Munich, Germany

Ludwig Maximilian University of Munich is a public research university located in Munich, Germany.The University of Munich is among Germany's oldest universities. Originally established in Ingolstadt in 1472 by Duke Ludwig IX of Bavaria-Landshut, the university was moved in 1800 to Landshut by King Maximilian I of Bavaria when Ingolstadt was threatened by the French, before being relocated to its present-day location in Munich in 1826 by King Ludwig I of Bavaria. In 1802, the university was officially named Ludwig-Maximilians-Universität by King Maximilian I of Bavaria in his as well as the university's original founder's honour.The University of Munich has, particularly since the 19th century, been considered as one of Germany's as well as one of Europe's most prestigious universities; with 34 Nobel laureates associated with the university, it ranks 13th worldwide by number of Nobel laureates. Among these were Wilhelm Röntgen, Max Planck, Werner Heisenberg, Otto Hahn and Thomas Mann. Pope Benedict XVI was also a student and professor at the university. The LMU has recently been conferred the title of "elite university" under the German Universities Excellence Initiative.LMU is currently the second-largest university in Germany in terms of student population; in the winter semester of 2013/2014, the university had a total of 50,542 matriculated students. Of these, 8,719 were freshmen while international students totalled 7,403 or almost 15% of the student population. As for operating budget, the university records in 2013 a total of 571.3 million Euros in funding without the university hospital; with the university hospital, the university has a total funding amounting to approximately 1.5 billion Euros. Wikipedia.

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PLS Design GmbH, Ludwig Maximilians University of Munich and Helmholtz Center Munich | Date: 2015-09-14

The invention relates to a pharmaceutical composition for the modulation of T cell and B cell responses made of one or more preparations and comprising a therapeutically effective dose of at least one inhibitor of TNFR1-mediated functions and of at least one antigen or allergen.

Ludwig Maximilians University of Munich | Date: 2016-11-30

The present invention relates to a method for detecting protein-protein interactions by assessing interaction in a eukaryotic cell of a first fusion protein that specifically binds to GFP and accumulates at distinct sites in the nucleus of the cell or interacts with structures accumulated at distinct sites in the nucleus of the cell; a second fusion protein comprising GFP and a bait (poly)peptide; and a third fusion protein comprising a fluorescent (poly)peptide having an excitation and/or emission wavelength that differs from that of GFP and a prey (poly)peptide. The emissions from the fluorescent parts of the fusion proteins are observed. Co-localization of the emissions from both fluorescent fusion proteins indicates interaction of the bait and the prey (poly)peptide. Methods for identifying a compound modulating the interaction of two (poly)peptides and methods of determining the relative strength of the interaction of two proteins with a third protein.

Weber M.F.,Ludwig Maximilians University of Munich | Frey E.,Ludwig Maximilians University of Munich
Reports on Progress in Physics | Year: 2017

This review provides a pedagogic and self-contained introduction to master equations and to their representation by path integrals. Since the 1930s, master equations have served as a fundamental tool to understand the role of fluctuations in complex biological, chemical, and physical systems. Despite their simple appearance, analyses of master equations most often rely on low-noise approximations such as the Kramers-Moyal or the system size expansion, or require ad-hoc closure schemes for the derivation of low-order moment equations. We focus on numerical and analytical methods going beyond the low-noise limit and provide a unified framework for the study of master equations. After deriving the forward and backward master equations from the Chapman-Kolmogorov equation, we show how the two master equations can be cast into either of four linear partial differential equations (PDEs). Three of these PDEs are discussed in detail. The first PDE governs the time evolution of a generalized probability generating function whose basis depends on the stochastic process under consideration. Spectral methods, WKB approximations, and a variational approach have been proposed for the analysis of the PDE. The second PDE is novel and is obeyed by a distribution that is marginalized over an initial state. It proves useful for the computation of mean extinction times. The third PDE describes the time evolution of a 'generating functional', which generalizes the so-called Poisson representation. Subsequently, the solutions of the PDEs are expressed in terms of two path integrals: a 'forward' and a 'backward' path integral. Combined with inverse transformations, one obtains two distinct path integral representations of the conditional probability distribution solving the master equations. We exemplify both path integrals in analysing elementary chemical reactions. Moreover, we show how a well-known path integral representation of averaged observables can be recovered from them. Upon expanding the forward and the backward path integrals around stationary paths, we then discuss and extend a recent method for the computation of rare event probabilities. Besides, we also derive path integral representations for processes with continuous state spaces whose forward and backward master equations admit Kramers-Moyal expansions. A truncation of the backward expansion at the level of a diffusion approximation recovers a classic path integral representation of the (backward) Fokker-Planck equation. One can rewrite this path integral in terms of an Onsager-Machlup function and, for purely diffusive Brownian motion, it simplifies to the path integral of Wiener. To make this review accessible to a broad community, we have used the language of probability theory rather than quantum (field) theory and do not assume any knowledge of the latter. The probabilistic structures underpinning various technical concepts, such as coherent states, the Doi-shift, and normal-ordered observables, are thereby made explicit. © 2017 IOP Publishing Ltd.

PURPOSE:: To describe the morphologic characteristics of the vitreomacular interface in intermediate age-related macular degeneration associated with tangential traction due to premacular membrane formation and to correlate with optical coherence tomography (OCT) findings and clinical data. METHODS:: Premacular membrane specimens were removed sequentially with the internal limiting membrane from 27 eyes of 26 patients with intermediate age-related macular degeneration during standard vitrectomy. Specimens were processed for immunocytochemical staining of epiretinal cells and extracellular matrix components. Ultrastructural analysis was performed using transmission electron microscopy. Spectral domain optical coherence tomography images and patient charts were evaluated in retrospect. RESULTS:: Immunocytochemistry revealed hyalocytes and myofibroblasts as predominant cell types. Ultrastructural analysis demonstrated evidence of vitreoschisis in all eyes. Myofibroblasts with contractile properties were observed to span between folds of the internal limiting membrane and vitreous cortex collagen. Retinal pigment epithelial cells or inflammatory cells were not detected. Mean visual acuity (Snellen) showed significant improvement from 20/72 ± 20/36 to 20/41 ± 20/32 (P < 0.001) after a mean follow-up period of 19 months (median, 17 months). During this period, none of the eyes required anti–vascular endothelial growth factor therapy. CONCLUSION:: Fibrocellular premacular proliferation in intermediate age-related macular degeneration predominantly consists of vitreous collagen, hyalocytes, and myofibroblasts with contractile properties. Vitreoschisis and vitreous-derived cells appear to play an important role in traction formation of this subgroup of eyes. In patients with intermediate age-related macular degeneration and contractile premacular membrane, release of traction by vitrectomy with internal limiting membrane peeling results in significantly functional and anatomical improvement. © 2017 by Ophthalmic Communications Society, Inc.

Bielec P.,Ludwig Maximilians University of Munich | Schnick W.,Ludwig Maximilians University of Munich
Angewandte Chemie - International Edition | Year: 2017

Nitridosilicates represent an intriguing class of materials and are typically made up of highly condensed tetrahedral network structures. Alkaline-earth nitridosilicates emerged as unique host materials for Eu2+ doped luminophores which found broad application in phosphor-converted (pc)-LEDs. In contrast to common strategies of preparing nitridosilicates by bottom-up syntheses, we have now succeeded to post-synthetically design nitridosilicates by ion exchange in metal halide melts. We describe the syntheses of hitherto unknown but predicted alkaline-earth nitridosilicates, Mg2Si5N8 and β-Ca2Si5N8. Both compounds were obtained by ion exchange starting from pre-synthesized nitridosilicates. In situ investigations of the ion-exchange process show that the Si–N network topology remains preserved. Therefore the reaction offers a significant increase of synthetic control with respect to classical bottom-up syntheses. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Storch G.,Ludwig Maximilians University of Munich | Trapp O.,Ludwig Maximilians University of Munich
Nature Chemistry | Year: 2017

The synthesis of enantiomerically pure compounds is of great importance in pharmaceuticals, fragrances and biological applications, and functions as a key to many processes in nature. Asymmetric catalysis using enantiomerically pure catalysts represents an efficient synthetic method to achieve this goal. The enantiomeric excess of the reaction product correlates with the enantiomeric purity of the catalysts, except for nonlinear behaviour, therefore the use of stereochemically flexible catalysts seems to complicate the control of stereoselectivity. Self-amplifying catalytic reactions are attractive, but a general rational design is highly challenging. Here we show that product interaction with chiral recognition sites attached to structurally flexible phoshoramidite-type catalysts can sense the chirality and induce enantioselectivity in the catalyst. Structural flexibility along with sensing of the chirality of the product molecules results in a rapid increase of enantioselectivity of the dynamic catalysts (Δe.e. of up to 76%) and a shift out of equilibrium. In contrast to stereodynamic catalysts controlled with cleavable chiral auxiliaries, the enantioselectivity does not decrease. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Grote V.,Ludwig Maximilians University of Munich
Pediatric Infectious Disease Journal | Year: 2016

BACKGROUND:: Although bacterial osteomyelitis (BO) is a commonly recognized diagnosis in pediatrics, it is often difficult to distinguish from nonbacterial osteitis (NBO). The goal of our study was to distinguish between the two disease entities and better define NBO. METHOD:: Using the German Surveillance Unit for Rare Diseases in Childhood (Erhebungseinheit für Seltene Paediatrische Erkrankungen (ESPED) in Deutschland) this prospective study during a 5 five year period captured 657 patients at first diagnosis of either BO (n=378) or NBO (n=279) while analyzing epidemiologic, clinical and radiologic data. RESULTS:: BO was reported in 1.2 per 100,000 children with a higher prevalence in younger male patients (58%), and NBO was reported in 0.45 per 100,000 children. BO patients tended to present with fevers (68%), elevated inflammation markers (82%) and local swelling (62%) but a shorter course of symptoms than NBO patients. NBO patients presented in good general health (86%) and were more likely to have multifocal lesions (66%). S. aureus was the most prominent pathogen (83%), with only one MRSA reported. Complications ranged from arthritis adjacent to the lesion to hyperostosis and vertebral fractures. CONCLUSION:: BO and NBO can be distinguished based on symptoms, associated diseases and inflammation markers. NBO should always be considered in pediatric patients presenting with bone lesions and pain, especially in young female patients presenting with good general health, minimal inflammation markers, and multifocal lesions in the vertebrae, clavicle and sternum. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Schneider H.,Ludwig Maximilians University of Munich
International Conference on Intelligent User Interfaces, Proceedings IUI | Year: 2017

Personal health and fitness technologies, such as activity trackers, bear the potential to impact health behaviors globally. However, most users abandon these technology quickly. Possible reasons are that provided feedback (often consisting of raw data) is not actionable, not relevant, or the provided advice is not easy to integrate into people's lives. One approach to tackle this problem, is to develop personalized or adaptive digital coaches that take users' individual differences and situation into account. Even though the first prototypes of personalized coaches have been presented and evaluated, this research is still in its infancy. In my thesis, I want to extend this research by (a) investigating the influences of individual differences on behaviors and motivations to use a digital fitness coach, (2) mapping and conceptually exploring the design space of personalized digital fitness coaches, (3) and iteratively prototyping and testing adaptations of personalized fitness coaches in a user-centered design process. Copyright is held by the author/owner(s).

Ilie N.,Ludwig Maximilians University of Munich | Stawarczyk B.,Ludwig Maximilians University of Munich
Journal of Dentistry | Year: 2014

Objective This study aimed to evaluate the amount of light (360-540 nm) passing through shaded zirconia with respect to material thickness, exposure distance, and different curing modes. Methods The specimens were divided into groups according to thickness as follows: 0.5, 1, 1.5, 2, 2.5, and 3 mm. Thirty-five zirconia and seven glass-ceramic (control group) specimens were fabricated for each group (N = 252). Zirconia was divided into five subgroups (n = 7) and stained to the following shades: CL1, CL2, CL3, and CL4. One zirconia group remained unstained (CL0). Irradiance passing through the different specimens was measured using a violet-blue LED curing unit in three curing modes (Xtra-power, high-power, and standard-power mode) with a fibre-optic USB4000 spectrometer. Irradiance was measured at varying exposure distances, ranging from direct contact of the curing unit with the surface to a distance of 7 mm from the surface, increasing in 1 mm steps. Data were analyzed using a multivariate analysis and linear mixed models (p < 0.05). Results The control group, the glass-ceramics, transmitted the highest irradiance values, followed by CL0 (unshaded zirconia), CL1 (∼A1/B1), CL2 (∼A3/A3.5/A4/B3/B4), and CL3 (∼A3.5/B3/B4/C3/D3), respectively. The highest transmitted irradiance was measured at a specimen thickness of 0.5 mm for all materials, decreasing exponentially with increased ceramic thickness. Within one type of ceramic, one thickness, and one polymerization mode, a decrease in transmitted irradiance with increased exposure distance could be observed only at a distance of 3 mm and above. Conclusions Unshaded zirconia was significantly less translucent compared with the glass-ceramic, but the translucency decreased slower with material thickness. The Beer-Lambert law describes well the decrease of transmitted irradiance with an increase of the specimens' thickness for all materials. Except for dark ceramics, this would allow for calculating the transmitted irradiance through any material thickness and any initial irradiance. Clinical significance The amount of light passing through ceramics is an important aspect for an adhesive cementation, since many dual-cured luting materials reveal a high sensitivity to additional occurrence of blue light. For restorations thicker than 1.5 mm in light-shaded zirconia and 0.5 mm in darker-shaded zirconia the use of less-light-sensitive dual-cured cements are recommended. © 2014 Elsevier Ltd. All rights reserved.

Hoechter D.J.,Ludwig Maximilians University of Munich
ASAIO Journal | Year: 2017

Extracorporeal circulation is an invaluable tool in lung transplantation. Over the past years, an increasing number of centers changed their standard for intraoperative extracorporeal circulation from cardiopulmonary bypass to extracorporeal membrane oxygenation – with differing results. This meta-analysis reviews the existing evidence.An online literature research on Medline, Embase, and Pubmed has been performed. Two persons independently judged the papers using the ACROBAT-NRSI tool of the Cochrane collaboration. Meta-analyses and meta-regressions were used to determine whether veno-arterial extracorporeal membrane oxygenation (ECMO) resulted in better outcomes compared to cardiopulmonary bypass (CPB).Six papers – all observational studies without randomization - were included into the analysis. All were considered to have serious bias due to heparinization as co-intervention. Forest plots showed a beneficial trend of ECMO regarding blood transfusions (packed red blood cells with an average mean difference of -0.46units [95% CI=-3.72,2.80], fresh-frozen plasma with an average mean difference of -0.65units [95% CI=-1.56,0.25], platelets with an average mean difference of -1.72units [95% CI=-3.67,0.23]). Duration of ventilator support with an average mean difference of -2.86days [95% CI=-11.43,5.71] and ICU length of stay with an average mean difference of -4.79days [95% CI=-8.17,-1.41] were shorter in ECMO patients. ECMO treatment tended to be superior regarding 3month mortality (odds ratio=0.46, 95% CI=0.21-1.02) and 1year mortality (odds ratio=0.65, 95% CI=0.37-1.13). However, only the ICU length of stay reached statistical significance. Meta-regression analyses showed that heterogeneity across studies (sex, year of ECMO implementation and underlying disease) influenced differences.These data indicate a benefit of the intraoperative use of ECMO as compared to CPB during lung transplant procedures regarding short-term outcome (ICU stay).There was no statistical significant effect regarding blood transfusion needs or long term outcome. The superiority of ECMO in lung transplantation patients remains to be determined in larger multi-center randomized trials. Copyright © 2017 by the American Society for Artificial Internal Organs

Graf I.R.,Ludwig Maximilians University of Munich | Frey E.,Ludwig Maximilians University of Munich
Physical Review Letters | Year: 2017

Transport of molecular motors along protein filaments in a half-closed geometry is a common feature of biologically relevant processes in cellular protrusions. Using a lattice-gas model we study how the interplay between active and diffusive transport and mass conservation leads to localized domain walls and tip localization of the motors. We identify a mechanism for task sharing between the active motors (maintaining a gradient) and the diffusive motion (transport to the tip), which ensures that energy consumption is low and motor exchange mostly happens at the tip. These features are attributed to strong nearest-neighbor correlations that lead to a strong reduction of active currents, which we calculate analytically using an exact moment identity, and might prove useful for the understanding of correlations and active transport also in more elaborate systems. © 2017 authors. Published by the American Physical Society. Published by the American Physical Society under the terms of the »» Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

Li G.-X.,Ludwig Maximilians University of Munich
Monthly Notices of the Royal Astronomical Society | Year: 2017

We study the evolution of structures in turbulent, self-gravitating media, and present an analytical criterion Mcrit ≈ εcascade 2/3 η -2/3G -1l5/3 (where Mcrit is the critical mass, l is the scale, εcascade ≈ ησv 3 /l is the turbulence energy dissipation rate of the ambient medium, G is the gravitational constant, σv is the velocity dispersion and η ≈ 0.2 is an efficiency parameter) for an object to undergo quasi-isolated gravitational collapse. The criterion also defines the critical scale (lcrit ≈ εcascade 1/2 η -1/2G -3/4ρ -3/4) for turbulent gravitational instability to develop. The analytical formalism explains the size dependence of the masses of the progenitors of star clusters (Mcluster ~ Rcluster 1.67) in our Galaxy. © 2016 The Authors.

Gussmann A.,Ludwig Maximilians University of Munich
Classical and Quantum Gravity | Year: 2017

The existence of the classical black hole solutions of the Einstein-Yang-Mills-Higgs equations with non-Abelian Yang-Mills-Higgs hair implies that not all classical stationary magnetically charged black holes can be uniquely described by their asymptotic characteristics. In fact, in a certain domain of parameters, there exist different spherically-symmetric, non-rotating and asymptotically-flat classical black hole solutions of the Einstein-Yang-Mills-Higgs equations which have the same ADM mass and the same magnetic charge but significantly different geometries in the near-horizon regions. (These are black hole solutions which are described by a Reissner-Nordström metric on the one hand and the black hole solutions with non-Abelian Yang-Mills-Higgs hair which are described by a metric which is not of Reissner-Nordström form on the other hand). One can experimentally distinguish such black holes with the same asymptotic characteristics but different near-horizon geometries classically by probing the near-horizon regions of the black holes. We argue that one way to probe the near-horizon region of a black hole which allows one to distinguish magnetically charged black holes with the same asymptotic characteristics but different near-horizon geometries is by classical scattering of waves. Using the example of a minimally-coupled massless probe scalar field scattered by magnetically charged black holes which can be obtained as solutions of the Einstein-Yang-Mills-Higgs equations with a Higgs triplet and gauge group SU(2) in the limit of an infinite Higgs self-coupling constant we show how, in this case, the scattering cross sections differ for the magnetically charged black holes with different near-horizon geometries but the same asymptotic characteristics. We find in particular that the characteristic glory peaks in the cross sections are located at different scattering angles. © 2017 IOP Publishing Ltd.

Malek E.,Ludwig Maximilians University of Munich
Journal of High Energy Physics | Year: 2017

In this paper we show how to obtain heterotic double field theory from exceptional field theory by breaking half of the supersymmetry. We focus on the SL(5) exceptional field theory and show that when the extended space contains a generalised SU(2)-structure manifold one can define a reduction to obtain the heterotic SO(3, n) double field theory. In this picture, the reduction on the SU(2)-structure breaks half of the supersymmetry of the exceptional field theory and the gauge group of the heterotic double field theory is given by the embedding tensor of the reduction used. Finally, we study the example of a consistent truncation of M-theory on K3 and recover the duality with the heterotic string on T3. This suggests that the extended space can be made sense of even in the case of non-toroidal compactifications. © 2017, The Author(s).

Berger B.,Ludwig Maximilians University of Munich
Pacific Asia Conference on Information Systems, PACIS 2016 - Proceedings | Year: 2016

Many content providers still struggle to establish viable revenue models on the Internet and thus try to tap new sources of income. Using content to drive sales of related products or services such as in affiliate marketing or content-driven commerce appears to be a promising solution for this issue. However, these commerce-oriented revenue models may cast doubt on the credibility of the content, which is an important success factor for the providers. Drawing upon credibility concepts and information processing theories from communication science, we conducted a vignette-based online experiment to investigate whether content credibility is affected by the provider's revenue model. Participants in the experiment were shown a screenshot of a website, which was monetized either by advertising, affiliate marketing or content-driven commerce. Our results indicate that content credibility in the affiliate marketing scenario was higher than in the content-driven commerce or the advertising scenario. A mediation analysis revealed that this effect was mediated by the content provider's trustworthiness. Our findings shed light on the relationship between credibility and monetization of content on the Internet. Moreover, they are helpful for practitioners in the media industry in designing optimal revenue generation strategies.

Ochmann U.,Ludwig Maximilians University of Munich
Allergologie | Year: 2016

Depending on the literature source 10-15% of all asthma diseases in adults are related to the workplace. Work related asthma can be triggered by allergens as well as by chemicals. The diagnostic of work related asthma includes work place related medical history, allergological tests for occupational allergens and the attempt to objectify the reported association of symptoms to the workplace, for example by monitoring lung function with and without exposure at the workplace. During career counselling patients with allergic asthma should be advised against taking a job with occupational allergen exposure. Also in patients with occupational asthma relations between psychological comorbidities like depression or anxiety can be stated. Quality of life in patients with occupational asthma is low compared to patients with fateful asthma, possibly due to extensive social and fnancial consequences. Psycho logical factors can also fake an occupational asthma, as it is known in vocal cord dysfunction, sick building syndrome or anxiety due to emissions of laser printers in offces. © 2016 Dustri-Verlag Dr. Karl Feistle.

Frivolt K.,Ludwig Maximilians University of Munich
Journal of Pediatric Gastroenterology and Nutrition | Year: 2017

OBJECTIVES:: Recent evidence points towards an active immunological role of intra-abdominal adipose tissue in Crohnʼs disease (CD). We quantified the abdominal adipose tissue compartments using magnetic resonance imaging (MRI) in 27 pediatric CD patients compared with 14 controls undergoing MRI examination for other reasons. METHODS:: Total (TAAT), subcutaneous (SCAT) and intra-abdominal (IAAT) adipose tissue areas were measured by semiautomatic segmentation on a transverse slice centered on the umbilicus (mean?±?standard deviation in cm) using standard T1 weighted sequences. IAAT/TAAT and IAAT/height ratios were calculated and analyzed for associations with disease duration, phenotype or therapy. RESULTS:: CD patients (median age 15.0 years, range 7.7–17.9, 18/27 males, median disease duration 29 months, range 0–136) compared to controls (median age 13.9 years, range 3.3–17.8, 4/14 males) had higher IAAT area (42.3?±?21.0 vs. 28.7?±?11.6, p=0.0494) but similar SCAT and TAAT areas (104.6?±?72.8 vs. 96.5?±?50.8, p?=?0.8170 and 146.9?±?87.3 vs. 125.3?±?61.5, p?=?0.7417, respectively). IAAT/TAAT ratio was higher in CD patients compared to controls (0.32?±?0.10 vs. 0.24?±?0.04, p?=?0.0081). Patients with disease duration over 2 years (n?=?14) had higher IAAT/TAAT ratio than those with shorter disease and controls (0.35?±?0.10 vs. 0.28?±?0.08, p?=?0.0288 and 0.24?±?0.04, p?=?0.0009, respectively). In these patients increased IAAT/height ratio was associated with complicated disease (p?=?0.043, r?=?0.573). No association was found between IAAT/TAAT ratio and actual disease activity or therapy. CONCLUSIONS:: IAAT is increased in pediatric CD and correlates with disease duration. Assessment of IAAT accumulation may be considered in future MRI scores for inflammation and bowel damage in CD and during follow-up of different therapeutic interventions. © 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

Hermanns C.,Ludwig Maximilians University of Munich
Oncogene | Year: 2017

Megakaryoblastic Leukemia 1 and 2 (MKL1/2) are transcriptional coactivators of Serum Response Factor (SRF) with an essential role for hepatocellular carcinoma (HCC) growth and oncogene-induced senescence. In this report, we identified myoferlin as a novel MKL/SRF target gene by gene expression profiling and verification in vivo in HCC xenografts. Myoferlin was overexpressed in human and murine HCCs triggered by conditional expression of constitutively active SRF-VP16 protein in hepatocytes. Furthermore, myoferlin was required for HCC cell invasion, proliferation and anchorage-independent cell growth. We provide evidence that myoferlin is a crucial gene target of MKL1/2 mediating its effect on oncogene-induced senescence by modulating the activation state of the EGFR and downstream MAPK and p16-/Rb pathways. Depletion of myoferlin in tumour cells from SRF-VP16-derived murine HCCs induced a senescence phenotype. These findings identify MKL1/2 and myoferlin as novel therapeutic targets to treat human HCC by a senescence-inducing strategy.Oncogene advance online publication, 23 January 2017; doi:10.1038/onc.2016.496. © 2017 Macmillan Publishers Limited, part of Springer Nature.

Medugorac I.,Ludwig Maximilians University of Munich
Nature Genetics | Year: 2017

The yak is remarkable for its adaptation to high altitude and occupies a central place in the economies of the mountainous regions of Asia. At lower elevations, it is common to hybridize yaks with cattle to combine the yak's hardiness with the productivity of cattle. Hybrid males are sterile, however, preventing the establishment of stable hybrid populations, but not a limited introgression after backcrossing several generations of female hybrids to male yaks. Here we inferred bovine haplotypes in the genomes of 76 Mongolian yaks using high-density SNP genotyping and whole-genome sequencing. These yaks inherited ∼1.3% of their genome from bovine ancestors after nearly continuous admixture over at least the last 1,500 years. The introgressed regions are enriched in genes involved in nervous system development and function, and particularly in glutamate metabolism and neurotransmission. We also identified a novel mutation associated with a polled (hornless) phenotype originating from Mongolian Turano cattle. Our results suggest that introgressive hybridization contributed to the improvement of yak management and breeding. © 2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Walliser I.,Ludwig Maximilians University of Munich | Gobel T.W.,Ludwig Maximilians University of Munich
Developmental and Comparative Immunology | Year: 2017

Interleukin 17 (IL-17) cytokines play a crucial role in host defense and inflammatory diseases. Of the six mammalian IL-17 members five are described in the chicken (gg) genome. A novel method that attached cytokines to the surface of cells via a GPI linker was established to generate two chicken IL-17A and one chicken IL-17F specific mab. Recombinant gg IL-17A and gg IL-17F that showed dimerization in Western blot were used to verify the antibodies specificity. The mab could detect gg IL-17 by intracellular cytokine staining as demonstrated on cells expressing recombinant IL-17. Furthermore IL-17A and lower amounts of IL-17F were detectable in CD4 positive T cells of stimulated splenocytes. In conclusion, we have generated novel tools to analyze chicken IL-17 in more detail and demonstrated that the surface expression of cytokines is a reliable method to generate specific mab applicable for intracellular cytokine staining. © 2017 Elsevier Ltd

Hao H.-D.,Ludwig Maximilians University of Munich | Trauner D.,Ludwig Maximilians University of Munich
Journal of the American Chemical Society | Year: 2017

Two complex norditerpenoids, caribenols A and B, were accessed from a common building block. Our synthesis of caribenol A features the diastereoselective formation of the seven-membered ring through a Friedel-Crafts triflation and a late-stage oxidation of a furan ring. The first synthesis of caribenol B was achieved using an intramolecular organocatalytic α-arylation. An unusual intramolecular aldol addition was developed for the assembly of its cyclopentenone moiety, and the challenging trans-diol moiety was installed through a selective nucleophilic addition to a hydroxy 1,2-diketone. Our overall synthetic strategy, which also resulted in a second-generation synthesis of amphilectolide, confirms the usefulness of furans as powerful nucleophiles and versatile synthons. © 2017 American Chemical Society.

Koletzko B.,Ludwig Maximilians University of Munich
Clinics in Perinatology | Year: 2017

Based on the available data, a high milk docosahexaenoic acid supply to very low-birth-weight infants and to extremely low-birth-weight infants at levels that support tissue accretion rates similar to the high rates of intrauterine deposition has the potential to enhance the early visual and cognitive development, and to reduce the occurrence of adverse events, such as severe developmental delay, bronchopulmonary dysplasia, necrotizing enterocolitis, and allergic manifestations in infancy and early childhood. Possibly subgroups of preterm infants achieve greater benefits as well as infants with genotypes predicting a low rate of endogenous long-chain polyunsaturated fatty acids formation. © 2016 The Author

Hofmann M.A.,Ludwig Maximilians University of Munich
Proceedings - Winter Simulation Conference | Year: 2017

Several papers have recently criticized the use of null hypothesis significance testing (NHST) in scientific applications of stochastic computer simulation. Their criticism can be underpinned by numerous articles from statistical methodologists. They have argued that focusing on p-values is not conducive to science, and that NHST is often dangerously misunderstood . A critical reflection of the arguments contra NHST shows, however, that although NHST is indeed ill-suited for many simulation applications and objectives it is by no means superfluous, neither in general, nor in particular for simulation. © 2016 IEEE.

Dichgans M.,Ludwig Maximilians University of Munich | Dichgans M.,German Center for Neurodegenerative Diseases | Dichgans M.,Synergy Systems | Leys D.,Lille University Hospital Center
Circulation Research | Year: 2017

Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts. © 2017 American Heart Association, Inc.

Pakalniskyte D.,Ludwig Maximilians University of Munich | Schraml B.U.,Ludwig Maximilians University of Munich
Advances in Immunology | Year: 2017

Dendritic cells (DCs) are versatile controllers of immunity, which sense infection or tissue damage and, accordingly, initiate innate and adaptive effector responses. In recent years, it has become evident that DCs exist as an independent hematopoietic lineage comprising several developmentally distinct and functionally specialized subsets that are strategically located in all organs to defend the organism against invading pathogens. Here, we review the diversity of DC subtypes found across tissues and discuss our current understanding of the tissue-specific functions of these cell types. © 2017 Elsevier Inc.

Schinner C.,Ludwig Maximilians University of Munich
Circulation Research | Year: 2017

RATIONALE:: The sympathetic nervous system is a major mediator of heart function. Intercalated discs (ICDs) composed of desmosomes, adherens junctions and gap junctions provide the structural backbone for coordinated contraction of cardiac myocytes. OBJECTIVE:: Gap junctions dynamically remodel to adapt to sympathetic signaling. However, it is unknown whether such rapid adaption also occurs for the adhesive function provided by desmosomes and adherens junctions. METHODS AND RESULTS:: Atomic force microscopy revealed that β-adrenergic signaling enhances both the number of desmoglein 2 (Dsg2) -specific interactions along cell junctions and the mean Dsg2-mediated binding forces, whereas N-cadherin-mediated interactions were not affected. This was accompanied by increased cell cohesion in cardiac myocyte cultures and murine heart slices. Enhanced Dsg2-positive contacts and increased junction length as revealed by immunofluorescence and electron microscopy reflected cAMP-induced reorganization of intercellular contacts. The mechanism underlying cAMP-mediated strengthening of Dsg2 binding was dependent on expression of the ICD plaque protein plakoglobin (Pg) and direct phosphorylation at S665 by PKA: Pg deficiency as well as overexpression of the phospho-deficient Pg-mutant S665A abrogated both cAMP-mediated junctional remodeling and increase of cohesion. Moreover, Pg knockout hearts failed to functionally adapt to adrenergic stimulation. CONCLUSIONS:: Taken together, we provide first evidence for positive adhesiotropy as a new cardiac function of sympathetic signaling. Positive adhesiotropy is dependent on Pg phosphorylation at S665 by PKA. This mechanism may be of high medical relevance because loss of junctional Pg is a hallmark of arrhythmogenic cardiomyopathy. © 2017 American Heart Association, Inc.

Alba V.,Ludwig Maximilians University of Munich | Haque M.,Max Planck Institute For Physik Komplexer Systeme | Lauchli A.M.,University of Innsbruck
Physical Review Letters | Year: 2013

We study the entanglement spectrum (ES) of the Bose-Hubbard model on the two-dimensional square lattice at unit filling, both in the Mott insulating and in the superfluid phase. In the Mott phase, we demonstrate that the ES is dominated by the physics at the boundary between the two subsystems. On top of the boundary-local (perturbative) structure, the ES exhibits substructures arising from one-dimensional dispersions along the boundary. In the superfluid phase, the structure of the ES is qualitatively different, and reflects the spontaneously broken U(1) symmetry of the phase. We attribute the basic low-lying structure to the "tower of states" Hamiltonian of the model. We then discuss how these characteristic structures evolve across the superfluid to Mott insulator transition and their influence on the behavior of the entanglement entropies. We briefly outline the implications of the ES structure on the efficiency of matrix-product-state based algorithms in two dimensions. © 2013 American Physical Society.

Ming R.,University of Illinois at Urbana - Champaign | Bendahmane A.,French National Institute for Agricultural Research | Bendahmane A.,King Saud University | Renner S.S.,Ludwig Maximilians University of Munich
Annual Review of Plant Biology | Year: 2011

Sex chromosomes in land plants can evolve as a consequence of close linkage between the two sex determination genes with complementary dominance required to establish stable dioecious populations, and they are found in at least 48 species across 20 families. The sex chromosomes in hepatics, mosses, and gymnosperms are morphologically heteromorphic. In angiosperms, heteromorphic sex chromosomes are found in at least 19 species from 4 families, while homomorphic sex chromosomes occur in 20 species from 13 families. The prevalence of the XY system found in 44 out of 48 species may reflect the predominance of the evolutionary pathway from gynodioecy towards dioecy. All dioecious species have the potential to evolve sex chromosomes, and reversions back from dioecy to various forms of monoecy, gynodioecy, or androdioecy have also occurred. Such reversals may occur especially during the early stages of sex chromosome evolution before the lethality of the YY (or WW) genotype is established. Copyright © 2011 by Annual Reviews. All rights reserved.

Roenneberg T.,Ludwig Maximilians University of Munich | Allebrandt K.V.,Ludwig Maximilians University of Munich | Merrow M.,University of Groningen | Vetter C.,Ludwig Maximilians University of Munich
Current Biology | Year: 2012

Obesity has reached crisis proportions in industrialized societies [1]. Many factors converge to yield increased body mass index (BMI). Among these is sleep duration [2-10]. The circadian clock controls sleep timing through the process of entrainment. Chronotype describes individual differences in sleep timing, and it is determined by genetic background, age, sex, and environment (e.g., light exposure) [11-14]. Social jetlag quantifies the discrepancy that often arises between circadian and social clocks, which results in chronic sleep loss [11, 15]. The circadian clock also regulates energy homeostasis [16], and its disruption - as with social jetlag - may contribute to weight-related pathologies [17-19]. Here, we report the results from a large-scale epidemiological study, showing that, beyond sleep duration, social jetlag is associated with increased BMI. Our results demonstrate that living "against the clock" may be a factor contributing to the epidemic of obesity. This is of key importance in pending discussions on the implementation of Daylight Saving Time and on work or school times, which all contribute to the amount of social jetlag accrued by an individual. Our data suggest that improving the correspondence between biological and social clocks will contribute to the management of obesity. Video Abstract: © 2012 Elsevier Ltd.

Doennig D.,Ludwig Maximilians University of Munich | Pickett W.E.,University of California at Davis | Pentcheva R.,Ludwig Maximilians University of Munich
Physical Review Letters | Year: 2013

Density functional theory calculations with an on-site Coulomb repulsion term reveal competing ground states in (111)-oriented (LaAlO3) M/(SrTiO3)N superlattices with n-type interfaces, ranging from spin, orbitally polarized (with selective eg′, a1g, or dxy occupation), Dirac point Fermi surface, to charge-ordered flat band phases. These phases are steered by the interplay of (i) Hubbard U, (ii) SrTiO3 quantum well thickness, and (iii) crystal field splitting tied to in-plane strain. In the honeycomb lattice bilayer N=2 under tensile strain, inversion symmetry breaking drives the system from a ferromagnetic Dirac point (massless Weyl semimetal) to a charge-ordered multiferroic (ferromagnetic and ferroelectric) flat band massive (insulating) phase. With increasing SrTiO3 quantum well thickness an insulator-to-metal transition occurs. © 2013 American Physical Society.

Vogeser M.,Ludwig Maximilians University of Munich | Seger C.,University of Innsbruck
Clinical Chemistry | Year: 2010

BACKGROUND: Novel mass spectrometric techniques such as atmospheric pressure ionization and tandem mass spectrometry have substantially extended the spectrum of clinical chemistry methods during the past decade. In particular, liquid chromatography tandem-mass spectrometry (LC-MS/MS) has become a standard tool in research laboratories as well as in many clinical laboratories. Although LC-MS/MS has features that suggest it has a very high analytical accuracy, potential sources of inaccuracy have recently been identified. CONTENT: The sources of inaccuracy in LC-MS/MS methods used in the routine quantification of small molecules are described and discussed. Inaccuracy of LC-MS/MS methods can be related to the process of ionization through the insource transformation of conjugate metabolites or target analytes and may also be attributable to ionization matrix effects that have a differential impact on target analytes and internalstandard compounds. Inaccuracy can also be associated with the process of ion selection, which mainly occurs when compounds from the sample matrix share mass transitions with a target analyte. In individual assays, most potential sources of inaccuracy can be controlled by sufficient LC separation-based sample workup before MS analysis. SUMMARY: LC-MS/MS methods should undergo rigorous and systematic validation before introduction into patient care. © 2010 American Association for Clinical Chemistry.

