methods to analyze these data for better individualized treatment of the disease, must be considered thoroughly. Using Parkinson's Disease (PD) as a prime example of a complex multifactorial disorder, the purpose of this article is to critically review the current state of research regarding the use of DMs, discuss open challenges and highlight emerging new directions. [less ▲]

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See detailReal-Time Integrated Learning and Decision Making for Cumulative Shock Degradation
Drent, Melvin UL; Drent, Collin UL; Kapodistria, Stella et al

in Manufacturing and Service Operations Management (2022)

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See detailNo Ensemble Averaging Below the Black Hole Threshold
Schlenker, Jean-Marc UL; Witten, Edward

in Journal of High Energy Physics (2022), 7

In the AdS/CFT correspondence, amplitudes associated to connected bulk manifolds with disconnected boundaries have presented a longstanding mystery. A possible interpretation is that they reflect the ... [more ▼]

In the AdS/CFT correspondence, amplitudes associated to connected bulk manifolds with disconnected boundaries have presented a longstanding mystery. A possible interpretation is that they reflect the effects of averaging over an ensemble of boundary theories. But in examples in dimension D≥3, an appropriate ensemble of boundary theories does not exist. Here we sharpen the puzzle by identifying a class of "sub-threshold" observables that we claim do not show effects of ensemble averaging. These are amplitudes that do not involve black hole states. To support our claim, we explore the example of D=3, and show that connected solutions of Einstein's equations with disconnected boundary never contribute to sub-threshold observables. To demonstrate this requires some novel results about the renormalized volume of a hyperbolic three-manifold, which we prove using modern methods in hyperbolic geometry. Why then do any observables show apparent ensemble averaging? We propose that this reflects the chaotic nature of black hole physics and the fact that the Hilbert space describing a black hole does not have a large N limit. [less ▲]

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See detailStress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1
Capelle, Christophe M.; Chen, Anna; Zeng, Ni et al

in Immunology (2022), 165(4), 428--444

Stress hormones are believed to skew the CD4 T-cell differentiation towards a Th2 response via a T-cell-extrinsic mechanism. Using isolated primary human naïve and memory CD4 T cells, here we show that ... [more ▼]

Stress hormones are believed to skew the CD4 T-cell differentiation towards a Th2 response via a T-cell-extrinsic mechanism. Using isolated primary human naïve and memory CD4 T cells, here we show that both adrenergic- and glucocorticoid-mediated stress signalling pathways play a CD4 naïve T-cell-intrinsic role in regulating the Th1/Th2 differentiation balance. Both stress hormones reduced the Th1 programme and cytokine production by inhibiting mTORC1 signalling via two parallel mechanisms. Stress hormone signalling inhibited mTORC1 in naïve CD4 T cells (1) by affecting the PI3K/AKT pathway and (2) by regulating the expression of the circadian rhythm gene, period circadian regulator 1 (PER1). Both stress hormones induced the expression of PER1, which inhibited mTORC1 signalling, thus reducing Th1 differentiation. This previously unrecognized cell-autonomous mechanism connects stress hormone signalling with CD4 T-cell differentiation via mTORC1 and a specific circadian clock gene, namely PER1. [less ▲]

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See detailApplication of carotenoids in sustainable energy and green electronics
Singh, Ajay UL; Mukherjee, Trinetra

in Materials Advances (2022)

In sustainable development, one of the key factors is the usage of non-toxic and biodegradable natural substances for the development of green energy and technology. Photovoltaics and photoelectrochemical ... [more ▼]

In sustainable development, one of the key factors is the usage of non-toxic and biodegradable natural substances for the development of green energy and technology. Photovoltaics and photoelectrochemical cells are the most promising candidates for renewable solar energy harvesting. Currently, photovoltaics and electronic device technologies are dominated by inorganic semiconductors. Thus, there is a continuous pursuit for alternative eco-friendly semiconductors both for electronics industry and renewable energy technologies. Carotenoids are naturally found coloured pigments which are of semiconducting nature. In nature, they form an integral part of light-harvesting photosystems in photosynthetic organisms, and are also present in several non-photosynthetic organisms playing other functional roles. The structural diversity of carotenoids and their molecular nature make them ideal candidates for devices requiring photo-sensitization, and controlled electrical conduction. Here, we review the potential application of carotenoids, with their advantages, limitations and prospects for further improvement in solar cell technology, photoelectrochemical cells, semiconductor surface modification, and organic electronics in general. We emphasize on the carotenoid based renewable energy production by using carotenoid based dye-sensitized solar cells and water-splitting photoelectrochemical cells. Thereafter, we summarize some of the studies with carotenoid based nanowire, light-emitting diodes, transistors and light sensors. Though, the application of carotenoids in renewable and sustainable technologies are still in nascent stage, prospects are high for carotenoid based solar harvesting and electronic devices that are cheaper, eco-friendly, biodegradable and biocompatible. [less ▲]

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See detailBenchmarking quantum annealing dynamics: The spin-vector Langevin model
Subires, David; Gómez-Ruiz, Fernando J.; Ruiz-García, Antonia et al

in Physical Review Research (2022)

The classical spin-vector Monte Carlo (SVMC) model is a reference benchmark for the performance of a quantum annealer. Yet, as a Monte Carlo method, SVMC is unsuited for an accurate description of the ... [more ▼]

The classical spin-vector Monte Carlo (SVMC) model is a reference benchmark for the performance of a quantum annealer. Yet, as a Monte Carlo method, SVMC is unsuited for an accurate description of the annealing dynamics in real-time.We introduce the spin-vector Langevin (SVL) model as an alternative benchmark in which the time evolution is described by Langevin dynamics. The SVL model is shown to provide a more stringent test than the SVMC model for the identification of quantum signatures in the performance of quantum annealing devices, as we illustrate by describing the Kibble-Zurek scaling associated with the dynamics of symmetry breaking in the transverse field Ising model, recently probed using D-Wave machines. Specifically, we show that D-Wave data are reproduced by the SVL model. [less ▲]

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See detailProbing quantum chaos in multipartite systems
Cao, Zan; Xu, Zhenyu; Del Campo Echevarria, Adolfo UL

in Physical Review Research (2022)

Understanding the emergence of quantum chaos in multipartite systems is challenging in the presence of interactions. We show that the contribution of the subsystems to the global behavior can be revealed ... [more ▼]

