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See detailA Pharmacophore Model for SARS-CoV-2 3CLpro Small Molecule Inhibitors and in Vitro Experimental Validation of Computationally Screened Inhibitors
Glaab, Enrico UL; Manoharan, Ganesh Babu UL; Abankwa, Daniel UL

in Journal of Chemical Information and Modeling (in press)

Among the biomedical efforts in response to the current coronavirus (COVID-19) pandemic, pharmacological strategies to reduce viral load in patients with severe forms of the disease are being studied ... [more ▼]

Among the biomedical efforts in response to the current coronavirus (COVID-19) pandemic, pharmacological strategies to reduce viral load in patients with severe forms of the disease are being studied intensively. One of the main drug target proteins proposed so far is the SARS-CoV-2 viral protease 3CLpro (also called Mpro), an essential component for viral replication. Ongoing ligand- and receptor-based computational screening efforts would be facilitated by an improved understanding of the electrostatic, hydrophobic and steric features that characterize small molecule inhibitors binding stably to 3CLpro, as well as by an extended collection of known binders. Here, we present combined virtual screening, molecular dynamics simulation, machine learning and in vitro experimental validation analyses which have led to the identification of small molecule inhibitors of 3CLpro with micromolar activity, and to a pharmacophore model that describes functional chemical groups associated with the molecular recognition of ligands by the 3CLpro binding pocket. Experimentally validated inhibitors using a ligand activity assay include natural compounds with available prior knowledge on safety and bioavailability properties, such as the natural compound rottlerin (IC50 = 37 µM), and synthetic compounds previously not characterized (e.g. compound CID 46897844, IC50 = 31 µM). In combination with the developed pharmacophore model, these and other confirmed 3CLpro inhibitors may provide a basis for further similarity-based screening in independent compound databases and structural design optimization efforts, to identify 3CLpro ligands with improved potency and selectivity. Overall, this study suggests that the integration of virtual screening, molecular dynamics simulations and machine learning can facilitate 3CLpro-targeted small molecule screening investigations. Different receptor-, ligand- and machine learning-based screening strategies provided complementary information, helping to increase the number and diversity of identified active compounds. Finally, the resulting pharmacophore model and experimentally validated small molecule inhibitors for 3CLpro provide resources to support follow-up computational screening efforts for this drug target. [less ▲]

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See detailBeyond the Colonizer-Colonized Mindset: Nonconformity of Léonora Miano’s Afrophonie
Nonoa, Koku Gnatuloma UL

in Amoo-Adare, Epifania; Siriwardane-de Zoysa, Rapti (Eds.) An Anthology of Non-Conformism: Rebel Women Words, Ways & Wonders (in press)

In her books Red in blue trilogy (2015) and L'impératif transgressif (The Transgressive Imperative) (2016a), the French-Cameroonian novelist Léonora Miano questions and elucidates, among other things, the ... [more ▼]

In her books Red in blue trilogy (2015) and L'impératif transgressif (The Transgressive Imperative) (2016a), the French-Cameroonian novelist Léonora Miano questions and elucidates, among other things, the repression of the history of “forgotten worlds” in relation to transatlantic human trafficking and colonialism and pleads for reinventing African imaginary by decolonizing the French-speaking world called Francophonie. Therefore, she invites sub-Saharan writers to use their verbs in a non-conformist way: it is about finding oneself beyond and freeing oneself from the colonizer-colonized mindset. In this regard, Miano coins the concept of Afrophonie as a form of countercultural re-examination and reorientation of the politics of perception stemming from the coloniality of the French language and the Francophonie. From a countercultural perspective, this contribution discusses the potentiality of the non-conformity of Léonora Miano´s writings beyond the colonizer-colonized mindset. [less ▲]

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See detailNegotiating Migration in European Theater in/beyond “Thinking-as-Usual”
Nonoa, Koku Gnatuloma UL

in Juvonen, Annimari; Lindemann Lino, Verena (Eds.) Negotiations of Migration Reexamining the Past and Present in Contemporary Europe (2021)

