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See detailInteroceptive accuracy, emotion recognition, and emotion regulation in preschool children
Schaan, Luca; Schulz, André UL; Nuraydin, Sevim et al

in International Journal of Psychophysiology (in press)

Little is known about the conscious experience of internal bodily sensations in preschool-aged children. Given that preschoolers are in the most rapid phase of brain development, and display profound ... [more ▼]

Little is known about the conscious experience of internal bodily sensations in preschool-aged children. Given that preschoolers are in the most rapid phase of brain development, and display profound emotional development, it was the aim of the present study to establish an adapted interoceptive accuracy paradigm and to investigate associations between sociodemographic (age, sex) and emotional variables with interoceptive accuracy. Forty-nine children (aged 4-6 years) completed the jumping jack paradigm, a heartbeat tracking paradigm, which includes a noninvasive physical perturbation via performing jumping jacks for 10 seconds. An interoceptive accuracy score was based on the comparison between self-reported and objectively recorded heart rate prior to and after completion of jumping jacks. Children also completed validated measures for emotion recognition and emotion regulation. Children’s objectively recorded heart rate significantly increased after the JJP by 20 bpm on average. There was a positive relationship between reactivity on self-reported heart rate and objectively recorded heart rate increase. The derived scores for interoceptive accuracy increased with age, suggesting older children to report more self-reported heart rate change than objectively recorded, but were unrelated to children’s sex or BMI. While emotion recognition and regulation significantly increased with age, the interoceptive accuracy score was unrelated to emotion recognition, but marginally associated to emotion regulation. Children with higher interceptive accuracy score (i.e., self-reporting more heart rate change than objectively recorded) received lower emotion regulation score. The present study is the first to depict a novel behavioral paradigm to assess interoceptive accuracy in preschool-aged children. [less ▲]

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See detailLower plasma insulin levels during overnight closed loop in schoolchildren with type 1 diabetes: potential advantage?
Schierloh, Ulrike; Wilinska, M.; Pit-Ten Cate, Ineke UL et al

in PLoS ONE (in press)

Background Studies have shown that overnight closed-loop insulin delivery can improve glucose control and reduce the risk of hypoglycemia and hence may improve metabolic outcomes and reduce burden for ... [more ▼]

Background Studies have shown that overnight closed-loop insulin delivery can improve glucose control and reduce the risk of hypoglycemia and hence may improve metabolic outcomes and reduce burden for children with type 1 diabetes and their families. However, research so far has not reported insulin levels while comparing closed-loop to open-loop insulin delivery in children. Therefore, in this study we obtained glucose levels as well plasma insulin levels in children with type 1 diabetes to evaluate the efficacy of a model - based closed-loop algorithm compared to an open-loop administration. Methods Fifteen children with type 1 diabetes, 6-12 years, participated in this open-label single center study. We used a randomized cross over design in which we compared overnight closed-loop insulin delivery with sensor augmented pump therapy for two nights in both the hospital and at home (i.e., 1 night in-patient stay and at home per treatment condition). Only during the in-patient stay, hourly plasma insulin and blood glucose levels were assessed and are reported in this paper. Results Results of paired sample t-tests revealed that although plasma insulin levels were significantly lower during the closed-loop than in the open-loop (Mean difference 36.51 pmol/l; t(13)=2.13, p=.03, effect size d= 0.57), blood glucose levels did not vary between conditions (mean difference 0.76 mmol/l; t(13)=1.24, p=.12, d=0.37). The administered dose of insulin was significantly lower during the closed-loop compared with the open-loop (mean difference 0.10 UI; t(12)=2.45, p=.02, d=0.68). Conclusions Lower insulin doses were delivered in the closed-loop, resulting in lower plasma insulin levels , whereby glucose levels were not affected negatively. This suggests that the closed-loop administration is better targeted and hence could be more effective. [less ▲]

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See detailWhat is meant by inclusion: On the effects of different definitions on attitudes toward inclusion.
Krischler, Mireille UL; Powell, Justin J W UL; Pit-Ten Cate, Ineke UL

in European Journal of Special Needs Education (in press)

Aiming to further our knowledge about what is meant by inclusion, we examined how various conceptualisations relate to people’s attitudes about inclusive education. We assign the varying characterisations ... [more ▼]

