H2020 Program Research Articles

Mutations in the stromal antigen 3 (STAG3) gene cause male infertility due to meiotic arrest.

Are sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males? Sequence variants affecting protein function of STAG3 cause male infertility due to meiotic arrest. In both women and men, STAG3 encodes for a meiosis-specific protein that is crucial for the functionality of meiotic cohesin complexes. Sequence variants in STAG3 have been reported to cause meiotic arrest in male and female mice and premature ovarian failure in human females, but not in infertile human males so far. The full coding region of STAG3 was sequenced directly in a cohort of 28 men with NOA due to meiotic arrest. In addition, a larger group of 275 infertile men that underwent whole-exome sequencing (WES) was screened for potential STAG3 sequence variants. Furthermore, meiotic spreads, immunohistochemistry, WES and population sampling probability (PSAP) have been conducted in the index case. This study included 28 infertile but otherwise healthy human males who underwent Sanger sequencing of the full coding region of STAG3. Additionally, WES data of 275 infertile human males with different infertility phenotypes have been screened for relevant STAG3 variants. All participants underwent karyotype analysis and azoospermia factor (AZF) screening in advance. In the index patient, segregation analysis, WES data, PSAP, lab parameters, testis histology and nuclear spreads have been added to suplort the findings. Two compound-heterozygous variants in STAG3 (c.[1262T>G];[1312C>T], p.[(Leu421Arg)];[(Arg438Ter)]) have been found to cause male infertility due to complete bilateral meiotic arrest in an otherwise healthy human male. Compound heterozygosity was confirmed by Sanger sequencing of the parents and the patient's brother. Other variants which may affect spermatogenesis have been ruled out through analysis of the patient's WES data and application of the PSAP pipeline. As expected from Stag3 knockout-mice meiotic spreads, germ cells did not develop further than zygotene and showed drastic chromosome aberrations. No rare variants in STAG3 were found in the 275 infertile males with other phenotypes. Our results indicate that STAG3 variants that negatively affect its protein function are a rare cause of NOA (<1% of cases). We identified only one patient with compound-heterozygous variants in STAG3 causing NOA due to meiotic arrest. Future studies should evaluate STAG3 variants in larger cohorts to support this finding. Identification of STAG3 sequence variants in infertile human males should improve genetic counselling as well as diagnostics and treatment. Especially before testicular sperm extraction (TESE) for ICSI, STAG3 variants should be ruled out to prevent unnecessary interventions with frustrating outcomes for both patients and clinicians. This work was carried out within the frame of the German Research Foundation (DFG) Clinical Research Unit 'Male Germ Cells: from Genes to Function' (CRU326). Work in the laboratory of R.J. is supported by a grant of the European Union H2020 program GermAge. The authors declare no conflicts of interest. Not applicable.

Research and development in the field of Artificial Intelligence in EU framework programmes

Abstract The aim of this contribution is to evaluate the cooperation of the European countries in projects related to the AI in the 7th Framework Programme (FP7) and in the current Horizon 2020 Programme. The analysis is based on the information obtained from European Commission database eCORDA (External COmmon Research DAtawarehouse). Dynamic scientometric maps were constructed to describe in more detail the collaboration of European subjects in the EC funded AI research. Within the FP7, 1223 projects in the AI field received roughly 2,8 billion €. In the current H2020 programme the EC has already provided 2,1 billion € for 1081 projects in AI. In the FP7, higher education institutions dominated in both the number of awarded project and the received financial support. In the H2020 programme, a profound shift favouring business enterprise sector occurred. Approximately one third of AI projects in the FP7 was in the thematic area Information and Communication Technologies. In the H2020 programme the EC extended the support further to other thematic areas including global societal challenges especially in the field of transport and security. The extent of the involvement of the member countries varies extensively. The countries above average participating in the AI projects are Germany, Italy, Austria, Spain, Portugal, and Slovenia. The Czech Republic falls in the group of less participating countries. The Czech Republic also exhibits a smaller increase of the participation between RP7 and H2020. Universities involved in approximately two thirds of AI project have dominated in the Czech participation in the FP7. In the H2020 program their share in the AI project decreased by approximately 10 percent points. On the other side, their share of financial support was conserved. The most participating universities were the Czech Technical University Prague (24 projects, and 30% share of the EC contribution for the Czech AI projects) and the Brno University of Technology (14 projects, and 12,4% financial share). In the business enterprise sector Honeywell International s. r. o. attained the highest participation. The Czech subjects collaborate most frequently with German, British, Italian and French research teams.