First, this contribution discusses “thinking-as-usual” in connection with to- day’s migration dilemma in Europe as the manifestation of a crisis from the per- spective of “social drama.” Secondly, the ... [more ▼]

First, this contribution discusses “thinking-as-usual” in connection with to- day’s migration dilemma in Europe as the manifestation of a crisis from the per- spective of “social drama.” Secondly, the present contribution seeks to question the discourse of “thinking-as-usual” and its performative character as observable units shaping perceptions and staging strategies in some contemporary theater and performance productions in Europe. Thirdly, it analyzes the response-ability and potentiality of some other theater and performance arts which productively address structures of belonging and exclusion stemming from “thinking-as-usual.” Finally, this analysis explores how de-essentializing epistemological approaches of European artistic habits can productively impact the negotiation of otherness and migration in the theater and performing arts. [less ▲]

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See detailZentrale Konzepte und Erkenntnisinteressen der kulturwissenschaftlichen Grenzforschung. Ein Überblick
Wille, Christian UL

Presentation (2021, June 28)

Von der Grenzforschung werden nicht nur verstärkt Antworten auf drängende gesellschaftliche Fragen erwartet, das multidisziplinäre Arbeitsfeld hat sich auch in seinen Ansätzen und Erkenntnisinteressen ... [more ▼]

Von der Grenzforschung werden nicht nur verstärkt Antworten auf drängende gesellschaftliche Fragen erwartet, das multidisziplinäre Arbeitsfeld hat sich auch in seinen Ansätzen und Erkenntnisinteressen erneuert. Daraus ist die kulturwissenschaftliche Grenzforschung hervorgegangen, die C. Wille in seinem Vortrag am 28. Juni vorstellt. In der Sommerschule “Grenzen und Migrationen in Europa” (Uni des Saarlandes) diskutieren Promovierende aus Deutschland und Frankreich. [less ▲]

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See detailThinking Borders and Border Thinking
Wille, Christian UL

Scientific Conference (2021, June 17)

Obwohl die Grenz- und Migrationsforschung große Überschneidungen aufweisen, unterscheiden sie sich z.B. hinsichtlich ihrer Erkenntnisinteressen und Theoretisierungen. Der Vortrag baut auf solchen ... [more ▼]

Obwohl die Grenz- und Migrationsforschung große Überschneidungen aufweisen, unterscheiden sie sich z.B. hinsichtlich ihrer Erkenntnisinteressen und Theoretisierungen. Der Vortrag baut auf solchen Gemeinsamkeiten und Unterschieden auf und zeigt zunächst die Verbindungen zwischen Grenz- und Migrationsforschung. Im zweiten Schritt werden aus Sicht der Grenzforschung verschiedene analytische Trends – insbesondere die komplexitätsorientierte Perspektive – und die damit verbundenen Grenzkonzepte vorgestellt. Abschließend werden die analytischen Trends mit der Methode „border thinking“ (Mignolo) in Zusammenhang gebracht und gefragt, inwiefern sie für die Migrationsforschung nützlich sein können. [less ▲]

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See detailThe BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) Glossary: developing a lingua franca to facilitate data harmonisation and cross-cohort analyses
Broderick, Conor; Christian, Nils; Apfelbacher, Christian et al

in British Journal of Dermatology (2021)

Dear Editor, BIOMAP (BIOMarkers in Atopic dermatitis and Psoriasis) is a large European consortium aiming to advance personalised medicine for atopic dermatitis and psoriasis by identifying biomarkers ... [more ▼]

