Koln, Germany
Koln, Germany

The University of Cologne is the sixth oldest university in Central Europe and, with 38,000 students and 4,000 postgraduates, one of the largest universities in Germany. It is furthermore the German founding member of the Global Alliance in Management Education . Since 2012 the university was awarded in the German Universities Excellence Initiative for its overall concept. Wikipedia.


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Behrens A.,Cancer Research UK Research Institute | Behrens A.,King's College London | Van Deursen J.M.,Rochester College | Rudolph K.L.,Leibniz Institute for Age Research | And 3 more authors.
Nature Cell Biology | Year: 2014

Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells. © 2014 Macmillan Publishers Limited. All rights reserved.


Foeldvari I.,Hamburger Zentrum fur Kinder und Jugendrheumatologie | Becker I.,University of Cologne
Arthritis Care and Research | Year: 2015

Objective Uveitis is a major extraarticular quality of life-restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX). Methods Patients' characteristics, treatment, and the reported first occurrence of uveitis as an adverse event were searched in the Biologics in Pediatric Rheumatology Registry. The rates per exposed patients, exposure time, and time until event were calculated. Results Uveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844 patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and 13 of 364 patients were receiving adalimumab. Patients with uveitis were younger (mean ± SD age 4.6 ± 4.2 versus 7.4 ± 4.5 years; P < 0.0001), more likely to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P < 0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with a uveitis diagnosis before starting treatment more often had a uveitis event (n = 28, 8.4%; OR 8.5, P < 0.0001), and more often received adalimumab (OR 2.15 [95% confidence interval 1.58-2.94], P < 0.0001). In 16 patients, a new uveitis event occurred: 11 while taking MTX (3.2 per 1,000 patient-years), 2 while taking etanercept monotherapy (1.9 per 1,000 patient-years), and 3 while taking etanercept and MTX combination (0.9 per 1,000 patient-years). A new uveitis event occurred early in the disease course after a median disease duration of 1.5 years (interquartile range [IQR] 1.3-3.8) while taking etanercept and 1.8 years (IQR 1.8-2.1) for the MTX cohort. A recurrent uveitis event was reported after a disease duration of 7.6 years (IQR 4.3-10.0) in the etanercept cohort and 4.8 years (IQR 1.0-5.8) in the MTX cohort. Univariate analysis showed that MTX, but not etanercept or adalimumab, led to a lower rate of uveitis. Conclusion Patients with a history of uveitis had higher risks for uveitis events while taking both etanercept and adalimumab. Methotrexate turned out to be protective. Few patients developed a first uveitis event while taking etanercept, while the rate is comparable to that with MTX. Uveitis may not be attributed to be an adverse drug reaction to etanercept. © 2015, American College of Rheumatology.


Balafoutas L.,University of Innsbruck | Nikiforakis N.,Abu Dhabi University | Rockenbach B.,University of Cologne
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Many interactions in modern human societies are among strangers. Explaining cooperation in such interactions is challenging. The two most prominent explanations critically depend on individuals' willingness to punish defectors: In models of direct punishment, individuals punish antisocial behavior at a personal cost, whereas in models of indirect reciprocity, they punish indirectly by withholding rewards. We investigate these competing explanations in a field experiment with real-life interactions among strangers. We find clear evidence of both direct and indirect punishment. Direct punishment is not rewarded by strangers and, in line with models of indirect reciprocity, is crowded out by indirect punishment opportunities. The existence of direct and indirect punishment in daily life indicates the importance of both means for understanding the evolution of cooperation.


Ilyas S.,University of Cologne | Ilyas M.,Max Planck Institute for Plant Breeding Research | Van Der Hoorn R.A.L.,Max Planck Institute for Plant Breeding Research | Mathur S.,University of Cologne
ACS Nano | Year: 2013

Superparamagnetic iron oxide nanoparticles (SPIONs) coated with azide groups were functionalized at the surface with biotin (biotin@SPIONs) and cysteine protease inhibitor E-64 (E-64@SPIONs) with the purpose of developing nanoparticle-based assays for identifying cysteine proteases in proteomes. Magnetite particles (ca. 6 nm) were synthesized by microwave-assisted thermal decomposition of iron acetylacetonate and subsequently functionalized following a click chemistry protocol to obtain biotin and E-64 labeled particulate systems. Successful surface modification and covalent attachment of functional groups and molecules were confirmed by FT-IR spectroscopy and thermal gravimetric analysis. The ability of the surface-grafted biotin terminal groups to specifically interact with streptavidin (either horseradish peroxidase [(HRP)-luminol-H2O2] or rhodamine) was confirmed by chemiluminescent assay. A quantitative assessment showed a capture limit of 0.55-1.65 μg protein/100 μg particles. Furthermore, E-64@SPIONs were successfully used to specifically label papain-like cysteine proteases from crude plant extracts. Owing to the simplicity and versatility of the technique, together with the superparamagnetic behavior of FeOx-nanoparticles, the results demonstrate that click chemistry on surface anchored azide group is a viable approach toward bioconjugations that can be extended to other nanoparticles surfaces with different functional groups to target specific therapeutic and diagnostic applications. © 2013 American Chemical Society.


Micklitz T.,Brazilian Center for Research in Physics (CBPF) | Muller C.A.,University of Konstanz | Muller C.A.,National University of Singapore | Altland A.,University of Cologne
Physical Review Letters | Year: 2014

Signatures of Anderson localization in the momentum distribution of a cold atom cloud after a quantum quench are studied. We consider a quasi-one-dimensional cloud initially prepared in a well-defined momentum state, and expanding for some time in a disorder speckle potential. Quantum interference generates a peak in the forward scattering amplitude which, unlike the common weak localization backscattering peak, is a signature of strong Anderson localization. We present a nonperturbative, and fully time resolved description of the phenomenon, covering the entire diffusion-to-localization crossover. Our results should be observable by present day experiments. © 2014 American Physical Society.


Frerigmann H.,University of Cologne | Berger B.,University of Adelaide | Gigolashvili T.,University of Cologne
Plant Physiology | Year: 2014

By means of yeast (Saccharomyces cerevisiae) two-hybrid screening, we identified basic helix-loop-helix transcription factor05 (bHLH05) as an interacting partner of MYB51, the key regulator of indolic glucosinolates (GSLs) in Arabidopsis (Arabidopsis thaliana). Furthermore, we show that bHLH04, bHLH05, and bHLH06/MYC2 also interact with other R2R3-MYBs regulating GSL biosynthesis. Analysis of bhlh loss-of-function mutants revealed that the single bhlh mutants retained GSL levels that were similar to those in wild-type plants, whereas the triple bhlh04/05/06 mutant was depleted in the production of GSL. Unlike bhlh04/06 and bhlh05/06 mutants, the double bhlh04/05 mutant was strongly affected in the production of GSL, pointing to a special role of bHLH04 and bHLH05 in the control of GSL levels in the absence of jasmonic acid. The combination of two specific gain-of-function alleles of MYB and bHLH proteins had an additive effect on GSL levels, as demonstrated by the analysis of the double MYB34-1D bHLH05D94N mutant, which produces 20-fold more indolic GSLs than bHLH05D94N and ecotype Columbia- 0 of Arabidopsis. The amino acid substitution D94N in bHLH05D94N negatively affects the interaction with JASMONATE-ZIM DOMAIN protein, thereby resulting in constitutive activation of bHLH05 and mimicking jasmonic acid treatment. Our study revealed the bHLH04, bHLH05, and bHLH06/MYC2 factors as novel regulators of GSL biosynthesis in Arabidopsis. © 2014 American Society of Plant Biologists. All Rights Reserved.


Popkov V.,University of Cologne | Popkov V.,University of Florence | Prosen T.,University of Ljubljana
Physical Review Letters | Year: 2015

We report a two-parametric irreducible infinitely dimensional representation of the Lax integrability condition for the Fermi Hubbard chain. In addition to being of fundamental interest, hinting at possible novel quantum symmetry of the model, our construction allows for an explicit representation of an exact steady state many-body density operator for a nonequilibrium boundary-driven Hubbard chain with arbitrary (asymmetric) particle source (sink) rates at the left (right) end of the chain and with arbitrary boundary values of chemical potentials. © 2015 American Physical Society.


Cowie M.R.,Imperial College London | Woehrle H.,ResMed | Woehrle H.,Sleep and Ventilation Center Blaubeuren | Wegscheider K.,University of Hamburg | And 8 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea. METHODS We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea-hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guidelinebased medical treatment alone (control). The primary end point in the time-toevent analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure. RESULTS In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P = 0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P = 0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P = 0.006). CONCLUSIONS Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343.). © 2015 Massachusetts Medical Society. All rights reserved.


Zander E.,University of Cologne | Nemec A.,National Institute of Public Health | Seifert H.,University of Cologne | Higgins P.G.,University of Cologne
Journal of Clinical Microbiology | Year: 2012

This study investigated the correlation between blaOXA-51 variants and Acinetobacter baumannii worldwide clonal lineages 1 to 8 (WW1 to -8). The blaOXA-51-like genes of 102 A. baumannii isolates were sequenced. Using DiversiLab repetitive-sequence-based PCR (rep-PCR) typing, 92 of these isolates had previously been assigned toWW1to -8 and 10 were unclustered. Clustering of DNA sequences was performed using the neighbor-joining method and the Jukes-Cantor phylogenetic correction. bla OXA-51variants were in good correlation with DiversiLab-defined clonal lineages. Sequence-based typing of blaOXA-51 variants has the potential to be applied for epidemiologic characterization of A. baumannii and to identify worldwide clonal lineages 1 to 8. Copyright © 2012, American Society for Microbiology. All Rights Reserved.


Fetchenhauer D.,University of Cologne | Fetchenhauer D.,University of Groningen | Dunning D.,Cornell University
Psychological Science | Year: 2010

People tend to grossly underestimate the trustworthiness of other people. We tested whether this cynicism grows out of an asymmetry in the feedback people receive when they decide to trust others. When people trust others, they painfully learn when other people prove to be untrustworthy; however, when people refrain from trusting others, they fail to learn of instances when the other person would have honored their trust. Participants saw short videos of other people and had to decide whether to trust each person in an economic game. Participants overall underestimated the trustworthiness of the people they viewed, regardless of whether they were given financial incentives to provide accurate estimates. However, people who received symmetric feedback about the trustworthiness of others (i.e., who received feedback regardless of their own decision to trust) exhibited reduced cynicism relative to those who received no feedback or asymmetric feedback (i.e., who received feedback only after they trusted the other person). © The Author(s) 2010.


Howard J.C.,University of Cologne | Howard J.C.,Stellenbosch University | Hunn J.P.,University of Cologne | Steinfeldt T.,University of Cologne
Current Opinion in Microbiology | Year: 2011

IRG proteins (immunity-related GTPases) provide an early defense mechanism in mice against the protozoal pathogen, Toxoplasma gondii. This is a particularly suitable time to provide a brief review of this host-pathogen interaction because the nature of the IRG resistance system, and to some extent its mode of action, have become known in the past few years. Likewise, forward genetic screens have recently drawn attention to a number of loci contributing to the differential virulence of T. gondii strains in mice. It is now clear that at least some important virulence mechanisms exert their action against components of the IRG resistance system. Thus these two mechanisms form the two poles of a dynamic host-pathogen virulence-resistance relationship with interesting and accessible properties. © 2011 Elsevier Ltd.


Moore D.B.,University of Oregon | Beekman M.,Oregon Institute of Technology | Disch S.,University of Oregon | Disch S.,University of Cologne | Johnson D.C.,University of Oregon
Angewandte Chemie - International Edition | Year: 2014

Telluride misfit layer compounds are reported for the first time. These compounds were synthesized using a novel approach of structurally designing a precursor that would form the desired product upon low-temperature annealing, which allows the synthesis of kinetically stable products that do not appear on the equilibrium phase diagram. Four new compounds of the [(PbTe) 1.17]m(TiTe2)n family are reported, and their structures were examined by a variety of X-ray diffraction techniques. Challenging the limits of solid-state synthesis: A synthetic method that entails the design of precursors to form targeted products that are not accessible by traditional solid-state synthesis is put to the test. This method is used to produce the first reported family of telluride misfit layer compounds. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Gandara D.R.,University of California at Davis | Hammerman P.S.,Dana-Farber Cancer Institute | Sos M.L.,University of Cologne | Lara P.N.,University of California at Davis | Hirsch F.R.,University of Colorado at Denver
Clinical Cancer Research | Year: 2015

Squamous cell lung cancer (SCC) represents an area of unmet need in lung cancer research. For the past several years, therapeutic progress in SCC has lagged behind the now more common non-small cell lung cancer histologic subtype of adenocarcinoma. However, recent efforts to define the complex biology underlying SCC have begun to bear fruit in a multitude of ways, including characterization of previously unknown genomic and signaling pathways, delineation of new, potentially actionable molecular targets, and subsequent development of a large number of agents directed against unique SCC-associated molecular abnormalities. For the first time, SCC-specific prognostic gene signatures and predictive biomarkers of new therapeutic agents are emerging. In addition, recent and ongoing clinical trials, including the Lung-MAP master protocol, have been designed to facilitate approval of targeted therapy-biomarker combinations. In this comprehensive review, we describe the current status of SCC therapeutics, recent advances in the understanding of SCC biology and prognostic gene signatures, and the development of innovative new clinical trials, all of which offer new hope for patients with advanced SCC. © 2015 AACR.


Chang L.,University of California at Davis | Lademann H.W.A.,University of Cologne | Bonekamp J.-B.,University of Cologne | Meerholz K.,University of Cologne | Moule A.J.,University of California at Davis
Advanced Functional Materials | Year: 2011

The performance of bulk-heterojunction (BHJ) solar cells is strongly correlated with the nanoscale structure of the active layer. Various processing techniques have been explored to improve the nanoscale morphology of the BHJ layer, e.g., by varying the casting solvent, thermal annealing, solvent annealing, and solvent additives. This paper highlights the role of residual solvent in the "dried" BHJ layer, and the effect of residual solvents on PCBM diffusion and ultimately the stability of the morphology. We show that solvent is retained within the BHJ film despite prolonged heat treatment, leading to extensive phase separation, as demonstrated by the growth in the size and quantity of PCBM agglomerates. The addition of a small volume fraction of nitrobenzene to the casting solution inhibits the diffusion of PCBM in the dry film, resulting in smaller PCBM agglomerates, and improves the fill factor of the BHJ device to 0.61 without further tempering. The addition of nitrobenzene also increases the P3HT crystalline content, while increasing the onset temperature for melting of P3HT side chains and backbone. The melting temperature for PCBM is also higher with the nitrobenzene additive present. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Vossel S.,Institute of Neuroscience and Medicine INM 3 | Vossel S.,University College London | Geng J.J.,University of California at Davis | Fink G.R.,Institute of Neuroscience and Medicine INM 3 | Fink G.R.,University of Cologne
Neuroscientist | Year: 2014

The idea of two separate attention networks in the human brain for the voluntary deployment of attention and the reorientation to unexpected events, respectively, has inspired an enormous amount of research over the past years. In this review, we will reconcile these theoretical ideas on the dorsal and ventral attentional system with recent empirical findings from human neuroimaging experiments and studies in stroke patients. We will highlight how novel methods - such as the analysis of effective connectivity or the combination of neurostimulation with functional magnetic resonance imaging - have contributed to our understanding of the functionality and interaction of the two systems. We conclude that neither of the two networks controls attentional processes in isolation and that the flexible interaction between both systems enables the dynamic control of attention in relation to top-down goals and bottom-up sensory stimulation. We discuss which brain regions potentially govern this interaction according to current task demands. © 2013 The Author(s).


Plosch T.,University of Groningen | Plosch T.,University of Cologne
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2013

Substantial evidence links early postnatal nutrition to the development of obesity later in life. However, the molecular mechanisms of this connection must be further elucidated. Epigenetic mechanisms have been indicated to be involved in this process, referred to as metabolic programming. Therefore, we propose here that early postnatal nutrition (breast and formula feeding) epigenetically programs the developing organs via modulation of the gut microbiome and influences the body weight phenotype including the predisposition to obesity. Specifically, the early-age food patterns are known to determine the gross composition of the early gut microbiota. In turn, the microbiota produces large quantities of epigenetically active metabolites, such as folate and short chain fatty acids (butyrate and acetate). The spectrum of these produced metabolites depends on the composition of the gut microbiota. Hence, it is likely that changes in gut microbiota that result in altered metabolite composition might influence the epigenome of directly adjacent intestinal cells, as well as other major target cell populations, such as hepatocytes and adipocytes. Nuclear receptors and other transcription factors (the PPARs, LXR, RXR, and others) could be physiologically relevant targets of this metaboliteinduced epigenetic regulation. Ultimately, transcriptional networks regulating energy balance could be manipulated. For these reasons, we postulate that early nutrition may influence the baby epigenome via microbial metabolites, which contributes to the observed relationship between early nutrition and adult obesity. © 2013 the American Physiological Society.


Savran D.,Helmholtz Center for Heavy Ion Research | Savran D.,Frankfurt Institute for Advanced Studies FIAS | Aumann T.,TU Darmstadt | Aumann T.,Helmholtz Center for Heavy Ion Research | Zilges A.,University of Cologne
Progress in Particle and Nuclear Physics | Year: 2013

The electric dipole response of atomic nuclei has attracted a lot of attention from experimentalists and theorists in the last decade. This review gives an overview about the present status of experimental approaches to study low-lying electric dipole strength (often denoted as Pygmy Dipole Resonance) in stable and radioactive atomic nuclei and discusses the implications of these findings. Data published until July 2012 have been taken into account.


Patent
Jülich Research Center, ANM Adaptive Neuromodulation GmbH and University of Cologne | Date: 2010-09-17

A device and method for desynchronizing a patients neuronal brain activity involving a neuron population firing in a pathologically synchronized manner. The device includes a stimulation unit configured to generate an acoustic stimulation signal to stimulate the neuron population when the acoustic stimulation signal is aurally received by the patient. Furthermore, the acoustic stimulation signal has a first frequency and a second frequency, with the first frequency provided to reset the phase of the neuronal brain activity in a first sub-population of the stimulated neuron population, and the second frequency provided to reset the phase of the neuronal brain activity in a second sub-population of the stimulated neuron population.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.75M | Year: 2015

Many tumor cells are characterized by the overexpression of certain antigens. Molecules that specifically recognize these structures are suitable as homing devices in tumor therapy. Conjugates of anticancer drugs with such a delivery vector targeting tumors would be a magic bullet according to the Nobel laureate Paul Ehrlich. Three antibody-drug conjugates (ADC) have already been approved for anticancer therapy. However, ADC have e.g. limitations with respect to tumor penetration, high manufacturing costs, and require challenging conjugation chemistry. Peptide-drug conjugates can have a high drug loading, easily penetrate tissue, and can be easily prepared in a homogenous form with straightforward and well-defined conjugation chemistry. The ETN MAGICBULLET will focus on chemistry-driven approaches toward conjugates between peptides (delivery vectors) that recognize tumors and anticancer drugs (payloads or warheads) in order to selectively fight cancer, a topic with a high demand of research activities. The ETN will develop and validate an array of new peptide-drug conjugates combining either known tumor-specific peptides or newly discovered tumor-homing peptides with potent cytotoxic drugs. The tumor-selective peptides are designed for cellular uptake mediated either by endocytosis or by cell-penetrating peptides. The consortium of the ETN MAGICBULLET covers tumor biology, biochemistry, pharmacology, synthetic chemistry, medicinal chemistry, spectroscopy, conformational analysis, and computational chemistry. The training program focuses on multidisciplinary research to explore and validate molecular targets for innovative treatment or investigations on the molecular mechanisms in organ-specific metastatic growth processes. It aims at scientific multilingualism and relies e.g. on concerted learning, a combination of introductory training, hands-on learning on the bench, teaching by peers, and training in additional skills.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: Ocean.2010-1 | Award Amount: 14.85M | Year: 2011

The Arctic is engaged in a deep climatic evolution. This evolution is quite predictable at short (year) and longer scales (several decades), but it is the decadal intermediate scale that is the most difficult to predict. This is because the natural variability of the system is large and dominant at this scale, and the system is highly non linear due to positive and negative feedback between sea ice, the ocean and atmosphere. Already today, due to the increase of the GHG concentration in the atmosphere and the amplification of global warming in the Arctic, the impacts of climate change in the region are apparent, e.g. in the reduction in sea ice, in changes in weather patterns and cyclones or in the melting of glaciers and permafrost. It is therefore not surprising that models clearly predict that Artic sea ice will disappear in summer within 20 or 30 years, yielding new opportunities and risks for human activities in the Arctic. This climatic evolution is going to have strong impacts on both marine ecosystems and human activities in the Arctic. This in turn has large socio-economic implications for Europe. ACCESS will evaluate climatic impacts in the Arctic on marine transportation (including tourism), fisheries, marine mammals and the extraction of hydrocarbons for the next 20 years; with particular attention to environmental sensitivities and sustainability. These meso-economic issues will be extended to the macro-economic scale in order to highlight trans-sectoral implications and provide an integrated assessment of the socio-economic impact of climate change. An important aspect of ACCESS, given the geostrategic implication of Arctic state changes, will be the consideration of Arctic governance issues, including the framework UNCLOS (United Nations Convention for the Law of the Sea). ACCESS dedicates a full work package to integrate Arctic climate changes, socioeconomic impacts and Arctic governance issues.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.80M | Year: 2012

DNA is tightly wrapped around histones to form chromatin, a highly dynamic structure that can adopt different conformations with contrasting degrees of compaction. Essential processes of DNA metabolism, such as DNA repair, replication or transcription operate in the context of chromatin and higher order chromosomal organization. Understanding how modulation of chromatin structure and repair influence cell fate decisions in development and disease or how genome surveillance factors interact with the chromatin structure to safeguard the genome is an emerging question that represents a major challenge for human health. The objectives of the aDDRess ITN are: 1. to establish a European research platform of excellence in the proposed field, 2. to create a Network dedicated for the training of ESR/ERs promoting their independent careers and prospects and 3. to transform our current collaborations into a stronger intellectual and training network with links to the industry. In addressing these aims, we have put forward a multidisciplinary approach to study this central thematic area at the molecular, cellular and systems level by assembling a group of scientists with cross disciplinary expertise and capabilities. This integrated approach is likely to provide a solid groundwork on genome maintenance and chromatin dynamics driven by DNA damage.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA | Phase: SPA.2011.1.5-02 | Award Amount: 27.65M | Year: 2011

MACC II (Monitoring Atmospheric Composition and Climate Interim Implementation) is designed to meet the requirements that have been expressed for prototype operational GMES services for the atmospheric domain. From late-2011 MACC II will continue the operation and development of the GMES service lines established by the MACC project and prepare for its transition in 2014 to become the atmospheric monitoring component of GMES Operations. MACC II will prepare for full operations in terms of continuity, sustainability and availability. It will maintain and further develop the efficiency and resilience of its end-to-end processing system, and will refine the quality of the products of the system. It will adapt the system to make use of observations from new satellites, in particular the first of the atmospheric Sentinels, and will interface with FP7 RTD projects that contribute towards long-term service improvement. MACC II will ensure that its service lines best meet both the requirements of downstream-service providers and end users, and the requirements of the global scientific user community. The service lines will cover air quality, climate forcing, stratospheric ozone and solar radiation. MACC II will deliver products and information that support the establishment and implementation of European policy and wider international programmes. It will acquire and assimilate observational data to provide sustained real-time and retrospective global monitoring of greenhouse gases, aerosols and reactive gases such as tropospheric ozone and nitrogen dioxide. It will provide daily global forecasts of atmospheric composition, detailed air-quality forecasts and assessments for Europe, and key information on long range transport of atmospheric pollutants. It will provide comprehensive web-based graphical products and gridded data. Feedback will be given to space agencies and providers of in situ data on the quality of their data and future observational requirements.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-2009-IAPP | Award Amount: 1.49M | Year: 2010

The STEMCAM project is a 4-years training and transfer of knowledge program between two distinguished academic groups in stem cell research, two highly innovative SMEs and a company leader in development of media for stem cell research, to foster long-term industry-academy collaboration and partnership in the field of stem cells research and applications. The scientific and industrial aim of STEMCAM is to study the role of the Neuronal Cell Adhesion Molecule NCAM and related growth factors in the maintenance, survival and differentiation of induced pluripotent stem (iPS) cells towards the neural and myocardial lineage, in comparison with embryonic stem cells. The project will take advantage of very unique and innovative pharmacological tools, the NCAM and growth factor mimetic peptides discovered by ENKAM. To achieve its aim STEMCAM will apply an interdisciplinary approach from cell biology (including innovative in vitro culture using bi- and three dimensional systems), immunocytochemistry, imaging, molecular biology, electrophysiology, to peptide chemistry and chemioinformatics. The project will run via a training and transfer of knowledge program structured to efficiently exploit the expertise and complementarities between the industrial and academic partners to reach the scientific goals of the project and provide high quality intersectorial training for the participating researchers. This is expected to be of high benefit for their individual career development. The STEMCAM project links intersectorial research activities in two very relevant areas of stem cell research, neurogenesis and cardiomyogenesis and will strictly collaborate with the IAPPs INDUSTEM and PARTNERS and the large FP7 IP ESNATS, complementing and expanding with its unique approach their research scope and transfer of knowledge. Thus STEMCAM will significantly contribute to progress of stem cell research in Europe with high potential impact on European competitiveness and regenerative medicine


Grant
Agency: Cordis | Branch: FP7 | Program: CPCSA | Phase: INFRA-2008-1.2.2 | Award Amount: 3.39M | Year: 2009

Many research groups and institutes within the European Research Area (ERA) are playing a central role in the production of a vast range of atomic and molecular (AM) data, data that is of critical importance across a wide range of applications such as astrophysics, atmospheric physics, fusion, environmental sciences, combustion chemistry and in industrial applications from plasmas to lighting.\n\nThrough the auspices of this infrastructure the Virtual Atomic and Molecular Data Centre (VAMDC) aims to build a secure, documented, flexible and interoperable e-science environment-based interface to the existing AM data. The VAMDC will be built upon the expertise of existing AM databases, data producers and service providers with the specific aim of creating an infrastructure that is easily tuned to the requirements of a wide variety of users in academic, governmental, industrial or public communities both within and outside the ERA. The project will cover the building of the core consortium, the development and deployment of the infrastructure and the development of interfaces to the existing AM databases as well as providing a forum for training potential users and dissemination of expertise across the ERA. It is expected that VAMDC becomes a European legal entity during the course of the project.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 4.01M | Year: 2016

Large Polycyclic Aromatic Hydrocarbon (PAH) molecules are deeply interwoven in the fabric of the Universe and lock up ~15% of the elemental carbon in the interstellar medium (ISM) of galaxies. They dominate the mid-infrared emission characteristics of galaxies that can be used to trace star formation locally as well as in the early universe, they influence the phase structure of the ISM and the star formation rate of galaxies, and they are the epitome of molecular complexity in space, heralding the importance of top-down chemistry. In spite of the influential role of PAHs in the ISM, their lifecycle, catalytic activity, interaction with interstellar radiation, gas and grains and their role in the organic inventory of solar system bodies is still poorly understood. The EUROPAH ETN aims to change this by creating a highly multidisciplinary network that combines astronomy, molecular physics, molecular spectroscopy, environmental science, quantum chemistry, surface sciences, and plasma physics in a comprehensive research and training program. EUROPAH will train 16 ESRs through cutting edge individual research and innovation projects investigating key physical and chemical processes of PAHs in space and related terrestrial settings and linking directly to R&D needs of our industrial beneficiaries. EUROPAH will engage all ESRs in industry driven innovation activities aimed at R&D of the industrial participants products and services, including outreach activities led by our industrial science communication beneficiary. Research and innovation training is complemented by an extensive program of network-wide training events to expose ESRs to all disciplines in the network and to instill in them a comprehensive set of transferable skills. This will provide the ESRs with a unique learning environment in a multidisciplinary setting aimed at developing a research oriented creative and innovative mind set and will place them well for a future career in academia or in industry.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-1 | Award Amount: 7.81M | Year: 2012

Neurodegenerative disorders such as, Alzheimers disease (AD), Mild Cognitive Impairment (MCI), stroke, Traumatic Brain Injury (TBI) and chronic stress create a major economic burden to society and a substantial reduction in quality of life for patients and families. The development of neuroregenerative therapies is notoriously difficult and requires significant investment. NeuroFGL will contribute to decrease these barriers through: (1) the clinical advancement of a promising novel regenerative therapy (FGLs) for neurological disorders, (2) hedging the clinical development by developing tests that enable early clinical assessments to be made, thereby maximising the chance that FGL and other neurogenerative therapies actually become developed to the benefit of patients and society; and (3) Selecting a target patient population with less variability and thereby easier to study reducing and time resources needed, and increase predictability . FGLs is a promising and novel regenerative therapy being the clinical lead development candidate selected from a group of allosteric FGF-receptor modulators (referred to as FGL) mimicking NCAM. FGL has demonstrated positive effects in a number of in vivo models of neurodegeneration, e.g. beta-amyloid induced toxicity, global ischemia and chronic stress. The in vivo effects of FGL suggest a disease-modifying activity in several neurodegenerative disorders, such as neurogenesis. A phase I clinical study has demonstrated a FGL peptide to be well tolerated and safe. NeuroFGL will refine existing and develop new tests and techniques, that will at an early stage of the clinical development: (1) provide better information on the mechanisms of action (NCAM mimicking allosteric FGF recoter modulation) in man, (2) deliver translational effects seen between animal and man, (3) provide results earlier and cheaper, increasing the iteratiation and (4) select patients with conditions associated with less variability, e.g. patients with AD with a specific EEG or patients progressing to AD identified in patients with MCI. These developments will together provide a more robust basis for the development of FGLs, other drugs with a similar mechanism of action and other therapies for neurodegenerative disorders.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.92M | Year: 2016

Mitochondria are essential organelles found in every eukaryotic cell, required to convert food into usable energy. The mitochondrial oxidative phosphorylation (OXPHOS) system, which produces the majority of cellular energy in the form of ATP, is controlled by two distinct genomes: the nuclear and the mitochondrial genome (mtDNA). Mutations in mitochondrial genes encoded by either genome could cause diseases affecting OXPHOS system, called mitochondrial diseases, whose prevalence has been estimated to be 1:8500. Moreover, dysfunction of mitochondrial OXPHOS system has emerged as a key factor in a myriad of common diseases, including neurodegenerative and metabolic disorders like Parkinsons and Alzheimers Disease, Type 2 Diabetes, and was linked to aging process. Despite all this, it is surprising that our understanding of the mechanisms governing the mitochondrial gene expression and its associated pathologies remain superficial and therapeutic interventions unexplored. The basic machineries for mtDNA replication, mtDNA transcription and mitochondrial translation are known, but the regulation of these processes in response to metabolic demands is poorly understood. The complex nature of mitochondrial gene expression that relies on two different genomes calls for a multidisciplinary approach where different teams of researchers join forces. Studies in this area are not only of basic scientific interest but may also provide new avenues towards treatment of mitochondrial dysfunction in a variety of human diseases. The key aim of the REMIX Network is combine the skills of European research groups to provide strategic training of the next generation of scientists through a programme that will progress in the elucidation of the molecular mechanisms and pathways that regulate mitochondrial gene expression.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2011-1.1.5. | Award Amount: 10.83M | Year: 2012

ECRIN is a distributed ESFRI-roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients. Servicing multinational trials started during its preparatory phase, and it now applies for an ERIC status by 2011. The ERIC budget will be restricted to core activities required to enable provision of services, and the ECRIN-IA project is designed to expand ECRIN partnerships and impact beyond this core activity. Networking activities will promote pan-European expansion, capacity building, and partnership with other world regions, and address the funding issue (WP2). ECRIN-IA will develop e-services, education material to train professionals and patients associations, and communication with users, patients, citizens and policymakers (WP3). It will support the structuring and connection to ECRIN of disease-, technology-, or product-oriented investigation networks and hubs focusing on specific areas: rare diseases (WP4), medical device (WP5), nutrition (WP6). Transnational access activities will support the cost of multinational extension of clinical trials on rare diseases, medical device and nutrition selected by the ECRIN scientific board (WP7). Joint research activities are designed to improve the efficiency of ECRIN services, through the development of tools for risk-adapted monitoring (WP8), and the upgrade of the VISTA data management tool (WP9). This project will build a consistent organisation for clinical research in Europe, with ECRIN developing generic tools and providing generic services to multinational studies, and supporting the construction of pan-European disease-oriented networks, that will in turn act as ECRIN users and provide the scientific content. Such organisation will improve Europes attractiveness for industry trials, boost its scientific competitiveness, and result in better healthcare for European citizens.