The Influence of the European H2020 Program on the Development of Regions: The Multiplier Impact of EU Funding in the Regions under Horizon 2020 in NUT III - North

The partnership agreement between the European Union and the Member States for the implementation of the European Structural and Investment Funds for the period 2014 to 2020 is in its final phase. This study analyzes the multiplier impact on regional investment of the European funds made available to the northern region of Portugal - NUTS III, until September 2018 and intends to answer the following questions: What is the amount invested in the regional economy for each euro of support allocated by the EU through the H2020 program, and what is the percentage distribution of community support versus investment per area of intervention?

Development of a Modular Retrofitting System for Residential Buildings and Experience from Pilot Installation

In order to significantly reduce energy consumption of its building stock, Europe has to focus on energy retrofitting of existing buildings. A usual building retrofitting process is very labour intensive and time consuming. It usually takes several weeks or even months to replace old windows by new, install new thermal insulation layers on the external walls and roofs of buildings and renew the heat distribution systems or to attach renewable energy sources on the building’s envelope. To make refurbishment more efficient and allow its scaling up, a European project Development and Advanced Prefabrication of Innovative, Multifunctional Building Envelope Elements for Modular Retrofitting and Connections (MORE-CONNECT) has been initiated under H2020 program. This project developed a system of prefabricated retrofitting modules, that enable to cut primary energy consumption of a typical residential building by 80 %, reduce on-site installation time bellow two weeks and improve the indoor environmental quality. At the same moment, the project aimed on implementation of systemic quality control over the whole design, pre-production, production and installation process in order to significantly reduce the number of warranty claims by the clients. The paper describes the design process of the modular retrofitting system and a pilot installation made on a mock-up building to test the concept, and presents the experience made.

Effect of CYP2D6 genotype on exposure and efficacy of risperidone and aripiprazole: a retrospective, cohort study