Understanding the emergence of quantum chaos in multipartite systems is challenging in the presence of interactions. We show that the contribution of the subsystems to the global behavior can be revealed by probing the full counting statistics of the local, total, and interaction energies. As in the spectral form factor, signatures of quantum chaos in the time domain dictate a dip-ramp-plateau structure in the characteristic function, i.e., the Fourier transform of the eigenvalue distribution. With this approach, we explore the fate of chaos in interacting subsystems that are locally maximally chaotic. Global quantum chaos can be suppressed at strong coupling, as illustrated with coupled copies of random-matrix Hamiltonians and of the Sachdev-Ye-Kitaev model. Our method is amenable to experimental implementation using single-qubit interferometry. [less ▲]

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See detailDigitized-counterdiabatic quantum approximate optimization algorithm
Chandarana, P.; Hegade, N. N.; Paul, K. et al

in Physical Review Research (2022)

The quantum approximate optimization algorithm (QAOA) has proved to be an effective classical-quantum algorithm serving multiple purposes, from solving combinatorial optimization problems to finding the ... [more ▼]

The quantum approximate optimization algorithm (QAOA) has proved to be an effective classical-quantum algorithm serving multiple purposes, from solving combinatorial optimization problems to finding the ground state of many-body quantum systems. Since the QAOA is an Ansatz-dependent algorithm, there is always a need to design Ansätze for better optimization. To this end, we propose a digitized version of the QAOA enhanced via the use of shortcuts to adiabaticity. Specifically, we use a counterdiabatic (CD) driving term to design a better Ansatz, along with the Hamiltonian and mixing terms, enhancing the global performance. We apply our digitized-CD QAOA to Ising models, classical optimization problems, and the P-spin model, demonstrating that it outperforms the standard QAOA in all cases we study. [less ▲]

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See detailConstruction and contextualization approaches for protein-protein interaction networks.
Badkas, Apurva UL; de Landtsheer, Sébastien UL; Sauter, Thomas UL

in Computational and structural biotechnology journal (2022), 20

Protein-protein interaction network (PPIN) analysis is a widely used method to study the contextual role of proteins of interest, to predict novel disease genes, disease or functional modules, and to ... [more ▼]

Protein-protein interaction network (PPIN) analysis is a widely used method to study the contextual role of proteins of interest, to predict novel disease genes, disease or functional modules, and to identify novel drug targets. PPIN-based analysis uses both generic and context-specific networks. Multiple contextualization methodologies have been described, such as shortest-path algorithms, neighborhood-based methods, and diffusion/propagation algorithms. This review discusses these methods, provides intuitive representations of PPIN contextualization, and also examines how the quality of such context-specific networks could be improved by considering additional sources of evidence. As a heuristic, we observe that tasks such as identifying disease genes, drug targets, and protein complexes should consider local neighborhoods, while uncovering disease mechanisms and discovering disease-pathways would gain from diffusion-based construction. [less ▲]

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See detailTen Quick Tips for Biomarker Discovery and Validation Analyses Using Machine Learning
Diaz-Uriarte, R.; Gómez de Lope, Elisa UL; Giugno, R. et al

in PLoS Computational Biology (2022), 18(8), 1010357

High-throughput experimental methods for biosample profiling and growing collections of clinical and health record data provide ample opportunities for biomarker discovery and medical decision support ... [more ▼]

High-throughput experimental methods for biosample profiling and growing collections of clinical and health record data provide ample opportunities for biomarker discovery and medical decision support. However, many of the new data types, including single-cell omics and high-resolution cellular imaging data, also pose particular challenges for data analysis. A high dimensionality of the data in relation to small numbers of available samples, influences of additive and multiplicative noise, large numbers of uninformative or redundant data features, outliers, confounding factors and imbalanced sample group numbers are all common characteristics of current biomedical data collections. While first successes have been achieved in developing clinical decision support tools using multifactorial omics data, there is still an unmet need and great potential for earlier, more accurate and robust diagnostic and prognostic tools for many complex diseases. Here, we provide a set of broadly applicable tips to address some of the most common pitfalls and limitations for biomarker signature development, including supervised and unsupervised machine learning, feature selection and hypothesis testing approaches. In contrast to previous guidelines discussing detailed aspects of quality control, statistics or study reporting, we give a broader overview of the typical challenges and sort the quick tips to address them chronologically by the study phase (starting with study design, then covering consecutive phases of biomarker signature discovery and validation, see also the overview in Fig. 1). While these tips are not comprehensive, they are chosen to cover what we consider as the most frequent, significant, and practically relevant issues and risks in biomarker development. By pointing the reader to further relevant literature on the covered aspects of biomarker discovery and validation, we hope to provide an initial guideline and entry point into the more detailed technical and application-specific aspects of this field. [less ▲]

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See detailDiscovering pesticides and their TPs in Luxembourg waters using open cheminformatics approaches
Krier, Jessy; Singh, Randolph R.; Kondic, Todor UL et al

in Environment International (2022), 158

The diversity of hundreds of thousands of potential organic pollutants and the lack of (publicly available) information about many of them is a huge challenge for environmental sciences, engineering, and ... [more ▼]

The diversity of hundreds of thousands of potential organic pollutants and the lack of (publicly available) information about many of them is a huge challenge for environmental sciences, engineering, and regulation. Suspect screening based on high-resolution liquid chromatography-mass spectrometry (LC-HRMS) has enormous potential to help characterize the presence of these chemicals in our environment, enabling the detection of known and newly emerging pollutants, as well as their potential transformation products (TPs). Here, suspect list creation (focusing on pesticides relevant for Luxembourg, incorporating data sources in 4 languages) was coupled to an automated retrieval of related TPs from PubChem based on high confidence suspect hits, to screen for pesticides and their TPs in Luxembourgish river samples. A computational workflow was established to combine LC-HRMS analysis and pre-screening of the suspects (including automated quality control steps), with spectral annotation to determine which pesticides and, in a second step, their related TPs may be present in the samples. The data analysis with Shinyscreen (https://gitlab.lcsb.uni.lu/eci/shinyscreen/), an open source software developed in house, coupled with custom-made scripts, revealed the presence of 162 potential pesticide masses and 96 potential TP masses in the samples. Further identification of these mass matches was performed using the open source approach MetFrag (https://msbi.ipb-halle.de/MetFrag/). Eventual target analysis of 36 suspects resulted in 31 pesticides and TPs confirmed at Level-1 (highest confidence), and five pesticides and TPs not confirmed due to different retention times. Spatio-temporal analysis of the results showed that TPs and pesticides followed similar trends, with a maximum number of potential detections in July. The highest detections were in the rivers Alzette and Mess and the lowest in the Sûre and Eisch. This study (a) added pesticides, classification information and related TPs into the open domain, (b) developed automated open source retrieval methods - both enhancing FAIRness (Findability, Accessibility, Interoperability and Reusability) of the data and methods; and (c) will directly support “L’Administration de la Gestion de l’Eau” on further monitoring steps in Luxembourg. [less ▲]