Dear Editor, BIOMAP (BIOMarkers in Atopic dermatitis and Psoriasis) is a large European consortium aiming to advance personalised medicine for atopic dermatitis and psoriasis by identifying biomarkers which predict therapeutic response and disease progression. BIOMAP brings together clinicians, researchers, patient organisations and pharmaceutical industry partners and encompasses data from over 60 individual studies, including randomised clinical trials, population-based cohorts and deeply-phenotyped disease registries. The curation and harmonisation of data and bio-samples from these established studies will facilitate cross-cohort clinical and molecular analyses, increasing the potential to identify small effect estimates and to better stratify disease subtypes. This letter serves to disseminate BIOMAP's pathway to data harmonisation and will inform future collaborative research endeavours. [less ▲]

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See detailLe Luxembourg, une nation vivante qui change
Scuto, Denis UL

Article for general public (2021)

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See detailGrenzregionen zwischen Covidfencing und Debordering. Zur zivilgesellschaftlichen Anfechtung von Grenzen in Zeiten der Pandemie
Wille, Christian UL

Presentation (2021, June 11)

Proteste, Demonstrationen oder symbolische Aktionen gegen das Covid-Grenzregime sind neue Phänomene in europäischen Grenzregionen. Beispiele für die jüngsten zivilgesellschaftlichen Anfechtungen von ... [more ▼]

Proteste, Demonstrationen oder symbolische Aktionen gegen das Covid-Grenzregime sind neue Phänomene in europäischen Grenzregionen. Beispiele für die jüngsten zivilgesellschaftlichen Anfechtungen von Grenzen stellt C. Wille in seinem Vortrag am 11. Juni vor. Zu dem Workshop „Pandemisches Virus – nationales Handeln: Covid-19 und die europäische Idee” an der Uni des Saarlandes sind Kultur-, Raum- und Rechtswissenschaftler*innen eingeladen. [less ▲]

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See detailScaling of urban heat island and nitrogen dioxide with urban population: a meta-analysis
Wei, Yufei UL; Caruso, Geoffrey UL; Lemoy, Rémi

Scientific Conference (2021, June 10)

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See detailRole of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications
Wolking, Stefan; Campbell, Ciarán; Stapleton, Caragh et al

in Frontiers in Pharmacology (2021), 12

Objective: Resistance to anti-seizure medications (ASMs) presents a significant hurdle in the treatment of people with epilepsy. Genetic markers for resistance to individual ASMs could support clinicians ... [more ▼]

Objective: Resistance to anti-seizure medications (ASMs) presents a significant hurdle in the treatment of people with epilepsy. Genetic markers for resistance to individual ASMs could support clinicians to make better-informed choices for their patients. In this study, we aimed to elucidate whether the response to individual ASMs was associated with common genetic variation.Methods: A cohort of 3,649 individuals of European descent with epilepsy was deeply phenotyped and underwent single nucleotide polymorphism (SNP)-genotyping. We conducted genome-wide association analyses (GWASs) on responders to specific ASMs or groups of functionally related ASMs, using non-responders as controls. We performed a polygenic risk score (PRS) analyses based on risk variants for epilepsy and neuropsychiatric disorders and ASM resistance itself to delineate the polygenic burden of ASM-specific drug resistance.Results: We identified several potential regions of interest but did not detect genome-wide significant loci for ASM-specific response. We did not find polygenic risk for epilepsy, neuropsychiatric disorders, and drug-resistance associated with drug response to specific ASMs or mechanistically related groups of ASMs.Significance: This study could not ascertain the predictive value of common genetic variants for ASM responder status. The identified suggestive loci will need replication in future studies of a larger scale. [less ▲]

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See detailStillborn Banking Union: Explaining Ineffective European Union Bank Resolution Rules
Howarth, David UL; Asimakopoulos, Ioannis

in Journal of Common Market Studies (2021)

Our contribution demonstrates and explains the ineffectiveness of European Union (EU) bank resolution rules, a core element of Banking Union. This inadequacy owes in large part to the limited access to ... [more ▼]