The polymorphic CYP2D6 enzyme metabolises the antipsychotic drugs risperidone and aripiprazole to their active metabolites, 9OH-risperidone and dehydroaripiprazole. The aim of this study was to quantify the effect of CYP2D6 genetic variability on risperidone and aripiprazole exposure and treatment in a large patient population. We retrospectively obtained patient data from a routine therapeutic drug monitoring database at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway, between Jan 1, 2005, and Oct 15, 2018. Individuals included in our analyses were CYP2D6-genotyped patients treated with risperidone or aripiprazole. Inclusion criteria for measurement of pharmacokinetic parameters (drug and metabolite serum concentrations) were oral administration of risperidone or aripiprazole, information known about prescribed daily dose and comedications, and aged older than 18 years. Exclusion criteria included polypharmacy with drugs known to be CYP2D6 inhibitors or CYP3A4 inducers or inhibitors. Treatment failure was analysed in all patients treated with risperidone or aripiprazole without these criteria. The first endpoint in our analysis was the metabolism of risperidone to 9OH-risperidone and aripiprazole to dehydroaripiprazole, estimated by the log-transformed ratio between the concentrations of metabolite and parent drug (ie, the metabolic ratio for risperidone [9OH-risperidone]/[risperidone] and the metabolic ratio for aripiprazole [dehydroaripiprazole]/[aripiprazole]). Endpoint two was measurement of drug exposure, quantified by the dose-normalised sum of parent drug and active metabolite serum concentrations (ie, active moiety). The third endpoint of treatment failure was measured as the number of patients switched from risperidone or aripiprazole to another antipsychotic drug within 1 year after the last therapeutic drug monitoring analysis of risperidone or aripiprazole. Patient subgroups were defined by CYP2D6 genotype-determined metaboliser status: poor metabolisers, intermediate metabolisers, normal metabolisers, and ultrarapid metabolisers. ANOVA was used to assess the differences in metabolic ratios, active moieties, and daily doses between individual metaboliser categories, and risperidone and aripiprazole therapeutic failures were compared by logistic regression using the normal metaboliser subgroup as a reference. 1288 risperidone-treated patients and 1334 aripiprazole-treated patients were included in the study, of whom 725 (56%) risperidone-treated and 890 (67%) aripiprazole-treated patients were eligible for the pharmacokinetic analyses. CYP2D6 genotype significantly changed risperidone and aripiprazole metabolism resulting in an approximately 1·6-times and 1·4-times increase in risperidone and aripiprazole active moiety exposure in poor and intermediate metabolisers compared with normal metabolisers, respectively (odds ratios [OR] for the risperidone dose-normalised active moiety concentration 1·568, 95% CI 1·401-1·736, and 1·373, 1·213-1·532; and for the aripiprazole dose-normalised active moiety concentration 1·585, 1·447-1·724, and 1·476, 1·263-1·688, respectively; p<0·0001 for all). Compared with doses for normal metabolisers, clinicians reduced daily doses of risperidone and aripiprazole administered to poor metabolisers by 19% (95% CI 5-35, p=0·010) and 15% (95% CI 1-28, p=0·033) respectively. The incidence of switching from risperidone to another antipsychotic was increased in ultrarapid metabolisers (OR 2·934, 95% CI 1·437-5·989, p=0·003) and poor metabolisers (1·874, 1·128-3·112, p=0·015); by contrast, the incidence of switching from aripiprazole to another antipsychotic was not significantly related to CYP2D6 metaboliser status. CYP2D6 genotype had a substantial clinical effect on risperidone and aripiprazole exposure and on the therapeutic failure of risperidone. Pre-emptive CYP2D6 genotyping would be valuable for individualising risperidone and aripiprazole dosing and treatment optimisation. H2020 program U-PGx, The Swedish Research Council, the Swedish Brain foundation, and the South-Eastern Norway Regional Health Authority.

Numerical Simulations of Fatigue Crack Growth in a Steam Turbine Rotor Blade Groove

With increasing share of renewable energy sources in the electricity production strict demands are placed on thermal power plants that have to cover the power shortages more frequently. Increasing number of steam turbine (ST) start-ups and shutdowns, as well as requirements on higher ramping of operating conditions, has detrimental effect on the overall lifetime of ST components. In the ST design process, this situation has to be dealt by applying advanced prediction methodologies handling the thermo-mechanical fatigue mechanism, for instance. On the other hand, in the case of currently operating STs, regular inspection and maintenance schedule as well as technologies for turbine operation control have to be reconsidered or newly developed. To cope with these challenges, the international consortium of energetic turbine producers and research institutes initiated the TURBO-REFLEX project funded by EU’s H2020 program. One of the principal aims of the project is development of a damage tolerance approach that may be suitable for scheduling the ST rotor maintenance, for instance. Decisive factors in this effort are ST rotor operating conditions, material fracture properties and geometry that constitute the crack initiation site and crack growth rate and direction. This forms a complex task that has to be handled numerically by using a Finite Element (FE)-based code accompanied by in-house scripts for detecting the most probable way of crack propagation. In this contribution, the adopted fracture–mechanics approach applied to low-pressure section of ST rotor and results that have been achieved are presented.

Supporting European Energy Consumers through Gamification and Competence-based Learning

The European energy market liberalization strategy aims to assign a new role to consumers and end-users’ communities so that they can become active participants on the energy market. In this paper we present the project SOCIALENERGY, EU-funded under the H2020 program. This project aims to promote the EU energy market transformation policy and to deliver supporting instruments. By developing innovative ICT-based tools, the project consortium will empower the EU energy consumers to become more energy efficient and competent. Apart from presenting the advanced features of SOCIALENERGY multi-modular platform, we will highlight the importance of the novel competence-based education (CBE) framework to support educational activities and to promote creation of social communities in the energy efficiency domain.ACM Computing Classification System (1998): J.1, K.3.1, K.4.3, K.5.2.

