7th Framework Programme Research Articles

Past, Present, and Future of Informed Consent in Pain and Genomics Research: Challenges Facing Global Medical Community.

In recent decades, there has been a revision of the role of institutional review boards with the intention of protecting human subjects from harm and exploitation in research. Informed consent aims to protect the subject by explaining all of the benefits and risks associated with a specific research project. To date, there has not been a review published analyzing issues of informed consent in research in the field of genetic/Omics in subjects with chronic pain, and the current review aims to fill that gap in the ethical aspects of such investigation. Despite the extensive discussion on ethical challenges unique to the field of genetic/Omics, this is the first attempt at addressing ethical challenges regarding Informed Consent Forms for pain research as the primary focus. We see this contribution as an important one, for while ethical issues are too often ignored in pain research in general, the numerous arising ethical issues that are unique to pain genetic/Omics suggest that researchers in the field need to pay even greater attention to the rights of subjects/patients. This article presents the work of the Ethic Committee of the Pain-Omics Group (www.painomics.eu), a consortium of 11 centers that is running the Pain-Omics project funded by the European Community in the 7th Framework Program theme (HEALTH.2013.2.2.1-5-Understanding and controlling pain). The Ethic Committee is composed of 1 member of each group of the consortium as well as key opinion leaders in the field of ethics and pain more generally.

One-year oral toxicity study on a genetically modified maize MON810 variety in Wistar Han RCC rats (EU 7th Framework Programme project GRACE).

The GRACE (GMO Risk Assessment and Communication of Evidence; www.grace-fp7.eu) project was funded by the European Commission within the 7th Framework Programme. A key objective of GRACE was to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of a 1-year feeding trial with a GM maize MON810 variety, its near-isogenic non-GM comparator and an additional conventional maize variety are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 452. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after a chronic exposure.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-016-1798-4) contains supplementary material, which is available to authorized users.

Abstract 2354: Cancer vaccine development for hepatocellular carcinoma - HEPAVAC

Abstract The HEPAVAC Consortium aims to develop a highly innovative, novel cancer vaccine approach for hepatocellular carcinoma (HCC). The international project consortium consists of 9 European Partners from academia and the biotech industry with complementary and substantial expertise in developing immunotherapeutic strategies to treat cancer. The project has started in September 2013 and is supported by the European Commission's 7th Framework Program (www.hepavac.eu). HCC/normal adjacent tissue matched samples have been collected for HLA immunopeptidome analysis. 17 HCC samples from HLA-A*02+ patients and 15 samples from HLA-A*24+ patients have been analysed by mass spectrometry (LC-MS/MS). RNA-expression profiles have been established for 12 HCC samples. HLA-presentation/expression of peptides and mRNA on primary HCC samples are compared to >140 normal tissue samples from relevant organs (including heart, brain, lung, kidney, liver, nerve, skin etc.) from Immatics’ database. A total of 9051 HLA-A*02-restricted different tumor-associated peptides (TUMAPs) have been identified from HLA-A*02+ samples, while a total of 3286 different HLA-A*24-restricted TUMAPs have been identified from HLA-A*24+ samples. Of these, 33 HLA-A*02+ TUMAPS and 33 HLA-A*24+ TUMAPs have been validated, including peptide synthesis, immunogenicity testing and pharmaceutical evaluation. Most promising TUMAP candidates show selective expression only in HCC samples and no expression in normal tissues. In parallel, more than 6600 HLA-DR TUMAPs have been identified in Hep3B cells transfected with CIITA as well as an average of 1500 HLA-DR TUMAPs have been identified in HCC samples. A total of 16 newly identified HCC-specific epitopes have been selected for the HEPAVAC vaccine cocktail and are currently synthesized according to GMP standard. Of these, 7 are restricted to HLA- class I A*02; 5 HLA-A*24 and 4 HLA class II. In parallel, preclinical studies assessing the formulation and combination of the immunological RNA-based adjuvant (RNAdjuvant®) with peptide cocktails are underway. A multi Center phase I/II clinical trial in early HCC patients is predicted to start in July 2016. Citation Format: Sarah Kutscher, Roberto Accolla, Yuk T. Ma, Regina Heidenreich, Francesco Izzo, Alfred Koenigsrainer, Markus Loeffler, Phillip Mueller, Andrea Mayer, Hans-Georg Rammensee, Bruno Sangro, Sven Francque, Danila Valmori, Toni Weinschenk, Harpreet Singh-Jasuja, Luigi Buonaguro. Cancer vaccine development for hepatocellular carcinoma - HEPAVAC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2354.