Aiming to further our knowledge about what is meant by inclusion, we examined how various conceptualisations relate to people’s attitudes about inclusive education. We assign the varying characterisations of inclusion of specific groups with differing involvement in the education system in Luxembourg, applying the influential systematisation of definitions of inclusion by Göransson and Nilholm (2014). Results of study 1 showed that members of the general population, pre-service and in-service teachers perceive inclusive education in importantly different ways. Although results showed relatively positive attitudes toward inclusive education for the whole sample, attitudes varied by group and in relation to the differential categorisation of definitions. As teachers’ attitudes and the extent to which they feel prepared to implement inclusive practice are crucial for the success of inclusive education, the latter aspect is further investigated in study 2. Results showed that teachers with more in-depth understanding of inclusive education reported more positive attitudes and felt better prepared to implement inclusive practices. Implications for education systems and society are discussed. [less ▲]

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See detailPre- and in-service teachers´ attitudes toward students with learning difficulties and challenging behavior.
Krischler, Mireille UL; Pit-Ten Cate, Ineke UL

in Frontiers in Psychology (in press)

The implementation of inclusive policies is largely dependent on teachers´ willingness to accommodate students with special educational needs (SEN) in mainstream classrooms, which is affected by their ... [more ▼]

The implementation of inclusive policies is largely dependent on teachers´ willingness to accommodate students with special educational needs (SEN) in mainstream classrooms, which is affected by their perceived competence and attitudes. This study investigated attitudes of pre- and in-service teachers toward students with two types of SEN: challenging behavior and learning difficulties. The three components of attitude (affective, cognitive, and behavioral) were assessed using indirect and direct measures. Results revealed that teachers held negative implicit attitudes toward challenging behavior and learning difficulties, however implicit attitudes did not vary as a function of the type of SEN. Ratings of the stereotypical dimensions warmth and competence and overall ratings of scholastic achievement were affected by professional status and type of SEN. Professional status, implicit attitudes and stereotypical knowledge together explained 52 and 43% of the variance in teachers´ ratings of academic proficiency for students with challenging behavior and learning difficulties, respectively. Results are interpreted within the theoretical framework and implications for teacher training are discussed. [less ▲]

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See detailAktuelle Entwicklungen im Steuerrecht in der Informationstechnologie 2017/2018 - Teil 2
Schmittmann, Jens; Sinnig, Julia UL

in Kommunikation und Recht (in press)

Teil 2 des Beitrags knüpft an Teil 1 in K&R 2019, 88 ff. an und fasst die wesentlichen Entwicklungen in Legislative und Judikative im deutschen Steuerrecht zusammen, soweit sich Bezüge zum ... [more ▼]

Teil 2 des Beitrags knüpft an Teil 1 in K&R 2019, 88 ff. an und fasst die wesentlichen Entwicklungen in Legislative und Judikative im deutschen Steuerrecht zusammen, soweit sich Bezüge zum Informationstechnologierecht ergeben. Er knüpft an die Beiträge des Verfassers Prof. Dr. Jens M. Schmittmann in den Vorjahren sowie die Vorträge der Verfasser in Bochum anlässlich der DSRI Herbstakademie 2018 an. [less ▲]

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See detailComputational Arithmetic of Modular Forms
Wiese, Gabor UL

in Buyukasik, Engin; Inam, Ilker (Eds.) Notes from the International Autumn School on Computational Number Theory: Izmir Institute of Technology 2017 (in press)

These course notes are about computing modular forms and some of their arithmetic properties. Their aim is to explain and prove the modular symbols algorithm in as elementary and as explicit terms as ... [more ▼]

These course notes are about computing modular forms and some of their arithmetic properties. Their aim is to explain and prove the modular symbols algorithm in as elementary and as explicit terms as possible, and to enable the devoted student to implement it over any ring (such that a sufficient linear algebra theory is available in the chosen computer algebra system). The chosen approach is based on group cohomology and along the way the needed tools from homological algebra are provided. [less ▲]

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See detailProblematic video game use as an emotional coping strategy: Evidence from a sample of MMORPG gamers.
Blasi, Maria Di; Giardina, Alessandro; Giordano, Cecilia et al

in Journal of behavioral addictions (in press)

BACKGROUND: A positive relationship between problematic gaming and escapism motivation to play video games has been well established, suggesting that problematic gaming may result from attempts to deal ... [more ▼]