Grant
Agency: Cordis | 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.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA | Phase: INFRA-2012-3.3. | Award Amount: 1.07M | Year: 2012

The Virtual Atomic and Molecular Data Centre (VAMDC) is a major new European initiative now building a unified, secure, documented, flexible and interoperable e-science environment-based interface to 17 existing A\M databases.\nThe SUP@VAMDC (Support at VAMDC) aims at building upon the VAMDC e-infrastructure, supporting different studies and actions linked to the VAMDC e-infrastructure that will in accord with the mission of INFRA-2012-3.3:.\n\tProvide operational, legal and technologicalsupport for studies aimed at developing a sustainable open scientific data e- infrastructure in Atomic and Molecular Data.\n\tProvide the support and medium for including authentication, authorisation and accounting (AAA) as well as licensing and tools within the VAMDC brand\n\tPromote and fashions future interoperability (technical, semantic, reference architecture, etc) across A&M data community through the promotion, monitoring and adoption of common standards.\n\tProvide support for dissemination actions aimed at raising the visibility of the VAMDC e-infrastructure towards wider audiences such as other domains which could use the VAMDC e-infrastructure for their own science or for their own dissemination of data, such as students and/or citizen-scientists. This programme includes the development of education-related tools linking VAMDCs scientific repositories and research data infrastructures, including establishing a free open access repository containing all peer-reviewed articles resulting from the VAMDC programme.\n\tProvide support in developing a globally connected and interoperable VAMDC e-infrastructure between EU and the rest of the world, including Brazil , South Africa, Asia, Australia, India through hosting workshops and supporting dialogue between such synergistic structures.\n\tAnalyse and evaluate possible business models for supporting an Open Science model (OPEN VAMDC) whilst assessing the impact of such a modeling in achieving financial sustainability.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-16-2015 | Award Amount: 6.03M | Year: 2016

Over 30 million Europeans are blind or visually impaired, leading to reduced quality of life and a tremendous loss of productivity in society. Corneal blindness is the second largest cause of blindness globally and while treatable, millions remain unnecessarily blind due to issues of access to transplantable tissue, lack of standardized treatments, and the lag in translating new regenerative medicine therapies to the clinic. The objective of ARREST BLINDNESS is therefore to develop and validate new regenerative-based therapies addressing a spectrum of blinding disorders of the cornea. These conditions either have no effective current treatments, depend on a scarce supply of donor tissue, or non-standardized methods are hindering validation of promising regenerative treatments. To achieve our objective, we will implant GMP-fabricated collagen-based bioengineered scaffolds to replace or regenerate the corneal stroma in cases of stromal thinning, scarring, dystrophy or trauma; deliver therapeutic epithelial stem and endothelial cells to the cornea to restore its transparency; deliver regenerative factors to promote neural growth and function; and actively maintain corneal immune privilege in high-risk situations by targeted therapeutic approaches to regress blood and lymphatic vessels. We will additionally develop advanced methods to image and monitor therapy throughout the cycle from GMP-compliant cell and scaffold preparation through the pre- and intra-operative stages, to postoperative follow-up and evaluation. After proof-of-concept and preclinical validation of key enabling components, these technologies will be used by one or several partners in preclinical models and in phase I/II human clinical studies. ARREST BLINDNESS directly addresses the translation of regenerative medicine, bio-artificial organs, tissue engineered scaffolds, and advanced cell and gene therapies into clinical use and will help to alleviate the worldwide problem of corneal blindness.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: INFRAIA-01-2016-2017 | Award Amount: 10.51M | Year: 2017

RadioNet is a consortium of 28 institutions in Europe, Republic of Korea and South Africa, integrating at European level world-class infrastructures for research in radio astronomy. These include radio telescopes, telescope arrays, data archives and the globally operating European Network for Very Long Baseline Interferometry (EVN). RadioNet is de facto widely regarded to represent the interests of radio astronomy in Europe. A comprehensive, innovative and ambitious suite of actions is proposed that fosters a sustainable research environment. Building on national investments and commitments to operate these facilities, this specific EC program leverages the capabilities on a European scale. The proposed actions include: - Merit-based trans-national access to the RadioNet facilities for European and for the first time also for third country users; and integrated and professional user support that fosters continued widening of the community of users. - Innovative R&D, substantially enhancing the RadioNet facilities and taking leaps forward towards harmonization, efficiency and quality of exploitation at lower overall cost; development and delivery of prototypes of specialized hardware, ready for production in SME industries. - Comprehensive networking measures for training, scientific exchange, industry cooperation, dissemination of scientific and technical results; and policy development to ensure long-term sustainability of excellence for European radio astronomy. RadioNet is relevant now, it enables cutting-edge science, top-level R&D and excellent training for its European facilities; with the Atacama Large Millimetre Array (ALMA) and the ESFRI-listed Square Kilometre Array (SKA) defined as global radio telescopes, RadioNet assures that European radio astronomy maintains its leading role into the era of these next-generation facilities by involving scientists and engineers in the scientific use and innovation of the outstanding European facilities.


Patent
Forschungsverbund Berlin E.V. and University of Cologne | Date: 2010-07-09

Substituted tricyclic diproline analogues of the formula (I): wherein the variables are as defined herein. Also disclosed are methods for the production thereof, the use thereof for the induction of an alpha-helix conformation in peptides and/or proteins, pharmaceuticals containing said compounds, methods for the production of a peptide library containing said compounds, and peptide libraries containing said compounds.


Patent
Jülich Research Center, University of Cologne and ANM Adaptive Neuromodulation GmbH | Date: 2013-03-12

A device and method for desynchronizing a patients neuronal brain activity involving a neuron population firing in a pathologically synchronized manner. The device includes a stimulation unit configured to generate an acoustic stimulation signal to stimulate the neuron population when the acoustic stimulation signal is aurally received by the patient. Furthermore, the acoustic stimulation signal has a first frequency and a second frequency, with the first frequency provided to reset the phase of the neuronal brain activity in a first sub-population of the stimulated neuron population, and the second frequency provided to reset the phase of the neuronal brain activity in a second sub-population of the stimulated neuron population.


Patent
Forschungsverbund Berlin E.V. and University of Cologne | Date: 2013-10-09

The present invention provides a compound comprising a general formula 1: In general formula 1, X is at least one of O and S. A is a ring bridge. Y^(1 )is at least one of H, alkyl, fluoroalkyl, aryl and heteroaryl. Z^(1), Z^(2), Z^(3 )are, individually or alternatively, at least one of H, carbonyl, OH, O-alkyl, O-acyl, NR^(1)R^(2 )(where R^(1 )or R^(2 )are, individually or alternatively, at least one of H, alkyl, acyl, and sulfonyl), alkyl, acyl, fluoroalkyl, aryl, and heteroaryl. R^(1 )is at least one of alkyl, acyl, alkoxycarbonyl, aryloxycarbonyl, and aminocarbonyl. R^(2 )is at least one of H, alkyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, aryloxycarbonyl, alkylsulfonyl, arylsulfonyl, aminoacyl and peptidyl. The present invention furthermore relates to the use of the compound as a pharmaceutical active compound, and to the use of the pharmaceutical active compound to treat bacterial diseases, neurodegenerative diseases and tumors.


Patent
ANM Adaptive Neuromodulation GmbH, University of Cologne and Jülich Research Center | Date: 2014-07-28

A device and method for desynchronizing a patients neuronal brain activity in which the neuron population is firing in a pathologically synchronized manner. The device includes a stimulation unit that generates an acoustic stimulation signal that includes both a first tone and a second tone. The first tone is provided to shift the phase of the neuronal brain activity of a first subpopulation of the neuron population relative to the phase of the neuronal brain activity of a second subpopulation of the neuron population when the first tone is acoustically received by the patient. Further, the second tone is provided to shift the phase of the neuronal brain activity of the second subpopulation relative to the phase of the neuronal brain activity of the first subpopulation when the second tone is acoustically received by the patient. As a result, the acoustic stimulation signal desynchronizes the stimulated neuron population.


Patent
Jülich Research Center, ANM Adaptive Neuromodulation GmbH and University of Cologne | Date: 2010-09-03

A device and method for providing stimulation signals that reset the phase of the neuronal activity of neurons in a patients brain. The device includes a control unit; and a stimulation unit that has a plurality of stimulation elements, and each stimulation element generates visual stimulation signals that reset the phase of the neuronal activity of the neurons when the signals are taken up via an eye of a patient and transmitted to neurons that are exhibiting a pathologically synchronous and oscillatory neuronal activity. The control unit is further capable of actuating the stimulation unit such that the stimulation elements generate the visual stimulation signals with a time offset in respect to one another and/or with differing phase and/or with differing polarity.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.2.1-4 | Award Amount: 16.45M | Year: 2013

DESIRE will focus on epileptogenic developmental disorders EDD, i.e. early onset epilepsies whose origin is closely related to developmental brain processes. A major cause of EDD are malformations of cortical development (MCD), either macroscopic or subtle. EDD are often manifested as epileptic encephalopathies (EE), i.e. conditions in which epileptic activity itself may contribute to severe cognitive and behavioral impairments. EDD are the most frequent drug-resistant pediatric epilepsies carrying a lifelong perspective of disability and reduced quality of life. Although EDD collectively represent a major medical and socio-economic burden, their molecular diagnosis, pathogenic mechanisms (PM) and rationale treatment are poorly understood. Specific objectives of DESIRE are to advance the state of the art with respect to: (1) the genetic and epigenetic causes and PM of EDD, particularly epileptogenic MCD, to elucidate molecular networks and disrupted protein complexes and search for common bases for these apparently heterogeneous disorders. (2) the diagnostic tools (biomarkers) and protocols through the study of a unique and well-characterized cohort of children to provide standardized diagnosis for patient stratification and research across Europe. (3) treatment of EDD using randomized, multidisciplinary clinical protocols and testing preclinical strategies in experimental models to also address novel preventative strategies. The workplan spans from clinical observation, to whole exome studies, cellular and animal models and basic research, identification of biomarkers and improvement of diagnostic methods, and back to the clinical trials and assessment of innovative, targeted treatment strategies. The consortium partners have an outstanding track record in genetics, basic neurophysiology, neuropathology and clinical research. Specialized expertise will be made available by the SMEs involved to develop novel diagnostic tools for tailored treatment approaches.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-1.3-1 | Award Amount: 15.59M | Year: 2008

ESNATS aims at developing a novel toxicity test platform based on embryonic stem cells (ESC), especially human ESC (hESC), to accelerate drug development, reduce R&D costs and propose a powerful alternative to animal tests (3 Rs). ESNATS will address current drug-testing shortcomings: - testing takes place late in the development cycle - animal test systems bear the risk of non-prediction due to inter-species variation - non-ESC assays rely on primary cells or cells of malignant origin that are hard-to-standardise and limited in regard to quantity, homogeneity and genetic diversity - existing assay systems based on primary animal cell lines do not reliably represent the physiological situation ESNATS will develop a battery of toxicity tests using hESC lines subjected to different standardised culture protocols. Tests will cover embryoid bodies in different developmental stages and differentiated derivatives including gamete and neuronal lineages, complemented with test systems for hepatic metabolism. Predictive toxicogenomics and proteomics markers will be identified. The individual tests will be integrated into an all-in-one test system. To enable future industrial use ESNATS will prepare automating and scaling up of hESC culture. The predictivity, quality and reproducibility of ESNATS will be evaluated in a proof of concept study. ESNATS benefits are to increase safety due to better predictivity of human test systems, to reduce, refine and replace animal tests, to lower testing cost, and to support medium/high throughput testing. ESNATS objectives will be achieved in a 5 year multi-disciplinary collaboration of leading European researchers in alternative testing, toxicology, ESC research, genomics, modelling, and automation. The consortium will also include representatives from regulatory bodies, the pharmaceutical industry and ethical advisors to provide guidance to ensure rapid applicability of the developed tests systems.


1 in 20 first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequently, clinicians are unable to offer targeted surveillance or known/emerging preventative strategies. Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, especially in the field of mass spectrometry and the comprehensive mapping of the blood metabolome and proteome. The overall objective of the IMPROvED project is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia. This will involve a multicentre, phase IIa clinical study to assess and refine novel and innovative prototype tests based on emerging metabolomic and proteomic technologies developed by SMEs within the consortium. The study will i) recruit 5000 first time pregnant women; ii) establish a high calibre biobank, augmented by accurate clinical metadata; iii) determine whether prototype predictive assays and algorithms translate to the clinical environment; iv) assess potential synergy of a combined metabolomic and proteomic approach and v) progress regulatory approval and development of the selected test into the clinical arena. The application of new technologies to identify at risk patients in early pregnancy will allow stratified care with personalized fetal and maternal surveillance, early diagnosis and timely intervention. If an effective test halved antenatal visits and administration of therapies (such as aspirin) to those at risk reduced the incidence of disease by only 20%, potential savings would approximate to 4 billion of the estimated 9 billion/yr spent in Europe providing antenatal care for nulliparous women and treatment for pre-eclampsia. Moreover, an accurate predictive test would be a crucial step in reducing the life-threatening complications of the disease.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: ENV.2007.1.1.2.1. | Award Amount: 3.96M | Year: 2008

We will determine the air pollution distribution and change in and around hotspots over the last decade from extensive satellite and in-situ observations and we will employ a series of different scale models in order to analyze the impacts of air pollution hot spots on regional and global air quality including potential future changes for various climate scenarios. Focus is on ozone and particulate matter with chemical and physical characterization, and their precursors. The Eastern Mediterranean (Istanbul, Athens, Cairo), the Po Valley, the BeNeLux region, the Pearl River Delta in China (with megacities Guangzhou and Hong Kong) and the hot and polluted European summer 2003 are chosen for intensive case studies. The consortium includes groups from China, Turkey, Greece and Italy, in addition to France, Germany, UK and Norway, with experts on the observations, emission data and models. A set of chemical transport models which connect all the most important spatial and temporal scales will be developed and used to quantify how the observed air pollution arises. The models and emission inventories will be evaluated, errors identified and improved on the urban, regional and global spatial scales. Climate change may cause changes in air pollution in and around hotspots, and hotspot pollution can change precipitation and temperature/albedo. These feedbacks will be studied in scale-bridging model systems based on global climate model scenarios, and in a coupled high resolution chemistry-climate model. The model systems evaluated in the project will be applied to analyse mitigation options in and around hotpots, also taking into account climate change. Best available technologies and sectoral changes will be studied. Several partners have key roles in the technical underpinning of policy. They will ensure that the improved emission inventories, scale-bridging model systems and the systematic observational evidence will have a significant, broad and lasting impact.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PROTEC-1-2015 | Award Amount: 3.23M | Year: 2016

ReDSHIFT will address barriers to compliance for spacecraft manufacturers and operators presented now and in the future by requirements and technologies for de-orbiting and disposal of space objects. This will be achieved through a holistic approach that considers from the outset opposing and challenging constraints for the safety of the human population when these objects re-enter the atmosphere, designed for demise, and for their survivability in the harsh space environment while on orbit. Ensuring robustness into the future, ReDSHIFT will take advantage of disruptive opportunities offered by 3D printing to develop highly innovative, low-cost spacecraft solutions, exploiting synergies with electric propulsion, atmospheric and solar radiation pressure drag, and astro-dynamical highways, to meet de-orbit and disposal needs, but which are also designed for demise. Inherent to these solutions will be structures to enhance spacecraft protection, by fracture along intended breakup planes, and re-entry demise characteristics. These structures will be subjected to functional tests as well as specific hypervelocity impact tests and material demise wind tunnel tests to demonstrate the capabilities of the 3D printed structures. At the same time, novel and complex technical, economic and legal issues of adapting the technologies to different vehicles, and implementing them widely across low Earth orbit will be tackled through the development of a hierarchical, web-based tool aimed at a variety of space actors. This will provide a complete debris mitigation analysis of a mission, using existing debris evolution models and lessons learned from theoretical and experimental work. It will output safe, scalable and cost-effective satellite and mission designs in response to operational constraints. Through its activities, ReDSHIFT will recommend new space debris mitigation guidelines taking into account novel spacecraft designs, materials, manufacturing and mission solutions.


Grant
Agency: Cordis | Branch: H2020 | Program: IA | Phase: REFLECTIVE-6-2015 | Award Amount: 2.60M | Year: 2016

The objectives of ArchAIDE are to support the classification and interpretation work of archaeologists with innovative computer-based tools, able to provide the user with features for the semi-automatic description and matching of potsherds over the huge existing ceramic catalogues. Pottery classification is of fundamental importance for the comprehension and dating of the archaeological contexts, and for understanding production, trade flows and social interactions, but it requires complex skills and it is a very time consuming activity, both for researchers and professionals. This tool would revolutionise archaeologists habits, behaviours and expectations, would meet real user needs and generate economic benefits, reducing time and costs, would create societal benefits from cultural heritage, improving access, re-use and exploitation of the digital cultural heritage in a sustainable way. These objectives will be achieved through the development of: - an as-automatic-as-possible procedure to transform the paper catalogues in a digital description, to be used as a data pool for search and retrieval process; - a tool (mainly designed for mobile devices) that will support archaeologists in recognising and classifying potsherds during excavation and post-excavation analysis, through an easy-to-use interface and efficient algorithms for characterization, search and retrieval of the visual/geometrical correspondences; - an automatic procedure to derive a complete potsherds identity card by transforming the data collected into a formatted electronic document, printable or visual; - a web-based real-time data visualization to improve access to archaeological heritage and generate new understanding; - an open archive to allow the archival and re-use of archaeological data, transforming them into common heritage and permitting economic sustainability. Those instruments will be tested and assessed on real-cases scenarios, paving the way to future exploitation.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: SPA-2007-1.1-01;SPA-2007-1.1-02 | Award Amount: 15.86M | Year: 2009

MACC (Monitoring Atmospheric Composition and Climate) is designed to meet the requirements that have been expressed for the pilot Core GMES Atmospheric Service. The project has been prepared by the consortia of the FP6 project GEMS and the GSE project PROMOTE, whose core service lines will provide the starting point for MACC. From mid-2009 MACC will continue, improve, extend, integrate and validate these service lines, so that the overall MACC system is ready near the end of 2011 for qualification as the operational GMES Atmospheric Core Service. MACC will prepare the core service in terms of implementation, sustained operation and availability. It will maintain and further develop the efficiency and resilience of the end-to-end pre-operational system, and will refine the scientific basis and quality of the products of the system. It will ensure that its service lines best meet both the requirements of downstream-service providers and end users at the European, national and local levels, and the requirements of the global scientific user community. The service lines will cover air quality, climate forcing, stratospheric ozone and solar radiation. MACC will deliver operational products and information that support the establishment and implementation of European policy and wider international programmes. It will acquire and assimilate observational data to provide sustained real-time and retrospective global monitoring of greenhouse gases, aerosols and reactive gases such as tropospheric ozone and nitrogen dioxide. It will provide daily global forecasts of atmospheric composition, detailed air-quality forecasts and assessments for Europe, and key information on long range transport of atmospheric pollutants. It will provide comprehensive web-based graphical products and gridded data on which downstream services may be based. Feedback will be given to space agencies and providers of in-situ data on the quality of their data and on future observational requirements.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: INT-09-2015 | Award Amount: 2.50M | Year: 2016

The EU and Turkey face mounting challenges both in relation to one another and internationally. The EU is confronted with an economic crisis which is likely to make differentiation a growing phenomenon. Turkey faces polarisation between different political forces, the state and civil society. The neighbourhood is unravelling to the east and south and a power shift is under way at global level. This questions the regional roles of Turkey and the EU. Accordingly, FEUTURE a consortium of 13 experienced universities and think tanks from the EU, Turkey and the neighbourhood aims to: (1) map the dynamics of EU-Turkey relations as to underlying narratives and thematic drivers; (2) substantiate most likely future scenario(s) and assess its implications; (3) draw policy recommendations. FEUTURE provides excellence and pursues an ambitious, inspiring and innovative programme in a three-phased structure of elaboration, exploration and extrapolation. It applies an inter-temporal, interdisciplinary and international approach by analysing drivers within six thematic dimensions (politics, security, economics, energy, migration, identity) and across four levels of analysis (EU, Turkey, neighbourhood, global). Phases 1 and 2 culminate in an extrapolation phase in which FEUTURE integrates new knowledge and tests the implications of 3 ideal-type future scenarios for EU-Turkey relations: conflict, cooperation and convergence. We engage in a trans-disciplinary exchange within an elite survey and with the knowledge-user community from the four levels of analysis exploiting the full range of virtual and social media as well as traditional means. FEUTUREs work plan guarantees coherence of its research approach by streamlining work in one conceptual, one synthesis, two organisational and six thematic work packages. Joint WP meetings and three FEUTURE conferences assure intensive horizontal exchange. FEUTURE will achieve academic, practical and structural impact beyond the project.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: ENV.2010.2.1.4-4 | Award Amount: 9.99M | Year: 2011

The strategic goal of EcoFINDERS is to provide the EC with tools to design and implement soil strategies aimed at ensuring sustainable use of soils, including: i) Characterisation of European soil biodiversity; ii) Determination of relations between soil biodiversity, soil functions and ecosystem services; iii) Design of policy-relevant and cost-effective indicators for monitoring soil biodiversity. The project will: i) Develop and standardise tools and procedures to measure microbial and faunal diversity; ii) Describe the diversity of soil organisms (microbes and fauna), iii) Decipher the interactions among soil organisms and with plants through foodwebs and iv) Determine the role played by soil organisms in soils ecosystem services (nutrient cycling, carbon storage, water retention, soil structure regulation, resistance to pests and diseases, and regulation of above-ground diversity); iii) Establish cost-effective bioindicators for measuring sustainability of the microbial and faunal diversity and their associated functions (using a combination of metrics and meta-analysis); iv) Evaluate the economic value of ecosystem services, the added value of these bioindicators; v) Develop and implement effective communication strategies to engage the European public around issues associated with the sustainability of soil biodiversity. The overall concept of the project is to develop and integrate the following activities: i) Decipher the links between soil biodiversity, activities, functioning and ecosystem services; ii) Combine three types of approach: observation, experimentation, and computation; iii) Assess the impact of environmental conditions; iv) Integrate information on microbes, fauna and plant communities and analyse how these compartments interact. The general hypotheses are: changes in soil biodiversity indicate the direction and rate of changes in soil functions and associated ecosystem services; application of cost-effective bioindicators brings an economic added value to sustainable soil management.


Grant
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: SPACE | Award Amount: 5.00M | Year: 2014

MACC-III is the last of the pre-operational stages in the development of the Copernicus Atmosphere Service. Its overall institutional objective is to function as the bridge between the developmental precursor projects - GEMS, PROMOTE, MACC and MACC-II- and the Atmosphere Service envisaged to form part of Copernicus Operations. MACC-III will provide continuity of the atmospheric services provided by MACC-II. Its continued provision of coherent atmospheric data and information, either directly or via value-adding downstream services, is for the benefit of European citizens and helps meet global needs as a key European contribution to the Global Climate Observing System (GCOS) and the encompassing Global Earth Observation System of Systems (GEOSS). Its services cover in particular: air quality, climate forcing, stratospheric ozone, UV radiation and solar-energy resources. MACC-IIIs services are freely and openly available to users throughout Europe and in the world. MACC-III and its downstream service sector will enable European citizens at home and abroad to benefit from improved warning, advisory and general information services and from improved formulation and implementation of regulatory policy. MACC-III, together with its scientific-user sector, also helps to improve the provision of science-based information for policy-makers and for decision-making at all levels. The most significant economic benefit by far identified in the ESA-sponsored Socio-Economic Benefits Analysis of Copernicus report published in July 2006 was the long-term benefit from international policy on climate change. Long-term benefit from air quality information ranked second among all Copernicus benefits in terms of present value. Immediate benefits can be achieved through efficiency gains in relation to current policies. The estimated benefits substantially outweigh the costs of developing and operating the proposed services.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SSH-2007-8.0-01 | Award Amount: 1.83M | Year: 2008

The research concerns the present role of FBOs in matters of poverty and other forms of social exclusion (such as homelessness or undocumented persons) in cities. We define FBOs as any organisation that refers directly or indirectly to religion or religious values, and functions as a welfare provider or as a political actor. The central assumption is that FBOs tend to fill the gap left after the supposed withdrawal of the welfare state in several domains of public life, particularly in social welfare and in social protection. At first sight, this looks like a return to the charity of former times, when such associations occupied the fore of social help in many countries. But we might as well witness the beginning of a new type of welfare regime with a stronger focus on local policies and strategies and new interplays between local authorities and civil society organisations. What is the position of FBOs in combating poverty and other forms of social distress cities? How has this role changed over time and how do these activities contribute to combating social exclusion and promoting social cohesion? What are the implications for policies and the governance of European cities? From both scientific and policy perspectives, there is a great need for better empirical and comparative data on what is going on in European cites in matters of poverty and exclusion policies and, in particular, the contribution of FBOs in the reduction (or deepening) of the problems. FBOs have direct entrance to the poor side of cities because of (1) their activities in deprived urban neighbourhoods and among excluded groups and (2) as in the case of many FBOs with a non-western background, because their members often belong to these deprived and excluded groups themselves.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.3.1-1 | Award Amount: 7.72M | Year: 2012

Background. Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, and old drug, is now the antimicrobial with greatest in vitro activity against MDR-GNB. However, no randomized clinical trial with colistin has been carried out. Additional aspects of colistin are also not well known, such as the appearance of resistant strains or alterations in the intestinal microbiome during treatment. Furthermore, conventional microbiological techniques take 48 to 72 hours to identify pathogens and determine their susceptibility. This is too long if empiric treatment is inappropriate. Objetives. The overall goal is the optimisation of the treatment of VAP caused by MDR-GNB, by defining a gold standard empiric therapy and reducing the period of time needed for the determination of the etiology and susceptibility of pathogens. Methods. MagicBullet proposes a randomized, open label, multicenter, clinical trial to compare the safety and efficacy of colistin vs. meropenem, both combined with levofloxacin, for empirical treatment of VAP. The pharmacokinetic and pharmacodynamic characteristics of colistin will be determined. Evaluation of the impact of the both treatments in the intestinal microbiome of patients and in the Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrug-resistant gramnegative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, and old drug, is now the antimicrobial with greatest in vitro activity against MDR-GNB. However, no randomized clinical trial with colistin has been carried out. Additional aspects of colistin are also not well known, such as the appearance of resistant strains or alterations in the intestinal microbiome during treatment. Furthermore, conventional microbiological techniques take 48 to 72 hours to identify pathogens and determine their susceptibility. This is too long if empiric treatment is inappropriate.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.4.1-10 | Award Amount: 16.21M | Year: 2009

Epidemiological and experimental evidence supports a link between chronic inflammation and cancer and indicates a role for inflammatory cells in the initiation, progression and metastasis of malignancy. The objective of the collaborative integrated project INFLA-CARE is to structure a European collective of scientific and technological excellence in the field of Inflammation & Cancer which will capitalise on the available expertise and develop effective anti-inflammatory strategies and novel agents for cancer prevention and treatment. The project will specifically seek to identify molecular and cellular targets for cancer therapy through the development and systematic study of state-of-the-art pre-clinical models of inflammation-driven cancer. By mobilising the outstanding research experience and technological capacities of the network participants, the program will accelerate the translation of knowledge obtained by basic research into new diagnostic and therapeutic strategies which will be used for the detection, prevention and improved management of several types of human cancer. INFLA-CARE will also ensure spreading of scientific excellence and dissemination of knowledge beyond the network, by encouraging innovation and transfer of knowledge and by raising public understanding of scientific and health issues. The impact of the program is therefore expected to be multi-dimensional, namely scientific, educational and innovation-related, enhancing European competitiveness and addressing major scientific issues and societal needs.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-05-2014 | Award Amount: 6.46M | Year: 2015

Breast cancer affects more than 360,000 women per year in the EU and causes more than 90,000 deaths. Identification of women at high risk of the disease can lead to disease prevention through intensive screening, chemoprevention or prophylactic surgery. Breast cancer risk is determined by a combination of genetic and lifestyle risk factors. The advent of next generation sequencing has opened up the opportunity for testing in many disease genes, and diagnostic gene panel testing is being introduced in many EU countries. However, the cancer risks associated with most variants in most genes are unknown. This leads to a major problem in appropriate counselling and management of women undergoing panel testing. In this project, we aim to build a knowledge base that will allow identification of women at high-risk of breast cancer, in particular through comprehensive evaluation of DNA variants in known and suspected breast cancer genes. We will exploit the huge resources established through the Breast Cancer Association Consortium (BCAC) and ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles). We will expand the existing datasets by sequencing all known breast cancer susceptibility genes in 20,000 breast cancer cases and 20,000 controls from population-based studies, and 10,000 cases from multiple case families. Sequence data will be integrated with in-silico and functional data, with data on other known risk factors, to generate a comprehensive risk model that can provide personalised risk estimates. We will develop online tools to aid the interpretation of gene variants and provide risk estimates in a user-friendly format, to help genetic counsellors and patients worldwide to make informed clinical decisions. We will evaluate the acceptability and utility of comprehensive gene panel testing in the clinical genetics context.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-1.4-7 | Award Amount: 3.91M | Year: 2009

The success of stem cell therapy is highly dependent on a safe and reliable supply of human stem cells and stem cell-derived differentiated cells, which must be assured by efficient and robust culture methods. Current culture of human embryonic and adult stem cells is not optimised (with regards to e.g. media, growth factors, supporting biomaterials, differentiation techniques) and is far from fulfilling the demands in terms of reproducibility and preciseness. Additionally, current methods do not allow fast screening of culture conditions for their systematic optimisation. These limitations currently slow down the development of stem cell applications and will be addressed and overcome by the Hyperlab project. To reach the overall aim of developing new and improved culture methods, media and protocols for stem cell cultivation and differentiation, Hyperlab will adapt novel microfluidics-based cell cultivation technologies to the specific needs of stem cell culture. The developed culture systems will have two major advantages over existing approaches: on the one hand, they will improve stem cell culture in terms of microenvironment control, reproducibility, robustness and efficiency. On the other hand, these microscale technologies, together with developed transgenic readout systems, will allow medium to high throughput screening of culture conditions, enabling determination of optimal protocols in shorter time. Once established, technologies, protocols and conditions will be evaluated for their upscalability and will be made GMP-compliant to form a solid basis for progress in human stem cell therapy. To implement this innovative strategy, Hyperlab follows an integrated approach, bringing together renowned experts from stem cell biology, microsystem technologies, biomaterial design and relevant regulatory bodies. Hyperlab is thus in a position to provide standardised, reproducible methods and tools to advance therapeutic stem cell research.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: SPA.2009.1.1.01 | Award Amount: 7.17M | Year: 2010

Air quality is a crucial environmental factor, e.g. evidenced by the fact that particles in the air are estimated to reduce the lifetime of the average European citizen by 8 months. Assessing and monitoring air quality are thus fundamental to improve Europes welfare. PASODOBLE will develop and demonstrate user-driven downstream information services for the public, regional and local air quality sectors by combining space-based and in-situ data with models in 4 thematic service lines: (1) Health community support for hospitals, pharmacies, doctors and people at risk, (2) public information for regions, cities, tourist industry and sporting event organizers, (3) compliance monitoring support on particulate matter for regional environmental agencies and (4) local forecast model evaluation support for local authorities and city bodies. Continuing on the achievements of the ESA GSE PROMOTE project, PASODOBLE will stimulate the development of quality-assured air quality services towards their application market by increasing the implementation efficiency of demonstrated and operational services in the future (new regions, users or parameter combinations, additional service providers). PASODOBLE objectives are: (1) evolution of existing and development of new sustainable air quality services for Europe on regional and local scales, (2) development and testing of a generic service framework for coordinated input data acquisition and customizable user-friendly access to services, (3) utilization of multiple cycles of delivery, use and assessment versus requirements and market planning in cooperation with users and (4) promotion and harmonisation of best practise tools for air quality communities. PASODOBLE comprises an initial phase of requirement analysis, service design, development and implementation, followed by 2 annual demonstration and evaluation cycles in which the services and the generic framework with regard to user needs and business planning will be assessed.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP-SICA | Phase: ENV.2009.1.2.1.2 | Award Amount: 4.72M | Year: 2010

One of the most dramatic and immediate impacts of climate variation is that on disease, especially the vector-borne diseases that disproportionally affect the poorest people in Africa. Although we can clearly see that, for example, an El Nino event triggers Rift Valley Fever epidemics, we remain poor at understanding why particular areas are vulnerable and how this will change in coming decades, since climate change is likely to cause entirely new global disease distributions. This applies to most vector borne disease. At the same time, we do not know currently the limit of predictability of the specific climate drivers for vector-borne disease using state-of-the-art seasonal forecast models, and how best to use these to produce skilful infection-rate predictions on seasonal timescales. The QWeCI project thus aims to understand at a more fundamental level the climate drivers of the vector-borne diseases of malaria, Rift Valley Fever, and certain tick-borne diseases, which all have major human and livestock health and economic implications in Africa, in order to assist with their short-term management and make projections of their future likely impacts. QWeCI will develop and test the methods and technology required for an integrated decision support framework for health impacts of climate and weather. Uniquely, QWeCl will bring together the best in world integrated weather/climate forecasting systems with heath impacts modelling and climate change research groups in order to build an end-to-end seamless integration of climate and weather information for the quantification and prediction of climate and weather on health impacts in Africa.


News Article | December 21, 2016
Site: www.eurekalert.org

DFG to fund 12 projects for the development of new technologies through new call/ New major research instrument for X-raying reinforced concrete components approved The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) is funding new instrumentation for various fields of knowledge-driven research through two calls. The Joint Committee of the largest research funding organisation and central self-governing organisation of the research community in Germany took the relevant funding decisions at its December session in Bonn. The first decision relates to the call for "New Instrumentation for Research", issued for the first time, which is designed to enable the development of new instrumentation technologies for research questions which cannot be answered with currently available equipment. The newly developed instrumentation should be made available to as many researchers as possible for the purposes of basic research. After the very strong response to the call issued in January 2016 - which attracted a total of 79 proposals - the DFG Joint Committee has now decided to fund twelve projects for an initial three years with a total funding volume of €8 million. The projects relate to natural sciences (including geosciences), life sciences, medical technology, and engineering sciences and are based at the following universities and non-university research institutions: Aalen University; Charité - Universitätsmedizin Berlin (university hospital); University of Bonn; Technical University of Darmstadt; Erlangen University Hospital, University Medical Center Freiburg and Radiological Institute, German Cancer Research Centre, Heidelberg; Leibniz Institute for Applied Geophysics, Hanover, and Leibniz Institute of Photonic Technology, Jena; Heidelberg University; University of Jena; University of Cologne, Leibniz Institute for Astrophysics, Potsdam, and Landessternwarte Königstuhl (state observatory), Heidelberg; Technical University of Munich, University of Greifswald and Max Planck Institute of Plasma Physics, Greifswald; University Hospital Münster; University of Würzburg and University of Mainz. The second decision relates to a major instrumentation initiative. Through this initiative, the DFG will make €8 million available for the construction and commissioning of a new type of system at the Technical University of Kaiserslautern that will be able to X-ray components made of reinforced concrete and other materials using computed tomography (CT). The system will use X-rays of 9 mega-electronvolts, much more powerful than medical X-ray systems, allowing it to probe reinforced concrete components up to 30 centimetres in diameter and 6 metres in length. It will even be possible to X-ray components while they are experiencing stress or destruction; the three-dimensional images of these processes will provide researchers with valuable information. The research carried out with the new equipment is intended to provide information about the durability and properties of established construction materials and also facilitate the development of improved materials and composites. For 20 percent of its usage time, the new X-ray system will also be available to other scientific working groups in Germany. For "New Instrumentation for Research": Dr Achim Tieftrunk, Scientific Instrumentation and Information Technology Division, tel. +49 228 885-2816, Achim.Tieftrunk@dfg.de For the major instrumentation initiative: Dr Michael Royeck, Scientific Instrumentation and Information Technology Division, tel. +49 228 885-2976, Michael.Royeck@dfg.de


News Article | November 2, 2016
Site: www.eurekalert.org

Imagine a group of travelers who witness two cases of littering at a train station. One person throws a coffee cup on the platform. Another person throws away not only a coffee cup, but an entire bag of trash. Who is more likely to be confronted and reprimanded by bystanders? Although throwing away a bag of trash is considered the bigger norm violation, this behavior does not elicit a stronger reaction in witnesses. That is the result of a study conducted by Bettina Rockenbach, Professor of Experimental and Behavioral Economics at the University of Cologne, Loukas Balafoutas (University of Innsbruck) and Nikos Nikiforakis (New York University Abu Dhabi). The research team investigated how people respond to large and small violations of social norms in public spaces. The results of the study, "Altruistic punishment does not increase with the severity of norm violations in the field," are published in Nature Communications. The study refutes the assumption that larger violations tend to be punished more severely than smaller offences. Rockenbach and her colleagues staged small violations (littering a coffee cup) and large violations (littering a coffee cup and bag of trash) at train stations in Germany and recorded how travelers responded in more than 800 trials. The implicit assumption was that bystanders would react more strongly if more garbage was littered, hence the norm violation was greater. This is a principle that has been widespread from the biblical "eye for an eye" to modern legal philosophy, which demands just punishment. It has also been substantiated in laboratory experiments. However, the size of the violation did not affect the likelihood that the litterer would be reprimanded - nor did it affect the intensity of the reprimand. Travelers have more negative emotions toward the larger violation and felt that it should be reprimanded more severely. Despite these emotional responses, however, the surveyed individuals admitted that they would be reluctant to confront or punish such violations in real-life settings. The scientists explain this reluctance with the perceived risk of retaliation by the norm violator. The greater the norm violation, the greater the retaliation might be. Bystanders feared that in cases of a more severe social norm violation, the person's reaction would be stronger when confronted or reprimanded. The study shows that social self-regulation has its limits. Up to a certain point, we reprimand each other for bad behavior. But in cases of more extreme norm violations, social self-regulation no longer works and we need authorities, police and security personnel. The paper "Altruistic punishment does not increase with the severity of norm violations in the field" is appearing in Nature Communications. | DOI: 10.1038/NCOMMS13327 http://www.