Abstract 2028: Transcriptional modules involving EWS-FLI1 and SRF in Ewing sarcoma

Abstract Ewing Sarcoma (ES) is an aggressive pediatric bone tumor with a high tendency to metastasize. The primary genetic aberration responsible for ES pathogenesis is EWS-FLI1, a chimeric gene, derived from the chromosomal translocation t(11;22)(q24;q12). EWS-FLI1 encodes an aberrant ETS transcription factor. However, due to its lack of enzymatic activity and intrinsically disordered structure it has yet not been successfully targeted. EWS-FLI1 is prone to rapidly engage in protein-protein complexes, enhancing its oncogenic activity. It has been reported to be involved in interactions with regulators of the basal transcriptional machinery, RNA processing and DNA repair. Furthermore, it has been shown that, similar to the ternary complex factors (TCF) SAP1a and ELK1, EWS-FLI1 is able to form a complex with the global transcriptional regulator Serum Response Factor (SRF) on ETS containing promoter elements. SRF binds to CArG motifs in serum response elements (SRE) and requires a transcriptional co-activator, which is commonly provided upstream via the Rho- or the Ras-axis. Upon serum induced Rho activation, polymerization of globular (G-) actin into filamentous (F-) actin takes place, thereby releasing the G-actin bound myocardin-related transcription factors A and B (MRTFA/B) to translocate to the nucleus and concertedly with SRF regulate transcription of target genes. Binding of MRTFs to SRF is mutually exclusive and competed by TCFs, which are activated downstream of Ras, and require presence of an ETS motif adjacent to CArG. In this study we aim to investigate a potential competition of EWS-FLI1 with MRTFs, which might uncouple SRF dependent transcription from upstream G-protein linked regulation and hence interfere with processes such as proliferation, migration and differentiation. To address this question, we performed gene expression profiling in A673 and SKNMC ES cell lines where we combined EWS-FLI1 knockdown with MRTFA/B knockdown under serum starved and serum induced (SI) conditions. We found that transcriptional activity of MRTFA/B is largely repressed by EWS-FLI1 and that upon combined knockdown conditions, EWS-FLI1 transcriptional effects are rescued by MRTFA/B. To further elucidate the underlying mechanisms of EWS-FLI1 and MRTFA/B gene regulation, we performed chromatin immunoprecipitation combined with massive parallel sequencing (ChIP-seq) of MRTFA, MRTFB, SRF and EWS-FLI1 in A673 ES cells. Preliminary results corroborate EWS-FLI1 and MRTF sharing a large number of target genes and indicate that MRTFA binds to DNA motifs, which are associated with activated and repressive EWS-FLI1 signatures. Ongoing experiments aim at a proteomic understanding of the EWS-FLI1 containing SRF complex as a basis for potential therapeutic intervention. This study was supported by the Liddy Shriver Sarcoma Initiative and the 7th framework program of the European Commission (FP7-259348, “ASSET”). Citation Format: Anna M. Katschnig, Maximilian O. Kauer, Dave N t Aryee, Raphaela Schwentner, Elizabeth Lawlor, Heinrich Kovar. Transcriptional modules involving EWS-FLI1 and SRF in Ewing sarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2028.

Abstract 1918: The role of miR17-92 in the miRegulatory landscape of Ewing sarcoma

Abstract MicroRNAs (miRNA) serve to fine-tune gene expression and thus play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a given tissue still poses a significant problem since the presence of a seed sequence in the 3′UTR of an mRNA and its expression modulation upon forced ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in ES. Recently, we reported on the EWS-FLI1 microRNA (miRNA) signature based on knockdown experiments in ES cell lines and on differential expression in primary tumors versus mesenchymal stem cells. Comparison of both datasets revealed the miR17-92 cluster to be the top EWS-FLI1 activated miRNA, which is one of the most potent oncogenic miRNAs. The whole cluster is among the small number of miRNAs down-regulated upon knockdown of EWS-FLI1 in multiple ES cell lines. We now report the use of a combination of AGO2 pull-down experiments by PAR-CLIP - to enrich and sequence RISC-associated RNAs - and of RNAseq upon miRNA depletion by ectopic sponge expression to identify the targetome of miR17-92 in Ewing sarcoma (ES) cells We found a significant enrichment of PAR-CLIP hits for members of the miR-17-92 cluster in the 3′UTRs of genes up-regulated in response to mir-17-92 but not miR9 and 10b specific sponge expression. Among them, we consistently identified known (i.e. CTGF, MXD1, CYLD1) and a multitude of so far unknown targets of the oncomir-1 cluster in ES in three PAR-CLIP experiments. Interestingly, approximately a quarter of these genes annotate to the TGFB/BMP pathway, the majority mapping downstream of SMAD signaling. Gene reporter assays using 3’UTRs of select novel candidate genes showed enhancement of luciferase activity upon transfection of a sponge specific to miR-17-92 and 20a, but not to unrelated miR-9 and 10b. Site directed mutagenesis of seed sequences in these 3’UTR confirmed the direct regulation of these genes by miR17-92. Current research focuses on the functional validation of TGFB pathway modulation by miR17-92. This study provides a paradigmatic approach to the comprehensive definition of the targetome for a defined group of miRNAs under physiological conditions. This study was supported by the 7th framework program of the European Commission (FP7-259348, “ASSET”) and the Austrian Science Fund FWF (24708-B21) Citation Format: Raphaela Schwentner, Maximilian Kauer, David Herrero-Martin, Heinrich Kovar. The role of miR17-92 in the miRegulatory landscape of Ewing sarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1918.

