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See detailFocal adhesion kinase plays a dual role in TRAIL resistance and metastatic outgrowth of malignant melanoma
Del Mistro, Greta; Riemann, Shamala; Schindler, Sebastian et al

in Cell Death and Disease (2022)

Despite remarkable advances in therapeutic interventions, malignant melanoma (MM) remains a life-threating disease. Following high initial response rates to targeted kinase-inhibition metastases quickly ... [more ▼]

Despite remarkable advances in therapeutic interventions, malignant melanoma (MM) remains a life-threating disease. Following high initial response rates to targeted kinase-inhibition metastases quickly acquire resistance and present with enhanced tumor progression and invasion, demanding alternative treatment options. We show 2nd generation hexameric TRAIL-receptor-agonist IZI1551 (IZI) to effectively induce apoptosis in MM cells irrespective of the intrinsic BRAF/NRAS mutation status. Conditioning to the EC50 dose of IZI converted the phenotype of IZI-sensitive parental MM cells into a fast proliferating and invasive, IZI-resistant metastasis. Mechanistically, we identified focal adhesion kinase (FAK) to play a dual role in phenotype-switching. In the cytosol, activated FAK triggers survival pathways in a PI3K- and MAPK-dependent manner. In the nucleus, the FERM domain of FAK prevents activation of wtp53, as being expressed in the majority of MM, and consequently intrinsic apoptosis. Caspase-8-mediated cleavage of FAK as well as FAK knockdown, and pharmacological inhibition, respectively, reverted the metastatic phenotype-switch and restored IZI responsiveness. FAK inhibition also re-sensitized MM cells isolated from patient metastasis that had relapsed from targeted kinase inhibition to cell death, irrespective of the intrinsic BRAF/NRAS mutation status. Hence, FAK-inhibition alone or in combination with 2nd generation TRAIL-receptor agonists may be recommended for treatment of initially resistant and relapsed MM, respectively. [less ▲]

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See detailIntersectional Inequalities in Science
Kozlowski, Diego UL; Larivière, Vincent; Sugimoto, Cassidy R. et al

in Proceedings of the National Academy of Sciences of the United States of America (2022), 119(2), 2113067119

The US scientific workforce is primarily composed of White men. Studies have demonstrated the systemic barriers preventing women and other minoritized populations from gaining entry to science; few ... [more ▼]

The US scientific workforce is primarily composed of White men. Studies have demonstrated the systemic barriers preventing women and other minoritized populations from gaining entry to science; few, however, have taken an intersectional perspective and examined the consequences of these inequalities on scientific knowledge. We provide a large-scale bibliometric analysis of the relationship between intersectional identities, topics, and scientific impact. We find homophily between identities and topic, suggesting a relationship between diversity in the scientific workforce and expansion of the knowledge base. However, topic selection comes at a cost to minoritized individuals for whom we observe both between- and within-topic citation disadvantages. To enhance the robustness of science, research organizations should provide adequate resources to historically underfunded research areas while simultaneously providing access for minoritized individuals into high-prestige networks and topics. [less ▲]

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See detailEnvironmental Detective Work: Environmental Cheminformatics and the Exposome
Schymanski, Emma UL

Presentation (2022, January 10)

The multitude of chemicals to which we are exposed is ever increasing, with over 110 million chemicals in the largest open chemical databases, over 350,000 in global use inventories, and over 70,000 ... [more ▼]

The multitude of chemicals to which we are exposed is ever increasing, with over 110 million chemicals in the largest open chemical databases, over 350,000 in global use inventories, and over 70,000 estimated to be in household use alone. Detectable molecules in exposomics can be captured using non-target high resolution mass spectrometry (HRMS), but despite the size of the chemical space, scientists cannot yet identify most of the tens of thousands of features in each sample, leading to critical bottlenecks in identification and data interpretation. This talk will cover European and worldwide community initiatives and resources to help connect environmental expert knowledge and observations towards a better understanding of the exposome, including various open cheminformatics and computational mass spectrometry approaches such as the NORMAN Suspect List Exchange, MassBank, MetFrag and PubChemLite for Exposomics. [less ▲]