BACKGROUND: A positive relationship between problematic gaming and escapism motivation to play video games has been well established, suggesting that problematic gaming may result from attempts to deal with negative emotions. However, to date, no study has examined how emotion dysregulation affects both escapism motives and problematic gaming patterns. METHODS: Difficulties in emotion regulation, escapism, and problematic involvement with video games were assessed in a sample of 390 World of Warcraft players. A structural equation modeling framework was used to test the hypothesis that escapism mediates the relationship between emotion dysregulation and problematic gaming. RESULTS: Statistical analyses showed that difficulties in emotion regulation predicted both escapism motives and problematic gaming, and that escapism partially mediated this relationship. CONCLUSION: Our findings support the view that problematic players are likely to escape in online games as a maladaptive coping strategy for dealing with adverse emotional experiences. [less ▲]

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See detailAn Empirical Study on the Potential Usefulness of Domain Models for Completeness Checking of Requirements
Arora, Chetan UL; Sabetzadeh, Mehrdad UL; Briand, Lionel UL

in Empirical Software Engineering (in press)

[Context] Domain modeling is a common strategy for mitigating incompleteness in requirements. While the benefits of domain models for checking the completeness of requirements are anecdotally known, these ... [more ▼]

[Context] Domain modeling is a common strategy for mitigating incompleteness in requirements. While the benefits of domain models for checking the completeness of requirements are anecdotally known, these benefits have never been evaluated systematically. [Objective] We empirically examine the potential usefulness of domain models for detecting incompleteness in natural-language requirements. We focus on requirements written as “shall”- style statements and domain models captured using UML class diagrams. [Methods] Through a randomized simulation process, we analyze the sensitivity of domain models to omissions in requirements. Sensitivity is a measure of whether a domain model contains information that can lead to the discovery of requirements omissions. Our empirical research method is case study research in an industrial setting. [Results and Conclusions] We have experts construct domain models in three distinct industry domains. We then report on how sensitive the resulting models are to simulated omissions in requirements. We observe that domain models exhibit near-linear sensitivity to both unspecified (i.e., missing) and under-specified requirements (i.e., requirements whose details are incomplete). The level of sensitivity is more than four times higher for unspecified requirements than under-specified ones. These results provide empirical evidence that domain models provide useful cues for checking the completeness of natural-language requirements. Further studies remain necessary to ascertain whether analysts are able to effectively exploit these cues for incompleteness detection. [less ▲]

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See detailDissociation in Problematic Gaming: a Systematic Review
Guglielmucci, Fanny; Monti, Massimiliano; Franzoi, Isabella G. et al

in Current Addiction Reports (in press)

Purpose of Review The present article consists of a systematic review of recent (2007–2018) empirical studies addressing the relationship between problematic gaming and dissociation. Nineteen peer ... [more ▼]

Purpose of Review The present article consists of a systematic review of recent (2007–2018) empirical studies addressing the relationship between problematic gaming and dissociation. Nineteen peer-reviewed empirical studies that examined the relationship between problematic gaming and dissociation were identified. Recent Findings The findings suggest that excessive video game use is linked to a variety of dissociative phenomena (e.g. depersonalisation experiences, escapism, psychotic-like experiences, game transfer phenomena). Summary Dissociative experiences are associated with problematic gaming. The findings support the hypothesis that problematic video game use can represent a maladaptive coping strategy onwhich people can rely to escape from disturbing mental states, adverse emotions or real-life problems. In these circumstances, dissociative symptoms might represent the side effects of an alteration in consciousness that is generated by excessive video game use. However, further research (especially experimental and longitudinal) is required in order to establish a potential causal link between problematic gaming patterns and dissociation. [less ▲]

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See detailValue-added modeling in primary school: What covariates to include?
Levy, Jessica UL; Brunner, Martin; Keller, Ulrich UL et al

Scientific Conference (2019, August)

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See detailBracketing in student writing: its uses (and abuses)
Deroey, Katrien UL

Scientific Conference (2019, July 23)

This paper reports on the use of bracketed text in a large corpus of student writing. The function of bracketing has been neglected in academic writing research and coursebooks. Yet it is closely related ... [more ▼]