Ochsenkuhn T.,Ludwig Maximilians University of Munich
Gut | Year: 2011

Past and ongoing therapeutic concepts for ulcerative colitis have only been moderately successful. A significant proportion of patients with ulcerative colitis will still have to undergo colectomy and overall half of the patients do not achieve sustained remission, leading to impairment of physical and mental health, social life, employment issues and sexual activity. Reluctance to treat patients early on with sufficiently potent drug regimens is obvious. Several popular misconceptions might have led to this situation. First, ulcerative colitis is still considered a more 'benign' disease than Crohn's disease. Furthermore, the general assumption is often that colectomy can 'cure' the disease. Mucosal healing as a therapeutic target has not been widely accepted. Finally, the use of antitumour necrosis factor antibodies in ulcerative colitis has been low because this treatment is considered to be less effective than in Crohn's disease. In the current review we try to disprove these misunderstandings by discussing relevant studies showing how harmful this disease can be and explaining why future studies targeting sustained suppression of inflammation could have an enormous impact on the natural course of the disease. Until these studies are available, we encourage physicians to intensify and maintain treatment until sustained remission and mucosal healing has been reached.

Dimou L.,Ludwig Maximilians University of Munich | Dimou L.,Institute for Stem Cell Research | Dimou L.,Synergy Systems | Gotz M.,Ludwig Maximilians University of Munich | And 2 more authors.
Physiological Reviews | Year: 2014

The diverse functions of glial cells prompt the question to which extent specific subtypes may be devoted to a specific function. We discuss this by reviewing one of the most recently discovered roles of glial cells, their function as neural stem cells (NSCs) and progenitor cells. First we give an overview of glial stem and progenitor cells during development; these are the radial glial cells that act as NSCs and other glial progenitors, highlighting the distinction between the lineage of cells in vivo and their potential when exposed to a different environment, e.g., in vitro. We then proceed to the adult stage and discuss the glial cells that continue to act as NSCs across vertebrates and others that are more lineage-restricted, such as the adult NG2-glia, the most frequent progenitor type in the adult mammalian brain, that remain within the oligodendrocyte lineage. Upon certain injury conditions, a distinct subset of quiescent astrocytes reactivates proliferation and a larger potential, clearly demonstrating the concept of heterogeneity with distinct subtypes of, e.g., astrocytes or NG2-glia performing rather different roles after brain injury. These new insights not only highlight the importance of glial cells for brain repair but also their great potential in various aspects of regeneration. © 2014 the American Physiological Society.

This project aims to understand what kind of social identity change is going on within European societies. For policy-making, the analysis of social identity is highly valuable because the social identity moderates the impact of policies. And this is particularly true in times of crisis. In particular, the project aims: A) to verify whether the symbolic universes grounding the social identity has undergone a major change within European societies, as a consequence of the socio-economic crisis; B) to draw strategic and methodological implications for policy-making from point A. This project includes 4 core scientific work packages: a) Multilevel Analysis of the Symbolic Universes, aimed at mapping structurally and developmentally the systems of meaning (i.e. the symbolic universes) grounding the social identity; b) Case Studies for policies, aimed at see how different policies have been organized and how their impact might or might not have been moderated by the symbolic dynamics at stake; c) the results of this analysis will be transformed into abstract criteria, contextualised in 5 different European macro-Regions, discussed with stakeholders, opinions leaders, policy-makers and finally stored within the guidelines; d) finally, the guidelines will be validated in terms of pertinence, effectiveness and the feasibility criteria, through seminars with the policy makers, opinion leaders and stakeholders, belonging to national, European, international Agencies involved in the construction and implementation of policies. Also, focus groups will be organized in each cultural context in order to study the impact of context-specific criteria.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.2-1 | Award Amount: 8.32M | Year: 2012

Chemotherapy is slowly being supplemented by a new generation of drugs that recognize specific targets in or on cancer cells and has proven to be more effective with markedly fewer side effects. During the course of the disease alternative oncogenic signaling pathways take over inevitably leading to drug resistance. As a consequence renewed tumor analysis is required to redefine the optimal treatment regiment. However a biopsy can frequently not be obtained without risk and or discomfort to the patient. Circulating tumor cells (CTC) may circumvent this problem. CTC refer to cells that detach from a primary tumor or metastatic site, circulate in the peripheral blood and may form metastasis. CTC represent a liquid biopsy that can be used to tailor treatment for individual patients. CTC are however rare and can only be obtained for further characterization in a small fraction of patients. In the CTCtrap consortium universities, research institutions and SMEs are linked in a common effort, starting from the simple, but innovative view of using Therapeutic Apheresis (TA), as a way to collect CTC from peripheral blood in cancer patients. A new TA column will be developed to capture CTC and then reintroduce the blood devoid of tumor cells back into the body with the promise to obtain CTC in all patients at risk for recurrence or diagnosed with metastatic disease. The molecular characterization of these CTC is expected to gather new knowledge on metastasis mechanism, provide a risk assessment and the optimal therapy choice during the course of the disease of cancer patients. The new knowledge on CTC heterogeneity within cancer type and within individuals will allow for the tuning of CTCapheresis to specific cancer types. Prospective pilot studies will be setup to investigate the feasibility of the CTCapheresis in the clinic and their potential therapeutic benefit. Success of CTCapheresis will lead to a radical change in the diagnosis and treatment of solid tumors.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.87M | Year: 2016

Cancer is a major social problem, and it is the main cause of death between the ages 45-65 years. In the treatment of cancer, radio therapy (RT) plays an essential role. RT with hadrons (protons and light ions), due to their unique physical and radiobiological properties, offers several advantages over photons for specific cancer types. In particular, they penetrate the patient with minimal diffusion, they deposit maximum energy at the end of their range, and they can be shaped as narrow focused and scanned pencil beams of variable penetration depth. Although significant progress has been made in the use of particle beams for cancer treatment, an extensive research and development program is still needed to maximize the healthcare benefits from these therapies. The Optimization of Medical Accelerators (OMA) is the aim of the here-proposed European Training Network, in line with the requirements of the ECs Medical Exposure Directive. OMA joins universities, research centers and clinical facilities with industry partners to address the challenges in treatment facility design and optimization, numerical simulations for the development of advanced treatment schemes, and in beam imaging and treatment monitoring. The proposed R&D program ranges from life sciences (oncology, cell and micro biology and medical imaging.), physics and accelerator sciences, mathematics and IT, to engineering. It is hence ideally suited for an innovative training of early stage researchers. By closely linking all above research areas, OMA will provide an interdisciplinary education to its Fellows. This will equip them with solid knowledge also in research areas adjacent to their core research field, as well as with business competences and hence give them a perfect basis for a career in research.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.67M | Year: 2016

DIAPHORA serves as a European research and training platform for collaborative research on the nature of philosophical problems, their resilience and the sources of persistent divergence of expert opinion about them, and their relation to conflicts in the practical sphere. More specifically, DIAPHORAs 3 principal research objectives are (A) to diagnose what makes philosophical problems so resilient and to clarify to what extent the sustained lack of convergence in philosophy can successfully be explained by the hardness of its problems; (B) to explain why the tendency has not been towards a general agnosticism about candidate solutions, but rather towards divergence, and to identify features of philosophical method that allow for such persistent peer disagreement; and (C) to explore whether the dynamics of philosophical debate, despite the subjects highly theoretical nature, bears important and instructive resemblances to the dynamics of debates about more practical matters and their political and socio-economical antecedents and hence whether philosophical problems and their attempted resolution can illuminate, and be illuminated by, the procedural and methodological difficulties besetting strategies for the adjudication of public affairs, thereby determining what philosophical thought might contribute to society at large. DIAPHORA joins 7 leading European research centres in philosophy, and 5 partner organisations, 3 of which from the non-academic sector, in the fields of international conflict management, mediation and policy-making, as well as the analysis of social conflict and cultural diversity. It undertakes to provide 14 Early Stage Researchers with the knowledge and skills necessary to meet the demands of top-level research within its remit, as well as professional complementary skills training in both the academic and non-academic sectors, with the goal of widening their potential societal contributions and improving their individual career prospects.

Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2013-IRSES | Award Amount: 285.60K | Year: 2014

As software becomes ever more ubiquitous in our lives, the need to ensure it runs without error becomes ever more important. Restarting a phone is a simple, if inconvenient task; restarting an aeroplane in mid-flight is not an option! Correct by construction programming offers a revolutionary approach to program verification where programs can contain not just computations as is normal, but also logical proofs of the correctness of these computations. The simple fact that such programs compile provides formal, i.e. mathematical, guarantees of the correctness of the program. In particular, there is no need for post-hoc testing of software etc. Fundamental to the implicit marriage of computation and logic inherent within correct by construction programming is the choice of the right logical systems and concepts upon which programming languages ought to be built. This reflects the symbiotic relationship between logic, programming, and the design of programming languagesany attempt to sever this connection will diminish each component. This proposal brings together internationally leading researchers from both inside Europe and outside Europe to work on exactly what logical structures are needed for correct by construction programming and how those logical structures can then by turned into concrete programming artefacts. In order to produce fundamental work which stands the test of time, we work not with specific programming languages but with mathematical abstractions of them. The recent development of dependently typed programming languages capable of supporting correct by construction programming makes this a very timely proposal, while the billions spent on software every year makes the potential impact of this proposal very significant.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 4.61M | Year: 2009

Chromatin packages a few meters of DNA into a nucleus measuring a few microns. This tight folding occurs by assembling DNA with histones into so-called nucleosomes, thus ensuring the mechanical stability of our genome. On the flipside, this makes nucleosomes a formidable obstacle to the machines that read, copy or repair its DNA message. One of the fundamental questions in biology is to understand how nucleosome structure is established, maintained and manipulated. Our Marie Curie Initial Training Network will carry out multidisciplinary, collaborative research projects focused on deciphering nucleosome structure and function in space and time (Nucleosome4D). Our main objective is to provide our young researchers with world-class research & training in nucleosome biology. We will use cutting-edge, interdisciplinary methods and collaborative projects to determine how nucleosomes are remodeled during transcription, when genes are silenced, as cell divide, as stem cells differentiate, during organismal development and in human disease. We utilize state-of-the-art approaches in structural biology, biophysics, cell biology, live-cell imaging, biochemistry, genetics, genomics and bioinformatics. We will implement a comprehensive training plan for scientific and career development using the best local approaches to research & training, by promoting exchanges, using the advise of our industrial partners and three Visiting Scientists, by sharing reagents and expertise, as well as through a structured set of scientific workshops and complementary skills training courses. Together, our effort will ensure the multidisciplinary and intersectorial training of a new cohort of young European researchers. This will allow our trainees to take the opportunities and meet the challenges of a successful career in the life science sector through excellent training, effective communication, great teamwork and proven project management skills.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.8.2 | Award Amount: 4.00M | Year: 2008

We are currently standing on the brink of a new era of computing systems: Moving on from desktop computers, computing intelligence will be woven into the fabric of everyday life, seamlessly and near-invisibly pervading our environment, sensing our presence, mood, and intentions, thus delivering services adapted to ourselves and our context of use.\n\nThe REFLECT project aims at developing new concepts and means for such pervasive-adaptive systems. To begin with, REFLECT researches ways of sensing users and their mood and intentions. Different aspects are taken into account: emotional state (e.g. annoyance), cognitive engagement (e.g. high mental workload) and physical conditions and actions (e.g. temperature and movement). All these together with human behavioural patterns form the personal awareness of the system. Additionally, information about the surroundings is gathered and used to establish environmental awareness.\n\nAugmenting these results, REFLECT investigates ways of realizing pervasive-adaptive environments. A software framework with a set of practical tools is developed which can be used for building pervasive, adaptable, self-organized systems that seamlessly collaborate with users and control their environments. \n\nThe resulting REFLECT system will be able to derive, suggest and perform actions to optimize user comfort and performance, assisting people in their specific activities (for example, in driving a vehicle). To illustrate the pragmatic orientation and results, the REFLECT project includes a number of case studies and a prototype from the automotive domain that shows how such systems can be deployed in practice.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE-2007-2-2-01 | Award Amount: 7.99M | Year: 2008

Current evidence on the effect of diet on mental performance (MP) is largely based on animal, retrospective studies, and short-term nutritional intervention studies in humans. NUTRIMENTHE will significantly improve this knowledge through studying the role, mechanisms, risks & benefits of specific nutrients & food components to respond to specific needs and improve the MP of children. The research will include quantification of the nutrient effects of early programming on later cognitive and mental disorders, effects of food on mental state and MP such as mood, activation, attention, motivation, effort, perception, memory & intelligence and the effects of food on mental illness. NUTRIMENTHE will establish: A team of leading international scientists (paediatricians, neurospsychologists, psychiatrics) from top academic centres and a leading Food Multinational, providing a critical mass of experts in the effect of diet on childrens MP Epidemiologic studies to analyse the long-term effects of pre- & early postnatal diet on childrens mental performance & illness Follow-up of randomised clinical intervention trials with specific nutrients initiated during pregnancy, infancy & childhood Quantitative requirements of n-3 LCPUFAs in children with restricted diet Quantitative assessment of the interaction between nutrition & genetic variation with respect to MP Development of a neuropsychological battery for an EU common assessment of MP Consistent & clear pan-European recommendations on dietary requirement for children An increase the EU public knowledge, specifically parents, teachers & industry, laying the basis for appropriate health claims about how diet influences MP in children Establish the economic opportunity for further product development within EU Development of a professional & public engaging dissemination programme, to increase excellence & innovation potentials & training in nutrition research linked to cognitive- & neuroscience

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2010-ITN | Award Amount: 3.77M | Year: 2011

Application of intense light fields opens the opportunity to image structures and dynamics of individual molecules with the combination of sub-Angstrom spatial and attosecond temporal resolution. However, intense light fields inevitably excite complex dynamics. The success of imaging techniques depends on our understanding of these largely unknown dynamics, creating demand for the theory of complex systems in intense fields. The scientific objective of the proposed network is to develop theoretical methods capable of (i) modeling multielectron dynamics in polyatomic molecules and clusters in intense light fields and (ii) reconstructing these dynamics from experimental observables. An important objective of the network is the development of a flexible software package for modeling intense-field multi-electron dynamics, addressed at the general scientific community. The overall project requires synergy of different areas in atomic and molecular physics, quantum chemistry, molecular spectroscopy and dynamics, and software development. Thus, the network will provide an ideal multidisciplinary environment for training young researchers in the combination of physics, chemistry and computational methods used by different communities and taught at different departments. Training its fellows by research at the forefront of sciences, the network will also deliver the forefront software technology.

Agency: European Commission | Branch: H2020 | Program: IA | Phase: ICT-17-2014 | Award Amount: 3.05M | Year: 2015

To an ever-increasing extent, web-based services are providing a frontline for healthcare information in Europe. They help citizens find answers to their questions and help them understand and find the local services they need. However, due to the number of languages spoken in Europe, and the mobility of its population, there is a high demand for these services to be available in many languages. In order to satisfy this demand, we need to rely on automatic translation, as it is infeasible to manually translate into all languages requested. The aim of HimL is to use recent advances in machine translation to create and deploy a system for the automatic translation of public health information, with a special focus on meaning preservation. In particular, we will include recent work on domain adaptation, translation into morphological rich languages, terminology management, and semantically enhanced machine translation to build reliable machine translation for the health domain. The aim will be to create usable, reliable, fully automatic translation of public health information, initially testing with translation from English into Czech, Polish, Romanian and German. In the HimL project we will iterate cycles of incorporating improvements into the MT systems, with careful evaluation and user acceptance testing.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRADEV-3-2015 | Award Amount: 31.03M | Year: 2015

The nations of Europe are distributed around some of the most complex and dynamic geological systems on the planet and understanding these is essential to the security of livelihoods and economic power of Europeans. Many of the solutions to the grand challenges in the geosciences have been led by European scientists the understanding of stratigraphy (the timing and distribution of layers of sediment on Earth) and the discovery of the concept of plate tectonics being among the most significant. Our ability to monitor the Earth is rapidly evolving through development of new sensor technology, both on- and below-ground and from outer space; we are able to deliver this information with increasing rapidity, integrate it, provide solutions to geological understanding and furnish essential information for decision makers. Earth science monitoring systems are distributed across Europe and the globe and measure the physico-chemical characteristics of the planet under different geological regimes. EPOS will bring together 24 European nations and combine national Earth science facilities, the associated data and models together with the scientific expertise into one integrated delivery system for the solid Earth. This infrastructure will allow the Earth sciences to achieve a step change in our understanding of the planet; it will enable us to prepare for geo-hazards and to responsibly manage the subsurface for infrastructure development, waste storage and the use of Earths resources. With a European Research Infrastructure Consortium (ERIC) to be located in Rome (Italy), EPOS will provide an opportunity for Europe to maintain world-leading European Earth sciences and will represent a model for pan-European federated infrastructure.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.91M | Year: 2017

The EU currently is negotiating a controversial Transatlantic Trade and Investment Partnership (TTIP) agreement with the USA, the main features of which will be the abolition of tariffs, the reduction of non-tariff barriers to trade between the EU and the USA and the introduction of a dispute settlement mechanism. The objective of the proposed TTIP Innovative Training Network (TTIP-ITN) is to foster interdisciplinary research into TTIP with a view to create a significantly increased European knowledge base and research capacity on TTIP, thus helping Europe to reap the benefits of TTIP (wealth, jobs, etc.) while addressing its challenges (democracy, accountability, environmental- and labour standards, etc.).The network is an interdisciplinary, intersectoral collaboration pooling world-leading researchers and practitioners from all relevant disciplines of law - EU constitutional, internal market, and external relations law, international trade law, and international law, as well as political science, international relations, business studies, and economics. TTIP-ITN fully integrates non-academic Beneficiaries and Partner Organisations, including think tanks, lobbyists, regulatory bodies, law firms, US academic institutions, and an international organisation. Furthermore, the network will support and enhance the process of converting research results into policy papers through partnership with high-impact policy research units at the forefront of European policy research and policy making. The work package consists of 3 substantive work packages on (1) transatlantic governance, (2) transatlantic regulation, and (3) multilateralism and regionalism. 15 PhD research projects will be supervised by academics of the 11 Beneficiaries with an interdisciplinary training programme covering the legal, political and economic foundations of TTIP and an interdisciplinary and intersectoral programme of secondments involving 22 Partner Organisations.

Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: ENV.2009. | Award Amount: 4.16M | Year: 2010

With regard to the objectives specified in ENV-2009., modeling capabilities must be improved and appropriate tools developed to advance the capability to assess climate effects on water resources and uses. The project consortium will employ a combination of novel field monitoring concepts, remote sensing techniques, integrated hydrologic (and biophysical) modeling and socioeconomic factor analyses to reduce existing uncertainties in climate change impact analysis and to create an integrated quantitative risk and vulnerability assessment tool. Together, these will provide the necessary information to design appropriate adaptive water resources management instruments and select suitable agricultural practices under climate change conditions. The integrated risk and vulnerability analysis tool will also enable assessment of risks for conflict-inducing actions, e.g. migration. The improved models, new assessment tools, and their results will be evaluated against current methodologies. Improvements will be communicated to stakeholders and decision makers in a transparent, easy-to-understand form, enabling them to utilize the new findings in regional water resource and agricultural management initiatives as well as in the design of mechanisms to reduce potential for conflict (linkage to SSH-2009.4.2.1).

Agency: European Commission | Branch: FP7 | Program: NOE | Phase: ICT-2007.4.3 | Award Amount: 6.38M | Year: 2009

STELLAR represents the effort of the leading institutions and projects in European TEL to unify our diverse TEL community. This Network of Excellence is motivated by the need for European research on Technology-Enhanced Learning (TEL) to build upon, synergize and extend the valuable work we have started by significantly building capacity in TEL research within Europe, which is required to allow the European Union to achieve its goals via the Bologna Agreement and the execution of the Lisbon Agenda. The European TEL agenda has been set for the last 4 years by the Kaleidoscope network with a huge strength in pedagogy and scientific excellence, and the Prolearn network with a complimentary strength in technical and professional excellence. We see integrating this excellence and moving on to the higher strategic formation of policy based in leading research is the challenge for the next three. STELLAR will move beyond the earlier networks by setting a new and critical foresight agenda for TEL via an annually reviewed Grand Challenge programme.\nThe Network will be executed via a series of integration instruments designed to increase the research capacity of European TEL at all levels. These instruments will act as the backbone of an interlocking set of 3 Grand Research Challenge actions, themed as Connecting People, Orchestration and Context. At the most general level the network will reach out to the wider stakeholder community via the organisation of strategic stakeholder communication vehicles whilst at the other end of the spectrum it will take its strategy and vision to an annual policy maker meeting of minds. The path between these two key instruments is designed to reach each key community and greatly increase its capacity to address the critical research issues at each level of capacity. The themes of the Networks instruments will be set by our community as the Grand Challenge for TEL.

Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: NMP-2008-2.6-3 | Award Amount: 1.23M | Year: 2009

The stability of thin films in contact with different materials is a critical issue for a wide range of modern devices, including high-k films in the microelectronics industry, metal electrodes for fuel cells, and nanometer sized particles on oxides for catalysis. Some groups are working on thermodynamic analysis of thin film stability, who correlate relative interface energies with dopant adsorption. While this provides important thermodynamic parameters which can be used to evaluate the stability of thin films, information on the detailed atomistic structure and chemistry of the same interfaces needs to be correlated with the thermodynamic approach. Other groups use advanced characterization approaches to determine local atomistic structure and chemistry, and theoretical groups explore interface structure and energy through computational methods. It is the goal of this project to bridge between these working groups. This project will establish an environment to promote communication and collaboration between groups using thermodynamic approaches with groups studying the atomistic structure of interfaces, since bridging this particular scientific gap has the potential to result in new design criteria for advanced material systems. The project is based on a core group of European, and International partners, who have realized that such a form of communication is critical to advancing the field of interface science and interface based technology. The partners will establish structured programs for discussion via focused public workshops and summer schools, and via scientific exchange. While the core group of partners is academic, European industry will be involved in the structured discussions. The expected impact from this four-year project is methods to correlate between thermodynamic analyses of interfaces with atomistic structure. This will provide new approaches to understanding interface stability, adhesion and interface dependent functional properties.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-2 | Award Amount: 3.88M | Year: 2012

Disorders of sex development (DSD) are a conglomerate of rare diseases with an estimated incidence of 1: 4500. The causes of DSD are mainly disorders with gonadal dysgenesis, decreased androgen synthesis or function in XY males or disorders with elevated androgen production in XX females. Decision on sex of rearing is difficult in some cases as the prenatal androgen imbalances result in ambiguous genitalia at birth and furthermore they are likely to influence psychosexual development. Genital constructive surgery is needed in most cases. Lifelong cortisone replacement is needed in DSD due to defects of cortisone synthesis. Sex hormone substitution is indicated in many cases of DSD in puberty and adult life. Decision of sex of rearing, genital surgery and hormone therapies have a life-long impact on the affected individuals, which become evident mainly after puberty. In many cases psychological counselling is advised. Interpretation of previous outcome studies of DSD is hampered by small patient numbers and conglomerates of diagnoses and therapies. The study DSD-Life investigates and compares the long-term outcome of different off-label treatments in adequate numbers of adolescents and adults with different known genetic entities of DSD to develop evidence base guidelines for treatment of DSD for which no dedicated treatment is currently approved. To reach this aim, the influences and interrelations of sex assignment, genital surgery, hormone therapy, metabolism, fertility, psychological intervention but also cultural influences and patients and parents views on psychosocial adaption, health related quality of life and psychological well-being and will be investigated. The long-term impact of the study will be improvement of care and subsequently higher quality of life with better integration and participation of individuals with DSD in the society.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.8.2 | Award Amount: 9.14M | Year: 2010

The overall objectives of the AQUTE project are\nA) To develop quantum technologies based on atomic, molecular and optical (AMO) systems for\n* scalable quantum computation;\n* entanglement-enabled technologies like metrology and sensing.\nB) To establish and exploit new interdisciplinary connections, coming from AMO physics, but also including concepts and experimental settings of solid state systems, in order to\n* reinforce interdisciplinary links at the frontiers of quantum information science, and other fields of physics or science in general;\n* conceive and realize novel hybrid systems that couple in a coherent way physically different quantum degrees of freedom.\nObj. A will be pursued along two complementary directions:\n* a bottom-up approach, where individually trapped atomic particles are combined into elementary general-purpose quantum processors including qubit interconnects;\n* a top-down approach, where many-particle atomic systems are employed to realize special-purpose quantum processors, for instance quantum simulators.\nGroundbreaking work in qualitatively new directions is also needed to lay the foundations for the future attainment of scalable fault-tolerant architectures. AQUTE will thus also\n* investigate new experimental systems that have become available in the laboratory and are of direct relevance for QIFT;\n* optimize existing and develop novel theoretical concepts for quantum processing.\nObj. B connects atomic quantum technologies for QIFT to a wider context, by\n* exploring hybrid approaches to QIFT beyond AMO physics;\n* improving connections between QIFT and science in general, following the emergence of a new quantum paradigm at the frontier of nanosciences and information sciences.\nThese research lines determine the structuring of the AQUTE workplan into four deeply interrelated Sub-Projects: Entangling gates and quantum processors, Hybrid quantum systems and interconnects, Quantum Simulators and Quantum Technologies.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRAIA-1-2014-2015 | Award Amount: 10.00M | Year: 2016

ENSAR2 is the integrating activity for European nuclear scientists who are performing research in three of the major subfields defined by NuPECC: Nuclear Structure and Dynamics, Nuclear Astrophysics and Nuclear Physics Tools and Applications. It proposes an optimised ensemble of Networking (NAs), Joint Research (JRAs) and Transnational Access Activities (TAs), which will ensure qualitative and quantitative improvement of the access provided by the current ten infrastructures, which are at the core of this proposal. The novel and innovative developments that will be achieved by the RTD activities will also assure state-of-the-art technology needed for the new large-scale projects. Our community of nuclear scientists profits from the diverse range of world-class research infrastructures all over Europe that can supply different ion beams and energies and, with ELI-NP, high-intensity gamma-ray beams up to 20 MeV. We have made great effort to make the most efficient use of these facilities by developing the most advanced and novel equipment needed to pursue their excellent scientific programmes and applying state-of-the-art developments to other fields and to benefit humanity (e.g. archaeology, medical imaging). Together with multidisciplinary and application-oriented research at the facilities, these activities ensure a high-level socio-economic impact. To enhance the access to these facilities, the community has defined a number of JRAs, using as main criterion scientific and technical promise. These activities deal with novel and innovative technologies to improve the operation of the facilities. The NAs of ENSAR2 have been set-up with specific actions to strengthen the communities coherence around certain resarch topics and to ensure a broad dissemination of results and stimulate multidisciplinary, application-oriented research and innovation at the Research Infrastructures.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.4.1 | Award Amount: 16.56M | Year: 2008

Text that is not digital is virtually invisible. Todays readers search the internet for electronically accessible texts rather than visit the reading room of a library. Born-digital and digitised contemporary materials contain the richness that allows tools such as text mining and the semantic web to offer superior accessibility but the story is very different for historic documents. A vital part of the European heritage, encompassing more than four centuries of historic books and bound periodicals is becoming less and less visible to the public at large.\nWith the i2010 vision of a European Digital Library, the EU has launched an ambitious plan for large scale digitisation projects transforming Europes printed heritage into digitally available resources. However, lack of institutional knowledge and expertise slows down the pace with which this vision can be realised. The state-of-the-art in OCR performance and machine understanding of the original document is inadequate, especially for historically important material with archaic fonts and spellings, newspapers with complex layouts, bound volumes, microfilm or typescript.\nThe IMPACT project will remove many of these barriers. It brings together fifteen national and regional libraries, research institutions and commercial suppliers - all centres of competence with unequalled experience of large-scale text digitisation processes and technologies. The project will let them share their know-how and best practices, develop innovative tools to enhance the capabilities of OCR engines and the accessibility of digitised text and lay down the foundations for the mass-digitisation programmes that will take place over the next decade. This project will facilitate a more collaborative approach to mass-digitisation. It will build capacity and lower the barriers to entry for organisations in the early stages of their own digitisation activity.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SSH-2007-1.2-03 | Award Amount: 1.27M | Year: 2008

The main purpose of FINESS is to get a clear understanding of the implications of ongoing financial market integration in Europe on economic growth, employment and competitiveness, to identify likely future paths of the development and to draw policy relevant conclusions. Several main breakthroughs will be achieved throughout the project. On the macroeconomic level, the role of financial systems and their transmission channels on growth will be explored by innovative and tailor made econometric techniques, taken dynamic interactions between financial, product and labour markets into account. A range of indicators to measure the degree of financial integration will be constructed, and their development in time will be addressed. Moreover, insights into the working of financial institutions will be provided for the microeconomic level. The comparative approach undertaken by FINESS is especially useful to uncover catalysts and bottlenecks in the architecture of financial systems. By investigating unique datasets, the role of the financial structure, i.e., the banking sector, markets for private equity and venture capital, for improving efficiency and sustainable expansion of start ups and established firms is studied. The impacts of different degrees of financial integration on the portfolio decisions of households are explored with simulation models. Topics specifically related to the transition period of the New Member States as well as the gender dimension in turning impulses from the financial system into efficiency and growth are covered by the project. By fulfilling its goals, FINESS will provide in-depth knowledge on the relationship between financial systems and sustainable economic growth in a changing environment.

Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH-2009-4.3.1-2 | Award Amount: 6.02M | Year: 2010

Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, is a neglected bacterial infection of the poor in remote rural areas, mostly affecting children. BUD, the third most common mycobacterial disease in immunocompetent humans after tuberculosis and leprosy, is most endemic in West Africa, but cases have been reported from more than 30 countries. BUD is a mutilating disease leading to severe disability. Treatment with antibiotics is possible but is long-lasting and requires injections, shows treatment failures and drug resistance may occur. A vaccine against M. ulcerans would protect persons at risk in highly endemic areas and could be used as a therapeutic vaccine to shorten duration of treatment and to prevent relapses. The general objective of BuruliVac is to identify and develop novel vaccine candidates suitable for translation into clinical application. This objective will be achieved by a multidisciplinary approach involving among others basic and applied research in immunology, bioinformatics, molecular genetics, tropical medicine, microbiology and clinical bacteriology. As currently no existing vaccine lead candidate is available, the consortium will identify and develop new vaccine candidates of different types, will evaluate them using bioinformatics, applied genomics and proteomics and will subject them to consecutive test systems. For evaluation of vaccine candidates regarding their application in humans, the consortium will also study the immune response and disease immunopathology to define correlates of protection. Essential pre-clinical testing in vitro and in vivo will select a small number of candidates that is amenable to be introduced into clinical studies.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP.2012.1.3-1 | Award Amount: 12.95M | Year: 2013

The NanoMILE project is conceived and led by an international elite of scientists from the EU and US with the aim to establish a fundamental understanding of the mechanisms of nanomaterial interactions with living systems and the environment, and uniquely to do so across the entire life cycle of nanomaterials and in a wide range of target species. Identification of critical properties (physico-chemical descriptors) that confer the ability to induce harm in biological systems is key to allowing these features to be avoided in nanomaterial production (safety by design). Major shortfalls in the risk analysis process for nanomaterials are the fundamental lack of data on exposure levels and the environmental fate and transformation of nanomaterials, key issues that this proposal will address, including through the development of novel modelling approaches. A major deliverable of the project will be a framework for classification of nanomaterials according to their impacts, whether biological or environmental, by linking nanomaterial-biomolecule interactions across scales (sub-cellular to ecosystem) and establishing the specific biochemical mechanisms of interference (toxicity pathway).

Agency: European Commission | Branch: FP7 | Program: CP-IP-SICA | Phase: HEALTH-2009-4.3.1-3 | Award Amount: 13.73M | Year: 2010

Worm infections are receiving increased attention due to: the wide geographic overlap in occurrence between worms and HIV, TB and malaria; the large proportion of individuals (minimal estimates around 25%) co-infected with worms and HIV/TB/ malaria; the potential risk of increasing disease burden; the very limited understanding of the impact by worm infections on HIV-, TB- and malaria-specific immune responses and on their clinical outcome; the lack of established intervention guidelines for treatment of worm infections; and the scarce information on the impact by worm infections on vaccination and vaccine-induced immune responses. In order to address these complex and challenging scientific issues, IDEA project will focus its efforts on four primary objectives: a) the worm-induced modulation of the functional and molecular profile of HIV-, TB- and malaria-specific immune responses, b) the impact by worm co-infections on measures of disease activity of PRDs, c) the immunologic markers of worm-, HIV-, TB- and malaria-specific immune responses associated with better control of pathogen replication and disease, and d) the modulation by worm co-infections of vaccine-induced immune responses. To achieve these objectives, IDEA project has developed a global and innovative strategy which includes: a) the alliance between African and European leading scientists in the field of worms, HIV, TB and malaria, b) the multidisciplinary expertise involving immunologists, parasitologists, epidemiologists, clinicians, and experts in vaccines, c) cutting edge immunology and the most innovative technologies to profile immune response, d) the access to large cohort studies bringing a number of centres working on worms and PRDs in Africa together, and e) the access to experimental HIV, TB and malaria vaccine candidates under clinical development in Africa.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SST.2008.4.1.1. | Award Amount: 3.47M | Year: 2009

The development of adaptive safety systems addressing vehicle occupant protection requires the use of in depth knowledge of various occupant features, specifically those related to the risk of injury. All occupants in passenger vehicles are at risk of sustaining whiplash injuries in a low severity crash. Whiplash associated disorders (WAD), so called whiplash injuries, resulting from car crashes, are a serious traffic safety issue, resulting in over 4 billion costs to European society. Yearly more than 300 000 European citizens suffer neck problems from these injuries and 15 000 result in long terms consequences. In the population, the females are at higher risk of these injuries than the males. The difference in risk between the robust, male, population and the vulnerable, female, part of the population is between 40-100%. This has been reported from epidemiological studies from all over the world since the end of the 1960s until today. Yet still, when assessing the vehicle safety the only available occupant model for these impact scenarios is an average male. Adaptive anti-whiplash systems need to be evaluated for their benefits both for males and females. If there are no improved protective systems, further rising costs for the European Society can be expected. This project aims at establishing the properties for a model of an average female and to implement those in a computational model in order to provide an improved tool for the development and evaluation of adaptive systems with special focus on protection against whiplash injuries. The project will result in a computational model of a female, in addition to the male model that already exists, for low severity testing. In addition, the computational models will be used in the design and evaluation of adaptive seat systems in order to provide enhanced neck injury protection from the seat.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-24-2015 | Award Amount: 18.47M | Year: 2016

The management of febrile patients is one of the most common and important problems facing healthcare providers. Distinction between bacterial infections and trivial viral infection on clinical grounds is unreliable, and as a result innumerable patients worldwide undergo hospitalization, invasive investigation and are treated with antibiotics for presumed bacterial infection when, in fact, they are suffering from self-resolving viral infection. We aim to improve diagnosis and management of febrile patients, by application of sophisticated phenotypic, transcriptomic (genomic, proteomic) and bioinformatic approaches to well characterised large-scale, multi-national patient cohorts already recruited with EU funding. We will identify, and validate promising new discriminators of bacterial and viral infection including transcriptomic and clinical phenotypic markers. The most accurate markers distinguishing bacterial and viral infection will be evaluated in prospective cohorts of patients reflecting the different health care settings across European countries. By linking sophisticated new genomic and proteomic approaches to careful clinical phenotyping, and building on pilot data from our previous studies we will develop a comprehensive management plan for febrile patients which can be rolled out in healthcare systems across Europe.