A holistic approach for assessing impact of extreme weather on critical infrastructure

Urban infrastructures are essential to the health, safety, security and economic well-being of citizens and organisations. Therefore, the managers of critical infrastructures (CI) and infrastructure systems in urban areas need to be constantly aware of and prepared for to any man-made and natural disasters. In this paper, we propose a structured approach to assess extreme weather impacts on CI and discuss how resilience and risk tolerance of critical infrastructure can be enhanced. The approach is aimed at supporting CI owners' and managers' decision-making on a strategic level. It follows a process flow from hazard and CI identification, vulnerability analysis, potential damage estimation, loss assessment to identification and assessment of measures. The approach incorporates many elements, phases and methods from hazard assessment, vulnerability assessment, risk assessment and cost-benefit analysis (CBA), and combines and incorporates them into one aggregated structure, thus providing a holistic view to risk management and CI protection. The proposed approach is flexible in the sense that it encompasses not only a rigorous quantitative assessment, but also allows for a semi-quantitative or qualitative assessment. In addition, the approach enhances transparency of decision making and contributes to more comprehensive use of available information. The paper is based on research carried out in the INTACT and HARMONISE projects, which are co-funded by the European Union under the 7th Framework Programme. © 2016 WIT Press.

Percutaneous vertebroplasty: a new animal model

Background ContextPercutaneous vertebroplasty (PVP) is a minimally invasive surgical procedure and is frequently performed in humans who need surgical treatment of vertebral fractures. PVP involves cement injection into the vertebral body, thereby providing rapid and significant pain relief. PurposeThe testing of novel biomaterials depends on suitable animal models. The aim of this study was to develop a reproducible and safe model of PVP in sheep. Study DesignThis study used ex vivo and in vivo large animal model study (Merino sheep). MethodsEx vivo vertebroplasty was performed through a bilateral modified parapedicular access in 24 ovine lumbar hemivertebrae, divided into four groups (n=6). Cerament (Bone Support, Lund, Sweden) was the control material. In the experimental group, a novel composite was tested—Spine-Ghost—which consisted of an alpha-calcium sulfate matrix enriched with micrometric particles of mesoporous bioactive glass. All vertebrae were assessed by micro-computed tomography (micro-CT) and underwent mechanical testing.For the in vivo study, 16 sheep were randomly allocated into control and experimental groups (n=8), and underwent PVP using the same bone cements. All vertebrae were assessed postmortem by micro-CT, histology, and reverse transcription-polymerase chain reaction (rt-PCR).This work has been supported by the European Commission under the 7th Framework Programme for collaborative projects (600,000–650,000 USD). ResultsIn the ex vivo model, the average defect volume was 1,275.46±219.29 mm3. Adequate defect filling with cement was observed. No mechanical failure was observed under loads which were higher than physiological. In the in vivo study, cardiorespiratory distress was observed in two animals, and one sheep presented mild neurologic deficits in the hind limbs before recovering. ConclusionsThe model of PVP is considered suitable for preclinical in vivo studies, mimicking clinical application. All sheep recovered and completed a 6-month implantation period. There was no evidence of cement leakage into the vertebral foramen in the postmortem examination.