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See detailLe criminel tient le civil en état à l’épreuve de l’article 6 de la Conv. EDH
Menetrey, Séverine UL

in Journal des Tribunaux Luxembourg (2022)

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See detailA pharmacogenomic assessment of psychiatric adverse drug reactions to levetiracetam.
Campbell, Ciarán; McCormack, Mark; Patel, Sonn et al

in Epilepsia (2022), 63(6), 1563-1570

OBJECTIVE: Levetiracetam (LEV) is an effective antiseizure medicine, but 10%-20% of people treated with LEV report psychiatric side-effects, and up to 1% may have psychotic episodes. Pharmacogenomic ... [more ▼]

OBJECTIVE: Levetiracetam (LEV) is an effective antiseizure medicine, but 10%-20% of people treated with LEV report psychiatric side-effects, and up to 1% may have psychotic episodes. Pharmacogenomic predictors of these adverse drug reactions (ADRs) have yet to be identified. We sought to determine the contribution of both common and rare genetic variation to psychiatric and behavioral ADRs associated with LEV. METHODS: This case-control study compared cases of LEV-associated behavioral disorder (n = 149) or psychotic reaction (n = 37) to LEV-exposed people with no history of psychiatric ADRs (n = 920). All samples were of European ancestry. We performed genome-wide association study (GWAS) analysis comparing those with LEV ADRs to controls. We estimated the polygenic risk scores (PRS) for schizophrenia and compared cases with LEV-associated psychotic reaction to controls. Rare variant burden analysis was performed using exome sequence data of cases with psychotic reactions (n = 18) and controls (n = 122). RESULTS: Univariate GWAS found no significant associations with either LEV-associated behavioural disorder or LEV-psychotic reaction. PRS analysis showed that cases of LEV-associated psychotic reaction had an increased PRS for schizophrenia relative to contr ols (p = .0097, estimate = .4886). The rare-variant analysis found no evidence of an increased burden of rare genetic variants in people who had experienced LEV-associated psychotic reaction relative to controls. SIGNIFICANCE: The polygenic burden for schizophrenia is a risk factor for LEV-associated psychotic reaction. To assess the clinical utility of PRS as a predictor, it should be tested in an independent and ideally prospective cohort. Larger sample sizes are required for the identification of significant univariate common genetic signals or rare genetic signals associated with psychiatric LEV ADRs. [less ▲]

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See detailEnhancing Participation in Probability-Based Online Panels: Two Incentive Experiments and Their Effects on Response and Panel Recruitment
Witte, Nils; Schaurer, Ines; Schröder, Jette et al

in Social Science Computer Review (2022)

This article investigates how mail-based online panel recruitment can be facilitated through incentives. The analysis relies on two incentive experiments and their effects on panel recruitment, and the ... [more ▼]

This article investigates how mail-based online panel recruitment can be facilitated through incentives. The analysis relies on two incentive experiments and their effects on panel recruitment, and the intermediate participation in the recruitment survey. The experiments were implemented in the context of the German Emigration and Remigration Panel Study and encompass two samples of randomly sampled persons. Tested incentives include a conditional lottery, conditional monetary incentives, and the combination of unconditional money-in-hand with conditional monetary incentives. For an encompassing evaluation of the link between incentives and panel recruitment, the article further assesses the incentives’ implications for demographic composition and panel recruitment unit costs. Multivariate analysis indicates that low combined incentives (€5/€5) or, where unconditional disbursement is unfeasible, high conditional incentives (€20) are most effective in enhancing panel participation. In terms of demographic bias, low combined incentives (€5/€5) and €10 conditional incentives are the favored options. The budget options from the perspective of panel recruitment include the lottery and the €10 conditional incentive which break-even at net sample sizes of 1000. [less ▲]

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See detailSharing calculations to understand arithmetical algorithms and parallel computing
Andrusiak, Rich; Perucca, Antonella UL

in Mathematics Teacher (2022)

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See detailDark solitons in a trapped gas of long-range interacting bosons
Beau, M.; Del Campo Echevarria, Adolfo UL; Frantzeskakis, D. J. et al

in Physical Review (2022)

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See detailVoir ou être vu : analyses de visibilité depuis le site de Chèvremont (commune de Chaudfontaine, Belgique)
van Ruymbeke, Muriel UL; Nys, Gilles-Antoine

in Bulletin de la Société Géographique de Liège (2022), 1

Le site de Chèvremont est connu dans l’histoire liégeoise depuis le Haut Moyen-Âge. L’archéologie a montré que la colline a été fréquentée depuis au moins la période néolithique. Intuitivement, tous les ... [more ▼]

Le site de Chèvremont est connu dans l’histoire liégeoise depuis le Haut Moyen-Âge. L’archéologie a montré que la colline a été fréquentée depuis au moins la période néolithique. Intuitivement, tous les auteurs qui se sont rendus sur le site décrivent un endroit d’où le panorama est impressionnant. Nous tentons ici d’utiliser les analyses de visibilité pour mesurer et comparer l’ampleur de la visibilité atteinte depuis plusieurs points du plateau sommital. [less ▲]

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See detailModeling How Different User Groups Perceive Webpage Aesthetics
Leiva, Luis A. UL; Shiripour, Morteza; Oulasvirta, Antti

in Universal Access in the Information Society (2022)

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See detailUn pas de plus vers une définition autonome de l’autorité de la chose jugée
Menetrey, Séverine UL

in Revue des procédures (2022)

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See detailHow to conduct a meta‑analysis in eight steps: a practical guide
Hansen, Christopher UL; Steinmetz, Holger; Block, Jörn

in Management Review Quarterly (2022), 72(1), 1-19

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See detailScience knowledge and trust in medicine affect individuals’ behavior in pandemic crises
Sailer, Michael; Stadler, Matthias UL; Botes, E'louise UL et al

in European Journal of Psychology of Education (2022), (37), 279-292

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See detailWhy are male students less likely to opt for social science courses? A theory-driven analysis
Haunberger, Sigrid; Hadjar, Andreas UL

in International Social Work (2022), 61(1), 17-34

In this article, we discuss the question of why only a few men decide to study social science courses such as social work. While the conceptual base of our analysis includes the theory of planned ... [more ▼]