Agency: European Commission | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-2011-IAPP | Award Amount: 1.78M | Year: 2012

PsychDPC contains leading European centres in genetics and psychiatry, richly endowed with expertise in both clinical and basic research. The partners bring together state-of-the-art technical facilities, high academic standards as well as established training activities, which will be utilized in concert to maximise the outcome of the project. The primary aim of PsychDPC is to translate data emerging from large-scale research efforts in genetic and genomic epidemiology of schizophrenia, conducted on large sets of well-characterized volunteer patients, into information of relevance to current practice and future clinical advances. PsychDPC will do this through effective integration of data between the partners. A range of complementary approaches will be applied with an initial focus on: 1) Discovery of novel genetic susceptibility variants from genome wide SNP association data through expanding the large sample sets accessible to partners and by imputing available sequence data into the large genotyped datasets, 2) study of the phenotypic stamp conferred by copy number variations (CNVs) and genes harbouring non-synonymous point mutations conferring high and moderate risk of schizophrenia, 3) powerful novel genetic approaches to genetic discovery including long range phasing combined with deep sequencing and 4) analysis of the relationship of uncovered variants conferring risk of schizophrenia with clinical, neurpsychological and brain structure phenotypes. The consortium has unique, very large samples from schizophrenia patients and the aim is to re-phenotype subjects carrying variants conferring high-risk to identify their specific cognitive and behavioural features. Combined with a refinement of familial risk assessment, using comprehensive national registry databases, we will utilise our findings to develop diagnostic tools, tools for early intervention and genetic counselling.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-04-2016 | Award Amount: 10.41M | Year: 2017

Early life is an important window of opportunity to improve health across the full lifecycle. European pregnancy and child cohort studies together offer an unique opportunity to identify a wide range of early life stressors linked with individual biological, developmental and health trajectory variations, and to the onset and evolution of non-communicable diseases. LIFECYCLE will establish the EuroCHILD Cohort Network, which brings together existing, successful pregnancy and child cohorts and biobanks, by developing a governance structure taking account of national and European ethical, legal and societal implications, a shared data-management platform and data-harmonization strategies. LIFECYCLE will enrich this EuroCHILD Cohort Network by generating new integrated data on early life stressors related to socio-economic, migration, urban environment and life-style determinants, and will capitalize on these data by performing hypothesis-driven research on early life stressors influencing cardio-metabolic, respiratory and mental health trajectories during the full lifecycle, and the underlying epigenetic mechanisms. LIFECYCLE will translate these results into recommendations for targeted strategies and personalized prediction models to improve health trajectories for current and future Europeans generations by optimizing their earliest phase of life. To strengthen this long-term collaboration, LIFECYCLE will organize yearly international meetings open to pregnancy and child cohort researchers, introduce a Fellowship Training Programme for exchange of junior researchers between European pregnancy or child cohorts, and develop e-learning modules for researchers performing life-course health studies. Ultimately, LIFECYCLE will lead to a unique sustainable EuroCHILD Cohort Network, and provide recommendations for targeted prevention strategies by identification of novel markers of early life stressors related to health trajectories throughout the lifecycle.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRAIA-01-2016-2017 | Award Amount: 10.00M | Year: 2017

Experimentation in mesocosms is arguably the single most powerful approach to obtain a mechanistic quantitative understanding of ecosystem-level impacts of stressors in complex systems, especially when embedded in long-term observations, theoretical models and experiments conducted at other scales. AQUACOSM builds on an established European network of mesocosm research infrastructures (RI), the FP7 Infra project MESOAQUA (2009-2012), where 167 users successfully conducted 74 projects. AQUACOSM greatly enhances that network on pelagic marine systems in at least 3 ways: first by expanding it to 10 freshwater (rivers and lakes), 2 brackish and 2 benthic marine facilities, and by involving 2 SMEs and reaching out to more, thereby granting effective transnational access to world-leading mesocosm facilities to >340 users on >11500 days; second, by integrating scattered know-how between freshwater and marine RI; and third, by uniting aquatic mesocosm science in an open network beyond the core consortium, with industry involved in an ambitious innovation process, to promote ground-breaking developments in mesocosm technology, instrumentation and data processing. A new dimension of experimental ecosystem science will be reached by coordinated mesocosm experiments along transects from the Mediterranean to the Arctic and beyond salinity boundaries. These efforts will culminate in a joint research activity (JRA) to assess aquatic ecosystem responses across multiple environmental gradients to a selected climate-related key stressor with repercussions for ecosystem services. Overall, AQUACOSM will fill a global void by forging an integrated freshwater and marine research infrastructure network. Long-term sustainability is sought through assessing governance models based on science priorities and economic innovation opportunities. Linkages to and synergies with ESFRI RI and other large initiatives are ensured by AQUACOSM partners and Advisory Board members in those programs.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.00M | Year: 2016

Up to 70% of cardiovascular events are not prevented by current therapeutic regimens. In search for additional, innovative strategies, immune cells have been recognized as key players contributing to atherosclerotic plaque progression and destabilization. Particularly the role of innate immune cells is of major interest, following the recent paradigm shift that innate immunity, considered to be incapable of learning ability, does exhibit a memory feature transduced via epigenetic modulation. Compelling evidence shows that atherosclerotic factors promote immune cell migration by pre-activation of innate immune cells. In this project called REPROGRAM, we aim to prove that innate immune cell activation via epigenetic reprogramming perpetuates the upheld systemic inflammatory state in cardiovascular disease which is common in other chronic inflammatory diseases. This opens a new therapeutic area in which epigenetic modulation of innate immune cells effectively decreases systemic inflammation impacting on chronic inflammation as well as the development of co-morbidities. The integrated use of in vitro, ex vivo and in vivo studies, including cells, mice and patients, allows translation from in vitro mechanisms to diseases (molecule-to-man) and extrapolation to cohorts (man-to-mass), enabling us to demonstrate relevance and therapeutic potential of targeting trained immunity in cardiovascular and chronic inflammatory diseases. Enforced by the promising data in oncology, the future prospects for epigenetic interventions in cardiovascular and chronic inflammatory diseases are eminent, attested by the large residual cardiovascular disease burden and the huge societal impact of other chronic inflammatory diseases. The REPROGRAM consortium consisting of key opinion leaders in the field of cardiovascular (systems) biology, immunology, epigenetic therapies and rheumatoid arthritis, with a large intersectoral network, guarantees rapid translation of early mechanistic discoveries

Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2016 | Award Amount: 1.46M | Year: 2017

The joint research in this programme will study important aspectsboth theoretical as well as appliedof computing with infinite objects. A central aim is laying the grounds for the generation of efficient and verified software in engineering applications. A prime example for infinite data is provided by the real numbers, most commonly conceived as infinite sequences of digits. While most applications in science and engineering substitute the reals with floating point numbers of fixed finite precision and thus have to deal with truncation and rounding errors, the approach in this project is different: exact real numbers are taken as first-class citizens and while any computation can only exploit a finite portion of its input in finite time, increased precision is always available by continuing the computation process. This project aims to bring together the expertise of specialists in mathematics, logic, and computer science to push the frontiers of our theoretical and practical understanding of computing with infinite objects. Three overarching motivations drive the proposed collaboration: Representability. Cardinality considerations tell us that it is not possible to represent arbitrary mathematical objects in a way that is accessible to computation. We will enlist expertise in topology, logic, and set theory, to address the question of which objects are representable and how they can be represented most efficiently. Constructivity. Working in a constructive mathematical universe can greatly enhance our understanding of the link between computation and mathematical structure. Not only informs us which are the objects of relevance, it also allows us to devise always correct algorithms from proofs. Efficient implementation. We also aim to make progress on concrete implementations. Theoretical insights from elsewhere will be tested in actual computer systems; obstacles encountered in the latter will inform the direction of mathematical investigation.

Soehnlein O.,Ludwig Maximilians University of Munich | Swirski F.K.,Harvard University
Trends in Endocrinology and Metabolism | Year: 2013

Atherosclerosis is characterized by the progressive accumulation of lipids and leukocytes in the arterial wall. Leukocytes such as macrophages accumulate oxidized lipoproteins in the growing atheromata and give rise to foam cells, which can then contribute to the necrotic core of lesions. Lipids and leukocytes also interact in other important ways. In experimental models, systemic hypercholesterolemia is associated with severe neutrophilia and monocytosis. Recent evidence indicates that cholesterol-sensing pathways control the proliferation of hematopoietic stem-cell progenitors. Here we review some of the studies that are forging this particular link between metabolism and inflammation, and propose several strategies that could target this axis for the treatment of cardiovascular disease. © 2012 Elsevier Ltd.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENV.2013.6.4-2 | Award Amount: 7.88M | Year: 2014

The EU population is increasingly exposed to new physical and chemical agents in the environment, some of which may be detrimental to public health. Of these, electromagnetic fields (EMF) are one of the most ubiquitous, with new EMF technologies and novel applications being actively developed and commercialised. To address pertinent questions on EMF and health, GERoNiMO proposes an integrated approach building upon existing European resources (epidemiological studies, exposure assessment techniques, mechanistic and animal models, expert networks), using, where appropriate, novel methods, to better understand potential mechanisms underlying possible health effects of EMF, to characterise population levels of exposure, and to further the state of knowledge on EMF and health. GERoNiMO will focus on radiofrequency fields (RF) as understanding of possible health effects is insufficient and a large proportion of the general population is exposed, with commercial applications continuing to grow and intermediate frequencies (IF) as applications are increasing and information on potential health effects is sparse. GERoNiMO will address all aspects of the call by meeting the following four main objectives: i) evaluate possible health effects (cognitive and behavioural development, cancer risk, and reproductive effects) of exposure to RF and IF in children and adults; ii) better understand mechanisms of biological effects (behavioural and reproductive effects, cancer, ageing, and Alzheimers disease) related to RF and IF; iii) collect better data on population exposure and improve health risk assessment for RF and IF; and iv) underpin policy development in Europe on RF and IF (including non-technological means of reducing exposure and best practices in risk communication to support EU policy makers). GERoNiMO represents a unique and timely opportunity for the development of a truly integrated approach to research into EMF and health in Europe.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE.2011.2.2-03 | Award Amount: 11.56M | Year: 2012

Nutrition during early development has an important impact on later health, particularly through greater obesity risk, as demonstrated by FP6 EARNEST. EarlyNutrition explores the current key hypotheses on likely causes and pathways to prevention of early life origins of obesity (specifically adiposity) and associated disorders. We bring extraordinary expertise and study populations of 470,000 individuals to investigate: The fuel mediated in utero hypothesis The accelerated postnatal weight gain hypothesis The mismatch hypothesis. Scientific and technical expertise in placental biology, epigenetics and metabolomics will provide understanding at the cellular and molecular level, and refined strategies for intervention in pregnancy and early post natal life to prevent obesity. Using existing cohort studies, ongoing and novel intervention studies and a basic science programme, we will provide the scientific foundations for evidence based recommendations for optimal EarlyNutrition that incorporate long-term health outcomes, focusing on 4 Target Groups: women before pregnancy; pregnant women; infants (incl. breastfeeding); young children. Evidence is produced from animal and placental studies (Theme 1; T1), prospective cohort studies (T2), and randomised controlled trials in pregnant women and infants (T3). T4 covers scientific strategic integration, recommendation development and dissemination, including systematic reviews and behaviour change approaches. A strong multi-disciplinary team of international leaders in the field including collaborators from USA and Australia achieves balance and complementarity. The projects impact comprises definitive evidence on early nutrition effects on health, enhanced EU and global policies, major economic benefits through obesity prevention and value-added nutritional products, and practical recommendations on optimal nutrition in Target Groups. Wide dissemination will be achieved through active engagement with stakeholders.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENV.2012.6.4-2 | Award Amount: 7.73M | Year: 2013

This project will improve the consortium capacity of assessment of volcanic hazards in Supersites of Southern Italy by optimising and integrating existing and new observation/monitoring systems, by a breakthrough in understanding of volcanic processes and by increasing the effectiveness of the coordination between the scientific and end-user communities. More than 3 million of people are exposed to potential volcanic hazards in a large region in the Mediterranean Sea, where two among the largest European volcanic areas are located: Mt. Etna and Campi Flegrei/Vesuvius. This project will fully exploit the unique detailed long-term in-situ monitoring data sets available for these volcanoes and integrate with Earth Observation (EO) data, setting the basic tools for a significant step ahead in the discrimination of pre-, syn- and post-eruptive phases. The wide range of styles and intensities of volcanic phenomena observed on these volcanoes, which can be assumed as archetypes of closed conduit and open conduit volcano, together with the long-term multidisciplinary data sets give an exceptional opportunity to improve the understanding of a very wide spectrum of geo-hazards, as well as implementing and testing a large variety of innovative models of ground deformation and motion. Important impacts on the European industrial sector are expected, arising from a partnership integrating the scientific community and SMEs to implement together new observation/monitoring sensors/systems. Specific experiments and studies will be carried out to improve our understanding of the volcanic internal structure and dynamics, as well as to recognise signals related to impending unrest or eruption. Hazard quantitative assessment will benefit by the outcomes of these studies and by their integration into the cutting edge monitoring approaches thus leading to a step-change in hazard awareness and preparedness and leveraging the close relationship between scientists, SMEs, and end-users.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 5.04M | Year: 2009

Storing CO2 in the subsurface to reduce global warming, finding hydrocarbon and other resources and monitoring their extraction, generating energy with Earths internal heat, and forecasting natural hazards (earthquake-induced ground motion, volcanic eruptions) requires high-resolution tomographic images of the Earths interior. The main goal of QUEST is research and training in the development of strategies for automated seismic imaging using the increasing power of 3-D simulation technology. While so far the observed information was severely reduced to determine Earths structure, the massive increase in available computational resources allows us now to make use of the complete information contained in the observations. With narrowing resources and increasing energy prizes the exploration industry is seeking highly skilled young scientists capable of driving the new computational technologies towards industrial problems. Earth Science graduating students are lacking profound theoretical and practical training in numerical methods and high-performance computing. QUEST intends to fill this gap offering the students excellent prospects in industry and academia as the combination of skills to be trained are highly in demand. We also expect substantial progress in understanding the dynamics of our planet, the quantification of natural hazards such as earthquakes, tsunamis, and volcanic eruptions. QUEST will link world-leading scientists in methodologies such as computational wave propagation, the theory of inverse problems and global tomography with two of the best industrial research laboratories in geophysics and computing world wide. QUEST will have a lasting impact on the practice of seismic tomography, leading to High-Performance-Computing solutions applicable to industrial and academic challenges, and a generation of young researchers capable of producing better Earth images that help us tackle the challenges of future energy-resource management and natural-hazard related research.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SPA.2011.2.1-02 | Award Amount: 2.44M | Year: 2012

The aim is to investigate the combined effects of hypoxia and sustained recumbency (bedrest), on human physiological systems. The partial pressure of oxygen in the environmental gas inside future planetary habitats will be lower than in atmospheric air. Prolonged exposure to low gravity will result in deconditioning of vital physiological systems, and may consequently constitute a threat to the health of the astronauts. However, it is unknown how prolonged exposure to both reduced gravity and hypoxia will affect health. The new knowledge has also implications for society in general, since chronic hypoxia and bedrest constitutes a model of the basic conditions experienced by patients suffering from respiratory insufficiency restricting them to a physically inactive life style. The challenge of the project lies in the complexity of the experimental interventions where healthy humans are confined to a hypoxic environment during prolonged bedrest. A series of studies will be conducted at the Planica hypoxia facility capable of housing 20 subjects at any simulated altitude. Subjects will remain in horizontal position (bedrest) or be ambulatory, but confined to the facility (ambulation) for 21 days/trial. Each subject will participate in three trials: hypoxic bedrest (simulated altitude 4000m), normoxic bedrest, and hypoxic ambulation. The effects will be investigated in experiments concerning metabolic, cardiorespiratory, musculoskeletal, haematological, immunological and thermoregulatory functions. In addition to the specific objectives, the study will be explorative in the sense that it will collect a broad spectrum of basic data corresponding to that obtained when 21-day bedrest experiments are conducted by ESA/NASA (bedrest core data). Thus, data from the experiments can readily be compared with core data from previous bedrest studies, and hence the added effects of hypoxia should be evident.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.3.2-2 | Award Amount: 3.89M | Year: 2013

The rise of complex, chronic diseases in an ageing European population led to the development of increasingly complex technologies. Current HTA is not well equipped to assess complex technologies due to a lack of attention to the diversity in patient characteristics and patient preferences, the limited consideration of context and implementation issues, and missing strategies to integrate all these aspects into a comprehensive assessment. We shall develop concepts and methods for HTA to enable a patient-centered, integrated assessment of the effectiveness, and the economic, social, cultural and ethical issues of complex technologies that takes context and implementation into account. We shall use palliative care for our case study as it is of extremely high relevance and it is an excellent example for a highly complex technology. More specifically, we shall adapt and develop methods and concepts - to assess the effectiveness and economic, social, cultural, and ethical issues of complex technologies, - to elicit patient preferences and patient-specific moderators of treatment - to include context, setting, and implementation - and, finally, to integrate these issues into a patient-centered, comprehensive assessment of complex technologies. Concepts and methods will be tested through assessing the complex technology Specialist palliative care. Revised guidance will be issued for comment to all relevant stakeholders. All partners of the consortium have an outstanding track record in the development of HTA methodology and are actively involved in major international initiatives in the field. The project will complement the work of similar initiatives and projects on HTA development, especially EUNetHTA/EUNetHTA JA and inform HTA agencies in all European countries. By focusing on an integrated assessment, we shall also match the need of policy-makers who prefer this to dealing with scattered information on innovative and complex technologies.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.01M | Year: 2012

Coding of biochemical information is commonly described to be based solely on nucleotides and amino acids, whereas carbohydrates, the most abundant type of molecule in Nature, appear sidelined in this respect. That carbohydrates, as part of cellular glycoconjugates, have exceptional talents for building biochemical signals is an emerging insight, at the heart of the concept of the Sugar Code. Intuitively, emergence of recognition partners for information transfer is expected, and this is the case. Thus, coding of bioinformation in glycans and information transfer via lectins is key to a wealth of medically relevant processes, e.g. infection, immune regulation and malignancy, now awaiting its full exploitation pharmaceutically. To do so, training in this exceptionally interdisciplinary field needs to be provided. With this aim, scientific and country/gender issues are strategically combined in this network. Its composition assures a continuous chain of research expertise, from computational and synthetic chemistry to state of the art biophysical chemistry and structural biology, then to biochemistry, molecular cell biology and pharmaceutical/biomedical sciences, generating innovative clinical approaches. Notably, academia is linked with industry, bringing in the essence of business acumen into the training programme. This activity and the research deliberately planned as interdisciplinary projects ensure an optimal training for young researchers in a dynamically developing area of conspicuous biopharmaceutical potential. Equally important, it lays the foundation to inspire novel strategies for the design of potent and selective inhibitors against lectins and the development of lectins (or suitably engineered variant(s)) as therapeuticals. As a boon for the success of the network, cooperations between several partners have already proven successful, especially increasing the core in Madrid and partners in Dublin, Munich and Prague.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-1-B | Award Amount: 15.82M | Year: 2012

EURenOmics will integrate several established consortia devoted to rare kidney diseases with eminent need and potential for diagnostic and therapeutic progress (i.e. steroid resistant nephrotic syndrome, membranous nephropathy, tubulopathies, complement disorders such a haemolytic uraemic syndrome, and congenital kidney malformations). The Consortium has access to the largest clinical cohorts assembled to date (collectively >10,000 patients) with detailed phenotypic information and comprehensive biorepositories containing DNA, blood, urine, amniotic fluid and kidney tissue. The project aims to (1) identify the genetic and epigenetic causes and modifiers of disease and their molecular pathways; (2) define a novel mechanistic disease ontology beyond phenotypical or morphological description; (3) develop innovative technologies allowing rapid diagnostic testing; (4) discover and validate biomarkers of disease activity, prognosis and treatment responses; and (5) develop in vitro and in vivo disease models and apply high-throughput compound library screening. For these purposes we will integrate comprehensive data sets from next generation exome and whole-genome sequencing, ChiP-sequencing, tissue transcriptome and antigen/epitope profiling, and miRNome, proteome/peptidome, and metabolome screening in different body fluids within and across conventional diagnostic categories. These data will be combined in a systems biology approach with high-resolution clinical phenotyping and findings obtained with a large array of established and novel in vitro, ex vivo and in vivo disease models (functiomics) to identify disease-associated genetic variants involved in monogenic or complex genetic transmission, disease-defining molecular signatures, and potential targets for therapeutic intervention. These efforts will converge in the development of innovative diagnostic tools and biomarkers and efficient screening strategies for novel therapeutic agents.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2011.2.2.1-3 | Award Amount: 8.07M | Year: 2011

This project will undertake pre-clinical and cohort studies that address susceptibility factors for paediatric and adolescent tic disorders, with a particular focus on comorbid obsessive-compulsive symptomatology, from clinical, epidemiological, genetic, microbiological and immunological angles. EMTICS aims to elucidate the complex aetiology of the onset and clinical course of chronic tic disorders and associated obsessive-compulsive symptoms, through disentangling the interplay between environmental factors and genetic background; translate research findings into clinical applications by developing disease prediction models and investigation of a treatment strategy; and will establish a Pan-European infrastructure for the study of tic disorders. We hypothesise that the onset and/or exacerbation of tic and comorbid obsessive-compulsive disorders is associated with increased preceding occurrence of Group A beta-haemolytic Streptococcus (GAS) infections of specific molecular subtypes, and that this association is based on genetic susceptibility factors and mediated through immunological mechanisms related to psychosocial stress and immunological factors in host and GAS strains. Large-scale cohort studies will involve affected patients and at-risk first-degree relatives within an integrated, multidisciplinary research strategy. Treatment effects of active surveillance and standardized antibiotic treatment of GAS colonisation, thus addressing one of the main environmental factors involved (GAS infections) will be evaluated. Our approach will result in the identification of genetic and environmental susceptibility factors and will greatly contribute to a better understanding of the underlying mechanisms of tic disorders, with a focus on elucidating the role of autoimmunity. Our consortium brings together the highest expertise in the field of tic disorders across Europe in academia and industry, including a number of SMEs and a professional management company.

Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: HEALTH-2007-2.1.2-7 | Award Amount: 1.12M | Year: 2009

In contrast to the reductionist approach of Western medicine that is based on modern anatomy, cell and molecular biology, Traditional Chinese Medicine (TCM) uses a unique theory system and an individualised and holistic approach to describe health and disease, based on the philosophy of Yin-Yang balance and an emphasis on harmony of functions. These two medicine systems disagree with each other in many situations as both of them may observe health from their limited perspective. GP-TCM aims to inform best practice and harmonise research of the safety and efficacy of TCM, especially Chinese herbal medicines (CHM) and acupuncture, in EU Member States using a functional genomics approach through exchange of opinions, experience and expertise among scientists in EU Member States and China. In 10 proposed work packages, we will take actions to review the current status, identify problems and solutions in the quality control, extraction and analysis of CHM. While these fundamental issues are addressed, discussion forums emphasising the use of functional genomics methodology in research of the safety, efficacy and mechanisms of CHM and acupuncture will be the core of this Coordination project. It will include the application of the technique in cell-based models, animal models and in clinical studies. Guidelines about good practice and agreed protocols in related research areas will be published to promote future TCM research in all the EU member states; online tools and research resources will be made available to EU member states; EU member states and additional China partners will be invited to join this network; The GP-TCM Research Association will be established during this project and kept running autonomously to continue the guidance and coordination of EU-China collaboration in TCM research.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.1-5 | Award Amount: 8.12M | Year: 2011

Among patients with adrenal masses Adrenocortical carcinoma (ACC) and malignant pheochromocytomas (MPH) are found with a low incidence but very unfavorable prognosis. Due to this poor clinical outcome, concomitant hormone dysregulation and limited treatment options the two cancer entities severely impact on affected patients. However, the rarity of the tumors also impedes clinical studies which are affected by fragmentation and low cohort sizes. The European Network for the Study of Adrenal Tumors (ENS@T) has recently implemented a collection of adrenal tumor related databases and defined an associated network of Biological Resource Centers devoted to research on adrenal tumors. The concurrence of recent achievements of this evolving network, the progress in the understanding of molecular mechanisms and increasing availability of specific diagnostic and therapeutic tools for adrenal cancers provides the unique opportunity to achieve unmatched progress in the implementation of both translation and clinical research dedicated to ACC and MPH. Specifically, the newly formed ENS@T-CANCER consortium will address the following topics: 1. Structuring European clinical and translational research through implementation of a virtual research environment, 2. Improving clinical outcome of patients with adrenal cancer by conducting interventional trials carried out by European centers of excellence, 3. Improvement of differential diagnosis and risk stratification of adrenal cancer, 4. Identification and validation of tools for follow-up of patients with adrenal cancer, 5. Identification of novel biomarkers for treatment response. The ultimate aim of the ENS@T-CANCER Consortium is to develop research in the field of adrenal cancers to improve diagnosis and treatment abilities. The Network will allow recruiting sufficient patients in all relevant European centers, to harmonize diagnosis criteria and to use the various technological approaches of a number of laboratories.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.3.3-1 | Award Amount: 16.37M | Year: 2011

To address the call for proposals Biology and control of vector-borne infections in Europe launched by the European Commission, we want to investigate the biological, ecological and epidemiological components of vector-borne diseases (VBD) introduction, emergence and spread, and to propose innovative tools for controlling them, building on the basis of acquired knowledge. We have selected the main groups of arthropod vectors involved in the transmission of vector-borne diseases in Europe: ticks, mosquitoes, sandflies, and biting midges (Culicoides). We have also selected the main diseases of actual or possible importance in human and veterinary public health. Rodents, insectivores and rodent-borne diseases have also been considered, both for their direct importance in public health, and for the major role of rodents and insectivores as reservoir hosts of many pathogens. We have put a strong focus on vector- and disease-quantitative modelling. The resulting predictive models will be used to assess climate or environmental change scenarios, as well as vector or disease control strategies. Human behaviour and risk perception are an important component of VBD introduction, emergence and spread. The consequences triggered by VBD for human and veterinary public health in Europe are just starting to emerge in public awareness. We will also account for this aspect of human and veterinary public health in our proposal. Finally, the set of innovative research methods, tools and results obtained during the project will be a step forward a generic approach of VBD in terms of disease monitoring and early warning systems, and will reinforce the general framework for an integrated pest and disease management system. For all these aspects, we will benefit from, and amplify the strong scientific results, capacity building, and research networks established by EDEN project on emerging, vector-borne diseases in a changing European environment.

Agency: European Commission | Branch: FP7 | Program: NoE | Phase: HEALTH.2010.2.1.2-2 | Award Amount: 16.04M | Year: 2010

The EpiGeneSys Network of Excellence aims to enable European epigenetics research to enter the arena of systems biology, a new step forward with major implications for human health. Many diseases, not explained solely by gene mutation, have rather been associated with epigenetic disorders. Following the identification of key epigenetic regulators, a move towards a systems biology approach is needed to understand their dynamic functional relationships. This NoE identified 4 areas aiming at: 1) characterizing the molecular dynamics of epigenetic systems at the single molecule and cell level, 2) linking genotypes to epigenotypes, 3) investigating how environmental, developmental and metabolic signals act upon the epigenome, and 4) understanding epigenetic inheritance through replication, mitosis and meiosis. The common objective is to address fundamental epigenetic mechanisms in quantitative terms both spatially and temporally. The ultimate goal is to express the underlying dynamic events in mathematical terms in order to model and predict how the balance between maintenance and erasure of epigenetic information varies in specific developmental contexts under normal or pathological conditions. A major effort on data management and technology will provide standardised protocols for processing, normalising, and analysing each type of epigenetics data set. Common platforms, tools and resources including a key multilayer toolbox will be implemented for wide use and easy access for researchers, within the NoE and the epigenetics community at large. This NoE will function as an essential bridge between epigenetics researchers and the systems biology community. In the NoE, 22 teams will join efforts to address Epigenetics questions from a systems biology perspective. The combination of a strong training plan together with extension through open targeted calls to recruit young talent will further contribute to build a coherent new EpiGeneSys Area of European Research.

Agency: European Commission | Branch: FP7 | Program: NoE | Phase: Fission-2009-3.1.1 | Award Amount: 21.29M | Year: 2010

The aim of DoReMi is to promote the sustainable integration of low dose risk research in Europe in order to aid the effective resolution of the key policy questions identified by the High Level Expert Group (HLEG) on Low Dose Risk Research ( DoReMi provides an operational tool for the development of the proposed MELODI platform (Multidisciplinary European Low Dose Risk Re-search Initiative) consisting of major national bodies and research programmes that have long term commitment in low dose risk research in Europe. A Letter of Intent between the core members of MELODI has been signed in April 2009. During the project, new members are expected to join the Initiative. The Joint Programme of Activities (JPA) of DoReMi includes: (i) a Joint Programme of Research (JPR) covering the issues outlined above and providing an overview of the needs for research infra-structures of pan-European interest and facilitating multilateral initiatives leading to better use and development of research infrastructures; (ii) a Joint Programme of Integration (JPI) to develop a coor-dinated European roadmap for the long term needs of the key players in Europe; and (iii) a Joint Pro-gramme for the Spreading of Excellence (JPSE), covering knowledge management, training and mo-bility and its implementation. The JPR focuses on the areas identified by the HLEG as the most prom-ising in terms of addressing/resolving the key policy questions, namely: the shape of dose response curve for cancer, individual susceptibilities and non-cancer effects. Radiation quality, tissue sensitivity and internal exposures will be addressed as cross cutting themes within the three main research areas. A substantial proportion of the JPA will be dedicated to the joint programme of research. The pro-gramme describes a multidisciplinary approach including interfaces with the broader biological toxico-logical and epidemiological communities. Strategic planning will be carried out in close collaboration with MELODI. The long term Strategic Research Agenda (SRA) will be developed by MELODI, whereas DoReMi research priorities are based on a shorter term Transitional Research Agenda (TRA), focusing on goals that are feasible to achieve within the 6 year project and areas where barriers need to be removed in order to proceed with the longer term strategic objectives.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2011.2.2.1-1 | Award Amount: 6.98M | Year: 2011

Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of rare hereditary neurodegenerative disorders characterized by high levels of brain iron. The most common form is pantothenate kinase-associated neurodegeneration (PKAN). Classic PKAN and most other NBIA cases are characterised by early childhood onset and rapid progression. Currently, there is no proven therapy to halt or reverse PKAN or any other NBIA. This is especially unfortunate as both the iron accumulation in NBIA and the biochemical defect in PKAN are predicted to be amenable to drug-based treatment. Thus, the current absence of clinical trials is not due to lack of therapeutic options but to rarity of the disease, lack of patient registries and fragmentation of therapeutic research worldwide. For example, the iron-chelating drug deferiprone has been administered to PKAN patients on an individual basis or in pilot trials, both precluding firm conclusions about its efficacy. With TIRCON, we will address this urgent and unmet need for NBIA/PKAN therapy with an ambitious and highly collaborative plan that leverages worldwide expertise. We propose a large investigator-driven randomized clinical trial of deferiprone in PKAN, bringing together leading centres and patient advocacy groups from Europe and the US to reach the required patient cohort size. In addition, together with a European SME, we propose to pursue preclinical development of pantethine and its derivatives which have shown promising efficacy in a Drosophila PKAN model. To facilitate future research, we will develop a harmonized patient registry and biomaterial bank to allow for natural history studies and biomarker development, two critical needs in NBIA research. TIRCON partners, apart from their unique clinical and basic science expertise in NBIA, have longstanding experience in investigator-driven and industry-driven randomized clinical trials. Importantly, they have been closely collaborating in recent years.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.0-1 | Award Amount: 6.97M | Year: 2013

Effectively protecting the general population from seasonal and pandemic influenza has proven to be a challenge, since influenza viruses continue to escape from and evade immunity. Current influenza vaccines fail to provide long-lasting and broad protection against multiple strains of influenza. For the development of a universal influenza vaccine, we have to do better than Nature, since even natural influenza virus infections fail to induce broad protective immunity. To induce broad-protective and long-lasting immunity an influenza vaccine should therefore be directed to conserved viral proteins or regions thereof that are insufficiently exposed upon natural infection. FLUNIVAC is a SME-targeted collaborative research project that aims to develop a candidate influenza vaccine based on recombinant MVA expressing both antibody and T-cell response-inducing proteins, ready to commence Phase I clinical trials within 4 years. We will generate recombinant MVAs that express nine conserved (regions of) influenza A virus proteins (surface proteins HA, NA, M2e, internal proteins M1, NP, NS1, and the polymerase proteins PB1, PB2, PA). These proteins are targets for both antibody and T-cell mediated immune responses, since the induction of solely one of both affords only modest protection against infection with influenza viruses of heterologous subtypes. These recombinant MVAs will be tested for their capacity to induce the desired broad-protective immune response individually and in selected combinations in vivo. In parallel, MVA-induced immune responses will be tested for their longevity and boostability as compared with those induced with adjuvanated vaccine preparations. Furthermore, the MVA platform will be optimized in terms of: i) kinetics and extent of protein-expression of the MVA vector to optimally activate the respective arms of the immune system; ii) a viable unified production process, independent of embryonated chicken eggs, will be designed and implemented.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE-2007-2-2-02 | Award Amount: 8.00M | Year: 2008

Major objective: It is our aim to develop a lipid based diet that is able to delay or prevent onset of Alzheimers disease and related diseases and has a stabilizing effect on cognitive performance in aging. Multiple lines of evidence suggest that there is a large overlap between risk factor of these three diseases. Importantly, there is equally strong evidence that prevention and treatment of these diseases can be efficiently addresses - especially in their first and their priclinical stages - by closely related or identical bio-molecules. Predominantly these molecules appear to belong to the class of lipids which are part of the human diet. However, very often they are consumed in far lesser than recommended amounts. Bearing in mind that all of these diseases have a long pre-clinical phase in which the disease remains undetected specifically designed nutrition may be requirred for effective prevention or for those who already progressed into the first clinical stage of the disease. Moreover, frequently the within the elderly population pathological changes by two or all of these diseases occur in combination thus targeting only one would be insufficient. Taking these aspects into consideration, dietary supplementation, composed to maximize benefit for all three of these in the elderly common diseases, appears to be the most suitable approach to provide a general health perspective improvement for this age group in the EU population.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.63M | Year: 2015

In the European Union, cancer is the leading cause of death and the overall cancer incidence is still increasing. As a result of expanding efforts to improve cancer outcome, a main paradigm change is occurring in cancer therapy towards individualized medicine. Antibody-based therapies form an integral and constantly growing part of this approach. Antibody-based therapies will strongly influence the coming decade of cancer care. The importance of immunotherapy has been highlighted by the prestigious Science journal as breakthrough of the year 2013, heralding the rising importance of immunotherapy. Accordingly the need for well-trained and skilled researchers in academia and industry is dramatically increasing in this field. IMMUTRAIN is a training network bringing together experts in the fields of monoclonal antibodies, dendritic cells, T-cells and immunomodulatory nucleic acids with a considerable industrial involvement. The network comprises nine academic research groups and five industrial partners in a total of seven European countries. IMMUTRAIN will actively create synergies between those sectors by forming and promoting young researchers to match the challenges of immunotherapies. Particular focus will be placed on combinatorial therapies and on the new emerging field of bispecific antibodies used to target both the tumor and the patients immune system. Fifteen Ph. D. students (early stage researchers, ESR) reinforced by the project leaders will investigate innovative therapeutic strategies and provide the rationale for future clinical trials. Throughout their projects, ESR will learn to integrate academic and industrial aspects and will sharpen their experimental and complementary skills in a well-designed and diversified training program.

Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.1.3-04 | Award Amount: 3.91M | Year: 2013

Good fertility is essential for the sustainability of livestock production. Of all livestock sectors, fertility of dairy cattle is raising the greatest cause for concern. Cow fertility has declined, particularly in Holstein cattle, from 80% pregnancy to first service 20 years ago to less than 40% today. Poor fertility is one of the main reasons for early culling, such that modern dairy cows complete fewer than 3 lactations, on average. The FECUND project will address the metabolic and genetic causes of low reproductive success of dairy cows in an interdisciplinary approach that will integrate in vivo and in vitro studies, biology, physiology, -omics technologies and bioinformatics. FECUND will focus on the early phases of reproduction from oocyte development to implantation of the conceptus. Starting from biological materials produced from high and low genetic merit cattle and from cows under energy stress of early lactation vs dry cows and heifers, FECUND will study, independently, the effects of genetics and metabolic stress on reproductive physiology to identify factors and early markers associated with high and low developmental potential, and with positive mother-conceptus interaction during the early stages of reproduction. These data will be mined to reveal physiological pathways and key candidate genes controlling variations of fertility. The biological knowledge created on early reproductive events in vivo will be validated in vitro, and extended to create further knowledge on the effects of the local environment on oocyte and embryo programming at the epigenetic level. Validated information will be used to improve herd management, gene assisted and genomic selection and assisted reproductive technologies, from in vitro ooctye maturation to optimised embryo culture. Information on biomarkers, indicator traits and improvements in assisted reproduction will be translated to applications that can be immediately implemented by SMEs.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: LCE-31-2016-2017 | Award Amount: 3.72M | Year: 2016

Considerable challenges remain today regarding Europes transition towards a decarbonised energy system that meets the economic and social needs of its citizens. Rebound effects, that is, a full or partial cancelling-out of efficiency gains over time through increased overall energy use, highlight the centrality of consumption in multi-scalar decarbonisation efforts, urgently requiring attention from scientists and policy makers. Calls also abound for innovative, research-led programmes to enhance the social acceptability of energy transition initiatives and technologies. Understanding how culture-specific views and practices and energy policy and governance both shape and reflect individual and collective energy choices is of paramount importance for the success of the Energy Union. ENERGISE responds directly to these challenges by engaging in frontier energy consumption scholarship. Recognising the persistence of diverse energy cultures, both within and between countries, ENERGISE offers an ambitious social science programme to enhance understanding of changes in energy consumption practices across 30 European countries. Moving beyond state-of-the-art research, ENERGISE theoretically frames and empirically investigates socio-economic, cultural, political and gender aspects of the energy transition. It also examines how routines and ruptures (re)shape household energy consumption practices. Adopting a cutting-edge Living Labs approach, designed specifically to facilitate cross-cultural comparisons, ENERGISE fuses tools for changing individual- and community-level energy consumption with a novel method for energy sustainability assessment. ENERGISE will open new research horizons and greatly enhance Europes capacity for high-impact, gender-sensitive consumption research. It also offers timely support for public- and private-sector decision-makers who grapple with the design and implementation of measures to effectively reduce household energy consumption.

Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: SiS-2008-;SiS-2008- | Award Amount: 1.03M | Year: 2009

The ComScience Network brings recent EU research results into local communities through science communicators from five different EU cities. Local scientific experts and representatives of local or regional administrations will participate and promote local scientific culture. Five chosen science topics address the concerns and interests of European citizens: stem cell research, the use of genetically modified organisms, obesity and type 2 diabetes, allergies and asthma as well as contaminants in our food. The project structure stimulates the exchange of know-how and best practices and enables Science City driven partnerships between local actors from different places in Europe. In three years ComScience will: i) consult key players to discuss content and format of the proposed activities ; ii) adapt disseminated materials from FP6 and FP7 research consortia ; iii) organise 25 public dissemination events ; and iv) produce extensive evaluation reports for policy input. The deliverables of the ComScience project goes beyond its immediate activities, namely to evaluate and document to what extent it is possible to: compile and re-work (edit, format) the information - that is produced by the many different EU funded research consortia as the output of their dissemination activities - in an international collective(s) of local dissemination actors create a generic methodology (best practice) that allows widespread dissemination of the the structured data on a significantly larger scale, in local settings while respecting regional differences. provide the means to keep the accumulated knowledge up to date and for a long term use by different communication organisations. To achieve these goals, ComScience has brought together a powerful team that represents not only different types of science communicators, but also represents different European regions and cities.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.1.2-5 | Award Amount: 3.84M | Year: 2009

The PluriSys project is aimed at increasing the fundamental knowledge of basic biological processes of cell pluripotency and differentiation by generating new holistic data on gene expression and epigenetic modifications associated with cell pluripotency. The project integrates the multidisciplinary excellence in Europe in cell biology, molecular biology and bioinformatics. It also builds on earlier efforts, as consortium partners are leading partners in several EU funded projects in these areas. The PluriSys project links for the first time research activities in different mammalian systems, including murine, porcine and bovine, and in different cell types, from pluripotent cells in pre-implantation embryos, through embryonic stem cells, to epiblast-derived stem cells. Novel bioinformatics approaches and tools will be developed to set common standards for data analyses among all consortium members and, at a wider scale, to provide an integrated data base matching the requirements of systems biologists. Training, education and outreach activities are structured to assure the maximum efficiency in developing and spreading the new standards and to increase the impact of the project for the European Health sector. The project integrates SME partners and academic institutions from 7 countries from all regions of the EU and will help to decrease the fragmentation of ERA. The main impact of the project is expected as integrating efforts in cell biology, cell therapy, molecular biology and bioinformatics for future applications of systems biology on the relevant questions of cell pluripotency and differentiation. Furthermore, the project is expected to yield pracically useful results, such as improved procedures for the derivation, maintenance and differentiation of pluripotent stem cell lines in mouse and large animals, with potential future applications in the fields of regenerative medicine and tissue engineering, and, beyond these areas, in pharmaceutical industry and

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENV.2013.6.4-1 | Award Amount: 14.89M | Year: 2013

Assessing individual exposure to environmental stressors and predicting health outcomes implies that both environmental exposures and epi/genetic variations are reliably measured simultaneously. HEALS (Health and Environment-wide Associations based on Large population Surveys) brings together in an innovative approach a comprehensive array of novel technologies, data analysis and modeling tools that support efficiently exposome studies. The general objective of HEALS is the refinement of an integrated methodology and the application of the corresponding analytical and computational tools for performing environment-wide association studies in support of EU-wide environment and health assessments. The exposome represents the totality of exposures from conception onwards, simultaneously identifying, characterizing and quantifying the exogenous and endogenous exposures and modifiable risk factors that predispose to and predict diseases throughout a persons life span. The HEALS approach brings together and organizes environmental, socio-economic, exposure, biomarker and health effect data; in addition, it includes all the procedures and computational sequences necessary for applying advanced bioinformatics coupling thus effective data mining, biological and exposure modeling so as to ensure that environmental exposure-health associations are studied comprehensively. The overall approach will be verified and refined in a series of population studies across Europe including twin cohorts, tackling different levels of environmental exposure, age windows of exposure, and socio-economic and genetic variability. The HEALS approach will be applied in a pilot environment and health examination survey of children including singletons and sets of twins with matched singletons (each twins pair having also a matched singleton) covering ten EU Member States (the EXHES Study). The lessons learned will be translated into scientific advice towards the development of protocols and guidelines for the setting up of a larger European environment and health examination survey.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: NMP-2008-1.1-1 | Award Amount: 4.60M | Year: 2009

The project aims at developing a new integrated and automated microfluidic tool for cancer cells screening. This instrument will have a reliability and power much beyond state of the art (capture yield increased by a factor from 10X to 100X and multimodal typing of the cells in 3D high resolution images), allowing earlier and more accurate diagnosis, prognosis and selection of treatments of cancers. CaMiNEMSs new approach will involve a new generation of bio-functionalised multifunctional magnetic nano and microparticles which will be self-assembled by a Hierarchial Templated Self-Assembly mechanism into high-aspect ratio reversible arrays. For highly automated molecular typing of cancers, this key innovation will be integrated with a unique fully automated flow control system working from nanolitres to millilitres and with innovative nano-optics tools and image analysis software. Technological developments will be validated regarding the analysis of circulating tumour cells or micrometastases and the molecular typing of minimally invasive microsamples from tumours. The project will also yield new tools for research and drug-discovery, allowing for the first time to study at the single molecule scale in single cancer cells from patients the fate and action of new generation anticancer drugs using innovative dynamic tracking of Quantum dots. To combine research excellence and societal impact, the consortium involves research groups with complementary competences in microfluidics, nano-optics, biophysics, nanoparticles, biochemistry, informatics, several forefront cancer centres for clinical validation and a research-intensive SME for exploitation.

Agency: European Commission | Branch: FP7 | Program: CP-SICA | Phase: KBBE-2008-1-4-08 | Award Amount: 3.85M | Year: 2009

VALORAM aims at exploring and valorizing Andean soil microbial diversity for the development of alternative, efficient technologies and crop management practices to improve the sustainability and productivity of Andean cropping systems benefiting rural farming households. The project will focus on potato because of its global importance for small-scale farmers in the central Andean highlands. The participants will use metagenomic, genomic, proteomic and metabolomic analysis to identify novel traits of microorganisms and characterize beneficial soil microbial communities, to achieve the objective. The project specific aims are to (1) explore the agro-ecosystem functions of soil microbes in potato-based cropping systems and preserve the components of this microflora in international culture collections, (2) elucidate the role of rhizosphere microorganisms and communities in promoting plant growth, suppressing soil borne disease and priming plant biotic defenses, developing eco-efficient technologies/products for sustainable crop production systems, (3) develop applied technologies and knowledge-based systems to improve the sustainability and resilience of potato based cropping systems for the benefit of the indigenous farmers and (4) promote the exchange of scientific knowledge and technologies among partners and the LA scientific community to impulse research in this area and support the continuous development of crop production technologies. The strategy for VALORAM implementation is to engage LA and EU partners in developing and further stengthening collaborative research activities in order to sustainably improve potato-based systems. This is supported by a multidisciplinary team of experts with highly complementary skills and based on a robust management structure with an efficient workshop and communication programme. The results will directly benefit the local partners and may also contribute to increase the productivity of organic potato production in the EU.

Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: ENV.2011.1.3.3-1 | Award Amount: 4.57M | Year: 2011

Our knowledge of the causative links between subsurface processes, resulting unrest signals and imminent eruption is, today, wholly inadequate to deal effectively with crises of volcanic unrest. The VUELCO project consortium has come together for a multi-disciplinary attack on the origin, nature and significance of volcanic unrest from the scientific contributions generated by collaboration of ten partners in Europe and Latin America. Dissecting the science of monitoring data from unrest periods at six type volcanoes in Italy, Spain, the West Indies, Mexico and Ecuador the consortium will create global strategies for 1) enhanced monitoring capacity and value, 2) mechanistic data interpretation and 3) identification of reliable eruption precursors; all from the geophysical, geochemical and geodetic fingerprints of unrest episodes. Experiments will establish a mechanistic understanding of subsurface processes capable of inducing unrest and aid in identifying key volcano monitoring parameters indicative of the nature of unrest processes. Numerical models will help establish a link between the processes and volcano monitoring data to inform on the causes of unrest and its short-term evolution. Using uncertainty assessment and new short-term probabilistic hazard forecasting tools the scientific knowledge base will provide the crucial parameters for a comprehensive and best-practice approach to 1) risk mitigation, 2) communication, 3) decision-making and 4) crisis management during unrest periods. The VUELCO project consortium efforts will generate guidance in the definition and implementation of strategic options for effective risk mitigation, management and governance during unrest episodes. Such a mechanistic platform of understanding, impacting on the synergy of scientists, policy-makers, civil protection authorities, decision-makers, and the public, will place volcanic unrest management on a wholly new basis, with European expertise at its peak.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 5.99M | Year: 2015

Type 2 diabetes will affect >500 million adults by 2040 and its secondary complications will generate enormous socioeconomic costs - in particular, diabetic kidney disease (DKD), which is already the most common cause of chronic kidney disease. DKD is associated with greatly increased mortality and frequently progresses to end stage renal failure. Pharmacotherapy, dialysis and transplantation represent the mainstay treatments for DKD but are costly and provide only limited protection against adverse outcomes. Mesenchymal Stromal Cell (MSC) therapy is a promising approach to halting the progression of DKD toward end-stage renal failure and may also have ancillary benefits in Type 2 diabetes. In preliminary research, we have demonstrated that a single dose of MSC simultaneously improves kidney function (glomerular filtration rate and albuminuria) as well as hyperglycaemia in animals with DKD. NEPHSTROM will conduct a multi-centre, placebo-controlled clinical trial of a novel MSC therapy for stabilization of progressive DKD, leading to superior clinical outcomes and long-term socioeconomic benefit. A key enabler for this trial is a novel MSC population (CD362\MSC, trade name ORBCEL-M) which delivers higher purity and improved characterisation compared to conventional plastic-adherent MSC. The NEPHSTROM Phase 1b/2a clinical trial will investigate the safety, tolerability and preliminary efficacy of a single intravenous infusion of allogeneic ORBCEL-M versus placebo in adults with progressive DKD. NEPHSTROM investigators will also determine the bio-distribution, mechanisms of action, immunological effects and economic impacts associated with ORBCEL-M therapy for DKD. This research will critically inform the optimal design of subsequent Phase 3 trials of ORBCEL-M. Stabilising progressive DKD through NEPHSTROMs next-generation MSC therapy will reduce the high all-cause mortality and end-stage renal failure risk in people with this chronic non-communicable disease

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-1.2-3 | Award Amount: 9.09M | Year: 2008

We aim develop in-vivo imaging biomarker of multidrug transporter function as a generic tool for the prediction, diagnosis, monitoring and prognosis of major CNS diseases, as well as to provide support and guidance for therapeutic interventions. Multidrug transporters actively transport substrates (including multiple CNS drugs) against concentration gradients across the blood-brain barrier (BBB). Overactivity of these efflux transporters results in inadequate access of CNS drugs to their targets and hampers the build up of adequate tissue levels of these drugs in the brain, greatly limiting their therapeutic efficacy. As such, this transporter hypothesis of drug resistance is applicable to a broad range of CNS drugs and patients with a variety of CNS diseases who critically depend on these drugs. Efflux transporters may also influence brain elimination of A, the hallmark of Alzheimers disease (AD). Impaired multidrug transporter function with reduced clearance of A could lead to accumulation within the extracellular space, contributing to the pathogenesis of AD. We will determine the contribution of multidrug transporters to impaired brain uptake of drugs for the prediction of therapeutic responses, or the contribution of impaired transporter function to reduced clearance of toxic substances for the early in-vivo diagnosis of AD. Circumvention of pharmacoresistance, or increasing clearance, may involve inhibitors of multidrug transporters or sophisticated alternative therapies, but demonstration of overexpression or underactivity of transporter function is an essential and necessary first step. An in-vivo imaging biomarker of multidrug transporter function is essential for identifying altered transporter activity in individual patients. If a relation between overexpression and therapy resistance, or underactivity and AD, can be demonstrated, such a biomarker will provide the means for predicting treatment response, or early diagnosis, in individual patients.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2011.1.1-2 | Award Amount: 7.99M | Year: 2011

Treatment resistant schizophrenia (TRS) is the most disabling of all psychiatric illnesses, affecting about 1/3 of patients (~1 million Europeans), a considerable economic and social burden. First-line treatments include atypical (e.g. olanzapine) and typical (e.g. haloperidol) antipsychotics. The original atypical, clozapine, is a final option, and although it is the only antipsychotic shown to be effective in TRS, about half of TRS patients are also resistant to clozapine. CRESTAR is an SME-driven projected, focusing on the development of pharmacogenomic biomarkers for schizophrenia. It aims to develop tools to predict i) who will NOT respond to usual antipsychotics, indicating treatment with clozapine as early as possible, ii) the 1% of patients who will develop potentially fatal side effects, agranulocytosis, which is the main factor limiting clozapine use, and diabetic ketoacidosis, occurring in up to 2% of patients, and often fatal. We will also predict patients likely to be non-responders to all antipsychotics, i.e. extreme TRS, so that they can be stratified in clinical trials. CRESTAR will address these questions by examining genome-wide association data, genome sequence, epigenetic biomarkers and epidemiological data in European patient cohorts characterized for treatment response, and adverse drug reaction using data from clozapine therapeutic drug monitoring and linked National population medical and pharmacy databases, alongside existing European projects (e.g. PSYCNVs and EU-GEI) national initiatives (e.g. UK10K genome sequencing) to identify predictive factors. In parallel CRESTAR will perform health economic research on potential benefits, and ethics and patient-centered research with stakeholders. The outcome of CRESTAR will be a genomic test and associated clinical decision making tools, designed to improve pharmacological treatment of schizophrenia in both efficacy and safety, piloted with existing and new clinical trials such as OPTiMiSE.

Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH.2010.1.1-3 | Award Amount: 4.87M | Year: 2011

Protein glycosylation is a post-translational phenomenon that is involved in most physiological and disease processes including cancer. Most of the known cancer-associated glycobiomarkers were discovered individually using liquid chromatography and mass spectroscopy. Though valuable, there is room for improvement in these approaches for the discovery phase. There is also a critical need for innovative, rapid, and high-throughput (HTP) technologies that will translate the discovery of cancer-associated glycobiomarkers from basic science to clinical application. The GlycoHIT consortium brings a highly experienced, innovative and interdisciplinary team of researchers from Europe, China and USA representing academia, industry and clinical fields to significantly enhance some of the existing glycoanalytical technologies and to advance novel HTP glycoanalytical technologies beyond current state of the art. Microchip technology and novel partitioning methods will be exploited for nanoscale HTP separations of serum glycoproteins for analysis by HPLC or LCMS. In parallel, lectin array technology will be radically improved by the innovative use of recombinant human lectins and lectin mimics derived by screening large phage displayed combinatorial libraries. Aptamer libraries will be exploited for identification of lectin mimics and development of a glycosignature platform Compatibility of the lectin/lectin mimic array technologies with novel label-free biosensors will be explored. Newly-developed technologies will be validated by analysis of serum samples from a variety of cancer patient cohorts and will be supported throughout by experimental interaction analysis, complex structural modelling and informatics. Effective project management, commercially-aware intellectual property management and targeted dissemination activities supplement the core science and ensure maximum impact for the project.

The CREDITS4HEALTH projects main goal is to develop a person centric approach based on the credits for health concept to reduce sedentary behavior and enhance the level of physical activity and healthy dietary styles in people living in Euro-Mediterranean Countries. The concept of credits is simple and effective: this means that each participant will earn credits from his local, regional or national Health Authority on the basis of his/her participation and involvement in the achievement of an healthy life-style, and his/her attitude to sponsor this philosophy in his community. The CREDITS4HEALTH vision is therefore to have people directly acting for their health and well being, operating on three fundamental levers to enhance the quality of their lives, through the reduction of sedentary behavior, the active participation to the social life and the adoption of an healthier diet. The CREDITS4HEALTH approach is virtuous and straightforward: 1)First, we will define personalised algorithms containing dietary and physical activity prescriptions, taking into account the medical, psychological, social, and economic background of each person; 2) Once screened by the local Credits4Health Committee, the participant receives an electronic card, which enables him to track his compliance to the regime through a dedicated web based platform; 3)With his electronic card, the participant also gets access to a full range of suppliers which offer him goods for fulfilling his health-related objectives;4)Suppliers must be certified by the local authority, according to a specified set of requirements and they must certify the products they intend to commercialise for this initiative;5)Participants gain credits as far as they comply with their daily, weekly and monthly goals; they are also subject to a six monthly mandatory assessment performed by the Credits4Health Committee, in which the algorithm can be modified and fine-tuned to the needs of the participant.

Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra-PP | Phase: INFRA-2010-2.2.7 | Award Amount: 6.99M | Year: 2010

Euro-BioImaging brings together imaging technologies stretching from basic biological imaging with advanced light microscopy, in vivo molecular imaging of single cells to animal models up to the clinical and epidemiological level of medical imaging of humans and populations. Euro-BioImaging, in close consultation with its stakeholders, will address the imaging requirements of both biological and medical imaging research communities by creating a coordinated and harmonized plan for infrastructure deployment in Europe. Euro-BioImaging infrastructures will be planned to provide access to state-of-the-art equipment as well as to provide training and continue the development of imaging technologies to be able to offer them as new services. The vision of Euro-BioImaging is to provide a clear path of access to imaging technologies for every biomedical scientist in Europe. The Euro-BioImaging infrastructure will be focused on imaging technologies grouped around different scales of biological organization, from the single molecule to the whole human organism. Euro-BioImaging will therefore develop a plan to construct and operate a set of complementary and strongly interlinked infrastructure facilities appropriately distributed across the European member states. To achieve this, Euro-BioImaging will define the legal and governance framework with its currently 22 member states and develop a finance plan in close cooperation with national funding bodies as well as with the European Commission. The key objective of the Euro-BioImaging preparatory phase project is to integrate these plans into an overarching business plan that provides a realistic basis for construction and operation of the Euro-BioImaging infrastructure. Through the combination of these technological and strategic objectives, Euro-BioImaging will be able to address the key elements of successful infrastructures: supporting research, training and innovation in biomedical imaging across Europe.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-01-2014 | Award Amount: 7.27M | Year: 2015

This programme of work will advance the understanding of the combined effects of factors that cause poor lung function, respiratory disability and the development of COPD . This will be achieved by examination of determinants of lung growth and lung function decline within existing cohorts that cover the whole life course, and which have followed, in detail, the respiratory health status of over 25000 European children and adults from the early 1990s to the present day. Following a comprehensive programme of risk factor identification we will generate a predictive risk score. The programme includes 1) identification of behavioural, environmental, occupational, nutritional, other modifiable lifestyle, genetic determinant of poor lung growth, excess lung function decline and occurrence of low lung function, respiratory disability and COPD within existing child and adult cohorts 2) generation of new data to fill gaps in knowledge on pre-conception and transgenerational determinants and risk factors 3) validation of the role of risk factors by integration of data from relevant disciplines, integration of data from the cohort-related population-based biobanks and exploitation of appropriate statistical techniques 4) generation of information on change in DNA methylation patterns to identify epigenetic changes associated with both disease development and exposure to specific risk factors 5) generation of a predictive risk score for individual risk stratification that takes account of the combined effects of factors that cause poor lung growth, lung function decline, respiratory disability, and COPD and 6) implementation of an online interactive tool for personalised risk prediction based which will be disseminated freely and widely to the population, patients and health care providers. The work will provide an evidence base for risk identification at individual and population level that can underpin future preventive and therapeutic strategies and policies.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-05-2014 | Award Amount: 8.44M | Year: 2015

Arterial hypertension affects up to 45% of the general population and is responsible for 7.1 million deaths per year worldwide. Although a large therapeutic arsenal exists, blood pressure control is sub-optimal in up to two thirds of patients. Yet, even small increments in blood pressure are associated with increased cardiovascular risk, with 62% of cerebrovascular disease and 49% of ischemic heart disease being attributable to hypertension. Detection of secondary forms of hypertension is key to targeted management of the underlying disease and prevention of cardiovascular complications. Endocrine forms of hypertension represent major targets for stratified approaches of health promotion. They include a group of adrenal disorders resulting in increased production of hormones affecting blood pressure regulation: primary aldosteronism (PA), pheochromocytoma/functional paraganglioma (PPGL) and Cushings syndrome (CS). These diseases are associated with increased cardiovascular and metabolic risk and with diminished quality of life. This project will develop and evaluate an omics-based stratified health promotion program for patients with endocrine forms of hypertension. We will define specific omics profiles for patients with PA, PPGL and CS by integrating high throughput genetics, genomics and metabolomics data with phenome annotations through bioinformatics modelling. Established profiles will be validated as stratification biomarkers and applied to the screening of referred hypertensive patients for both stratifying primary forms of hypertension for effective and cost efficient therapy as well as improving identification of endocrine causes for curative treatment and prevention of cardiovascular and metabolic complications. Omics-based profiling should allow identification of patients with preclinical phenotypes along with those hypertensives that cluster into specific endocrine groups who may benefit from personalised treatment.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.1.1-3 | Award Amount: 7.86M | Year: 2012

Users of NGS technologies, producing large and numerous distinct types of omics data, demands statistical methods to combat data and knowledge fragmentation and inappropriate procedures for data analysis. Yet, the current a gap between the available tools for analysis of a single omics data-type versus the requirement of biomedical scientists to understand the integrated results derived from several omics data-types, threatens to further increase due to the accelerated capacity of data production. STATegra will therefore improve and develop new statistical methods enabling accurate collection and integration of omics data while providing user-friendly packaging of STATegra tools targeting biomedical scientists. To close the gap between the present sub-optimal utilization of omics data and the power of statistics, STATegra develops statistical methods targeting efficient experimental design, data gathering, missing data, noisy data, current knowledge, meta-analysis and integrative data analysis. Importantly, STATegra facilitates understanding and use of omics data by forcing abstract concepts including knowledge, design, dirty data, visualization, causality and integration to be embedded in a real yet prototypical biomedical context. STATegra is positioned to ensure that the collective output of the statistical STATegra methods is relevant and subject to statistical and experimental validation and iteration. STATegra mimics a user-driven IT development strategy, by involving real biomedical users as beta-testers. To deliver beyond current exploratory tools, our consortium accumulates the necessary strong statistical, technological, and molecular expertise. The strong lead by research intensive SMEs, with proven track-record in software deployment, translates STATegra to a wide existing community base. STATegra accelerates the production of relevant statistical tools impacting a broad community of biomedical scientists in research, industry, and healthcare.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-2 | Award Amount: 3.85M | Year: 2012

OPTIMISTIC is a proposal for a European collaborative project of doctors, scientists, relevant stakeholders (TREAT-NMD, patient organizations) and SMEs with the aim to improve clinical practice for patients suffering from a rare, inherited, and neglected disease, myotonic dystrophy type 1 (DM1). It is one of the most variable human diseases with complex, multi-systemic and progressively worsening clinical manifestations. Despite the huge impact of DM1 on the daily life of both patients and their family members, DM1 patients fail to receive the quality of healthcare that is available as they are not assertive users of the health care system. There is no cure for DM1. The aim of treatment is to relieve impairments, reduce limitations and support participation in everyday activities. Based on our DM1-specific model which shows that physical activity and experienced fatigue are main determinants of DM1 health status (Kalkman 2007), OPTIMISTIC investigates the effect of cognitive behavioural therapy (CBT) in combination with exercise training to improve functional capacity and to stimulate an active lifestyle. OPTIMISTIC compares the outcome of a treatment regimen with regular management in a multi-centre, assessor-blinded, randomized controlled trial, designed to 1) result in evidence-based clinical guidelines on exercise and cognitive behavioural therapy in DM1, 2) capture clinically meaningful changes in existing and novel outcome measures, and 3) identify both individual and composite biomarkers as surrogate treatment outcome measures that are reflective of the disease state. There is an urgent need for an European clinical trial infrastructure for DM1. High prioritization of this is required to enhance the speed of clinical development of new putative DM1 therapeutics approaching the market. OPTIMISTIC will provide this and safeguard the rapid uptake of the developed clinical guidelines ensuring improvements in DM1 care and quality of life.

Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2010-1.1.31 | Award Amount: 8.95M | Year: 2011

Nanoscale objects interact with living organisms in a fundamentally new manner, ensuring that a fruitful marriage of nanotechnology and biology will long outlast short term imperatives. Therefore, investment in an infrastructure to drive scientific knowledge of the highest quality will have both immediate benefits of supporting the safety assessment of legacy nanomaterials, as well as pointing towards future (safe) applications with the lasting benefits to society. There are immediate priorities, for few doubt that serious damage to confidence in nanotechnology, unless averted, could result in missed opportunities to benefit society for a generation, or more. QNano will materially affect the outcome, at this pivotal moment of nanotechnology implementation. The overall vision of QNano is the creation of a neutral scientific & technical space in which all stakeholder groups can engage, develop, and share scientific best practice in the field. Initially it will harness resources from across Europe and develop efficient, transparent and effective processes. Thereby it will enable provision of services to its Users, and the broader community, all in the context of a best-practice ethos. This will encourage evidence-based dialogue to prosper between all stakeholders. However, QNano will also pro-actively seek to drive, develop and promote the highest quality research and practices via its JRA, NA and TA functions, with a global perspective and mode of implementation. QNano will also look to the future, beyond the current issues, and promote the growth and development of the science of nanoscale interactions with living organisms. By working with new and emerging scientific research communities from medicine, biology, energy, materials and others, it will seek to forge new directions leading to new (safe, responsible, economically viable) technologies for the benefit of European society.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: ENV.2008. | Award Amount: 6.08M | Year: 2009

The rapid worldwide increase in mobile phone use in adolescents and, more recently, children has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. The current project aims to assess the potential carcinogenic effects of childhood and adolescent exposure to RF and ELF from mobile telephones on tumours of the central nervous system. The study will include approximately 1,000 cases of malignant and benign brain tumours aged 10 to 24 years and their respective controls from 15 countries (7 of which have funding under this contract). The project will build upon the methodological experience (both in terms of exposure assessment and epidemiological design) collected within the INTERPHONE study. Particular attention will be paid to issues of: potential selection bias related to the very low response rates of population-based controls by selecting hospitalized controls with specific diagnoses, representative of the general population and unrelated to mobile phone use ; and potential recall errors by validating questionnaire responses with the help of network operators and repeat questionnaires. Improved exposure indices for RF will be derived taking into account spatial distribution of energy in the brain at different ages; ELF from the phones will also be considered, as well as other important sources of EMF in the general environment of young people. The proposed age range is the most cost efficient to answer the question (because of latency) of brain cancer risk from exposure in childhood and adolescence. The timing of the project is optimal (2010-2014) because of the increasing prevalence of heavy use among adolescents and, in the last 5-10 years, children, without hands-free kits, particularly in Southern European countries and Israel.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.6.3 | Award Amount: 13.61M | Year: 2008

The GENESIS Project has the objective of providing Environment management and Health actors with an innovative solution based on advanced ICT. Relying on interoperability standards and harmonization process, GENESIS helps to constitute complex information networks, by combining benefits of various information systems with a collaborative systems approach. The proposed generic solution allows easy deployment and customization to thematic needs on a wide range of applications, at regional, national or Europe levels for various thematic fields. The main benefits of GENESIS solution are two-fold :-to improve and facilitate actors daily practices in relation with the management of environmental data; -to perform an essential step in the deployment of the Single Information Space for the environment in Europe. The GENESIS solution will be validated through dedicated scenarios addressing thematic fields of Air Quality, Water Quality and their impact on Health. For the final benefits and information of European citizens, the needs of Environment and Health stakeholders are covered through fundamental services like : -environment monitoring,\n-multi-criteria finding of the information; -visualization and combination of static or near-real-time information; -fusion of various sources of environmental data; -correlation between environmental with health data; -support of decision making processes; -support of the risk management and response to crisis; -near-real-time information of citizens. The GENESIS generic solution is open and sustainable as based on de facto and emerging standards (OGC, OASIS, INSPIRE,...). Moreover, the GENESIS project development integrates current state of the art and innovative researches of major EC or ESA projects. GENERIS project represents an important step in operational environmental management in Europe thus paving the way to an effective wide deployment of the solution as part of the future Single European Information Space for Environment.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-1.4-4 | Award Amount: 14.73M | Year: 2009

For many disabling or fatal diseases, there is pre-clinical or clinical evidence of the potential therapeutic efficacy of gene therapy and, yet, the limitations of current gene transfer technologies have prevented success or even caused serious adverse events leading to termination of trials. PERSIST will explore the use of highly innovative gene-modifying and delivery technologies and capitalize on recent discoveries in gene expression control to develop radical solutions to the problem of precisely controlling the fate and expression of exogenous genetic information in gene therapy with applications in these and other deadly diseases. Our proposal combines 20 of Europes outstanding experts from 8 countries in the field of genetic engineering for persisting gene expression. Partners have pioneered the use of Zinc Finger Nucleases, engineered recombinases and transposases for gene targeting, synthetic promoters, epigenetic switches and micro-RNA for regulating gene expression, developed state-of-the-art gene delivery platforms based on lentiviral, AAV and gutless adenoviral vectors, conducted front-line clinical trials, and productively collaborated in previous FP projects. PERSIST includes 16 work packages of which 6 focus on vector innovations (part A: emerging technologies), 6 on applications & evaluation (part B), 1 on process development and the remaining 2 on training/dissemination and project management including IPR issues. Targeting deadly diseases, such as inherited immunodeficiencies, storage disorders and haemophilias, PERSIST is in line with the Strategic Research Agenda (SRA) of the Innovative Medicines Initiative (IMI) and will result in: faster discovery and development of better medicines; more attractive professional environment for scientists; better European expertise and know-how to attract biomedical R&D investment in Europe; and a stronger competitive advantage for SMEs, spin-offs and start-ups to enhance Europes economy.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: NMP.2013.1.1-2 | Award Amount: 5.28M | Year: 2013

The major bottleneck for plant biomass processing is fiber saccharification: the conversion of cell wall lignocellulosic biomass into fermentable sugars (en route to production of value-added chemicals like second generation biofuels). Some microbes enhance this step by using natural self-assembling proteinaceous nanocatalists known as cellulosomes. CellulosomePlus targets rational design of optimized cellulosomes to overcome this problem.This would allow efficient production of biofuels from low-value raw materials like inedible parts of plants and industrial residues (which are all renewable, sustainable and inexpensive). First we propose to characterize the physicochemical and structural properties (including mechanostability) as well as interactions of enzymes and scaffolds from natural cellulosomes and non-cellulosomal components. In parallel, we will characterize a suitable residual substrate from municipal waste (organic fraction of municipal solid waste) and develop improved assays to reliably follow cellulosomal enzymatic activity. The acquired knowledge will be complemented with rapid computational modelling at the atomic and supramolecular levels for testing and predictions. Experimental and theoretical knowledge will be then integrated to design improved cellulosomes (with high-selectivity, activity and cost-effectiveness). Further improvement will be obtained by iteration using high throughput screening of components. The improved cellulosomes generated through this innovative multidisciplinary approach represent a step towards green chemistry since they are biodegradable proteinaceous materials and therefore by-products and/or wastes are minimized due to the high enzymatic selectivity. Finally, the production of the optimized cellulosomes (and the process involved) will be scaled up to preindustrial scale to demonstrate their viable commercial production. These results will be patented and a roadmap will be drawn up towards future standardization.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.4.2 | Award Amount: 3.80M | Year: 2008

The objective of the project KIWI is to develop an advanced knowledge management system (the KIWI system) based on a semantic wiki. This system will support collaborative knowledge creation and sharing, and use semantic descriptions and reasoning as a means to intelligently author, change and deliver content. A particularly salient aspect of combining wikis with advanced semantic technologies is that the wiki still is a generic and flexible tool, but semantic technologies allow to provide specific support for the user based on domain, context, role, and experience.\n\nThe main outcomes of the project will be (1) an enhanced wiki vision (the KIWI vision) describing how the convention over configuration paradigm of wikis combined with semantic technologies can lead to flexible and problem-oriented knowledge management, (2) a collaborative, web-based environment (the KIWI system) that provides support for knowledge sharing, knowledge creation, and coordination in software and project knowledge management, (3) the evaluation of this system in two concrete, representative use cases at our industry partners, and (4) the KIWI handbook, describing the project vision, the KIWI system functionalities, as well as giving recommendations and best practices for using the system in concrete knowledge management scenarios.\n\nThe KIWI consortium brings together leading research groups (SRFG, AAU, BUT, LMU Munich) in the areas of semantic wikis, reasoning, information extraction, personalisation, and knowledge management for software processes. These are matched by two large international corporations in knowledge intensive areas (Sun Microsystems and WM-data) that offer use cases demonstrating a clear need for the advanced knowledge management we envision in the project, and by a SME specialised in dissemination of semantic technologies to industry.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE-2007-2-2-07 | Award Amount: 7.77M | Year: 2009

Europe is facing major diet related health problems. Attitudes to eating habits have to be changed and the benefits of alternative treatment regimes substantiated. This can only be achieved by providing guidelines regulating health claims based on scientific data. Thus, there is a unique opportunity to use gut flora in potential treatment regimes and as a preventive target for major diet related health problems. TORNADO consortium proposes a systemic and comprehensive mechanistic approach to deliver scientific data that can be compiled as guidelines for European authorities. TORNADO will determine the influence of diet on the gut flora and highlight the impact of gut flora on the immune system/other organ systems. TORNADO aims to investigate molecular targets that are subject to regulation by gut flora and diet that sustain health. This will be done by an increasing level of specificity, from (1) investigations of dietary habits and health in population cohorts, through (2) intervention studies in humans and animals and (3) analyses of the intestine and immune system, and also organs like adipocyte tissue, liver & brain, to pinpointing the impact of dietary influence on (4) cells and (5) potential functional molecular targets. TORNADO will deliver data that can be used to recommend biomarkers for evaluating effects of diet or microbes; refute, substantiate or improve health claims of existing products; generate novel functional food products. TORNADOs approach of microbe-to-mouse-to-man validation of dietary influence will enable more solid evidence for health claims and provide concrete deliverables e.g. Roadmaps to Health, Tailor-made Health-monitoring. Continuous state-of-the-art dissemination programs will increase impact. TORNADOs program will accelerate future design of personalized functional food for specific target groups. The evidence-based data delivered by TORNADO will have long lasting effects on health among European citizens well beyond 2012.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.2.1-3 | Award Amount: 14.90M | Year: 2010

OPTiMiSE (OPtimization of Treatment and Management of Schizophrenia in Europe) will focus on two goals: optimising current treatments in Schizophrenia and explore novel therapeutic options for schizophrenia. The project intends to both address basic, but so far unanswered, questions in the treatment of schizophrenia and develop new and experimental interventions. It is expected that the project will lead to evidence that is directly applicable to treatment guidelines, will explore the development of novel treatments and will identify potential mechanisms for new drug development. To achieve these goals we have assembled a European team of experts that is second to none in the world. Together we will pursue the following objectives: -To use MRI to optimise treatment outcome and to facilitate prediction of response to treatment; - To provide a rational basis for antipsychotic choices in the treatment of first episode schizophrenia or schizophreniform disorder; - To improve functional outcome and reduce drug discontinuation by means of psychosocial interventions. - To explore the potential of cannabidiol CBD, a modulator of endocannabinoid functioning, as an alternative to D2 based antipsychotics - To validate a new approach to improve cognitive performance in patients with cognitive deficits on the basis of their genetic make up; - To use theoretically driven neurochemical imaging (MRS) and empirically driven genetic/genomic markers as predictors of response to treatment.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 3.10M | Year: 2009

Cardiovascular diseases are the leading cause of death and disability in the European population and represent a great burden of suffering and costs. Their complex etiology originates from different pathological stimuli and involves different cell types, resident in the vascular wall or infiltrating from the blood. The adaptation of the vasculature to physiological and pathophysiological forces depends on both the communication between its cellular components and their interaction with the extracellular matrix (ECM). When subjected to enhanced stretch, cyclic mechanical strain, or shear stress, blood vessels undergo typical transformations in wall shape that are always associated with alterations of the ECM and cellular composition, collectively described as vascular remodelling. Remodelling processes occur specifically in small arteries and arterioles, which show extreme changes in their size and function (microvascular remodelling). This is especially the case in hypertensive or diabetic patients, and contributes to a vicious cycle resulting in organ dysfunction and progression of vascular disease. A multidisciplinary approach is required to better understand vascular remodelling processes. We propose an interdisciplinary ITN to promote excellence in vascular biology, with focus on small vessels/arteries and their ECM. This will enhance the interaction between 8 academic groups and one SME in 7 European countries, specialized in physiology, signalling mechanisms, cell-cell and cell-matrix interactions in vascular endothelium and smooth muscle, as well as in drug discovery and development. The ITN will provide a specialized training ground by connecting investigations of the biology of vascular cells and their surrounding ECM in an innovative manner. It will therefore promote the careers of young investigators by specialising them in a field of vascular biology with a great potential for the future.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.56M | Year: 2015

Gene therapy is expected to play a key role in next-generation medicine by correcting the underlying genetic causes of disease, thereby facilitating personalised medicine. Current gene therapy methods possess undesirable side effects, including insertional mutagenesis, toxicity, low efficiency and off-target cutting. Questions also remain regarding the optimal methods for delivering nucleases into cells and tissues. These limitations will be addressed through the original and innovative approach of the ClickGene network. ClickGenes research objectives are to train 14 ESRs in the field of biomaterials development with specific focus on, i.) site-selective genetic engineering, ii.) liposomal nanoparticle drug delivery, and iii.) optogenetic diagnostic probes for epigenetic base detection. Most of our academic partners are key members of COST Action CM1201: Biomimetic Radical Chemistry and all have outstanding international reputations as scientific leaders in their field. This COST Action will play a vital role in both networking and training elements of ClickGene, and in combination with transferable skills training, intersectorial and cross-disciplinary secondment, and industry targeted workshops, the education of biomaterials chemists with expertise in click-chemistry and cutting edge application areas of gene therapy, nanotechnology and biological diagnostics will be achieved. The training provided will match the skills required by next-generation research leaders in biopharmaceutical, nanotechnology, biodiagnostic and other industries. Allied to academic strength in this network, ClickGene features highlycompetitive industry partners with expertise in commercialisation of nucleic acid click-chemistry (baseclick, ATDBio) and liposomal and lipidome technology (LipiNutraGen). Thus, synergy between both commercial and academic partners will enable ESRs to develop gene-targeted technology within a highly productive, engaging, and exciting training network.