Design and Testing of a Highly Reconfigurable Fixture With Lockable Robotic Arms

The paper describes an innovative fixture created within the AUTORECON project of the European Commission's 7th Framework Program. The fixture is designed to respond to the automotive industry's needs of high modularity and full flexibility, by allowing the secure multishape grasping of a very wide range of (often large and heavy) metal workpieces typical for car-assembly operations. The fixture is used as an end-effector of an industrial robot, which in turn acts in cooperation with other machines, such as other robots performing machining or other processes on the part. The fixturing device is both a highly reconfigurable structure and a robotic mechanism: moving as a programmable robot to reconfigure and acting as a supporting structure once a hold on the part has been established. This dual functioning has been made possible by the development of a key component, a stepless lockable revolute joint, described herein. In order to get a readily modifiable system, all parts of the fixture are designed as modules. Prototypes of the main parts and the whole fixture have been fabricated and experiments validating the design are reported.

Money Talks: Gender Budgeting in the University of Iceland

The article addresses the financial framework, decision-making and budgeting processes of the University of Iceland from a gender perspective. The newly appointed rector of the University of Iceland (elected 2015) together with the university council is currently revising the UI system of the distribution formula of budget allocation. This provides an opportunity to examine the system which is inspired by New Public Management, with emphasis on global competition and performance based indicators. The aim of the article is to scrutinize the current system of budget allocation and distribution and its significance when it comes to gender. We ask how the, allegedly gender neutral, system plays out for different schools and disciplines and for academics in different ranks, when the gender dimension is taken into account. We draw on empirical data collected as part of the GARCIA research project, Gendering the Academy and Research combating Career Instability and Asymmetries, which is supported by the 7th Framework Programme of the European Union. To shed a light on the process we focus on the male-dominated School of Engineering and Natural Sciences (SENS) and the more feminised School of Social Sciences (SSS). The exploration shows that the financial framework, decision-making and budgeting processes at the University of Iceland are rather non-transparent, and biased in favour of the natural sciences. This applies to funding from the state; third party funding; the allocation of funding in the teaching part of the budgeting, as well as the research part. From the article it can be concluded that the current system contains an internal, though unintended, gender bias that needs to be corrected.

Ionic Liquid Electrolytes for Safer Lithium Batteries: II. Performance in NMC and Graphite Electrodes

Actually, the research on lithium battery materials is pushed towards large capacity anodes and high voltage cathodes. While graphite still represents the best choice as the anode material, the need for well-performing cathode materials is more and more stringent. Lithium-containing, mixed nickel-manganese-cobalt oxide (NMC) is one of the most investigated high operative voltage (> 4 V) cathode material also due to its large capacity value [1]. However, safety is still an open issue. Ionic liquids (ILs), molten salts at room temperature, were successfully proposed as non-flammable and non-volatile solvents for replacing the conventional, hazardous, toxic, organic compounds in lithium battery systems, aiming to enhance the safety of the device [2]. ILs can be favorably combined to obtain mixtures with improved properties, often not exhibited by single ionic liquid materials. Therefore, we have properly developed ternary IL mixtures, based on a blend of N-methyl-N-propyl pyrrolidinium bis(trifluoromethane sulfonyl)imide, PYR13TFSI, and methyl-N-propylpyrrolidinium bis(fluoro sulfonyl)imide, PYR13FSI, ionic liquids [3], to be addressed as electrolytes for lithium batteries. In the present work, we report the electrochemical performance of NMC cathodes and graphite anodes, manufactured using fluorine-free, water-soluble, natural binders as carboxymethylcellulose sodium salt (CMC), in LiTFSI-PYR13TFSI-PYR13FSI electrolyte. Results and Discussions The voltage vs. capacity profile of selected charge-discharge cycles, performed on NMC cathode tapes at 23 °C and 0.1C in LiTFSI-PYR13TFSI-PYR13FSI and (1M)LiPF6-EC/DMC (1:1 in weight) electrolytes, is reported in Figure 1. It is worth to note that both the charge (with the exception of the first half-cycle) and discharge features are practically overlapped, indicating high reversibility of the Li+ intercalation process and high columbic efficiency. The results clearly evidence how NMC cathodes are able, in the selected ionic liquid electrolyte, to deliver 90 % of the capacity discharged in organic solutions with a somewhat similar operative voltage. Cycling tests have revealed very good capacity retention with efficiency close to 100 % in the 0 -50 °C temperature range. Interesting capacity values (≥ 100 mA h g-1) were exhibited even at low temperatures (0 °C), but at low current rates (≤ 0.05), due to diffusive phenomena within the IL electrolytes. Figure 2 compares the voltage vs. capacity profile of selected discharge-charge cycles, performed on graphite anode tapes in LiTFSI-PYR13TFSI-PYR13FSI and (1M)LiPF6-EC/DMC (1:1 in weight) electrolytes. A small EC amount, e.g., 5 wt.%, was incorporated to the IL electrolyte in order to promote SEI growth onto graphite anode. The results have evidenced good reproducibility of the cycle features, indicating high reversibility of the lithium intercalation process, very good capacity retention and high coulombic efficiency. More than 90 % of the capacity value, delivered in conventional organic solutions, was exhibited in LiTFSI-PYR13TFSI-PYR13FSI + 5 wt.% electrolyte. Acknowledgements The authors wish to thank the financial support of the European Commission for the GREENLION project within the 7th Framework Program (Grant agreement n°: 28526).