In this article, we discuss the question of why only a few men decide to study social science courses such as social work. While the conceptual base of our analysis includes the theory of planned behaviour and theories centring on gender role orientations, the empirical base is a random cluster sample of high-school graduates in Switzerland. The results show different gender effects, as well as direct and indirect effects, for all the theory of planned behaviour factors. Gender role orientations and the question of how a social science profession fits one’s own gender identity appear to be of particular importance only among male students. [less ▲]

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See detailSingle-cell transcriptional profiling and gene regulatory network modeling in Tg2576 mice reveal gender-dependent molecular features preceding Alzheimer-like pathologies
Ali, Muhammad UL; Huarte, Oihane; Heurtaux, Tony UL et al

in Molecular Neurobiology (2022), in press (doi:10.1007/s12035-022-02985-2)(in press),

Alzheimer’s disease (AD) onset and progression is influenced by a complex interplay of several environmental and genetic factors, one of them gender. Pronounced gender differences have been observed both ... [more ▼]

Alzheimer’s disease (AD) onset and progression is influenced by a complex interplay of several environmental and genetic factors, one of them gender. Pronounced gender differences have been observed both in the relative risk of developing AD and in clinical disease manifestations. A molecular level understanding of these gender disparities is still missing, but could provide important clues on cellular mechanisms modulating the disease and reveal new targets for gender-oriented disease-modifying precision therapies. We therefore present here a comprehensive single-cell analysis of disease-associated molecular gender differences in transcriptomics data from the neocortex, one of the brain regions most susceptible to AD, in one of the most widely used AD mouse models, the Tg2576 model. Cortical areas are also most commonly used in studies of post-mortem AD brains. To identify disease-linked molecular processes that occur before the onset of detectable neuropathology, we focused our analyses on an age with no detectable plaques and microgliosis. Cell-type specific alterations were investigated at the level of individual genes, pathways, and gene regulatory networks. The number of differentially expressed genes (DEGs) was not large enough to build context-specific gene regulatory networks for each individual cell type, and thus, we focused on the study of cell types with dominant changes and included analyses of changes across the combination of cell types. We observed significant disease-associated gender differences in cellular processes related to synapse organization and axonogenesis, and identified a limited set of transcription factors, including Egr1 and Klf6, as key regulators of many of the disease-associated and gender-dependent gene expression changes in the model. Overall, our analyses revealed significant celltype-specific gene expression changes in individual genes, pathways and subnetworks, including gender-specific and gender-dimorphic changes in both upstream transcription factors and their downstream targets, in the Tg2576 AD model before the onset of overt disease. This opens a window into molecular events that could determine gender-susceptibility to AD, and uncovers tractable target candidates for potential gender-specific precision medicine for AD. [less ▲]

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See detailHow Germany achieved a record share of renewables during the COVID-19 pandemic while relying on the European interconnected power network
Halbrügge, Stephanie; Buhl, Hans Ulrich; Fridgen, Gilbert UL et al

in Energy (2022)

In 2020, Germany reached a maximum share of 50.5% intermittent renewables in electricity generation. Such a high share results in an increasing need for flexibility measures such as international ... [more ▼]

In 2020, Germany reached a maximum share of 50.5% intermittent renewables in electricity generation. Such a high share results in an increasing need for flexibility measures such as international transmission flexibility, i.e., electricity imports and exports. In fact, during the COVID-19 pandemic, Germany changed from a former electricity net exporter to a net importer. This paper, therefore, analyzes what we can learn from the resulting development of German electricity imports as a flexibility measure from a market, environmental, and network perspective. We analyze data on electricity imports/exports, generation, prices, and interconnection capacities of 38 bidding zones, respectively 11 countries within the ENTSO-E. In particular, we formulate three hypotheses to partition our overarching research question. Our results reveal that from a market perspective, Germany's increased need for transmission flexibility did not generally result in increased prices for German electricity imports. Also, from an environmental perspective, Germany increasingly relied on electricity imports from countries that exhibited a lower share of renewables. Finally, during the COVID-19 pandemic some of Germany's interconnection capacities to its neighboring countries exhibited a higher utilization. In view of our results, German policymakers may reflect on decarbonization policies considering a holistic European perspective. [less ▲]

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See detailMapping the clouds: The matter of data centres
Carr, Constance UL; Bast, Desmond UL; Madron, Karinne Lynda UL et al

in Journal of Maps (2022)

The social spatial geographies of telecommunications and their infrastructures have long interested scholars in the social sciences, and in urban geography specifically. This paper focuses on data centers ... [more ▼]

The social spatial geographies of telecommunications and their infrastructures have long interested scholars in the social sciences, and in urban geography specifically. This paper focuses on data centers. Much effort has been placed in preserving the notion that data centers are ‘clouds’, a terminology that obfuscates the real human geographies of cyberplaces. In this map-making exercise, we visualize the sociopolitical human geographies of data centers, and provoke the reader to consider the impacts that data centers have on residents and their environments. The maps shown in this paper suggest four trends. First, hyperscale data center owners are building near large waterways, signifying a shift in location preferences. Second, data centers stress local administrations, financing, and availability of upstream resources, as hyperscale data centers step up their input needs. Third, data center development is state-led. Fourth the competition for data center industries unfolds across a multi-level governance context. [less ▲]

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See detailExploring Spillover Effects for COVID-19 Cascade Prediction
Chen, Ninghan; Chen, Xihui UL; Zhong, Zhiqiang UL et al

in Entropy (2022), 24(2),

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See detailBeyond the bubble: will NFTs and digital proof of ownership empower creative industry entrepreneurs
Chalmers, Dominic; Fisch, Christian UL; Matthews, Russell et al

in Journal of Business Venturing Insights (2022), 17

Non-fungible Tokens (NFTs) are blockchain-enabled cryptographic assets that represent proof-of-ownership for digital objects. The use of NFTs has been pioneered by creative industry entrepreneurs who have ... [more ▼]

