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See detailAbsence of regulator of G-protein signaling 4 does not protect against dopamine neuron dysfunction and injury in the mouse 6-hydroxydopamine lesion model of Parkinson's disease
Ashrafi, Amer UL; Garcia, Pierre UL; Kollmus, Heike et al

in Neurobiology of Aging (in press)

Regulator of G-Protein Signaling 4 (RGS4), a member of the RGS family of proteins that inactivate G-proteins, has gained interest as a potential drug target for neurological disorders, such as epilepsy ... [more ▼]

Regulator of G-Protein Signaling 4 (RGS4), a member of the RGS family of proteins that inactivate G-proteins, has gained interest as a potential drug target for neurological disorders, such as epilepsy and Parkinson’s disease (PD). In the case of PD, the main current option for alleviating motor symptoms are dopamine replacement therapies, which have limitations because of side effects, and reduced effectiveness over the long term. Research on new non-dopaminergic PD drug targets has indicated that inhibition of RGS4 could be an effective adjuvant treatment option. The effectiveness of RGS4 inhibition for an array of PD-linked functional and structural neuroprotection endpoints has not yet been demonstrated. Here, we use the 6-Hydroxydopamine (6-OHDA) lesioning model of the nigrostriatal pathway in mice to address this question. We observe, using a battery of behavioral and pathological measures, that mice deficient for RGS4 are not protected from 6-OHDA induced injury, and show enhanced susceptibility in some measures of motor function. Our results suggest that inhibition of RGS4 as a non-dopaminergic target for PD should be approached with caution. [less ▲]

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See detailExperimental design trade-offs for gene regulatory network inference: an in silico study of the yeast Saccharomyces cerevisiae cell cycle
Markdahl, Johan UL; Colombo, Nicolo UL; Thunberg, Johan UL et al

in Proceedings of the 56th IEEE Conference on Decision and Control (in press)

Time-series of high throughput gene sequencing data intended for gene regulatory network (GRN) inference are often short due to the high costs of sampling cell systems. Moreover, experimentalists lack a ... [more ▼]

Time-series of high throughput gene sequencing data intended for gene regulatory network (GRN) inference are often short due to the high costs of sampling cell systems. Moreover, experimentalists lack a set of quantitative guidelines that prescribe the minimal number of samples required to infer a reliable GRN model. We study the temporal resolution of data vs.quality of GRN inference in order to ultimately overcome this deficit. The evolution of a Markovian jump process model for the Ras/cAMP/PKA pathway of proteins and metabolites in the G1 phase of the Saccharomyces cerevisiae cell cycle is sampled at a number of different rates. For each time-series we infer a linear regression model of the GRN using the LASSO method. The inferred network topology is evaluated in terms of the area under the precision-recall curve (AUPR). By plotting the AUPR against the number of samples, we show that the trade-off has a, roughly speaking, sigmoid shape. An optimal number of samples corresponds to values on the ridge of the sigmoid. [less ▲]

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See detailNaturwissenschaftliche Bildung aus lerntheoretischer Perspektive
Andersen, Katja Natalie UL

in Hugoth, Matthias (Ed.) Handbuch für Träger von Kindertageseinrichtungen (in press)

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See detailGesellschaftskritische Orientierungen linker Aktivisten – Ergebnisse einer qualitativen Studie.
Kühnel, Wolfgang; Willems, Helmut UL

in Behrmann, Günter C.; Schürmann, Eberhard; Willems, Helmut (Eds.) Der Felsengärtner. Freundesgabe für Roland Eckert. (in press)

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See detailSmart Bound Selection for the Verification of UML/OCL Class Diagrams
Clarisó, Robert; Gonzalez Perez, Carlos Alberto UL; Cabot, Jordi

in IEEE Transactions on Software Engineering (in press)

Correctness of UML class diagrams annotated with OCL constraints can be checked using bounded verification techniques, e.g., SAT or constraint programming (CP) solvers. Bounded verification detects faults ... [more ▼]