Chronic aortic aneurysms are permanent and localized dilations of the aorta that remain asymptomatic for long periods of time but continue to increase in diameter before they eventually rupture. Left untreated, the patients prognosis is dismal, since the internal bleeding of the rupture brings about sudden death. Although successful treatment cures the disease, the risky procedures can result in paraplegia from spinal cord ischaemia or even death, particularly for aneurysms extending from the thoracic to the abdominal aorta and thus involving many segmental arteries to the spinal cord, i.e. thoracoabdominal aortic aneurysms of Crawford type II. Although various strategies have achieved a remarkable decrease in the incidence of paraplegia, it is still no less than 10 to 20%. However, it has been found that the deliberate occlusion of the segmental arteries to the paraspinous collateral network finally supplying the spinal cord does not increase rates of permanent paraplegia. A therapeutic option, minimally invasive segmental artery coil embolization has been devised which proceeds in a staged way to occlude groups of arteries under highly controlled conditions after which time must be allowed for arteriogenesis to build a robust collateral blood supply. PAPA-ARTiS is a phase II trial to demonstrate that a staged treatment approach can reduce paraplegia and mortality dramatically. It can be expected to have both a dramatic impact on the individual patients quality of life if saved from a wheelchair, and also upon financial systems through savings in; 1) lower costs in EU health care; 2) lower pay-outs in disability insurance (est. at 500k in Year 1), and; 3) loss of economic output from unemployment. Approx. 2500 patients a year in Europe undergo these high risk operations with a cumulative paraplegia rate of over 15%; therefore >100M per year in costs can be avoided and significantly more considering the expected elimination of type II endoleaks.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENV.2013.6.2-1 | Award Amount: 9.99M | Year: 2014

Water and water-related services are major components of the human wellbeing, and as such are major factors of socio-economic development in Europe; yet freshwater systems are under threat by a variety of stressors (organic and inorganic pollution, geomorphological alterations, land cover change, water abstraction, invasive species and pathogens. Some stressors, such as water scarcity, can be a stressor on its own because of its structural character, and drive the effects of other stressors. The relevance of water scarcity as a stressor is more important in semi-arid regions, such as the Mediterranean basin, which are characterized by highly variable river flows and the occurrence of low flows. This has resulted in increases in frequency and magnitude of extreme flow events. Furthermore, in other European regions such as eastern Germany, western Poland and England, water demand exceeds water availability and water scarcity has become an important management issue. Water scarcity is most commonly associated with inappropriate water management, with resulting river flow reductions. It has become one of the most important drivers of change in freshwater ecosystems. Conjoint occurrence of a myriad of stressors (chemical, geomorphological, biological) under water scarcity will produce novel and unfamiliar synergies and most likely very pronounced effects. Within this context, GLOBAQUA has assembled a multidisciplinary team of leading scientists in the fields of hydrology, chemistry, ecology, ecotoxicology, economy, sociology, engineering and modeling in order to study the interaction of multiple stressors within the frame of strong pressure on water resources. The aim is to achieve a better understanding how current management practices and policies could be improved by identifying the main drawbacks and alternatives.

Geldmacher C.,Ludwig Maximilians University of Munich | Koup R.A.,National Institute of Allergy and Infectious Diseases
Trends in Immunology | Year: 2012

During HIV infection, it is unclear why different opportunistic pathogens cause disease at different CD4 T cell count thresholds. Early work has shown that CD4 T cell depletion is influenced both by cellular activation status and expression of viral entry receptors. More recently, functional characteristics of the CD4 T cells, such as cytokine and chemokine production, have also been shown to influence cellular susceptibility to HIV. Here, we examine how functional differences in pathogen-specific CD4 T cells could lead to their differential loss during HIV infection. This may have implications for when different opportunistic infections occur, and a better understanding of the mechanisms for functional imprinting of antigen-specific T cells may lead to improvements in design of vaccines against HIV and opportunistic pathogens. © 2012 Elsevier Ltd.

Papenfort K.,Princeton University | Papenfort K.,Ludwig Maximilians University of Munich | Vanderpool C.K.,University of Illinois at Urbana - Champaign
FEMS Microbiology Reviews | Year: 2015

Bacterial small regulatory RNAs (sRNAs) are commonly known to repress gene expression by base pairing to target mRNAs. In many cases, sRNAs base pair with and sequester mRNA ribosome-binding sites, resulting in translational repression and accelerated transcript decay. In contrast, a growing number of examples of translational activation and mRNA stabilization by sRNAs have now been documented. A given sRNA often employs a conserved region to interact with and regulate both repressed and activated targets. However, the mechanisms underlying activation differ substantially from repression. Base pairing resulting in target activation can involve sRNA interactions with the 5' untranslated region (UTR), the coding sequence or the 3' UTR of the target mRNAs. Frequently, the activities of protein factors such as cellular ribonucleases and the RNA chaperone Hfq are required for activation. Bacterial sRNAs, including those that function as activators, frequently control stress response pathways or virulence-associated functions required for immediate responses to changing environments. This review aims to summarize recent advances in knowledge regarding target mRNA activation by bacterial sRNAs, highlighting the molecular mechanisms and biological relevance of regulation. © 2015 FEMS.

Steinhoff M.,University of California at San Francisco | Schauber J.,Ludwig Maximilians University of Munich | Leyden J.J.,University of Pennsylvania
Journal of the American Academy of Dermatology | Year: 2013

Rosacea is a common, chronic inflammatory skin disease of poorly understood origin. Based on its clinical features (flushing, chronic inflammation, fibrosis) and trigger factors, a complex pathobiology involving different regulatory systems can be anticipated. Although a wealth of research has shed new light over recent years on its pathophysiology, the precise interplay of the various dysregulated systems (immune, vascular, nervous) is still poorly understood. Most authors agree on 4 major clinical subtypes of rosacea: erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea. Still, it needs to be elucidated whether these subtypes develop in a consecutive serial fashion or if any subtypes may occur individually as part of a syndrome. Because rosacea often affects multiple family members, a genetic component is also suspected, but the genetic basis of rosacea remains unclear. During disease manifestation and early stage, the innate immune system and neurovascular dysregulation seem to be driving forces in rosacea pathophysiology. Dissection of major players for disease progression and in advanced stages is severely hampered by the complex activation of the innate and adaptive immune systems, enhanced neuroimmune communication, profound blood vessel and possibly lymphatic vessel changes, and activation of almost every resident cell in the skin. This review discusses some of the recent findings and aims to build unifying hypotheses for a modern understanding of rosacea pathophysiology. © 2013 by the American Academy of Dermatology, Inc.

Astumian R.D.,University of Maine, United States | Astumian R.D.,Ludwig Maximilians University of Munich
Biophysical Journal | Year: 2010

Molecular motors are first and foremost molecules, governed by the laws of chemistry rather than of mechanics. The dynamical behavior of motors based on chemical principles can be described as a random walk on a network of states. A key insight is that any molecular motor in solution explores all possible motions and configurations at thermodynamic equilibrium. By using input energy and chemical design to prevent motion that is not wanted, what is left behind is the motion that is desired. This review is focused on two-headed motors such as kinesin and Myosin V that move on a polymeric track. By use of microscopic reversibility, it is shown that the ratio between the number of forward steps and the number of backward steps in any sufficiently long time period does not directly depend on the mechanical properties of the linker between the two heads. Instead, this ratio is governed by the relative chemical specificity of the heads in the front-versus-rear position for the fuel, adenosine triphosphate and its products, adenosine diphosphate and inorganic phosphate. These insights have been key factors in the design of biologically inspired synthetic molecular walkers constructed out of DNA or out of small organic molecules. © 2010 by the Biophysical Society.

Rock J.,University of California at San Francisco | Konigshoff M.,Ludwig Maximilians University of Munich
American Journal of Respiratory and Critical Care Medicine | Year: 2012

The exploration of the endogenous regenerative potential of the diseased adult human lung represents an innovative and exciting task. In this pulmonary perspective, we discuss three major components essential for endogenous lung repair and regeneration: epithelial progenitor populations, developmental signaling pathways that regulate their reparative and regenerative potential, and the surrounding extracellular matrix in the human diseased lung. Over the past years, several distinct epithelial progenitor populations have been discovered within the lung, all of which most likely respond to different injuries by varying degrees. It has become evident that several progenitor populations are mutually involved in maintenanceandrepair,which is highly regulatedbydevelopmental pathways, such as Wnt or Notch signaling. Third, endogenous progenitor cells and developmental signaling pathways act in close spatiotemporal synergy with the extracellular matrix. These three components define and refine the highly dynamic microenvironment of the lung, which is altered in a disease-specific fashion in several chronic lung diseases. The search for the right mixture to induce efficient and controlled repair and regeneration of the diseased lung is ongoing and will open completely novel avenues for the treatment of patients with chronic lung disease. Copyright © 2012 by the American Thoracic Society.

Schermelleh L.,Ludwig Maximilians University of Munich | Heintzmann R.,King's College London | Heintzmann R.,Friedrich - Schiller University of Jena | Heintzmann R.,Institute of Photonic Technology | Leonhardt H.,Ludwig Maximilians University of Munich
Journal of Cell Biology | Year: 2010

For centuries, cell biology has been based on light microscopy and at the same time been limited by its optical resolution. However, several new technologies have been developed recently that bypass this limit. These new super-resolution technologies are either based on tailored illumination, nonlinear fluorophore responses, or the precise localization of single molecules. Overall, these new approaches have created unprecedented new possibilities to investigate the structure and function of cells. © 2010 Schermelleh et al.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.1.1-7 | Award Amount: 15.68M | Year: 2008

Despite major efforts, identifying susceptibility genes for common human diseases - cancer, cardiovascular, inflammatory and neurological disorders - is difficult due to the complexity of the underlying causes. The dog population is composed of ~ 400 purebred breeds; each one is a genetic isolate with unique characteristics resulting from persistent selection for desired attributes or from genetic drift / inbreeding. Dogs tend to suffer from the same range of diseases than human but the genetic complexity of these diseases within a breed is reduced as a consequence of the genetic drift and due to long-range linkage disequilibrium the number of SNP markers needed to perform whole genome scans is divided by at least ten. Here, we propose a European effort gathering experts in genomics to take advantage of this extraordinary genetic model. Veterinary clinics from 12 European countries will collect DNA samples from large cohorts of dogs suffering from a range of thoroughly defined diseases of relevance to human health. Once these different cohorts will be built, DNA samples will be sent to a centralized, high-throughput SNP genotyping facility. The SNP genotypes will be stored in central database and made available to participating collaborating centres, who will analyze the data with the support of dedicated statistical genetics platforms. Following genome wide association and fine-mapping candidate genes will be followed up at the molecular level by expert animal and human genomics centers. This innovative approach using the dog model will ultimately provide insights into the pathogenesis of common human diseases its primary goal.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.56M | Year: 2014

Explosive volcanic eruptions are an unavoidable natural hazard: Volcanic ash, the ejected lethal mixture of crystals, lava, glass and older rocks, is the most far-reaching threat. In April 2010, the ash cloud from Eyjafjall volcano in Iceland, a comparatively small event, paralysed large parts of Europe for up to one week in a manner unique in history. The impact was dramatic: several million passengers were grounded due to closed air pace and decelerated or halted industrial production caused several billion Euros of estimated economic loss. This scenario was largely amplified by the quasi-Babylonian lack of understanding and interaction amongst volcanologists, meteorologists, atmospheric researchers, engineers, private sector and politics. This eruption was not a singular accident: Europe has active volcanoes and is surrounded by others and must be prepared for similar future events. This requires a comprehensive and supra-disciplinary approach to allow for an encompassing mechanistic and quantitative understanding of the physico-chemical processes during the lifecycle of volcanic ash: from formation in a volcano, through changes during the dispersal in the atmosphere to the impacts on life and society. VERTIGO will address this challenging issue with a unique and innovative portfolio of partners from academia, research institutes and the private sector from eight European countries. We will offer an unmatched platform for research and training for highly-skilled students with a background in geology/volcanology, petrology/chemistry, informatics, biology, toxicology, fluid dynamics and/or engineering. The research-through-training projects for 13 students accomplish the EUROPE2020 strategy for a modern system of education. They will be educated in scientific and transferable skills, spiced with experience in private sector applications, to qualify for career opportunities in academia, research institutes, civil protection and private sector.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.41M | Year: 2013

CALIPSO is a genuine interdisciplinary and intersectorial research network composed of nine academic research institutions and three industrial partners, thus presenting an example of true translational research and training of young researchers in communicating and transferring achievements from different model organisms directly to industrial partners. CALIPSO aims at identifying environmentally triggered regulatory calcium signals and protein phosphorylation events that control photosynthesis and metabolism. CALIPSO partners work with a wide range of different organisms covering the full phylogenetic spectrum from algae to higher plants including economically important crops. They combine a wide spectrum of newest technologies in molecular biology, biochemistry, proteomics, metabolomics, genetics, bioinformatics and systems biology to uncover how photosynthetic organisms acclimate to changing environmental conditions or stress. This novel combination of scientific expertise combined with industrial applications is one of the major strengths of CALIPSO, exposing the participating researchers to different schools of thought. The active participation of Bayer CropScience Gent and Ecoduna as full network partners, and Photon Systems Instruments as associated partner, will enable intersectorial industry-academia cooperation with the long term objectives of (i) improving yield and stress robustness of crops and (ii) developing microalgal-biotechnology. The integrated systematic training programme of CALIPSO will boost the future employability of the young researchers by acquisition of technical skills for their work in academia or the private sector and also essential complementary skills for their future career. The training programme comprises three workshops on state-of-the art techniques - and one on industrial-relevant skills. This is completed by secondments to partner laboratories and industry and network-wide training events in further complementary skills.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.2-1 | Award Amount: 7.88M | Year: 2013

Atherosclerosis and its most disabling sequelae, coronary artery disease (CAD) and stroke, are leading causes of death in Europe. Until now, preventive and therapeutic interventions for these diseases aim at ameliorating the effects of established cardiovascular risk factors. More recently, results of genome-wide association (GWA) studies added to our perception of mechanisms leading to atherosclerosis. At present, over 40 CAD and several genomic risk loci have been identified, the majority through efforts led by the applicants. Some genes at these loci work through known risk factors such as lipids and, in fact, are already established or evolving treatment targets. However, this is not true for the majority of risk variants, which implies that key pathways leading to atherosclerosis are yet to be exploited for therapeutic intervention. This EU network (CVgenes@target), which brings together an equal number of SME- and academic partners, will utilize genomic variants affecting atherosclerosis risk for identification of both underlying genes and affected pathways in order to identify, characterize, and validate novel therapeutically relevant targets for prevention and treatment of CAD and stroke. In programme 1 we will investigate molecular mechanisms at the genomic loci in order to further unravel causal genes, in programme 2 we will explore in vitro and in vivo whether the pathways disturbed by causal genes are suitable for therapeutic intervention, and in programme 3 we will establish assays and initiate high throughput screens to tackle therapeutically attractive targets. Our resources including large OMICs and state-of-the-art bioinformatics platforms as well as multiple, already established in vitro and in vivo models support the feasibility of the approach. In fact, two genomic risk loci (ADAMTS7 (CAD); HDAC9 (stroke and CAD)), both identified in GWA studies under direction of the applicants, already revealed attractive targets for therapeutic intervention.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 4.07M | Year: 2013

DNA Nanotechnology is an emerging interdisciplinary area that will underpin the development of future nanoscience-based technologies for areas such as medicine, diagnostic tools, optics and electronics. DNA nanotechnology is based on the unique self-assembly properties of DNA which allow the rational design and synthesis of complex nanoscale structures with predictable form and function. Many other materials can be integrated in such DNA structures to create highly functional nanodevices. The Marie Curie ITN EScoDNA will establish a sustainable European School of DNA Nanotechnology. By providing high quality training to young scientists, EScoDNA will improve their career prospects in both public and private sectors; it will also strengthen the competitive position of European research and industry in this promising strategic field. A network of leading European researchers, two SMEs and a major commercial research institute will work together to foster the development of a new generation of scientists with the skills required to meet future challenges in DNA nanotechnology, from fundamental science to novel applications. The training program will involve collaborative research projects, including international secondments and exchange of data through a web-based Lab-Wiki Journal, and through summer schools and workshops. The industrial partners will be integrated in the training programme, and the two SMEs will coordinate training related to the commercial exploitation of new technologies, management and entrepreneurial skills. They will also take a lead in managing the protection and commercialization of new technologies arising from research with the ITN. The programme is designed to create a pool of highly qualified researchers prepared for a wide range of careers in bionanotechnology and nanofabrication and, especially, capable of contributing to the development of a strong European centre for the scientific and commercial development of DNA nanotechnology.

Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2012-IRSES | Award Amount: 269.20K | Year: 2012

Our society relies more and more on the finding of new materials for the advancement of technology. Prior to being used for applications and in order to be tailored to specific properties, materials have to be carefully characterized and the connection between their properties and underlying electronic, magnetic and crystallographic structure must be clearly understood. This is where electron and photon spectroscopies come into play. Thanks to their unique specificities and the use of synchrotron radiation, they have the capability to access all the requested information at the nanoscopic and the atomic levels with enhanced accuracy. However, this accuracy can only be achieved by comparison to a calculation based on a suitable theoretical model, as no reliable inversion of the experimental data can directly achieve such a necessary accuracy. Moreover, recent breakthroughs in their theoretical modelling make us hopeful that in the coming years calculations of the experimental signal will reach a predictive level, thereby offering the possibility to by-pass some expensive experiments. Multiple scattering is a major issue in the devising of an accurate and flexible framework that can deal in the same way with periodic and non-periodic materials, with nanostructures and over a very wide range of energies. The purpose of the present project is to offer the scientific community a unique computing platform able to deal with the characterization of all sorts of materials using various spectroscopies. To this purpose, we will gather the expertise of nine participants, all specialized in the multiple scattering description of spectroscopies. The sharing of complementary expertise will allow us to propose to the user (experimentalists and theoreticians) a coherent set of computer programs that will have the generality and the multi-technique capability lacking in the actual individual codes.

Agency: European Commission | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-2011-IAPP | Award Amount: 3.65M | Year: 2012

The current diagnosis of psychiatric disorders such as schizophrenia and mood disorders, is highly subjective, due to the lack of empirical markers or objective tests specific for these diseases. PSYCH-AID searchers to fill the gap thrpugh the in-parallel study of schizophrenia and mood disorder patients combining, validating and registering 4 sets of biomarker tests already in advanced stage of development in two other EU-FP7 projects of partners (MOODINFLAME and SchizDX). Biomarkers are based on activated immune response system in conjunction with an abnormal neuro-endocrine set point. PSYCH-AID aims at the developm,ent of clinically applicable blood assays identifying pateints/individuals with such activated set points by combining the efforts of academia and industry. PSYCH-AID unites 9 European partners excelling in this field: 5 academia and 5 SMEs. The intersectoral and interdisciplinary collaboration and exchange of researchers will foster the translation of fundamental clinical research into practical solutions for the diagnosis and treatment of people affected by schizophrenia or mood disorders. This fit perfectly with the IAPP scheme. PSYCH-AID contributes to building a long lasting collaboration between the partners, the first consortium in the world to put objective diagnostic and prognostic tests for psychiatric disorders into practice. European industry will benefit from this competitive lead. Since the disorders have a serious impact on the quality of life of the individuals affected, an improved diagnosis and prognosis will substantially contribute to improving their quality of life. Furthermore, PSYCH-AID gives the researchers involved a platform to acquire complementary skills, thus ameliorating their professional career opportunities.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP-2010-1.3-1 | Award Amount: 12.48M | Year: 2011

While there are standard procedures for product life cycle analysis, exposure, hazard, and risk assessment for traditional chemicals, is not yet clear how these procedures need to be modified to address all the novel properties of nanomaterials. There is a need to develop specific reference methods for all the main steps in managing the potential risk of ENM. The aim of MARINA is to develop such methods. MARINA will address the four central themes in the risk management paradigm for ENM: Materials, Exposure, Hazard and Risk. The methods developed by MARINA will be (i) based on beyond-state-of-the-art understanding of the properties, interaction and fate of ENM in relation to human health and the quality of the environment and will either (ii) be newly developed or adapted from existing ones but ultimately, they will be compared/validated and harmonised/standardised as reference methods for managing the risk of ENM. MARINA will develop a strategy for Risk Management including monitoring systems and measures for minimising massive exposure via explosion or environmental spillage.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-09-2015 | Award Amount: 28.14M | Year: 2016

Many HIV vaccine concepts and several efficacy trials have been conducted in the prophylactic and therapeutic fields with limited success. There is an urgent need to develop better vaccines and tools predictive of immunogenicity and of correlates of protection at early stage of vaccine development to mitigate the risks of failure. To address these complex and challenging scientific issues, the European HIV Vaccine Alliance (EHVA) program will develop a Multidisciplinary Vaccine Platform (MVP) in the fields of prophylactic and therapeutic HIV vaccines. The Specific Objectives of the MVP are to build up: 1.Discovery Platform with the goal of generating novel vaccine candidates inducing potent neutralizing and non-neutralizing antibody responses and T-cell responses, 2. Immune Profiling Platform with the goal of ranking novel and existing (benchmark) vaccine candidates on the basis of the immune profile, 3. Data Management/Integration/Down-Selection Platform, with the goal of providing statistical tools for the analysis and interpretation of complex data and algorithms for the efficient selection of vaccines, and 4. Clinical Trials Platform with the goal of accelerating the clinical development of novel vaccines and the early prediction of vaccine failure. EHVA project has developed a global and innovative strategy which includes: a) the multidisciplinary expertise involving immunologists, virologists, structural biology experts, statisticians and computational scientists and clinicians; b) the most innovative technologies to profile immune response and virus reservoir; c) the access to large cohort studies bringing together top European clinical scientists/centres in the fields of prophylactic and therapeutic vaccines, d) the access to a panel of experimental HIV vaccines under clinical development that will be used as benchmark, and e) the liaison to a number of African leading scientists/programs which will foster the testing of future EHVA vaccines through EDCTP

Max Planck Gesellschaft Zur Forderung Der Wissenschaften E.V., Jülich Research Center and Ludwig Maximilians University of Munich | Date: 2010-03-22

The present invention relates to a process for the hydrogenation, in particular the selective hydrogenation of unsaturated hydrocarbon compounds, such as the selective hydrogenation of acetylene to ethylene, using a hydrogenation catalyst comprising an ordered intermetallic compound, namely an ordered cobalt-aluminum or iron-aluminum intermetallic compound. According to another aspect, the present invention relates to a catalyst comprising a support and at least one specific ordered cobalt-aluminum and/or iron-aluminum intermetallic compound supported thereon, as well as to the use of specific ordered intermetallic cobalt-aluminum and iron-aluminum intermetallic compounds as catalysts. The ordered cobalt-aluminum and iron-aluminum intermetallic compounds proved to be highly selective and long-term stable catalysts, e.g. in the selective hydrogenation of acetylene to ethylene in a large excess of ethylene.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRAIA-1-2014-2015 | Award Amount: 10.13M | Year: 2015

ACTRIS-2 addresses the scope of integrating state-of-the-art European ground-based stations for long term observations of aerosols, clouds and short lived gases capitalizing work of FP7-ACTRIS. ACTRIS-2 aims to achieve the construction of a user-oriented RI, unique in the EU-RI landscape. ACTRIS-2 provides 4-D integrated high-quality data from near-surface to high altitude (vertical profiles and total-column), relevant to climate and air-quality research. ACTRIS-2 develops and implements, in a large network of stations in Europe and beyond, observational protocols that permit harmonization of collected data and their dissemination. ACTRIS-2 offers networking expertise, upgraded calibration services, training of users, trans-national access to observatories and calibration facilities, virtual access to high-quality data products. Through joint research activities, ACTRIS-2 develops new integration tools that will produce scientific or technical progresses reusable in infrastructures, thus shaping future observation strategies. Innovation in instrumentation is one of the fundamental building blocks of ACTRIS-2. Associated partnership with SMEs stimulates development of joint-ventures addressing new technologies for use in atmospheric observations. Target user-groups in ACTRIS-2 comprise a wide range of communities worldwide. End-users are institutions involved in climate and air quality research, space agencies, industries, air quality agencies. ACTRIS-2 will improve systematic and timely collection, processing and distribution of data and results for use in modelling, in particular towards implementation of atmospheric and climate services. ACTRIS-2 invests substantial efforts to ensure long-term sustainability beyond the term of the project by positioning the project in both the GEO and the on-going ESFRI contexts, and by developing synergies with national initiatives.

Klinikum Darmstadt Gmbh, TU Darmstadt and Ludwig Maximilians University of Munich | Date: 2011-09-20

Subject of the present invention are compounds with high affinity for the A protein, -synuclein or for Tau-PHF aggregates, which are suitable as preferably fluorescent probes for the in vivo diagnosis of neurodegenerative disorders like e.g. Alzheimers disease and Parkinsons disease. The compounds are characterized by suitable physicochemical properties (excitation wavelength, emission wavelength, Stokes shift, extinction) as well as a high affinity and selectivity for the target proteins.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SSH-2007-1.1-03 | Award Amount: 1.42M | Year: 2008

In 2000, EU leaders committed to the objective of making Europe the most dynamic and competitive knowledge-based economy in the world, capable of sustainable economic growth, with more and better jobs, greater social cohesion and respect for the environment. They drew up the Lisbon agenda to achieve this goal by 2010. The central strategy was based on policies to encourage investment in knowledge. Knowledge as a public good with potential spillovers is the rationale behind intellectual property protection and subsidies for investments in innovations that will potentially lead to high spillovers. University research that creates basic knowledge is a leading example of this. But research shows that spillovers are also generated from private firms R&D and that firms can therefore benefit from the presence of more innovative and more productive firms. But which universities and which firms are more innovative? And how does globalization influence the answer to these questions? Finally, how can policy influence the innovation process? This project aims at answering these questions, without forgetting their implications in terms of income inequality and volatility, which impacts on the political sustainability of the innovation dynamics.To do this, the first part of the project will focus more specifically on the knowledge sector itself. This second part of the project will look at the bigger picture, looking at the overall organization of firms in the global knowledge economy, as well as its implications on markets and inequality. The third part will contain a summary and policy recommendations: while the project brings together researchers at the frontier of academic knowledge on these topics, its outcomes will be highly policy-relevant. We plan to end the project with a summary and set of policy conclusions on research and innovation in the global knowledge economy.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.83M | Year: 2016

Metabolic disorders are at pandemic levels. Based on recent estimates, ~50% of Europeans are overweight, 20% are obese and 10% have type II diabetes. Obesity and insulin resistance impact European health to the tune of 110 billion per year. These disorders have genetic, nutritional and lifestyle causes. However, the molecular mechanisms that link nutrients and lifestyle to gene activity and chromatin are poorly understood, and drug targets are only starting to be identified. Pioneering experiments by ChroMe labs now reveal how sugars, exercise, the gut microbiome and novel drugs regulate chromatin. These novel links promise to substantially improve our understanding and treatment of metabolic disorders. National governments and the EU invest major resources to address the burden of the metabolic syndrome. However, there is an urgent need for expert human capital able to dissect metabolic diseases, exploit new targets and establish innovative therapies. No local nor international program currently provides adequate training at this emerging interface of chromatin and metabolism. ChroMe establishes a timely and intersectorial ETN that exploits Europes strengths in epigenetics, physiology and medicine to translate our molecular knowledge of chromatinmetabolism interactions into therapies. Our ESRs receive advanced training in emerging technologies, bioinformatic and translational approaches, and all engage in collaborative PhD projects co-supervised by academia and industry. ChroMes extensive transferable skills, dissemination and public engagement program equips our ESRs with the experience and personal network needed for a career in metabolic health. By systematically involving the non-academic sector at every level in our research, training and management, ChroMe will craft future European leaders with the necessary knowledge and skills to fight the metabolic syndrome pandemic.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SSH.2011.1.1-1 | Award Amount: 3.59M | Year: 2012

LLLightinEurope LifeLong Learning, Innovation, Growth and Human capital Tracks in Europe Among all Europeans between 24 and 65 years old who had a tertiary educational degree in 2010, 82.8% were working. In the same age group, 68.3% who completed secondary schooling were working. Only 46% of those who did not complete secondary schooling were working. It is apparent that if Europe wants to be working, higher education is the necessary foundation for being competitive in the labor market. Since this is not only true for generations of future workers currently in school, but equally so for those who are today in their 30s, 40s and 50s, Lifelong Learning must be essential to continued employability. The cumulative investment necessary to generate higher education degrees alone for adults over the next two decades across Europe may be 3.5 trillion euros or about 1.4% of European GDP per year. Even higher investments are required in non-formal and informal Lifelong Learning. To help guide this investment, this research project will find answers to the following urgent questions: 1. How do successful enterprises actively employ Lifelong Learning for their competitive advantage? 2. Which public policy environments facilitate Lifelong Learning for such enterprises and entrepreneurs? 3. How does Lifelong Learning interact with and promote innovativeness on the enterprise level? 4. How much of which skills do European adults actually have? 5. What are the actual learning mechanisms in adult life that lead to these skills? 6. What are the causal effects of these skills on growth, competitiveness and social cohesion? The research consortium includes nine universities and research institutes from four academic disciplines macro-econometrics, innovation dynamics, educational systems, psychometrics to establish empirically proven answers. All outputs of the project (models, reports and tools) are designed to guide, support and facilitate best practice and strategy among public policy officials, enterprise strategists, individual citizens and fellow scientists.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 2.30M | Year: 2009

Cellular differentiation from stem cells to fully functional mature cells is a multi step process executed by complex transcription programs. Once differentiated, cells must faithfully maintain their identity through cellular memory mechanisms. The utilisation of genetic information stored in linear DNA sequence occurs within the three dimensional context of chromatin, chromosomes and the nucleus, all of which contribute to gene regulation mechanisms. The main aim of this ITN is to get a comprehensive view on the mechanisms controling gene expression during cell differentiation by integrating studies on multiple regulatory levels from DNA binding transcription factors through to nuclear organization. We will take a multi-faceted approach addressing the functions of: (i) transcription factors and their co-factors (ii) chromatin domains and histone variants, (iii) epigenetic mechanisms of cellular memory and identity, (iv) global gene interactions in nuclear space and (iv) nuclear territories of gene activity. Genomics approaches will be employed to describe global changes in gene target networks and gene interactions in the nucleus during ES cell differentiation into the hepatic, neuronal and hematopoietic lineages. Proteomics will be employed for the characterization of transcription factor and epigenetic modifying complexes and of the in vivo protein composition of specialized chromatin domains. The research activities of this ITN are organized in the context of a multidisciplinary Training Program, which provides unique opportunities for the training of early stage researchers to address fundamental biological questions with far reaching implications in biotechnology and human health.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-5 | Award Amount: 3.91M | Year: 2012

The project aims to develop novel inhibitors of chronic autoimmune and inflammatory diseases by targeting members of the Src tyrosine kinase family. Src-family kinases have recently emerged as major therapeutic targets in malignant diseases but their suitability as potential targets of inflammatory diseases has not yet recieved widespread acceptance. On the other hand, members of the applicant consortium have recently obtained genetic evidence showing that myeloid Src-family kinases (Hck, Fgr and Lyn) are indispensable for murine models of autoimmune inflammatory diseases such as rheumatoid arthritis or blistering skin diseases. They also developed a number of novel Src-family kinase inhibitors that also block inflammation-related in vitro leukocyte functions. The applicants will test and further develop novel Src-family kinase inhibitors as anti-inflammatory compounds, using several in vitro and in vivo inflammation assays to optimize the structure of the selected molecules. They will also test whether Src-family inhibitors already in clinical use in oncology patients also inhibit inflammatory processes. Finally, they will use Src-family kinase-deficient mice in several inflammation models to test the role of those kinases in more detail and to provide further reference information for the consortiums preclinical drug development activity. The selected inhibitors and mutant mice will be pre-screened using various inflammation-related in vitro leukocyte functions and short-term in vivo inflammation models, and then analyzed in detail using a number of in vivo mouse models of chronic autoimmune and inflammatory diseases. The project is expected to result in development of novel preclinical drug candidates against chronic autoimmune and inflammatory disease with novel mechanism of action, as well as novel knowledge on the role of Src-family kinases in inflammatory diseases. The project will be performed in close cooperation between European and Brazilian scientists.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 5.10M | Year: 2015

Common mechanisms and pathways in Stroke and Alzheimers disease. It has long been recognized that stroke and (Alzheimers Disease) AD often co-occur and have an overlapping pathogenesis. As such, these two diseases are not considered fellow travelers, but rather partners in crime. This multidisciplinary consortium includes epidemiologists, geneticists, radiologists, neurologists with a longstanding track-record on the etiology of stroke and AD. This project aims to improve our understanding of the co-occurrence of stroke and AD. An essential concept of our proposal is that stroke and AD are sequential diseases that have overlapping pathyphysiological mechanisms in addition to shared risk factors. We will particularly focus on these common mechanisms and disentangle when and how these mechanisms diverge into causing either stroke, or AD, or both. Another important concept is that mechanisms under study will not only include the known pathways of ischemic vasculopathy and CAA, but we will explore and unravel novel mechanisms linking stroke and AD. We will do so by exploiting our vast international network in order to link various big datasets and by incorporating novel analytical strategies with emerging technologies in the field of genomics, metabolomics, and brain MR-imaging.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.2.1-2 | Award Amount: 15.03M | Year: 2010

The aim of EU-GEI is to identify the interactive genetic, clinical and environmental determinants involved in the development, severity and outcome of schizophrenia (EU-GEI, Schiz. Res. 2008; 102: 21-6). In order to identify these interactive determinants, EU-GEI will employ family-based, multidisciplinary research paradigms, which allow for the efficient assessment of gene-environment interactions. In order to go beyond old findings from historical convenience cohorts with crude measures of environmental factors and clinical outcomes, the focus in EU-GEI will be on recruitment of new, family-based clinical samples with state-of-the-art assessments of environmental, clinical and genetic determinants as well as their underlying neural and behavioural mechanisms. New statistical tools will be developed to combine the latest multilevel epidemiological with the latest genome-wide genetic approaches to analysis. Translation of results to clinical practice will be facilitated by additional experimental research and risk assessment bioinformatics approaches. This will result in the identification of modifiable biological and cognitive mechanisms underlying gene-environment interactions and the construction of Risk Assessment Charts and Momentary Assessment Technology tools which can be used for (i) early prediction of transition to psychotic disorder in help-seeking individuals with an at-risk mental state and (ii) early prediction of course and outcome after illness onset. In order to reach these goals, EU-GEI has assembled a multidisciplinary team of top schizophrenia researchers who have the range of skills required to deliver a program of research that meets all the calls requirements and who have access to / will collect a number of unique European samples. The partners in EU-GEI represent the nationally funded schizophrenia / mental health networks of the UK, Netherlands, France, Spain, Turkey and Germany as well as other partners.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: NMP.2012.1.4-2 | Award Amount: 5.18M | Year: 2013

UNION will develop nanoparticle (NP) assembly techniques, and assembly monitoring technologies to prepare novel hierarchically-ordered nanoparticle clusters (NPCs). By improving control over the synthesis and assembly of NPs we will produce materials with tailored and predictable properties. Furthermore, by incorporating hierarchical control into the assembly (through the type, size and spatial distribution of the NPs) it will be possible to assess the influence of the hierarchy on properties and develop new functionalities. UNION will investigate how the emergent properties of the assemblies are determined by the architecture of the assembly, the extent of order, and the properties of the component NPs. This will enable tuning of the primary NP properties and the assembly processes to develop significant breakthroughs in nano-devices and next generation complex nanotechnology products. As the ultimate aim is commercial exploitation of our results, in each stage of the development process we will use application driven, scalable and cost-effective processes, incorporating EHS assessment and roadmap preparation towards future industrial deployment. UNION will achieve its objectives through a three stage approach. - Improved NP preparation providing optimised surface chemistry for subsequent assembly - Novel NPC formation (hierarchical nanoparticle assembly) methods - Roll-out of NPCs for three application areas NPC applications will be developed within three core areas corresponding to the different hierarchical structural levels; in suspensions of individual NPCs (biomedical), in supported 2D NPC arrays (optical), and in 3D arrays or nanocomposites (thermoelectric). Our consortium is comprised of multidisciplinary research groups involving 8 partners with ex-pertise in preparation and application of nano-materials. It includes significant industrial participation with 4 companies with specific knowledge and testing capability for the target application areas.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: EO-2-2015 | Award Amount: 2.99M | Year: 2016

With the start of the SENTINEL era, an unprecedented amount of Earth Observation (EO) data will become available. Currently there is no consistent but extendible and adaptable framework to integrate observations from different sensors in order to obtain the best possible estimate of the land surface state. MULTIPY proposes a solution to this challenge. The project will develop an efficient and fully traceable platform that uses state-of-the-art physical radiative transfer models, within advanced data assimilation (DA) concepts, to consistently acquire, interpret and produce a continuous stream of high spatial and temporal resolution estimates of land surface parameters, fully characterized. These inferences on the state of the land surface will be the result from the coherent joint interpretation of the observations from the different Sentinels, as well as other 3rd party missions (e.g. ProbaV, Landsat, MODIS). The framework allows users to exchange components as plug-ins according to their needs. The proposal is based on the EO-LDAS concepts developed within several ESA-funded projects, which have shown the feasibility of producing estimates of the land surface parameters by combining different sets of observations through the use of radiative transfer models. We will provide a fully generic flexible data retrieval platform for Copernicus services that provides integrated and consistent data products in an easily accessible virtual machine with advanced visualisation tools. Users will be engaged throughout the process and trained. Moreover, user demonstrator projects include applications to crop monitoring & modelling, forestry, biodiversity and nature management. Another user demonstrator project involves providing satellite operators with an opportunity to cross-calibrate their data to the science-grade Sentinel standards.

Neumann J.,Ludwig Maximilians University of Munich | Gottschalk K.E.,Ludwig Maximilians University of Munich | Astumian R.D.,University of Maine, United States
ACS Nano | Year: 2012

Figure Persented: Great progress has been made in the design and synthesis of molecular motors and rotors. Loosely inspired by biomolecular machines such as kinesin and the FoF1 ATPsynthase, these molecules are hoped to provide elements for construction of more elaborate structures that can carry out tasks at the nanoscale corresponding to the tasks accomplished by elementary machines in the macroscopic world. Most of the molecular motors synthesized to date suffer from the drawback that they operate relatively slowly (less than kHz). Here we show by molecular dynamics studies of a diethyl sulfide rotor on a gold(111) surface that a high-frequency oscillating electric field normal to the surface can drive directed rotation at GHz frequencies. The maximum directed rotation rate is 10 10 rotations per second, significantly faster than the rotation of previously reported directional molecular rotors. Understanding the fundamental basis of directed motion of surface rotors is essential for the further development of efficient externally driven artificial rotors. Our results represent a step toward the design of a surface-bound molecular rotary motor with a tunable rotation frequency and direction. © 2012 American Chemical Society.