Ionic Liquid Electrolytes for Safer Lithium Batteries: I. Investigation Around Optimal Formulation

Ionic liquids (ILs) are more and more investigated as substitutes of volatile and flammable organic electrolyte solvents in rechargeable lithium-ion battery systems [1] to enhance safety of the electrochemical device. So far, single ILs do not generally match or fully satisfy the requirements and/or operative conditions of practical devices, even if the ionic liquid properties could be finely tuned by suitably modifying their architecture [1]. A promising approach is represented by properly combining different ionic liquids, leading to beneficial synergic effects on the physicochemical properties of the resulting IL mixture [1]. In the present work, we have developed ternary mixtures by incorporating different fractions of the LiTFSI salt into the proper PYR13TFSI-PYR13FSI blend. Pyrrolidinium-based ILs were successfully proposed for lithium batteries [1]; the TFSI anion has proved to be stable toward oxidation and thermally robust [1] whereas FSI exhibits high conductivity even at low temperature coupled with protective film-forming capability onto electrodes [1]. Results and Discussions An eco-friendly procedure route [2] allowed to synthesize high purity, anhydrous, clear, colorless and odorless ionic liquid samples with yields ranging from 85 to 90 mol.% and water content below 2 ppm. Proper PYR13TFSI-PYR13FSI formulations have shown ion conduction approaching 10-3 S cm-1 at -20 °C whereas the pure IL materials, still in solid state, exhibit conductivity values four orders of magnitude lower. This behavior is likely due to different hindrance of the anions, resulting in worse ion packing. On the basis of the obtained results, the TFSI:FSI mole ratio was selected equal to 2:3. The LiTFSI-PYR13TFSI-PYR13FSI mixtures (Figure 1) have exhibited high conductivity (about 10-3 S cm-1), even at low temperatures (-20 °C), in good agreement with the thermal and rheological properties. Cyclic voltammetries (Figure 2) have indicated electrochemical stability up to 5 V in conjunction with the possibility to reversibility intercalate Li+ ions into carbonaceous anodes, this also suggesting good mobility of lithium at the interface with electrodes. Acknowledgements The authors wish to thank the financial support of the European Commission for the GREENLION project within the 7th Framework Program (Grant agreement n°: 28526).

Highly Conductive, Ionic Liquid-Rich Polymer Electrolytes

Introduction Lithium polymer batteries (LPBs) are considered excellent candidates for the next generation power sources since their high energy density and flexible characteristics. Nevertheless, the performance of LPBs is limited by the low ionic conductivity of the solvent-free polymer electrolytes at room temperature. A very promising approach for overcoming this drawback is represented by the incorporation of ionic liquids (ILs) into the polymer electrolytes. In the last years, it was successfully demonstrated [1] that incorporation of N-alkyl-N-methylpyrrolidinium perfluorosulfonylimide ILs enhances the room temperature ionic conductivity of solid polymer electrolytes (SPEs) above 10-4 Scm-1 with a good compatibility with respect to the lithium anode even after prolonged storage time. However, faster transport properties are required, especially in practical devices operating at high current rates. In the frame of the MARS-EV project we have developed SPEs based on the polyethyleneoxide (PEO) or the polymethylmetaacrylate (PMMA) and incorporating the ionic liquid N-methyl-N-propylpyrrolidinium bis (trifluoromethanesulfonylimide, PYR13FSI. This latter material is well known for its high ion conduction, low melting point and good-film forming ability on lithium and graphite anodes [2]. Also, the addition of proper additive (EC) in small amount, aiming to improve the interface with graphite anodes, was considered. Results and Discussions The PEO-LiTFSI-PYR13FSI and PMMA-LiTFSI-PYR13FSI electrolytes were prepared accordingly to a solvent-free procedure route reported elsewhere [1]. PYR13:Li mole ratio was ranged from 0.5 to 7.0. Appreciable mechanical properties were exhibited even at high ionic liquid contents (Figure 1) in conjunction good chemical stability as indicated by the absence of feature change of the AC plots upon prolonged storage periods (Figure 2). The impedance measurements evidenced a progressive reduction of the electrolyte resistance during the initial storage days, likely due to internal structural reorganization of the SPE samples, followed by stable ion conduction upon long period times. The incorporation of PYR13FSI results in large conductivity increase, especially at room temperature or below. For instance, conduction values approaching 10-3 S cm-1 and overcoming 10-4 S cm-1 at 20 and -20 °C, respectively, were detected. In addition, the IL addition was seen to prevent the polymer host crystallization, in good agreement with the DSC results. Acknowledgements The authors wish to thank the financial support of the European Commission for the MARS-EV project within the 7th Framework Program (Grant agreement n°: 609201).