Gamma signatures of the C-BORD Tagged Neutron Inspection System

In the frame of C-BORD project (H2020 program of the EU), a Rapidly relocatable Tagged Neutron Inspection System (RRTNIS) is being developed to non-intrusively detect explosives, chemical threats, and other illicit goods in cargo containers. Material identification is performed through gamma spectroscopy, using twenty NaI detectors and four LaBr3 detectors, to determine the different elements composing the inspected item from their specific gamma signatures induced by fast neutrons. This is performed using an unfolding algorithm to decompose the energy spectrum of a suspect item, selected by X-ray radiography and on which the RRTNIS inspection is focused, on a database of pure element gamma signatures. This paper reports on simulated signatures for the NaI and LaBr3 detectors, constructed using the MCNP6 code. First experimental spectra of a few elements of interest are also presented.

SAFEPOWER project: Architecture for safe and power-efficient mixed-criticality systems

With the ever increasing industrial demand for bigger, faster and more efficient systems, a growing number of cores is integrated on a single chip. Additionally, their performance is further maximized by simultaneously executing as many processes as possible without regarding their criticality. Even safety critical domains like railway and avionics apply these paradigms under strict certification regulations. As the number of cores is continuously expanding, the importance of cost-effectiveness grows. One way to increase the cost-efficiency of such System on Chip (SoC) is to enhance the way the SoC handles its power resources. By increasing the power efficiency, the reliability of the SoC is raised because the lifetime of the battery lengthens. Secondly, by having less energy consumed, the emitted heat is reduced in the SoC which translates into fewer cooling devices. Though energy efficiency has been thoroughly researched, there is no application of those power saving methods in safety critical domains yet. The EU project SAFEPOWER11This project and the research leading to these results has received funding from the European Communitys H2020 program [H2020-ICT-2015] under grant agreement 687902. targets this research gap and aims to introduce certifiable methods to improve the power efficiency of mixed-criticality real-time systems (MCRTES). This article will introduce the requirements that a power efficient SoC has to meet and the challenges such a SoC has to overcome.

SANSA—hybrid terrestrial–satellite backhaul network: scenarios, use cases, KPIs, architecture, network and physical layer techniques

SummaryShared Access terrestrial–satellite backhaul Network enabled by Smart Antennas (SANSA) is a project funded by the EU under the H2020 program. The main aim of SANSA is to boost the performance of mobile wireless backhaul networks in terms of capacity, energy efficiency and resilience against link failure or congestion while easing the deployment in both rural and urban areas and assuring at the same time an efficient use of the spectrum. This paper provides an overview and the first results of the project, and, more specifically, it describes the regulatory environment, the State of The Art of mobile backhauling technologies regarding Ka band, the scenarios, the use cases and the key performance indicators along with the SANSA architecture, network (NET) and physical (PHY) layer techniques used to enhance wireless backhauling capabilities. Copyright © 2017 John Wiley &amp; Sons, Ltd.

CAREGIVERSPRO-MMD: Community Services, Helping Patients with Dementia and Caregivers Connect with Others for Evaluation, Support and to Improve the Care Experience

In this paper, we present the design of a mHealth application that is specifically targeted to caregivers and persons with mild to moderate dementia. The result is CAREGIVERSPRO-MMD: a tool integrating a broader diagnostic approach, incorporating the live-in family caregiver-patient dyad and considering this dyad as the unit of care. CAREGIVERSPRO-MMD will provide value-added services based on social networks, tailored interventions, clinical strategies and gamification for improving the quality of life for people living with dementia and their caregivers, allowing them to live in the community for as long as possible. CAREGIVERSPRO-MMD is an EU project funded under the H2020 program.