Non-fungible Tokens (NFTs) are blockchain-enabled cryptographic assets that represent proof-of-ownership for digital objects. The use of NFTs has been pioneered by creative industry entrepreneurs who have sought to generate new revenue streams and modes of stakeholder engagement. Despite rapid growth in popularity, concerns have been raised around the legal ownership of NFT assets and the prevalence of speculation and fraud associated with NFT trading. In this rapid response article, we explore the value of NFTs for creative industry entrepreneurs. First, we examine the novel digital affordances of the technology; second, we analyse NFTs through the prism of the recent Initial Coin Offering (ICO) boom and bust; and finally, we take a longer-term historical perspective to consider how past speculative waves inform the present NFT economy. While we identify some potentially valuable artistic and financial opportunities for creative industry entrepreneurs, we conclude that NFTs should be approached with caution. [less ▲]

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See detailDer Witz der Urteilskraft. Zur politischen Dimension des Humors
Mein, Georg UL

in andererseits – Yearbook of Transatlantic German Studies (2022), 9/10

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See detailVers l’implémentation du modèle de Réponse à l’Intervention dans les systèmes éducatifs européens francophones ?
de Chambrier, Anne-Françoise; Dierendonck, Christophe UL

in Année Psychologique (2022), 122

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See detailSingle-cell transcriptomics of human iPSC differentiation dynamics reveal a core molecular network of Parkinson’s disease
Novak, Gabriela; Kyriakis, Dimitrios UL; Grzyb, Kamil UL et al

in Communications Biology (2022), 5(1), 1--19

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly ... [more ▼]

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly understood and there is no treatment to reverse PD progression. Here, we investigated the disease mechanism using mDA neurons differentiated from human induced pluripotent stem cells (hiPSCs) carrying the ILE368ASN mutation within the PINK1 gene, which is strongly associated with PD. Single-cell RNA sequencing (RNAseq) and gene expression analysis of a PINK1-ILE368ASN and a control cell line identified genes differentially expressed during mDA neuron differentiation. Network analysis revealed that these genes form a core network, members of which interact with all known 19 protein-coding Parkinson’s disease-associated genes. This core network encompasses key PD-associated pathways, including ubiquitination, mitochondrial function, protein processing, RNA metabolism, and vesicular transport. Proteomics analysis showed a consistent alteration in proteins of dopamine metabolism, indicating a defect of dopaminergic metabolism in PINK1-ILE368ASN neurons. Our findings suggest the existence of a network onto which pathways associated with PD pathology converge, and offers an inclusive interpretation of the phenotypic heterogeneity of PD. [less ▲]

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See detailEditorial: Digital Innovation and Data-Driven Research in Neurodegenerative Diseases
Gu, Wei UL; Rong, Panying; Hofmann-Apitius, Martin et al

in Frontiers in Neurology (2022), 13

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See detailCross-border everyday lives on the Luxembourg border? An empirical approach: the example of cross-border commuters and residential migrants
Wille, Christian UL; Roos, Ursula

in ARL Reports (2022), 33

Luxembourg is characterized by phenomena of mobility that include cross-border commuters and residential migrants. While both groups have been mainly examined from a socioeconomic perspective, this paper ... [more ▼]

Luxembourg is characterized by phenomena of mobility that include cross-border commuters and residential migrants. While both groups have been mainly examined from a socioeconomic perspective, this paper adopts a sociocultural approach. We will focus on the question of the extent to which cross-border mobility in everyday life promotes cross-border lifeworlds. This will involve examining people’s social contacts at their place of work and/or place of residence as well as the spatial organization of practices of the everyday life of both groups. The paper gives insights into everyday lives at the EU’s internal borders, whose organization into nation states is subordinate and at the same time constitutive. [less ▲]

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See detailGamified web-delivered attentional bias modification training for adults with chronic pain: Protocol for a randomized, double-blind, placebo-controlled trial
Vermeir, Julie F; White, Melanie J; Johnson, Daniel et al

in JMIR Research Protocols (2022)

Background: Research to date has found variable success in using attentional bias modification training (ABMT) procedures in pain samples. Several factors could contribute to these mixed findings ... [more ▼]

Background: Research to date has found variable success in using attentional bias modification training (ABMT) procedures in pain samples. Several factors could contribute to these mixed findings, including boredom and low motivation. Indeed, training paradigms are repetitive, which can lead to disengagement and high drop-out rates. A potential approach to overcome some of these barriers is to attempt to increase motivation and engagement through gamification (ie, the use of game elements) of this procedure. To date, research has yet to explore the gamified format of ABMT for chronic pain and its potential for transfer of benefits. Objective: The aim of this study is to investigate the effects of a gamified web-delivered ABMT intervention in a sample of adults with chronic pain via a randomized, double-blind, placebo-controlled trial. Methods: One hundred and twenty adults with chronic musculoskeletal pain, recruited from clinical (hospital outpatient waiting list) and non-clinical (wider community) settings, will be included in this randomized, double-blind, placebo-controlled, 3-arm trial. Participants will be randomly assigned to complete six online sessions of dot-probe non-gamified sham control ABMT, non-gamified standard ABMT, or gamified ABMT, across a period of three weeks. Active ABMT conditions will aim to train attention away from pain-relevant words. Participant outcomes will be assessed at pre-training, during training, immediately post-training and at 1-month follow-up. Primary outcomes include pain intensity, pain interference, and behavioral and self-reported engagement. Secondary outcomes include attentional bias for pain, anxiety, depression, interpretation bias for pain, and perceived improvement. Results: The ethical aspects of this research project have been approved by the Human Research Ethics Committees of the Royal Brisbane and Women’s Hospital (HREC/2020/QRBW/61743) and Queensland University of Technology (2000000395). This trial is currently in the active participant recruitment phase (since August 2021). Data collection and analysis are expected to conclude by October 2022 and January 2023, respectively. Conclusions: This trial will be the first to evaluate the effects of gamification techniques in a pain ABMT intervention. The findings will provide important information on the potential therapeutic benefits of gamified pain ABMT programs, shed light on the motivational influences of certain game elements in the context of pain, and advance our understanding of chronic pain. Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12620000803998 [less ▲]

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See detailMolecular mechanisms defining penetrance of LRRK2-associated Parkinson’s disease
Trinh, Joanne; Schymanski, Emma UL; Smajic, Semra UL et al

in Medizinische Genetik (2022), 34(2), 103--116

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See detailIn-Work poverty in the EU - EU Law Live Special Issue (II)
Ratti, Luca UL; Garcia Munoz Alhambra, Manuel Antonio UL

in EU Law Live - Weekend Edition (2022)

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See detailSetting out for new Shores! An explorative Analysis of Agency in Youth Employment Mobility
Skrobanek, Jan; Vysotskaya, Volha UL

in Journal of Education and Work (2022)