This paper reports on the use of bracketed text in a large corpus of student writing. The function of bracketing has been neglected in academic writing research and coursebooks. Yet it is closely related to important text construction issues such as information packaging, coherence, clarity, conciseness, intertextual framing and sourcing. With a view to informing academic writing description and instruction, we examined the relationship between bracketed text and its cotext in a wide variety of disciplines and assignment genres. The relationships are described using an adaptation of Halliday and Matthiessen’s (2014) logico-semantic framework of clausal relationships. To better understand and teach the use of this information packaging feature, we studied the relationship between bracketed text and its cotext in the British Academic Written English (BAWE) corpus of high-graded student assignments. Using Sketch Engine and corpus query language, we extracted a random sample of 2000 instances of bracketing in running text only. This subcorpus is composed of 500 instances from each of the four main disciplinary groupings (Arts and Humanities, Life Sciences, Physical Sciences, Social Sciences) and contains instances from most of the BAWE assignment genres. The concordances were imported into a database table in FileMaker Pro. This database programme facilitates coding by limiting choices depending on previous selections and thus guiding the coder through the analytical steps. For the analysis of the data, it offers flexibility for grouping records and aggregating results on different levels. The logico-semantic framework used in systemic functional linguistics to classify the relationships between clauses (Halliday & Matthiessen, 2014) served as our starting point to classify the relationships between bracketed text and cotext. This framework distinguishes two fundamental logico-semantic relationships: expansion, which ‘relates phenomena as being of the same order of experience’, and projection, which ‘relates phenomena of one order of experience (the processes of saying and thinking) to phenomena of a higher order (semiotic phenomena – what people say and think)’ (p. 443). The latter contains three subtypes: elaboration (‘one clause elaborates on the meaning of another by further specifying or describing it’) (p. 461), enhancement (‘one clause (or subcomplex) enhances the meaning of another by qualifying it) (p. 476) and extension (‘one clause extends the meaning of another by adding something new to it’) (p. 471). This framework was refined and expanded through several stages of interrating and discussion in order to reflect our findings. We first analysed a random sample of 1000 instances from the whole BAWE corpus. With the resulting adapted classificatory framework we next independently analysed a quarter of our subcorpus of 2000 concordances. This led to further refinement of the framework and classificatory criteria. Finally, we each analyzed a different set of concordances from the disciplinary groupings. Disciplinary informants were consulted where needed. Our analysis revealed four major logico-semantic relationships between the bracketed text and cotext: in addition to Halliday & Matthiessen’s (2014) projection (1) and expansion (elaboration (2), enhancement (3, 4), extension (5)), we identified bracketed text functioning as intratextual reference (6) and code (7). The few instances that could not be confidently classified were assigned to a ‘hard to classify’ category. (1) However the anticipated number of children per woman in Europe and the USA is still near or above two (Bongaarts, 1999), showing that many are still having children. (2) Many of these injures are healed fractures and breaks occurring around the torso (upper body). (3) It is dated to the reign of Nectanebo II (360-343 BC). (4) Acetanilide (4.78g, 35.4 mmol) was dissolved in cold, glacial acetic acid (25ml, 437.1 mmol) (5) Parmenides decision to include a cosmology that he has already (apparently) proved to be flawed is an interesting one to say the least. (6) This is called circular polarization (figure 5) and is the natural state of white light. (7) Stronger field ligands such as (PPh 3) and (NCS) increase the splitting. Projection was –perhaps not surprisingly- the most common relationship by far, although markedly less frequent in the Physical Sciences. Expansion was mainly achieved through elaboration, with restatements (2) and abbreviations predominating. Enhancement relationships were mostly temporal locations (3) or measurements (4). Extension was relatively rare (5). Intratextual references (6) took various forms, such as figures, appendices, equations, and line numbers for quoted text. Bracketed code was a marked feature of the Physical Sciences, occurring in formulae and enclosing symbols or abbreviations (7). Overall, students’ use of bracketed text appeared to reflect disciplinary conventions and reflected the genre goals of assignments by demonstrating knowledge, understanding and appropriate source use. Contrary to expectations, instances where the bracketed text seemed superfluous or adversely affected coherence were rare. We conclude by discussing what these findings mean for academic writing instruction. Reference Halliday, M. A. K., & Matthiessen, C. M. I. M. (2014). Halliday's introduction to functional grammar (4 ed.). Abingdon: Routledge. [less ▲]