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See detailDairy Intake and Parkinson's Disease: A Mendelian Randomization Study
Domenighetti, Cloé; Sugier, Pierre-Emmanuel; Ashok Kumar Sreelatha, Ashwin et al

in Movement Disorders (2022)

Abstract Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained ... [more ▼]

Abstract Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective The aim is to examine the association between genetically predicted dairy intake and PD using two-sample Mendelian randomization (MR). Methods We genotyped a well-established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage-PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Results Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95 confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003; P-difference with women = 0.029). Conclusions Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society [less ▲]

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See detailInterpolating Nonadiabatic Molecular Dynamics Hamiltonian with Artificial Neural Networks
Bipeng Wang; Weibin Chu; Tkatchenko, Alexandre UL et al

in Journal of Physical Chemistry Letters (2022)

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See detailMAGNETOHYDRODYNAMIC ENHANCED ENTRY SYSTEM FOR SPACE TRANSPORTATION (MEESST) AS A KEY BUILDING BLOCK FOR LOW-COST INTERPLANETARY MISSIONS
La Rosa Betancourt, Manuel; Collier-Wright, Marcus; Boegel, Elias et al

in Journal of the British Interplanetary Society (2022), 74(12), 448-453

Aside from the launch environment, atmospheric re-entry imposes one of the most demanding environments which a spacecraft can experience. The combination of high spacecraft velocity and the presence of ... [more ▼]

Aside from the launch environment, atmospheric re-entry imposes one of the most demanding environments which a spacecraft can experience. The combination of high spacecraft velocity and the presence of atmospheric particles leads to partially ionised gas forming around the vehicle, which significantly inhibits radio communications, and leads to the generation of high thermal loads on the spacecraft surface. Currently, the latter is solved using expensive, heavy, and often expendable thermal protection systems (TPS). The use of electromagnetic fields to exploit Magnetohydrodynamic (MHD) principles has long been considered as an attractive solution for this problem. By displacing the ionised gas away from the spacecraft, the thermal loads can be reduced, while also opening a magnetic window for radio waves, mitigating the blackout phenomenon. The application of this concept has to date not been possible due to the large magnetic fields required, which would necessitate the use of exceptionally massive and power-hungry copper coils. High Temperature Superconductors (HTS) have now reached industrial maturity. HTS coils can now offer the necessary low weight and compactness required for space applications. The MEESST consortium the has been awarded a grant from the EU Horizon 2020 programme for the development and demonstration of a novel HTS-based re-entry system based with its foundation on MHD principles. The project will first harmonize existing numerical codes, and then design, manufacture, and test a HTS magnet. The study shows that the use of MEESST technology can have a positive impact on the cost-effectiveness and available payload of interplanetary missions. [less ▲]

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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 detailNormative Coherence for Development and Regionalism: Gender equality in ASEAN’s migration policies
Häbel, Sandra; Koff, Harlan UL; Adam, Marie

in Development Policy Review (2022)

Motivation:The United Nations2030 Agenda recognizesregions as important actors in implementing the sustainable development agenda.At the same time, regions are often criticized for lackingeffective ... [more ▼]

Motivation:The United Nations2030 Agenda recognizesregions as important actors in implementing the sustainable development agenda.At the same time, regions are often criticized for lackingeffective implementation, especially in relation to gender equality.Purpose:This study examines whether the Association of Southeast Asian Nations (ASEAN) implements its global commitment to gender equality at a regional level. Methods and approach:We apply qualitative analysis of key ASEAN documents in order to determinehow gender equality is implemented regionally. We particularly focus onframeworks related to female migrant workers in ASEAN. Findings: The analysis shows that ASEAN is formally committed to improving gender equality at a regional level, however, female migrants often end up in unfavourable conditions and precarious work relationships without any institutionalized protection because ASEAN's gender equality initiatives are largely concentrated in the Cultural Community and absent from the Economic Community, indicating an absence of normative coherence for developmentwith regard to gender equality. Policy implications:This limited impact of emerging regional commitments to gender equality arises from incoherencies in ASEAN’s normative governance. [less ▲]