News Article | December 14, 2016
Site: www.eurekalert.org

The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) is establishing seven new Research Units, following a decision by the DFG Senate during its winter session in Bonn. The research collaborations will enable researchers to pursue pressing current issues in their research areas and take innovative directions in their work. Research Units can be funded for a maximum of two periods of three years each. In the initial funding period, the seven new groups will receive approximately €17 million in total. Together with the new collaborations, the DFG will be funding a total of 242 Research Units, including Clinical Research Units. The New Research Units (In alphabetical order by spokesperson's university) How does extreme flooding occur in rivers and how does it develop in spatio-temporal terms? This is the question that will be examined by the "Space-Time Dynamics of Extreme Floods (SPATE)" Research Unit, by carrying out the first systematic analysis of hydrological and meteorological data on six major river basins in Germany and Austria. The researchers will study four topic areas: sequence of events, spatial and temporal fluctuations and the resulting predictability of extreme floods. (Spokesperson: Professor Dr. Andreas H. Schumann, University of Bochum) Robots that interact with humans are able to register situations in real time. However, they cannot predict the actions of a human, and the situations that may result, in order to adapt their own behaviour accordingly. The "Anticipating Human Behaviour" Research Unit therefore aims to develop technologies which enable the creation of applications based on predicting human movement patterns. It will take a holistic approach that comprises the recording, modelling and prediction of human motion sequences and behavioural patterns in everyday environments. (Spokesperson: Professor Dr. Jürgen Gall, University of Bonn) Research that relies on animal experimentation must strictly comply with the 3Rs principle (Replace, Reduce, Refine) - not only on ethical grounds but also to ensure that the data obtained is comparable. Central to this is the assessment of pain, stress or lasting damage caused during animal experiments. Such assessments are now required by European and national guidelines, but there is a lack of suitable, generally accepted methods for objective evaluation. The "Severity Assessment in Animal Based Research" Research Unit intends to remedy this deficit and further develop model standardised methods for severity assessment. The focus will also be on non-invasive methods. It is hoped that a more objective assessment will enhance the quality of animal-based research and also identify approaches with which to minimise animal stress in animal experimentation. (Spokesperson: Professor Dr. André Bleich, Hannover Medical School) The Research Unit entitled "Functional Dynamics of Ion Channels and Transporters - DynIon" will combine experimental methods used in electrophysiology, biochemistry and structural biology with computer-based theoretical approaches to study ion channels and transporters. Its focus will be on dynamic processes on various time scales, particularly the activation of ion channels by chemical signals. In this way, the Research Unit intends not only to provide new insights into selected ion channels and transporters, but also to advance theoretical and experimental approaches in ion channel research. (Spokesperson: Professor Dr. Klaus Benndorf, University of Jena) The philosophy-centred "Inductive Metaphysics" Research Unit intends to illuminate the non-analytical aspect of metaphysics. It is firstly concerned with the history of so-called inductive approaches in metaphysics, and secondly with a metaphilosophical discussion of these ideas. This means, above all, accurately identifying and categorising inductive approaches, and then their methodological foundation. Finally, the researchers aim to apply and test inductive methods in established metaphysical questions. (Spokesperson: Professor Dr. Andreas Hüttemann, University of Cologne) Expectations of knowledge-based action are increasing, the importance of directly applicable research is growing, and the pressure for legitimation in science and the humanities, in view of expanding discourses on risk, uncertainty and ignorance, is becoming more urgent. But how do known facts such as data, findings or conclusions achieve the quality characteristic of evidence? And how does the proffered evidence influence decisions in different contexts? The Research Unit entitled "Practicing Evidence - Evidencing Practice in Science, Medicine, Technology and Society PEEP" will address these questions by investigating both the growing importance of evidence in the knowledge society and its functionalisation. (Spokesperson: Professor Dr. Karin Zachmann, Technical University of Munich) The Research Unit "Matter Under Planetary Interior Conditions - High-Pressure, Planetary and Plasma Physics" will focus on matter under extreme conditions. The researchers will study the behaviour of rocks and complex molecular mixtures, which is essential to our understanding of the most frequently discovered planets: so-called super-Earths and Neptune-like planets. It is intended that their findings will contribute to the development of new models explaining how these types of planets are formed and evolve. They will also be used to evaluate observation data from ongoing and future satellite missions. (Spokesperson: Professor Dr. Ronald Redmer, University of Rostock) Further information will be provided by the spokespersons of the established units. Further information on the DFG Research Units: http://www.


News Article | November 2, 2016
Site: www.sciencedaily.com

When bystanders become witnesses of a social norm violation, they will confront the culprit -- all the more if the violation is severe. Although this appears to make sense, in fact the opposite is true. The more severe the norm violation, the more reluctant people will be to reprimand the person who committed it. Their fear of retaliation is too great. Imagine a group of travelers who witness two cases of littering at a train station. One person throws a coffee cup on the platform. Another person throws away not only a coffee cup, but an entire bag of trash. Who is more likely to be confronted and reprimanded by bystanders? Although throwing away a bag of trash is considered the bigger norm violation, this behavior does not elicit a stronger reaction in witnesses. That is the result of a study conducted by Bettina Rockenbach, Professor of Experimental and Behavioral Economics at the University of Cologne, Loukas Balafoutas (University of Innsbruck) and Nikos Nikiforakis (New York University Abu Dhabi). The research team investigated how people respond to large and small violations of social norms in public spaces. The results of the study, "Altruistic punishment does not increase with the severity of norm violations in the field," are published in Nature Communications. The study refutes the assumption that larger violations tend to be punished more severely than smaller offences. Rockenbach and her colleagues staged small violations (littering a coffee cup) and large violations (littering a coffee cup and bag of trash) at train stations in Germany and recorded how travelers responded in more than 800 trials. The implicit assumption was that bystanders would react more strongly if more garbage was littered, hence the norm violation was greater. This is a principle that has been widespread from the biblical "eye for an eye" to modern legal philosophy, which demands just punishment. It has also been substantiated in laboratory experiments. However, the size of the violation did not affect the likelihood that the litterer would be reprimanded -- nor did it affect the intensity of the reprimand. Travelers have more negative emotions toward the larger violation and felt that it should be reprimanded more severely. Despite these emotional responses, however, the surveyed individuals admitted that they would be reluctant to confront or punish such violations in real-life settings. The scientists explain this reluctance with the perceived risk of retaliation by the norm violator. The greater the norm violation, the greater the retaliation might be. Bystanders feared that in cases of a more severe social norm violation, the person's reaction would be stronger when confronted or reprimanded. The study shows that social self-regulation has its limits. Up to a certain point, we reprimand each other for bad behavior. But in cases of more extreme norm violations, social self-regulation no longer works and we need authorities, police and security personnel.


News Article | October 28, 2015
Site: www.nature.com

Overall, this project comprised tumour samples from 217 German patients with neuroblastoma (Extended Data Table 1a). Patients were diagnosed between 1991 and 2014 and were registered and treated according to several clinical trials of the Gesellschaft für Pädiatrische Onkologie und Hämatologie. The trials were approved by the Ethics Committee of the Medical Faculty, University of Cologne. The Institutional Review Board approved collection and use of all specimens in this study. Informed consent was obtained from all patients. The MYCN gene copy number was determined as a routine diagnostic method using FISH analysis. DNA and total RNA was isolated from tumour samples with at least 60% tumour cell content as evaluated by a pathologist. TERT rearrangements were established as a novel molecular marker in a discovery cohort of 56 patients. In this set, TERT rearrangements (n = 12) occurred exclusively in high-risk patients (n = 39). We sought to validate this finding in a larger, representative neuroblastoma cohort, comprising approximately 40% high-risk patients. Allowing for a potential occurrence of TERT rearrangements in up to 10% of non-high-risk patients and ensuring a statistical power of 80%, we estimated that at least 75 non-high-risk patients were required for validation. We therefore investigated 161 additional tumours derived from 86 non-high-risk and 75 high-risk patients (including 39 and 36 tumours with and without MYCN amplification, respectively). The experiments were not randomized. The investigators were not blinded to allocation during experiments and outcome assessment. Neuroblastoma cell lines LAN-6, GI-ME-N, as well as SK-N-FI were directly purchased from the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ, Braunschweig, Germany) or American Type Culture Collection (ATCC/LGC Standards, Molsheim Cedex, France), respectively. Furthermore, SK-N-BE(2)C, IMR-5/75, and CLB-GA were provided by the laboratories of H. Deubzer, F. Westermann and J. H. Schulte, respectively. All cell lines not directly purchased from ATCC or DSMZ were authenticated by STR profiling at the DSMZ. IMR-5/75, SK-N-BE(2)C, GI-ME-N, and CLB-GA were grown in RPMI1640 with 10% FBS; LAN-6 and SK-N-FI were cultured in DMEM with 20% FBS. All cell lines were cultured without antibiotics and routinely tested negative for mycoplasma. DNA was extracted from fresh-frozen tumour tissue and the corresponding matched normal of 56 patients using the Puregene Core Kit A (Qiagen) and NucleoSpin Blood DNA extraction kit (Macherey-Nagel), respectively, according to the manufacturers’ instructions. DNA was eluted in 1 × TE buffer, diluted to a working concentration of 100 ng µl−1 and stored at −80 °C. Libraries were prepared with the TruSeq DNA PCR-free sample preparation kit (Illumina) followed by size selection using SPRI beads (Beckman Coulter Genomics). The final libraries were then sequenced on an Illumina HiSeq 2000 instrument with a paired-end read length of 2 × 100 nucleotides. Raw sequencing reads were aligned to the human genome (NCBI build 37/hg19) by using BWA (version 0.6.1-r104; https://github.com/lh3/bwa). Possible PCR duplicates were then masked in the resulting alignment files by searching for concordant read pairs. Next, somatic mutations were called using a further development of our in-house mutation caller. The major improvements to previous versions25 of the caller were that identified variants were filtered against a library of more than 500 normals (mixed whole-exome and whole-genome) and that the error model contained contributions of human library contamination which were estimated from the sequencing data. With these modifications we were able to gain a larger sensitivity and specificity (data not shown). Rearrangements as well as copy number changes were analysed as described previously25. Patterns of recurrent genomic rearrangements were identified by scanning the genomes for breakpoint clusters that occur within 100 kb regions in a similar approach to that described in ref. 7. To compute the telomere ratio from whole-genome sequencing data, raw sequencing reads containing the telomere repeat sequence (TTAGGG) or its reverse complement were counted5, and the ratio between the tumour and matched normal was determined. This ratio was then normalized to the absolute amount of sequenced DNA using the total amount of reads from the tumour and the normal. In the validation cohort, hybrid-capture-based target enrichment followed by massively parallel sequencing of the genomic region encompassing TERT and CLPTM1L was used to detect TERT rearrangements. Alignment and the detection of genomic rearrangements were performed analogous to whole-genome sequencing. We reported only those TERT rearrangements that had been detected both by FISH analysis and by targeted sequencing. RNA sequencing and gene expression analysis was performed as described previously26. Briefly, a Dynabeads mRNA Purification Kit (Invitrogen) was used to purify mRNA from total RNA. Library construction was performed according to the standard TruSeq protocol. Clusters were generated according to the TruSeq PE cluster Kit version 3 reagent preparation guide (for cBot-HiSeq/HiScanSQ). High-throughput shotgun sequencing was performed on the IlluminaHiSeq 2000 platform. Paired-end reads with lengths of 100 nucleotides were generated. Raw data processing, read mapping, and gene expression quantification were done using the Magic-AceView analysis pipeline as described27. The Magic analysis tool is accessible at ftp://ftp.ncbi.nlm.nih.gov/repository/acedb/Software/Magic; AceView served as primary transcriptome reference (http://www.aceview.org). RNA sequencing was also used to identify MYCN-regulated genes in IMR5/75 cells expressing MYCN shRNA under the control of the tet repressor. Briefly, for IMR5/75 shRNA inducible cells, 1 µg ml−1 tetracycline or the equivalent of volume of 70% ethanol was added to the cells, and cells were incubated for 24 h and then harvested for RNA extraction using RNeasy mini kit (Qiagen). Five micrograms of RNA from each sample was processed using the RiboGold kit (Epicentre) to remove rRNA from samples to increase reads from mRNA. The concentration of the resulting RNA was measured using the Qubit RNA assay (Life Technologies). One microgram of RNA was then used to prepare libraries for sequencing using the NEB Ultra directional RNA library prep lit for Illumina (New England Bioscience) according to the manufacturer’s instructions. Single-colour gene expression profiles were generated using customized 4×44 K oligonucleotide microarrays produced by Agilent Technologies. Labelling and hybridization was performed following the manufacturer’s protocol. Microarray expression profiles were generated using Agilent’s Feature Extraction software (version 9.5.1). Data were normalized using quantile normalization. Rearrangements of the TERT locus were validated by dideoxy sequencing in both diagnostic and relapsed tumour samples. Dideoxy sequencing was performed by Seqlab. BAC clones CTD-2191M2 (to detect the region proximal of CLPTM1L) and CTD-2511M20 (to detect the TERT/SLC6A18/SLC6A19 loci) were labelled with digoxigenin and biotin, respectively (see also Fig. 3a). Cell line cytospin preparations were pre-treated with 2 × SSC solution at 37 °C for 30 min, digested with Digest-All III (dilution 1:2, Invitrogen) at 37 °C for 6 min, fixed in 4% formaldehyde, and subsequently dehydrated in a graded ethanol series. FISH probes and human Cot-1 DNA (Life Technologies) in hybridization buffer (50% formamide, 10% dextran sulfate sodium, in 2 × SSC) were co-denatured at 85 °C for 4 min and hybridized overnight at 37 °C. Post-hybridization washing was done with 0.5 × SSC at 75 °C for 5 min, followed by washes in PBS, a blocking step with CAS-block (Life Technologies, with 10% normal goat serum in PBS) and a 1 h post-incubation with streptavidin–Alexa-555 conjugates (1:500, Life Technologies) and anti-digoxigenin-FITC (1:500, Roche), to enable fluorescence detection. After three subsequent washes in PBS, samples were mounted with VectaShield mounting media containing 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI; Vectorlabs). Images were acquired using an Olympus Fluoview FV10 scanning confocal microscope system. Telomerase activity in cell lines was determined with a PCR-based telomeric repeat amplification protocol (TRAP) enzyme-linked immunosorbent assay (ELISA) kit (TeloTAGGG Telomerase PCR ELISAPLUS, Roche) according to the manufacturer’s protocol. Formaldehyde cross-linking of cells, cell lysis, sonication, ChIP procedure, and library preparation were performed as described previously28, starting with approximately 4 × 106 cells (1 × 106 cells per individual immunoprecipitation). Direct cell lysis for each sample was achieved by incubation for 30 min in 950 µl RIPA I on ice (10 mM Tris-HCl pH 8.0, 1 mM EDTA pH 8.0, 140 mM NaCl, 0.2% SDS, 0.1% DOC). Tissue disruption, formaldehyde fixation, and sonication of tumour material were done according to a previously published protocol29. Approximately 30 mg of fresh-frozen tumour tissue was used per individual ChIP-seq experiment. All subsequent steps were performed analogous to cell line experiments. The Bioruptor Plus sonication device (Diagenode) was used for high intensity sonication for 30–60 min each with intervals of 30 s on and 30 s off. Library preparation was performed using the NEBNext Ultra DNA Library Prep Kit (New England Biolabs) according to the manufacturer’s protocol. Samples were mixed in equal molar ratios and sequenced on an Illumina sequencing platform. Single-end reads were aligned to the hg19 genome using Bowtie2 (version 2.1.0). Only uniquely aligned reads were kept. BAM files of aligned reads were further processed using the deepTools suite (https://github.com/fidelram/deepTools). Input files were subtracted from the treatment files using the bamCompare tool, applying the SES method for normalization of signal to noise. Resulting signals were normalized to an average 1× coverage to produce signal (bigWig) files. Peaks were called using the MACS 1.4 tool using default parameters. DNA was isolated from snap-frozen neuroblastoma tissue. Genome-wide DNA methylation was assessed using an Infinium HumanMethylation450 BeadChip (Illumina) according to the manufacturer’s instructions. Probes were removed on the basis of the following criteria: (1) proportion of non-detectable β values >0.3 (n = 379), (2) single nucleotide polymorphism at or near the targeted CpG site according to R-Forge package IMA (https://rforge.net/IMA/, n = 92,600), (3) control probes (n = 65), and (4) mapping to the X or Y chromosome (n = 10,351). Together, 382,182 probes were kept for further analysis. The k-nearest neighbours method was used to impute missing values, and a subset quantile normalization was applied. TERT-related CpGs were annotated using the assignGenomeAnnotation program of the HOMER tool suite (http://homer.salk.edu/homer). Both assays have been performed as described previously21. Briefly, genomic DNA was purified and digested with AluI and MboI. For restriction-fragment analysis, 10 μg of digested DNA was electrophoresed on a 0.8% TBE-agarose gel. Subsequently, telomeric DNA was detected by Southern blotting using a [32P]dATP end-labelled (CCCTAA) oligonucleotide probe. For the C-circle assay, DNA samples (7.5 ng, 10 µl) diluted in ultraclean water were combined with 10 μl BSA (NEB; 0.2 mg ml−1), 0.1% Tween, 0.2 mM each dATP, dGTP, dTTP, and 1 × Φ29 Buffer (NEB) in the presence or absence of 7.5 U ΦDNA polymerase (NEB), incubated at 30 °C for 8 h and then at 65 °C for 20 min. Reaction products were diluted to 100 μl with 2 × SSC and dot-blotted onto a 2 × SSC-soaked nylon membrane. DNA was ultraviolet cross-linked onto the membrane and hybridized with a 32P-end-labelled (CCCTAA) oligonucleotide probe to detect C-circle amplification products. All blots were washed, exposed to PhosphoImager screens, scanned, and quantified using a Typhoon 9400 PhosphoImager (Amersham, GE Healthcare). Genomic DNA from ALT-positive (U2OS) cells served as positive control and reference for the quantification of C-circles detected in other cell lines. ALT-associated promyelocytic leukaemia (PML) bodies were visualized by a combination of immunofluorescence with an anti-PML antibody and FISH using Alexa-488-(TTAGGG)n PNA probes as described previously21. Tumours were sliced into 4 μm sections, paraffin fixed, embedded in formalin, and mounted onto positively charged glass microscope slides. Mounted sections were incubated for 30 min at 55 °C, washed three times for 5 min in xylene, rinsed in successive 100%, 95%, and 70% ethanol baths, and washed in double-distilled H O and 1% Tween before being placed in antigen unmasking solution in a boiling kitchen steam for 30 min. Next, slides were rinsed in double-distilled H O and dehydrated in successive ethanol washes of 70%, 95%, and 100%. Slides were incubated at 72 °C for 10 min with an Alexa-488 telomeric-C PNA probe and hybridized overnight in a dark humidity chamber. Slides were washed with PNA wash buffer and PBST and incubated for 10 min in DAPI solution. After washing in double-distilled H O, slides were mounted with prolong anti-fade mounting medium. Images were taken on a Nikon 90i fluorescent light microscope at ×63 resolution. Full z-stacks were taken at 0.5 μm and projected and focused using Elements software. SPSS (package release 20.0.0, IBM Armonk), R (version 3.1.2), and GraphPad Prism (version 6.05 GraphPad Software) were applied for statistical analyses and data presentation. Overall survival was calculated as the time from diagnosis to death from disease or the last follow-up if the patient survived. Event-free survival was calculated from diagnosis to the time of tumour progression, relapse, or death from disease, or to the last follow-up if no event occurred. Survival curves were estimated according to Kaplan–Meier and compared with the log-rank test (R survival package version 2.15.0). Associations of genomic alterations with clinical risk factors were examined using Fisher’s exact test. Multivariable Cox regression models were used to analyse the simultaneous prognostic impact of TERT rearrangements and established clinical markers (stage (1–3, 4S versus 4), MYCN (non-amplified versus amplified), and age (<18 months versus >18 months)) on overall survival and event-free survival. Since TERT rearrangements were observed only in patients aged >18 months in this study, multivariable model building was restricted to this cohort (n = 125) and the variables TERT status, stage, and MYCN status. First, the proportional hazard assumption was assessed for each predictor one-at-a-time using the goodness-of-fit test of ref. 30 showing no deviation from the proportional hazard assumption. The proportional hazard assumption was considered valid whenever the P value of the goodness-of-fit test was >0.05. In addition, predicted survival curves under the Cox model were compared with the Kaplan–Meier estimates for each predictor supporting adequateness of model fit. Multivariable models were then built using a backwards selection procedure including the variables TERT status, stage, and MYCN status (inclusion criterion, P value of the score test ≤0.05; exclusion criterion, P value of the likelihood ratio test >0.1). The variables identified at this step formed the model of main effects. Finally, the factors selected in the model of main effects were fitted with all pairwise interactions in a second block by a stepwise forward selection (inclusion criterion, P value of the score test ≤ 0.05; exclusion criterion, P value of the likelihood ratio test >0.1), resulting in the final model. For the final model, the proportional hazard assumption was assessed using the goodness-of-fit test of ref. 30 as well as by fitting extended Cox models including the prognostic factors from the final model in a first block and the product terms of the prognostic factors with some function of time g(t) in a second block with stepwise forward selection in the second block (inclusion criterion, P value of the score test ≤0.05; exclusion criterion, P value of the likelihood ratio test >0.1). Choices for g(t) were g(t) = t and g(t) = log(t) with t denoting survival time. The proportional hazard assumption was considered as valid if no time-dependent factor was selected in any of the extended Cox models and if, additionally, any P value of goodness-of-fit test was >0.05. Analyses of TERT expression levels and methylation between subgroups were investigated by Mann–Whitney tests and corrected for multiple hypotheses testing using a Bonferroni correction. To test for mutual exclusivity between TERT rearrangements (TERT), MYCN amplifications (MNA), and ATRX mutations (ATRX) in the high-risk group, Fisher’s exact tests were performed between every alteration and the combination of the remaining two alterations (TERT versus MNA and ATRX; MNA versus TERT and ATRX; ATRX versus TERT and MNA). The largest P value was finally reported.


Creutzig T.,TU Darmstadt | Hikida Y.,Keio University | Ronne P.B.,University of Cologne
Journal of High Energy Physics | Year: 2013

In a previous work we have proposed that the Prokushkin-Vasiliev higher spin N = 2 supergravity on AdS3 is dual to a large N limit of the N = (2,2) ℂPN Kazama- Suzuki model. There is now strong evidence supporting this proposal based on symmetry and spectrum comparison. In this paper we will give further evidence for the duality by studying correlation functions. We compute boundary three point functions with two fermionic operators and one higher spin bosonic current in terms of the bulk supergravity theory. Then we compare with the results in the dual CFT, where the supersymmetry of the theory turns out to be very helpful. In particular we use it to confirm results conjectured in the bosonic case. Moreover, correlators with a fermionic current can be obtained via supersymmetry. © 2013 SISSA, Trieste, Italy.


Roth G.,University of Bremen | Walkowiak W.,University of Cologne
Cold Spring Harbor Perspectives in Biology | Year: 2015

In amphibians, nerve cell size is highly correlated with genome size, and increases in genome and cell size cause a retardation of the rate of development of nervous (as well as nonnervous) tissue leading to secondary simplification. This yields an inverse relationship between genome and cell size on the one hand and morphological complexity of the tectum mesencephali as the main visual center, the size of the torus semicircularis as the main auditory center, the size of the amphibian papilla as an important peripheral auditory structure, and the size of the cerebellum as a major sensorimotor center. Nervous structures developing later (e.g., torus and cerebellum) are more affected by secondary simplification than those that develop earlier (e.g., the tectum). This effect is more prominent in salamanders and caecilians than in frogs owing to larger genome and cells sizes in the former two taxa. We hypothesize that because of intragenomic evolutionary processes, important differences in brain morphology can arise independently of specific environmental selection. © 2015 Cold Spring Harbor Laboratory Press. All rights reserved.


Cornely O.A.,University of Cologne | Bohme A.,Onkologikum Frankfurt am Museumsufer | Schmitt-Hoffmann A.,Basilea Pharmaceutica International Ltd. | Ullmann A.J.,Johannes Gutenberg University Mainz | Ullmann A.J.,University of Würzburg
Antimicrobial Agents and Chemotherapy | Year: 2015

Isavuconazole is a novel broad-spectrum triazole antifungal agent. This open-label dose escalation study assessed the safety and pharmacokinetics of intravenous isavuconazole prophylaxis in patients with acute myeloid leukemia who had undergone chemotherapy and had preexisting/expected neutropenia. Twenty-four patients were enrolled, and 20 patients completed the study. The patients in the low-dose cohort (n = 11) received isavuconazole loading doses on day 1 (400/200/200 mg, 6 h apart) and day 2 (200/200 mg, 12 h apart), followed by once-daily maintenance dosing (200 mg) on days 3 to 28. The loading and maintenance doses were doubled in the high-dose cohort (n = 12). The mean±standard deviation plasma isavuconazole areas under the concentration-time curves for the dosing period on day 7 were 60.1±22.3 μg · h/ml and 113.1±19.6 μg · h/ml for the patients in the low-dose and high-dose cohorts, respectively. The adverse events in five patients in the low-dose cohort and in eight patients in the high-dose cohort were considered to be drug related. Most were mild to moderate in severity, and the most common adverse events were headache and rash (n = 3 each). One patient in the high-dose cohort experienced a serious adverse event (unrelated to isavuconazole treatment), and two patients each in the low-dose and high-dose cohorts discontinued the study due to adverse events. Of the 20 patients who completed the study, 18 were classified as a treatment success. In summary, the results of this analysis support the safety and tolerability of isavuconazole administered at 200 mg and 400 mg once-daily as prophylaxis in immunosuppressed patients at high risk of fungal infections. Copyright © 2015, American Society for Microbiology.


Creutzig T.,TU Darmstadt | Hikida Y.,Keio University | Ronne P.B.,University of Cologne
Journal of High Energy Physics | Year: 2013

We propose a duality between a higher spin N=1 supergravity on AdS 3 and a large N limit of a family of N=(1,1) superconformal field theories. The gravity theory is an N=1 truncation of the N=2 supergravity found by Prokushkin and Vasiliev, and the dual conformal field theory is defined by a supersymmetric coset model. We check this conjecture by comparing one loop partition functions and find agreement. Moreover, we study the symmetry of the dual coset model and in particular compute fields of the coset algebra of dimension 3/2, 2, 2 and 5/2 explicitly. © 2013 SISSA, Trieste, Italy.


Chraibi M.,Jülich Research Center | Seyfried A.,Jülich Research Center | Schadschneider A.,University of Cologne
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2010

A spatially continuous force-based model for simulating pedestrian dynamics is introduced which includes an elliptical volume exclusion of pedestrians. We discuss the phenomena of oscillations and overlapping which occur for certain choices of the forces. The main intention of this work is the quantitative description of pedestrian movement in several geometries. Measurements of the fundamental diagram in narrow and wide corridors are performed. The results of the proposed model show good agreement with empirical data obtained in controlled experiments. © 2010 The American Physical Society.


Berkessel A.,University of Cologne | Elfert S.,University of Cologne | Etzenbach-Effers K.,University of Cologne | Teles J.H.,BASF
Angewandte Chemie - International Edition | Year: 2010

Surprises from a classic: The Breslow intermediate of triazolylidene- catalyzed benzoin condensations was characterized for the first time by NMR spectroscopy in its keto form (K, energetic minimum). The hitherto unknown spiro-dioxolane S, generated from the carbene catalyst and two equivalents of aldehyde, is the resting state of the catalytic system. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Berkessel A.,University of Cologne | Elfert S.,University of Cologne | Yatham V.R.,University of Cologne | Neudorfl J.-M.,University of Cologne | And 2 more authors.
Angewandte Chemie - International Edition | Year: 2012

54 years later: Saturated imidazolidin-2-ylidenes react with aldehydes to smoothly produce the elusive 2,2-diamino enols A ("Breslow intermediates", first postulated in 1958) of carbene-catalyzed umpolung reactions. The 2,2-diamino enols A react with additional aldehyde in a cross-benzoin reaction. The methylated Breslow intermediates B are accessible by deprotonation of methoxymethyl azolium salts. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Behrens M.,German Institute of Human Nutrition | Korsching S.I.,University of Cologne | Meyerhof W.,German Institute of Human Nutrition
Molecular biology and evolution | Year: 2014

Bitter taste perception in vertebrates relies on a variable number of bitter taste receptor (Tas2r) genes, ranging from only three functional genes in chicken to as many as approximately 50 in frogs. Humans possess a medium-sized Tas2r repertoire encoding three broadly and several narrowly tuned receptors plus receptors with intermediate tuning properties. Such tuning information is not available for bitter taste receptors of other vertebrate species. In particular it is not known, whether a small Tas2r repertoire may be compensated for by broad tuning of these receptors, and on the other side, whether a large repertoire might entail a preponderance of narrowly tuned receptors. To elucidate this question, we cloned all three chicken Tas2rs, the two turkey Tas2rs, three zebra finch Tas2rs, and six Tas2rs of the Western clawed frog representative of major branches of the phylogenetic tree, and screened them with 46 different bitter compounds. All chicken and turkey Tas2rs were broadly tuned, the zebra finch Tas2rs were narrowly tuned, and frog Tas2rs ranged from broadly to narrowly tuned receptors. We conclude that a low number of functional Tas2r genes does not imply a reduced importance of bitter taste per se, as it can be compensated by large tuning width. A high number of functional Tas2r genes appears to allow the evolution of specialized receptors, possibly for toxins with species-specific relevance. In sum, we show that variability in tuning breadth, overlapping agonist profiles, and staggered effective agonist concentration ranges are shared features of human and other vertebrate Tas2rs. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.


Popovych O.V.,Jülich Research Center | Tass P.A.,Jülich Research Center | Tass P.A.,University of Cologne
Frontiers in Human Neuroscience | Year: 2012

Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders. © 2012 Popovych and Tass.


Cheng L.E.,University of California at San Francisco | Hartmann K.,University of Cologne | Roers A.,Carl Gustav Carus Institute | Krummel M.F.,University of California at San Francisco | Locksley R.M.,Howard Hughes Medical Institute
Immunity | Year: 2013

Mast cells are tissue-resident immune cells that play a central role in allergic disease. These contributions are largely dependent on the acquisition of antigen-specific immunoglobulin E (IgE). Despite this requirement, studies of mast cell and IgE interactions have overlooked the mechanism by which mast cells acquire IgE from the blood. To address this gap, we developed reporter IgE molecules and employed imaging techniques to study mast cell function in situ. Our data demonstrate that skin mast cells exhibit selective uptake of IgE based on perivascular positioning. Furthermore, perivascular mast cells acquire IgE by extending cell processes across the vessel wall to capture luminal IgE. These data demonstrate how tissue mast cells acquire IgE and reveal a strategy by which extravascular cells monitor blood contents to capture molecules central to cellular function. © 2013 Elsevier Inc.


Schumacher S.,University of Cologne | Forster D.F.,University of Cologne | Rosner M.,University of Bremen | Wehling T.O.,University of Bremen | Michely T.,University of Cologne
Physical Review Letters | Year: 2013

Intercalation of Eu under graphene on Ir(111) results in patterns oriented along the graphene moiré and quantized in size by its unit mesh. The patterns are formed by stripes, compact islands, and channels. Over a wide range of intercalated amounts the step concentration of the pattern has a rather constant saturation value. These findings are explained by the chemically modulated binding of graphene to the substrate and the preexisting strain in graphene due to its cooldown from the growth temperature. Local variations in the intercalation step density appear to reflect local variations in the preexisting strain. © 2013 American Physical Society.


Tefferi A.,Mayo Medical School | Thiele J.,University of Cologne | Vannucchi A.M.,University of Florence | Barbui T.,Papa Giovanni XXIII Hospital
Leukemia | Year: 2014

Disease-specific mutations facilitate diagnostic precision and drug target discovery. In myeloproliferative neoplasms (MPN), this is best exemplified by the chronic myeloid leukemia-associated BCR-ABL1. No other mutation in MPN has thus far shown a similar degree of diagnostic accuracy or therapeutic relevance. However, JAK2 and KIT mutations are detected in more than 90% of patients with polycythemia vera and systemic mastocytosis, respectively, and are therefore used as highly sensitive clonal markers in these diseases. JAK2 and MPL mutations also occur in essential thrombocythemia (ET) and primary myelofibrosis (PMF), but their diagnostic value is limited by suboptimal sensitivity and specificity. The molecular diagnostic gap in JAK2/MPL-unmutated ET/PMF is now partially addressed by the recent discovery of calreticulin (CALR) mutations in the majority of such cases. However, bone marrow morphology remains the central diagnostic platform and is essential for distinguishing ET from prefibrotic PMF and diagnosing patients those do not express JAK2, MPL or CALR (triple-negative). The year 2013 was also marked by the description of CSF3R mutations in the majority of patients with chronic neutrophilic leukemia (CNL). Herein, we argue for the inclusion of CALR and CSF3R mutations in the World Health Organization classification system for ET/PMF and CNL, respectively. © 2014 Macmillan Publishers Limited.


Petermann F.,University of Bremen | Lehmkuhl G.,University of Cologne
Kindheit und Entwicklung | Year: 2010

Previous studies have shown that a high number of young people have experienced violent behavior - as a victim as well as an offender. High monetary and psychosocial costs demand effective programs for the prevention of aggressive behavior, and interventions addressing individual circumstances. Various approaches to prevent the development of aggressive behavior and intervention programs care presented, which are directed at children as well as at parents and teachers. The main focus will be on early recognition and prevention as it is of high importance to prevent its development as early as possible. © Hogrefe Verlag, Göttingen 2010.