Agency: European Commission | Branch: FP7 | Program: CSA | Phase: INFRA-2012-3.2. | Award Amount: 884.74K | Year: 2012

Hydro-Meteorology Research (HMR) is an area of critical scientific importance and of high societal relevance. It plays a key role in guiding predictions relevant to the safety and prosperity of humans and ecosystems from highly urbanized areas, to coastal zones, and to agricultural landscapes. Of special interest and urgency within HMR is the problem of understanding and predicting the impacts of severe hydro-meteorological events, such as flash-floods and landslides in complex orography areas, on humans and the environment, under the incoming climate change effects.\nThus, building on existing but regional projects such as DRIHM (Distributed Research Infrastructure for Hydro-Meteorology, EU) and CESM (Community Earth System Model, US), DRIHM2US project will help in understanding the utilization of e-Infrastructures for advancing scientific collaboration on both sides of the Atlantic towards improving the predictive ability of severe storms and utilization of these predictions for hazard prediction and control under climate change effects. As such, HMR serves as a key example for the utilization of e-Infrastructures in Advancing Science of Service to Society and can be a lighthouse for broader directions within HMR and for other scientific disciplines.\nAlong these lines DRIHM2US will promote international cooperation between Europe and the USA for the development of a joint/common e-Infrastructure using Hydro-Meteorology Research (HMR) as an example, to ensure persistent availability and effective sharing of data and models across scientific disciplines, institutions, and national boundaries, specifically across the Atlantic.\nThe goal will be achieved by creating a forum of collaboration, based on a sequence of networking actvities with EU and US participants.

Agency: European Commission | Branch: FP7 | Program: CSA | Phase: INFRA-2012-3.3. | Award Amount: 1.22M | Year: 2012

The FedSM project aims at formalising IT Service Management (ITSM) and introducing industry-standards-based ITSM processes in Federated e-Infrastructures. In the last decade, Federated e-Infrastructures have evolved from a set of ad-hoc academic services to a European scale resource for the science and technology sector.\n\nITSM approaches (like ITIL or ISO/IEC 20000) provide sets of processes and good practices, widely used in the commercial sector, that are used to build business and service provisioning models, structure business and management activities, and define, agree and operate services based on binding, well-understood agreements (service level agreements, SLAs) or contracts.\n\nFedSM will act in a way analogous to commercial ITSM consultancy, engaging with three client organisations: two National Grid Infrastructures and the European Grid Initiative, which are all part of the project consortium and committing to adopting an ITSM approach. FedSM will analyse their specific situations, provide new models for their processes and support them in assessing and implementing this new ITSM approach. To this end, FedSM will focus on (1) supporting the definition and implementation of business models, services, processes and a proto standard for Federated Infrastructure ITSM, (2) building up ITSM knowledge in the client organisations through professional training and internationally recognised certification, and (3) consulting the client organisations in defining their specific requirements for automated solutions and selecting adequate tools.\n\nFedSM will not be limited to supporting the involved client organisations in implementing ITSM. Based on the client-specific ITSM programs and the lessons learned, a generic conceptual framework for implementing ITSM in Federated e-Infrastructures based on different business models in the areas of Grids and federated clouds will be developed.

Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: INFRA-2011-1.2.1. | Award Amount: 4.78M | Year: 2011

Predicting weather and climate and its impacts on the environment, including hazards such as floods and landslides, is still one of the main challenges of the 21st century, with significant societal and economic implications. At the heart of this challenge, as also suggested by the DRIHMS (Distributed Research Infrastructure for Hydro-Meteorology Study) project, lies the ability to have easy access to hydro-meteorological data and models, and to facilitate the collaboration between meteorologists, hydrologists, and Earth science experts for accelerated scientific advances in hydrometeorological research (HMR).\nThe proposed DRIHM (Distributed Research Infrastructure for Hydro-Meteorology) project intends to develop a prototype e-Science environment to facilitate this collaboration, and provide end-to-end HMR services (models, datasets and post-processing tools) at the European level, with the ability to expand to the global scale. The objectives of DRIHM are to lead the definition of a common long-term strategy, to foster the development of new HMR models and observational archives for the study of severe hydrometeorological events, to promote the execution and analysis of high-end simulations, and to support the dissemination of predictive models as decision analysis tools.\nDRIHM combines the European expertise in HMR, and in Grid and High Performance Computing (HPC). Joint research activities will improve the efficient use of European e-Infrastructures, notably Grid and HPC, for HMR modeling and observational databases, model evaluation tool sets and access to HMR model results. Networking activities will disseminate DRIHM results at the European and global levels in order to increase the cohesion of European and possibly worldwide HMR communities, and to increase the awareness of the potential of ICT for HMR. Service activities will deploy the end-to-end DRIHM services and tools in support of HMR networks and virtual organizations on top of the existing European e-Infrastructures.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.69M | Year: 2013

MARATONE is a Marie Curie Initial Training Network proposal that directly addresses the need for high-level training and career pathways in mental health to increase the inter-sectorial and trans-national employability of young scientists in the academic, public and private sectors to meet the enormous challenge of the 2009 EU Parliament Resolution on Mental Health. The Resolution set out recommendations for a comprehensive and integrated mental health strategy for Europe. MARATONE is designed to address the biggest challenge to implementing this ambitious strategy: the lack of training for career pathways for young scientists in multidisciplinary mental health research. MARATONE is built on the innovative theoretical premise of horizontal epidemiology, the view that psychosocial difficulties associated with mental health disorders are not exclusively determined by the diagnosis of the particular disorder in a vertical, silo-like pattern but horizontally in a manner that reflects commonalities in the lived experience of people with diverse mental health problems. Grounded in this theoretical foundation, MARATONEs multidisciplinary network of partners will collaboratively develop methodologies for measuring the individual and social impact of mental health disorders, so as to create strategies for the social and private sector responses to mental ill health in the form of health promotion and prevention programmes, and at the national level, strategies for human rights protections in policies and programming. The consortium will provide young researchers with scientific expertise in mental health, as well as basic technical and communication skills, including research development and management, international human rights commitments, and commercial exploitation and dissemination.

Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2010-1.1.16 | Award Amount: 11.60M | Year: 2011

Climate change is for a large part governed by atmospheric processes, in particular the interaction between radiation and atmospheric components (e.g. aerosols, clouds, greenhouse and trace gases). Some of these components are also those with adverse health effects influencing air quality. Strengthening the ground-based component of the Earth Observing System for these key atmospheric variables has unambiguously been asserted in the IPCC Fourth Assessment Report and Thematic Strategy on air pollution of the EU. However, a coordinated research infrastructure for these observations is presently lacking. ACTRIS (Aerosols, Clouds and Trace gases Research InfraStructure Network) aims to fill this observational gap through the coordination of European ground-based network of stations equipped with advanced atmospheric probing instrumentation for aerosols, clouds and short-lived trace gases. ACTRIS is a coordinated network that contributes to: providing long-term observational data relevant to climate and air quality research produced with standardized or comparable procedures; supporting transnational access to large infrastructures strengthening collaboration in and outside the EU and access to high quality information and services to the user communities; developing new integration tools to fully exploit the use of atmospheric techniques at ground-based stations, in particular for the calibration/validation/integration of satellite sensors and for the improvement of global and regional-scale climate and air quality models. ACTRIS supports training of new users in particular young scientists in the field of atmospheric observations and promotes the development of new technologies for atmospheric observation of aerosols, clouds and trace gases through close partnership with SMEs. ACTRIS will have the essential role to support integrated research actions in Europe for building the scientific knowledge required to support policy issues on air quality and climate change.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.91M | Year: 2013

Cardiovascular disease remains a major cause of morbidity and mortality in Europe. Small arteries form a key element in the pathogenesis. Thus, these vessels dictate local perfusion and blood pressure by adaptation of their caliber. Structural changes towards smaller caliber, small artery remodelling, cause hypertension and decreased organ perfusion, leading to acute events and chronic end organ dysfunction. Despite this role, these vessels are poorly studied and therapeutic options based on these arteries are lacking. SmArteR (Small Artery Remodelling) collects 13 academic and SME partners who have set up a training programme for 12 ESRs and 3 ERs. We address the interaction between cells, extracellular matrix and mechanical loading in an integrative way, taking advantage of the multidisciplinary partnership. Thus, we will unravel the processes in small artery remodelling at the molecular, cellular and integrative physiology level, and we will develop novel and marketable technology aimed at studying these vessels in vitro under the right biomechanical conditions. The ESRs and ERs are trained in not only cardiovascular R&D, but also in a range of skills required to form the new generation of frontrunners in biomedical research in academia and industry.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.42M | Year: 2012

Organic solar cells (OSC) feature several advantages over classical silicon solar cells: low cost, energy effective production, low weight and semi-transparency. This makes them apt for novel applications like, building-integrated photovoltaics (BIPV) with high market potential. However, both the efficiency and the long-term stability must be enhanced for OSCs to become profitable. POCAONTAS will develop highly efficient and stable OSCs based on tailored blends of polymers (P) with single wall carbon nanotubes (SWNT), that are ideally suited for OSCs due to their inherent stability, high carrier mobility and the tunability of optical gaps. Up to now, no breakthrough in SWNT based OSC has been achieved due to challenges with the control of SWNT-chirality, -aggregation, orbital energy mismatch and nanoscale sample morphology. Our consortium will address these issues: We will synthesize functional polymers that (i) allow for a tailored selection of SWNT chiralities, and (ii) match the SWNT energy levels to polymers for maximization of efficiency. The introduction of SWNT-P exchange protocols enables us to optimize (i) and (ii) with different polymers, avoiding compromises in performance. We will obtain optimized donor-acceptor blends, in which the SWNTs are light antenna and charge transporter. We unify leading European groups in time- (down to 10 fs) and spatially (down to 10 nm) resolved spectroscopies providing unique insights into SWNT-P interactions at the molecular level. Experts in multi-scale quantum chemical modeling will develop greater predictive power of charge transport. FLEXINK, a startup in optoelectronics materials, will provide tailored polymers. KONARKA, world leader in commercial OSCs, will build and test solar cells using our blends. Both full partners can directly exploit the projects outcome to strengthen their market position. Three associated industrial partners provide industry internships for each ESR maximizing their career perspectives.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: KBBE.2011.1.4-02 | Award Amount: 1.12M | Year: 2012

ComFish takes the view that it is not sufficient to focus on pressing issues in fisheries or on communication impasses between stakeholders in isolation (scientists industry policy makers). A broader view is necessary, and this is very much in line with the ecosystem approach of the revision of the Common Fisheries Policy to be implemented in 2012. In this frame of mind, ComFish aims to identify important fisheries topics with long term impacts and ascertain whether scientific results have been properly communicated to fisheries stakeholders. If yes, why and how was this done? If not, then the question must be answered which communication needs must be addressed. What are the related challenges, needed actions and possible solutions? ComFish will identify these topics and through five regional participatory stakeholder events address these communication impasses. Next, ComFish will use the outcome of the events to prepare Information Packages, that include audio-visual materials, and communicate the identified priority issues to a wider circle of stakeholders as well as to EU citizens. Finally, ComFish will organise a Partnering Event to facilitate network building amongst stakeholders, to jointly address and overcome communication impasses and to stimulate collaborations. All activities are supported by a robust science based impact analysis. ComFish has nine partners in eight EU countries: four are communication specialists and five are institutions engaged in marine research and policy advice. The project benefits from an extensive Advisory Board with representation from all major fisheries stakeholders in Europe as well as over 40 Project Associated Members, mostly FP6/FP7 research project co-ordinators. The project lasts 36 months.

Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: HEALTH-2009-2.2.1-5 | Award Amount: 1.68M | Year: 2010

The overall prevalence of brain disorders both neurological and psychiatric is very high in Europe. Although it is well known that the burden and costs of these disorders are high, there is evidence that the overall, personal, social and economic costs of brain disorders have been underestimated because of the lack of valid and reliable information regarding the full range of psychosocial difficulties that actually shape the lived experience of persons with these disorders and affect their quality of life. Current European data on psychosocial difficulties are derived from the diagnostic criteria of each disorder and so take the form of narrow information silos that are neither comprehensive nor comparable across disorders. Distinct information silos means that treatment planning, treatment evaluation and outcome assessment ignores commonalities of psychosocial consequences across disorders, undermining treatment efficiency and effectiveness, and ultimately increasing the costs of health and social care provision. The coordination action called PARADISE has the general objective of coordinating the development of a comprehensive and cross-cutting or horizontal epidemiology of psychosocial difficulties associated with brain disorders. Since a horizontal epidemiology accounts for the psychosocial difficulties that are actually experienced by people with brain disorders, independently of the brain disorder associated with them, it concentrates on what is more relevant to the lives of people with brain disorders. This leads to more effective intervention planning and management, and therefore to improved quality of life along the continuum of care, in the community, and across the life span. PARADISE coordinates the existing expertise in partners from eight European countries in relation to research literature, data documentation and analysis strategies for a representative range of brain disorders. These disorders are dementia, depression, epilepsy, migraine, multiple sclerosis, Parkinsons Disease, schizophrenia, stroke and substance use disorders. PARADISE will pave the way to future investigations that more meaningfully track the trajectories of psychosocial difficulties of brain disorders.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: SEC-2009-4.3-03 | Award Amount: 4.21M | Year: 2010

The project EMILI (Emergency Management in Large Infrastructures) is a capability project which aims at a new generation of data management and control systems for large Infrastructures (CIs) including appropriate simulation and training capabilities. This new generation of control systems is needed in order to improve the security of large Infrastructures like power grids and telecommunication systems, airports and railway systems, oil and gas pipelines under future technical, economic, organisational, political, and legal conditions. This is especially important in the case of emergencies and crises. Large Infrastructures are cost intensive, large, complex technical systems. They are frequently operated at their limits. Today, they are changing their characteristics rapidly in various respects. These CIs depend on each other and interact with each other in many ways. Even small disturbances may trigger avalanches of failures in the same system and in depending ones. Quick and adequate reactions are key factors in safe and efficient operations of Critical Infrastructures today. Currently used data management and control systems of large Infrastructures mainly collect data from their own system and process them in a more or less pre-defined way. In order to adapt todays control systems to the new challenges - especially to an efficient management of emergencies - we need a new generation of these control systems, their methodology and technology.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SSH.2013.4.2-1 | Award Amount: 3.22M | Year: 2014

INFOCORE focuses on the conditions that bring about different media roles in the cycle of conflict and peace building. It generates knowledge on (1) the social processes underlying the production of conflict news, and (2) the inherent dynamics of conflict news contents, (3) in a systematically comparative fashion. Based on this perspective, we identify the conditions under which media play specific constructive or destructive roles in preventing, managing, and resolving violent conflict, and building sustainable peace. The project will provide detailed knowledge on the process of conflict news production. Specifically, INFOCORE focuses on interactions between (1) professional journalists (in various media), (2) political actors (including public authorities, military), (3) experts/NGOs (in intelligence, peacekeeping, conflict prevention/resolution, and media assistance), and (4) lay publics (individuals and groups, including economic actors). INFOCORE analyzes these actors different roles (as sources/advocates, mediators, and users/audiences) in the production of (1) professional news media, (2) social media, (3) and semi-public intelligence/expert analysis. To assess the roles of media for shaping lay publics and political actors conflict perceptions and responses to ongoing conflicts, we analyze the dynamics of conflict news content over time. We identify recurrent patterns of information diffusion and the polarization/consolidation of specific frames and determine the main contextual factors that influence the roles media play in conflict and peace building. Specifically, we assess the roles of individual agendas and resources, professional norms, media organizations and systems, political systems, and characteristics of the conflict situation. INFOCORE implements a gender-sensitive perspective throughout the project, contributing to the ECs efforts to enable and strengthen the participation of women in peace and security matters.

Objective The ToyBox proposal addresses KBBE-2009-2-1-03 - Behavioural models for prevention of obesity, with a particular focus on children. It will primary aim to influence childrens behaviours and prevent obesity in early childhood. Strategy The proposal will identify key behaviours related to early childhood obesity and their determinants and evaluate behavioural models and educational strategies. Based on the obtained insights at a local level, a multidisciplinary team will develop and implement a school based family involved intervention programme that could be applied on a European scale. Process, impact, outcome and cost-effectiveness evaluation will be conducted to support decision making for European Public Health Policy. Methods The combined use of Precede-Proceed Model and Intervention Mapping will provide the framework for the development, implementation and evaluation of the ToyBox intervention. To achieve this, the project will be subdivided into 10 WPs. This carefully planned stepwise approach will include systematic reviews, secondary analyses of existing data sets, focus group research and school policies overview. Consortium The ToyBox project consortium spans the necessary multidisciplinary variety of experts such as public health experts, epidemiologists, nutritionists, physical activity experts, pedagogists, psychologists, behavioural scientists, nutritionists, paediatricians, early childhood psychologists, health economists, totalling 15 partners, from 10 countries. The consortium, consists of 11 universities, 1 research institute, 2 advocacy groups and an SME representing all regions of Europe. The consortium has ample experience in conducting and coordinating multi-centre international research as well as undertaking dissemination activities to all relevant stakeholders.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.2.1-7 | Award Amount: 5.08M | Year: 2008

Neuronal circuits in mammalian brain act predominantly via excitatory synapses on dendritic spines. Formation of new spines in adult brain constitutes the structural basis of neuronal plasticity. The underlying molecular mechanisms remain largely unknown but depend essentially on kinase-dependent signalling pathways. Final formation of synapses on spines depends on dynamic interactions of microtubuli and actin-filaments that are also controlled by kinases. Deterioration of these processes to different extents are thought to cause the cognitive decline in normal ageing as well in Alzheimers disease (AD) and familial fronto-temporal dementia (FTD). Protein tau is a microtubule associated protein and GSK-3 kinases are proposed as the major tau-kinases in vivo. Their exact contributions remain to be functionally defined in vivo both in normal neuronal plasticity and in degeneration. We develop pre-clinical models for AD and FTD that have tauopathy in common as essential pathogenic component and will explore the GSK-3 kinases in vivo by manipulating their activity genetically, pharmacologically and biochemically. Inhibitors are wanted that are effective and specific and enter brain in vivo. This proposal engages in three activities: (i) elucidate physiological functions of GSK-3 kinases in synaptic plasticity in adult and ageing brain, and in degenerating brain; define fundamental neuron-specific functions of GSK-3 kinases in vivo in novel mouse models; define contributions of GSK-3 kinases to amyloid and to tau pathology, separately and combined in vivo in validated mouse models (ii) design novel inhibitors of GSK-3 kinases and alternative tools to inhibit GSK-3 activity in vivo (iii) test pharmacological and peptidometic inhibitors of GSK-3 in validated mouse models of neurodegeneration for their restorative potential; analyse their mode of action and their acute and chronic effects by multi-parametric analysis

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.2.2-2 | Award Amount: 8.56M | Year: 2011

Healthy aging requires maintenance of homeostatic control of the physiological systems and functions that are integrated by the hypothalamus. Driven by work in previous EU projects (Crescendo/Lifespan) highlighting insulin signalling and the hypothalamic/pituitary/adrenal and thyroid axes in the regulation of aging, SWITCHBOX will examine the flexibility of these neuroendocrine systems in response to environmental challenges in three established human cohorts with variable aging potential. These human cohorts include offspring of exceptionally long-lived siblings and their partners (controls), people with good vs bad cognitive performance or with high vs low cognitive engagement. Maintaining brain function is emphasised as it reflects an individuals overall well-being, a major goal in aging research, and because age-related brain disorders represent a major socioeconomic burden. To determine the genetic and cellular underpinnings of the findings in humans, hypothesis-based studies in rodents sharing phenotypes with the human cohorts will be carried out. To clarify the role of the brain in the differential regulation of endocrine axes critical for healthy aging, SWITCHBOX will examine the neuroendocrine and metabolic effects of intranasal (humans) and intra-cerebroventricular (rodents) administration of peptides involved in controlling metabolic homeostasis (e.g. insulin, -MSH). State-of-the-art technology will be used to measure circadian endocrine and metabolic profiles, brain structure and function (fMRI) and cognitive performance, as well as cellular and molecular features. All data will be entered into an already operational open access database. The work aims to take key findings from basic research and translate them into clinically relevant concepts. It will benefit from combining expertise of gerontologists, endocrinologists, molecular and cellular neuroscientists and neuropsychologists. SWITCHBOX ultimately aims to develop conceptually new approaches for the prevention and treatment of age-related disorders.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.58M | Year: 2012

The principal strategic objective of INTERCROSSING is the cultivation of a new type of young researcher to deal with challenges of exploiting the latest Next Generation Sequencing (NGS) technologies individuals with rigorous training in three disciplines hardly ever found together any one young scientist: population genetics, informatics and statistics. The need for this supra-disciplinary combination of skills reflects the extraordinary new demands produced by technologies that allow us to sequence whole genomes, and to quantify their regulation and expression in many samples from the same species in multiple locations. This torrent of data overwhelms current computational, genetic and statistical approaches for distinguishing the biologically relevant patterns from the background noise. The consortium behind INTERCROSSING including five universities and seven SMEs spanning nine EU countries are all using the NGS technologies, but have found the recruitment of appropriate Early Stage Researchers (ESRs) a major obstacle to building on their innovations. This fundamental shortage in the EU research community is slowing the scientific and industrial exploitation of these groundbreaking new data streams; the shortage of key talent occurs worldwide, and has attracted major investment in other regions (e.g. at the Beijing Genome Institute). A combination of industrial and academic partners will deliver training courses equipping the ESRs to traverse the barriers between these disciplines. Taught courses will provide practical experience of NGS data acquisition, computational methods, model-based statistical inference and population genetics. These skills will allow the ESRs to implement state-of-the art methods to the new data. The ESRs will also be trained in a suit of research skills to deploy this understanding across the industrial and academic sectors, and will be employed in a project in which they move between the sectors.

Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH.2010.1.2-4 | Award Amount: 3.85M | Year: 2010

Chronic hepatitis C is one of the most common chronic viral infections of humans and a major cause of chronic liver disease, cirrhosis and liver cancer. Still about 4 million new infections occur world-wide each year with 50-85% of patients progressing to chronic hepatitis C. Currently there is no marker to predict spontaneous viral clearance and to guide treatment decisions. The major objectives of the HepaCute proposal are to develop biomarkers predicting the outcome of acute hepatitis C, improving the management of the related patients and thus decreasing the health burden of hepatitis C in Europe and Mediterranean partner countries (MPC). The HepaCute consortium has evolved from a series of EC-funded projects on hepatitis C (HCVacc/HepCvax/Virgil/HEPACIVAC) and consists of world leading experts in HCV epidemiology, immunology, and virology, including partners from Egypt and Morocco, who have strongly influenced the current management of patients with acute hepatitis C in their respective regions, and contributed considerably to our understanding of mechanisms of spontaneous viral clearance. The HepaCute proposal is closely connected to ongoing national, European, and Egyptian networks on HCV research (HepNet, EASL, STDF), which will support HepaCute to make it a success.Together with another pertinent EU-funded research project, SPHINX, it actively contributes to coordinating EU-funded hepatitis C research with pertinent research projects funded in the MCP countries, in particular with hepatitis research projects funded under the Egyptian Science and Technology Development Fund (STDF). Within HepaCute the most innovative technologies will be employed such as genome-wide association studies, transcriptomics, proteomics, and ultra-deep sequencing to better understand the early events in acute hepatitis C and to translate these results into readily practicable diagnostic tools to predict spontaneous viral clearance. HepaCute has firmly integrated partners from Egypt and Morocco with preexisting research collaborations with European partners into the scientific research programm and we expect this continuing partnership between European and Mediterranean countries to have a strong impact on the care of patients with acute hepatitis C both in Europe and MPC.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.2.1-8;HEALTH-2007-2.4.1-12 | Award Amount: 13.76M | Year: 2008

Partners come from 10 European countries to achieve two main objectives: A) The further exploration of 3 animal models (the OBX rat, GS rat and NOD mouse) characterized by an activated immune response system (IRS), an abnormal tryptophan catabolism and a depressive-like behaviour to study the pathogenesis of inflammation-related mood disorders and the efficacy/working mechanism of anti-inflammatory and tryptophan metabolism restoring drugs. B) The in-parallel study of mood disorder patients to validate two sets of already developed biomarker tests to identify patients and individuals at risk for a mood disorder and characterized by an activated IRS to be able to treat these patients/individuals with drugs counteracting the consequences of the activated IRS/disturbed catabolism of tryptophan. Five strategic approaches (broken down in 12 workpackages) are used: 1) Study of the animal models for depressive-like behavior and aberrancies in monocytes/ macrophages, the tryptophan metabolism and the microglia-astrocyte-neuron interaction. 2/3) The validation of a high-throughput biomarker mRNA blood monocyte signature test and a biomarker test to detect an abnormal tryptophan catabolism. 4) Correlation studies between the outcomes of these biomarker tests in patients to various clinical variables, a.o. gene polymorphisms and the brain scan. 5) The therapeutic targetting of the activated IRS/abnormal tryptophan catabolism using a PDE4 inhibitor, a COX-2 inhibitor and a KMO-inhibitor in the animal models and in a phase II intervention study in depressed patients. Novel approaches are the prospective assessment of patients/individuals to identify whether changes in the IRS have any prognostic value and that the program aims at a personalized treatment of patients on the basis of their activated IRS. We heavily rely in this on the study of the animal models, which allow us to test anti-inflammatory therapeutics and to know their mechanism of action at the brain.

Agency: European Commission | Branch: FP7 | Program: NOE | Phase: ICT-2009.1.4 | Award Amount: 5.25M | Year: 2010

The Network of Excellence on Engineering Secure Future Internet Software Services and Systems (NESSoS) aims at constituting and integrating a long lasting research community on engineering secure software-based services and systems.\n\nThe NESSoS engineering of secure software services is based on the principle of addressing security concerns from the very beginning in system analysis and design, thus contributing to reduce the amount of system and service vulnerabilities and enabling the systematic treatment of security needs through the engineering process. In light of the unique security requirements the Future Internet will expose, new results will be achieved by means of an integrated research, as to improve the necessary assurance level and to address risk and cost during the software development cycle in order to prioritize and manage investments. NESSoS will integrate the research labs involved; NESSoS will re-address, integrate, harmonize and foster the research activities in the necessary areas, and will increase and spread the research excellence. NESSoS will also impact training and education activities in Europe to grow a new generation of skilled researchers and practitioners in the area. NESSoS will collaborate with industrial stakeholders to improve the industry best practices and support a rapid growth of software-based service systems in the Future Internet.\n\nThe research excellence of NESSoS will contribute to increase the trustworthiness of the Future Internet by improving the overall security of software services and systems. This will support European competitiveness in this vital area.

Puchner E.M.,University of California at San Francisco | Gaub H.E.,Ludwig Maximilians University of Munich
Annual Review of Biophysics | Year: 2012

The ability of cellular signaling networks to sense, process, and respond to internal and external stimuli relies on their specific detection and transduction based on molecular recognition. The molecular mechanisms by which force is specifically sensed by mechanoenzymatic processes, translated into biochemical signals, and wired to cellular signaling networks recently became accessible with single-molecule force spectroscopy. By stretching such mechanobiochemical converters along their natural reaction coordinate, complex mechanical activation pathways and subsequent biochemical reactions may be measured in a dynamic and highly precise manner. The discovered mechanisms have in common well-tuned force-induced conformational changes that lead to exposure of active recognition sites. Newly developed strategies allow investigators to test different conformational states for activity and to elucidate mechanical architectures leading to highly specific mechanical activation pathways. Here, we discuss the advances in the new field of single-molecule mechanoenzymatics and highlight complementary examples studied in bulk and in vivo. © 2012 by Annual Reviews. All rights reserved.

Agency: European Commission | Branch: FP7 | Program: CSA | Phase: INFRA-2010-3.3 | Award Amount: 606.60K | Year: 2010

Service Level Management (SLM) is considered a vital discipline in the management of todays information technology infrastructures. The widespread and commonly approved international standard for IT Service Management, ISO/IEC 20000, describes the objective of Service Level Management as follows: To define, agree, record and manage levels of service. All of these aspects are crucial when bringing the new e-Infrastructure technologies, processes and services to new user communities. Only by having a framework for establishing a common understanding of these four aspects of the services provided and used, can the e-Infrastructure maintain a sufficient customer satisfaction on sustainable level.\n\nHowever, SLM has not been successfully implemented and deployed in any of the next generation IT infrastructures (e-infrastuctures). To remedy this situation, grid environments are seen as a very promising starting point. By establishing grid-wide service catalogs and service agreements between customers and a virtual grid provider, grid services can be delivered in a more deterministic fashion. As the cross-organisational collaboration models are evolving rapidly in the Grid domain through the EGI initiative, gSLM project can act as a crucial enabler for the application of grid technology and the grid concept in general also in environments where predictable service utility and warranty are seen as significant requirements.\n\nThe goal of the proposed gSLM project is to bring together European experts from the grid and service management community and promote the development of SLM solutions that are well tailored to the requirements of and operational conditions in the e-infrastructure service provision today and in the future.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: NMP-2009-1.1-1 | Award Amount: 2.62M | Year: 2011

Nanoscience and nanotechnology are currently revolutionizing sectors such as medicine, information technologies, environmental or materials sciences, and creating new opportunities for our societies. In this context, magnetic nanoparticles (MNP) are key components to the development of novel nano- and biotechnologies. Magnetosomes are unique hybrid magnetic MNP produced by magnetotactic bacteria (MB). They are employed in applications ranging from extraction of DNA to the development of immunoassays and uses in spintronics are envisaged. However, only a very limited amount of MNP (few mg per day) can be formed by MB, and the formation principles remain to be tackled. Biomimetics, i.e. combining biological principles with chemistry, will pave the way to understand biomineralization of tailored MNP and to find out high-value high-yield synthetic routes to solve scientific and technological challenges. Specifically, we aspire at bridging the gap between different fields of science. For the first time, we will blend biological and genetic approaches with chemical and physical knowledge to understand the key parameters controlling the size, shape, composition and assembly of hybrid MNP in vivo and in vitro. We will combine nanoscience and nanotechnology to modify these properties and develop an ensemble of magnetic nanomaterials of higher values. This approach will lead to original contributions of innovative nature based on the combined skills of the partners to manufacture and characterize the biological, chemical, structural and magnetic properties of the MNP. The industrial partner will have key importance in managing and assessing the applicability of the MNP in Magnetic Resonance Imaging (MRI). Finally, our cell biologist partner will test the biocompatibility of the designed systems. In 3 years, we aim at being able to synthesize hybrid MNP with tailored magnetic and size properties by low-cost high-yield synthesis for applications in MRI.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETHPC-1-2014 | Award Amount: 2.87M | Year: 2015

Many aspects of our life, but also cutting-edge research questions, hinge on the solution of large systems of partial differential equations expressing conservation laws. Such equations are solved to compute accurate weather forecast, complex earthquake physics, hematic flows in patients, or the most catastrophic events in the universe. Yet, our ability to exploit the predictive power of these models is still severely limited by the computational costs of their solution. Thus, the simulation of earthquakes and their induced hazards is not yet accurate enough to prevent human losses. And our ability to model astrophysical objects is still insufficient to explain our observations. While exascale supercomputers promise the performance to tackle such problems, current numerical methods are either too expensive, because not sufficiently accurate, or too inefficient, because unable to exploit the latest supercomputing hardware. Exascale software needs to be redesigned to meet the disruptive hardware changes caused by severe constraints in energy consumption. We thus develop a new exascale hyperbolic simulation engine based on high-order communication-avoiding Finite-Volume/Discontinuous-Galerkin schemes yielding high computational efficiency. We utilize structured, spacetree grids that offer dynamic adaptivity in space and time at low memory footprint. And we consequently optimise all compute kernels to minimise energy consumption and exploit inherent fault-tolerance properties of the numerical method. As a general hyperbolic solver, the exascale engine will drive research in diverse areas and relieve scientist from the burden of developing robust and efficient exascale codes. Its development is driven by precise scientific goals, addressing grand challenges in geo- and astrophysics, such as the dynamic rupture processes and subsequent regional seismic wave propagation, or the modeling of relativistic plasmas in the collision of compact stars and explosive phenomena.

News Article | December 9, 2016

Lyncean Technologies, Inc., manufacturer of the Lyncean Compact Light Source, today announced the successful raising of $650,000 in a Series A funding round. The funding will be used to further grow commercial activity in the academic research market and the exploration of vertical market opportunities in the semiconductor and healthcare fields. "Our recent sales and marketing efforts have validated our belief that world-class researchers value the ability to conduct synchrotron quality experiments in their own laboratory and we need to be ready to support the expected business operationally," said Lyncean CEO Dr. Michael Feser. "Having the additional financial support will also help us begin to execute our vision of expanding into one of several potential vertical markets." "X-ray based technologies are playing a growing role not only in scientific applications but also in industrial and medical applications. We see tremendous opportunity for the Lyncean Compact Light Source to enable more important, high-value solutions for industry." said Lucian Wagner, General Partner at EuroUS Ventures, who coordinated and led the group of participating investors. Lyncean Technologies, Inc. is located in Fremont, California and was founded in 2001 to develop the Compact Light Source (CLS), a miniature synchrotron x-ray source based on research performed at the SLAC National Accelerator Laboratory and Stanford University. Unlike stadium-sized synchrotron radiation sources that require a highly technical support staff, the CLS fits in a typical laboratory space and is designed to be operated directly by academic or industrial end-users. By replacing the conventional "undulator" magnets found in the large synchrotrons by laser technology, the entire device scales down in size by a factor of 200. Unlike traditional laboratory sources, the CLS makes a narrow beam of nearly monochromatic X-rays which are adjustable in energy. The first commercial Lyncean CLS was purchased in December 2012 by researchers from the newly formed Center for Advanced Laser Applications in Germany, a joint project of the Ludwig Maximilians University of Munich and the Technical University Munich (TUM). The Munich CLS was delivered at the end of 2014 and has been in routine operation since April 2015. For more information visit: http://www.

Gerdes N.,Ludwig Maximilians University of Munich | Zirlik A.,Albert Ludwigs University of Freiburg
Thrombosis and Haemostasis | Year: 2011

A plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front-runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co-inhibitory signals. In addition, many of these proteins enfold T cell-independent pro-atherogenic functions on a variety of cell types. Accordingly they represent potential targets for immune- modulatory and/or anti-inflammatory therapy of atherosclerosis. This review focuses on the diverse role of co-stimulatory molecules of the B7 and tumour necrosis factor (TNF)-superfamily and their down-stream signalling effectors in atherosclerosis. In particular, the contribution of CD28/CD80/CD86/CTLA4, ICOS/ICOSL, PD-1/PDL-1/2, TRAF, CD40/CD154, OX40/OX40L, CD137/CD137L, CD70/CD27, GITR/GITRL, and LIGHT to arterial disease is reviewed. Finally, the potential for a therapeutic exploitation of these molecules in the treatment of atherosclerosis is discussed. © Schattauer 2011.

Heine J.,University of Marburg | Schmedt Auf Der Gunne J.,Ludwig Maximilians University of Munich | Dehnen S.,University of Marburg
Journal of the American Chemical Society | Year: 2011

Self-assembly of ZnCl2 and the ligand 2,4,6-tris(4-pyridyl) pyridine (pytpy) in solution yields [(ZnCl2)12(pytpy) 8]n·xCHCl3, a polycatenane consisting of a strand of mechanically interlocking icosahedral cages with an inner volume of more than 2700 Å3. This can be used to encapsulate guest molecules of appropriate size and polarity, forming a precisely defined three-dimensional array of solvent nanodroplets within the crystalline framework. The dynamic composition of these droplets was studied using quantitative solid-state NMR spectroscopy. © 2011 American Chemical Society.

Schollwock U.,Ludwig Maximilians University of Munich | Schollwock U.,Germany Institute for Advanced Study Berlin
Annals of Physics | Year: 2011

The density-matrix renormalization group method (DMRG) has established itself over the last decade as the leading method for the simulation of the statics and dynamics of one-dimensional strongly correlated quantum lattice systems. In the further development of the method, the realization that DMRG operates on a highly interesting class of quantum states, so-called matrix product states (MPS), has allowed a much deeper understanding of the inner structure of the DMRG method, its further potential and its limitations. In this paper, I want to give a detailed exposition of current DMRG thinking in the MPS language in order to make the advisable implementation of the family of DMRG algorithms in exclusively MPS terms transparent. I then move on to discuss some directions of potentially fruitful further algorithmic development: while DMRG is a very mature method by now, I still see potential for further improvements, as exemplified by a number of recently introduced algorithms. © 2010.

Bravin A.,European Synchrotron Radiation Facility | Coan P.,Ludwig Maximilians University of Munich | Suortti P.,University of Helsinki
Physics in Medicine and Biology | Year: 2013

Phase-contrast x-ray imaging (PCI) is an innovative method that is sensitive to the refraction of the x-rays in matter. PCI is particularly adapted to visualize weakly absorbing details like those often encountered in biology and medicine. In past years, PCI has become one of the most used imaging methods in laboratory and preclinical studies: its unique characteristics allow high contrast 3D visualization of thick and complex samples even at high spatial resolution. Applications have covered a wide range of pathologies and organs, and are more and more often performed in vivo. Several techniques are now available to exploit and visualize the phase-contrast: propagation- and analyzer-based, crystal and grating interferometry and non-interferometric methods like the coded aperture. In this review, covering the last five years, we will givean overview of the main theoretical and experimental developments and of the important steps performed towards the clinical implementation of PCI. © 2013 Institute of Physics and Engineering in Medicine.

Halimeh J.C.,Ludwig Maximilians University of Munich | Wegener M.,Karlsruhe Institute of Technology
Optics Express | Year: 2013

Carpet or ground-plane invisibility cloaks hide an object in reflection and inhibit transmission experiments by construction. This concept has significantly reduced the otherwise demanding material requirements and has hence enabled various experimental demonstrations. In contrast, free-space invisibility cloaks should work in both reflection and transmission. The fabrication of omnidirectional three-dimensional freespace cloaks still poses significant challenges. Recently, the idea of the carpet cloak has been carried over to experiments on unidirectional freespace invisibility cloaks that only work perfectly for one particular viewing direction and, depending on the design, also for one linear polarization of light only. Here, by using photorealistic ray tracing, we visualize the performance of four types of such unidirectional cloaks in three dimensions for different viewing directions and different polarizations of light, revealing virtues and limitations of these approaches in an intuitive manner. © 2013 Optical Society of America.