Our contribution demonstrates and explains the ineffectiveness of European Union (EU) bank resolution rules, a core element of Banking Union. This inadequacy owes in large part to the limited access to and insufficient availability of EU resolution funds and inadequate national deposit guarantee schemes in most EU member states, in conjunction with the relatively high minimum requirements for own funds and eligible liabilities (MREL) for many EU banks. In many cases, these requirements are unlikely ever to be met – particularly for retail banks most likely to require resolution in the euro periphery. We offer a liberal intergovernmentalist analysis to explain the inadequacy of the EU resolution regime by examining German and French government preferences on EU rules on bank capital requirements agreed earlier in 2013 and national deposit guarantee schemes agreed in 2014. These government preferences were shaped significantly by the preferences of national banks and bank associations. [less ▲]

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See detailInternational Round Table: “Different Cultures in Digital History”
Schafer, Valerie UL

Presentation (2021, June 08)

The aim of the round table is to bring together specialists in digital history and experts who use digital tools in historical research and education. History as an academic field is undergoing major ... [more ▼]

The aim of the round table is to bring together specialists in digital history and experts who use digital tools in historical research and education. History as an academic field is undergoing major changes as a result of the transformative impact of digital technologies. These technologies affect the very nature of sources, the practice of data collection and processing, and also the way in which historical knowledge is acquired and disseminated. The task of defining “digital history” has given rise to much debate and discussion, but developing an understanding of the field and the wide-ranging potential for interaction between history and digital technologies can offer insights into the future development of historical research and education. Analysing the challenges and opportunities of this interdisciplinary union can inform and enrich the various cultures within digital history and beyond. A number of prominent speakers from different cultures of digital history and related disciplines will participate in the round table: Prof. Leonid Borodkin is a Professor of the History Faculty of Lomonosov Moscow State University, the Chair of the Department for Historical Information Science, Corresponding Member of the Russian Academy of Science (Russia). Prof. Hannu Salmi is a Professor of Cultural History at the University of Turku and has been Academy Professor since 2017 (Finland). Prof. Peter Gautschi is a Professor of History Education, Head of the Lucerne Institute of History Education and Memory Cultures, UTE Lucerne (Switzerland). Prof. Valérie Schafer has been a Professor in Contemporary European History at the C²DH (Luxembourg Centre for Contemporary and Digital History) at the University of Luxembourg since February 2018. Dr Mareike König is deputy director of the German Historical Institute in Paris. She is also director of its library and its digital humanities department. The round table will be organised and moderated by Nadezhda Povroznik (Center for Digital Humanities) and Frédéric Clavert (C²DH). [less ▲]

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See detailDe la poussière à la lumière bleue. Émotions, récits, gestes de l'archive à l'ère numérique
Muller, Caroline; Clavert, Frédéric UL

in Signata - Annales des sémiotiques (2021), 12(12),

For a great many historians, Arlette Farge’s book The Allure of the Archives remains a seminal description of working with archives, at least in France. In the past few years however, a clear disparity ... [more ▼]

For a great many historians, Arlette Farge’s book The Allure of the Archives remains a seminal description of working with archives, at least in France. In the past few years however, a clear disparity has emerged between this book and the actual experience and practice of historical research because of the rise in digital technologies, which have prompted a dramatic change in historians’ relationship with archives. Based on the collective online book Le Goût de l’archive à l’ère numérique (“The allure of the archives in the digital age” – https://www.gout-numerique.net/) and on a study day held in 2018 at the French National Archives, this paper aims to investigate the changing relationship of historians with archives: their emotional engagement, their relations with archivists and their practices when consulting paper, digitised or born-digital archives. From dusty shelves to blue light, the entire profession of historian has changed, often in discreet, implicit ways, such as the recent practice of taking photos at archival centers, a consequence of the widespread ownership and use of digital cameras. Do archives still elicit the same emotions when they are merely one snapshot among many on a hard disk, or when they are turned into data and published online in a corpus? If the emotion attached to archives is no longer the same, does this change the way in which we interpret them? How should we reflect on our own practices so that we can see past the algorithms that drive the search engines and software we now use? [less ▲]