Grefkes C.,University of Cologne | Grefkes C.,Max Planck Institute for Neurological Research | Grefkes C.,Jülich Research Center | Fink G.R.,University of Cologne | Fink G.R.,Jülich Research Center
The Lancet Neurology | Year: 2014

After focal damage, cerebral networks reorganise their structural and functional anatomy to compensate for both the lesion itself and remote effects. Novel developments in the analysis of functional neuroimaging data enable us to assess in vivo the specific contributions of individual brain areas to recovery of function and the effect of treatment on cortical reorganisation. Connectivity analyses can be used to investigate the effect of stroke on cerebral networks, and help us to understand why some patients make a better recovery than others. This systems-level view also provides insights into how neuromodulatory interventions might target pathological network configurations associated with incomplete recovery. In the future, such analyses of connectivity could help to optimise treatment regimens based on the individual network pathology underlying a particular neurological deficit, thereby opening the way for stratification of patients based on the possible response to an intervention. © 2014 Elsevier Ltd.


Choi Y.,Centers for Disease Control and Prevention | Dienes H.-P.,University of Cologne | Krawczynski K.,Centers for Disease Control and Prevention
PLoS ONE | Year: 2013

The relationships among micro RNA-122 (miR-122) expression in the liver, hepatitis C virus (HCV) replication and hepatic damage were analyzed in three chimpanzees observed for 180 days after inoculation with HCV genotype 1a. Levels of miR-122 in the liver and serum were measured by real-time RT PCR in serial liver biopsies and serum samples. Hepatic miR-122 levels were normalized separately for each of three chimpanzees with small RNAs and microRNAs that are endogenous to the liver and are stably expressed. Two- to 4-fold rise in hepatic miR-122 levels was observed at the onset of HCV infection (the first 4 weeks) when HCV titers in the liver and serum increased rapidly in all three chimpanzees in concordance with in vitro data indicating the miR-122 significance for HCV replication. Between 10 to 14 weeks after inoculation, when hepatic and serum HCV RNA titers exceeded 3 logs and alanine aminotransferase (ALT) activity was elevated, hepatic miR-122 levels were in decline. Cumulative data derived from all three chimpanzees from 180 days of observation documented an inverse (negative) correlation between hepatic miR-122 and HCV RNA in the liver and serum and positive correlation between level of serum miR-122 and HCV replication. Subsequent rise of miR-122 level during HCV clearance and ALT normalization suggested a tri-phasic occurrence of the relationship among hepatic miR-122 expression, HCV replication and hepatic destruction, which was the most apparent in one chimpanzee but less evident in two other animals. In vivo kinetics of hepatic and serum miR-122, HCV replication and hepatic destruction reflects complexities of the virus-host interaction during the acute phase of HCV infection.


Altland A.,University of Cologne | Beri B.,University of Birmingham | Egger R.,Heinrich Heine University Düsseldorf | Tsvelik A.M.,Brookhaven National Laboratory
Physical Review Letters | Year: 2014

We study the multichannel Kondo impurity dynamics realized in a mesoscopic superconducting island connected to metallic leads. The effective "impurity spin" is nonlocally realized by Majorana bound states and strongly coupled to lead electrons by non-Fermi liquid correlations. We explore the spin dynamics and its observable ramifications near the low-temperature fixed point. The topological protection of the system raises the perspective to observe multichannel Kondo impurity dynamics in experimentally realistic environments. © 2014 American Physical Society.


Adamchic I.,Jülich Research Center | Toth T.,Jülich Research Center | Hauptmann C.,Jülich Research Center | Tass P.A.,Jülich Research Center | Tass P.A.,University of Cologne
Human Brain Mapping | Year: 2014

Acoustic Coordinated Reset (CR) neuromodulation is a patterned stimulation with tones adjusted to the patient's dominant tinnitus frequency, which aims at desynchronizing pathological neuronal synchronization. In a recent proof-of-concept study, CR therapy, delivered 4-6 h/day more than 12 weeks, induced a significant clinical improvement along with a significant long-lasting decrease of pathological oscillatory power in the low frequency as well as γ band and an increase of the α power in a network of tinnitus-related brain areas. As yet, it remains unclear whether CR shifts the brain activity toward physiological levels or whether it induces clinically beneficial, but nonetheless abnormal electroencephalographic (EEG) patterns, for example excessively decreased δ and/or γ. Here, we compared the patients' spontaneous EEG data at baseline as well as after 12 weeks of CR therapy with the spontaneous EEG of healthy controls by means of Brain Electrical Source Analysis source montage and standardized low-resolution brain electromagnetic tomography techniques. The relationship between changes in EEG power and clinical scores was investigated using a partial least squares approach. In this way, we show that acoustic CR neuromodulation leads to a normalization of the oscillatory power in the tinnitus-related network of brain areas, most prominently in temporal regions. A positive association was found between the changes in tinnitus severity and the normalization of δ and γ power in the temporal, parietal, and cingulate cortical regions. Our findings demonstrate a widespread CR-induced normalization of EEG power, significantly associated with a reduction of tinnitus severity. © 2013 Wiley Periodicals, Inc.


Rahi S.J.,Massachusetts Institute of Technology | Kardar M.,Massachusetts Institute of Technology | Emig T.,University of Cologne | Emig T.,University Paris - Sud
Physical Review Letters | Year: 2010

We examine whether fluctuation-induced forces can lead to stable levitation. First, we analyze a collection of classical objects at finite temperature that contain fixed and mobile charges and show that any arrangement in space is unstable to small perturbations in position. This extends Earnshaw's theorem for electrostatics by including thermal fluctuations of internal charges. Quantum fluctuations of the electromagnetic field are responsible for Casimir or van der Waals interactions. Neglecting permeabilities, we find that any equilibrium position of items subject to such forces is also unstable if the permittivities of all objects are higher or lower than that of the enveloping medium, the former being the generic case for ordinary materials in vacuum. © 2010 The American Physical Society.


Brizuela D.,University of the Basque Country | Brizuela D.,University of Cologne
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

The classical and quantum evolution of a generic probability distribution is analyzed. To that end, a formalism based on the decomposition of the distribution in terms of its statistical moments is used, which makes explicit the differences between the classical and quantum dynamics. In particular, there are two different sources of quantum effects. Distributional effects, which are also present in the classical evolution of an extended distribution, are due to the fact that all moments cannot be vanishing because of the Heisenberg uncertainty principle. In addition, the noncommutativity of the basic quantum operators add some terms to the quantum equations of motion that explicitly depend on the Planck constant and are not present in the classical setting. These are thus purely quantum effects. Some particular Hamiltonians are analyzed that have very special properties regarding the evolution they generate in the classical and quantum sector. In addition, a large class of inequalities obeyed by high-order statistical moments, and in particular uncertainty relations that bound the information that is possible to obtain from a quantum system, are derived. © 2014 American Physical Society.


Popovych O.V.,Jülich Research Center | Yanchuk S.,Humboldt University of Berlin | Tass P.A.,Jülich Research Center | Tass P.A.,University of Cologne
Physical Review Letters | Year: 2011

For a feedforward loop of oscillatory Hodgkin-Huxley neurons interacting via excitatory chemical synapses, we show that a great variety of spatiotemporal periodic firing patterns can be encoded by properly chosen communication delays and synaptic weights, which contributes to the concept of temporal coding by spikes. These patterns can be obtained by a modulation of the multiple coexisting stable in-phase synchronized states or traveling waves propagating along or against the direction of coupling. We derive explicit conditions for the network parameters allowing us to achieve a desired pattern. Interestingly, whereas the delays directly affect the time differences between spikes of interacting neurons, the synaptic weights control the phase differences. Our results show that already such a simple neural circuit may unfold an impressive spike coding capability. © 2011 American Physical Society.


Welterlich I.,University of Cologne | Charov O.,University of Cologne | Charov O.,University of Bremen | Tieke B.,University of Cologne
Macromolecules | Year: 2012

Synthesis and characteristic properties of polymers P1-P4 containing 1,3,4,6-tetraarylated pyrrolo[3,2-b]pyrrole-2,5-dione (isoDPP) units in the main chain are described. P1 and P2 were prepared upon palladium-catalyzed polycondensation of 3,6-bis(4-bromophenyl)-1,4-bis(4-tert-butylphenyl)pyrrolo[3, 2-b]pyrrole-2,5-dione (M1) or 1,4-bis(4-bromophenyl)-3,6-bis(4-tert-butylphenyl) pyrrolo[3,2-b]pyrrole-2,5-dione (M2) and 2,2′-(9,9-dihexyl-9H-fluoren-2,7- diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (M4), while P3 and P4 were synthesized upon polycondensation of 3,6-bis(5-bromothien-2-yl)-1,4-bis(4- dodecylphenyl)pyrrolo[3,2-b]pyrrole-2,5-dione (M3) and 2,5-bis(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene (M5) or 9-(2-ethylhexyl)-2,7- bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)carbazole (M6). Deeply colored polymers with molecular weights between 3.5 and 22 kDa were obtained. The polymers were soluble in common organic solvents such as dichloromethane, chloroform, and tetrahydrofuran. All polymers exhibit broad absorption bands with high extinction coefficients (ε > 2 × 10 4 L mol -1 cm -1) but weak fluorescence, the quantum yields being below 1%. Although P1 and P2 are isomers, their optical properties are rather different. P1 with polyconjugated backbone exhibits an absorption maximum at 409 nm, while P2 has a maximum at 360 nm due to interruption of χ-conjugation at the lactam N atoms. The presence of thienyl-isoDPP units in the backbone causes a red-shift of the absorption to 489 nm (P3) and 435 nm (P4). All polymers exhibit nearly irreversible oxidation and reduction behavior. Bandgaps of the polymers with phenyl-substituted isoDPP units (P1 and P2) are at about 2 eV, while those of polymers with thienyl-substituted isoDPP (P3 and P4) are at about 1.5 eV. © 2012 American Chemical Society.


Doerfler W.,Erlangen University Medical School | Doerfler W.,University of Cologne
Reviews in Medical Virology | Year: 2011

The insertion of foreign DNA into mammalian or plant genomes is a frequent event in biology. My laboratory has pursued a long-standing interest in the structure of integrated adenovirus genomes and in the mechanism of foreign DNA insertions in mammalian cells. The long-term consequences of the integration of alien DNA are only partly known, and even less well understood are the mechanisms that bring them about. Evidence from viral systems has contributed to the realization that foreign DNA insertions entail a complex of sequelae that have also become apparent in non-viral systems: (i) The de novo methylation of integrated foreign DNA sequences has frequently been observed. (ii) Alterations of DNA methylation patterns in the recipient genome at and remote from the site of foreign DNA insertion have been demonstrated but it remains to be investigated how generally this phenomenon occurs. Many viral genomes find and have found entry into the genomes of present-day organisms. A major portion of mammalian genomes represents incomplete retroviral genomes that frequently have become permanently silenced by DNA methylation. It is still unknown how and to what extent the insertion of retroviral or retrotransposon sequences into established genomes has altered and shaped the methylation and transcription profiles of present day genomes. An additional reason for concern about the effects of foreign DNA integration is the fact that in all fields of molecular biology and medicine, the generation of transgenic or transgenomic cells and organisms has become a ubiquitously applied experimental technique. © 2011 John Wiley & Sons, Ltd.


Dewald A.,University of Cologne | Moller O.,TU Darmstadt | Petkov P.,Bulgarian Academy of Science
Progress in Particle and Nuclear Physics | Year: 2012

In this article, the Recoil Distance Doppler-Shift (RDDS) method which is extensively used in nuclear structure physics to determine level lifetimes and absolute transition probabilities is reviewed. Especially, it is aimed to present new developments and variants of the technique which have evolved mainly in the past 25 years. After a short and comprehensive description of the basic elements of the plunger technique, the new variants are presented. This comprises the RDDS technique using γγ-coincidences, RDDS measurements in combination with particle detectors for selecting specific reaction channels, RDDS after Coulomb excitation, RDDS after fission and RDDS using a gas target. In addition, the concept of a differential plunger is discussed with respect to its specific features and typical experimental setups. Examples of differential plunger measurements with recoil tagging, recoil decay tagging and after deep inelastic reactions, Coulomb excitation in inverse reaction kinematics as well as after reactions with fast radioactive beams at energies of 50-100 MeV/u are given. The second focus of the review is dedicated to today's plunger devices and related hardware. The concepts of specific plunger devices which accommodate the specific demands of the aforementioned RDDS applications including specific feedback systems for controlling target-stopper/degrader separations in-beam are presented. Also discussed are target and stopper/degrader foil related issues like foil preparation, mounting and stretching as well as specific features of the foil behavior in-beam (temperature, blistering, wrinkling and carbon build-up). The third focus is devoted to the data analysis. The concept of the Differential Decay Curve Method (DDCM) is presented as an alternative approach for the analysis of RDDS data measured as singles or as γγ-coincidences. For the latter, different gating possibilities are discussed, e.g. gating from above and gating from below the level of interest and gating on fractional components. Finally, the simulation of line-shapes and its application is presented. © 2011 Elsevier B.V. All rights reserved.


Creutzig T.,TU Darmstadt | Hikida Y.,Keio University | Ronne P.B.,University of Cologne
Journal of High Energy Physics | Year: 2012

Vasiliev's higher spin supergravity theory on three dimensional anti-de Sitter space is studied and, in particular, the partition function is computed at one loop level. The dual conformal field theory is proposed to be a large N limit of the N = (2, 2) ℂP N Kazama-Suzuki model in two dimensions. The proposal is based on symmetry considerations and comparison of the bulk partition function with the conformal field theory. Our findings suggest that the theory is strong-weak self-dual. © SISSA 2012.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH-2007-2.4.5-7 | Award Amount: 1.39M | Year: 2008

Hearing loss is one of the most common chronic health conditions in the elderly population with important implications for patient quality of life. The diminished ability to hear and to communicate is frustrating in and of itself, but the strong association of hearing loss with depression and functional decline adds further to the burden on individuals who are hearing impaired. Hearing loss can limit communications skills: not to hear means not to understand what is being said. Hence deafness does not produce compassion but do often produce a sense of irritation. Despite the prevalence and burden of hearing loss, hearing impairment is largely underdiagnosed in older persons and undertreated. The reason for this is that one of the most conspicuous signs of a hearing loss is that it cannot be seen! Actually, this is the reason why deafness does not receive the necessary attention. Too often, the public and still too many health care professionals underestimate the dramatic effects of deafness. Novel strategies should be explored to make screening and early intervention a feasible part of routine care. Project AHEAD III has been specifically designed to: - Provide evidence of the effects of hearing impairment in adults and particularly in the elderly - Analyse costs associated with the implementation of integrated large scale programmes of hearing screening and intervention in the elderly - Provide quality standards and minimum requirements for screening methods and related diagnostic techniques - Develop guidelines and recommendations on how to implement successful screening programmes to be tuned to the local, social, and economical conditions of a country.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-1-B | Award Amount: 16.85M | Year: 2012

Neurodegenerative (ND) and neuromuscular (NM) disease is one of the most frequent classes of rare diseases, affecting life and mobility of 500,000 patients in Europe and millions of their caregivers, family members and employers. This NEUROMICS project brings together the leading research groups in Europe, five highly innovative SMEs and relevant oversea experts using the most sophisticated Omics technologies to revolutionize diagnostics and to develop pathomechanism-based treatment for ten major ND and NM diseases. Specifically we aim to: (i) use next generation WES to increase the number of known gene loci for the most heterogeneous disease groups from about 50% to 80%, (ii) increase patient cohorts by large scale genotyping by enriched gene variant panels and NGS of so far unclassified patients and subsequent phenotyping, (iii) develop biomarkers for clinical application with a strong emphasis on presymptomatic utility and cohort stratification, (iv) combine -omics approaches to better understand pathophysiology and identify therapeutic targets, (v) identify disease modifiers in disease subgroups cohorts with extreme age of onset (vi) develop targeted therapies (to groups or personalized) using antisense oligos and histone deacetylase inhibitors, translating the consortiums expertise in clinical development from ongoing trials toward other disease groups, notably the PolyQ diseases and other NMD. To warrant that advances affect a large fraction of patients we limited the selection to a number of major categories, some of which are in a promising stage of etiological and therapeutic research while some others are in great need of further classification. The efforts will be connected through a NEUROMICS platform for impact, communication and innovation that will provide tools and procedures for ensuring trial-readiness, WP performance, sustainability, interaction with the chosen Support IRDiRC and RD-Connect project and involvement of stakeholders in the NDD/NMD field.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.1.1-1 | Award Amount: 15.78M | Year: 2013

The aim of SYBIL is to carry out extensive functional validation of the genetic determinants of rare and common skeletal diseases and the age related factors contributing to these painful conditions. To achieve this goal SYBIL will gather complementary translational and transnational scientists, systems biologists, disease modellers, leading SMEs and industrialists that will perform in-depth characterisation (complete molecular phenotyping) of pre-clinical models (cellular and animal) for a variety of common and rare skeletal diseases. SYBIL will establish a systematic pipeline of in vitro, ex vivo and in vivo models of increasing complexity and will also make use of novel technologies such as iPS cells and exclusive Virtual Patient software to identify potential therapeutic targets for further validation through simultaneous modelling of fundamental and complex physiological pathways. SYBIL will rely on i) an Omics Knowledge Factory for systematically generating new knowledge on skeletal disease pathophysiology and to generate the relevant Omics profiles necessary to detect and validate new disease determinants, biomarkers and therapeutic targets for future clinical developments, and ii) a Systems Biology Hub to integrate the high-throughput and data-dense information, to gain a global understanding of pathophysiological commonalities between different skeletal diseases and recognize predominant shared pathways and mechanisms that may represent new targeted routes to treatment. SYBIL will also identify potential modifier genes and study the epigenome that will ultimately influence the timing and efficacy of new personalised treatments. Overall SYBIL achievements will tremendously boost the efficient pre-clinical assessment and development of therapeutics against skeletal diseases and thus indirectly reduce their social and healthcare burden.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.97M | Year: 2013

The strong temporal dynamics of the East African landscape and natural-resource distributions have always encouraged people to innovate and adapt to changing conditions. However, increasing population growth, changes in patterns of land tenure, industrialization, weak systems of governance, and global climate change have exacerbated previously localized environmental problems such as soil erosion, depletion of water catchments, loss of forests and grazing land, falling soil fertility and biodiversity. Novel approaches for resolving these challenges are thus urgently needed. Based on the premise that the past is key to understanding the present and planning for the future, this ITN will establish a leading European training network devoted to combining state-of-the-art research methods to tap into under-appreciated knowledge of how indigenous peoples have previously adapted to East Africas intrinsically unstable climate and land/water resources. By bringing together ecologists, archaeologists, anthropologists, geographers, historians and agronomists the ITN will provide cross-disciplinary training to a new generation of researchers, enabling them to interpret data relating to past and present socio-cultural and ecological dynamics from across the environmental and social sciences and the humanities. Organized by researchers from seven European universities in partnership with Bayer East Africa and U&We, the ITN will co-operate closely with academic counterparts, private-sector stakeholders, NGOs and local communities in East Africa. It will highlight how detailed awareness of the complex history of human-environment interaction in East Africa is central to well-founded and ecologically sustainable resource management, thereby restore the important function of indigenous know-how crucial for devising development policies and climate-risk management for specific areas, and train a new generation of future ecosystem-service managers, policy makers and entrepreneurs.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.1.1-1 | Award Amount: 15.31M | Year: 2010

In recent years, the zebrafish has emerged as a new vertebrate model organism for biomedical research which offers a unique combination of traits: a short generation time, small size and efficient breeding procedures make it the best choice among vertebrates for forward genetic screening and small-molecule screens, including toxicology, while the transparent embryo and larva offers unique opportunities for imaging of cell movement and gene expression in a developing organism. Building on recent advances in the zebrafish field, we will conduct high-throughput phenotyping of at least a thousand regulatory genes relevant for common human diseases, by behavioural assays (for viable mutants), 3D / 4D imaging and expression profiling (including high-throughput sequencing). We will include mutants generated by TILLING and by the new zinc finger nuclease method, as well as mutants from earlier forward-genetics screens. A phenotyping effort of this scale has never been undertaken before in any vertebrate organism. Complementing the study of mutants relevant for neurological disorders, we will produce an atlas of gene expression in the brain, the most comprehensive one in a vertebrate. We will further perform a genome-wide characterisation of regulatory elements of potential disease genes by a combination of bioinformatics and transgenics. Small-molecule screening for mutant rescue or disease-relevant processes will identify candidate drugs and provide insights into gene function. Our increasing knowledge on the regulators and their interactions with regulatory targets will be integrated with knowledge at cellular and organismic level. By capitalising on the virtues of the zebrafish system, this systems biology approach to the regulome will gain unique knowledge complementing ongoing work in mammalian systems, and provide important new stimuli for biomedical research.


Grant
Agency: Cordis | 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.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2011-1.1.21. | Award Amount: 11.58M | Year: 2012

RadioNet is an I3 that coordinates all of Europes leading radio astronomy facilities in an integrated cooperation to achieve transformational improvement in the quality and quantity of the scientific research of European astronomers. RadioNet3 includes 27 partners operating world-class radio telescopes and/or performing cutting-edge R&D in a wide range of technology fields important for radio astronomy. RadioNet3 proposes a work plan that is structured into 6 NAs, 7 TNAs and 4 JRAs with the aim to integrate and optimise the use and development of European radio astronomy infrastructures. The general goals of RadioNet3 are to: - facilitate, for a growing community of European researchers, access to the complete range of Europes world-leading radio-astronomical facilities, including the ALMA telescope; - secure a long-term perspective on scientific and technical developments in radio astronomy, pooling resources and expertise that exist among the partners; - stimulate new R&D activities for the existing radio infrastructures in synergy with ALMA and the SKA; - contribute to the implementation of the vision of the ASTRONET Strategic Plan for European Astronomy by building a sustainable and world leading radio astronomical research community. RadioNet3 builds on the success of two preceeding I3s under FP6 and FP7, but it also takes a leap forward as it includes facilitation of research with ALMA via a dedicated NA, and 4 pathfinders for the SKA in its TNA Program. It has a transparent and efficient management structure designed to optimally support the implementation of the project. RadioNet is now recognized by funding agencies and international project consortia as the European entity representing radio astronomy and facilitating the access to and exploitation of excellent facilities in this field. This is of paramount importance, as a dedicated, formal European radio astronomy organisation to coordinate and serve the needs of this community does not yet exist.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: NMP-2007-2.3-1 | Award Amount: 15.47M | Year: 2008

Angiogenesis underlies almost all biological processes of morphogenesis, including those in tissue repair and regeneration. Physiological angiogenesis is controlled by a complex interplay between cells and their environment: the extracellular matrix (ECM) provides signaling via numerous ECM adhesion molecules and growth factors bound to ECM polysaccharide components; and cells locally degrade and remodel the ECM to create pores into which angiogenic endothelial cells migrate. This observation, that physiological angiogenesis proceeds in response to solid-phase cues motivates our approach, namely creating bioactive resorbable materials as scaffolds that contain bound molecular signals to induce physiological angiogenesis in situations of tissue repair and regeneration. In some of our scaffold materials, porosity is inherent by virtue of fabrication, and in others porosity is created by cell-associated proteolysis as it is in physiological angiogenesis. All materials will be designed so as to be injectable or implantable into the human body. In some work, the final injectable/implantable material will comprise only materials and bioactive biomolecular signals, and in other cases it will also comprise cells. Thus, the concept of ANGIOSCAFF is to create materials that are bioresponsive (to environmental signals including pH and redox potential, and to cellular signals such as proteases), that are bioactive (by virtue of bound peptide or recombinant protein adhesion ligands and bound and releasable growth factors), and that are capable of carrying cellular therapeutics. To realize ANGIOSCAFF, we have assembled a team comprising both industrial and academic expert groups in biomaterials design and development, experts in the science and application of angiogenesis, in imaging in animal models, and in applications demanding biomaterials-based, angiogenesis-demanding tissue engineering therapies, including repair of bone, skin, cardiac muscle, skeletal muscle and nerve.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 4.66M | Year: 2008

The remarkable physical properties of transition metal oxides result from the strong interactions between orbitals, charges, spins and lattice. The discovery and the understanding of these properties superconductivity, thermoelectricity, magnetoresistance is based on a close relationship between solid-state chemists, able to design new crystallographic structures in which the ligand field stabilizes different types of cations, and solid-state physicists and specialists of spectroscopic techniques, such as absorption at the transition-metals and oxygen edges or local probes, who are able to extract the characteristic electronic and magnetic features of these cations. In the scope of this network, the search for new compounds will be made by standard solid state chemistry in Caen (CRISMAT) and Bordeaux (ICMB) laboratories, also in charge of the structural and physical property characterizations, by high pressure techniques in Liverpool and Madrid, and by hydrothermal synthesis in Timisoara. The origin of physical properties will be studied in close relationship by different spectroscopy techniques (XANES, dichrosm: Kln University; Raman, IR conductivity, inelastic neutron scattering: MPI Stuttgart). The collaboration between new oxides discoverers and specialists of the orbital/spin physics will allow the creation of a unique training and research potential on metal-transition oxides. Furthermore, the involvement of the industrial partner (NXP) will provide strong benefit to all members of the network by demonstrating how to iterate fundamental science advances into technology and process development. The proposed investigation, being at the spearhead of the modern condensed matter physics and solid state chemistry, will give an excellent opportunity to teach and train young researchers in this new and challenging field.


Grant
Agency: Cordis | 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.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2008-1.1.1 | Award Amount: 14.19M | Year: 2009

RadioNet is an integrating activity that has pulled together ALL of Europes leading radio astronomy facilities to produce a focused, coherent and integrated proposals that will significantly enhance the quality and quantity of science performed by European astronomers. RadioNet FP7 has 25 partners. They range from operators of major radio telescope facilities to laboratories that specialise in micro-electronics. This proposal has brought these institutes together in a unique partnership that builds and extends on RadioNet FP6. The programme of work includes: 7 Networking activities, 4 joint research activities and 9 transnational access projects. The three main objectives are to: (i) provide European astronomers access to world-class radio astronomy facilities; (ii) embark on a research and development plan that will further enhance and improve these facilities, and (iii) nurture and support a rapidly growing community of radio astronomers and engineers, so that can fully exploit the upgraded and next generation radio facilities that will become available over the next few years.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: KBBE.2010.2.2-01 | Award Amount: 11.79M | Year: 2011

Full4Health is a multidisciplinary European collaboration of internationally renowned laboratories investigating the mechanisms of hunger, satiety and feeding behaviour, effects of dietary components and food structure on these processes, and their possible exploitation in addressing obesity, chronic disease and under-nutrition. The proposal integrates investigation of both human volunteers (dietary/exercise intervention studies and administration of encapsulated nutrients) and laboratory animals with emphasis on neuronal, hormonal, molecular, physiological and psychological responses to food at different stages of the life course. We will apply imaging and other cutting edge technologies in both humans and rodents to answer critical research questions at different levels of the food-gut-brain axis. In human volunteers, responses to diet will be investigated from childhood through to the elderly, whereas wide-ranging cutting-edge rodent studies will investigate related issues such as early developmental programming the food-gut-brain axis, multiple feedback signalling interactions, and inflammation-induced anorexia. The project will examine the interaction of food and dietary components with the gastrointestinal tract, and will characterise the role of gut endocrine secretions, the vagus nerve, and hindbrain, hypothalamic and forebrain structures in signalling and integration of hunger and satiety. Physiological and psychological responses to food may change as we develop and age, with impact on food choices and preferences. This is a critical issue in the battle against food intake-related chronic disease, most commonly driven by over-consumption, but also in consideration of relative under-nutrition in the elderly and clinically compromised.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-1 | Award Amount: 7.74M | Year: 2012

Neovascular glaucoma (NVG) is a very aggressive and rare type of glaucoma: yet, it contributes disproportionately to blindness from all eye diseases. NVG is also the second most common cause for the removal of the eye-ball across all eye diseases, usually because of intractable pain. The major cause of NVG is Ischaemic Central Retinal Vein Occlusion (CRVO) leading to neovascularisation, obstruction of aqueous humour outflow and increased intraocular pressure. Todays therapeutic approaches are insufficient: they include destruction of the retina by coagulation, or off-label anti-VEGF injection into the eye. It is proposed to develop a better treatment by assessing the topical administration of Aganirsen: it is an antisense oligonucleotide able to interrupt the production of Vascular Endothelial Growth Factor, which plays a major role in the pathogenesis of NVG. Aganirsen is developed by GENE SIGNAL, a SME with expertise in topical ophthalmic treatments for orphan diseases, and manufactured by AMATSI. Under the coordination of the Mainz University Medical Center, a Phase II/III randomised, double-masked, 3-group, placebo-controlled trial (STRONG) is therefore presented to assess Aganirsens efficacy in reducing the rate of anterior and posterior segment neovascularisation and NVG development after CRVO. Involving 333 subjects within more than 30 clinical sites, the study is operationalized via a disease specific network (EVICR.net) and a contract research organization managed by GENE SIGNAL. The study aims at assessing a new therapeutic approach for NVG for which conditional authorization will be sought at the end of the project. STRONG also delivers new insights into the natural course of the disease and its risk factors, analysing one of the largest patient cohorts ever. It also allows for a novel classification of NVG, yields novel image analysis tools, and proposes biomarkers able to differentiate between high- and low-risk patients and drug responders.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2012.4.1-4 | Award Amount: 970.62K | Year: 2012

The ECRAN (European Communication on Research Awareness Needs) project is designed to develop a portfolio of open educational resources, including a film, for the general population about the challenges raised by independent clinical research. The European Commission (FP7 Health Priority) decided to allocate substantial funding to independent (investigator-driven) clinical trials. Together with member states, the FP7 infrastructure unit supports the preparation and operation of a pan-European infrastructure for clinical trials (ECRIN). Through these instruments, Europe has the capacity to design and conduct independent, multinational clinical trials. The objective of the ECRAN project is to develop tools to communicate key messages to citizens, patients, healthcare professionals, researchers, policymakers and society about independent, multinational clinical research. These messages will focus on: i) the importance of public understanding of the need for and basic principles of clinical trials, fostering active involvement of patients in trials and of their representatives in trial design; ii) the need for independent clinical trials driven by healthcare issues, to optimise treatment strategies through comparison of benefits and harms of multiple therapeutic options, supporting evidence-based clinical practice and reduction in healthcare inequalities; iii) the need for transparency and optimal use of data, to promote the cost-effectiveness of treatments and to reduce the economic burden of diseases; iv) the need for multinational cooperation, taking advantage of Europes population size and diversity, and of its medical expertise. These objectives will be addressed using communication tools, including: a website, with an online database of open educational resources in different European languages; a film on clinical trials, dubbed in many languages, which is envisaged as a keystone of this initiative; an international event on multinational clinical trials.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.4.5-12 | Award Amount: 14.81M | Year: 2008

Objective: To delineate the biological and molecular pathways that initiate and drive chronic inflammatory disease and to transform the knowledge obtained into the development of novel anti-inflammatory interventions. Focus will be given to Rheumatoid Arthritis (RA) since longitudinal data indicate that intensive treatment can prevent persistency and chronicity. State of the Art and beyond: The first generation of targeted therapies in chronic inflammatory disease used RA as prototype disease for clinical development. These therapies are now also used in other inflammatory disorders. Although treatments have been developed that are effective in a proportion of patients, they are aspecific, relatively toxic and do not mediate cure. Currently, it is unknown which molecular effects need to be induced and/or targeted to prevent induction or persistency of RA. However, this is within reach through a strong international consortium of world-leading European groups that cover both basic- and translational research. Work plan: The general strategy for the project is to enable parallel studies that are focussed on critical switch moments in the biological processes that drive chronicity of inflammation. As the consortium consists of a multidisciplinary team with basic- and clinical expertise, translational research will be conducted to delineate the molecular basis of dysregulated inflammation, the RA-specific autoimmune-response and organ specific pathobiology. The final aim is to develop novel- and specific anti-inflammatory therapies. Impact of the project: This project will (i) identify the molecular networks underlying chronic inflammation and thereby (ii) will define novel targets for drug-development as well as (iii) algorithms that will predict outcome of therapy. Moreover, within this project European SMEs will evaluate new interventions (iv) and this project will (v) offer a platform to rapidly develop ideas and patents into new therapies.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.3-4 | Award Amount: 3.86M | Year: 2008

The TOBI project aims to analyse mechanisms provoking adipokine-mediated crosstalk and an inflammatory drift in obese patients. It will be the remit of this project to develop novel strategies to reduce or reverse major adipokine-mediated adverse interactions in peripheral tissues and by periorganic adipose tissue, namely insulin resistance and vascular dysfunction, respectively. Special attention will be given to the study of novel lipid-derived adipokines and the identification of targets for drug development that could interfere with the obesity-associated inflammatory drift. TOBI research focuses on molecular mechanisms initiating and promoting inflammatory signalling pathways in adipocytes and adipose tissue macrophages that cause a shift to inflammatory adipokines to interfere with insulin sensitivity and vascular function. Adipocyte dysfunction by alterations in ER stress signalling and lipolysis will be analysed as probable starting points of adipocyte inflammatory alterations. Signalling pathways and transcription factors controlling expression of inflammatory adipokines and anti-inflammatory adipokines will be studied. TOBI will particularly investigate lipid-derived adipokines that have been little studied to date. Key molecules of pathophysiological relevance will be validated for their potential as targets for drug development. The TOBI consortium will mount a comprehensive collaborative program for analysing the molecular mechanisms underlying regulation of adipokine production and their function in target tissues using genetic, molecular and biochemical approaches. The consortium combines all necessary expertise to investigate the basis of the obesity-associated inflammatory drift. A TOBI toolbox will be developed that strengthen collaboration and comparability of results. In addition the consortium includes relevant partners to exploit the results by translating them into new treatment strategies for obesity-associated adipokine-mediated disorders.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.4.3-3 | Award Amount: 3.85M | Year: 2009

The past decade has seen tremendous progress in our understanding of homeostatic regulators controlling energy balance. Insights from human and murine genetics have illuminated multiples pathways within the hypothalamus, brainstem and higher brain regions that play a key role in the control of food intake, whilst physiological studies focusing on the gastrointestinal tract have revealed a panoply of hormones that are secreted in response to or in anticipation of food intake and act centrally to regulate appetite. EurOCHIP brings together world leaders specializing in both areas in order to explore the interaction between the periphery and the brain in the control of energy homeostasis. Our programme of research will comprise four interdependent work-packages: i) characterising the interaction of gastrointestinal hormones with the hypothalamus and brainstem, with the aim of identifying novel molecules and pathways that mediate food intake; ii) using imaging techniques and behavioural phenotyping to explore the response of brain areas involved in higher cognitive and affective functions to these gastrointestinal hormones; iii) harnessing the power of human genetics to determine the role of sequence variation in and around newly identified candidate genes in appetitive behaviour and response to dietary interventions, focusing in particular on childhood obesity and iv) determining the effects of specific dietary interventions on gastrointestinal hormone secretion and using pharmacological studies in humans to mimic the hormonal milieu seen after a meal or bariatric surgery.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 4.04M | Year: 2013

The Digital Scholarly Editions Initial Training Network (DiXiT) is concerned with one of the most dynamic and pioneering research areas at the intersection of the humanities and computer sciences focused on digital scholarly editions. While the digital turn has challenged the theoretical understanding of and the methodological approach to the core research activity in most of the humanities, there is hardly any university institution which is able to provide the infrastructure and the resources in order to train the next generation of young scholars and researchers in all subjects and methods of this quickly developing field according to the needed standards. Therefore, only an international training network can provide this infrastructure and the scholarly resources for doctoral training and supervision. For this reason ten leading European institutions from universities and academies closely collaborating with the private sector and cultural heritage institutions intend to form one of the most innovative training networks for a new generation of scholars in the field of digital scholarly editing. DiXiT training programme offers a combination of network-wide training modules (Camps & Conventions) and local specialist training in connection with individual research projects, which not only will stand out in Europe, but will be able to compete with the worldwide leading centres and networks in the field of Digital Humanities research, cultural heritage, software and publishing industries. Moreover, DiXiT will help to create a training trajectory for the emerging supra-disciplinary field of Digital Humanities and thus anchoring it in an institutionalized, structured education scheme. The participating SMEs have a genuine interest in the achievement of the objectives of DiXiT because they actually need to recruit new professions in the domain of digital scholarly editions, with international and cross-disciplinary preparation, which is still not fully available on the professional market. This provides sound basis and guarantees a concrete approach to the exploitation and sustainability plan of the project.


