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Selenium is a well-known health-relevant element related with cancer chemoprevention, neuroprotective roles, beneficial in diabetes, and in several infectious diseases, among others. It is naturally present in some foods, but deficiency in people led to the production of nutraceuticals, supplements, and functional food enriched in this element. There is a U-shaped link between selenium levels and health and a narrow range between toxic and essential levels, and thus, supplementation should be performed carefully. Omics methodologies have become valuable approaches to delve into the responses of dietary selenium in mammals that allowed a deeper knowledge about the metabolism of this element as well as its biological role. In this review, we discuss omics approaches from the workflows to their applications that has been previously used to deep insight into the metabolism of dietary selenium. There is a special focus on selenoproteins, metabolomics responses in blood and tissues (e.g., brain, reproductive organs, etc.) as well as the impact on gut microbiota and its metabolites profile. Thus, we mainly reviewed heteroatom-tagged proteomics, metallomics, metabolomics, and metataxonomics, usually combined with transcriptomics, genomics, and other molecular methods.

Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic actions of counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic neddylation levels. Mechanistically, fasting or caloric restriction of mice leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1) at three lysine residues—K278, K342, and K387. We find that mutating the three PCK1 lysines that are neddylated reduces their gluconeogenic activity rate. Molecular dynamics simulations show that neddylation of PCK1 could re-position two loops surrounding the catalytic center into an open configuration, rendering the catalytic center more accessible. Our study reveals that neddylation of PCK1 provides a finely tuned mechanism of controlling glucose metabolism by linking whole nutrient availability to metabolic homeostasis.

Background Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitisation as a major determinant. Objective We aimed to see if there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitisation, in a multi-centre population-based study. Methods A total of 741 subjects with current asthma and 4,155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitisation status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO was assessed in adjusted multivariate regression models and test for interaction with perennial sensitisation and asthma on the relation between UAID and FeNO were made. Results UAID were associated with higher FeNO after adjusting for perennial sensitisation, asthma and other confounders: with 4.4 (0.9?7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7?9.2)% higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitisation was found in the relationship between current rhinitis and FeNO (p=0.03) and between rhinoconjunctivitis and FeNO (p=0.03). After stratification by asthma and perennial sensitisation, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitisation, with 12.1 (0.2?25.5) % higher FeNO in subjects with current rhinitis than in those without. Conclusions & Clinical Relevance Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitisation. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the

Introduction Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR. Methods We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction. Results Our sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %). Implications Our findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR.

Objective: To establish a workflow for mitochondrial DNA (mtDNA) CpG methylation using Nanopore whole-genome sequencing and perform first pilot experiments on affected Parkin biallelic mutation carriers (Parkin-PD) and healthy controls. Background: Mitochondria, including mtDNA, are established key players in Parkinson's disease (PD) pathogenesis. Mutations in Parkin, essential for degradation of damaged mitochondria, cause early-onset PD. However, mtDNA methylation and its implication in PD is understudied. Herein, we establish a workflow using Nanopore sequencing to directly detect mtDNA CpG methylation and compare mtDNA methylation between Parkin-related PD and healthy individuals. Methods: To obtain mtDNA, whole-genome Nanopore sequencing was performed on blood-derived from five Parkin-PD and three control subjects. In addition, induced pluripotent stem cell (iPSC)-derived midbrain neurons from four of these patients with PD and the three control subjects were investigated. The workflow was validated, using methylated and unmethylated 897 bp synthetic DNA samples at different dilution ratios (0, 50, 100% methylation) and mtDNA without methylation. MtDNA CpG methylation frequency (MF) was detected using Nanopolish and Megalodon. Results: Across all blood-derived samples, we obtained a mean coverage of 250.3X (SD ± 80.5X) and across all neuron-derived samples 830X (SD ± 465X) of the mitochondrial genome. We detected overall low-level CpG methylation from the blood-derived DNA (mean MF ± SD = 0.029 ± 0.041) and neuron-derived DNA (mean MF ± SD = 0.019 ± 0.035). Validation of the workflow, using synthetic DNA samples showed that highly methylated DNA molecules were prone to lower Guppy Phred quality scores and thereby more likely to fail Guppy base-calling. CpG methylation in blood- and neuron-derived DNA was significantly lower in Parkin-PD compared to controls (Mann-Whitney U-test p < 0.05). Conclusion: Nanopore sequencing is a useful method to investigate mtDNA m