Fischer J.,Karlsruhe Institute of Technology | Heun V.,Ludwig Maximilians University of Munich
SIAM Journal on Computing | Year: 2011

Given a static array of n totally ordered objects, the range minimum query problem is to build a data structure that allows us to answer efficiently subsequent on-line queries of the form "what is the position of a minimum element in the subarray ranging from i to j?". We focus on two settings, where (1) the input array is available at query time, and (2) the input array is available only at construction time. In setting (1), we show new data structures (a) of size 2n/c(n) -Θ(n lg lg n/c(n) lg n) bits and query time O(c(n)) for any positive integer function c(n) ε O(nε) for an arbitrary constant 0 < ε < 1, or (b) with O(nHk) + o(n) bits and O(1) query time, where Hk denotes the empirical entropy of kth order of the input array. In setting (2), we give a data structure of size 2n+o(n) bits and query time O(1). All data structures can be constructed in linear time and almost in-place. Copyright © by SIAM.

Boulesteix A.-L.,Ludwig Maximilians University of Munich | Sauerbrei W.,Albert Ludwigs University of Freiburg
Briefings in Bioinformatics | Year: 2011

Hundreds of 'molecular signatures' have been proposed in the literature to predict patient outcome in clinical settings from high-dimensional data, many of which eventually failed to get validated. Validation of such molecular research findings is thus becoming an increasingly important branch of clinical bioinformatics. Moreover, in practice well-known clinical predictors are often already available. From a statistical and bioinformatics point of view, poor attention has been given to the evaluation of the added predictive value of a molecular signature given that clinical predictors or an established index are available. This article reviews procedures that assess and validate the added predictive value of high-dimensional molecular data. It critically surveys various approaches for the construction of combined prediction models using both clinical and molecular data, for validating added predictive value based on independent data, and for assessing added predictive value using a single data set. © The Author 2011. Published by Oxford University Press.

Halimeh J.C.,Ludwig Maximilians University of Munich | Wegener M.,Karlsruhe Institute of Technology
Optics Express | Year: 2012

As invisibility cloaking has recently become experimental reality, it is interesting to explore ways to reveal remaining imperfections. In essence, the idea of most invisibility cloaks is to recover the optical path lengths without an object (to be made invisible) by a suitable arrangement around that object. Optical path length is proportional to the time of flight of a light ray or to the optical phase accumulated by a light wave. Thus, time-of-flight images provide a direct and intuitive tool for probing imperfections. Indeed, recent phase-sensitive experiments on the carpet cloak have already made early steps in this direction. In the macroscopic world, time-of-flight images could be measured directly by light detection and ranging (LIDAR). Here, we show calculated time-of-flight images of the conformal Gaussian carpet cloak, the conformal grating cloak, the cylindrical free-space cloak, and of the invisible sphere. All results are obtained by using a ray-velocity equation of motion derived from Fermat's principle. © 2011 Optical Society of America.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: ENV.2008. | Award Amount: 961.99K | Year: 2009

The ComEnvir project aims to narrow the gap between EU sponsored environmental research and European citizens. Water (resources, quality, pollution and biodiversity issues) has been chosen as a common theme to be addressed by the project. It will cover environmental stressors, waste treatment, health effects, biodiversity, risks and therefore the role of water quality in its different environmental locations (fresh water, marine, soil, air). The project will last 48 months. The project will communicate results and activities of EU environmental research with two specific target groups. The primary target group are teachers and students. The second target group is the general public. The overall project objectives are to: empower the European citizens to constructively engage in scientific dialogue and debate inform European consumers of the latest scientific advances in the food sector strengthen science education in classrooms and promote scientific curiosity among the youth The ComEnvir project will achieve its set objectives through a number of innovative approaches and strategies that have already been piloted in 2006 and 2007. These approaches centre around three key elements: creation of knowledge packages on EU environmental research and will include films, film clips, FAQs, news, background reading materials, a glossary and links effective dissemination measures (broadcast media, DVDs and internet) and thorough evaluation of on-going project deliverables The nine project members, located in Denmark, France, Germany, Italy, The Netherlands, Norway and the UK possess complementary expertise that assures successful project outcome. The project will last 48 months.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SST-2007-4.1-02 | Award Amount: 5.85M | Year: 2009

The objectives of CASPER are to reduce fatalities and injuries of children in traffic accidents. A badly injured child or a dead child is everything nobody can tolerate. Children are more and more often involved in all modes of transportations; they have no choice; they are bind to the adult careers, taking for granted that the adults will take good care of them. CASPER will address two main aspects: - on one hand, the improvement of the efficiency of child protection through the development of innovative tools, such as new sensors, dummies models and child human models, completed by test procedures in frontal and lateral configurations, with associated injury criteria, in order to provide to CRS manufacturers the possibility to develop and test their products at a lower cost, with new methods, and at a same guarantee of efficiency. - on another hand, the analysis of the reasons and consequences of misuse of child restraint systems and of the influence of the real conditions of transportation of children, as compared to the certification test procedures. The main deliverables will be the improvement of biomechanical behaviour of existing dummies associated to new measurements sensors, as well as dummies and child human numerical models, with improved test procedures, which will allow solving the issues for improvement of children protection. Reports on the conditions of use of child restraint systems and consequences in accidents, including campaigns of information will be made in order to solve the problem of children involved in traffic accidents. Seven European countries are involved in this Consortium, with 14 partners who all have a long experience in the field of child safety. They have complementary profiles and were chosen for their high level of competence as regards crash investigations, test performance, computer simulations, experience on dummies and instrumentation, injury biomechanics, computer modelling and virtual testing.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETPROACT-01-2016 | Award Amount: 8.65M | Year: 2016

The goal of BrainCom is to develop a new generation of neuroprosthetic devices for large-scale and high density recording and stimulation of the human cortex, suitable to explore and repair high-level cognitive functions. Since one of the most invalidating neurospychological conditions is arguably the impossibility to communicate with others, BrainCom primarily focuses on the restoration of speech and communication in aphasic patients suffering from upper spinal cord, brainstem or brain damage. To target broadly distributed neural systems as the language network, BrainCom proposes to use novel electronic technologies based on nanomaterials to design ultra-flexible cortical and intracortical implants adapted to large-scale high-density recording and stimulation. The main challenge of the project is to achieve flexible contact of broad cortical areas for stimulation and neural activity decoding with unprecedented spatial and temporal resolution. Critically, the development of such novel neuroprosthetic devices will permit significant advances to the basic understanding of the dynamics and neural information processing in cortical speech networks and the development of speech rehabilitation solutions using innovative brain-computer interfaces. Beyond this application, BrainCom innovations will enable the study and repair of other high-level cognitive functions such as learning and memory as well as other clinical applications such as epilepsy monitoring using closed-loop paradigms. BrainCom will be carried out by a consortium assembled to foster the emergence of a new community in Europe acting towards the development of neural speech prostheses. Thanks to its high interdisciplinarity involving technology, engineering, biology, clinical sciences, and ethics, BrainCom will contribute advances to all levels of the value chain: from technology and engineering to basic and language neuroscience, and from preclinical research in animals to clinical studies in humans.

Agency: European Commission | Branch: FP7 | Program: CSA | Phase: INFRA-2009-3.3 | Award Amount: 320.92K | Year: 2009

In the Lisbon strategy, the 2005 European Council identified knowledge and innovation as the engines of sustainable growth and stated that it is essential to build a fully inclusive information society. In parallel, the World Conference on Disaster Reduction (Hyogo, 2005), defined among its thematic priorities the improvement of international cooperation in hydrometeorology research activities.\nHydrometeorological science has made strong progress over the last decade at the European and worldwide level: new modelling tools, post processing methodologies and observational data are available.\nIn principle, a huge amount of hydrometeorological data and information is available for the European region, but enormous scientific and technical obstacles have to be overcome when mining the data.\nRecent European efforts in developing a platform for e-science, like EGEE (Enabling Grids for E-sciencE), SEE-GRID-SCI (South East Europe -GRID e-Infrastructure for regional e-Science), and the German C3-Grid, provide an ideal basis for the sharing of complex hydrometeorological data sets and tools. Despite these early initiatives, however, the awareness of the potential of the Grid technology as a catalyst for future hydrometeorological research is still low and both the adoption and the exploitation have astonishingly been slow, not only within individual EC member states, but also on a European scale.\nWith this background in mind, the goal of the Distributed Research Infrastructure for Hydro-Meteorology Study (DRIHMS) project is the promotion of the Grid culture within the European hydrometeorological research community through the diffusion of a Grid platform for e-collaboration in this earth science sector: the idea is to further boost European research excellence and competitiveness in the fields of hydrometeorological research and Grid research by bridging the gaps between these two scientific communities.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.8.2 | Award Amount: 6.51M | Year: 2010

Quantum entanglement has the capacity to enable disruptive technologies that solve outstanding issues in: - Trust, privacy protection, and security in two- and multi-party transactions; - Novel or enhanced modes of operation of ICT devices; - Reference standards, sensing, and metrology. The development of entanglement-based strategies addresses these challenges and provides the foundations for quantum technologies of the 21st century. The practical exploitation of entanglement requires groundbreaking levels of robustness and flexibility for deployment in real-world environments. This ambitious goal can be reached only through radically new designs of protocols, architectures, interfaces, and components. Q-ESSENCE will achieve this by a concerted application-driven effort covering relevant experimental, phenomenological, and fundamental aspects. Our consortium will target three main outcomes: 1) Development of entanglement-enabled and entanglement-enhanced ICT devices: atomic clocks, quantum sensors, and quantum random-number generators; 2) Novel physical-layer architectures for long-distance quantum communication that surpass current distance limitations through the deployment of next-generation components; 3) Distributed quantum information protocols that provide disruptive solutions to multiuser trust, privacy-protection, and security scenarios based on multipartite entanglement. These outcomes will be reached through the underpinning science and enabling technologies of: light-matter interfaces providing faithful interconversion between different physical realizations of qubits; entanglement engineering at new scales and distances; robust architectures protecting quantum information from decoherence; quantum information concepts that solve problems of limited trust and privacy intrusion. The project builds on the outstanding expertise of the consortium demonstrated by pioneering works over the past decades, enhanced by a strong industrial perspective.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETOPEN-1-2014 | Award Amount: 3.38M | Year: 2016

Optical quantum technologies use light as a carrier of quantum information or to probe and control other quantum systems. They offer transformational advances in ultra-secure communication, sensing that surpasses classical limits, simulation of quantum systems and computation. To meet the high demands of these applications, systems with multiple quantum degrees of freedom that can be addressed by light and coupled to other quantum systems in hybrid architectures are strongly needed. However, current solid-state devices, which are highly desirable for technological development, do not fulfill these requirements. The goal of NanOQTech is to build nanoscale hybrid quantum devices that strongly couple to light. To achieve this breakthrough, we will create solid-state nanostructures that exploit the uniquely narrow optical transitions of rare earth ions. Our objectives are to develop RE nanostructures with long optical and spin coherences; couple these structures to optical micro-cavities to demonstrate single-ion optical quantum memories, two-qubit gates and deterministic narrowband single photon sources at 1.5 m; build hybrid RE-graphene devices to achieve plasmon mediated ion-ion interactions; fabricate hybrid RE nano-resonators to reach the strong coupling regime; guide the experimental effort and prepare further advances by developing comprehensive theoretical tools. The project gathers 9 leading experimental and theoretical European teams in inorganic chemistry, solid-state and atomic physics, quantum optics and information processing, nano-electronics and photonics and nano-mechanics. including a young industrial start-up specialized in real-time signal processing and control. Within a three-year research project, we propose to develop materials and explore functionalities to establish RE nanostructures as a radically new platform that will broadly impact research and technology in quantum communications, information processing and sensing.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-18-2015 | Award Amount: 8.19M | Year: 2016

Liver cancer in the paediatric population is rare with an incidence approximately 1-1.5 per million population. The commonest tumour seen in the childhood population is hepatoblastoma (HB), usually seen in young children and infants. Much rarer (about 10% of paediatric liver cancers) is hepatocellular carcinoma (HCC), usually seen in the teenage population and sometimes associated with underlying cirrhotic liver diseases. The ChiLTERN project relates to topic PHC 18 establishing effectiveness of health care interventions in the paediatric population. The ChiLTERN project builds on a unique opportunity to undertake a comprehensive research programme linked to an ambitious global partnership which will see the single largest clinical trial (the Paediatric Hepatic International Tumour Trial - PHITT) ever undertaken in this population of patients, with several randomised questions in six subgroups of patients. ChiLTERN will allow us to move towards an era of personalised therapy in which each patient will receive the correct amount of chemotherapy and will undergo has the best surgical operation (surgical resection or liver transplant). By using both clinical and biological information, we can assign patients more accurately to risk groups based on their survival. Using genetic tests and biomarkers, we will determine those children who may be at risk of developing long term side effects (deafness, heart failure, kidney damage). In addition, biomarkers will allow us to monitor during therapy and detect toxicities early before serious damage is done so that we can adapt treatment and prevent these problems. Finally, we will be using imaging technology tools which will help our surgeons plan liver operations more safely and effectively. Ultimately ChiLTERN will allow us to cure more children with liver cancer, expose fewer children to toxic chemotherapy and ensure their surgery is both effective and safe.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.3-1 | Award Amount: 7.70M | Year: 2008

Preliminary data indicate that there is a strong association between the incidence of immune-mediated diseases and improving standard of living and hygiene. One of the steepest gradient in standard of living worldwide is present at the border between Russian Karelia and Finland with a sevenfold difference in the gross national product, while Estonia represents a country in rapid transition. These three populations comprise a living laboratory providing a unique possibility to test the hygiene hypothesis in the development of immune-mediated diseases. The incidence of type 1 diabetes (T1D) is six times lower in Russian Karelia than in Finland, whereas there are very limited differences in the frequency of risk HLA genotypes in the background population. This proposal aims at comparing (i) the frequency of beta-cell autoimmunity and other organ-specific autoantibodies; (ii) the frequency of IgE-specific sensitisation and signs of allergy; (iii) the frequency of various infections; (iv) the gut microbial flora; and (v) dietary intake in young children between the three populations. The birth cohort arm of the study aims at (i) delineating the ontogeny of the immune system by using modern tools of functional genomics; (ii) comparing the functional characteristics of regulatory T cells; (iii) characterising the gut microbial colonisation in infants; (iv) assessing the timing of exposure to foreign proteins in infancy (v) defining the interrelations between dietary factors, gut microbial flora and acute microbial infections. The objectives will be approached by studying 1600 children at the age of 3 and 5 years and by observing a birth cohort comprising about 320 subjects with HLA-conferred susceptibility to autoimmunity from birth up to the age of 3 years in each country. This proposal is expected to provide new data on the reasons and mechanisms behind the increasing rates of T1D and other immune-mediated diseases seen in most developed countries after World War II.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.3-1 | Award Amount: 8.24M | Year: 2012

50 million diabetic EU citizens are using approved anti-diabetic agents to control their glycaemia. However, suboptimal glycemic control leads to 6 progressive diabetic complications, namely: nephropathy, retinopathy, cardiomyopathy, neuropathy and foot ulceration. In 2010, 11% of EU adult deaths (634,000) were caused by diabetic complications. These distinct disorders have few effective medicines and present challenging management issues for clinicians. Stromal Stem Cells (SSC) are a mixed population of plastic-adherent (PA) cells isolated from adult bone marrow. PA-SSC secrete potent immunosuppressive and angiogenic proteins and over 100 clinical trials are testing PA-SSC in 40 distinct autoimmune and ischemic diseases. Notably, preclinical studies show a single intravenous administration of un-modified PA-SSC can control rodent hyperglycaemia, prompting 10 recent clinical safety studies in diabetic patients. REDDSTAR will comprehensively examine if SSC can safely repair all 6 damaged tissues and control glycaemia in three different species. To facilitate this we identified an antibody (S2) that prospectively isolates comparable, equivalent S2\SSC from human, rat, mouse and rabbit marrow, enabling testing of pure S2\/- SSC and mixed PA-SSC from each species for the first time. Furthermore, separation of PA-SSC into S2\ and S2- fractions reveal functionally distinct populations. REDDSTAR partners have collectively developed five distinct clinically-relevant in vivo models of the 6 key diabetic complications. We will assess if S2\, S2- and PA-SSC exert differing control of glycaemia and tissue repair in each model. Finally, REDDSTAR partners are developing the first benchtop GMP-grade nanosorter, enabling clinical purification of S2\ and S2- SSC for human safety trials. We will dissect how S2\ and S2- SSC simultaneously repair tissue damage and maintain glycaemic control, an effect not observed with any current therapy.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.8.5 | Award Amount: 7.94M | Year: 2010

Future software-intensive systems, such as sensor networks, power grids, satellite and robot swarms, will generally exhibit a number of characteristic features:* Massive numbers of nodes, nodes with complex behavior, or complex interactions between nodes.* Operation in open and non-deterministic environments with variable network topology.* Need for adaptation, e.g., to changing environments and requirements.We call this future generation of software-intensive systems ensembles. The potentially huge impact - both positive and negative - of ensembles means that we need to understand ways to reliably and predictably model, design, and program them.Although there is a lot of research in this area, so far no theoretically well-founded technique for building ensembles exists. The goal of the ASCENS project is to develop such a method and to demonstrate its feasibility in three important application domains: robot swarms, cloud computing and e-mobility.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.47M | Year: 2015

RELENT is multidisciplinary group of scientists and clinical investigators whose goal is to develop individualized treatment for chronic autoimmune diseases, such as rheumatoid arthritis and vasculitis, that cause considerable mortality and morbidity, both from uncontrolled disease and treatment associated co-morbidities, like infection and malignancy. This requires the need to stratify patients by their outcome and to tailor immunosuppression based on much deeper knowledge of the mechanisms that control initiation and persistence of the pathogenic immune responses. The RELENT Consortium has been formed to generate this knowledge with the ultimate goal of developing treatments tailored to the specific needs of individual patients. RELENT combines the resources of seven leading European Investigators and two from US and Australia whose expertise is not available elsewhere in the world but necessary for the ambitious work program. Three SMEs will supply specific reagents and translate the results to biomarker development. This will enable RELENT to deliver its four specific research aims, namely to: i) Combine subset analysis of genome wide association studies with classical cell biology to uncover pathways that influence and ii) use multiplexed antigen arrays, whole proteome analysis and rapid mass analysis to identify protein signatures that predict outcome and response to treatment in chronic autoimmune disease. iii) Characterise T and B cell abnormalities that predispose to autoimmunity and infection by studying the ageing immune system in health and disease. iv) Analyse pathogenic effector T cells and their control by macrophages and dendritic cells and the molecules they secrete using in vivo models. We anticipate to identify common mechanisms responsible for the persistence and outcomes in severe autoimmune and inflammatory diseases in females and males and that the results should be rapidly translatable into clinical practice for the benefit of patients.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC5-01-2014 | Award Amount: 15.00M | Year: 2015

CRESCENDO brings together seven Earth System Modelling (ESM) groups with three Integrated Assessment Modelling teams, as well as experts in ESM evaluation, ESM projection and feedback analysis, climate impacts and science communication to address the following goals; (i) improve the process-realism and simulation-quality of European ESMs in order to increase the reliability of future Earth system projections; (ii) develop and apply a community ESM evaluation tool allowing routine ESM performance benchmarking, process-based ESM evaluation and the analysis of Earth system projections. The resulting tool will be installed and made openly-available on the Earth System Grid Federation (ESGF); (iii) further develop the discipline of emergent constraints in order to better constrain the representation of key biogeochemical and aerosol feedbacks in ESMs and thereby reduce overall uncertainty in Earth system projections; (iv) quantify the effective radiative forcing of key biogeochemical and aerosol feedbacks in ESM projections; (v) contribute to the development of a new set of combined socio-economic and climate emission scenarios that more explicitly link future socio-economic development pathways with global radiative forcing; (vi) apply the project ESMs to these new scenario data to generate an ensemble of Earth system projections for the coming century and, in combination with the underlying socio-economic scenarios, use these projections to assess joint risks and co-benefits related to climate change, climate impacts, adaptation and mitigation; (vii) ensure data produced by CRESCENDO is available to the international community through timely archival on the ESGF and work closely with climate impact assessment and regional downscaling teams to ensure maximum uptake and use of these data in such complementary areas of science; (viii) actively disseminate knowledge generated in CRESCENDO to fellow scientists, policymakers and the general public.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.92M | Year: 2013

IN-SENS is an interdisciplinary, cutting-edge European industry-academia collaborative effort for a novel training of scientists in molecular psychiatry with the prospect of discovering the biology of schizophrenia and actively promote drug discovery. Mental illnesses are a major burden to patients, relatives, and public health worldwide. IN-SENS therefore aims to profoundly change the academic-industry research landscape in European psychiatry by an unprecedented, innovative strategy. The extended intra- and intercellular signalling pathway of disrupted-in-schizophrenia 1 (DISC1), the best characterized gene known to cause schizophrenia and other chronic mental illnesses (CMI), will be used as a molecular Rosetta stone for this purpose. Expected results of IN-SENS include profound training, including clinical psychiatry, industrial, and translational medicine exposure, of a new generation of European ESRs capable of understanding the molecular underpinnings of CMI in academia, industry and other non-academic sectors. ESRs will explore how molecules related to the extended DISC1 pathway translate to the different biochemical, genetic, and neurodevelopmental hypotheses and data proposed so far as being important players in the molecular pathology of CMI. Further, they will play an active role in the generation of new analytical tools and therapeutic agents for the diagnosis and treatment of CMI in close collaboration with the industrial sector. IN-SENS will have immediate and longterm benefits for the European academic-industry research landscape in psychiatry by fostering scientific creativity and entrepreneurial skills of ESRs, generating novel research networks in Europe, enhancing mutual recognition and introducing novel models and of public-private cooperations. At the end of IN-SENS, exceptionally trained ESRs will be ready to extend these studies in academia and/or the private sector, and be able to move confidently to a fruitful professional career.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: MG-3.4-2014 | Award Amount: 2.90M | Year: 2015

European countries face great challenges because the demographic structure in the EU is changing rapidly, due to reducing birth rates and increasing life expectancies. In 2012, 17% of Europeans were aged 65 and older and in 2020 this will rise to 28%. Meanwhile, the mobility needs of the elderly are also changing. Maintaining a drivers licence is an important issue of independence today, both for males and females. Also technological developments like the introduction of e-bikes enables access to other means of transport. These demographic and behavioural changes are of growing concern to mobility and road safety. While accident data show a decreasing number of fatalities and serious injuries on EU roads, recent data from the ERSO show an increasing proportion of elderly in the fatality statistics. This trend is a serious threat to the achievements of recent decades and poses a challenge that must be addressed to meet goals set for further reduction of road fatalities. Furthermore, there is an increasing rate of obesity in EU populations, which introduces changes in injury patterns and risks. The SENIORS project focuses on the protection of elderly and obese road users also by transferring nowadays younger generations safety standards. The objective is to develop the required understanding of accident scenarios, injury mechanisms and risks and to implement these findings in test tools and test and assessment procedures. An integrated approach considering the elderly in multiple transport modes is applied to reduce the portion of elderly fatalities. The small-scale project focuses on providing tools to encourage wider adoption of advanced restraint and pedestrian protection systems improving the protection of older and obese vulnerable road users. The activities consolidate results from previous EU projects such as THORAX and AsPeCSS and meet the needs defined by the GRSP IWG on Frontal Impact working on a near-term (2015) and mid-term (2020) update of UN-R94.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-01-2014 | Award Amount: 5.92M | Year: 2015

The Gluco-Psychosocial Axis (GPA) concerns the interplay of factors determining glucose metabolism and insulin sensitivity and the neuroendocrine response resulting from exposure to psychosocial stress. A sub-optimal GPA influences the development of type 2 diabetes and related impairments with varying degrees of interplay between genetics and early growth (particularly adiposity and cognitive function), and social, occupational, and other modifiable lifestyle factors. Many exposures apply from throughout life, and potential exposure to a sub-optimal GPA lead to a cumulative risk of ill health and decreased economic prospects for the ageing. Understanding these factors, interactions and extent they contribute to the preservation of glucose homeostasis and psychosocial functioning is important for the development of preventive and therapeutic measures promoting healthy and active ageing. DynaHEALTH will contribute to implementing a dynamic model for early GPA risk identification and validation, allowing development of risk-based prevention tools and policies that will help to inform policy makers on the best periods to invest in cost-effective and sustainable healthcare strategies. DynaHEALTH comprises 13 partners from academic/private sectors and will leverage data from 21 birth cohorts and intervention studies, involving 1.5 million Europeans. By identifying biological and psychosocial determinants of the GPA and characterising metabolic and epigenetic factors, whilst quantifying the impact of exposure to an optimal lifelong GPA, DynaHEALTH will influence weight gain, glucose homeostasis, employability, health deterioration and disease accumulation as individuals age. DynaHEALTH includes the potential to exploit the results for new technologies and strategies, adding to our understanding of pathways related to healthy and active ageing, underpinning options for targeted, personalised healthcare and mitigating the effects of sub-optimal GPA on ageing.

The main objective of this research proposal is to identify and elaborate those characteristics of ENM that determine their biological hazard potential. This potential includes the ability of ENM to induce damage at the cellular, tissue, or organism levels by interacting with cellular structures leading to impairment of key cellular functions. These adverse effects may be mediated by ENM-induced alterations in gene expression and translation, but may involve also epigenetic transformation of genetic functions. We believe that it will be possible to create a set of biomarkers of ENM toxicity that are relevant in assessing and predicting the safety and toxicity of ENM across species. The ENM-organism interaction is complex and depends, not simply on the composition of ENM core, but particularly on its physico-chemical properties. In fact, important physico-chemical properties are largely governed by their surface properties. All of these factors determine the binding of different biomolecules on the surface of the ENM, the formation of a corona around the ENM core. Thus, any positive or negative biological effect of ENM in organisms may be dynamically modulated by the bio-molecule corona associated with or substituted into the ENM surface rather than the ENM on its own. The bio-molecule corona of seemingly identical ENM cores may undergo dynamic changes during their passage through different biological compartments; in other words, their biological effects are governed by this complex surface chemistry. We propose that understanding the fundamental characteristics of ENM underpinning their biological effects will provide a sound foundation with which to classify ENM according to their safety. Therefore, the overarching objective of this research is to provide a means to develop a safety classification of ENM based on an understanding of their interactions with living organisms at the molecular, cellular, and organism levels based on their material characteristics.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 2.80M | Year: 2009

The proposed ITN will support close collaboration between 8 highly experienced and complementary European teams, who in all cases are working at the forefront of semiconductor science, photonics and materials technology. The real value that is offered by our collaboration will be realized by the generation of new, genuinely disruptive hybrid-semiconductor optoelectronic technologies. It will also train the next generation of scientists at the highest level, producing a skilled cadre of researchers who will contribute the Europes competitiveness in emerging optoelectronic technologies. Our network has world-leading experience in the field of structure fabrication and material synthesis (both organic and inorganic), together with a strong focus in ultra-fast spectroscopy, nano-optics, photonics, non-linear optics and device engineering. We also have a significant experience in high-level theoretical analysis of the optical properties of organic and inorganic semiconductors, as well as experience in industrial research. The establishment of ICARUS will thus realize the creation of new hybrid systems, their characterization and their implementation in photonic and optoelectronic devices.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-2 | Award Amount: 3.85M | Year: 2012

Children with diffuse lung disease, also called childhood interstitial lung diseases (chILD), may have one of more than 200 entities, the biggest group of respiratory orphan lung diseases. Frequently undiagnosed because of lack of awareness or complex differential diagnosis, they lead to much morbidity, mortality (about 15%) and psychosocial stress for the families. Current lack of evidence based guidelines reflects the absence of any real scientific evidence for management. All current therapeutic options are off label. We propose that leading European clinical scientists and paediatric pulmonologists collaborate to assemble cohorts in which children with well defined disease entities, verified by international panels of clinicians, radiologists, geneticists and pathologists are followed in a pan-European database and biobank compatible with others worldwide to allow common projects. Outcomes and treatment schemes will be rigorously defined and their value systematically assessed. We will put defined treatment protocols systematically into practice to allow their evaluation and perform a randomised controlled trial in line with the EU recommendations, to put prescribing for children on an evidence based footing. This will give evidence to use medicines available based on their objectively determined effects and side effects. The project will lead to accepted evidence-based and consensus-agreed diagnostic and management clinical guidelines, to a better care of patients afflicted by rare chILD and lead to improved quality of life for children with these incurable diseases.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.2.2 | Award Amount: 10.43M | Year: 2009

The ROSETTA project develops a new generation of robot controller technology for human-like industrial robots working together with humans. The control system uses a variety of sensor-based skills, together with knowledge about how to adapt them on-line to the concrete situation. The controller executes complex tasks with a high degree of autonomy, because it has network access to a knowledge repository and management system. The knowledge repository receives feedback from a population of installed robot systems, that have received their programmes from the repository earlier, and that now share their individual improvements and experiences. The knowledge repository can thus improve and extend itself at an unprecedented fast rate.\nThis will result in:\n- A new paradigm for engineering & instructing of robots, based on robot task and skill representations. Human programmers will be able to build a robot application using task-level instructions, embedding knowledge about the sensing, planning, control and decision making that is appropriate for the task. A breakthrough will be finding representations of all types of knowledge required in the envisaged production application. These results will be implemented on a controller and tested in an assembly application with human-like robots, with on-line error detection and error recovery, using adaptive hybrid control for self-improvement, and natural language interaction.\n- New sensing, control and decision making methods for safe physical human-robot interaction. This includes new functionalities that are human-centred: the controller has knowledge about how it could inflict injuries on humans, and how to avoid them, and it is equipped with sensors, sensor processing and reasoning capabilities to find the optimal trade-off between effective progress in its task and safe and psychologically acceptable physical interaction with the human co-worker(s), which will be subject to standardisation efforts.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.2.1 | Award Amount: 7.87M | Year: 2008

Compared to humans or primates, the ability of contemporary robotic hands is suprisingly limited, they can grasp only few objects in constricted poses with limited grasping postures and position. The aim of GRASP is the design of a cognitive system capable of performing tasks in open-ended environments, dealing with uncertainty and novel situations. We have decided to study the problem of object manipulation and grasping, by providing theoretical and measurable basis for system design that are valid in both human and artificial systems. We believe that this is of utmost importance for the design of artificial cognitive systems that are to be deployed in real environments and interact with humans and other artificial agents. Such systems need the ability to exploit the innate knowledge and self-understanding to gradually develop cognitive capabilities. To demonstrate the feasibility of our approach, we will instantiate, implement and evaluate our theories on robot systems with different emobodiments and levels of complexity. These systems will operate in real-world scenarios, with and without human intervention and tutoring.\n\nGRASP will develop means for robotic systems to reason about graspable targets, to explore and investigate their physical properties and finally to make artificial hands grasp any object. We will use theoretical, computational and experimental studies to model skilled sensorimotor behavior based on known principles governing grasping and manipulation tasks performed by humans. Therefore, GRASP sets out to integrate a large body of findings from disciplines such as neuroscience, cognitive science, robotics, multi-modal perception and machine learning to achieve a core capability: Grasping any object by building up relations between task setting, embodied hand actions, object attributes, and contextual knowledge.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: KBBE-2007-2-2-06 | Award Amount: 3.92M | Year: 2008

Allergy has developed into a major health concern in Europe. Allergic diseases can currently be managed effectively but not cured. The onset of allergies stars early in life and there is increasing evidence that exogenous factors affecting the incidence of these illnesses exert their effect early in life, in part even prenatally. The highly interdisciplinary EFRAIM project will prospectively investigate the main protective factors in early life influencing the development of allergies in birth cohorts conducted in allergy protective environments in five European countries. These birth cohorts have been enrolling over 1,000 children and have collected detailed information on the onset of allergic illnesses, objective measures of allergies and a vast amount of information about a number of environmental exposures. Large biobanks with a variety of biological samples have been established. In the EFRAIM project particular attention will be given to the potential role of dietary exposures, lifestyle and other environmental (e.g. microbial) exposures early in life which are causal determinants rather than triggers of the illness. The mechanisms mediating these protective exposures such as the maturation of immune responses, gut colonisation, the mucosal barrier function and the genetic and epigenetic factors interacting with the environmental exposures will be investigated. The knowledge about protective exposures early in life can be turned into the development of preventive strategies. The EFRAIM project will actively address two routes of preventive interventions in animal models and in vitro studies: the development of an allergy protective milk formula and the development of an allergy vaccine. Both approaches are based on knowledge gained in the human studies. The EFRAIM project is expected to produce ground-breaking new insights on protective agents and their mechanisms that can be used to prevent the further development of allergies.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.78M | Year: 2015

The cell nucleus is organized and compartmentalized into a highly ordered structure that contains DNA, RNA, chromosomal and histone proteins which make up a structure called chromatin. The dynamics associated with these various components are responsible for regulating physiological processes and the overall stability of the genome. The destabilization of such regulatory mechanisms that act on the chromatin structure are implicated in pathologies such as cancer. Higher order organization of chromatin results in chromosomes which occupy discrete territories within the cell nucleus. Most nuclear processes occur or at least being initiated onto the chromosomes which makes them the main organizing factors in the nucleus. Several proteins that are involved in the replication of DNA, gene transcription and the processing of RNA are found enriched in discrete focal structures. An emerging question is how these structures assemble and are maintained in the absence of membranes and moreover what are the kinetics of stable binding and/or rapid exchange of their components. The dynamic assembly and modification of chromatin during developmental processes as well as the deregulation of such chromatin dynamics during the onset of disease lacks mechanistic insights at present. To address these questions we have put forward a multidisciplinary approach which involves molecular, cellular and systems level approaches by assembling a group of scientists from academia and industry with cross disciplinary expertise and capabilities.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: NMP-2008-1.1-2 | Award Amount: 1.53M | Year: 2009

The NANOTOTOUCH proposal aims to create innovative environments for the broad public to learn about and to discuss nano research by directly involving the actors of research themselves. We propose to do this by taking the laboratory environment and the research work out of enclosed academic campuses and relocating them right in the midst of the public in science museums and science centres. Three science museums and three science centres will closely cooperate with local university partners to create three permanent Open Nano Lab locations (in Munich, Milan and Gothenburg) and three Nano Researcher Live areas (in Mechelen, Tartu and Naples). In these places the visitors will experience live the day-to-day practices and processes of nano research conducted by young scientists. This peer-to-peer dialogue on an equal basis between lay public and nano-researchers not only creates a bidirectional feedback, it also minimises the expert-to-lay bias (top-down approach) inherent present science communication processes with authoritative top researchers. In order to prepare the young scientists for this novel method of communication, NANOTOTOUCH also includes a strong communication skills training component. NANOTOTOUCH will also establish new role models for choosing science as a career: young adults thinking of entering science will be able to discuss various aspects with young researchers who themselves made this decision recently, whilst upcoming researchers will learn that communication is a self-evident part of their professional identity. Thus, NANOTOTOUCH pushes science communication to its extreme, merging communication and research in a powerful way and responding to the need for more transparency and accessibility in science. Furthermore, the strong synergetic network approach of the project enables contents and models to be developed for further distribution and implementation in educational and scientific communities.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-2 | Award Amount: 9.24M | Year: 2013

Affective and non-affective psychoses have a major negative impact on human society. They account for 6.3% of the global burden of disease and cost 207 billion per year in Europe alone, making them the most expensive brain-related disorders and even more expensive than cardiovascular diseases. This socioeconomic burden is largely caused by two core disease features: onset in adolescence and early adulthood and long-term disabling disease courses. Both factors lead to enduring social and vocational exclusion and contribute to 8-20 times higher suicide rates in affected patients. Reliable and accessible prognostic tools will alleviate this burden by enabling individualised risk prediction, thus facilitating the targeted prevention of psychoses. Thus, we will first use routine brain imaging and complementary data to optimise our candidate biomarkers for the prediction and staging of psychoses and generate a prognostic system that generalises well across mental health services. Secondly, we will implement new multi-modal risk quantification tools to predict mental health-related disability in young help-seekers. The fusion of these tools with clinical knowledge will produce cybernetic prognostic services that accurately identify help-seekers at the highest risk of psychosis, poor functioning and suicide-related mortality. During this project we will secure our intellectual property rights and transform into a European company to commercially exploit these prognostic services through internet-based telemedicine applications. This will provide psychosis risk profiling tools to diverse target groups in the healthcare markets, including care-givers, the pharmaceutical industry and research institutions. By disseminating objective risk quantification, these products will provide firm diagnostic grounds for preventive therapy, improving outcomes and reducing costs. Thus, they will offer a unique selling proposition to the mental health sectors in Europe and beyond.