Grant
Agency: Cordis | Branch: FP7 | Program: NoE | Phase: SEC-2011.7.4-1 | Award Amount: 8.18M | Year: 2012

The EUROFORGEN-NoE proposal aims to develop a network of excellence for the creation of a European Virtual Centre of Forensic Genetic Research. Forensic genetics is a highly innovative field of applied science with a strong impact on the security of citizens. However, the genetic methods to identify offenders as well as the creation of national DNA databases have caused concerns to the possible violation of privacy rights. Furthermore, studies to assess the societal dimension of security following the implementation of even more intrusive methods such as the genetic prediction of externally visible characteristics are highly relevant for their public acceptance. The network includes some of the leading groups in European forensic genetic research. It aims to create a closer integration of existing collaborations, as well as establishing new interactions in the field of security, as all key players are addressed: scientists, stakeholders, end-users, educational centres and scientific societies. Only if a long-term collaborative network can be established it will become possible to connect all scientific groups active in the field of forensic genetics, and to initiate a sustained effort covering all aspects of research. These efforts have to be combined with identifying and selecting the most innovative ideas to meet the challenges of analyzing biological crime scene samples compromised by degradation or indentified as mixtures of traces from multiple human sources. The proposal integrates five working packages. WP 1 is devoted to management and coordination. WP 2 will lead the activities aimed at the creation of the virtual centre of research. WP 3 will carry out exemplar projects as models of collaboration and integration of cutting edge research, later complemented by a competitive call for new research projects. The societal dimension of security as well as the ethical and legal aspects wil be addressed in WP 4, whereas WP 5 is devoted to education and training.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ENERGY.2013.2.9.2 | Award Amount: 3.78M | Year: 2013

Concentrating solar technologies (CST) have proven to be very efficient sources of clean power for the electrical grid. The efficient operation of concentrating solar technologies requires reliable forecasts of the incident irradiance for two main reasons. First, such forecasts yield a better management of the thermodynamic cycle because it becomes possible to dynamically fine tune some of its parameters such as the flow rate of the working fluid or the defocusing mirrors. Second, the electricity production can be optimally connected to the grid. Currently, forecasts are made by several techniques, which have their own merits and drawbacks. The uncertainty in the forecast of the DNI is still too large and must be reduced. Therefore, we propose a concept of portfolio of innovative or improved methods and possibly hardware that can be assembled by company experts to answer the specific needs of a given plant. To fulfil the objective, the Consortium will follow a strategy based on interactions with potential users of the system nowcastings, i.e., the plant operators. Requirements expressed by users will be collected and then converted into requirements on optical properties of the clear atmosphere and clouds for the design or improvements of methods. Users feedback on the advances will be later collected in the course of the project where intermediate results will be shown. A final workshop will be held for the demonstration of the final version of the methods and their combinations. Additionally, bilateral face-to-face meetings will collect technical views that cannot be expressed in a general forum comprising competitors. These individual meetings will help in addressing the issue of the further commercial exploitation of the assembled know-how. A detailed plan for the scientific dissemination was developed.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.1-6 | Award Amount: 3.85M | Year: 2011

Lung cancer (LC) is still the most lethal type of cancer worldwide. The extremely poor prognosis for LC patients is partly due to the lack of effective therapies. At present, most patients with pulmonary carcinomas are treated with chemotherapy. This essentially consists of classic cytotoxic drugs which only improve survival in small cohorts in few cases. In spite of the rapidly growing understanding of the epigenetic and genetic profile of LC, such knowledge has contributed little to improving therapeutics. This scenario, however, is likely to change soon because several specific cancer therapies, targeting molecules that are altered in cancer, are being developed or are already undergoing clinical trials. Thinking ahead, our proposal focuses, on the one hand, on validating novel and specific therapeutic strategies, with particular emphasis on discovering (epi)genetic alterations that could act as novel targets for therapies, and, on the other, on defining the (epi)genetic markers that could determine the efficacy response or resistance to targeted therapies as well as the acquired resistance of the tumours to therapy. To reach our goals, we have designed an integrative and interdisciplinary approach involving leading European clinical scientists of international renown with prominent preclinical and basic research groups using high throughput and state-of-the art platforms for genomics and gene expression analysis. To date, no such comprehensive information exists. The results will be of great value for the stratification of lung tumours according to their genetic background for tailored treatments. The development of an (epi)genetic-based therapeutic prediction model will hopefully set the basis for future tailored treatment of LC as well as of other epithelial cancers.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.69M | Year: 2012

This proposal brings together a group of universities, research organisations and high-tech companies from different disciplines (meteorology, geosciences, physics, electrical engineering, mathematics) with the aim to foster training and further development in the area of remote sensing of the atmosphere. The last years have brought a rapid development in instrumental techniques, i.e. lidar, radar, radiometry, that have great potential to monitor atmospheric composition and dynamics in unprecedented detail. Such instrumentation is urgently needed to address important topics related to climate change, numerical weather forecasting, and atmospheric pollution. Most prominently aerosol-cloud interaction as the single largest uncertainty in current climate projections requires the exploitation of emerging observational techniques to improve the parameterisation of aerosol and cloud processes in atmospheric models. Because todays curricula do not reflect these issues, ITARS (Initial Training for Atmospheric Remote Sensing) aims to impart an in-depth understanding of instrumentation and algorithms needed to retrieve geophysical quantities and atmospheric applications, to foster the synergy of different sensors by bringing together experts from the individual techniques, to develop and implement pan-European courses on atmospheric remote sensing by exploiting new web-based techniques, and to close the gap between the specialized development of single instruments and atmospheric applications by training a new generation of scientists in academia and the private sector.


Grant
Agency: Cordis | 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.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.3.2 | Award Amount: 4.04M | Year: 2008

Mobile communication has changed the way we live and will continue to do so. In future mobile multimedia will be a key driver for mobile communication. As handsets become more video oriented (TV, DVD, MP4, games etc) the small size of handsets forces a more restrictive limit to the size of display. High definition wearable virtual displays for hands-free viewing and low-cost low-power mobile-integrated micro-projection will overcome this restriction. The target of HYPOLED is the development of a next-generation high-specification virtual display platform using novel electronic and optical component technologies. The project will cover innovative device concepts and improved manufacturing concepts for a new generation of photonic system-on-chip for highly integrated display solutions. At the centre of the project is a new microdisplay technology. Microdisplays are very small displays that are viewed under optical magnification. They combine a high quality virtual image similar in size to that seen from a desktop monitor, with very low power consumption. This approach enables video, web pages or high-resolution still images to be viewed on portable consumer products with extended battery life. Microdisplays are already deployed as electronic viewfinders in camcorders and cameras. In future they will be seen in hands-free (wearable) systems and micro-projectors for use with 3G mobile phones, computed games and personal DVD/MP4 players. The project objectives are to develop a hands-free multimedia viewing system that uses the best and most suitable component technologies - emissive OLED microdisplay, light-weight optics and maximum electronic integration to provide the most appropriate technical specification and value for money for the targeted consumer markets.


Niermann D.,University of Cologne | Waschkowski F.,University of Cologne | De Groot J.,Jülich Research Center | Angst M.,Jülich Research Center | Hemberger J.,University of Cologne
Physical Review Letters | Year: 2012

We show results of broadband dielectric measurements on the charge ordered, proposed to be multiferroic material LuFe 2O 4. The temperature and frequency dependence of the complex permittivity as investigated for temperatures above and below the charge-order transition near T CO≈320K and for frequencies up to 1 GHz can be well described by a standard equivalent-circuit model considering Maxwell-Wagner-type contacts and hopping induced ac conductivity. No pronounced contribution of intrinsic dipolar polarization could be found, and thus the ferroelectric character of the charge order in LuFe 2O 4 has to be questioned. © 2012 American Physical Society.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.1-4;HEALTH-2007-2.4.1-2 | Award Amount: 3.85M | Year: 2008

Early detection accomplished through an efficient screening programme remains the most promising approach to improve the long-term survival of cancer patients. Therefore there is a pressing need for the development of biomarkers, which detect the early changes for cancers where clinical symptoms only appear when the cancer has progressed, and treatment is ineffective. Our proposal, which addresses this problem at the European level, combines two unique features: i) large unique collections of sera with the potential for evaluation of diagnostic serum biomarkers with high statistical power, and ii) a novel technological approach involving specific immuno-detection of cancer-associated Post-Translationally Modified (PTM) glycoproteins in serum and of auto-antibodies to these glycoproteins. Glycosylation of proteins is one of the most abundant and complex forms of post translation modifications and the most important for the cell surface and secreted proteomes. O-glycosylation (O-PTM) is always altered in carcinomas, creating novel O-PTM epitopes which induce auto-antibodies. Our Main Objectives are therefore to:- 1.Use a novel glycopeptide microarray technology to identifiy, evaluate and validate an O-PTM auto-antibody signature as an early diagnostic biomarker, focusing on breast, ovarian, pancreatic and lung cancers. 2. Develop and validate novel ELISA-type assays for cancer specific glycoforms of the MUC1 and MUC16 glycoproteins (targets of current serum biomarker assays). The project brings together a Consortium with participants from 5 member States to fully exploit the potential of the unique serum banks at a European level by A. Integrating the expertise of world leaders in Glycobiology with Cancer Physicians and experts in biomarker assays. B. Establishing a functional interaction between Academic groups and Commercial enterprises committed to improving cancer therapy and diagnosis.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 2.54M | Year: 2017

The EN-ACTI2NG program (European Network on Anti-Cancer Immuno-Therapy Improvement by modification of CAR and TCR Interactions and Nanoscale Geometry) emanates from the recent clinical evidence that T cells expressing engineered tumor-specific immune receptors can eradicate certain tumors that do not respond to conventional treatment. To obtain T cells with reactivity to a wider array of tumors and to improve efficiency and on- and off-target toxicity are current challenges Therefore the EN-ACTI2NG program aims 1) to train PhD students with expertise in development of new and improved T cell-mediated cancer immuno-therapies; 2) to endow the PhD students with the ability to establish efficient communication between the academic and industrial research environments and between scientists and the general public; 3) to improve T cell mediated anti-cancer immuno-therapy by the identification and development of new cancer-specific immune receptors and enhancing their function by identifying and modifying their molecular mechanism of action. To reach these objectives we have designed individual research projects ranging from biophysical analysis of immune receptors, via molecular modification of their structure and testing their tumor killing capacity in cell-based and pre-clinical assays to product development. Secondments will assure that each PhD student will be exposed to these complementary approaches and that there will be synergic feedback between the projects, producing innovative results that could otherwise not be achieved. Extensive training in research-specific skills, career development and a continuous training in communication skills will allow the PhD students to become facilitators of the process of transformation of scientific innovation into products with social and economic value. As such, the EN-ACTI2NG program should contribute to overcoming the more general challenge of converting the European Community into an innovation-driven society.


Bonnet M.,University of Cologne | Preukschat D.,University of Cologne | Welz P.-S.,University of Cologne | Van Loo G.,Ghent University | And 4 more authors.
Immunity | Year: 2011

Epidermal keratinocytes provide an essential structural and immunological barrier forming the first line of defense against potentially pathogenic microorganisms. Mechanisms regulating barrier integrity and innate immune responses in the epidermis are important for the maintenance of skin immune homeostasis and the pathogenesis of inflammatory skin diseases. Here, we show that epidermal keratinocyte-restricted deficiency of the adaptor protein FADD (FADD E-KO) induced severe inflammatory skin lesions in mice. The development of skin inflammation in FADD E-KO mice was triggered by RIP kinase 3 (RIP3)-mediated programmed necrosis (termed necroptosis) of FADD-deficient keratinocytes, which was partly dependent on the deubiquitinating enzyme CYLD and tumor necrosis factor (TNF)-TNF receptor 1 signaling. Collectively, our findings provide an in vivo experimental paradigm that regulation of necroptosis in keratinocytes is important for the maintenance of immune homeostasis and the prevention of chronic inflammation in the skin. © 2011 Elsevier Inc.


News Article | November 29, 2016
Site: www.eurekalert.org

Research networks to investigate topics such as practices of comparison, neutrinos, dark matter, and the robustness of vision; around €120 million in funding for an initial 4-year period The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) will establish 14 new Collaborative Research Centres (CRCs). This was decided by the responsible Grants Committee during its autumn session in Bonn. The new CRCs will receive a total of 117.4 million euros in funding. There will also be a 22 percent programme allowance for indirect project costs. Seven of the 14 networks set up are CRC/Transregios, which will be spread across multiple research sites. All of the new CRCs will be funded for an initial four-year period starting on 1 January 2017. In addition to the 14 new Collaborative Research Centres, the Grants Committee also approved the extension of 15 existing CRCs for an additional funding period. As a result, the DFG will be funding a total of 268 Collaborative Research Centres from January 2017. The new Collaborative Research Centres in detail (in alphabetical order by their host universities, including the name of the applicant universities): Little is currently known about the history, social and cultural causes, functions and impacts of comparison - despite frequent speculation about the increase in comparisons in certain epochs and in modern societies. In the Collaborative Research Centre "Practices of Comparisons: Ordering and Changing the World", researchers from the fields of history, literature studies, philosophy, history of art, political science and law will investigate how the historically variable practices of comparison link to routines, rules, institutions and discourses - and can thus create structures but also trigger medium-range dynamics or overarching change. (Host university: Bielefeld University, Spokesperson: Professor Dr. Angelika Epple) Industrial forming processes for metals cause damage within the material. It is not known how the damage caused by forming processes such as rolling or deep-drawing is influenced, how it changes throughout the process chain or what impact it has on subsequent component behaviour. The CRC/Transregio "Damage Controlled Forming Processes" therefore aims to develop new methods and technologies to control and predict damage as well as component characteristics. (Host university: Technical University of Dortmund, Spokesperson: Professor Dr.-Ing. A. Erman Tekkaya; additional applicant university: RWTH Aachen University) The aim of the CRC/Transregio "Mobile Material Characterisation and Localisation by Electromagnetic Sensing" is to trial new approaches to mobile material detectors. This would enable the material properties of any object to be determined, even if it were concealed behind a wall, making it possible to locate unconscious persons in a building filled with smoke or contaminated with poisonous gases, or to detect burning cables inside walls, for example. To achieve this it is necessary to develop mobile detectors that record data in a frequency range from several gigahertz to terahertz, which can be used to precisely localise and characterise a complex environment. (Host university: University of Duisburg-Essen, Spokesperson: Professor Dr.-Ing. Thomas Kaiser; additional applicant university: University of Bochum) Myeloid cells - the immune cells of the brain - play an important role in the function of the central nervous system. They are the focus of the work of the CRC/Transregio "Development, Function and Potential of Myeloid Cells in the Central Nervous System (NeuroMac)". Using some of the latest methods in molecular immunology and neuroscience, such as in-vivo microscopy and genome editing, the researchers will investigate the role of myeloid cells in diseases such as stroke, multiple sclerosis, Alzheimer's and Huntington's disease. (Host university: University of Freiburg, Spokesperson: Professor Dr. Marco Prinz; additional applicant universities: Free University of Berlin and Humboldt University of Berlin) The Collaborative Research Centre "N-Heteropolycycles as Functional Materials" is concerned with the field of organic electronics and will investigate new, entirely organic semiconductors. As the fundamental building blocks for semiconductors, the research network will use what are known as N-heteropolycycles and study their characteristics. The researchers intend to address the complete spectrum of chemical synthesis, method development and the physical and theoretical characterisation of organic semiconductors, including the question of the effects of the material properties of N-heteropolycycles in optoelectronic components, such as solar cells. (Host university: University of Heidelberg, Spokesperson: Professor Dr. Lutz H. Gade) In algebra, where exact calculations are essential, modern high-performance computers with mathematical software have enormous computing potential which so far has not been fully exploited. The researchers in the CRC/Transregio "Symbolic Tools in Mathematics and their Application" plan to further develop existing computer algebra systems which they have largely developed themselves and in doing so, answer fundamental questions in mathematics. They also plan to make the software available as an open-source system. (Host university: Technical University of Kaiserslautern, Spokesperson: Professor Dr. Gunter Malle; additional applicant universities: RWTH Aachen University; Saarland University) Symplectic geometry has its roots in classical mechanics, where it enables a coordinate-free formulation of the basic equations of motion and therefore a deeper understanding of the underlying dynamics. The CRC/Transregio "Symplectic Structures in Geometry, Algebra and Dynamics" will investigate symplectic structures and the application of symplectic techniques to topics in geometry, algebra, dynamic systems, topology, combinatorics and optimisation. The network will forge links with disciplines in which the potential of a symplectic approach has been little or not fully realised or which themselves can contribute new methodologies to the study of symplectic questions, for example computer science. (Host university: University of Cologne, Spokesperson: Professor Dr. Hansjörg Geiges; additional applicant university: University of Bochum) How is information organised and structured in language? The factor of 'prominence' plays a central role in the formation of language structures. Through its formulated question, the Collaborative Research Centre "Prominence in Language" will bring together many areas of linguistics, such as phonetics/phonology, morphology, syntax, semantics, pragmatics and discourse. It will also investigate the relationships between linguistic prominence and general cognitive mechanisms such as the accentuation of attention, thus forging links with psychology and clinical linguistics. (Host university: University of Cologne, Spokesperson: Professor Dr. Klaus von Heusinger) Contrary to a long-held view, bacteria are highly organised units whose function is guaranteed by the precise positioning of biomolecules inside them. The CRC/Transregio "Spatiotemporal Dynamics of Bacterial Cells" will consider many different aspects of cellular organisation, such as the spatiotemporal regulation of cell division, growth and morphogenesis, the organisation and segregation of chromosomal DNA and the dynamics of the formation of (membrane) protein complexes. In this way, the CRC/Transregio aims to identify the molecular systems responsible for controlling these cellular processes and better understand the spatiotemporal dynamics of bacterial cells. (Host university: University of Marburg, Spokesperson: Professor Dr. Martin Rudolf Thanbichler; additional applicant university: LMU Munich) The CRC/Transregio "Rationality and Competition: The Economic Performance of Individuals and Firms" brings together representatives of behavioural economics and neoclassical economics. They aim to explain how distortions and anomalies in the behaviour of individuals and companies are connected and what economic policy measures can effectively protect consumers and employees against poor decisions and exploitation. (Host university: LMU Munich, Spokesperson: Professor Dr. Klaus Schmidt; additional applicant university: Humboldt University of Berlin) A Munich-based Collaborative Research Centre will investigate "Neutrinos and Dark Matter in Astro- and Particle Physics (NDM)". The researchers are primarily interested in neutrinos, the most common particles of matter in the universe, and dark matter, which is responsible for cosmic dynamics on galactic and even larger scales. Among the topics they will address is the still unanswered question of whether neutrinos are their own antiparticles and whether they have sterile partners. The answer to this question could explain why our world consists of more matter than antimatter. (Host university: Technical University of Munich, Spokesperson: Professor Dr. Elisa Resconi) The high resource demands of construction, a fast-growing world population, especially in urban areas, and the changing needs of inhabitants create a need for fundamentally new architectural concepts. The aim of the Collaborative Research Centre "Adaptive Envelopes and Structures for the Future Built Environment" is therefore to develop concepts for adaptive buildings. The network will investigate the potential of adaptive elements for load-bearing structures, envelope systems and interior fittings, with a view to designing buildings which can actively react to external influences. (Host university: University of Stuttgart, Spokesperson: Professor Dr.-Ing. Werner Sobek) Our sense of sight enables us to identify objects reliably even under very different conditions; we therefore have robust visual inference. This ability demands complex calculations, which are performed by the nerve cells in the visual system. The aim of the Collaborative Research Centre "Robust Vision - Inference Principles and Neural Mechanisms" is to uncover the principles and algorithms that make robust vision possible. The researchers will also use technical algorithms of human learning and computer vision research to draw conclusions about biological vision. (Host university: University of Tübingen, Spokesperson: Professor Dr. Matthias Bethge) Predicting the extent to which pollutants will remain in and alter our landscapes in the long term is a major challenge in geosciences and environmental research, all the more so as the extremely complex processes are very difficult to measure with laboratory experiments. The Collaborative Research Centre "Catchments as Reactors: Metabolism of Pollutants on the Landscape Scale (CAMPOS)" will therefore investigate the transport and conversion of pollutants in the large-scale and long-term process chains found in nature. The researchers will utilise innovative observation systems and numerical landscape models with a view to laying the foundations for more reliable predictions about future soil and water quality in the face of climate and land use change. (Host university: University of Tübingen, Spokesperson: Professor Dr. Peter Grathwohl) Further information will be provided by the spokespersons of the Collaborative Research Centres. Contact at the DFG Head Office: Dr. Klaus Wehrberger, Head of the Research Centres Division, Tel. +49 228 885-2355, Klaus.Wehrberger@dfg.de More details about the funding programme and the funded Collaborative Research Centres are available at: http://www.


News Article | December 14, 2016
Site: www.eurekalert.org

The latest recipients of Germany's most prestigious research funding prize have been announced. In Bonn today, the Joint Committee of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) chose ten researchers, three women and seven men, to receive the 2017 Leibniz Prize. The recipients of the prize were selected by the Nominations Committee from 134 nominees. Of the ten new prizewinners, three are from the natural sciences, three from the humanities and social sciences, two from the life sciences and two from the engineering sciences. Each of the ten winners will receive €2.5 million in prize money. They can use these funds for their research work in any way they wish, without bureaucratic obstacles, for up to seven years. The awards ceremony for the 2017 Leibniz Prizes will be held on 15 March in Berlin. The following researchers will receive the 2017 "Funding Prize in the Gottfried Wilhelm Leibniz Programme" awarded by the DFG: The Gottfried Wilhelm Leibniz Prize has been awarded by the DFG annually since 1986. Each year a maximum of ten prizes can be awarded, each with prize money of €2.5 million. With the ten prizes for 2017, a total of 348 Leibniz Prizes have been awarded to date. Of these, 115 were bestowed on researchers in the natural sciences, 101 in the life sciences, 79 in the humanities and social sciences, and 53 in the engineering sciences. The number of award recipients is higher than the number of awarded prizes because, in exceptional cases, the prizes and money can be shared. Accordingly, a total of 374 nominees have received the prize, including 326 men and 48 women. The Leibniz Prize is the most significant research prize in Germany. Seven past prizewinners have subsequently received the Nobel Prize: 1988 Professor Dr. Hartmut Michel (Chemistry), 1991 Professor Dr. Erwin Neher and Professor Dr. Bert Sakmann (Medicine), 1995 Professor Dr. Christiane Nüsslein-Volhard (Medicine), 2005 Professor Dr. Theodor W. Hänsch (Physics), 2007 Professor Dr. Gerhard Ertl (Chemistry) and most recently in 2014 Professor Dr. Stefan W. Hell (Chemistry). Professor Dr. Lutz Ackermann (43), Organic Molecular Chemistry, Institute of Organic and Biomolecular Chemistry, University of Göttingen Lutz Ackermann has been selected for the 2017 Leibniz Prize for his outstanding work in the field of organic chemistry. His international reputation is based especially on his research into the catalytic activation of carbon-hydrogen bonds. These bonds, which occur in all organic substances, are usually extremely inert and permit only very poor and frequently non-selective transformation. The methods developed by Ackermann and his colleagues have paved the way for fundamentally new and low-impact manufacturing methods for important chemical products including active substances, agrochemicals and fine chemicals. Through his other work, Ackermann has also created new concepts for environmentally friendly chemical synthesis. Lutz Ackermann studied chemistry in Kiel, and, after further studies in Rennes and Mülheim an der Ruhr, he obtained his doctorate from the University of Dortmund. He did postdoctoral research at Berkeley before going to Munich in 2003 to work as the leader of a DFG-funded Emmy Noether independent junior research group. Ackermann has held his current chair in Göttingen since 2007 and has headed the Institute of Organic and Biomolecular Chemistry there since 2015. He is one of the most frequently cited researchers in his field in the world. Professor Dr. Beatrice Gründler (52), Arabic Studies, Seminar for Semitic and Arabic Studies, Free University of Berlin Beatrice Gründler will receive the Leibniz Prize for her studies on the diversity of voices in Arabic poetry and culture. She has been interested in the medium of script and its fundamental importance to Arabic traditions since an early stage in her career, as evidenced for example by her book "The Development of the Arabic Script" (1993). Through her research she has developed a complex media history of the Arab world, from the introduction of paper to book printing and beyond - indeed, she refers to an 'Arabic book revolution'. In a pilot project for a critical, annotated digital edition of the "Kalila wa-Dimna", begun in 2015, Gründler has unravelled the history of the text, development and impact of this collection of fables, considered one of the earliest Arabic prose works and a central text of Arabic wisdom literature. Gründler's own approach puts into practice in an exemplary way the encounters between Arabic and European knowledge traditions that she investigates in her work - another reason for the importance of her research. Beatrice Gründler studied at Strasbourg, Tübingen and Harvard, where she received her doctorate in 1995. After a period at Dartmouth College, she began teaching at Yale University in 1996, first as an assistant professor and from 2002 as Professor of Arabic Literature. In 2014 she returned to Germany, and has since been undertaking research at the Free University of Berlin. Ralph Hertwig will be recognised with the 2017 Leibniz Prize for his pioneering work in the psychology of human judgement and decision-making. His research has expanded our understanding of the possibilities and limitations of human rationality. Hertwig investigates the strategies which humans use, faced with limited knowledge, limited cognitive resources and often limited time, to nonetheless make good decisions and organise their actions. Central to his work is the question why a limitation also constitutes a strength, in other words how adaptive heuristics, as simple rules of thumb for problem-solving, can be as effective as complex optimisation models. Another of Hertwig's important contributions to decision research is the distinction between experience-based and description-based assessment of risk. This explains why the dramatic consequences of climate change, for example, are systematically underestimated by society, because although there is plenty of information available to describe the problem, there is little everyday experience - the main thing that people base their decisions on. Ralph Hertwig has been the director of the Max Planck Institute for Human Development since 2012 and heads the Center for Adaptive Rationality. Hertwig began his scientific career in 1995 at the Max Planck Institute for Psychological Research in Munich. In 1997 he moved to the Max Planck Institute in Berlin. Between 2000 and 2002 he was a Research Fellow at Columbia University. In 2003 he obtained his habilitation from the Free University of Berlin. In 2005 he was appointed Professor of Cognitive Science and Decision Psychology at the University of Basel, and moved from there to his current position. Karl-Peter Hopfner will receive the Leibniz Prize for his outstanding work in structural molecular biology and genome biology, with which he has made pioneering contributions to the field of DNA repair and the cellular detection of foreign nucleic acids. Hopfner's research focused on the molecular mechanisms of multiprotein complexes, which play an important role in the detection of damaged or viral nucleic acids. These detection processes are crucial to the protection of the genome; errors in detection and repair are among the main reasons for the development of cancer. Building on that work, Hopfner has carried out essential work on DNA double-strand break repair and in recent years has decoded the mechanism of the central MRN complex Mre11-Rad50-Nbs1, a DNA damage sensor. He also contributed substantially to answering the question of how cellular sensors of the innate immune system recognise viral or bacterial nucleic acids in the case of infection. Here, the sensors must distinguish between the body's own RNA and foreign RNA. Karl-Peter Hopfner studied biology in Regensburg and in St. Louis, USA. He completed his doctorate at the Max Planck Institute for Biochemistry in Martinsried as part of the Division led by Nobel Prize winner Robert Huber. Between 1999 and 2001 he carried out postdoctoral research at the Scripps Research Institute in La Jolla, before accepting a tenure track professorship at the Gene Center at LMU Munich. He has been a full professor at LMU since 2007. Professor Dr. Frank Jülicher (51), Theory of Biological Physics, Max Planck Institute for the Physics of Complex Systems, Dresden The award of the Leibniz Prize to Frank Jülicher recognises a world-leading researcher in biophysics with the ability to identify universal physical principles in the complex world of living matter. He had already attracted attention with his early work on the physics of hearing and cell mechanics. Through his investigation of active matter - the components of which exhibit autonomous activity, such as molecular motors, which play a key role in cell movement and division - Jülicher has established a new field of research. This raises many fundamental questions in non-equilibrium physics and has also inspired numerous new applications as well as biomimetic design. In collaboration with French researchers, the biophysicist laid the foundations for the dynamics of active matter by formulating a general hydrodynamic theory of active matter. Most recently, Jülicher has turned his attention to the control and organisation of cells in tissue. His seminal work is contributing to our understanding of cell self-organisation in tissue. This phenomenon, as yet poorly understood, is of enormous importance to developmental biology and medical applications. Frank Jülicher studied physics in Stuttgart and Aachen, received his doctorate in Cologne in 1994 and then spent two years researching in the USA and Canada. He subsequently worked with leading researchers in Paris in the field of soft matter and biophysics, before obtaining his habilitation in 2000 at Paris Diderot University (Paris 7). Since 2002, Jülicher has been the director of the Max Planck Institute for the Physics of Complex Systems in Dresden and Professor of Biophysics at the Technical University of Dresden. Professor Dr. Lutz Mädler (45), Mechanical Process Engineering, Stiftung Institut für Werkstofftechnik (IWT) and Department of Production Engineering, University of Bremen Lutz Mädler will receive the Leibniz Prize in recognition of his pioneering work in the targeted reactive formation of nanoparticles in the gas phase and their effect on living matter. He has developed an improved variant of flame spray pyrolysis for the cost-effective synthesis of nanoparticles, involving the thermochemical splitting of organic compounds. His work has made flame spray pyrolysis available for industrial applications. Mädler subsequently refined this pyrolysis technique when he discovered the droplet explosion phenomenon in flame sprays and its effects on material synthesis. However, as well as looking at the tailored synthesis of nanoparticles, Mädler has also investigated how toxic these particles are to the human body. This is important because many applications, for example paints, textiles and dental fillings, have direct impacts on humans. Mädler was able to demonstrate that interactions between synthetic nanoparticles and biological tissue produce reactive oxygen species which can trigger undesirable reactions. Lutz Mädler studied physics at the Technical University of Zwickau and then process engineering at Technische Universität Bergakademie Freiberg, where he obtained his doctorate in 1999. He completed his habilitation at ETH Zurich and then, with the support of a DFG fellowship, became a Senior Researcher at the University of California, Los Angeles. In 2008 he was appointed professor at the University of Bremen. Britta Nestler has been selected to receive the 2017 Leibniz Prize for her significant, internationally recognised research in computer-assisted materials research and the development of new material models with multiscale and multiphysical approaches. Nestler has developed extremely flexible and high-performing simulation environments to simulate the microstructure of materials for use on supercomputers. These are based on her own quantitative models for the description of multicomponent systems. She has thus achieved a new quality of microstructure representation in the thermomechanical simulation of materials and the simulation of solidification processes and thus depicted these processes through realistic 3D simulation for the first time. Through her creative application and further development of the phase field method, Nestler has achieved outstanding fundamental insights which are also of enormous practical relevance. For example, her simulation calculations are used to predict the spread of cracks in design materials such as brake discs and therefore help to extend their lifetime. Britta Nestler studied physics and mathematics in Aachen, where she also received her doctorate. Research visits took her to Southampton, UK and Paris. In 2001 Nestler accepted a professorship in the Faculty of Computer Science at Karlsruhe University of Applied Sciences and in 2009 her current chair at KIT. Professor Dr. Joachim P. Spatz (47), Biophysics, Max Planck Institute for Intelligent Systems, Stuttgart, and Institute of Physical Chemistry, University of Heidelberg Joachim Spatz will be recognised with the Leibniz Prize for his outstanding research at the boundaries of materials sciences and cell biophysics. His research is concerned with cell adhesion, that is, the adhesion and bonding of cells to one another and to surfaces. His exemplary experimental approach has garnered precise insights into the control of cell adhesion and indeed physiological processes. To achieve this, Spatz used artificial, molecularly structured boundary surfaces to reduce possible interactions to a minimum of molecular components. Joachim Spatz' scientific achievement lies in the fact that he can study the communication mechanisms between cells in a new way with the help of concepts from materials science and physics. Using these resources, he was able to explain how the molecular mechanism of collective cell migration works in wound healing. Joachim Spatz studied physics in Ulm and at Colorado State University. He obtained his doctorate in macromolecular chemistry in Ulm, and it was also there that he completed his habilitation with a topic on cell mechanics. Since 2000 he has been a professor of biophysical chemistry in Heidelberg. In 2004 he was appointed director of the Max Planck Institute for Metals Research, now the Max Planck Institute for Intelligent Systems, in Stuttgart. Since 2008 he has also held a visiting professorship in molecular cell biology at the Weizmann Institute in Rehovot, Israel. Professor Dr. Anne Storch (48), African Studies, Institute for African Studies and Egyptology, University of Cologne In awarding the 2017 Leibniz Prize to Anne Storch, the DFG is honouring an extremely innovative and world-renowned researcher in African Studies who has contributed to a far-reaching reorientation of her field through her pioneering work. Drawing on questions and methods from cultural anthropology and the social sciences, Storch has introduced new thematic and methodological dimensions, both theoretical and practical, to African Studies. Her exemplary studies have also shown how linguistically based analyses can be used in an interdisciplinary approach to develop a cultural-anthropological understanding of contemporary Africa. Of particular significance was her study of taboos and secret languages in central Africa, published in 2011, which describes linguistic observations in such a way that they lead to complex sociological descriptions of power practices and political mechanisms of effect. Storch's case studies, rooted in, yet transcending, linguistic speech description, have become internationally significant model studies for a modern, self-critical approach to African Studies. Anne Storch has been Professor of African Studies in Cologne since 2004. She trained in anthropology, African Studies, Oriental Studies and archaeology in Frankfurt am Main and Mainz. Between 2006 and 2009 she served as president of the Fachverband Afrikanistik, the specialist society for Africa-related scholarship in Germany. Since 2014 she has been the president of the International Association for Colonial and Postcolonial Linguistics. Awarding the Leibniz Prize to Jörg Vogel recognises one of the world's leading researchers in the field of ribonucleic acid biology. He was selected for his pioneering contributions to our understanding of regulatory RNA molecules in infection biology. Vogel recognised the importance of RNA biochemistry in prokaryotes very early on and has done pioneering work in the application and development of high-throughput sequencing for RNA analysis. Using this method, he has studied the influence of pathogens on the host cell. Vogel has also discovered how small regulatory RNA molecules control protein synthesis and the breakdown of RNA. This in turn has contributed to the development of new methods which can be used in gene therapy. Together with Emmanuelle Charpentier, who won the Leibniz Prize in 2016, Vogel was able to understand tracrRNA (trans-activating RNA) and its function, which made the application of the CRISPR/Cas9 system possible. Vogel thus uncovered general biological principles which play a major role in our understanding of pathogenic microorganisms and are resulting in new treatment approaches. Jörg Vogel studied biochemistry at the Humboldt University of Berlin, where he also obtained his doctorate on RNA splicing in plants. After doing postdoctoral research in Uppsala and Jerusalem, in 2004 he was appointed Head of Division at the Max Planck Institute for Infection Biology in Berlin. Since 2009 he has been a professor at the University of Würzburg, where he heads the Institute for Molecular Infection Biology. The Leibniz Prizes will be awarded on 15 March 2017 at 3.00 pm at the Berlin-Brandenburg Academy of Sciences and Humanities in Berlin. A separate invitation will be sent to members of the media. Additional information about the 2017 prizewinners can be requested at the start of the new year by contacting the DFG Press and Public Relations Office or at http://www. . Detailed information about the Gottfried Wilhelm Leibniz Programme is available at: http://www.