In the space of less than 150 years, the population of the Grand Duchy of Luxembourg, more than doubled, which is largely attributable to immigration. Today, almost half of the population are foreigners. The authors argue that that the current immigration policy of Luxembourg is based on a strategy of accommodation. They identify three major pillars of this strategy. The first pillar creates conditions favourable to adaptation with the host society. The second pillar brings liberal provisions for naturalization, and the third one offers an open and generous admission of refugees

Two of the most attractive characteristics of Concentrated Solar Power are the high-quality heat exploitable and its capacity for thermal energy storage, which enhance the energy dispatchability in comparison with other renewable sources such as photovoltaics or wind. Consistent efforts are therefore direct to the research of sui- table thermodynamic cycles and energy storage systems with low thermal losses and high operating tempera- tures. However, in the most developed technologies, based on sensible and latent heat storage, high thermal losses are the direct consequence of high operating temperatures. As alternative, Thermochemical Energy Storage systems are gaining attention in the last years. The present work investigates the adoption of a novel Calcium-Looping system for Thermochemical Energy Storage, focusing on the integration on carbonator side. This key integration is directly linked to the energy delivery from the energy storage system and therefore power generation capacity of the plant. An optimization of the carbonator side plant is performed for a direct integration layout, where carbon dioxide from the car- bonator evolves through the power block. This analysis aims to maximize the system efficiency acting both on the process components operation and on the thermal transfer between the involved streams. The optimization relies on a novel method based on a genetic algorithm. The pinch analysis is adopted for this study and proper constraints are provided to obtain a configuration exploiting only the renewable energy source. A multi-ob- jective optimization is performed to find out the heat exchanger network topology changes that occur for dif- ferent operating conditions and derived from this analysis suggestion for systems integration are provided.

The effects of continuous and intermittent (simulating a day-night cycle) exposure to ozone enriched atmosphere (from 1.6 to 60 mg kg−1) at 5 °C for 28 d and subsequent shelf life at 20 °C for 15 d on six citrus varieties (two mandarins: Fortune and Ortanique; and four oranges: Navelate, Lanelate, Salustiana and Valencia) were investigated. In vitro and in vivo growth of Penicillium digitatum and Penicillium italicum was first assessed. Based on the results obtained, continuous 60 mg kg−1 ozone and intermittent 1.6 mg kg−1 ozone were selected for industrial trials, and decay and oleocellosis incidence, colour, firmness, weight losses and juice (content, soluble solids, pH, titratable acidity and vitamin C) were analysed. Results showed that the application of ozone was not detrimental to fruit quality. Furthermore, the application of both continuous and intermittent ozone delayed decay and oleocellosis incidence and slowed down the development of the colouring process, while reducing firmness and weight losses. For industrial applications, the advantage of using ozone 12 h d−1, simulating a day-night cycle, is that workers would not be exposed to ozone inside the cold storage room during the day shift.