Correctness of UML class diagrams annotated with OCL constraints can be checked using bounded verification techniques, e.g., SAT or constraint programming (CP) solvers. Bounded verification detects faults efficiently but, on the other hand, the absence of faults does not guarantee a correct behavior outside the bounded domain. Hence, choosing suitable bounds is a non-trivial process as there is a trade-off between the verification time (faster for smaller domains) and the confidence in the result (better for larger domains). Unfortunately, bounded verification tools provide little support in the bound selection process. In this paper, we present a technique that can be used to (i) automatically infer verification bounds whenever possible, (ii) tighten a set of bounds proposed by the user and (iii) guide the user in the bound selection process. This approach may increase the usability of UML/OCL bounded verification tools and improve the efficiency of the verification process. [less ▲]

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See detailLessons from social network analysis to Industry 4.0
Omar, Yamila UL; Minoufekr, Meysam UL; Plapper, Peter UL

in Manufacturing Letters (in press)

With the advent of Industry 4.0, a growing number of sensors within modern production lines generate high volumes of data. This data can be used to optimize the manufacturing industry in terms of complex ... [more ▼]

With the advent of Industry 4.0, a growing number of sensors within modern production lines generate high volumes of data. This data can be used to optimize the manufacturing industry in terms of complex network topology metrics commonly used in the analysis of social and communication networks. In this work, several such metrics are presented along with their appropriate interpretation in the field of manufacturing. Furthermore, the assumptions under which such metrics are defined are assessed in order to determine their suitability. Finally, their potential application to identify performance limiting resources, allocate maintenance resources and guarantee quality assurance are discussed. [less ▲]

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See detailDer Felsengärtner. Freundesgabe für Roland Eckert.
Behrmann, Günter C.; Schürmann, Eberhard; Willems, Helmut UL

Book published by Spurbuch Verlag (in press)

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See detailMacroprudential policy and household wealth inequality
Carpantier, Jean-Francois; Olivera, Javier; van Kerm, Philippe UL

in Journal of International Money & Finance (in press)

Macroprudential policies, such as caps on loan-to-value (LTV) ratios, have become part of the policy paradigm in emerging markets and advanced countries alike. Given that housing is the most important ... [more ▼]

Macroprudential policies, such as caps on loan-to-value (LTV) ratios, have become part of the policy paradigm in emerging markets and advanced countries alike. Given that housing is the most important asset in household portfolios, relaxing or tightening access to mortgages may affect the distribution of household wealth in the country. In a stylised model we show that the final level of wealth inequality depends on the size of the LTV ratio, housing prices, credit cost and the strength of a bequest motive, and therefore it is not possible to predict an unequivocal effect of LTV ratios on wealth inequality. These trade-offs are illustrated with estimations of `Gini Recentered Influence Function' regressions on household survey data from 12 Euro-zone countries that participated in the first wave of the Household Finance and Consumption Survey. The results show that, among the households with active mortgages, high LTV ratios at the time of acquisition are related to high contributions to wealth inequality today, while house price increases are negatively related to inequality contributions. A proxy for the strength of bequest motives tends to be negatively related with wealth inequality, but credit cost does not show a significant link to the distribution of wealth. [less ▲]

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See detailSchulische und außerschulische Jugendbildung. Konzepte, Zielsetzung, pädagogische Ansätze.
Würtz, Stefanie; Willems, Helmut UL

in Behrmann, Günter C.; Schürmann, Eberhard; Willems, Helmut (Eds.) Der Felsengärtner. Freundesgabe für Roland Eckert. (in press)

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See detailUne cour constitutionnelle différente des autres. Etendue, raisons & avenir de l'originalité de la Cour constitutionnelle luxembourgeoise
Heuschling, Luc UL

in Gerkrath, Jörg (Ed.) Les 20 ans de la Cour Constitutionnelle: trop jeune pour mourir? (in press)

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See detailA structure-activity relationship linking non-planar PCBs to functional deficits of neural crest cells: new roles for connexins
Nyffeler, Johanna; Chovancova, Petra; Dolde, Xenia et al

in Archives of Toxicology (in press)

Migration of neural crest cells (NCC) is a fundamental developmental process, and test methods to identify interfering toxicants have been developed. By examining cell function endpoints, as in the ... [more ▼]