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See detailRegionalgeschichte als Nationalgeschichte. Traditionen, Institutionen und Perspektiven in Luxemburg
Pauly, Michel UL

in Hirbodian, Sigrid; Jörg, Christian; Wegner, Tjark (Eds.) Zwischen Region, Nation und Europa. Landesgeschichte in europäischer Perspektive (2022)

Der Beitrag erläutert Entstehung und Entwicklung der landesgeschichtlichen Forschung in Luxemburg seit dem 19. Jahrhundert, präsentiert die entsprechrenden Institutionen bis hin zur Gründung einer ... [more ▼]

Der Beitrag erläutert Entstehung und Entwicklung der landesgeschichtlichen Forschung in Luxemburg seit dem 19. Jahrhundert, präsentiert die entsprechrenden Institutionen bis hin zur Gründung einer Universität (2003) und versucht ausländische Einflüsse zu identifizieren sowie Zukunftsperspektiven zu skizzieren. [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 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 detailIntergenerationality in the light of indeterminacy
Boulanger, Dany; Albert, Isabelle UL; Abbey, Emily

in Integrative Psychological and Behavioral Science (2022), 56(1),

This Special Issue aims to shed light on the undetermined nature of intergenerational trajectories. Indeterminacy has been suggested to the author as an avenue to tackle the dynamic aspect –which entails ... [more ▼]

This Special Issue aims to shed light on the undetermined nature of intergenerational trajectories. Indeterminacy has been suggested to the author as an avenue to tackle the dynamic aspect –which entails looking at tensions in an unfolding process— of intergenerationality. We present the paper in this Special Issue by insisting on their main contributions, we identify HOW they define the concept of generation, particularly in reference to indeterminacy. [less ▲]

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See detail"Le chant de la sirène d'une Europe recalibrée"
Roelens, Nathalie UL

Conference given outside the academic context (2022)

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See detailBreaking and Fixing Vote Privacy of the Estonian E-Voting Protocol IVXV
Mueller, Johannes UL

in Workshop on Advances in Secure Electronic Voting 2022 (2022)

We revisit the e-voting protocol IVXV that is used for legally-binding political elections in Estonia from a privacy perspective. We demonstrate that IVXV is vulnerable to attacks against vote privacy in ... [more ▼]

We revisit the e-voting protocol IVXV that is used for legally-binding political elections in Estonia from a privacy perspective. We demonstrate that IVXV is vulnerable to attacks against vote privacy in those threat scenarios that were considered for IVXV originally. We explain how to improve IVXV so that it protects against the privacy issues we discovered. [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 detailPhysics-Based Cognitive Radar Modeling and Parameter Estimation
Sedighi, Saeid UL; Mysore Rama Rao, Bhavani Shankar UL; Mishra, Kumar Vijay et al

in IEEE Radar Conference (2022)

We consider the problem of channel response estimation in cognitive fully adaptive radar (CoFAR). We show that this problem can be expressed as a constrained channel estimation problem exploiting the ... [more ▼]

We consider the problem of channel response estimation in cognitive fully adaptive radar (CoFAR). We show that this problem can be expressed as a constrained channel estimation problem exploiting the similarity between the channel impulse responses (CIRs) of the adjacent channels. We develop a constrained CIR estimation (CCIRE) algorithm enhancing estimation performance compared to the unconstrained CIR estimation where the similarity between the CIRs of the adjacent channels is not employed. Further, we we derive the Cram\'{e}r-Rao bound (CRB) for the CCIRE and show the optimality of the proposed CCIRE through comparing its performance with the derived CRB. [less ▲]

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See detailIntroduction: The International Journal of the History of Sport Collection from the 2020 ISHPES Congress
Heck, Sandra UL; Hedenborg, Susanna; Nardini, Dario

in The International Journal of the History of Sport (2022)

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