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See detailHow can we support lecturers in English-medium instruction?
Deroey, Katrien UL

Scientific Conference (2019, April 13)

English-medium instruction (EMI) is a worldwide phenomenon. EMI language and communication issues (e.g. Hu et al., 2014; Murray, 2015; Werther et al., 2014) have led to calls for EAP practitioners to ... [more ▼]

English-medium instruction (EMI) is a worldwide phenomenon. EMI language and communication issues (e.g. Hu et al., 2014; Murray, 2015; Werther et al., 2014) have led to calls for EAP practitioners to collaborate with lecturers and other HE stakeholders to explore ways in which these lecturers can be supported and teaching standards ensured (Coleman, 2006; Doiz et al., 2013; Dubow & Gundermann, 2017). The design and implementation of EMI training and support programmes can be an especially challenging task for EAP practitioners. First, lecturers may not recognize the need for support and may be reluctant to be assessed. Second, we need to factor in practical considerations such as their limited availability and possible reluctance to attend ‘classes’ with colleagues. Third, we have limited resources in terms of specialized standardized tests, training materials and research literature that could inform our 'course' design. Innovative approaches are therefore needed to factor in all these circumstances. This paper has two main parts. First I summarize research on the challenges EMI lecturers face, including the results of a needs analysis among lecturers at the University of Luxembourg and my work on lecture discourse organization (Deroey, 2015). From the relatively few studies that exist, we will see that lecturers tend to believe they have sufficient English language skills and that reduced interactivity is a particularly common issue. Second, I survey different support and training schemes at HE institutions across the world. Here, it will become clear that work on relevant pedagogical skills needs to be included and an apparently ‘remedial’ approach should be avoided if we want to get lecturers on board. [less ▲]

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See detailPricing Perspective for SWIPT in OFDM-based Multi-User Wireless Cooperative Systems
Gautam, Sumit UL; Lagunas, Eva UL; Vuppala, Satyanarayana UL et al

Scientific Conference (2019, April)

We propose a novel formulation for joint maximization of total weighted sum-spectral efficiency and weighted sum-harvested energy to study Simultaneous Wireless Information and Power Transfer (SWIPT) from ... [more ▼]

We propose a novel formulation for joint maximization of total weighted sum-spectral efficiency and weighted sum-harvested energy to study Simultaneous Wireless Information and Power Transfer (SWIPT) from a pricing perspective. Specifically, we consider that a transmit source communicates with multiple destinations using Orthogonal Frequency Division Multiplexing (OFDM) system within a dual-hop relay-assisted network, where the destination nodes are capable of jointly decoding information and harvesting energy from the same radio-frequency (RF) signal using either the time-switching (TS) or power-splitting (PS) based SWIPT receiver architectures. Computation of the optimal solution for the aforementioned problem is an extremely challenging task as joint optimization of several network resources introduce intractability at high numeric values of relays, destination nodes and OFDM sub-carriers. Therefore, we present a suitable algorithm with sub-optimal results and good performance to compute the performance of joint data processing and harvesting energy under fixed pricing methods by adjusting the respective weight factors, motivated by practical statistics. Furthermore, by exploiting the binary options of the weights, we show that the proposed formulation can be regulated purely as a sum-spectral efficiency maximization or solely as a sum-harvested energy maximization problem. Numerical results illustrate the benefits of the proposed design under several operating conditions and parameter values. [less ▲]

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See detailWelcome or not? – Natives’ security feelings, attachment and attitudes toward acculturation of immigrants
Goedert, Christine UL; Albert, Isabelle UL; Barros Coimbra, Stephanie UL et al

in International Journal of Intercultural Relations (2019), 69

Cultural diversity due to immigration has become a key topic in many societies today. The question of how the native population experiences these developments is of prime importance for intercultural ... [more ▼]