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

E-print/Working paper (2021)

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

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

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

E-print/Working paper (2021)

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

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

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See detailReplicating the Kinora: 3D modelling and printing as heuristics in digital media history
van der Heijden, Tim UL; Wolf, Claude UL

Scientific Conference (2021, June 02)

This presentation reflects on the Kinora replica project, an interdisciplinary collaboration between the Luxembourg Centre for Contemporary and Digital History (C2DH) and the Department of Engineering ... [more ▼]

This presentation reflects on the Kinora replica project, an interdisciplinary collaboration between the Luxembourg Centre for Contemporary and Digital History (C2DH) and the Department of Engineering (DoE) of the University of Luxembourg. Combining historical inquiry with a hands-on and technical approach – involving the latest 3D modelling and desktop additive manufacturing engineering techniques – it provides insights into the process of making a working replica of the Kinora motion picture technology from the early 1900s. [less ▲]

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See detailGlobale Warenketten und ungleiche Entwicklung
Hesse, Markus UL

in Zeitschrift für Wirtschaftsgeographie (2021)

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See detailThe good, the bad, and the asymmetric: Evidence from a new conditional density model
Kostyrka, Andreï UL; Malakhov, Dmitry

E-print/Working paper (2021)

We propose a novel univariate conditional density model and decompose asset returns into a sum of copula-connected unobserved ‘good’ and ‘bad’ shocks. The novelty of this approach comes from two factors ... [more ▼]

We propose a novel univariate conditional density model and decompose asset returns into a sum of copula-connected unobserved ‘good’ and ‘bad’ shocks. The novelty of this approach comes from two factors: we explicitly model correlation between unobserved shocks and allow for the presence of copula-connected discrete jumps. The proposed framework is very flexible and subsumes other models, such as ‘bad environments, good environments’. Our model shows certain hidden characteristics of returns, explains investors’ behaviour in greater detail, and yields better forecasts of risk measures. The in-sample and out-of-sample performance of our model is better than that of 40 popular GARCH variants. A Monte-Carlo simulation shows that the proposed model recovers the structural parameters of the unobserved dynamics. We estimate the model on S&P 500 data and find that time-dependent non-negative covariance between ‘good’ and ‘bad’ shocks with a leverage-like effect is an important component of total variance. Asymmetric reaction to shocks is present almost in all characteristics of returns. Conditional distribution of seems to be very time-dependent with skewness both in the centre and tails. We conclude that continuous shocks are more important than discrete jumps at least at daily frequency. [less ▲]

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See detailSecure Energy Efficiency Maximization in Cognitive Satellite-Terrestrial Networks
Lu, Weixin; An, Kang; Liang, Tao et al

in IEEE Systems Journal (2021), 15(2), 2382-2385

This article investigates the secure energy efficiency (EE) optimization problem in a cognitive satellite-terrestrial network with a capable eavesdropper. The objective is to maximize the secure EE for ... [more ▼]

This article investigates the secure energy efficiency (EE) optimization problem in a cognitive satellite-terrestrial network with a capable eavesdropper. The objective is to maximize the secure EE for the primary satellite network while satisfying the allowable signal-to-interference-plus-noise ratio requirements of the secondary and primary users along within the transmit power limitation of both satellite and the terrestrial base station. Owing to the nonconvexity and intractability of the original optimization problem, a beamforming scheme and associated transformation algorithms are proposed by jointly applying the Taylor approximation, fraction programming, and alternating search to cope with the implementation difficulty. The key is to convert the original optimization problem into a simple convex framework and obtain the optimal solution step by step. Finally, numerical simulations are given to verify the feasibility and practicability of the proposed optimization algorithms. [less ▲]

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