News Article | December 8, 2016
Site: www.eurekalert.org

With the awarding of the Leibniz Prize to Anne Storch, a highly innovative and internationally renowned scholar was chosen. With her groundbreaking work, she has contributed to a far-reaching reorientation of her field. Storch applied theoretical and practical questions and methods from cultural anthropology and the social sciences to African studies, thus contributing important new perspectives to the research field. In exemplary studies, she has moreover shown how linguistic analyses can be applied to a cultural-anthropological understanding of contemporary Africa. Her study on taboo and secret language in central Africa from 2011 was particularly significant. Her linguistic observations allow for complex sociological descriptions of power practices and political modes of action. Storch's case studies, which are grounded in linguistic descriptions, but go far beyond them, have become international model studies for a modern and self-critical orientation in African studies. Anne Storch became professor or African studies at the University of Cologne in 2004. She did her doctorate in Frankfurt/Main and Mainz in anthropology, African studies, Oriental studies and archaeology. From 2006 to 2009, she headed the Fachverband Afrikanistik, the German association of African studies. Since 2014, she has been serving as the president of the International Association for Colonial and Postcolonial Linguistics. The Gottfried Wilhelm Leibniz Prize is the most important research award in Germany. The Leibniz Programme, established in 1985, aims to improve the working conditions of outstanding scientists and academics, expand their research opportunities, relieve them of administrative tasks, and help them employ particularly qualified young researchers. A maximum of 2.5 million euros is provided per award. Prize winners are first chosen from a slate of nominations put forward by third parties. The final selection is made by the Joint Committee on the basis of a recommendation from the Leibniz Nominations Committee. The Leibniz Prizes will be officially awarded on 15 March 2017 at the Berlin-Brandenburg Academy of Sciences in Berlin.


Saugel B.,University of Hamburg | Grothe O.,University of Cologne | Grothe O.,Karlsruhe Institute of Technology | Wagner J.Y.,University of Hamburg
Anesthesia and Analgesia | Year: 2015

When comparing 2 technologies for measuring hemodynamic parameters with regard to their ability to track changes, 2 graphical tools are omnipresent in the literature: the 4-quadrant plot and the polar plot recently proposed by Critchley et al. The polar plot is thought to be the more advanced statistical tool, but care should be taken when it comes to its interpretation. The polar plot excludes possibly important measurements from the data. The polar plot transforms the data nonlinearily, which may prevent it from being seen clearly. In this article, we compare the 4-quadrant and the polar plot in detail and thoroughly describe advantages and limitations of each. We also discuss pitfalls concerning the methods to prepare the researcher for the sound use of both methods. Finally, we briefly revisit the Bland-Altman plot for the use in this context. © 2015 International Anesthesia Research Society.


Harrison F.E.,Vanderbilt University | Bowman G.L.,Oregon Health And Science University | Polidori M.C.,University of Cologne
Nutrients | Year: 2014

This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer's disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Sengle G.,University of Cologne | Sakai L.Y.,Oregon Health And Science University
Matrix Biology | Year: 2015

The fibrillins, large extracellular matrix molecules, are polymerized to form "microfibrils." The fibrillin microfibril scaffold is populated by microfibril-associated proteins and by growth factors, which are likely to be latent. The scaffold, associated proteins, and bound growth factors, together with cellular receptors that can sense the microfibril matrix, constitute the fibrillin microenvironment. Activation of TGFβ signaling is associated with the Marfan syndrome, which is caused by mutations in fibrillin-1. Today we know that mutations in fibrillin-1 cause the Marfan syndrome as well as Weill-Marchesani syndrome (and other acromelic dysplasias) and result in opposite clinical phenotypes: tall or short stature; arachnodactyly or brachydactyly; joint hypermobility or stiff joints; hypomuscularity or hypermuscularity. We also know that these different syndromes are associated with different structural abnormalities in the fibrillin microfibril scaffold and perhaps with specific cellular receptors (mechanosensors). How does the microenvironment, framed by the microfibril scaffold and populated by latent growth factors, work? We must await future investigations for the molecular and cellular mechanisms that will answer this question. However, today we can appreciate the importance of the fibrillin microfibril niche as a contextual environment for growth factor signaling and potentially for mechanosensation. © 2015.


Hutter M.,University of Heidelberg | Sweldens S.,Marketing Area | Stahl C.,University of Cologne | Unkelbach C.,University of Cologne | Klauer K.,Albert Ludwigs University of Freiburg
Journal of Experimental Psychology: General | Year: 2012

Whether human evaluative conditioning can occur without contingency awareness has been the subject of an intense and ongoing debate for decades, troubled by a wide array of methodological difficulties. Following recent methodological innovations, the available evidence currently points to the conclusion that evaluative conditioning effects do not occur without contingency awareness. In a simulation, we demonstrate, however, that these innovations are strongly biased toward the conclusion that evaluative conditioning requires contingency awareness, confounding the measurement of contingency memory with conditioned attitudes. We adopt a process-dissociation procedure to separate the memory and attitude components. In 4 studies, the attitude parameter is validated using existing attitudes and applied to probe for contingency-unaware evaluative conditioning. A fifth experiment incorporates a time-delay manipulation confirming the dissociability of the attitude and memory components. The results indicate that evaluative conditioning can produce attitudes without conscious awareness of the contingencies. Implications for theories of evaluative conditioning and associative learning are discussed. © 2011 American Psychological Association.


Glockner A.,BDH Klinik Greifswald | Cornely O.A.,University of Cologne
Mycoses | Year: 2013

Recent guideline recommendations on the management of candidaemia provide valuable treatment guidance for routine clinical practice, but need to be interpreted in the light of the actual situation of the patient and the local epidemiology of fungal infections. Echinocandins emerge as the generally preferred primary treatment. Treatment should be initiated immediately after notification of a Candida-positive blood culture in all patients. Ambiguous issues include the definition of optimum duration of treatment, the indication and time point to step down to oral azoles, catheter management, and the appropriate approach in critically ill patients at high risk for candidaemia in the absence of definitive proof of infection. Patients with clinical suspicion of antifungal treatment failure need prompt workup for adequacy of treatment, focal sources of sustained infection and potential superinfection. © 2012 Blackwell Verlag GmbH.


Schiffels S.,University of Cologne | Szollosi G.J.,University Claude Bernard Lyon 1 | Mustonen V.,Wellcome Trust Sanger Institute | Lassig M.,University of Cologne
Genetics | Year: 2011

In nonrecombining genomes, genetic linkage can be an important evolutionary force. Linkage generates interference interactions, by which simultaneously occurring mutations affect each other's chance of fixation. Here, we develop a comprehensive model of adaptive evolution in linked genomes, which integrates interference interactions between multiple beneficial and deleterious mutations into a unified framework. By an approximate analytical solution, we predict the fixation rates of these mutations, as well as the probabilities of beneficial and deleterious alleles at fixed genomic sites. We find that interference interactions generate a regime of emergent neutrality: all genomic sites with selection coefficients smaller in magnitude than a characteristic threshold have nearly random fixed alleles, and both beneficial and deleterious mutations at these sites have nearly neutral fixation rates. We show that this dynamic limits not only the speed of adaptation, but also a population's degree of adaptation in its current environment. We apply the model to different scenarios: stationary adaptation in a time-dependent environment and approach to equilibrium in a fixed environment. In both cases, the analytical predictions are in good agreement with numerical simulations. Our results suggest that interference can severely compromise biological functions in an adapting population, which sets viability limits on adaptive evolution under linkage. © 2011 by the Genetics Society of America.


Bercioux D.,Albert Ludwigs University of Freiburg | De Martino A.,University of Cologne
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

We address the problem of spin-resolved scattering through spin-orbit nanostructures in graphene, i.e., regions of inhomogeneous spin-orbit coupling on the nanometer scale. We discuss the phenomenon of spin-double refraction and its consequences on the spin polarization. Specifically, we study the transmission properties of a single and a double interface between a normal region and a region with finite spin-orbit coupling, and analyze the polarization properties of these systems. Moreover, for the case of a single interface, we determine the spectrum of edge states localized at the boundary between the two regions and study their properties. © 2010 The American Physical Society.


Gnambs T.,University of Osnabrück | Kaspar K.,University of Cologne
Behavior Research Methods | Year: 2015

In surveys, individuals tend to misreport behaviors that are in contrast to prevalent social norms or regulations. Several design features of the survey procedure have been suggested to counteract this problem; particularly, computerized surveys are supposed to elicit more truthful responding. This assumption was tested in a meta-analysis of survey experiments reporting 460 effect sizes (total N =125,672). Self-reported prevalence rates of several sensitive behaviors for which motivated misreporting has been frequently observed were compared across self-administered paper-and-pencil versus computerized surveys. The results revealed that computerized surveys led to significantly more reporting of socially undesirable behaviors than comparable surveys administered on paper. This effect was strongest for highly sensitive behaviors and surveys administered individually to respondents. Moderator analyses did not identify interviewer effects or benefits of audio-enhanced computer surveys. The meta-analysis highlighted the advantages of computerized survey modes for the assessment of sensitive topics. © 2014, Psychonomic Society, Inc.


Maier P.,Albert Ludwigs University of Freiburg | Reinhard T.,Albert Ludwigs University of Freiburg | Cursiefen C.,University of Cologne
Deutsches Arzteblatt International | Year: 2013

Background: Technical innovations in corneal transplantation have now made it possible to replace only the diseased part of the cornea, rather than the entire cornea as in penetrating keratoplasty (PKP). Patients with endothelial insufficiency due to Fuchs endothelial dystrophy, bullous keratopathy, or endothelial failure after keratoplasty can be treated with the new methods of posterior lamellar corneal transplantation: Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). It remains unclear which of these methods is better in the individual case.Methods: We review the pertinent literature retrieved by a selective search in Medline and the Cochrane Library employing the terms "DMEK," "DSAEK," "DSEK," and "posterior lamellar keratoplasty." The publications considered in this article are those that contain important clinical information on the operative techniques.Results: No randomized controlled trials of these techniques have been published to date. Numerous case series have shown that patients who undergo DSAEK (postoperative visual acuity ≥0.5 in 38-100%), and especially those who undergo it in early or intermediate stages of endothelial insufficiency, achieve a better functional result more rapidly than patients treated with PKP (postoperative visual acuity ≥0.5 in 47-61%). Only 23-47% of DSAEK patients achieve a visual acuity of 0.8 or more, compared to 36-79% of DMEK patients. Moreover, transplant rejection is seen in only 1-3% of cases of DMEK, compared to 0-8% after DSAEK and 1-23% after PKP.Conclusion: Numerous case series show clear advantages of DMEK over DSAEK, which, in turn, has better results than PKP. Nonetheless, randomized controlled trials are needed to determine which operative method is best in each stage of corneal disease.


Arndt M.,University of Marburg | Dindaroglu M.,University of Cologne | Schmalz H.-G.,University of Cologne | Hilt G.,University of Marburg
Organic Letters | Year: 2011

The absolute control of the regiochemistry of a cobalt-catalyzed 1,4-hydrovinylation reaction is achieved by alternation of the ligands applied. While the dppe/dppp ligands led to the formation of the branched product, the herein described application of the SchmalzPhos ligand generates the corresponding linear product in both excellent yields and regioselectivities. The catalyst system exhibits a high tolerance toward functional groups, and the very mild reaction conditions allow the synthesis of 1,4-dienes without isomerization into conjugated systems. © 2011 American Chemical Society.


Lohnert U.,University of Cologne | Maier O.,Federal Office of Meteorology and Climatology
Atmospheric Measurement Techniques | Year: 2012

The motivation of this study is to verify theoretical expectations placed on ground-based microwave radiometer (MWR) techniques and to confirm whether they are suitable for supporting key missions of national weather services, such as timely and accurate weather advisories and warnings. We evaluate reliability and accuracy of atmospheric temperature profiles retrieved continuously by the microwave profiler system HATPRO (Humidity And Temperature PROfiler) operated at the aerological station of Payerne (MeteoSwiss) in the time period August 2006-December 2009. Assessment is performed by comparing temperatures from the radiometer against temperature measurements from a radiosonde accounting for a total of 2107 quality-controlled all-season cases. In the evaluated time period, the MWR delivered reliable temperature profiles in 86% of all-weather conditions on a temporal resolution of 12-13 min. Random differences between MWR and radiosonde are down to 0.5 K in the lower boundary layer and increase to 1.7 K at 4 km height. The differences observed between MWR and radiosonde in the lower boundary layer are similar to the differences observed between the radiosonde and another in-situ sensor located on a close-by 30 m tower. Temperature retrievals from above 4 km contain less than 5% of the total information content of the measurements, which makes clear that this technique is mainly suited for continuous observations in the boundary layer. Systematic temperature differences are also observed throughout the retrieved profile and can account for up to ±0.5 K. These errors are due to offsets in the measurements of the microwave radiances that have been corrected for in data post-processing and lead to nearly bias-free overall temperature retrievals. Different reasons for the radiance offsets are discussed, but cannot be unambiguously determined retrospectively. Monitoring and, if necessary, corrections for radiance offsets as well as a real-time rigorous automated data quality control are mandatory for microwave profiler systems that are designated for operational temperature profiling. In the analysis of a subset of different atmospheric situations, it is shown that lifted inversions and data quality during precipitation present the largest challenges for operational MWR temperature profiling. © 2012 Author(s). CC Attribution 3.0 License.


Chaves R.,Albert Ludwigs University of Freiburg | Chaves R.,University of Cologne
Physical Review Letters | Year: 2016

It is a recent realization that many of the concepts and tools of causal discovery in machine learning are highly relevant to problems in quantum information, in particular quantum nonlocality. The crucial ingredient in the connection between both fields is the mathematical theory of causality, allowing for the representation of arbitrary causal structures and providing a rigorous tool to reason about probabilistic causation. Indeed, Bell's theorem concerns a very particular kind of causal structure and Bell inequalities are a special case of linear constraints following from such models. It is thus natural to look for generalizations involving more complex Bell scenarios. The problem, however, relies on the fact that such generalized scenarios are characterized by polynomial Bell inequalities and no current method is available to derive them beyond very simple cases. In this work, we make a significant step in that direction, providing a new, general, and conceptually clear method for the derivation of polynomial Bell inequalities in a wide class of scenarios. We also show how our construction can be used to allow for relaxations of causal constraints and naturally gives rise to a notion of nonsignaling in generalized Bell networks. © 2016 American Physical Society.


Carr S.T.,Karlsruhe Institute of Technology | Bagrets D.A.,University of Cologne | Bagrets D.A.,Karlsruhe Institute of Technology | Schmitteckert P.,Karlsruhe Institute of Technology
Physical Review Letters | Year: 2011

We present a general technique to obtain the zero temperature cumulant generating function of the full counting statistics of charge transfer in interacting impurity models out of equilibrium from time-dependent simulations on a lattice. We demonstrate the technique with application to the self-dual interacting resonant level model, where very good agreement between numerical simulations using the density matrix renormalization group and those obtained analytically from the thermodynamic Bethe ansatz is found. We show from the exact form of counting statistics that the quasiparticles involved in transport carry charge 2e in the low bias regime and e/2 in the high bias regime. © 2011 American Physical Society.


Brask J.B.,University of Geneva | Chaves R.,Albert Ludwigs University of Freiburg | Chaves R.,University of Cologne | Kolodynski J.,ICFO - Institute of Photonic Sciences | Kolodynski J.,University of Warsaw
Physical Review X | Year: 2015

Under ideal conditions, quantum metrology promises a precision gain over classical techniques scaling quadratically with the number of probe particles. At the same time, no-go results have shown that generic, uncorrelated noise limits the quantum advantage to a constant factor. In frequency estimation scenarios, however, there are exceptions to this rule and, in particular, it has been found that transversal dephasing does allow for a scaling quantum advantage. Yet, it has remained unclear whether such exemptions can be exploited in practical scenarios. Here, we argue that the transversal-noise model applies to the setting of recent magnetometry experiments and show that a scaling advantage can be maintained with one-axistwisted spin-squeezed states and Ramsey-interferometry-like measurements. This is achieved by exploiting the geometry of the setup that, as we demonstrate, has a strong influence on the achievable quantum enhancement for experimentally feasible parameter settings. When, in addition to the dominant transversal noise, other sources of decoherence are present, the quantum advantage is asymptotically bounded by a constant, but this constant may be significantly improved by exploring the geometry.


Kaller C.P.,Albert Ludwigs University of Freiburg | Unterrainer J.M.,University Medical Center Mainz | Stahl C.,University of Cologne
Psychological Assessment | Year: 2012

In clinical and experimental settings, planning ability is typically assessed using the Tower of London (ToL) or one of its variants. For enhancing the comparability across studies, a common ToL problem set was recently suggested comprising a collection of 4- to 7-move problems. Based on previous theoretical and empirical analyses of problem space and task structure, development of the problem set accounted particularly for the influence of structural problem parameters on the detection of individual differences in planning ability. To assess its adequacy as a clinical and research instrument, the present study evaluated the psychometric properties of the suggested problem set. Results showed a clear and nearly perfect linear increase of task difficulty across minimum moves. Given a broad range of item difficulty, high- and low-achieving subjects could be well discriminated. The test scores' split-half reliability (r = .72) and internal consistency (α= .69) were satisfactory. Taken together, the ToL problem set evaluated here proved to have good psychometric qualities and constitutes a conceptually sound basis for diagnostic and research purposes. © 2011 American Psychological Association.


Dittrich K.,Albert Ludwigs University of Freiburg | Stahl C.,University of Cologne
Journal of Experimental Psychology: Human Perception and Performance | Year: 2012

Load theory predicts that concurrent cognitive load impairs selective attention. For visual stimuli, it has been shown that this impairment can be selective: Distraction was specifically increased when the stimulus material used in the cognitive load task matches that of the selective attention task. Here, we report four experiments that demonstrate such selective load effects for auditory selective attention. The effect of two different cognitive load tasks on two different auditory Stroop tasks was examined, and selective load effects were observed: Interference in a nonverbal-auditory Stroop task was increased under concurrent nonverbal-auditory cognitive load (compared with a no-load condition), but not under concurrent verbal-auditory cognitive load. By contrast, interference in a verbal-auditory Stroop task was increased under concurrent verbal-auditory cognitive load but not under nonverbal-auditory cognitive load. This double-dissociation pattern suggests the existence of different and separable verbal and nonverbal processing resources in the auditory domain. © 2011 American Psychological Association.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SST.2008.4.1.1. | Award Amount: 5.81M | Year: 2009

ASSESS mobilises the European research community and car industry to develop a relevant set of test and assessment methods applicable to a wide range of integrated vehicle safety systems. Methods will be developed for driver behavioural aspects, pre crash sensing performance and crash performance under conditions influenced by pre crash driver and vehicle actions. The gained know-how will be implemented in proposals for test and assessment procedures that will be evaluated on the basis of actual systems currently offered to the market. ASSESS aims to stimulate the introduction of new crucial technologies in vehicles to further reduce road fatalities and injuries to car occupants in Europe and to make the traffic environment safer for road users. The project also aims to increase the level of competitiveness of the European automobile industry; safety is a proven selling point. This is underlined by a substantial involvement of European car industry (OEMs and suppliers) in this project and their willingness to provide systems and relevant know-how to this project. Specific project goals to develop harmonized and standardized assessment procedures and related tools for selected integrated safety systems. Procedures will be developed for driver behaviour evaluation, pre crash system performance evaluation, crash performance evaluation and socio economic assessment. To create acceptance and accelerate the implementation of the results in test and assessment procedures for type approval and consumer rating purposes, an advisory board consisting of leading EU OEMs, EuroNCAP and UTAC will be consulted on an annual basis or more often when needed. The direct involvement of EuroNCAP will raise the public awareness of the benefits of these new advanced safety systems by means of easy understandable rating systems. To provide and overview of legal barriers that obstruct the introduction of such systems and the potential socio-economic benefits of selected systems


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP-2007-1.3-2 | Award Amount: 4.31M | Year: 2008

Engineered nanomaterials (ENs) present tremendous opportunities for industrial growth and development, and hold great promise for the enrichment of the lives of citizens, in medicine, electronics, and numerous other areas. However, there are considerable gaps in our knowledge concerning the potential hazardous effects of ENs on human health and the environment. Our EU-US partnership is committed to filling these knowledge gaps through a comprehensive assessment of ENs, with particular focus on effects on the immune system. The immune system is designed to respond to pathogens and foreign particles, and a core concept underpinning the current project is that the recognition versus non-recognition of ENs by immune-competent cells will determine the distribution as well as the toxicological potential of these materials. Our multidisciplinary consortium will focus on the procurement, synthesis and detailed physico-chemical characterization of representative categories of ENs, and the monitoring of potential hazardous effects using an array of in vitro and in vivo systems, as well as transcriptomic and oxidative lipidomic testing to determine specific nanotoxic profiles (signatures) of these materials. The final and integrative component of our research project is risk assessment of potential adverse effects of ENs on human health, and the dissemination of our findings. Through our comprehensive approach, which combines analytical procedures from many different disciplines and leading experts from several national institutes devoted to occupational and environmental safety, we aim to establish a panel of read-out systems for the prediction of the toxic potential of existing and emerging ENs, thus enabling a continuous and sustainable growth of the nanotechnologies. Overall, the results generated through this international program will contribute to the understanding and mitigation of possible adverse effects of nanomaterials.


Tian C.-S.,University of Cologne | Cheung S.-K.,Hong Kong University of Science and Technology | Zhang Z.-Q.,Hong Kong University of Science and Technology
Physical Review Letters | Year: 2010

We report a first-principles study of static transport of localized waves in quasi-one-dimensional open media. We find that such transport, dominated by disorder-induced resonant transmissions, displays novel diffusive behavior. Our analytical predictions are entirely confirmed by numerical simulations. We show that the prevailing self-consistent localization theory is valid only if disorder-induced resonant transmissions are negligible. Our findings open a new direction in the study of Anderson localization in open media. © 2010 The American Physical Society.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.44M | Year: 2012

Complex decision making in enterprises should involve mathematical optimization methods, because a best choice has to be made out of a huge number of feasible options. A mathematical description of such decision processes typically involves both continuous and discrete decisions. If the latter are present, the customary modelling approach is to use integer variables, which are also used to represent all possible nonlinearities, so that the remaining part of the model is linear. This leads to Mixed-Integer Linear Optimization (MILO) problems, which can be handled nowadays by many packages, but are often very difficult to solve. Difficulty of MILO problems is often due to the fact that objective functions or constraints that are structurally nonlinear (e.g., quadratic) are linearized by introducing new integer variables. In many cases, it was observed that this is not the best way to proceed, as facing the nonlinearity directly without the new variables leads to much better results. Algorithmic technology for the resulting Mixed-Integer Nonlinear Optimization (MINO) problems is still at its early stage. The present situation is that enterprises facing a MINO problem generally give up due to the lack of efficient solvers, or try to convert it to a MILO one often too hard to be solved in practice. On the other hand, in the academia there is now an increasing expertise in MINO, which is however hardly exported outside due to the lack of interaction with the industrial world. It is the purpose of this project to help satisfy the increasing demand for highly qualified researchers receiving, at the same time, a state-of-the-art scientific training from the academia and hands-on experience with real-world applications from the industry. The researchers formed within this project, once recruited by an enterprise at the end of their training, will have the potential to apply all the available knowledge to optimize complex decision making in the real-world.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.2-1 | Award Amount: 6.47M | Year: 2012

The IMPACT project is about improving the lives of brain diseased patients through a novel approach that leaps beyond currently available Deep Brain Stimulation (DBS) devices and procedures. The initial project focus is on Parkinsons Disease (PD), but further brain-disease indications will be included in the later phase of the project. The personalized approach that IMPACT brings is essential in delivering full therapeutic benefits to DBS patients while preventing the stimulation-induced side-effects that occur with todays DBS implants. PD is well known for its characteristic symptoms: shaking, rigidity, slowness of movement and postural instability. Millions are suffering from PD including famous people like Michael J. Fox. Drugs are used as first treatment, but as the disease progresses they become ineffective and increasingly higher doses are needed. This leads to many side-effects, while symptoms still persist. DBS is a pacemaker for the brain, analogous to the function of pacemakers for the heart: mild electrical stimuli are delivered to brain tissue to suppress unwanted activity and restore desired neuronal functions. When stimulation is optimal, the impact of DBS is spectacular: shaking and rigidity are strongly improved, and medication doses may be lowered significantly. Despite its successes, DBS is still in its infancy. Programming for optimal therapy is complicated since physicians lack the appropriate tools to support them. Around 15 30% of DBS patients suffer from stimulation-induced side-effects resulting from stimulation leaking outside intended target regions. IMPACT addresses these barriers to adoption exploiting the directivity provided by next generation high-resolution implants. IMPACT delivers a physician tool for tuning the high-resolution implant based on a personalized patient brain stimulation model that takes into account imaging data (MRI, X-ray) as well as pre-operative data (local field potentials).


Grant
Agency: Cordis | Branch: FP7 | Program: CSA | Phase: ICT-2007.6.1 | Award Amount: 2.11M | Year: 2007

The FESTA Support Action is a vital step in the realisation of scientifically robust and efficiently run Field Operational Tests which aim to evaluate key ICT functions. A consortium of European experts with a wide range of skills has been formed to allow the development of a best-practise handbook which will guide the design and implementation of an FOT. The consortium involves the participation of academic institutes and national research laboratories, vehicle manufacturers and system providers, along with representatives of national road authorities. This allows the dovetailing of scientific integrity and practical considerations. This Support Action will consider the whole lifecycle of an FOT, from the analysis of stakeholders needs, the choice of behavioural and other (performance and individual) indicators, the methods by which they are measured (data acquisition), and analysed, reported and integrated and legal, ethical and procedural considerations. In addition, a whole range of ICT functions will be considered, ranging from vehicle systems (e.g. collision warning systems), cooperative systems (e.g. traffic management systems) and nomadic devices such as driver information systems. Running alongside the standard management functions, will be the development of two key workshops to involve wider participation of stakeholders. They will provide the opportunity to undertake needs analyses and dissemination activities. The potential for exploitation of the results and outputs of the FESTA Support Action are high, given the specific EC call for FOTs in the near future.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SSH.2012.3.2-2 | Award Amount: 3.06M | Year: 2013

DISCIT aims to produce new knowledge enabling Member States, affiliated European countries and the European Union to achieve full and effective participation of persons with disabilities in society and the economy. In investigating the social and political conditions for making such participation a reality, the project adopts a multifaceted understanding of Active Citizenship. Adopting a multilevel and institutional perspective, DISCIT examines how different types of policies (social benefits, social services and social regulation instruments) can be mutually supportive in enhancing Active Citizenship for persons with disabilities. Using the UN Convention on the Rights of Persons with Disabilities (CRPD) as a framework of reference, DISCIT identifies more effective ways to remove and prevent physical, attitudinal, social and organisational barriers to Active Citizenship and participation on an equal basis with others, in a context of rapid social and economic change and evolving conceptions of disability across European societies. DISCIT synthesises policy lessons from a strategic sample of European states: Liberal (Ireland, United Kingdom), Conservative (Germany, Italy), Social Democratic (Norway, Sweden) and Post-Communist (Czech Republic, Serbia) regimes. DISCIT involves consortium members from all these countries in addition to Switzerland and Belgium. DISCITs results provide new insight into how the European Union can support Member States and affiliated European countries in working towards the realization of the rights of persons with disabilities as expressed in the Fundamental Rights under the EC Treaty and the CRPD. By clarifying the possibilities for a strengthened synergy between policies at diverse levels of governance, DISCIT contributes to knowledge for realizing the ambitions of the EU Disability Strategy 2010-2020 and the Europe 2020 Strategy for Smart, Sustainable and Inclusive Growth. DISCIT has a duration of 36 months; is coordinated by Norwegian Social Research (NOVA); the consortium members are universities, research institutes and two civil society organisations (EDF and MDRI-S). The consortium is supported by a Scientific Advisory Committee with distinguished members mainly from countries not covered by the consortium members, a European Stakeholder Committee and eight National Stakeholder Committees. www.discit.eu


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SPA.2013.2.1-01 | Award Amount: 2.83M | Year: 2013

The goal of this project is to investigate in detail the dynamics and composition of the middle and lower atmosphere of Venus by combining data from Venus Express instruments (VIRTIS, VMC) with simultaneous data acquired from several ground-based telescope facilities. The project will perform coordinated observations to provide a detailed analysis of dynamical and chemical couplings between different levels of the atmosphere that are probed simultaneously by different instruments. It is time critical in the context of (1) the extension of the Venus Express (VEx) mission until the end of 2014 and with the possibility of only 1-2 years beyond; (2) the expertise and coordination in wind and trace species measurements developed in our institutions, currently unique in the world; (3) the availability of new techniques of ground-based investigation of Venus atmosphere, which will benefit from coordination and cross-calibration with in-orbit Venus Express payload instruments. Venus is Earths closest sibling, but it has ended up with a radically different climate. Venus atmospheric science is thus increasingly important in an era in which we are trying to understand the divergent evolutionary outcomes for terrestrial planets, whether we are considering the future of our Earth or the habitability in other solar systems. The European Space Agencys Venus Express is the only spacecraft at Venus prior to Venus Express, the last Venus orbiter was launched in 1989 so European scientists now lead the world in Venus research (in marked contrast to the status for most other planets). This project will (a) enhance the legacy of Venus Express data through cross-validation with complementary ground-based telescopic observations; (b) position European ground-based researchers to continue to lead Venus research after the end of the Venus Express mission, and (c) strengthen the position of European researchers in the emerging field of comparative planetology.