Cultural diversity due to immigration has become a key topic in many societies today. The question of how the native population experiences these developments is of prime importance for intercultural relations and sets the base for acculturation of immigrants. Drawing on attachment and multiculturalism research, we supposed here that general and specific feelings of security might be related to more positive attitudes toward cultural diversity, whereas feelings of threat might be related to less openness. More precisely, the present study investigated how natives’ general attachment (secure or fearful) as well as their specific feelings of (cultural or economic) security might be related to their expectations about acculturation of immigrants in the multicultural context of Luxembourg. The sample included N = 134 Luxembourg nationals with an average age of M = 45.02 (SD = 17.41) who filled out an online questionnaire. Results revealed that self-reported fearful general attachment was positively related to more unwelcoming acculturation orientations. Relations between general attachment and acculturation orientations were mediated by feelings of cultural security, which had strong effects on host nationals’ (un)welcoming acculturation orientations over and above general attachment. Findings suggest that (un)welcoming orientations toward immigrants, entailing openness for cultural contact and exchange, are related to feelings of cultural and economic security which are partly biased by a general secure or fearful attachment. Feelings of security seem thus to provide a secure base for tolerance and openness to cultural diversity which are needed in order to deal successfully with the challenges of today’s multicultural societies. [less ▲]

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See detailOPTICAL ANALYSIS OF EFFICIENCY LIMITATIONS OF CU(IN,GA)SE2 GROWN UNDER COPPER EXCESS
Babbe, Finn UL

Doctoral thesis (2019)

Solar cells made from the compound semiconductor Cu(In,Ga)Se2 reach efficiencies of 22:9 % and are thus even better than multi crystalline silicon solar cells. All world records are achieved using ... [more ▼]

Solar cells made from the compound semiconductor Cu(In,Ga)Se2 reach efficiencies of 22:9 % and are thus even better than multi crystalline silicon solar cells. All world records are achieved using absorber layers with an overall copper deficient composition, but Cu-rich grown samples have multiple favourable properties. However, especially losses in the open circuit voltage limit the device performance. Within this work these efficiency limitations of chalcopyrites grown with copper excess are investigated. The work has been divided into four chapters addressing different scientific questions. (i) Do alkali treatments improve Cu-rich absorber layers? The alkali treatment, which lead to the recent improvements of the efficiency world record, is adapted to CuInSe2 samples with Cu-rich composition. The treatment leads to an improvement of the VOC which originates roughly equally from an improvement of the bulk and the removal of a defect close to the interface. The treatment also improves the VOC of Cu-poor samples. In both cases, the treatment increases the fill factor (FF) and leads to a reduction of copper content at the surface. (ii) Is the VOC limited by deep defects in Cu-rich Cu(In,Ga)Se2? A deep defect, which likely limits the VOC, is observed in photoluminescence measurements (PL) independent of a surface treatment. The defect level is proposed to originate from the second charge transition of the CuIn antisite defect (CuIn(-1/-2)). During the investigation also a peak at 0:9 eV is detected and attributed to a DA-transition involving a third acceptor situated (135 ± 10) meV above the valence band. The A3 proposed to originate from the indium vacancy (VIn). Furthermore the defect was detected in admittance measurements and in Cu(In,Ga)Se2 samples with low gallium content. (iii) Is the diode factor intrinsically higher in Cu-rich chalcopyrites? Cu-rich solar cells exhibit larger diode ideality factors which reduce the FF. A direct link between the power law exponent from intensity dependent PL measurements of absorbers and the diode factor of devices is derived and verified using Cu-poor Cu(In,Ga)Se2 samples. This optical diode factor is the same in Cu-rich and Cu-poor samples. (iv) Is the quasi Fermi level splitting (qFLs) of Cu-rich Cu(In,Ga)Se2 absorber layers comparable to Cu-poor samples? Measuring the qFLs of passivated Cu-rich and Cu-poor Cu(In,Ga)Se2 samples, on average a 120 meV lower splitting is determined for Cu-rich samples. This difference increases with gallium content and is likely linked to a defect moving deeper into the bandgap, possibly related to the second charge transition of the CuIn antisite defect. Overall, samples with Cu-rich composition are not limited by the diode factor. However, a deep defect band causes recombination lowering the qFLs and thus the VOC. This defect is not removed by alkali treatments. A key component to improve Cu-rich solar cells in the future, especially Cu(In,Ga)Se2, will be to remove or passivate this defect level. [less ▲]

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See detailLa Roumanie, une synthèse des diversités
Danescu, Elena UL

Article for general public (2019)

Lors de la onzième présidence luxembourgeoise du Conseil de l’UE, l’Europe accueille deux nouveaux membres – la Roumanie et la Bulgarie – qui signent le Traité d’adhésion le 25 avril 2005, à l’Abbaye de ... [more ▼]