Les migrations par le mariage, pour le mariage, ou l’étude des pratiques de régulation des flux par le biais conjugal font l’objet d’une attention de plus en plus importante dans les littératures académiques francophones et anglophones aujourd’hui. Certains mariages binationaux, parce qu’ils présentent un risque migratoire au regard des discours politiques, sont ainsi placés « sous haute surveillance » (D’Aoust 2012). Pénétrer à l’intérieur des institutions qui mettent en pratique ce contrôle des individus permet la mise en lumière des acteurs de ces nouvelles polices de l’intime. Dans cette communication à deux voix, nous souhaitons aborder la question du traitement différentiel des entretiens des conjoints avant la délivrance d’une capacité à mariage entre des femmes russes et des femmes françaises dites d’origine marocaine, au sein des consulats français au Maroc et français en Russie. À travers l’analyse des observations réalisées durant les auditions des couples, nous interrogerons la co-construction et l’activation de perspectives néo-orientalistes par les autorités consulaires ou comment, à travers des catégories, les femmes sont réduites à des concepts sexistes et essentialistes. L’objectif est double :rendre compte des pratiques réelles et éventuels rites d’interaction entre les agents consulaires et les candidat-e-s au mariage ainsi que d’objectiver socialement la construction des rapports sociaux de sexe, de classe et de race à travers les différences d’application d’une même circulaire., info:eu-repo/semantics/nonPublished

Objective: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. Wereport retention, efficacy, and tolerability in a cohort of patients with MTLE-HS. Methods: Clinical data were collected from a European database of patients with epilepsy. We estimated retention, 12-month seizure freedom, and adverse drug reaction (ADR) rates for the 10 most commonly used AEDs in patients with MTLE-HS. Results: Seven hundred sixty-seven patients with a total of 3,249 AED trials were included. The highest 12-month retention rates were observed with carbamazepine (85.9%), valproate (85%), and clobazam (79%). Twelve-month seizure freedom rates varied from 1.2% for gabapentin and vigabatrin to 11% for carbamazepine. Response rates were highest for AEDs that were prescribed as initial treatment and lowest for AEDs that were used in a third or higher instance. ADRs were reported in 47.6% of patients, with the highest rates observed with oxcarbazepine (35.7%), topiramate (30.9%), and pregabalin (27.4%), and the lowest rates with clobazam (6.5%), gabapentin (8.9%), and lamotrigine (16.6%). The most commonly reported ADRs were lethargy and drowsiness, dizziness, vertigo and ataxia, and blurred vision and diplopia. Significance: Our results did not demonstrate any clear advantage of newer versus older AEDs. Our results provide useful insights into AED retention, efficacy, and ADR rates in patients with MTLE-HS.

Neutron-proton pairing correlations are investigated in detail via np transfer reactions in N = Z sd-shell nuclei. In particular, we study the cross-section ratio of the lowest 0+ and 1+ states as an observable to quantify the interplay between T = 0 (isoscalar) and T = 1 (isovector) pairing strengths. The experimental results are compared to second-order distorted-wave Born approximation calculations with proton-neutron amplitudes obtained in the shell-model formalism using the universal sd-shell interaction B. Our results suggest underestimation of the nonneglible isoscalar pairing strength in the shell-model descriptions at the expense of the isovector channel.

Peaceful coexistence is a major implementation issuefor both cognitive radios and ultra wideband (UWB) systems.Accordingly, the UWB impulse radio (UWB-IR) based WirelessPersonal Area Network (WPAN) standard IEEE 802.15.4a hassuggested using linear combination of pulse to limit interfer-ence to coexisting primary systems. In this paper, motivatedby implementing the IEEE 802.15.4a based UWB-IR systemsfor peaceful coexistence, we consider the implementation oflinear combination of pulses as suggested by the standard.Accordingly, we (i) design possible linearly combined pulses thatconform to the standard requirements, (ii) consider coherentand noncoherent receiver structures that can be adapted for thephysical layer of the IEEE 802.15.4a standard, (iii) investigatethe effect of channel models on the system performance, and(iv) study the UWB-IR system performance in the presenceof narrowband and orthogonal frequency division multiplexing(OFDM) based wideband primary systems with various band-widths and subcarriers. The study shows that the UWB-IR systemperformance can be significantly improved by selecting suitablepulses for transmission and employing appropriate filteringtechniques at the receiver when the primary system is active.For the implementation of IEEE 802.15.4a based UWB systemscomplying with coexistence requirements, the results of this studyshould be carefully considered.