Grant
Agency: Cordis | 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.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.3.1 | Award Amount: 4.08M | Year: 2008

A big challenge awaits for technological developments to keep up with the demands in the market due to both the large variety of wireless communication channels as well as the fact that they are essentially all used at the same time by widely varying applications. For planned developments of wireless communication channels in the SHF and EHF bands, IC design automation tools are indispensable. These tools are needed to develop nanoscale designs of unprecedented complexity and performance and, in addition, enable the achievement of single-pass design success to avoid costly re-spins and the loss of market opportunities.\nCurrently it is impossible to provide accurate simulations of such a system, or even a smaller section of it encompassing just the RF front-end. The advent of multi-standard and software defined radios requires a new generation of transceiver architectures and corresponding CAD tools. Dealing with centre frequencies in the GHz range, the noise figure is a limitation for state-of-the-art designs. Many transceivers have to work in a mobile environment. Therefore low power consumption is mandatory which must be traded off with the circuits linearity and gain.\nThe key for enabling the realisation of single-chip integration of high-GHz wireless modules is resolving the shortcomings in available design flows. According to the 2006 Sematech roadmap this step in technology requires novel CAD tools and mathematical methods to deal with analogue/digital mixed signal simulation, with challenges in system design and methodologies, parasitic extraction, device and EM simulation, model extraction and optimisation tools. The ICESTARS project will deliver the methodologies and prototype tools to make this possible, by combining the research results of several domains to achieve a clear view on the dependencies between different parts of the complete RF design.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-SICA | Phase: HEALTH-2007-2.3.3-8 | Award Amount: 2.97M | Year: 2008

Despite widespread immunization, influenza still kills thousand of people, and costs to US, Europe and Asia enormous amount of money in term of healthcare expenses and productivity losses. While immunization remains an important approach to prevent influenza, small-molecule antiviral agents represent a novel opportunity for effective prevention and therapy of flu. Inhibitors of neuraminidase, essential enzyme for viral replication in all three classes of influenza viruses, has been recently found. Two of these inhibitors have reached the market, namely, zanamivir (GSKBs Relenza (1) in July 1999, and oseltamivir phosphate (Gilead Bs Tamiflu (2), also marketed by Roche) in October 1999. The recent healthy problem related to avian flu, has increase the public demand for stockpiles of Tamiflu, both as a reasonable frontline therapy against a possible flu pandemic and as a preventive agent. However, natural sources of drug (Shikimic acid) are scarcely, and increasing demand for oseltamivir phosphate has placed further pressure on Roche and the chemical community in general to develop new routes to the drug that do not involve complex natural products. In addition, the described synthesis are expensive and difficult. Moreover, in this synthesis use of hazardous azide-based reagents was necessary. New routes to Tamiflu have been recently described, but more than 12 steps in one case and 17 in another are needed. In order to find new drug candidates, cut the drug costs and improving availability as well as efficiency, new chemical synthesis are necessary. We propose a new domino reaction based on an organocatalytic approach to the synthesis of new Tamiflu derivatives. The chemistry involved in this project is easy to perform, and well adapt to industrial contest. Moreover, new chemical structures will be prepared and evaluated as potential drug against virulent and mutated flu viruses.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-3.1-2 | Award Amount: 3.92M | Year: 2009

Context Hospitals in European countries apply a wide range of quality improvement strategies; however, knowledge on the effectiveness of these strategies is limited. Objectives We propose to study the effectiveness of quality improvement systems in European hospitals. Specific research objectives are: a) to develop a maturity classification model for the assessment of organizational quality improvement systems in EU hospitals; b) to investigate associations between the maturity of quality improvement systems and measures of organizational culture, professional involvement and patient empowerment (at hospital level); c) to investigate associations between the maturity of quality improvement systems and measures of clinical effectiveness, patient safety and patient involvement (at patient and departmental level); d) to identify factors influencing the uptake of quality improvement activities by hospitals including external pressure as enforced by accreditation, certification or external assessment programmes. Design DUQUE will apply multi-method approaches to data collection, measurement and analysis. Data will be collected at hospital, departmental, professional and patient level. We will employ a multi-level study design in which patient-level data is nested in hospital departments, which are nested in hospitals in different EU countries. Setting We will collect data at hospital and departmental level in the Czech Republic, France, Germany, Poland, Portugal, Spain, Turkey and the United Kingdom in 30 randomly selected hospitals. In each country, for 12 of these 30 hospitals we will carry out additional data collection at the patient-level. Expected outcomes The products of DUQUE will include a catalogue of instruments to build a department and/or hospital specific quality and safety programme and an appraisal scheme to assess the maturity of the quality improvement system.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.65M | Year: 2012

Ageing is an inexorable homeostatic failure of largely unknown aetiology that leads to increased vulnerability to disease limiting the quality of life in the elderly and creating high costs to the society. Until recently, the daunting complexity of the ageing process, the conspicuous lack of tools to study it, and a dearth of experimentally tractable model systems have greatly hindered any hypothesis-driven reductionist approaches to understand the molecular basis of ageing. Whereas molecular and cellular damage is thought to be a cause of ageing and age-related pathologies, little is known about the molecular events that underlie ageing or determine longevity. A large number of progeroid syndromes that are characterized by an early onset of age-related pathology are linked to inborn defects in genome maintenance thus pointing towards damage in (nuclear) DNA as a major culprit of ageing and age-related pathology. DNA damage fuelled by intrinsic and environmental sources of genotoxic insult and by errors of genome maintenance mechanisms invariably accumulates with advancing age. The outcome of DNA damage is diverse and generally adverse: DNA lesions may physically obstruct essential processes including DNA replication and transcription. In addition, DNA damage activates checkpoint responses that lead to a reduction in cell proliferation potential (cellular senescence) or to an increase in cell death. As a result, depending on the type and severity of DNA injuries and the cellular response to DNA damage, these cellular mechanisms impair organ maintenance and function during ageing. The CodAge ITN proposes an integrated approach in studying the role of Chronic DNA damage in Ageing and age-related pathology.


News Article | December 15, 2016
Site: www.eurekalert.org

The Sobek Foundation honors Professor Ari Waisman for his groundbreaking achievements in research into multiple sclerosis (MS). His research results are regarded as crucial for the understanding of the mechanisms underlying the disease and as a major contribution to the successful development of modern anti-inflammatory and immunomodulatory therapies. Moreover, Waisman's discoveries on the damage to tissues associated with MS may well form the basis of new preventative treatments to limit tissue degeneration. Professor Ari Waisman is Director of the Institute for Molecular Medicine at the University Medical Center of Johannes Gutenberg University Mainz (JGU). His research has enabled "a deeper insight into the role and regulation of inflammatory cells in the brain," the Sobek Foundation argued. Waisman prepared the ground for the analysis of certain harmful cell functions. In doing so, he has made a major contribution to our understanding of the mechanisms of auto-immune diseases, which are the cause of chronic inflammatory tissue damage. Thus he has "contributed to the successful development of modern anti-inflammatory and immunomodulatory therapies." The Sobek Foundation also regards Waisman as being the driving force behind the development of so-called neuro-protective forms of therapy. These are treatments designed to slow down the progression of a neurodegenerative disease and alleviate its symptoms. In concrete terms, these forms of therapy are aimed at counteracting tissue degeneration. Ari Waisman, who was born in Rio de Janeiro, studied biology in Israel and completed his PhD on immuno-biology in Rehovot, Israel. He conducted research under renowned immunologists in Israel and later at the University of Cologne. In 2005, he was appointed Professor of Immunology at the Mainz University Medical Center, where he was section head in the Department of Internal Medicine I for five years. In 2010, he was promoted to the post of Director in the Institute for Molecular Medicine of the Mainz University Medical Center. At the award ceremony for the current Sobek Research Prize, laudator Ulrich Steinbach, Director General in the Ministry of Science, Culture and Art in Baden-Württemberg, highlighted the wide international recognition for Professor Ari Waisman's research achievements. Dr. Ari Waisman has published the results of his research in over 170 scientific papers since 1990, including many successful collaborations with other scientists in the field of MS research. The Research Prize of the Roman, Marga and Mareille Sobek Foundation, this year awarded jointly with AMSEL e.V. and the German Multiple Sclerosis Society (DMSG), has now been awarded 17 times for research into multiple sclerosis research.


Bock F.,University of Cologne | Maruyama K.,Tohoku University | Regenfuss B.,University of Cologne | Hos D.,University of Cologne | And 3 more authors.
Progress in Retinal and Eye Research | Year: 2013

The cornea is one of the few tissues which actively maintain an avascular state, i.e. the absence of blood and lymphatic vessels (corneal [lymph]angiogenic privilege). Nonetheless do several diseases interfere with this privilege and cause pathologic corneal hem- and lymphangiogenesis. The ingrowths of pathologic blood and lymphatic vessels into the cornea not only reduce transparency and thereby visual acuity up to blindness, but also significantly increases the rate of graft rejections after subsequent corneal transplantation. Therefore great interest exists in new strategies to target pathologic corneal (lymph)angiogenesis to promote graft survival. This review gives an overview on the vascular anatomy of the normal ocular surface, on the molecular mechanisms contributing to the corneal (lymph)angiogenic privilege and on the cellular and molecular mechanisms occurring during pathological neovascularization of the cornea. In addition we summarize the current preclinical and clinical evidence for three novel treatment strategies against ocular surface diseases based on targeting pathologic (lymph)angiogenesis: (a) modulation of the immune responses after (corneal) transplantation by targeting pathologic (lymph)angiogenesis prior to and after transplantation, (b) novel concepts against metastasis and recurrence of ocular surface tumors such as malignant melanoma of the conjunctiva by anti(lymph)angiogenic therapy and (c) new ideas on how to target ocular surface inflammatory diseases such as dry eye by targeting conjunctival and corneal lymphatic vessels. Based on compelling preclinical evidence and early data from clinical trials the novel therapeutic concepts of promoting graft survival, inhibiting tumor metastasis and dampening ocular surface inflammation and dry eye disease by targeting (lymph)angiogenesis are on their way to translation into the clinic. © 2013 Elsevier Ltd.


Sela E.,University of Cologne | Pereira R.G.,University of Sao Paulo
Physical Review B - Condensed Matter and Materials Physics | Year: 2011

Motivated by the quasi-one-dimensional antiferromagnet CaV 2O4, we explore spin-orbital systems in which the spin modes are gapped but orbitals are near a macroscopically degenerate classical transition. Within a simplified model we show that gapless orbital liquid phases possessing power-law correlations may occur without the strict condition of a continuous orbital symmetry. For the model proposed for CaV2O 4, we find that an orbital phase with coexisting order parameters emerges from a multicritical point. The effective orbital model consists of zigzag-coupled transverse field Ising chains. The corresponding global phase diagram is constructed using field theory methods and analyzed near the multicritical point with the aid of an exact solution of a zigzag XXZ model. © 2011 American Physical Society.


Cornely O.A.,University of Cologne | Crook D.W.,John Radcliffe Hospital | Esposito R.,Clinica delle Malattie Infettive e Tropicali | Poirier A.,Center Hospitalier Regional Of Trois Rivieres | And 5 more authors.
The Lancet Infectious Diseases | Year: 2012

Background: Infection with Clostridium difficile is the primary infective cause of antibiotic-associated diarrhoea. We aimed to compare efficacy and safety of fidaxomicin and vancomycin to treat patients with C difficile infection in Europe, Canada, and the USA. Methods: In this multicentre, double-blind, randomised, non-inferiority trial, we enrolled patients from 45 sites in Europe and 41 sites in the USA and Canada between April 19, 2007, and Dec 11, 2009. Eligible patients were aged 16 years or older with acute, toxin-positive C difficile infection. Patients were randomly allocated (1:1) to receive oral fidaxomicin (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was clinical cure, defined as resolution of diarrhoea and no further need for treatment. An interactive voice-response system and computer-generated randomisation schedule gave a randomisation number and medication kit number for each patient. Participants and investigators were masked to treatment allocation. Non-inferiority was prespecified with a margin of 10%. Modified intention-to-treat and per-protocol populations were analysed. This study is registered with ClinicalTrials.gov, number NCT00468728. Findings: Of 535 patients enrolled, 270 were assigned fidaxomicin and 265 vancomycin. After 26 patients were excluded, 509 were included in the modified intention-to-treat (mITT) population. 198 (91·7%) of 216 patients in the per-protocol population given fidaxomicin achieved clinical cure, compared with 213 (90·6%) of 235 given vancomycin, meeting the criterion for non-inferiority (one-sided 97·5% CI -4·3%). Non-inferiority was also shown for clinical cure in the mITT population, with 221 (87·7%) of 252 patients given fidaxomicin and 223 (86·8%) of 257 given vancomycin cured (one-sided 97·5% CI -4·9%). In most subgroup analyses of the primary endpoint in the mITT population, outcomes in the two treatment groups did not differ significantly; although patients receiving concomitant antibiotics for other infections had a higher cure rate with fidaxomicin (46 [90·2%] of 51) than with vancomycin (33 [73·3%] of 45; p=0·031). Occurrence of treatment-emergent adverse events did not differ between groups. 20 (7·6%) of 264 patients given at least one dose of fidaxomicin and 17 (6·5%) of 260 given vancomycin died. Interpretation: Fidaxomicin could be an alternative treatment for infection with C difficile, with similar efficacy and safety to vancomycin. Funding: Optimer Pharmaceuticals. © 2012 Elsevier Ltd.


Maier B.,University of Cologne | Wong G.C.L.,California Nano Systems Institute
Trends in Microbiology | Year: 2015

The bacterial type IV pilus (T4P) is a versatile molecular machine with a broad range of functions. Recent advances revealed that the molecular components and the biophysical properties of the machine are well conserved among phylogenetically distant bacterial species. However, its functions are diverse, and include adhesion, motility, and horizontal gene transfer. This review focusses on the role of T4P in surface motility and bacterial interactions. Different species have evolved distinct mechanisms for intracellular coordination of multiple pili and of pili with other motility machines, ranging from physical coordination to biochemical clocks. Coordinated behavior between multiple bacteria on a surface is achieved by active manipulation of surfaces and modulation of pilus-pilus interactions. An emerging picture is that the T4P actively senses and responds to environmental conditions. © 2015 Elsevier Ltd.


Plickert G.,University of Cologne | Frank U.,National University of Ireland | Muller W.A.,University of Heidelberg
International Journal of Developmental Biology | Year: 2012

Hydractinia, a representative marine colonial hydroid, was the first organism in the history of biology in which migratory precursors of germ cells were described and termed "stem cells" (Weismann, 1883). These stem cells, now known as interstitial cells (i-cells), are thought to remain pluripotent throughout their life. Using animals depleted of their own stem cells and repopulated with allogeneic mutant donor stem cells, it was shown that Hydractinia i-cells differentiate into any cell type including epithelial cells and germ cells that express germ line markers such as Vasa, Piwi and Nanos. In Hydra, i-cells also provide germ cells and somatic cells with the exception of epithelial cells. The latter derive from two subpopulations of differentiated epithelial cells with self-renewal capacity. In Hydractinia, forced expression of the Oct4-like transcription factor, Polynem (Pln), in epithelial cells transforms them into stem cells that develop neoplasms. I-cells express the Wnt-receptor Frizzled and are Wnt responsive. Activation of Wnt signaling induces the production of numerous nematocytes (stinging cells) and nerve cells. In parallel, supernumerary tentacles develop. I-cells also express Myc and Nanos. Their misexpression causes severe developmental defects. Hydractinia polyp buds arise from aggregating stem cells, in contrast to Hydra buds, which derive from evaginating epithelial cells. Wnt activation increases budding frequency and the emergence of ectopic head structures. The potential of stem cells to invade neighbors may have provided selection pressure for the evolution of allorecognition and histo-incompatibility. Hence, Hydractinia have now attained the position of a powerful model in stem cell research, axis formation and allorecognition. © UBC Press.


Gellermann J.,Charité - Medical University of Berlin | Weber L.,University of Cologne | Pape L.,Hannover Medical School | Tonshoff B.,University of Heidelberg | And 2 more authors.
Journal of the American Society of Nephrology | Year: 2013

The severe side effects of long-term corticosteroid or cyclosporin A (CsA) therapy complicate the treatment of children with frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). We conducted a randomized, multicenter, open-label, crossover study comparing the efficacy and safety of a 1-year treatmentwithmycophenolate mofetil (MMF; target plasmamycophenolic acid trough level of 1. 5-2. 5 μg/ml) orCsA (target trough level of 80-100 ng/ml) in 60 pediatric patientswith FR-SSNS. We assessed the frequency of relapse as the primary endpoint and evaluated pharmacokinetic profiles (area under the curve [AUC]) after 3 and 6 months of treatment. More relapses per patient per year occurred with MMF thanwith CsA during the first year (P=0. 03), but not during the second year (P=0. 14). No relapses occurred in 85% of patients during CsA therapy and in 64% of patients during MMF therapy (P=0. 06). However, the time without relapse was significantly longer with CsA than withMMF during the first year (P<0. 05), but not during the second year (P=0. 36). In post hoc analysis, patients with low mycophenolic acid exposure (AUC<50 μg·h/ml) experienced 1. 4 relapses per year compared with 0. 27 relapses per year in those with high exposure (AUC>50 μg·h/ml; P<0. 05). There were no significant differences between groups with respect to BP, growth, lipid levels, or adverse events. However, cystatin clearance, estimated GFR, and hemoglobin levels increased significantly with MMF compared with CsA. These results indicate thatMMF is inferior to CsA in preventing relapses in pediatric patients with FR-SSNS, but may be a less nephrotoxic treatment option. Copyright © 2013 by the American Society of Nephrology.


Schafer G.,University of Cologne | Narasimha M.,Tata Institute of Fundamental Research | Vogelsang E.,University of Cologne | Leptin M.,University of Cologne
Journal of Cell Science | Year: 2014

Epithelial-to-mesenchymal transition (EMT) is typically accompanied by downregulation of epithelial (E-) cadherin, and is often additionally accompanied by upregulation of a mesenchymal or neuronal (N-) cadherin. Snail represses transcription of the E-cadherin gene both during normal development and during tumour spreading. The formation of the mesodermal germ layer in Drosophila, considered a paradigm of a developmental EMT, is associated with Snailmediated repression of E-cadherin and the upregulation of Ncadherin. By using genetic manipulation to remove or overexpress the cadherins, we show here that the complementarity of cadherin expression is not necessary for the segregation or the dispersal of the mesodermal germ layer in Drosophila. However, we discover different effects of E- and N-cadherin on the differentiation of subsets of mesodermal derivatives, which depend on Wingless signalling from the ectoderm, indicating differing abilities of E- and Ncadherin to bind to and sequester the common junctional and signalling effector β-catenin. These results suggest that the downregulation of E-cadherin in the mesoderm might be required to facilitate optimal levels of Wingless signalling. © 2014. Published by The Company of Biologists Ltd.


Tian C.,University of Cologne | Tian C.,Tsinghua University | Altland A.,University of Cologne | Garst M.,University of Cologne
Physical Review Letters | Year: 2011

We present the first microscopic theory of transport in quasiperiodically driven environments ("kicked rotors"), as realized in recent atom optic experiments. We find that the behavior of these systems depends sensitively on the value of a dimensionless Planck constant h̃: for irrational values of h̃/(4π) they fall into the universality class of disordered electronic systems and we describe the corresponding localization phenomena. In contrast, for rational values the rotor-Anderson insulator acquires an infinite (static) conductivity and turns into a "supermetal. " We discuss the ensuing possibility of a metal-supermetal quantum phase transition. © 2011 American Physical Society.


Cejnar P.,Charles University | Jolie J.,University of Cologne | Casten R.F.,Yale University
Reviews of Modern Physics | Year: 2010

Signatures of criticality in the evolution of the nuclear ground-state shapes across the N×Z plane are discussed. Attention is paid to specific data indicating sudden structural changes in various isotopic and isotonic chains of medium-mass and heavy even-even nuclei, as well as to diverse theoretical aspects of the models used to describe these changes. The interacting boson model and the geometric collective model, in particular, are discussed in detail, the former providing global predictions for the evolution of collective observables in nuclei between closed shells and the latter yielding a parameter-efficient description of nuclei at the critical points of shape transitions. Some issues related to the mechanism of first- and second-order quantum phase transitions in general many-body systems are also outlined. © 2010 The American Physical Society.


Erren T.C.,University of Cologne | Reiter R.J.,University of Texas Health Science Center at San Antonio
Naturwissenschaften | Year: 2013

In this Concepts & Synthesis paper, we expand the definition of chronodisruption in humans by proposing that it can be operationalized as the split nexus of internal and external times. With this premise, we suggest how chronotype may be used as a temporal marker (chronomarker) of exposure to chronodisruption in studies of cancer, and beyond, offer cancer risk predictions for observational research on the basis of a chronotype-related hypothesis and corollary, and point to first empirical data in humans. In an a priori way, we examine possible outcomes and perspectives for preventive measures following from our rationale and the suggested chronobiology-driven studies and close with overall advances of chronodisruption research. © 2013 Springer-Verlag Berlin Heidelberg.


Wang Q.,University of Rochester | Uhlirova M.,University of Cologne | Bohmann D.,University of Rochester
Developmental Cell | Year: 2010

FGF signaling is a central regulator of branching morphogenesis processes, such as angiogenesis or the development of branched organs including lung, kidney, and mammary gland. The formation of the air sac during the development of the Drosophila tracheal system is a powerful genetic model to investigate how FGF signaling patterns such emerging structures. This article describes the characterization of the Drosophila matrix metalloprotease Mmp2 as an extracellular inhibitor of FGF morphogenetic function. Mmp2 expression in the developing air sac is controlled by the Drosophila FGF homolog Branchless and then participates in a negative feedback and lateral inhibition mechanism that defines the precise pattern of FGF signaling. The signaling function for MMPs described here may not be limited to branching morphogenesis processes. © 2010 Elsevier Inc. All rights reserved.


Tompkins A.M.,Abdus Salam International Center For Theoretical Physics | Ermert V.,University of Cologne
Malaria Journal | Year: 2013

Background: The relative roles of climate variability and population related effects in malaria transmission could be better understood if regional-scale dynamical malaria models could account for these factors. Methods. A new dynamical community malaria model is introduced that accounts for the temperature and rainfall influences on the parasite and vector life cycles which are finely resolved in order to correctly represent the delay between the rains and the malaria season. The rainfall drives a simple but physically based representation of the surface hydrology. The model accounts for the population density in the calculation of daily biting rates. Results: Model simulations of entomological inoculation rate and circumsporozoite protein rate compare well to data from field studies from a wide range of locations in West Africa that encompass both seasonal endemic and epidemic fringe areas. A focus on Bobo-Dioulasso shows the ability of the model to represent the differences in transmission rates between rural and peri-urban areas in addition to the seasonality of malaria. Fine spatial resolution regional integrations for Eastern Africa reproduce the malaria atlas project (MAP) spatial distribution of the parasite ratio, and integrations for West and Eastern Africa show that the model grossly reproduces the reduction in parasite ratio as a function of population density observed in a large number of field surveys, although it underestimates malaria prevalence at high densities probably due to the neglect of population migration. Conclusions: A new dynamical community malaria model is publicly available that accounts for climate and population density to simulate malaria transmission on a regional scale. The model structure facilitates future development to incorporate migration, immunity and interventions. © 2013 Tompkins and Ermert; licensee BioMed Central Ltd.


Osman C.,University of Cologne | Haag M.,University of Heidelberg | Wieland F.T.,University of Heidelberg | Brugger B.,University of Heidelberg | And 2 more authors.
EMBO Journal | Year: 2010

Cardiolipin (CL), a unique dimeric phosphoglycerolipid predominantly present in mitochondrial membranes, has pivotal functions for the cellular energy metabolism, mitochondrial dynamics and the initiation of apoptotic pathways. Perturbations in the mitochondrial CL metabolism cause cardiomyopathy in Barth syndrome. Here, we identify a novel phosphatase in the mitochondrial matrix space, Gep4, and demonstrate that it dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol, an essential step during CL biosynthesis. Expression of a mitochondrially targeted variant of Escherichia coli phosphatase PgpA restores CL levels in Gep4-deficient cells, indicating functional conservation. A genetic epistasis analysis combined with the identification of intermediates of CL biosynthesis allowed us to integrate Gep4 in the CL-biosynthetic pathway and assign an essential function during early steps of CL synthesis to Tam41, which has previously been shown to be essential for the maintenance of normal CL levels. Our experiments provide the framework for the further dissection of mechanisms that are required for accumulation and maintenance of CL levels in mitochondria. © 2010 European Molecular Biology Organization.


Dunning D.,Cornell University | Anderson J.E.,Cornell University | Schlosser T.,University of Cologne | Ehlebracht D.,University of Cologne | Fetchenhauer D.,University of Cologne
Journal of Personality and Social Psychology | Year: 2014

Trust is essential for a secure and flourishing social life, but many economic and philosophical approaches argue that rational people should never extend it, in particular to strangers they will never encounter again. Emerging data on the trust game, a laboratory economic exchange, suggests that people trust strangers excessively (i.e., far more than their tolerance for risk and cynical views of their peers should allow). What produces this puzzling "excess" of trust? We argue that people trust due to a norm mandating that they show respect for the other person's character, presuming the other person has sufficient integrity and goodwill even if they do not believe it privately. Six studies provided converging evidence that decisions to trust follow the logic of norms. Trusting others is what people think they should do, and the emotions associated with fulfilling a social duty or responsibility (e.g., guilt, anxiety) account for at least a significant proportion of the excessive trust observed. Regarding the specific norm in play, trust rates collapse when respect for the other person's character is eliminated as an issue. © 2014 American Psychological Association.


Schacht E.,ZORG Zurich Osteoporosis Research Group | Ringe J.D.,University of Cologne
Rheumatology International | Year: 2012

We investigated the effect of daily therapy with 1 mcg alfacalcidol (Doss ®-TEVA/AWD-pharma) on muscle power, muscle function, balance performance and fear of falls in an open, multi-centered, uncontrolled, prospective study on a cohort of patients with reduced bone mass. Among the 2,097 participants, 87.1% were post-menopausal women and 12.9% were men. Mean age was 74.8 years and mean body mass index (BMI) 26.3 kg/m2. A total of 75.3% of the study population had osteoporosis, 81% a diagnosis of "increased risk of falls" and 70.1% had a creatinine clearance (CrCl) of <65 ml/min. Participants underwent muscle function and muscle power tests at onset and after 3 and 6 months: the timed up and go test (TUG) and the chair rising test (CRT). At baseline and after 6 months, participants performed the tandem gait test (TGT) and filled out a questionnaire evaluating fear of falling. Successful performance in the muscle tests is associated with a significantly lower risk of falls and non-vertebral fractures in elderly patients (successful test performance: TUG ≤ 10 s (sec), CRT ≤ 10 s, TGT ≥ 8 steps). A significant improvement in the performance of the two muscle tests was proved already after 3 months of treatment with alfacalcidol and further increased by the end of the therapeutic intervention. There were significant increases in the number of participants able to successfully perform the tests: 24.6% at baseline and 46.3% at the end of trial for the TUG (P < 0.0001) and 21.7% at baseline and 44.2% at the end for the CRT test (P = 0.0001). The mean time used for the TUG was decreased by 3.0 s from the average onset value of 17.0 s and by 3.1 s from the initial average 16.5 s for the CRT. The percentage of participants able to perform the balance test (TGT) increased from 36.0% at onset to 58.6% at the end of the trial (P < 0.0001). An increased fear of falling was reduced by the end of the study in 74.4% of the patients. Throughout the study, there were 26 adverse drug reactions in 11 out of 2,097 patients (incidence 0.52%). No serious adverse drug reactions and no cases of hypercalcemia were documented. We conclude that treatment with alfacalcidol is safe, increases muscle power, muscle function and balance and reduces fear of falls. The significant improvement in the three muscle and balance tests and fear of falls may have a preventative effect on falls and fractures. We suggest that the quantitative risk tests used in this study could be reliable surrogate parameters for the risk of falls and fractures in elderly patients. © 2010 Springer-Verlag.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: SPA.2009.3.5.01 | Award Amount: 345.76K | Year: 2009

The main objective of the SP4ESP project is to develop a new approach for the procurement of joint ESA/ EU space programmes. It will constitute the first ever attempt for a concentrated, creative and coherent study in this field. The one year project will elaborate a set of mandatory and facultative criteria for a new European procurement regulation. It will solve the intrinsic conflict of the respective procurement rules. EC rules based on fair competition collide with ESA rules based on the principle of geographic return. This conflict is the main obstacle to the implementation of the ESA/ EU cooperation and their European Space Policy (ESP). Its solution will not only facilitate further programme collaboration. Leading eventually to a third way, also the political cooperation will be fostered. The study is divided into three main parts. Firstly, the current regulatory state of the above mentioned procurement rules for EU and ESA financed programs will be assessed. The experience of new EU and ESA Member States in the transition to procurement rules will provide practical impetus. Secondly, the space market industry will be analysed. Together with proponent opinions of stakeholders this will provide the necessary factual background for the development of a space industry specific procurement law. Thirdly, based on the findings of the first and second part, a third way will be developed. This third way will be based on comprehensive comparisons with similar industries and should account for proponent benefits of both procurement types. At the end, a set of modules will be formulated. With these, the relevant organs will be enabled to formulate a single common approach. This approach will be specifically designed for the space industry. The pragmatic solution of the biggest legal conflict will give the ESP fresh impetus for future collaborative projects to come.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SSH-2007-4.3-02 | Award Amount: 1.98M | Year: 2009

This project seeks to understand the EUs contribution to effective multilateralism. We consider evolving and conflicting (culturally-defined) meanings of multilateralism; its uncertain future on a global scale; the EU system of external relations in the light of the Reform Treaty and its implications for the Unions ability to shape multilateralism; and whether and how multilateralism is compatible with the EUs shift towards inter-regionalism and strategic partnerships. Arguably, the EU has done more than most of its partners to acknowledge new global challenges and rising demand for multilateralism. Its own positions frequently become focal points for international negotiations on conflict resolution. Nevertheless, essential questions remain unanswered about the viability of a European way of multilateralism. Can multilateralism be defined in a way that transcends divisions within as well as beyond Europe, between states, nations and cultures, strong and weak, rich and poor? Is there a concept of multilateralism that overcomes theoretical schisms? Is it possible for the EU or its member states (or anyone else) to define and pursue a selfless, benign, credible doctrine of multilateralism, as opposed to one that serves its own interests? The problem of matching supply to demand for effective multilateralism will be the leitmotif for MERCURY, a research programme that will elaborate and clarify forms of multilateralism, develop specific theses about the EUs contribution to multilateralism, and test them in line with best scientific practice. Its remit extends to the interactions of the EU and its member states with regions outside Europe, strategic partners, and global organisations. It is interdisciplinary, drawing on expertise in law, politics, economics, and international relations. It advances a clear intellectual agenda to explore, explain, and evaluate different conceptions of multilateralism while aiming to achieve practical policy relevance.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 2.84M | Year: 2009

Considerable resources are devoted to fighting cancer throughout Europe, yet these efforts are not producing the results that health practitioners and citizens might expect. This is partly due to the fragmentation and duplication of research efforts within Member states and the lack of co-ordination at European level. However it can also be attributed to the need to retain and most importantly develop researchers within the EU who have the research skills required to make a real contribution to cancer treatment. The need for quality researchers is particularly acute within the emerging interdisciplinary field of Adoptive Cell Therapy. This promising advance in cancer treatment is based on the exploitation of tumour immunology and genetic technology and built on the specific ideas and techniques originally proposed by the European and Israeli scientists who are members of the ATTRACT network. To facilitate further development within the field of adoptive cell therapy, it is crucial that a co-ordinated and intersectoral approach (combining both the research community and industry) is taken, an approach that broadens the portfolio of skills currently retained within the EU research community. Through the integration Europes undisputed leaders in the field of adoptive cell therapy established in the 2005 FP6 ATTACK project, the ATTRACT network aims to foster the development of a pool of ESRs and ERs by equipping them with the multidisciplinary and complementary skills needed to not only initiate further advances in the field but to become future leaders within the field of adoptive cell therapy for cancer treatment. Such skills are global in demand making each researcher a highly desirable candidate for employment and very mobile across the different career domains.


Grant
Agency: Cordis | Branch: FP7 | Program: CPCSA | Phase: INFRA-2011-1.2.2. | Award Amount: 3.68M | Year: 2011

The EU nowadays witnesses increasing demands with regard to chemical safety. In particular, animal-based test models need to be replaced preferably by robust, non-animal assays in vitro/in silico which better predict human toxicity in vivo, are less costly, and are socially better acceptable. Consumers and patients health will benefit and competitiveness of EUs chemical manufacturing industry will be increased. For developing such assays, FP6/FP7 Research Programmes are exploiting the revenues of data-dense genomics technologies. However, till date, there is no infrastructure foreseen which aims at capturing all data produced by toxicogenomics (TGX) projects, in a standardized, harmonized and sustainable manner. Data may thus evaporate. The lack of such an infrastructure also prevents innovative breakthroughs from meta-analyses of joint databases and systems modeling.\nDriven by these needs of the TGX research community, diXa will focus on networking activities, for building a web-based, openly accessible and sustainable e-infrastructure for capturing TGX data, and for linking this to available data bases holding chemico/physico/toxicological information, and to data bases on molecular medicine, thus crossing traditional borders between scientific disciplines and reaching out to other research communities. To advance data sharing, diXa will ensure clear communication channels with and deliver commonly agreed core service support to the TGX research community, by providing SOPs for seamless data sharing, and by offering quality assessments and newly developed tools and techniques for data management, all supported by hands-on training. Through its joint research initiative, by using data available from its data infrastructure, diXa will demonstrate the feasibility of its approach by performing cross-platform integrative statistical analyses, and cross-study meta-analyses, to create a systems model for predicting chemical-induced liver injury.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 2.63M | Year: 2010

The Initial Training Network Integrated Training Programme for Analysis, Assessment and Advice on EUs External Action and its Institutional Architecture (EXACT) aims at preparing 12 Early Stage Researchers (ESR) for professional and academic careers in universities as well as in the public and private sector in academically based consulting for policy makers. The training network focuses its research on major current and future challenges of the EU in the fields of Commercial Policy, Common Foreign and Security Policy, Common European Defence Policy and Development Cooperation (e.g. EU crisis management in Georgia). The training provided through EXACT intends to bridge the gap between Ph.D. training within the academic world on the one hand and the down-to-earth need of potential employers in consulting or advisory circles on the other. Therefore, the project pursues an integrated two track curriculum that involves three universities and six think tanks: The scientific track concentrates on academic training leading to a Ph.D. degree, track II focuses on the training of professional skills. Given the growing market for academically trained EU experts in both public and private sectors, the integrated curriculum develops a triple A catalogue of skills: theory-led Analysis and Assessment of potential future scenarios in the field of EUs external action and Advice for strategies. The early stage researchers will attend a 36 month training programme including local and network-wide activities (e.g. individual research projects and Network Seminars) provided by universities and think tanks in the network. The early stage researchers will be given the opportunity to obtain a double PhD degree (co-tutelle) from two participating universities as well as the EXACT Certificate issued by all participating organisations.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.96M | Year: 2012

One of achievements of developed societies has been the remarkable extension of human lifespan. In the upcoming decades the number of Europeans with advanced age will increase dramatically. It is evident that age-associated diseases will become much more prevalent. This poses challenges for society but also opportunities for commercial enterprises that develop strategies to combat deleterious consequences of ageing. However, our understanding of the mechanisms that contribute to ageing and its associated pathologies remain superficial and therapeutic or nutritional interventions unexplored. The complex nature of ageing as a scientific field calls for a multidisciplinary approach where teams of academic and industrial researchers join forces. The objective of this Network is to provide training in the biology of ageing to 11 Early Stage and 4 Experienced Researchers. We have assembled a premier group of scientists that focus their activities on the molecular mechanisms that underlie ageing, with an emphasis on how maintenance of genomic integrity in self-renewing tissues is preserved under different metabolic rates. The key aim of this training program is the elucidation of the molecular pathway by which intrinsic genomic integrity can be modified by the extrinsic rate of metabolism. Our Network consists of 10 full and 2 associated partners, representing 7 Member states and Switzerland and Canada, and include 4 commercial enterprises. Multiple complementary training schemes have been implemented in the Network. These include specific research projects (including multiple academic and industrial secondments), a variety of dedicated courses organized by the academic partners of the Network, and finally, training organized by the industrial partners of the Network. Trainees will become experts in the multidisciplinary field of ageing, and are expected to constitute future leaders in the field of ageing science and shape commercial activities in this realm.