Lors de la onzième présidence luxembourgeoise du Conseil de l’UE, l’Europe accueille deux nouveaux membres – la Roumanie et la Bulgarie – qui signent le Traité d’adhésion le 25 avril 2005, à l’Abbaye de Neumünster. En ce début d’année, la Roumanie entame sa première présidence européenne, dont le point d’orgue est le sommet de Sibiu (Hermannstadt) du 9 mai 2019. Si son passé récent est plus connu car souvent présent dans les médias, l’histoire ancienne de la Roumanie, ses affinités multiséculaires avec le Luxembourg et leur héritage culturel commun le sont moins et méritent d’être davantage mis en exergue. [less ▲]

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See detailMany ways to resistance: How melanoma cells evade targeted therapies
Kozar, Ines UL; Margue, Christiane UL; Rothengatter, Sonja et al

in Biochimica et Biophysica Acta (BBA) - Reviews on Cancer (2019), 1871(2), 313-322

Melanoma is an aggressive malignancy originating from pigment-producing melanocytes. The development of targeted therapies (MAPK pathway inhibitors) and immunotherapies (immune checkpoint inhibitors) led ... [more ▼]

Melanoma is an aggressive malignancy originating from pigment-producing melanocytes. The development of targeted therapies (MAPK pathway inhibitors) and immunotherapies (immune checkpoint inhibitors) led to a substantial improvement in overall survival of patients. However, the long-term efficacy of such treatments is limited by side effects, lack of clinical effects and the rapidly emerging resistance to treatment. A number of molecular mechanisms underlying this resistant phenotype have already been elucidated. In this review, we summarise currently available treatment options for metastatic melanoma and the known resistance mechanisms to targeted therapies. A focus will be placed on “phenotype switching” as a mechanism and driver of drug resistance, together with an overview of novel approaches to circumvent resistance. A large body of recent data and literature suggests that tumour progression and phenotype switching could be better controlled and development of resistance prevented or at least delayed, by combining drugs targeting fast- and slow-proliferating cells. [less ▲]

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See detailFunctional Interpretation of Single Amino Acid Substitutions in 1,330 Disease-Associated Genes
Iqbal, Sumaiya; Jespersen, Jakob Berg; Perez-Palma, Eduardo et al

in Biophysical Journal (2019, February 15), 116(3), 420-421

Elucidating molecular consequences of amino-acid-altering missense variants at scale is challenging. In this work, we explored whether features derived from three-dimensional (3D) protein structures can ... [more ▼]

Elucidating molecular consequences of amino-acid-altering missense variants at scale is challenging. In this work, we explored whether features derived from three-dimensional (3D) protein structures can characterize patient missense variants across different protein classes with similar molecular level activities. The identified disease-associated features can advance our understanding of how a single amino acid substitution can lead to the etiology of monogenic disorders. For 1,330 disease-associated genes (>80%, 1,077/1,330 implicated in Mendelian disorders), we collected missense variants from the general population (gnomAD database, N=164,915) and patients (ClinVar and HGMD databases, N=32,923). We in silico mapped the variant positions onto >14k human protein 3D structures. We annotated the protein positions of variants with 40 structural, physiochemical, and functional features. We then grouped the genes into 24 protein classes based on their molecular functions and performed statistical association analyses with the features of population and patient variants. We identified 18 (out of 40) features that are associated with patient variants in general. Specifically, patient variants are less exposed to solvent (p<1.0e-100), enriched on b-sheets (p<2.37e-39), frequently mutate aromatic residues (p<1.0e-100), occur in ligand binding sites (p<1.0e-100) and are spatially close to phosphorylation sites (p<1.0e-100). We also observed differential protein-class-specific features. For three protein classes (signaling molecules, proteases and hydrolases), patient variants significantly perturb the disulfide bonds (p<1.0e-100). Only in immunity proteins, patient variants are enriched in flexible coils (p<1.65e-06). Kinases and cell junction proteins exhibit enrichment of patient variants around SUMOylation (p<1.0e-100) and methylation sites (p<9.29e-11), respectively. In summary, we studied shared and unique features associated with patient variants on protein structure across 24 protein classes, providing novel mechanistic insights. We generated an online resource that contains amino-acid-wise feature annotation-track for 1,330 genes, summarizes the patient-variant-associated features on residue level, and can guide variant interpretation. [less ▲]

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