Based on biographical interviews from an intra-European youth mobility study in Luxembourg and Norway the article aims to contribute to the debate on how to understand and account for complexities of ... [more ▼]

Based on biographical interviews from an intra-European youth mobility study in Luxembourg and Norway the article aims to contribute to the debate on how to understand and account for complexities of agency in youth intra-European employment mobility. Critically reflecting and operationalising Emirbayer and Misches’s conceptualisation of agentic orientations in the field of intra-European employment mobility of young people, we a) explore the usefulness of researching agency from a relational perspective, we b) elaborate on how young mobile reflect their manoeuvring under perceived contingent moments and we c) augment our ken of the complex interlacement of habit, imagination and judgement with (contingent) employment mobility contexts and young people’s concrete employment mobility practices. Our results emphasise the importance of considering how differently agentic orientations interlace with contingent employment mobility contexts ranging from radical self-realisation, adaptive interplay of self-realisation and situational constraints and agentic orientations strongly bounded by situational constraints. In addition, the empirical analysis shows that some of the theoretical propositions of Emirbayer and Mische’s approach have to be revisited. [less ▲]

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See detailEnhanced Optical Spectroscopy for Multiplexed DNA and Protein-Sequencing with Plasmonic Nanopores: Challenges and Prospects
Li, Wang; Zhou, Juan; Maccaferri, Nicolò UL et al

in Analytical Chemistry (2022), 94(2), 503-514

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See detailLe financement du plan de relance européen : audaces fortuna juvat
Allemand, Frederic UL

in Revue des Affaires Européennes (2022), 2022(2), 797-806

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See detailDescribing UI Screenshots in Natural Language
Leiva, Luis A. UL; Hota; Oulasvirta, Antti

in ACM Transactions on Intelligent Systems and Technology (2022)

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See detailMaking meaning of multilingualism at work: from competence to conviviality
Lovrits, Veronika UL

in Journal of Multilingual and Multicultural Development (2022)

The present study contributes to recent renewed interest in the social construction of folk linguistic knowledge and directs its focus to a multilingual workplace. The article reports on an in-depth ... [more ▼]

The present study contributes to recent renewed interest in the social construction of folk linguistic knowledge and directs its focus to a multilingual workplace. The article reports on an in-depth sociolinguistic investigation in a European institution in Luxembourg. Data were collected in 2020-2021 with trainees and permanent staff in a terminology and communication unit. The data collection triangulated qualitative techniques of longitudinal interviewing, reflective drawing, writing reflection, and observation. Analysis of participants’ stances uncovered a varying understanding of what multilingualism means in the workplace, how it changes and to what effect. During reflective participation, the trainees heightened their socio-pragmatic awareness of diversity in the meaning-making process. Moreover, they ceased to construct their personal multilingualism as proof of professional competence and started to see it as the basis of their own well-being, personal self-realisation and growth. As such, they re-coupled the social and linguistic aspect of their language use and aligned their stances with the permanent staff. This study aims to inspire more innovative approaches with a potential direct effect in multilingual workplaces, especially in those welcoming workers from monolingual or otherwise homogenous social environments. [less ▲]

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See detailIntroduction
Steveker, Lena UL; Frenk, Joachim

in Zeitschrift für Anglistik und Amerikanistik (2022), 70(2), 123-130

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See detailThe story of a bank through the architecture of its headquarters
Duval, Cécile UL; Gabellini, Marco UL; Mouton, Victoria UL

in Bulletin - Finance and Photography (2022), 2

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See detailExcitonic-insulator instability and Peierls distortion in one-dimensional semimetals
Barborini, Matteo UL; Calandra, Matteo; Mauri, Francesco et al

in Physical Review. B (2022), 105(7), 075122

The charge density wave instability in one-dimensional semimetals is usually explained through a Peierls-like mechanism, where the coupling of electrons and phonons induces a periodic lattice distortion ... [more ▼]

The charge density wave instability in one-dimensional semimetals is usually explained through a Peierls-like mechanism, where the coupling of electrons and phonons induces a periodic lattice distortion along certain modes of vibration, leading to a gap opening in the electronic band structure and to a lowering of the symmetry of the lattice. In this work, we study two prototypical Peierls systems: the one-dimensional carbon chain and the monatomic hydrogen chain with accurate ab initio calculations based on quantum Monte Carlo and hybrid density functional theory. We demonstrate that in one-dimensional semimetals at T=0, a purely electronic instability can exist independently of a lattice distortion. It is induced by spontaneous formation of low energy electron-hole pairs resulting in the electronic band gap opening, i.e., the destabilization of the semimetallic phase is due to an excitonic mechanism. [less ▲]

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See detailLa qualité pour agir dans l’intérêt collectif
Menetrey, Séverine UL

in Revue Critique de Jurisprudence Belge (2022)

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See detailSulfide Chalcopyrite Solar Cells–Are They the Same as Selenides with a Wider Bandgap?
Siebentritt, Susanne UL; Lomuscio, Alberto UL; Adeleye, Damilola UL et al

in Physica Status Solidi. Rapid Research Letters (2022), 2200126

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See detailImpact of COVID-19 Pandemic on (Health) Care Situation of People with Parkinson’s Disease in Germany (Care4PD)
Fründt, Odette; Hanff, Anne-Marie UL; Mai, Tobias et al

in Brain Sciences (2022), 12(1 62),

The Care4PD study examined the impact of the COVID-19 pandemic on the care situation of people (PwP) with Parkinson’s disease in Germany. A comprehensive, nationwide, anonymous questionnaire for PwP was ... [more ▼]

The Care4PD study examined the impact of the COVID-19 pandemic on the care situation of people (PwP) with Parkinson’s disease in Germany. A comprehensive, nationwide, anonymous questionnaire for PwP was distributed by the members’ journal of the German Parkinson’s Disease Association and in several PD specialized in- and outpatient institutions. PwP subjectively evaluated their general care situation and individual impairments during the pandemic. We analyzed 1269 eligible out of 1437 returned questionnaires (88.3%) and compared PwP with (p-LTC) and without (np-LTC) professional long-term care. Both groups rated the general pandemic-related consequences as being rather mild to moderate (e.g., worsening of symptom or concerns). However, familial/social contact restrictions were indicated as most compromising, whereas access to outpatient professional health care providers was less affected. PwP with professional LTC reported more impairment than those without. COVID-19 vaccination rates and acceptance were generally high (p-LTC: 64.3%, np-LTC: 52.3%) at the time of the study, but realization of sanitary measures—especially wearing masks as a patient during care sessions—still needs to be improved. Technical options for telemedicine were principally available but only rarely used. Altogether, during the COVID-19 pandemic, PwP in Germany seemed to have a relatively stable health care access, at least in outpatient settings, while mainly social isolation compromised them. The p-LTC group was more impaired in everyday live compared with the np-LTC group. [less ▲]