Superior Performance and Ageing Robustness of 17 a h Class, Graphite/NMC Stacked Cells Manufactured through Eco-Friendly Materials and Processes

Lithium-ion batteries represent one the best chances for the next BEV and HEV generation [1]. Taking into account the actual lithium-ion technology, the safety and cost appear the main drawbacks holding the introduction of these storage systems into the automotive market. However, the current Li-ion battery manufacturing process has been greatly advancing in the last twenty years and those developments are also the basis for the production of large format cells demanded for automotive application. The GREENLION consortium, a large scale collaborative project within the FP7 (GC.NMP.2011-1) [2] was aimed to tackle these issues, leading to the manufacturing of greener and cheaper lithium-ion batteries for electric vehicle applications via the use of water soluble, fluorine-free, high thermally stable binders, which would eliminate the use of organic compounds as solvent in the electrode coating process and reduce the cell assembly cost. The GREENLION project has identified three key levels in the value scale before the final battery pack integration for EVs, namely electrode processing, cell manufacturing and battery module assembly, which are the backbone of the lithium-ion battery production line. Here, the performance and ageing robustness of 17 A h class, graphite/NMC stacked cells designed, developed and manufactured within GREENLION project, are reported. Results and Discussions The cells exhibited analogous behavior in terms of charge/discharge features, displaying resistance below 5 m and nominal capacity equal or exceeding 17 A h at 23 °C (Figure 1). Slightly higher values, i.e., around 18 A h, are delivered at 45 °C whereas, at 0 °C, the cells are able to still deliver more than 80 % of their nominal capacity. Excellent cycling performance, reported in Figure 2, was exhibited, e.g., practically 100 % of the initial capacity was delivered after more than 500 full charge/discharge cycles run at 100 % DOD. The graphite/NMC stacked cells were subjected to prolonged ageing tests, carried out holding the GREENLION cells at 45 °C and monitoring their capacity every 4 weeks. The results, plotted in Figure 3 as capacity evolution recorded during storage tests, have revealed very remarkable robustness towards ageing phenomena. For instance, from 86 to 88 % of the initial capacity is retained upon 4 months. These characteristics, in combination with the excellent electrochemical performance, are clear indications of the good cell design and manufacturing of the GREENLION cells based on eco-friendly electrodes. Acknowledgements The authors wish to thank the financial support of the European Commission for the GREENLION project within the 7thFramework Program (Grant agreement n°: 285268).

PUBLIC TRANSPORT USERS' PREFERENCES AND WILLINGNESS TO PAY FOR A PUBLIC TRANSPORTATION MOBILE APP IN MADRID

Today, smart cities are presented as a solution to achieve a more sustainable urban development while increasing the quality of life of its citizens through the use of new technologies (Neirotti, 2013). Smart Mobility is based on innovative and sustainable ways to provide transport for the inhabitants of cities, enhancing the use of fuels or vehicle propulsion systems that respect the environment, supported by technological tools and a proactive behaviour of citizenship (Neirotti, 2013). In urban mobility, the purpose of the Smart Cities is to develop flexible systems for real-time information to support decision-making in the use and management of different transport modes, generating a positive impact, saving users time and improving efficiency and quality of service. In this context, several solution types are being introduced in the world’s cities. They enable the improvement of the abovementioned factors acting on the demand side resulting in more efficient journeys for individual travelers, and improved satisfaction with the service. (Skelley et Al., 2013) with a lower level of investment than that of infrastructure deployment or an increase in the level of service. One of the most extended solutions is the use of mobile apps for providing the user with contextualized -static and real time- transport information. The study is based on a survey carried out among users of public transport in Madrid under the European OPTICITES project of the 7th Research Framework Programme. The survey contained items on their transportation habits, their level of skills and technological capabilities, and their main expectations about the possibility of using a new application, the main desired capabilities and willingness to pay for use. The study results show the preferences of users of public transport capacity, static, real-time search and in-app services for a multimodal real-time application and willingness to pay for this service, all analyzed by different Slicers users. The results also establish the basis for an estimate of the usefulness of these applications for users of public transport. DOI: http://dx.doi.org/10.4995/CIT2016.2016.3498