Migration of neural crest cells (NCC) is a fundamental developmental process, and test methods to identify interfering toxicants have been developed. By examining cell function endpoints, as in the ‘migration-inhibition of NCC (cMINC)’ assay, a large number of toxicity mechanisms and protein targets can be covered. However, the key events that lead to the adverse effects of a given chemical or group of related compounds are hard to elucidate. To address this issue, we explored here, whether the establishment of two overlapping structure–activity relationships (SAR)—linking chemical structure on the one hand to a phenotypic test outcome, and on the other hand to a mechanistic endpoint—was useful as strategy to identify relevant toxicity mechanisms. For this purpose, we chose polychlorinated biphenyls (PCB) as a large group of related, but still toxicologically and physicochemically diverse structures. We obtained concentration-dependent data for 26 PCBs in the cMINC assay. Moreover, the test chemicals were evaluated by a new high-content imaging method for their effect on cellular re-distribution of connexin43 and for their capacity to inhibit gap junctions. Non-planar PCBs inhibited NCC migration. The potency (1–10 μM) correlated with the number of ortho-chlorine substituents; non-ortho-chloro (planar) PCBs were non-toxic. The toxicity to NCC partially correlated with gap junction inhibition, while it fully correlated (p < 0.0004) with connexin43 cellular re-distribution. Thus, our double-SAR strategy revealed a mechanistic step tightly linked to NCC toxicity of PCBs. Connexin43 patterns in NCC may be explored as a new endpoint relevant to developmental toxicity screening. [less ▲]

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See detailThe Matthew Effect in Electoral Campaigns: Increase in Policy Congruence Inequality During the Campaign
Walgrave, Stefaan; Lesschaeve, Christophe UL

in Electoral Studies : An International Journal (in press)

Previous studies have almost consistently found differences between lower and higher educated voters regarding their policy congruence, the policy position agreement between voters and their party. This ... [more ▼]

Previous studies have almost consistently found differences between lower and higher educated voters regarding their policy congruence, the policy position agreement between voters and their party. This study analyses the role of a campaign herein. Based on novel panel evidence with an extensive battery of policy statements, combined with a survey of party leaders using the same items, we find that, more than the lowly educated, the highly educated profit from the campaign to increase their policy congruence. The reason for the increased inequality is that the later switch parties more often during the campaign than the former. Our evidence also suggests that the higher educated switch parties because this may increase their policy congruence. In sum, the campaign produces a Matthew effect. Those already having a higher policy congruence increase their congruence even further, while those with a lower congruence to start with, do not make any significant progress. [less ▲]

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See detailResearch on Meaning Making in Luxembourgish Primary Science Education: Implications of a Space-Time-Analysis
Andersen, Katja Natalie UL

in Siry, Christina; Schreiber, Catherina; Gomez Fernandez, Roberto (Eds.) et al Critical methodologies for researching teaching and learning (in press)

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See detailAn Experience Report On Applying Software Testing Academic Results In Industry: We Need Usable Automated Test Generation
Arcuri, Andrea UL

in Empirical Software Engineering (in press)

What is the impact of software engineering research on current practices in industry? In this paper, I report on my direct experience as a PhD/post-doc working in software engineering research projects ... [more ▼]

What is the impact of software engineering research on current practices in industry? In this paper, I report on my direct experience as a PhD/post-doc working in software engineering research projects, and then spending the following five years as an engineer in two different companies (the first one being the same I worked in collaboration with during my post-doc). Given a background in software engineering research, what cutting-edge techniques and tools from academia did I use in my daily work when developing and testing the systems of these companies? Regarding validation and verification (my main area of research), the answer is rather short: as far as I can tell, only FindBugs. In this paper, I report on why this was the case, and discuss all the challenging, complex open problems we face in industry and which somehow are ``neglected'' in the academic circles. In particular, I will first discuss what actual tools I could use in my daily work, such as JaCoCo and Selenium. Then, I will discuss the main open problems I faced, particularly related to environment simulators, unit and web testing. After that, popular topics in academia are presented, such as UML, regression and mutation testing. Their lack of impact on the type of projects I worked on in industry is then discussed. Finally, from this industrial experience, I provide my opinions about how this situation can be improved, in particular related to how academics are evaluated, and advocate for a greater involvement into open-source projects. [less ▲]

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See detailComputational systems biology approaches for Parkinson's disease
Glaab, Enrico UL

in Cell and Tissue Research (in press)

Parkinson’s disease (PD) is a prime example of a complex and heterogeneous disorder, characterized by multifaceted and varied motor- and non-motor symptoms and different possible interplays of genetic and ... [more ▼]