VILLA (ANR, DFG, NWO) investigates the very first phases of foreign language acquisition under controlled input conditions. Our learners, total beginners with five different native languages (French, German, Dutch, English, Italian) were exposed to 14 hours of target language Polish. Regular tasks in Polish documented the acquisitional path of all learners., Le projet VILLA (ANR, DFG, NWO) examine les premières étapes d'acquisition d'une langue étrangère dans des conditions contrôlées. Des vrais débutants (de 5 langues maternelles différentes: néerlandais, anglais, français, allemand, italien) ont été exposés à 14 h d'une nouvelle langue (polonais). Les tâches en polonais ont permis de suivre leurs itinéraires acquisitionnels.

As views on the democratic deficit of the EU and its search for legitimacy have changed dramatically over recent years, understanding what and how people think about European integration appears crucial. Our objective in this paper is to reintroduce temporality in the analysis of citizens’ attitudes (Lindberg & Scheingold, 1970). We claim that temporality is important not only to understand institutions and public policies, as shown by recent studies (Goetz et al., 2009) but also to comprehend citizens’ attitudes towards European integration. Recent studies propose a research agenda on EU timescale (JEPP, 2009, 16(2)). They however lack to investigate the effect of temporality at the citizens’ level. We postulate that national visions of Europe and its impact derive from different perceptions of what the Union was (in the past), is (present) and where it is going (expected and desired future(s)) (Belot, 2000; Medrano, 2012: 193). In the wake of crisis in Europe, citizens’ beliefs that reality will meet their expectations – whatever these expectations are based on : peace, democracy, citizenship or economy to name a few – might play as an important role in their attitudes towards the EU as other factors such as utilitarian and identity based factors. Our analyses are based both on two sets of qualitative data (interviews and focus-groups collected at ten years distance (mid 1990 and 2006) in France and Britain).

Have European citizens become increasingly Eurosceptic over the last two decades, turning their backs on European integration? Though many journalists, politicians and academics argue that they have, this paper suggests that reactions to European integration cannot be reduced uniquely to a rise in Euroscepticism, but that indifference and ambivalence need also to be brought into the picture when studying EU legitimacy and its politicization. As the enhanced politicization of the European integration has marked the EU post-Maastricht development, this text aims at understanding how this politicization has impacted on the acceptance and the appropriation of the political order by lay citizens. This paper challenges the idea that a growing politicization leads necessarily to a polarization of citizens’ attitudes towards the EU. I propose an alternative interpretation, which argues that the acceptance of a European political order stems from at least two rationales. On one hand, amongst the elites (understood in a broad sense as political or economic or even simply citizens interested in the political sphere) one observes indeed a polarization of opinion characterized by a decline in support and a reinforcement of opposition to the processes of European integration. This tendency is emphasized and explained by the model of “constraining dissensus”. On the other hand, one observes the reinforcement of indifference and indecision amongst ordinary citizens not expert in political matters, faced with this same process. In the latter case, the politicization of the EU leads ordinary citizens at the same time to develop more ambivalent attitudes towards the integration process and to consider the EU as “normal politics”. Through these two mechanisms, the enhanced politicization of the EU leads to indifference, in one case by ambivalence and in the other by defection. Drawing on evidence from survey data, and from 24 focus groups conducted in francophone Belgium, France and Gr

info:eu-repo/semantics/nonPublished

The neutron Time-of-Flight facility at CERN was built to measure the neutron capture and fission cross sections. A short description of the facility, the detectors and the data analysis techniques will be illustrated. A short review of the preliminary results on the fission cross sections is presented together with the implications in fundamental nuclear physics and in nuclear technologies. Future perspectives both for the experimental campaign and for the upgrade of the facility are discussed.