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See detailTechnocratic urban development: Large digital corporations as power brokers of the digital age
Carr, Constance UL; Hesse, Markus UL

in Planning Theory and Practice (2022)

Large digital corporations such as Amazon.com or Alphabet Inc. are forging their position in cities by promoting themselves as the sole providers of so-called essential urban infrastructures. In this ... [more ▼]

Large digital corporations such as Amazon.com or Alphabet Inc. are forging their position in cities by promoting themselves as the sole providers of so-called essential urban infrastructures. In this paper, we reflect on how the behaviours of these current-day ‘tech giants’ are similar to those of the mid-20th century, a time period also known for dramatic infrastructural change in North American and Europe. Specifically, we are reminded of Robert Moses and how he pushed for infrastructural change in New York City and State, which were also supposedly the height of state-of-the-art urban planning at the time. He pushed his agenda, however, by brokering power and strong-arming the urban and regional development field. We reflect on Alphabet Inc.’s project in Toronto and Amazon’s search for a second headquarters in New York City and how these LDCs were similarly armed with executive and financial power and an ability to bully the field of urban development in their own interest. Behaving as digital-age power brokers, they engaged managerial-technocratic modes of urban governance to instigate projects that ultimately failed. We argue that Alphabet’s and Amazon’s strategies not only resemble those of Moses, but that all three deploy tactics that debase planning practice itself. [less ▲]

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See detailPreschool predictors of learning to read and spell in an additional language: a two-wave longitudinal study in a multilingual context.
Wealer, Cyril UL; Fricke, Silke; Loff, Ariana et al

in Reading and Writing (2022)

The study explores whether foundational skills of reading and spelling in preschool (age 5–6) predict literacy skills cross-linguistically in an additional language in Grade 1 (age 6–7). A sample of ... [more ▼]

The study explores whether foundational skills of reading and spelling in preschool (age 5–6) predict literacy skills cross-linguistically in an additional language in Grade 1 (age 6–7). A sample of linguistically diverse preschool children completed tasks of phonological awareness, letter-sound knowledge, verbal-short term memory, rapid automatized naming, and lexical knowledge in the language of preschool instruction Luxembourgish. The children were followed-up in Grade 1 where literacy skills were assessed in the language of schooling, i.e., German, after fve months of literacy instruction. German was a non-native language for all children. Longitudinal correlations confrm that individual diferences in single word/pseudoword reading and spelling in German in Grade 1 can be predicted by all the foundational literacy skills that were assessed in Luxembourgish. Path analyses showed that phonological awareness in Luxembourgish emerged as the strongest unique predictor of Grade 1 literacy skills in German. The second unique preschool predictor of Grade 1 literacy skills was letter-sound knowledge. Results are consistent with the view that literacy development in an additional language builds upon similar building blocks as literacy acquisition in a frst language, at least for languages that are typologically close. However, current fndings suggest that respective contributions between predictors and literacy skills in children learning to read in an additional language may vary from patterns observed in studies with children acquiring literacy in their frst language. [less ▲]

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See detailQuelle solution pour le conflit de procédures conservatoires en droit judiciaire européen?
Cuniberti, Gilles UL

in Revue Critique de Droit International Privé (2022)

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See detailRandom Encounters and Information Diffusion about Product Quality
Zanaj, Skerdilajda UL

in Journal of Economics and Management Strategy (2022)

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See detailTaxes and declared profits: evidence from gold mines in Africa
Zanaj, Skerdilajda UL

in Resources Policy (2022)

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See detailEmpirical Perturbation Analysis of Two Adversarial Attacks: Black Box versus White Box
Chitic, Raluca; Topal, Ali Osman UL; Leprevost, Franck UL

in Applied Sciences (2022), 12(14), 7339

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See detailTax competition and phantom FDI
Zanaj, Skerdilajda UL

in Journal of Public Economic Theory (2022)

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See detailThe quizzing effect depends on hope of success and can be optimized by cognitive load-based adaptation
Heitmann, Svenja; Grund, Axel UL; Fries, Stefan et al

in Learning and Instruction (2022), 77(online first), 101526

It is well established that quizzing fosters learning. However, some gaps in the literature relating to the fit of quizzing to learner characteristics and learner perceptions during quizzing still need to ... [more ▼]

It is well established that quizzing fosters learning. However, some gaps in the literature relating to the fit of quizzing to learner characteristics and learner perceptions during quizzing still need to be addressed. The present study focuses on two of these aspects: achievement motives and perceptions of cognitive load. First, quizzing entails that learners’ performance is judged against some standard of excellence. This might make it appealing and effective for learners with high hope of success and low fear of failure in particular. Second, it is an open question whether providing quiz questions that are adapted to learners’ perceived level of cognitive load during quizzing would be beneficial. To address these questions, we randomly assigned learners to either non-adaptive quizzing, adaptive quizzing, or note-taking. We found that quizzing benefits concerning learning outcomes were moderated by hope of success. Furthermore, the adaptation via cognitive load ratings substantially increased the quizzing effect. [less ▲]

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See detailExplicit Kummer generators for cyclotomic extensions
Hoermann, Fritz; Perucca, Antonella UL; Sgobba, Pietro UL et al

in JP Journal of Algebra, Number Theory and Applications (2022)

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See detailThe Corona Pandemic and Its Implications for the Mental Health and Mental Healthcare of Older Adults
Albert, Isabelle UL; Kornadt, Anna Elena UL

in GeroPsych: Journal of Gerontopsychology and Geriatric Psychiatry (2022), 35(1),

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See detailMorphological principles of neuronal mitochondria
Mendelsohn, Rachel; Garcia, Guadalupe C.; Bartol, Thomas M. et al

in Journal of Comparative Neurology (2022), 530(6), 886--902

In the highly dynamic metabolic landscape of a neuron, mitochondrial membrane architectures can provide critical insight into the unique energy balance of the cell. Current theoretical calculations of ... [more ▼]