Parkinson’s disease (PD) is a prime example of a complex and heterogeneous disorder, characterized by multifaceted and varied motor- and non-motor symptoms and different possible interplays of genetic and environmental risk factors. While investigations of individual PD-causing mutations and risk factors in isolation are providing important insights to improve our understanding of the molecular mechanisms behind PD, there is a growing consensus that a more complete understanding of these mechanisms will require an integrative modeling of multifactorial disease-associated perturbations in molecular networks. Identifying and interpreting the combinatorial effects of multiple PD-associated molecular changes may pave the way towards an earlier and reliable diagnosis and more effective therapeutic interventions. This review provides an overview of computational systems biology approaches developed in recent years to study multifactorial molecular alterations in complex disorders, with a focus on PD research applications. Strengths and weaknesses of different cellular pathway and network analyses, and multivariate machine learning techniques for investigating PD-related omics data are discussed, and strategies proposed to exploit the synergies of multiple biological knowledge and data sources. A final outlook provides an overview of specific challenges and possible next steps for translating systems biology findings in PD to new omics-based diagnostic tools and targeted, drug-based therapeutic approaches. [less ▲]

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See detailA Roundtrip – Inspired by Gustav Jahoda: Observations of a Mature Student
Murdock, Elke UL

in Culture & Psychology (in press)

There was a brief overlap between Gustav Jahoda’s path towards the end of his academic (pre-emeritus) career and my own as a student at the Saarland University – a prominent place in the development of ... [more ▼]

There was a brief overlap between Gustav Jahoda’s path towards the end of his academic (pre-emeritus) career and my own as a student at the Saarland University – a prominent place in the development of cultural psychology. This article highlights some of Jahoda’s fruitful collaborations with Saarbruecken colleagues on the history of (cross-) cultural psychology as well as definitions of perspectives within the field. Gustav Jahoda has also inspired me to pursue the field of cross-cultural psychology and a personal account of this journey will be provided leading to some general observations about Gustav Jahoda’s legacy from a mature student’s perspective. [less ▲]

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See detailThe competence to conclude the new generation of free trade agreements: lessons from Opinion 2/15
Neframi, Eleftheria UL

in Chaisse, Julien (Ed.) China-European Union Investment Relationships (in press)

Opinion 2/15 addresses the question of the external competence of the EU to conclude a free trade agreement with Singapore (EUSFTA). The nature of the EU’s competence determines the conclusion of an EU ... [more ▼]

Opinion 2/15 addresses the question of the external competence of the EU to conclude a free trade agreement with Singapore (EUSFTA). The nature of the EU’s competence determines the conclusion of an EU-only agreement, or a mixed agreement, jointly by the Union and its Member States. The Court of Justice of the European Union held that the EU competence to conclude the EUSFTA is not exclusive, as long as provisions concerning non-direct investments and dispute settlement fall under the shared competence of the Union and its Member States. The Court of Justice made valuable contributions to the interpretation of the scope of the Union’s competence in the field of common commercial policy, comprising sustainable development provisions, as well as to the interpretation of implied external competences, and clarified the status of non-substantive provisions. However, uncertainty remains as far as the meaning and the impact of a shared competence are concerned. [less ▲]

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See detailInduced sadness increases persistence in a simulated slot machine task among recreational gamblers
Devos, Gaëtan; Clark, Luke; Maurage, Pierre et al

in Psychology of Addictive Behaviors : Journal of the Society of Psychologists in Addictive Behaviors (in press)

Gambling may constitute a strategy for coping with depressive mood, but a direct influence of depressive mood on gambling behaviors has never been tested via realistic experimental designs in gamblers ... [more ▼]

Gambling may constitute a strategy for coping with depressive mood, but a direct influence of depressive mood on gambling behaviors has never been tested via realistic experimental designs in gamblers. The current study tested whether experimentally induced sadness increases persistence on a simulated slot machine task using real monetary reinforcement in recreational gamblers. Sixty participants were randomly assigned to an experimental (sadness induction) or control (no emotional induction) condition, and then performed a slot machine task consisting of a mandatory phase followed by a persistence phase. Potential confounding variables (problem gambling symptoms, impulsivity traits, gambling cognitions) were measured to ensure that the experimental and control groups were comparable. The study showed that participants in the sadness condition displayed greater gambling persistence than control participants (p = .011). These data support the causal role of negative affect in decisions to gamble and persistence, which bears important theoretical and clinical implications [less ▲]

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