Community-based 4-level approach: Background, implementation and evidence for efficacy

The community-based 4-level-intervention concept developed within the “European Alliance against Depression” (http://www.eaad.net/) combines two important aims: to improve the care and treatment of patients with depression and to prevent suicidal behavior. It has been shown to be effective concerning the prevention of suicidal behavior [1–4] and is worldwide the most broadly implemented community-based intervention targeting depression and suicidal behavior. The 4-level intervention concept comprises training and support of primary care providers (level 1), a professional public relation campaign (level 2), training of community facilitators (teacher, priests, geriatric caregivers, pharmacists, journalists) (level 3), and support for self-help of patients with depression and for their relatives (level 4). In order to deepen the understanding of factors influencing the effectiveness of the intervention, a systematic implementation research and process analysis was performed within the EU-funded study “Optimizing Suicide Prevention Programs and Their Implementation in Europe” (http://www.ospi-europe.com/; 7th Framework Programme) [5]. These analyses were based on data from four intervention and four control regions from four European countries. In addition to intervention effects on suicidal behaviour, a variety of intermediate outcomes (e.g. changes in attitude or knowledge in different populations) were considered. Strong synergistic as well as catalytic effects were identified as a result of being active simultaneously at four different levels. Predictable and unpredictable obstacles to a successful implementation of such community-based programs will be discussed. Via the EAAD, the intervention concept and materials (available in eight different languages) are offered to interested region in and outside of Europe.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Predicciones de calidad del aire a alta resolución en el Mediterráneo occi-dental para los proyectos MACC, MACC-II y MACC-III

The European Earth observation programme Copernicus, formerly known as GMES (Global Monitoring for Environment and Security) is establishing a core global and regional environmental atmospheric service as a component of the Europe’s Copernicus/GMES initiative through successive R&D projects led by ECMWF (European Center for Medium-range Weather Forecasting) and funded by the 6th and 7th European Framework Programme for Research and Horizon 2020 Programme: GEMS, MACC, MACC-II and MACC-III. AEMET (Spanish State Meteorological Agency) has participated in the projects MACC and MACC-II and continues participating in MACC-III (http://atmosphere.copernicus.eu). AEMET has contributed to those projects by generating high-resolution (0.05 degrees) daily air-quality forecasts for the Western Mediterranean up to 48 hours aiming to analyse the dependence of the quality of forecasts on resolution. We monitor the evolution of different chemical species such as NO2, O3, CO y SO2 at surface and different vertical levels using the global model MOCAGE and the MACC Regional Ensemble forecasts as chemical boundary conditions. We will show different case-studies, where the considered chemical species present high values and will show a validation of the air-quality by comparing to some of the available air-quality observations (EMEP/GAW, regional -autonomous communities- and local -city councils- air-quality monitoring networks) over the forecast domain. The aim of our participation in these projects is helping to improve the understanding of the processes involved in the air-quality forecast in the Mediterranean where special factors such as highly populated areas together with an intense solar radiation make air-quality forecast-ing particularly challenging.

Phenotypic and Histopathological Tumor Characteristics According to CDKN2A Mutation Status among Affected Members of Melanoma Families

Phenotypic and Histopathological Tumor Characteristics According to CDKN2A Mutation Status among Affected Members of Melanoma Families

Multi-disciplinary, community-oriented design of low-noise aircraft: the COSMA project

Abstract The EC-funded project COSMA (Community Oriented Solutions to Minimize aircraft noise Annoyance, 7th Framework Programme) started in June 2009 with an ambitious, twofold goal: improve the understanding of the annoyance induced by aircraft noise on the population and identify the engineering guidelines to establish appropriate design strategies and operational procedure to reduce these effects. The project was conceived within the context of the X-Noise Collaborative Network, a worldwide network of experts and institutions committed to the commercial aviation noise challenge. The COSMA objectives were addressed using a highly multi-disciplinary approach, integrating competences pertaining to psychoacoustics, sound engineering, and aeronautical engineering. The work of twenty-three research groups from nine European countries was structured in six, strongly interconnected work packages. Aim of the present paper is the review of this cross-disciplinary research from the point of view of the aircraft designer. The attention is focused on the Optimisation of Airport Noise Scenarios work package, where the aeronautical technology contextwas established in detail and where, eventually, the design criteria and operational recommendation were defined on the basis of the outcomes of the annoyance examination experimental campaign.