Agency: European Commission | Branch: FP7 | Program: ERC-SG | Phase: ERC-SG-SH4 | Award Amount: 1.94M | Year: 2010

This project aims to uncover and clarify phylogenetic relationships between native South American languages. Very little is known about the historical development of the linguistic diversity in this part of the world, and more detailed insights will have a major impact not only on linguistics, but also on genetics, archeology, and cultural anthropology. The approach taken is to digitize available lexical information about the languages in question, and to develop new and innovative computer-assisted methods to quantify the analysis of this information. This quantification will be based on the techniques and experiences of the traditional historical-comparative method, and not use the Swadesh-style approach using wordlists. This novel quantitative approach makes it possible to process more data in a more consistent and faster manner, and as a consequence uncover more evidence for genealogical relations. The availability of more evidence is essential to push back the phylogenetic time-depth beyond the few thousand years to which historical linguistics is traditionally limited. A second key objective of this project is to transform historical-comparative linguistics from a primarily handcrafted scholarly endeavor, performed by individual researchers, into a quantitative and collaborative field of research, involving linguists, mathematicians and computer scientists alike. The project will build a truly interdisciplinary team to improve the interaction between linguistics and mathematics. In this way, not just historical linguistics will profit from methods and insights previously developed in mathematics and computer science, but the special requirements posed by language variation and language change will also reframe and further extend current phylogenetic methods.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SEC-2012.4.1-2;SEC-2012.4.3-1 | Award Amount: 4.77M | Year: 2013

With the overall objective to improve psycho-social support in crisis management, the proposed project PsyCris (36-months) has the following goals: (1) status quo analysis of psychological and medical support in crises in European countries, (2) improvement of support strategies for victims and crisis managers, (3) enhancement of psycho-medical preparedness for major incidents (contingency planning), (4) development of interventions to deal with stress and reduce stress related disorders of crisis management personnel and authorities, (4) providing efficient self-help strategies to communities affected by crises and (5) investigation of long-term psychosocial, societal and cultural impact of crises. The 11 partners of the consortium comprise research centres, public bodies, small / medium enterprises and stakeholder / end-user organisations from Germany, Spain, Israel, Lithuania, Luxembourg and Austria. As its main product, the project will provide a set of tool kits enabling (1) efficient handling of relevant data, (2) transfer of knowledge and practical competences relevant for crisis management, stress control and social support and (3) rapid decision-making in concrete crises. The tool kits are integrated within a computerised knowledge system combining e-learning and face-to-face teaching. Research and development are based on a multi-disciplinary approach including methods from psychology (e.g. stress management, human resources management, psycho-trauma intervention), education sciences (e.g. knowledge management), informatics (e.g. decision making heuristics), engineering, sociology and health sciences. Current and possible changes in society, health systems and climate as well as cross-cultural and gender aspects are carefully considered. PsyCris will propose guidelines for preparedness, prevention and intervention for crises. The results will have a significant impact on public health, community resilience, international cooperation and cost containment.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 2.84M | Year: 2008

COSI integrates young researchers in a network of 10 leading European research centres, including Bayer BioScience as industrial partner. We aim at identification of regulatory principles governing chloroplast metabolism, a crucial factor for agricultural productivity. Specifically we want to identify chloroplast-related protein kinases and their targets and associated calcium signals. A long term objective of COSI is increased plant productivity under stress conditions. COSI has expertise in various aspects of photosynthesis in algae and higher plants and in plant signal transduction. This unique combination will be used to identify major regulatory principles of plant organellar metabolism principally also applying far beyond the plant field. Thus training and knowledge can be transferred to many other fields in life sciences. An integrated working programme consisting of working packages, jointly coordinated by two groups of the network, guarantees maximal use of complementary expertises and strengthens ongoing interactions between partners. In addition to intensive exchange and collaboration of the involved young researchers, special training courses will introduce the young researchers in basic methods, which are required for their work and furthermore help them to develop complementary skills. Early stage researchers will be supported by a mentoring programme to enhance their personnel development. Special emphasis will be placed on promotion of women. A training course at Bayer BioScience will expose young researchers to an industrial environment and provide them with industrial relevant skills. COSI will offer hands-on training in cutting-edge technologies such as bioinformatics, live-cell imaging, mass spectrometry and metabolomics and establish an outstanding European research community in organellar signal transduction, an emerging new and competitive research field of central importance in life sciences.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.2.1-4 | Award Amount: 4.02M | Year: 2008

MEMOSAD aims at defining the molecular mechanisms of Abeta- and Tau-induced synaptotoxicity and at developing disease-modifying therapeutics for the prevention of memory loss in Alzheimer disease (AD). Insoluble aggregates of the two proteins provide the pathological hallmarks of this incurable brain disorder. Early stage AD is characterized by a remarkably pure impairment of declarative memory and several lines of evidence suggest that this memory impairment is independent of the insoluble aggregates, does not require neuronal death and is caused by subtle and transient synaptic changes. The toxic Abeta and Tau species that cause synaptic dysfunction, their mechanism of toxicity and the link between both pathologies remain largely unknown, but recent data suggest that Abeta accumulation triggers Tau pathology. Consequently, primary neuronal cultures and animal models (C.elegans,zebrafish,mouse) will be employed to define the pathologic pathways leading from Abeta through Tau to synaptotoxicity. Initial experiments will investigate the effect of well-defined Abeta species on long term potentiation, synaptic morphology, gene expression, Tau phosphorylation/aggregation, axonal transport and behaviour. Similarly, we will investigate the functional consequences of Tau misfunction, aggregation, hyperphosphorylation and missorting in various cell culture systems (retinal ganglion cells, primary hippocampal neurons, organotypical slices) and animal models, especially with regard to intraneuronal trafficking and synaptic function. Once the toxic Abeta and Tau species are known and their mechanism of toxicity are defined, we will investigate how these pathways interact. Unravelling the pathologic pathways that lead from Abeta through Tau to synaptotoxicity and memory loss should reveal novel points for therapeutic intervention. Our aim is to deliver 3 or 4 validated therapeutic targets and at least 2 compounds with demonstrated therapeutic efficacy in mouse models of AD.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.73M | Year: 2014

Powered Two Wheelers (PTWs) are an efficient and flexible transport system and their use is beneficial especially in the more and more congested European cities. Unfortunately the PTW riders are exposed to a high risk of becoming a victim in a crash mainly due to the difficulty to control a PTW under all circumstances but also due to limited conspicuity. In addition when PTW riders are crash victims limited protection is offered to prevent injuries when compared to vehicle occupants. The aim of the research activities within the project is to make the use of PTWs safer such that fewer accidents occur and if an accident is unavoidable the consequences for the rider to sustain injuries are minimal. The project is divided in three work packages (WPs) with three separate but related goals . The first work package aims to improve the riders skills with training strategies that are derived from in-depth accident data and from a quantification of rider behaviour in critical situations. The second work package aims at developing advanced safety systems that improve the interaction between the rider and the PTW by modelling the rider, also based on the in WP1 quantified rider behaviour. The third work package considers the cases where the crash is unavoidable and will develop personal protective equipment to protect the riders, given the input conditions from WP2 at the moment right before impact. The end result of this project will be a set of rider training guidelines that are proven to be effective, safety system concepts implemented on PTWs and improved personal protective equipment and accompanying standards. These can be used by PTW industry partners in product development processes and by stakeholders such as ACEM and the EU to educate riders. This will ultimately improve the safety of PTWs and moreover the perceived safety, which will make more people decide to use a PTW as a good alternative to other means of transport.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.00M | Year: 2016

Stroke and dementia rank among the most pressing health issues in Europe. Cerebral small vessel diseases (SVDs) have emerged as a central link between these two major co-morbidities. SVDs account for more than 30% of strokes and at least 40% of dementia cases. They encounter multiple distinct diseases that can be separated based on their underlying genetic defects, risk factors, and clinical presentations. Despite this profound impact on human health, there are no treatments with proven efficacy against SVDs. The applicants have made major progress in identifying key mechanisms involved in SVDs and their co-morbidities. We recently identified blood pressure variability as a major independent risk factor for multiple SVDs, stroke, and dementia and illuminated the roles of the blood brain barrier and the extracellular matrix in small vessel function. We further identified novel molecular pathways (TIMP3, LTBP1, TGF) that are shared between different SVDs and thus point towards common mechanisms. This EU network, which brings together basic scientists and academic clinicians, will make use of novel animal models and expertly phenotyped patient cohorts to identify key mechanisms common to multiple SVDs and determine how these mechanisms contribute to individual SVDs. We will: i) identify common molecular, cellular, and physiological mechanisms that compromise the function of microvessels in different SVDs; ii) determine how these common mechanistic defects intersect to drive brain damage; and iii) validate the relevance of mechanisms through interventions in experimental systems (isolated microvessels and in vivo) and in patients (exploratory proof of concept trials). Our resources including novel animal models and state-of-the art technologies (e.g. proteomics & ultra-high field MRI) as well as expertise in clinical trials support the feasibility of the approach. In fact, studies by the applicants already revealed novel attractive targets for therapeutic intervention.

Ideguchi T.,Max Planck Institute of Quantum Optics | Poisson A.,CNRS Orsay Institute for Molecular Science | Guelachvili G.,CNRS Orsay Institute for Molecular Science | Picque N.,Ludwig Maximilians University of Munich | Hansch T.W.,Ludwig Maximilians University of Munich
Nature communications | Year: 2014

The spectrum of a laser frequency comb consists of several hundred thousand equally spaced lines over a broad spectral bandwidth. Such frequency combs have revolutionized optical frequency metrology and they now hold much promise for significant advances in a growing number of applications including molecular spectroscopy. Despite an intriguing potential for the measurement of molecular spectra spanning tens of nanometres within tens of microseconds at Doppler-limited resolution, the development of dual-comb spectroscopy is hindered by the demanding stability requirements of the laser combs. Here we overcome this difficulty and experimentally demonstrate a concept of real-time dual-comb spectroscopy, which compensates for laser instabilities by electronic signal processing. It only uses free-running mode-locked lasers without any phase-lock electronics. We record spectra spanning the full bandwidth of near-infrared fibre lasers with Doppler-limited line profiles highly suitable for measurements of concentrations or line intensities. Our new technique of adaptive dual-comb spectroscopy offers a powerful transdisciplinary instrument for analytical sciences.

Mashaghi A.,FOM Institute for Atomic and Molecular Physics | Kramer G.,University of Heidelberg | Lamb D.C.,Ludwig Maximilians University of Munich | Mayer M.P.,University of Heidelberg | Tans S.J.,FOM Institute for Atomic and Molecular Physics
Chemical Reviews | Year: 2014

Single-molecule methods provide an exciting new tool to address many of the long-standing questions in chaperone-assisted protein folding. Single-molecule methods allow one not only to study the conformation and dynamics of chaperones and their influence on the conformation of substrates but also to investigate the protein-folding landscape. As chaperone-assisted folding pathways involve a number of players and interactions, one of the next steps for single molecule experiments on chaperones is to increase the complexity of the systems. Microfluidic devices can be used to allow rapid mixing and dilution for investigating protein unfolding and refolding. The ultimate single molecule assay on chaperone-assisted protein folding would be to follow protein folding inside the highly crowded living cell. Many steps toward single-molecule folding experiments in live cells have already been taken, including the first live-cell folding experiments on the ensemble level and single-molecules measurements in living cells and bacteria.

Murayama K.,University of California at Los Angeles | Murayama K.,Japan Society for the Promotion of Science | Pekrun R.,Ludwig Maximilians University of Munich | Fiedler K.,University of Heidelberg
Personality and Social Psychology Review | Year: 2014

Recent studies have indicated that research practices in psychology may be susceptible to factors that increase false-positive rates, raising concerns about the possible prevalence of false-positive findings. The present article discusses several practices that may run counter to the inflation of false-positive rates. Taking these practices into account would lead to a more balanced view on the false-positive issue. Specifically, we argue that an inflation of false-positive rates would diminish, sometimes to a substantial degree, when researchers (a) have explicit a priori theoretical hypotheses, (b) include multiple replication studies in a single paper, and (c) collect additional data based on observed results. We report findings from simulation studies and statistical evidence that support these arguments. Being aware of these preventive factors allows researchers not to overestimate the pervasiveness of false-positives in psychology and to gauge the susceptibility of a paper to possible false-positives in practical and fair ways. © 2013 by the Society for Personality and Social Psychology, Inc.

Elliot A.J.,University of Rochester | Maier M.A.,Ludwig Maximilians University of Munich
Annual Review of Psychology | Year: 2014

Color is a ubiquitous perceptual stimulus that is often considered in terms of aesthetics. Here we review theoretical and empirical work that looks beyond color aesthetics to the link between color and psychological functioning in humans. We begin by setting a historical context for research in this area, particularly highlighting methodological issues that hampered earlier empirical work. We proceed to overview theoretical and methodological advances during the past decade and conduct a review of emerging empirical findings. Our empirical review focuses especially on color in achievement and affiliation/attraction contexts, but it also covers work on consumer behavior as well as food and beverage evaluation and consumption. The review clearly shows that color can carry important meaning and can have an important impact on people's affect, cognition, and behavior. The literature remains at a nascent stage of development, however, and we note that considerable work on boundary conditions, moderators, and real-world generalizability is needed before strong conceptual statements and recommendations for application are warranted. We provide suggestions for future research and conclude by emphasizing the broad promise of research in this area. © Copyright ©2014 by Annual Reviews. All rights reserved.

Krausz F.,Ludwig Maximilians University of Munich | Krausz F.,Max Planck Institute of Quantum Optics | Stockman M.I.,Ludwig Maximilians University of Munich | Stockman M.I.,Max Planck Institute of Quantum Optics | Stockman M.I.,Georgia State University
Nature Photonics | Year: 2014

The accurate measurement of time lies at the heart of experimental science, and is relevant to everyday life. Extending chronoscopy to ever shorter timescales has been the key to gaining real-time insights into microscopic phenomena, ranging from vital biological processes to the dynamics underlying high technologies. The generation of isolated attosecond pulses in 2001 allowed the fastest of all motions outside the nucleus-electron dynamics in atomic systems-to be captured. Attosecond metrology has provided access to several hitherto immeasurably fast electron phenomena in atoms, molecules and solids. The fundamental importance of electron processes for the physical and life sciences, technology and medicine has rendered the young field of attosecond science one of the most dynamically expanding research fields of the new millennium. Here, we review the basic concepts underlying attosecond measurement and control techniques. Among their many potential applications, we focus on the exploration of the fundamental speed limit of electronic signal processing. This endeavour relies on ultimate-speed electron metrology, as provided by attosecond technology. © 2014 Macmillan Publishers Limited.

Chagnaud B.P.,Ludwig Maximilians University of Munich | Chagnaud B.P.,Cornell University | Bass A.H.,Cornell University
Journal of Neuroscience | Year: 2013

Corollary discharge is essential to an animal's ability to filter self-generated from external stimuli. This includes acoustic communication, although direct demonstration of a corollary discharge that both conveys a vocal motor signal and informs the auditory system about the physical attributes of a self-generated vocalization has remained elusive for vertebrates. Here, we show the underlying synaptic activity of a neuronal vocal corollary discharge pathway in the hindbrain of a highly vocal species of fish. Neurons carrying the vocal corollary discharge are specifically adapted for the transmission of duration information, a predominant acoustic cue. The results reveal that vertebrates, like some insects, have a robust corollary discharge conveying call duration. Along with evidence for the influence of vocal duration on auditory encoding in mammals, these new findings suggest that linking vocal motor and corollary discharge pathways with pattern generating, call duration neurons is a shared network character across the animal kingdom. © 2013 the authors.

Gabius H.-J.,Ludwig Maximilians University of Munich | Kaltner H.,Ludwig Maximilians University of Munich | Kopitz J.,University of Heidelberg | Andre S.,Ludwig Maximilians University of Munich
Trends in Biochemical Sciences | Year: 2015

The profile of cell surface molecules, the biochemical platform for cellular communication, can be likened to a molecular fingerprint. Historically, raising monoclonal antibodies by immunization with cells has been instrumental in obtaining tools suited for phenotyping and functional analysis. Initially for leukocyte antigens, the resulting cluster of differentiation (CD) nomenclature has become a popular system for classification. Glycans presented on proteins or lipids and receptors for carbohydrate structures (lectins) are part of the CD list. Our review presents biochemical and biomedical highlights of the respective CD entries. © 2015 Elsevier Ltd.

Dreyling M.,Ludwig Maximilians University of Munich | Ferrero S.,University of Turin | Hermine O.,University of Paris Pantheon Sorbonne
Leukemia | Year: 2014

Mantle cell lymphoma (MCL) is no longer a hopeless disease. Considered to carry a uniformly dismal prognosis so far, during the last years it has been rediscovered as a heterogeneous clinical and biological entity. Such a complexity has been highlighted by molecular genetics, unraveling different pathways of cell survival and progression. Concurrently, the application of new therapeutic paradigms including rituximab, high-dose cytarabine and stem cell transplantation dramatically improved treatment activity and the introduction of innovative targeted molecules has already led to new patient perspectives. In this completely new and continually evolving landscape, the clinical hemato-oncologist might feel disoriented on what are the best current strategies to handle such a critical disease and the gold standard therapeutic options for MCL. Here we address some burning questions on how to manage MCL patients, spacing from prognostic issues to the dilemma of personalized treatment in different scenarios of the disease: how to diagnose an MCL? Which are the fundamental staging procedures? What are the most reliable prognosticators? Is there a place for watch and wait? Which are the best treatment options for younger, elderly and frail patients? Which patients are addressable to high-dose therapy? What is the role of allogeneic transplantation? What is the most appropriate approach for relapsing disease in different categories of patients? What novelties are going to be introduced in the near future? The practical algorithms here discussed represent an evidence-based approach derived from results of multicenter and randomized trials.

Loew A.,Max Planck Institute for Meteorology | Schlenz F.,Ludwig Maximilians University of Munich
Hydrology and Earth System Sciences | Year: 2011

Validating coarse scale remote sensing soil moisture products requires a comparison of gridded data to point-like ground measurements. The necessary aggregation of in situ measurements to the footprint scale of a satellite sensor (>100 km2) introduces uncertainties in the validation of the satellite soil moisture product. Observed differences between the satellite product and in situ data are therefore partly attributable to these aggregation uncertainties. The present paper investigates different approaches to disentangle the error of the satellite product from the uncertainties associated to the up-scaling of the reference data. A novel approach is proposed, which allows for the quantification of the remote sensing soil moisture error using a temporally adaptive technique. It is shown that the point-to-area sampling error can be estimated within 0.0084 [m3/m3]. © 2011 Author(s).

Bloch I.,Ludwig Maximilians University of Munich | Bloch I.,Max Planck Institute of Quantum Optics | Dalibard J.,Kastler-Brossel Laboratory | Nascimbene S.,Ludwig Maximilians University of Munich | Nascimbene S.,Kastler-Brossel Laboratory
Nature Physics | Year: 2012

Ultracold quantum gases offer a unique setting for quantum simulation of interacting many-body systems. The high degree of controllability, the novel detection possibilities and the extreme physical parameter regimes that can be reached in these 'artificial solids' provide an exciting complementary set-up compared with natural condensed-matter systems, much in the spirit of Feynman's vision of a quantum simulator. Here we review recent advances in technology and discuss progress in a number of areas where experimental results have already been obtained. © 2012 Macmillan Publishers Limited. All rights reserved.

Pan J.-W.,Anhui University of Science and Technology | Chen Z.-B.,Anhui University of Science and Technology | Lu C.-Y.,Anhui University of Science and Technology | Weinfurter H.,Ludwig Maximilians University of Munich | And 6 more authors.
Reviews of Modern Physics | Year: 2012

Multiphoton interference reveals strictly nonclassical phenomena. Its applications range from fundamental tests of quantum mechanics to photonic quantum information processing, where a significant fraction of key experiments achieved so far comes from multiphoton state manipulation. The progress, both theoretical and experimental, of this rapidly advancing research is reviewed. The emphasis is given to the creation of photonic entanglement of various forms, tests of the completeness of quantum mechanics (in particular, violations of local realism), quantum information protocols for quantum communication (e.g., quantum teleportation, entanglement purification, and quantum repeater), and quantum computation with linear optics. The scope of the review is limited to "few-photon" phenomena involving measurements of discrete observables. © 2012 American Physical Society.

Lindner R.,University of Heidelberg | Friedel C.C.,Ludwig Maximilians University of Munich
PLoS ONE | Year: 2012

Transcriptome sequencing (RNA-Seq) overcomes limitations of previously used RNA quantification methods and provides one experimental framework for both high-throughput characterization and quantification of transcripts at the nucleotide level. The first step and a major challenge in the analysis of such experiments is the mapping of sequencing reads to a transcriptomic origin including the identification of splicing events. In recent years, a large number of such mapping algorithms have been developed, all of which have in common that they require algorithms for aligning a vast number of reads to genomic or transcriptomic sequences. Although the FM-index based aligner Bowtie has become a de facto standard within mapping pipelines, a much larger number of possible alignment algorithms have been developed also including other variants of FM-index based aligners. Accordingly, developers and users of RNA-seq mapping pipelines have the choice among a large number of available alignment algorithms. To provide guidance in the choice of alignment algorithms for these purposes, we evaluated the performance of 14 widely used alignment programs from three different algorithmic classes: algorithms using either hashing of the reference transcriptome, hashing of reads, or a compressed FM-index representation of the genome. Here, special emphasis was placed on both precision and recall and the performance for different read lengths and numbers of mismatches and indels in a read. Our results clearly showed the significant reduction in memory footprint and runtime provided by FM-index based aligners at a precision and recall comparable to the best hash table based aligners. Furthermore, the recently developed Bowtie 2 alignment algorithm shows a remarkable tolerance to both sequencing errors and indels, thus, essentially making hash-based aligners obsolete. © 2012 Lindner, Friedel.

Schliesser A.,Ecole Polytechnique Federale de Lausanne | Schliesser A.,Max Planck Institute of Quantum Optics | Picque N.,Max Planck Institute of Quantum Optics | Picque N.,Ludwig Maximilians University of Munich | And 3 more authors.
Nature Photonics | Year: 2012

Laser frequency combs are coherent light sources that emit a broad spectrum of discrete, evenly spaced narrow lines whose absolute frequency can be measured to within the accuracy of an atomic clock. Their development in the near-infrared and visible domains has revolutionized frequency metrology while also providing numerous unexpected opportunities in other fields such as astronomy and attosecond science. Researchers are now exploring how to extend frequency comb techniques to the mid-infrared spectral region. Versatile mid-infrared frequency comb generators based on novel laser gain media, nonlinear frequency conversion or microresonators promise to significantly expand the applications of frequency combs. In particular, novel approaches to molecular spectroscopy in the 'fingerprint region', with dramatically improved precision, sensitivity, recording time and/or spectral bandwidth may lead to new discoveries in the various fields relevant to molecular science. © 2012 Macmillan Publishers Limited. All rights reserved.

Fountoulakis K.N.,Aristotle University of Thessaloniki | Moller H.-J.,Ludwig Maximilians University of Munich
International Journal of Neuropsychopharmacology | Year: 2011

Recently there has been much debate on the true usefulness of antidepressant therapy especially after the publication of a meta-analysis by Kirsch et al. (PLoS Medicine 2008, 5, e45). The aim of the current paper was to recalculate and re-interpret the data of that study. Effect-size and mean-score changes were calculated for each agent separately as well as pooled effect sizes and mean changes on the basis of the data reported by Kirsch et al. The weighted mean improvement was (depending on the method of calculation) 10.04 or 10.16 points on the Hamilton Depression Rating Scale (HAMD) in the drug groups, instead of 9.60, and thus the correct drug-placebo difference is 2.18 or 2.68 instead of 1.80. Kirsch et al. failed to report that that the change in HAMD score was 3.15 or 3.47 points for venlafaxine and 3.12 or 3.22 for paroxetine, which are above the NICE threshold. Still the figures for fluoxetine and nefazodone are low. Thus it seems that the Kirsch et al.'s meta-analysis suffered from important flaws in the calculations; reporting of the results was selective and conclusions unjustified and overemphasized. Overall the results suggest that although a large percentage of the placebo response is due to expectancy this is not true for the active drug and effects are not additive. The drug effect is always present and is unrelated to depression severity, while this is not true for placebo. © CINP 2010.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-05-2014 | Award Amount: 7.99M | Year: 2015

While prevention of most female specific cancers (ovarian, breast, endometrial) has not progressed substantially in recent years, significant progress has been made with cervical cancer due to accessibility of the cell of origin (cervical smear) and availability of a test for the causal agent (human papilloma virus); together these enable identification of high risk individuals and interventions to prevent infection or halt progression to invasive cancer. Our consortium has developed an exciting opportunity to utilise clinically abundant cervical cells in tandem with a multi-omics enabled (genome, epigenome, metagenome) analysis pipeline to understand an individuals risk of developing a female specific cancer and to direct a personalised screening and prevention strategy. Cervical cells currently collected within cervical cancer screening provide an ideal window into other female specific cancers because they are (i) an excellent non-invasive source of high quality DNA, (ii) provide a readout for environmental exposure, (iii) are part of the Mllerian tract and (iv) are hormone sensitive, recording (via the epigenome) various hormonal conditions over a lifetime that trigger cancer development. The FORECEE project is aligned with the novel concept of P4 Medicine (predictive, preventive, personalized, and participatory): it aims to translate the risk prediction tools output into personalised recommendations for screening and prevention of female cancers. Our consortium comprises a multi-disciplinary team of experts in clinical oncology, risk-benefit communication, omics technologies, decision analysis, health economics and public health. We will examine the effectiveness of the proposed cervical cell omics analysis method and investigate the legal, social, ethical and behavioural issues related to implementation of the risk prediction tool, through direct interaction with stakeholder groups, to ensure its rapid translation into clinical practice across Europe.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.56M | Year: 2015

GLYCOVAX is a network for the education of promising young scientists who will learn how to rationally design a next generation of well-defined and innovative glycoconjugate vaccines to improve current preventive therapies and to tackle unmet medical needs. Glycoconjugate vaccines represent the key for success of vaccination in children. The covalent linkage to proteins renders carbohydrates able to evoke a T-cell memory response. Current vaccines are prepared from heterogeneous mixtures of sugars linked by unspecific methods to the carrier protein giving complex mixtures of products. Due to this intricate structure, it has not been possible to apply a medicinal chemistry approach in the development of glycoconjugate vaccines and to fully understand their mechanism of action. Combination of novel approaches for glycan synthesis and site-selective conjugation methods now gives access to conjugates defined in sugar component and attachment site, thus leading to robust structure-immunogenicity relationship. Advancements in structural biophysics can be applied to select the optimal glycan antigen. By combining the beneficiaries expertise in carbohydrate synthesis, bioconjugation, high throughput screening, structural glycobiology, vaccinology and immunology, together with the experience in project management, GLYCOVAX will create a multidisciplinary environment where 14 young researchers will contribute to develop a novel route towards improved, safer and better characterized glycoconjugate vaccines, and contemporarily acquire transferable skills which will lead them to become the new leaders of academic or industrial research. The network will involve 9 academic groups and 2 industrial partners as Beneficiaries, and one SME as Partner Organization. The profound interaction between academy and industry will aid the students to get new concepts and visions for translating their ideas from the bench to the manufacturing of the next generation of glycoconjugate vaccines.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SSH-2007-6.2-01;SSH-2007-6.1-01 | Award Amount: 1.77M | Year: 2008

This project aims to develop and collect novel science and technology indicators covering Europe, Japan and the United States. These indicators will be used in empirical models that can contribute to improve European, national and regional policies on the following four topics: 1) Economic use of patents, i.e. unused patents and strategic patents, licensing, entrepreneurship; 2) Science-industry linkages and innovation performance; 3) Gender, education and mobility of inventors, 4) Economic value of patents. The project will carry out the following four sets of activities aimed at the creation of new indicators. First, we will carry out a new survey data collection, PatVal-EU II, which will build on the previous PatVal-EU I survey of inventors. The new survey will interview inventors of about 30,000 EPO patents in 20 European countries and will ask questions about the inventors, the invention process, the motivations to patent, the use and the value of the patent, the links between science and patented inventions. Second, we will carry out two complementary survey data collections in US and JP, PatVal-JP and PatVal-US, by using the questionnaire developed for European inventors. Third, the project will develop indicators for industry-science links based on patent citations to science for all OECD countries, over time, across industries, by firms and by firms to universities and public research institutions. These indicators will be validated through the results of the PatVal-EU II survey. Fourth, we will build complementary indicators at the level of patents (citations, oppositions, etc.), inventors, companies, regions, sectors, that will be integrated with the survey data. The resulting integrated datasets will be used in empirical models and policy assessments on the four topics of this project. In particular, the project will develop adequate empirical methods that take simultaneously into account a variety of factors affecting the impact of policies.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.2-1 | Award Amount: 7.65M | Year: 2012

CLINICAL NEED Every year in the EU ~45,300 and 330,000 women are diagnosed with ovarian and breast cancer respectively & 28,800 and 90,000 of these two groups of women will die as a consequence of these diseases. Currently there are no tools available that allow for: a) Effective screening of ovarian and/or breast cancer of sufficient sensitivity and specificity to avoid potential over-diagnosis, or; b) Stratification of patients into optimal personalised therapy regimes in ovarian/breast cancer. EpiFemCare ADVANCES Progress in personalised cancer medicine will only be possible with the development of bioassays involving the analysis of easy accessible biomaterials that contain stable target molecules reflective of disease. We will establish and clinically validate a series of blood tests based upon DNA methylation technology that will facilitate both early detection and prediction of therapeutic outcome in breast and ovarian cancer. CONSORTIUM Our pan-European academic-industrial consortium demonstrates diverse clinical, scientific & industrial expertise. We have access to the latest state of the art technologies and, integrally, the best available cohort and clinical trial sample sets required to ensure the success of the EpiFemCare program. GATC-Biotech and Genedata are Europes leading providers of DNA sequencing and bioinformatics for biomarker development and have developed serum DNA based prenatal tests. The clinical partners have access to unique cohort and clinical samples collected from >200,000 women well in advance of disease (UK Collaborative Trial of Ovarian Cancer Screening) or before and during treatment (SUCCESS Trial). IMPACT As a result of refined and improved patient stratification, EpiFemCare will: - Reduce the late stage presentation of ovarian & breast cancer by 50% - Reduce the requirement for 50% of breast cancer patients to have adjuvant therapies - Reduce female cancer related fatalities as well as treatment-related morbidity by 20%

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.1.6 | Award Amount: 4.43M | Year: 2010

Designed to route information between computers, the Internet is evolving into an Internet of services, media and things (devices and other Real World Objects connected to or tracked via the Internet). In this new Internet, the main interest is no longer on machines but on items of content. Today, users locate and access content via servers (e.g. search engines) that connect them to the machines where it is physically stored. CONVERGENCE aims at enhancing the Internet with a content-centric, publish-subscribe service model, based on a common container for any kind of digital data, including representations of people and Real World Objects. This common container, named Versatile Digital Item (VDI), is a package of digital information with a unique identifier, independent of the machine where the VDI is hosted. VDIs will be designed to handle all possible kinds of digital information, from media to information about services, people and physical objects, independently of the structure or geographical location of the content. The CONVERGENCE architecture will provide scalable mechanisms allowing professional providers and individual users to publish and subscribe to VDIs, maintain access to VDIs when they move from one host to another; search for VDIs, as well as updating and deleting VDIs which have already been published. CONVERGENCE will allow both professional providers and consumers to define their own policies for authenticating and protecting VDIs and supporting digital forgetting (ensuring that VDIs are deleted when they pass a user-defined expiry date). CONVERGENCE will test its proposal in two tracks dedicated respectively to real-life business scenarios and to network experimentation using large scale facilities. The framework proposed by CONVERGENCE will be proposed to relevant standardization bodies. Software developed in the project (including middleware and applications) will be made available to the Open Source community.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.14M | Year: 2015

ENHANCE (Environmental Humanities for a Concerned Europe) will provide the first fully coordinated training programme for Environmental Humanities in Europe. It will train twelve early-stage researchers, joining three leading universities for environmental researchthe University of Leeds, Ludwig-Maximilians-University Munich, and the Royal Institute of Technology, Stockholmwith Europes largest science and technology museum, the Deutsches Museum, and a further five Associated Partners from the private and third sectors. ENHANCE aims to provide ESRs with the skills training to be at the forefront of a new generation of Environmental Humanities research, and to be employable in a range of careers including environmental consultancy, risk assessment, research and development, green business management, media and communications, and not-for-profit work (environmental and wildlife NGOs). Research and training will concentrate on three major research areasnatural disasters and cultures of risk, history of science and technology, and environmental ethicsand will address a series of core interlocking issues: wilderness and conservation; flooding and drought; waste, environmental justice, and environmental health. ENHANCE offers a unique framework for bridging the arts and the sciences by training ESRs to integrate cutting-edge research across a range of Environmental Humanities subjectsfrom science and technology studies to history, literature, geography, and anthropologywith policy-oriented actions and cross-sector concerns. The training programme will offer ethical insights into contemporary environmental problems by addressing how these have occurred at different historical moments and across different cultures; how they have been represented in art, literature, film, historical archives, and the media; and how we might imagine and implement alternative environmental practices in a technologically empowered but ecologically endangered world.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETPROACT-3-2014 | Award Amount: 2.00M | Year: 2015

Quantum simulators promise to provide unprecedented insights into physical phenomena not accessible with classical computers and have the potential to enable radically new technologies. In this proposal, we argue that analog dynamical quantum simulators are currently realisable and constitute a most promising class of architectures to fulfil the ultimate promise to devise quantum machines outperforming classical computers. The approach taken is two-pronged: On the one hand, we devise versatile and practical platforms for dynamical simulators making use of systems of ultra-cold atoms in optical lattices and the continuum, as well as cavity polaritons. We suggest a concerted and interdisciplinary research programme of certifying quantum devices and assess them in their computational capabilities, addressing largely unexplored key questions on the power of quantum simulators. On the other, we make use of those devices to probe important questions in fundamental and applied physics, ranging from technology-relevant problems, concerning transport processes or glassy dynamics, via long-standing challenges in the physics of non-equilibrium and thermalisation phenomena, through puzzles in notions of quantum turbulence, to questions in the study of quantum gravity.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 4.33M | Year: 2009

Mathematical logic is a rapidly-developing subject with sophisticated techniques and many applications in algebra, geometry, number theory, analysis, and computer science. Even though the branches of logic share vital concepts and techniques, in recent years increased specialism has meant that most researchers are trained in just one branch of logic, and there is a need in Europe for researchers who have an overview of techniques from logic. To meet this need, this project will provide a broad training for early stage researchers across the main areas of mathematical logic and its many applications. 18 early-stage researchers (ESRs) will be trained for 36 months each, and a further 20 ESRs, undertaking doctoral studies elsewhere, will be appointed for 3--6 months each. Doctoral research projects for ESRs have been prepared in model theory, aspects of complexity theory (proof complexity, finite model theory), proof theory, computability theory, set theory, and real valued logics. Network-wide training will be provided through three 7-day training workshops, two 3-day and one 5-day research workshops, and a 5-day final conference. Some secondments of ESRs, and short ESR appointments, will be coordinated around a special semester in model theory in Lyon, and a later one in logical aspects of complexity theory in Prague. Complementary training is provided by the hosts, and through the training workshops. The network consists of 8 full partners, each a major logic group with strength in more than one branch of logic and experience in the training of early stage researchers, and each based in a major European university. The partners have been chosen to complement each other in strengths, and together to cover most branches of mathematical logic. In addition to the 8 full partners, training is provided by an academic Associated Partner (University of East Anglia) and two industrial Associated Partners (Onera and BT Group, each at Level 2).

Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2011-IRSES | Award Amount: 777.30K | Year: 2012

**The joint exchange programme Non-equilibrium dynamics of soft and active matter (SoftActive) aims at bringing closer communities of physicists working at the forefront of statistical/nonlinear physics of out-of-equilibrium systems. Although many aspects of this very wide topic will be covered, the project is centered on the dynamics and fluctuations in soft and active matter, a subject of crucial importance in quantitative biology/biophysics. **The three countries involved, France, Germany, and Japan, and indeed almost all the participants of SoftActive, have a long history of collaboration on these topics, which are well-developed in each country. But these past and present collaborations have remained, so far, mostly bilateral, and it has become clear that further integration is needed. In particular, the groups involved in this proposal are leaders of the emerging field of active matter which is so far particularly well represented in France, Germany, and Japan. It is now time to structure international ties, which will strengthen the quality of research and allow for a rapid and organized growth. **The SoftActive project mirrors the Dynamics of Nonequilibrium Soft and Active Matter project just approved recently within the Core-to-Core program of the Japanese Society for the Promotion of Science (JSPS). It is divided into four main scientific topics, in parallel to the JSPS-funded Core-to-Core project: -Nonlinear response and non-equilibrium dynamics of liquid crystals and related problems -Slow dynamics of colloids and related problems -Dynamics and fluctuations far from equilibrium -Dynamics of active soft matter **The scientific goals will be reached via the exchange of researchers, notably young ones for long-enough periods of time to insure efficient transfer of knowledge, plus a comprehensive calendar of project-wide events in the form of schools and workshops.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETOPEN-1-2014 | Award Amount: 3.97M | Year: 2015

Atomic clocks are the backbone of our modern communication and navigation technology, e.g. through the global positioning system (GPS). Improving these clocks will open up exciting new applications in geodesy, fleet tracking, autonomous vehicles, augmented reality and shed light on some of the most fundamental questions in research. Todays best atomic clocks lose only 1 second in 30 billion years, making them the most precise measurement devices ever built. However, such clocks are extremely delicate and susceptible to external perturbations; they can only be operated in specialized laboratories. We propose to develop a novel type of clock, based on a unique nuclear transition in Thorium-229. This nuclear clock will be fundamentally different from existing atomic clocks, which are based on transitions in the electron shell. It will be largely inert to perturbations, simpler by design, and holds the potential to outperform existing atomic clocks in terms of precision. So far, progress towards an application of the Thorium nuclear transition has been hampered by the extreme technological challenges related to the scarcity of 229Th, insufficient detector resolution, and exotic lasers frequencies. Suitable technology is only becoming available just now. Furthermore, this research demands supreme expertise in a variety of fields, encompassing nuclear and atomic physics, quantum optics, metrology, as well as detector- and laser technology. Our interdisciplinary consortium is assembled to precisely match these requirements, joining for the first time Europes leading research groups in the respective fields. The work will focus on two objectives; (i) finding clear evidence of the transition and measuring its frequency, and (ii) developing all key components required for operation of a nuclear clock. We are certain that next-generation satellite-based navigation technology and other precision timing applications will greatly benefit from more precise and robust clocks.

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