In the highly dynamic metabolic landscape of a neuron, mitochondrial membrane architectures can provide critical insight into the unique energy balance of the cell. Current theoretical calculations of functional outputs like adenosine triphosphate and heat often represent mitochondria as idealized geometries, and therefore, can miscalculate the metabolic fluxes. To analyze mitochondrial morphology in neurons of mouse cerebellum neuropil, 3D tracings of complete synaptic and axonal mitochondria were constructed using a database of serial transmission electron microscopy (TEM) tomography images and converted to watertight meshes with minimal distortion of the original microscopy volumes with a granularity of 1.64 nanometer isotropic voxels. The resulting in-silico representations were subsequently quantified by differential geometry methods in terms of the mean and Gaussian curvatures, surface areas, volumes, and membrane motifs, all of which can alter the metabolic output of the organelle. Finally, we identify structural motifs present across this population of mitochondria, which may contribute to future modeling studies of mitochondrial physiology and metabolism in neurons. [less ▲]

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See detailTrademarks and how they relate to the sustainability and economic outcomes of social startups
Hirschmann, Mirko UL; Block, Jörn

in Journal of Cleaner Production (2022)

Prior research shows that trademarks positively relate to startups' growth and survival. However, empirical evidence on the impact of intellectual property rights (IPRs), especially trademarks, on the ... [more ▼]

Prior research shows that trademarks positively relate to startups' growth and survival. However, empirical evidence on the impact of intellectual property rights (IPRs), especially trademarks, on the development of social startups' hybrid outcomes is limited. Our study aims to fill this gap by investigating how early trademarking relates to the sustainability and economic outcomes of social startups. Based on a sample of 485 social startups from Germany, we find that social startups that register a trademark within the first three years of their existence have both significantly higher sustainability and economic outcomes. Additionally, we identify that the geographical scope of a trademark relates differently to social startups' outcomes. Our results contribute to the emerging literature on startups’ role to achieve sustainability outcomes and to IPR research that lacks an understanding of the importance of trademarks for sustainable entrepreneurship. We provide several practical implications for social startups, impact investors, and policy-makers. [less ▲]

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See detailInformation thermodynamics for deterministic chemical reaction networks
Penocchio, Emanuele UL; Avanzini, Francesco UL; Esposito, Massimiliano UL

in Journal of Chemical Physics (2022), 157(3), 034110

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See detailCorrection to: Performance assessment of the relative gravimeter Scintrex CG-6
Francis, Olivier UL

in Journal of Geodesy (2022), 96(1), 1-1

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See detailWeakly Inscribed Polyhedra
chen, hao; Schlenker, Jean-Marc UL

in Transactions of the American Mathematical Society. Series B (2022), 9

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See detailOn unavoidable families of meromorphic functions
Meyrath, Thierry UL

in Canadian Mathematical Bulletin (2022)

We prove several results on unavoidable families of meromorphic functions. For instance, we give new examples of families of cardinality three that are unavoidable with respect to the set of meromorphic ... [more ▼]

We prove several results on unavoidable families of meromorphic functions. For instance, we give new examples of families of cardinality three that are unavoidable with respect to the set of meromorphic functions on $\C$. We further obtain families consisting of less than three functions that are unavoidable with respect to certain subsets of meromorphic functions. In the other direction, we show that for every meromorphic function $f$, there exists an entire function that avoids $f$ on $\C$. [less ▲]

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See detailHow we explore, interpret, and solve complex problems: A cross-national study of problem-solving processes
Molnar, G; Alrababah, A. A.; Greiff, Samuel UL

in Heliyon (2022), (8), 08775

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See detailAssociations between coronavirus crisis perception, perceived economic risk of coronavirus, general self-efficacy, and coronavirus anxiety at the start of the pandemic. Differences by gender and race.
Garcia, Samantha; Hopfer, Suellen; Botes, E'louise UL et al

in International Journal of Environmental Research and Public Health (2022), (19), 2872

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See detailDas lateinische Homiliar-Legendar des Dominikanerinnenklosters Marienthal (Brüssel KBR, Hs. 831-34). Zugleich ein Beitrag zur Kontextualisierung der Lebensbeschreibung der Priorin Yolanda von Vianden
Dubuisson, Bastien UL

in Hemecht: Zeitschrift für Luxemburger Geschichte (2022), 74(1), 5-47

The Marienthal homiliarium-legendarium represents a unique example of a Latin hagiographical collection from the early period of the Ordo fratrum Praedicatorum originating from a nunnery. In addition, it ... [more ▼]

The Marienthal homiliarium-legendarium represents a unique example of a Latin hagiographical collection from the early period of the Ordo fratrum Praedicatorum originating from a nunnery. In addition, it is a rare example of a 'traditional' Dominican hagiographical collection unlike the abbreviated collections written during the 13th century by members of the Dominican Order, which redefined the landscape of Latin hagiographical edition. Based on a detailed codicological study as well as an analysis of the texts contained in the legendarium section of the factice codex, this article questions the context of production and use of the book object. A key point is whether the legendarium was the product of a Dominican enterprise or not. The detailed study of the literary tradition of several of the texts also sheds light on the provenance of the collection. As a book belonging to a young female community of the Order, the homiliarium-legendarium also raises questions about the history of the conventual library and of its concrete use by the nuns. Like other manuscripts, it could be linked to the prioress Yolanda of Vianden whose life story is not unlike that of the saints in the legendarium. [less ▲]

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See detailLoss-of-function variants in the KCNQ5 gene are implicated in genetic generalized epilepsies
Krüger, Johanna; Schubert, Julian; Kegele, Josua et al

in eBioMedicine (2022), 84

Summary Background De novo missense variants in KCNQ5, encoding the voltage-gated K+ channel KV7.5, have been described to cause developmental and epileptic encephalopathy (DEE) or intellectual disability ... [more ▼]

Summary Background De novo missense variants in KCNQ5, encoding the voltage-gated K+ channel KV7.5, have been described to cause 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 homology modelling. Findings 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 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 R359C variant altered PI(4,5)P2-interaction. Interpretation Our study identified deleterious KCNQ5 variants in GGE, partially combined with mild to moderate ID. The disease mechanism is a LOF partially with dominant-negative effects through functional deficits. LOF of KV7.5 channels will reduce the M-current, likely resulting in increased excitability of KV7.5-expressing neurons. Further studies on network level are necessary to understand which circuits are affected and how this induces generalized seizures. Funding DFG/FNR Research Unit FOR-2715 (Germany/Luxemburg), BMBF rare disease network Treat-ION (Germany), foundation ‘no epilep’ (Germany). [less ▲]

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