Evaluation framework in Cooperative Intelligent Transport Systems (C-ITS) for freight transport: the case of the CO-GISTICS speed advice service

The transport sector has relevant impacts on economic and social aspects in the European Union. Freight transportation had an increasing role in this context with road transport that covers 45% of the total billion ton-kilometres in 2012. Cooperative intelligent transport systems (ITS) are promising solutions to adopt in order to increase the efficiency and reduce the environmental impacts of freight road transportation. In recent years, the European Community has founded several projects concerning C-ITS applications in freight transportation. A valuable evaluation of their impacts represents a new challenge. The current paper overviews the impact assessment methodologies applied in recent founded projects with the aim of defining an evaluation framework for the ongoing 7th Framework Program project “COoperative loGISTICS for sustainable mobility of goods (CO-GISTICS)”. Moreover, a complete case study of the Priority and Speed Advice service is detailed, highlighting both qualitative and quantitative asp...

ROS sensitive collagen fibers with gradient concentration of MnO2 nanoparticles inhibit annulus fibrosus cell apoptosis.

Event Abstract Back to Event ROS sensitive collagen fibers with gradient concentration of MnO2 nanoparticles inhibit annulus fibrosus cell apoptosis. Christos Tapeinos1, Akshay Srivastava1, Sahana Ganesh1 and Abhay Pandit1 1 National University of Ireland Galway, Center for Research in Medical Devices, Ireland Introduction: The term inflammation is used to characterize a number of biological processes that take place when natural (tissue injury) or pathogenic (microbes, bacteria) factors attack the human body. Inflammation can occur in any tissue and one of the main characteristics of these inflamed tissues is the low levels of oxygen. The hypoxic microenvironment that is created around these inflamed tissues is one of the reasons responsible for the production of ROS. We hypothesize that collagen fibers with concentration gradients of manganese dioxide (MnO2) nanoparticles (NPs) can increase oxygen levels in a control manner through the reaction of MnO2 NPs with hydrogen peroxide (H2O2) resulting in attenuated hypoxia in inflamed tissues. Hence, our specific objective in this study is to fabricate collagen fibers embedded with MnO2 NPs (Fig. 1), with controlled degradability that are able to scavenge H2O2 and generate O2 to inhibit Annulus Fibrosus (AF) cell apoptosis under inflamed condition. Materials and Methods: MnO2 NPs were synthesized using a previously described method[1],[2]. The NPs were characterized structurally (XRD & IR) and morphologically (TEM) and their charge was measured with DLS. The same characterizations applied also on the fibers embedded with the NPs. An oxygen sensor was used to measure the increase in oxygen levels after the reaction of the NPs with various H2O2 concentrations. The NPs were mixed with Type I bovine collagen (3.5 mg/ml) in various concentrations and fibers were synthesized by the fiber extrusion method (Fig. 1A). The degradation profile as well as oxygen levels after reaction with H2O2 were assessed. Cytotoxicity of the NPs and of the fibers embedded with NPs was carried out on 3T3 fibroblast and IL-1β induced inflamed AF cells (Fig. 2D). Changes in the apoptosis rate and intracellular ROS levels in cultured inflamed AF cells were measured by flow cytometry. Results and Discussion: MnO2 NPs were successfully fabricated and embedded inside the collagen fibers in different concentrations creating a gradient along the fibers. Oxygen was generated following the reaction of the NPs with H2O2 (Fig. 2B) and the increase in oxygen was found to be proportional to the nanoparticles’ concentration. In vitro studies on 3T3 fibroblast cells after treatment with H2O2 before and after treatment with MnO2 NPs demonstrated that cells’ metabolic activity is higher after reaction with MnO2, indicating the scavenging effect of the NPs (Fig. 2C). Flow cytometry results showed that MnO2 loaded collagen fibers exhibit increased cell viability, decreased ROS formation and significantly reduced apoptosis. Conclusions: Modified collagen-MnO2 fibers with controlled degradation rates were successfully fabricated. These fibers were able to generate oxygen after treatment with various concentrations of H2O2. In vitro studies demonstrated a subsequent reduction in ROS levels and inflamed AF cell apoptosis after treatment with the modified fibers. Future studieds will involve measuring altered mitochondrial membrane potential of AF cells and molecular markers involved in extracellular matrix production. This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant Number 13/RC/2073; This material is based upon works supported by the European Union funding under the 7th Framework Programme under Grant Agreement Number 317304