Grant
Agency: Cordis | Branch: FP7 | Program: ERC-AG | Phase: ERC-AG-SH6 | Award Amount: 2.50M | Year: 2014

Rome was connected to its Mediterranean provinces by commercial routes articulated through networks of ports acting as poly-functional nodes. Ships, people and goods moved along these, drawing the micro-regions of the Mediterranean into closer economic and commercial relationships with the City. Central to the success of these networks were the major ports through which were channelled major commercial flows moving between Rome and its maritime hub at Portus, and its Mediterranean provinces, and their relationships to lesser regional and anchorages. All of them can be described in terms of loosely configured port-systems that ensured the movement of ships and their cargoes around the Mediterranean. Some of these, particularly in the eastern Mediterranean, can be traced back to the Hellenistic or earlier periods. ROMP will address specific questions relating to the capacities of and inter-connections between a range of 30 ports in ways that will allow us to better understand their role in helping ensure the cohesion and integrity of the Roman Mediterranean during the imperial era. These concern (1) the layout of Roman ports, (2) the organization of commercial activity focused at them, (3) hierarchies of ports, and (4) pan-Mediterranean commercial and social connections between ports. In addressing them, the project will apply suites of existing techniques in archaeology, ancient history and palaeo-environmental studies to a range of ports. It is an approach that builds upon the PIs belief in the value of integrating archaeological techniques and historical approaches to the study of the past, and the interpretation of individual port sites within a broader Mediterranean context. In so doing, the project moves beyond the state of the art in port studies, and raises issues that are key to better understanding the unprecedented degree of economic, social and political convergence that was achieved by the Roman empire during the imperial era.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-15-2015 | Award Amount: 8.38M | Year: 2016

Osteogenesis imperfecta (OI) is, in its severe forms, a devastating inherited disorder characterised by brittle bones. A person with severe OI is affected throughout their lifetime with repeated, multiple fractures, considerable pain and handicap. There is no curative or effective treatment for OI. Our preclinical studies and initial clinical cases have demonstrated that transplantation of fetal mesenchymal stem cells (MSC) is a promising approach for treatment of OI. We receive regular requests for MSC transplantation from patients and their physicians; patient organisations support our approach. The principal objective of the BOOSTB4 project is to conduct a Phase I/II clinical trial of the safety and efficacy of pre- and/or postnatal MSC transplantation in the severest forms of OI (type III, severe type IV). Transplantation before birth at the onset of disease should lead to greater efficacy and engraftment with less rejection than transplantation after birth. Postnatal transplantation will be evaluated in cases where prenatal diagnosis was not made. The trials primary outcome is safety; secondary outcomes relate to efficacy (fracture frequency, growth, bone mineral density and quality of life). All patients will undergo molecular diagnosis to confirm OI before inclusion in the trial. Non-invasive prenatal diagnosis will be developed and validated. The BOOSTB4 consortium is led by experts in MSC, prenatal therapy and OI at the Karolinska Institutet (KI), which will also lead the international multicentre trial; five additional EU centres of excellence are included. Ethical and regulatory applications are underway to conduct this clinical trial. These are facilitated by the ethical and regulatory approvals for prenatal MSC transplantation in 10 cases of OI that have already been granted at KI. Successful prenatal transplantation represents a major step forward in the management of patients with severe OI, and beyond, to a range of other inherited birth defects.


News Article | March 4, 2016
Site: www.nature.com

When psychologist Courtenay Norbury came across a paper this week that had similar conclusions to research she published 12 years ago, she turned to social media with a question. Norbury, who studies children with autism spectrum disorders at University College London, tweeted: Dorothy Bishop, a developmental neuropsychologist at the University of Oxford, UK, who helped to write a report on how to improve the reliability of biomedical research, tweeted in response that some fields can get stuck on the same research questions: The problem of irreproducibility in science has gained widespread attention, but one aspect that is discussed less often is how to find the right balance between replicating findings and moving a field forward from well-established ones. Norbury has for years reported that people who have autism and poor language skills can find it difficult to make inferences, decipher ambiguous phrases and understand metaphors or jokes. She has also shown that this is not necessarily the case for people with autism who are more linguistically capable1, 2. The latest study, published in Research in Developmental Disabilities on 18 February3, mirrored the work by suggesting that people with autism who have good language skills do well on such tasks. Psychologists Melanie Eberhardt at the University of Cologne in Germany and Aparna Nadig at McGill University in Montreal, Canada, authors of the latest study, acknowledge that this evidence is clear and convincing for researchers in this area, but say: “We find that unfortunately there are many lay, professional and academic circles where this result is still not understood.” They add, “Therefore we found it important to add to the convergent evidence on this question.” “Replication is important but it would be nice sometimes to take a bigger leap forward,” says Norbury. She adds that the next “obvious” step in this research involves intervention, which is challenging to do. “But I’d love to start thinking of how to overcome these obstacles, rather than just repeatedly demonstrating that language impairment has negative impacts for children with autism,” she says. Brett Buttliere, a research assistant at the Leibniz Institute for Knowledge Media in Tübingen, Germany, tweeted: “It is obvious that not publishing when something doesn’t work is bad, but so is doing the same thing over and over again without learning something new,” Buttliere said in an interview. Virginia Barbour, executive officer of the Australasian Open Access Support Group in Brisbane, Australia, posted her observations: In response, Bishop later tweeted a link to a paper published in The Lancet that looked at reducing waste in biomedical research4. The 2014 article said that many studies are done without referencing systematic reviews of the literature, which leads to waste. Paul Glasziou, a clinician and researcher at Bond University in Queensland, Australia, who is a co-author of the Lancet paper, says that the bar for reproducibility can be set at different heights. For example, he says, the US Food and Drug Administration requires a minimum of two positive randomized control trials to show effectiveness of a new drug — a rule that Glasziou says is “reasonable” as long as the trials are “well done and adequately powered”. He adds, however, that clinical studies are usually repeated more than once, pointing to one analysis of systematic reviews that found that a review cited on average 16 similar papers5. One issue could be that researchers are unaware of similar studies. For example, a study of 1,523 clinical-trial reports published between 1963 and 2004 found that, on average, each report cited less than 25% of the previous similar trials that were relevant6. Barbour added in an interview that one way of deciding whether a claim has been reproduced enough could be to analyse reviews and meta-analyses of studies from the same field. Using novelty as a criterion for publication in journals may solve the problem, notes Norbury, who is an editor of the Journal of Child Psychology and Psychiatry. By contrast, many researchers have called for journals to de-emphasize new findings and instead publish numerous replications; Norbury says that she agrees “to a certain extent”. But, she adds, “my heart sometimes sinks when I see yet another paper exploring what I consider to be well-trodden ground. I’m not looking for ‘sexy’ findings, but I am looking for something that has the potential to change practice or move the field forward.”


PORTLAND, Ore., Nov. 02, 2016 (GLOBE NEWSWIRE) -- Entia Biosciences, Inc. (OTCQB:ERGO) has been informed that the European Patent Office has granted European Patent Number 1 761 784 with the title “Identification of Ergothioneine Transporter and Therapeutic Uses Thereof” of the University of Cologne, Germany.  Through a predecessor entity, Entia exclusively licensed this patent, its European Application (Number 5745195.7-2401) and the technology associated therewith in a license agreement with the University of Cologne in December of 2008. Previous companion patents for the same inventions were granted in the United States, Canada and Israel and were exclusively licensed to Entia under the aforementioned license. “The grant of this European patent further strengthens our exclusive intellectual property position in this technology across a significant geographic market,” stated Marvin S. Hausman MD, Entia Chief Science and Technology Officer.  “Through our soon-to-be-introduced medical food products, we look forward bringing this technology to bear on chronic kidney disease, psoriasis, Parkinson’s disease, multiple sclerosis and autism.” Entia (OTCQB:ERGO) discovers, scientifically validates, develops and markets patented, pharmaceutical-grade organic compounds that include its revolutionary ErgoD2®.  The Company is a leading authority on the clinical effects of oxidative stress, iron-related disorders and free radical reactions in mammals; it is bringing this expertise to the nutraceutical and medical foods markets.  Entia also develops and markets health-related cosmeceuticals. Entia Biosciences, Inc. is headquartered in Sherwood, Oregon, a Portland suburb. Any statements contained in this press release that relate to future plans, events or performance are forward-looking statements that involve risks and uncertainties including, but not limited to, the risks associated with the transaction described in this press release, and other risks identified in the filings by Entia Biosciences, Inc. with the Securities and Exchange Commission.  Further information on risks faced by the Company and its shareholders are detailed in the Form 10-K for the year ended December 31, 2015 and in its subsequent Quarterly Reports on Form 10-Q.  These filings are or will become available on a website maintained by the Securities and Exchange Commission at http://www.sec.gov.  The information contained in this press release is accurate as of the date indicated.  Actual results, events or performance may differ materially.  Entia does not undertake any obligation to publicly release the result of any revision to these forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.


PORTLAND, Ore., Nov. 02, 2016 (GLOBE NEWSWIRE) -- Entia Biosciences, Inc. (OTCQB:ERGO) has been informed that the European Patent Office has granted European Patent Number 1 761 784 with the title “Identification of Ergothioneine Transporter and Therapeutic Uses Thereof” of the University of Cologne, Germany.  Through a predecessor entity, Entia exclusively licensed this patent, its European Application (Number 5745195.7-2401) and the technology associated therewith in a license agreement with the University of Cologne in December of 2008. Previous companion patents for the same inventions were granted in the United States, Canada and Israel and were exclusively licensed to Entia under the aforementioned license. “The grant of this European patent further strengthens our exclusive intellectual property position in this technology across a significant geographic market,” stated Marvin S. Hausman MD, Entia Chief Science and Technology Officer.  “Through our soon-to-be-introduced medical food products, we look forward bringing this technology to bear on chronic kidney disease, psoriasis, Parkinson’s disease, multiple sclerosis and autism.” Entia (OTCQB:ERGO) discovers, scientifically validates, develops and markets patented, pharmaceutical-grade organic compounds that include its revolutionary ErgoD2®.  The Company is a leading authority on the clinical effects of oxidative stress, iron-related disorders and free radical reactions in mammals; it is bringing this expertise to the nutraceutical and medical foods markets.  Entia also develops and markets health-related cosmeceuticals. Entia Biosciences, Inc. is headquartered in Sherwood, Oregon, a Portland suburb. Any statements contained in this press release that relate to future plans, events or performance are forward-looking statements that involve risks and uncertainties including, but not limited to, the risks associated with the transaction described in this press release, and other risks identified in the filings by Entia Biosciences, Inc. with the Securities and Exchange Commission.  Further information on risks faced by the Company and its shareholders are detailed in the Form 10-K for the year ended December 31, 2015 and in its subsequent Quarterly Reports on Form 10-Q.  These filings are or will become available on a website maintained by the Securities and Exchange Commission at http://www.sec.gov.  The information contained in this press release is accurate as of the date indicated.  Actual results, events or performance may differ materially.  Entia does not undertake any obligation to publicly release the result of any revision to these forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.


PORTLAND, Ore., Nov. 02, 2016 (GLOBE NEWSWIRE) -- Entia Biosciences, Inc. (OTCQB:ERGO) has been informed that the European Patent Office has granted European Patent Number 1 761 784 with the title “Identification of Ergothioneine Transporter and Therapeutic Uses Thereof” of the University of Cologne, Germany.  Through a predecessor entity, Entia exclusively licensed this patent, its European Application (Number 5745195.7-2401) and the technology associated therewith in a license agreement with the University of Cologne in December of 2008. Previous companion patents for the same inventions were granted in the United States, Canada and Israel and were exclusively licensed to Entia under the aforementioned license. “The grant of this European patent further strengthens our exclusive intellectual property position in this technology across a significant geographic market,” stated Marvin S. Hausman MD, Entia Chief Science and Technology Officer.  “Through our soon-to-be-introduced medical food products, we look forward bringing this technology to bear on chronic kidney disease, psoriasis, Parkinson’s disease, multiple sclerosis and autism.” Entia (OTCQB:ERGO) discovers, scientifically validates, develops and markets patented, pharmaceutical-grade organic compounds that include its revolutionary ErgoD2®.  The Company is a leading authority on the clinical effects of oxidative stress, iron-related disorders and free radical reactions in mammals; it is bringing this expertise to the nutraceutical and medical foods markets.  Entia also develops and markets health-related cosmeceuticals. Entia Biosciences, Inc. is headquartered in Sherwood, Oregon, a Portland suburb. Any statements contained in this press release that relate to future plans, events or performance are forward-looking statements that involve risks and uncertainties including, but not limited to, the risks associated with the transaction described in this press release, and other risks identified in the filings by Entia Biosciences, Inc. with the Securities and Exchange Commission.  Further information on risks faced by the Company and its shareholders are detailed in the Form 10-K for the year ended December 31, 2015 and in its subsequent Quarterly Reports on Form 10-Q.  These filings are or will become available on a website maintained by the Securities and Exchange Commission at http://www.sec.gov.  The information contained in this press release is accurate as of the date indicated.  Actual results, events or performance may differ materially.  Entia does not undertake any obligation to publicly release the result of any revision to these forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.


PORTLAND, Ore., Nov. 02, 2016 (GLOBE NEWSWIRE) -- Entia Biosciences, Inc. (OTCQB:ERGO) has been informed that the European Patent Office has granted European Patent Number 1 761 784 with the title “Identification of Ergothioneine Transporter and Therapeutic Uses Thereof” of the University of Cologne, Germany.  Through a predecessor entity, Entia exclusively licensed this patent, its European Application (Number 5745195.7-2401) and the technology associated therewith in a license agreement with the University of Cologne in December of 2008. Previous companion patents for the same inventions were granted in the United States, Canada and Israel and were exclusively licensed to Entia under the aforementioned license. “The grant of this European patent further strengthens our exclusive intellectual property position in this technology across a significant geographic market,” stated Marvin S. Hausman MD, Entia Chief Science and Technology Officer.  “Through our soon-to-be-introduced medical food products, we look forward bringing this technology to bear on chronic kidney disease, psoriasis, Parkinson’s disease, multiple sclerosis and autism.” Entia (OTCQB:ERGO) discovers, scientifically validates, develops and markets patented, pharmaceutical-grade organic compounds that include its revolutionary ErgoD2®.  The Company is a leading authority on the clinical effects of oxidative stress, iron-related disorders and free radical reactions in mammals; it is bringing this expertise to the nutraceutical and medical foods markets.  Entia also develops and markets health-related cosmeceuticals. Entia Biosciences, Inc. is headquartered in Sherwood, Oregon, a Portland suburb. Any statements contained in this press release that relate to future plans, events or performance are forward-looking statements that involve risks and uncertainties including, but not limited to, the risks associated with the transaction described in this press release, and other risks identified in the filings by Entia Biosciences, Inc. with the Securities and Exchange Commission.  Further information on risks faced by the Company and its shareholders are detailed in the Form 10-K for the year ended December 31, 2015 and in its subsequent Quarterly Reports on Form 10-Q.  These filings are or will become available on a website maintained by the Securities and Exchange Commission at http://www.sec.gov.  The information contained in this press release is accurate as of the date indicated.  Actual results, events or performance may differ materially.  Entia does not undertake any obligation to publicly release the result of any revision to these forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.


PORTLAND, Ore., Nov. 02, 2016 (GLOBE NEWSWIRE) -- Entia Biosciences, Inc. (OTCQB:ERGO) has been informed that the European Patent Office has granted European Patent Number 1 761 784 with the title “Identification of Ergothioneine Transporter and Therapeutic Uses Thereof” of the University of Cologne, Germany.  Through a predecessor entity, Entia exclusively licensed this patent, its European Application (Number 5745195.7-2401) and the technology associated therewith in a license agreement with the University of Cologne in December of 2008. Previous companion patents for the same inventions were granted in the United States, Canada and Israel and were exclusively licensed to Entia under the aforementioned license. “The grant of this European patent further strengthens our exclusive intellectual property position in this technology across a significant geographic market,” stated Marvin S. Hausman MD, Entia Chief Science and Technology Officer.  “Through our soon-to-be-introduced medical food products, we look forward bringing this technology to bear on chronic kidney disease, psoriasis, Parkinson’s disease, multiple sclerosis and autism.” Entia (OTCQB:ERGO) discovers, scientifically validates, develops and markets patented, pharmaceutical-grade organic compounds that include its revolutionary ErgoD2®.  The Company is a leading authority on the clinical effects of oxidative stress, iron-related disorders and free radical reactions in mammals; it is bringing this expertise to the nutraceutical and medical foods markets.  Entia also develops and markets health-related cosmeceuticals. Entia Biosciences, Inc. is headquartered in Sherwood, Oregon, a Portland suburb. Any statements contained in this press release that relate to future plans, events or performance are forward-looking statements that involve risks and uncertainties including, but not limited to, the risks associated with the transaction described in this press release, and other risks identified in the filings by Entia Biosciences, Inc. with the Securities and Exchange Commission.  Further information on risks faced by the Company and its shareholders are detailed in the Form 10-K for the year ended December 31, 2015 and in its subsequent Quarterly Reports on Form 10-Q.  These filings are or will become available on a website maintained by the Securities and Exchange Commission at http://www.sec.gov.  The information contained in this press release is accurate as of the date indicated.  Actual results, events or performance may differ materially.  Entia does not undertake any obligation to publicly release the result of any revision to these forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.


Dejanovic B.,University of Cologne | Dejanovic B.,Max Delbrück Center for Molecular Medicine
PLoS biology | Year: 2014

Postsynaptic scaffolding proteins regulate coordinated neurotransmission by anchoring and clustering receptors and adhesion molecules. Gephyrin is the major instructive molecule at inhibitory synapses, where it clusters glycine as well as major subsets of GABA type A receptors (GABAARs). Here, we identified palmitoylation of gephyrin as an important mechanism of strengthening GABAergic synaptic transmission, which is regulated by GABAAR activity. We mapped palmitoylation to Cys212 and Cys284, which are critical for both association of gephyrin with the postsynaptic membrane and gephyrin clustering. We identified DHHC-12 as the principal palmitoyl acyltransferase that palmitoylates gephyrin. Furthermore, gephyrin pamitoylation potentiated GABAergic synaptic transmission, as evidenced by an increased amplitude of miniature inhibitory postsynaptic currents. Consistently, inhibiting gephyrin palmitoylation either pharmacologically or by expression of palmitoylation-deficient gephyrin reduced the gephyrin cluster size. In aggregate, our study reveals that palmitoylation of gephyrin by DHHC-12 contributes to dynamic and functional modulation of GABAergic synapses.


Brinkmann K.,Center for Molecular Medicine Cologne | Brinkmann K.,University of Cologne | Kashkar H.,Center for Molecular Medicine Cologne | Kashkar H.,University of Cologne
Cell Death and Disease | Year: 2014

Acquired resistance toward apoptosis represents one of the hallmarks of human cancer and a major cause of the inefficacy of most anticancer treatment regimens. Based on its ability to inhibit apoptosis, the B-cell lymphoma/leukemia 2 (Bcl-2) protein family has garnered the most attention as a promising therapeutic target in cancer. Accordingly, efforts have lately been focused on the development of drugs targeting Bcl-2 proteins with considerable therapeutic success, particularly in hematologic malignancies. Here, we review the previous studies and highlight the pivotal role of the Bcl-2 protein family in the homeostasis of hematologic tissue compartment. This knowledge provides more insight into why some cancers are more sensitive to Bcl-2 targeting than others and will foster the clinical evaluation of Bcl-2-targeting strategies in cancer by avoiding severe on-target side effects in the development of healthy tissues. © 2014 Macmillan Publishers Limited All rights reserved.


Elgar F.J.,McGill University | Pfortner T.-K.,University of Cologne | Moor I.,Martin Luther University of Halle Wittenberg | De Clercq B.,Ghent University | And 2 more authors.
The Lancet | Year: 2015

Background Information about trends in adolescent health inequalities is scarce, especially at an international level. We examined secular trends in socioeconomic inequality in five domains of adolescent health and the association of socioeconomic inequality with national wealth and income inequality. Methods We undertook a time-series analysis of data from the Health Behaviour in School-aged Children study, in which cross-sectional surveys were done in 34 North American and European countries in 2002, 2006, and 2010 (pooled n 492 788). We used individual data for socioeconomic status (Health Behaviour in School-aged Children Family Affluence Scale) and health (days of physical activity per week, body-mass index Z score [zBMI], frequency of psychological and physical symptoms on 0-5 scale, and life satisfaction scored 0-10 on the Cantril ladder) to examine trends in health and socioeconomic inequalities in health. We also investigated whether international differences in health and health inequalities were associated with per person income and income inequality. Findings From 2002 to 2010, average levels of physical activity (3·90 to 4·08 days per week; p<0·0001), body mass (zBMI -0·08 to 0·03; p<0·0001), and physical symptoms (3·06 to 3·20, p<0·0001), and life satisfaction (7·58 to 7·61; p=0·0034) slightly increased. Inequalities between socioeconomic groups increased in physical activity (-0·79 to -0·83 days per week difference between most and least affluent groups; p=0·0008), zBMI (0·15 to 0·18; p<0·0001), and psychological (0·58 to 0·67; p=0·0360) and physical (0·21 to 0·26; p=0·0018) symptoms. Only in life satisfaction did health inequality fall during this period (-0·98 to -0·95; p=0·0198). Internationally, the higher the per person income, the better and more equal health was in terms of physical activity (0·06 days per SD increase in income; p<0·0001), psychological symptoms (-0·09; p<0·0001), and life satisfaction (0·08; p<0·0001). However, higher income inequality uniquely related to fewer days of physical activity (-0·05 days; p=0·0295), higher zBMI (0·06; p<0·0001), more psychological (0·18; p<0·0001) and physical (0·16; p<0·0001) symptoms, and larger health inequalities between socioeconomic groups in psychological (0·13; p=0·0080) and physical (0·07; p=0·0022) symptoms, and life satisfaction (-0·10; p=0·0092). Interpretation Socioeconomic inequality has increased in many domains of adolescent health. These trends coincide with unequal distribution of income between rich and poor people. Widening gaps in adolescent health could predict future inequalities in adult health and need urgent policy action. Funding Canadian Institutes of Health Research. © 2015 Elsevier Ltd.


Becker M.,IRD Montpellier | Karpytchev M.,CNRS Coastal and Marine Environment Laboratory | Lennartz-Sassinek S.,University of Cologne
Geophysical Research Letters | Year: 2014

Detection and attribution of human influence on sea level rise are important topics that have not yet been explored in depth. We question whether the sea level changes (SLC) over the past century were natural in origin. SLC exhibit power law long-term correlations. By estimating Hurst exponent through Detrended Fluctuation Analysis and by applying statistics of Lennartz and Bunde [], we search the lower bounds of statistically significant external sea level trends in longest tidal records worldwide. We provide statistical evidences that the observed SLC, at global and regional scales, is beyond its natural internal variability. The minimum anthropogenic sea level trend (MASLT) contributes to the observed sea level rise more than 50% in New York, Baltimore, San Diego, Marseille, and Mumbai. A MASLT is about 1mm/yr in global sea level reconstructions that is more than half of the total observed sea level trend during the XXth century. Key Points Long-term persistence impacts on sea level rise estimation Sea level change is clearly unnatural in two thirds of the longest tidal records Sea level change magnitude cannot be explained without human influence © 2014. American Geophysical Union. All Rights Reserved.


Denzel M.S.,Max Planck Institute for Biology of Ageing | Storm N.J.,Max Planck Institute for Biology of Ageing | Gutschmidt A.,University of Cologne | Baddi R.,Max Planck Institute for Biology of Ageing | And 8 more authors.
Cell | Year: 2014

Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases. © 2014 Elsevier Inc.


Steinwachs C.F.,University of Cologne | Kamenshchik A.Y.,National Institute of Nuclear Physics, Italy | Kamenshchik A.Y.,Russian Academy of Sciences
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

Using the generalized Schwinger-DeWitt technique, we calculate the divergent part of the one-loop effective action for gravity nonminimally coupled to a multiplet of scalar fields. All the calculations are consistently done in the Jordan frame. © 2011 American Physical Society.


Wood W.,University of Bath | Eming S.A.,University of Cologne
EMBO Reports | Year: 2012

The fourth EMBO conference on 'The Molecular and Cellular Basis of Regeneration and Repair', held in September 2012, brought together researchers from both the regeneration and wound-healing fields. The meeting spanned a wide range of research topics from basic science to clinical application, and a veritable melting pot of model organisms and approaches resulted in an excellent fourth conference in this series. © 2012 European Molecular Biology Organization.


Hillenbrand C.-D.,British Antarctic Survey | Melles M.,University of Cologne | Kuhn G.,Alfred Wegener Institute for Polar and Marine Research | Larter R.D.,British Antarctic Survey
Quaternary Science Reviews | Year: 2012

The history of grounded ice-sheet extent on the southern Weddell Sea shelf during the Last Glacial Maximum (LGM) and the timing of post-LGM ice-sheet retreat are poorly constrained. Several glaciological models reconstructed widespread grounding and major thickening of the Antarctic Ice Sheet in the Weddell Sea sector at the LGM. In contrast, recently published onshore data and modelling results concluded only very limited LGM-thickening of glaciers and ice streams feeding into the modern Filchner and Ronne ice shelves. These studies concluded that during the LGM ice shelves rather than grounded ice covered the Filchner and Ronne troughs, two deep palaeo-ice stream troughs eroded into the southern Weddell Sea shelf.Here we review previously published and unpublished marine geophysical and geological data from the southern Weddell Sea shelf. The stratigraphy and geometry of reflectors in acoustic sub-bottom profiles are similar to those from other West Antarctic palaeo-ice stream troughs, where grounded ice had advanced to the shelf break at the LGM. Numerous cores from the southern Weddell Sea shelf recovered sequences with properties typical for subglacially deposited tills or subglacially compacted sediments. These data sets give evidence that grounded ice had advanced across the shelf during the past, thereby grounding in even the deepest parts of the Filchner and Ronne troughs. Radiocarbon dates from glaciomarine sediments overlying the subglacial deposits are limited, but indicate that the ice grounding occurred at the LGM and that ice retreat started before ~15.1 corrected 14Ckyrs before present (BP) on the outer shelf and before ~7.7 corrected 14CkyrsBP on the inner shelf, which is broadly synchronous with ice retreat in other Antarctic sectors.The apparent mismatch between the ice-sheet reconstructions from marine and terrestrial data can be attributed to ice streams with very low surface profiles (similar to those of " ice plains" ) that had advanced through Filchner Trough and Ronne Trough at the LGM. Considering the global sea-level low-stand of ~130m below present, a low surface slope of the expanded LGM-ice sheet in the southern Weddell Sea can reconcile grounding-line advance to the shelf break with limited thickening of glaciers and ice streams in the hinterland. This scenario implies that ice-sheet growth in the Weddell Sea sector during the LGM and ice-sheet drawdown throughout the last deglaciation could only have made minor contributions to the major global sea-level fluctuations during these times. © 2011 Elsevier Ltd.


Altland A.,University of Cologne | Haake F.,University of Duisburg - Essen
New Journal of Physics | Year: 2012

We discuss the unitary quantum dynamics of the Dicke model (spin and oscillator coupled). A suitable quasi-probability representing the quantum state turns out to obey a Fokker-Planck equation, with drift terms representing the underlying classical Hamiltonian flow and diffusion terms describing quantum fluctuations. We show (by projecting the dynamics onto a co-moving Poincaré section) how the interplay of deterministic drift and quantum diffusion generates equilibration to the microcanonical density, under conditions of global classical chaos. The pertinent photon statistics reveals macroscopic quantum fluctuations. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.


Gutkin B.,University of Duisburg - Essen | Al Osipov V.,University of Cologne
Nonlinearity | Year: 2013

In the framework of the semiclassical approach, the universal spectral correlations in Hamiltonian systems with classical chaotic dynamics can be attributed to the systematic correlations between the actions of periodic orbits which (up to the switch in the momentum direction) pass through approximatey the same points of the phase space. By considering symbolic dynamics of the system one can introduce a natural ultrametric distance between periodic orbits and organize them into clusters of orbits approaching each other in the phase space. We study the distribution of cluster sizes for the baker fs map in the asymptotic limit of long trajectories. This problem is equivalent to the one of counting degeneracies in the length spectrum of the de Bruijn graphs. Based on this fact, we derive the probability Pk that k randomly chosen periodic orbits belong to the same cluster. Furthermore, we find asymptotic behaviour of the largest cluster size |Cmax| and derive the probability P (t) that a random periodic orbit belongs to a cluster smaller than t Cmax|, t ε [0, 1]. © 2013 IOP Publishing Ltd & London Mathematical Society.


Pasparakis M.,University of Cologne | Vandenabeele P.,Ghent University
Nature | Year: 2015

Regulated cell death has essential functions in development and in adult tissue homeostasis. Necroptosis is a newly discovered pathway of regulated necrosis that requires the proteins RIPK3 and MLKL and is induced by death receptors, interferons, toll-like receptors, intracellular RNA and DNA sensors, and probably other mediators. RIPK1 has important kinase-dependent and scaffolding functions that inhibit or trigger necroptosis and apoptosis. Mouse-model studies have revealed important functions for necroptosis in inflammation and suggested that it could be implicated in the pathogenesis of many human inflammatory diseases. We discuss the mechanisms regulating necroptosis and its potential role in inflammation and disease.


Anton F.,University of Cologne | Dittmar G.,Max Delbrück Center for Molecular Medicine | Langer T.,University of Cologne | Langer T.,Max Planck Institute for Biology of Ageing | Escobar-Henriques M.,University of Cologne
Molecular Cell | Year: 2013

Mitofusins, conserved dynamin-related GTPases in the mitochondrial outer membrane, mediate the fusion of mitochondria. Here, we demonstrate that the activity of the mitofusin Fzo1 is regulated by sequential ubiquitylation at conserved lysine residues and by the deubiquitylases Ubp2 and Ubp12. Ubp2 and Ubp12 recognize distinct ubiquitin chains on Fzo1 that have opposing effects on mitochondrial fusion. Ubp2 removes ubiquitin chains that initiate proteolysis of Fzo1 and inhibit fusion. Ubp12 recognizes ubiquitin chains that stabilize Fzo1 and promote mitochondrial fusion. Self-assembly of dynamin-related GTPases is critical for their function. Ubp12 deubiquitylates Fzo1 only after oligomerization. Moreover, ubiquitylation at one monomer activates ubiquitin chain formation on another monomer. Thus, regulation of mitochondrial fusion involves ubiquitylation of mitofusin at distinct lysine residues, intermolecular crosstalk between mitofusin monomers, and two deubiquitylases that act as regulatory and quality control enzymes. © 2013 Elsevier Inc.


Schrage J.M.,Creighton University | Fink A.H.,University of Cologne
Monthly Weather Review | Year: 2012

Some spatiotemporal characteristics and possible mechanisms controlling the onset of the widespread, lowlevel nocturnal stratiform clouds that formed during May-October 2006 over southern tropical West Africa are investigated using cloudiness observations from surface weather stations, data from various satellite platforms, and surface-based remote sensing profiles at Nangatchori in central Benin. It is found that the continental stratus is lower than the maritime stratus over the Gulf of Guinea and persists well into the noon hours. For the study period, a clear seasonal cycle was documented, as well as a dependence on latitude with the cloudiest zone north of the coastal zone and south of approximately 98N. It is also shown that nonprecipitating clear and cloudy nights observed at Nangatchori in central Benin often reflect clearer and cloudier than normal conditions over a wide region of southern West Africa. At Nangatchori, on average the stratus developed at 0236 UTC (about local time) with an extremely low cloud base at 172 m (above ground level) when averaged over all cloudy nights. About 2-3 h before cloudiness onset, a distinct nighttime lowlevel jet formed that promoted static destabilization and a low Richardson number flow underneath it. The ensuing vertical upward mixing of moisture that accumulated under the near-surface inversion after sunset caused the cloud formation. It is argued that a strong shear underneath the nighttime low-level jet is the major process for cloud formation, but the low-level static stability and the time scale of the shear-driven mixing are other potential factors. © 2012 American Meteorological Society.


Altland A.,University of Cologne | Haake F.,University of Duisburg - Essen
Physical Review Letters | Year: 2012

We demonstrate effective equilibration for unitary quantum dynamics under conditions of classical chaos. Focusing on the paradigmatic example of the Dicke model, we show how a constructive description of the thermalization process is facilitated by the Glauber Q or Husimi function, for which the evolution equation turns out to be of Fokker-Planck type. The equation describes a competition of classical drift and quantum diffusion in contractive and expansive directions. By this mechanism the system follows a "quantum smoothened" approach to equilibrium, which avoids the notorious singularities inherent to classical chaotic flows. © 2012 American Physical Society.


Ko P.-C.,Research Training Group | Hank K.,University of Cologne
Journals of Gerontology - Series B Psychological Sciences and Social Sciences | Year: 2014

Objectives. To provide an overview of the prevalence and profiles of grandparents providing childcare to grandchildren in 2 East Asian countries, China and South Korea, characterized by similar demographic developments and a shared cultural background but having very different contemporary institutional and socioeconomic circumstances. Method. We apply logistic models to analyze pilot data from the China Health and Retirement Longitudinal Study (CHARLS) and data from the Korean Longitudinal Study of Aging (KLoSA; Wave 2). Our analytic sample comprises 772 Chinese respondents and 4,958 Korean respondents aged 45-79. Results. The proportions of grandparents providing childcare to grandchildren differ considerably between China (58%) and South Korea (6%). Still, the determinants of grandparents' involvement in childcare (e.g., age, geographic proximity) are fairly similar in both countries. However, financial support from adult children to grandparents is found to be significant in China only, whereas Korean grandparents exhibit a greater propensity to care for their (employed) daughters' children than for their sons' children. Discussion. Our analysis suggests that in South Korea, patrilineal considerations may begin to lose some of their importance in shaping downward functional solidarity between generations and that instead (grand-)children's actual needs, particularly those related to maternal employment, receive more attention. We find no such evidence in our Chinese sample. © 2013 The Author.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.4-1 | Award Amount: 3.93M | Year: 2008

In the eurIPFnet consortium, leading European basic and clinical scientists in the field of interstitial lung diseases associate to jointly decipher the natural course and molecular pathomechanisms of Idiopathic Pulmonary Fibrosis (IPF) and to develop new therapeutic strategies for patients with IPF. This devastating disease affects about 360.000 patients in the EU and causes a substantial socioeconomic burden. IPF patients experience a gradual decrease in quality of life due to progressive dyspnoe and coughing, and usually die within 3-5 years upon diagnosis. There is currently no approved treatment available. Our translational research programme includes implementation of a European IPF registry (eurIPFreg), in which data with regard to natural course, familiar background and susceptibility factors of IPF will be collected, and of a European IPF biobank (eurIPFbank) of blood, bronchoalveolar lavage fluid, cells and tissue specimen of IPF. In these samples, we will perform transcriptome, proteome, phosphoproteome and lipidome analysis, cellular studies and genetic analysis to unravel the molecular pathways underlying IPF and to identify and establish new diagnostic and prognostic markers. Candidate gene verification will be performed in cell culture and animal studies, including siRNA and gene transfection technologies and development of genetically altered mice and will result in the development of new animal models of IPF. Identification of new therapeutic targets in these models will be followed by rapid commercial exploitation and early preclinical and early clinical evaluation. Ultimately, we wish to establish a unique, sustainable and internationally unrivalled European infrastructure for investigation and treatment of IPF. Our mission statement is straight-forward and clear: Fighting for improved survival in Idiopathic Pulmonary Fibrosis.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP-2007-1.1-1 | Award Amount: 3.95M | Year: 2008

90% of bacteria are found attached to solid surfaces forming structures (bio-films), that are inaccessible to drugs and antibiotics. These bio-films represent a major problem in European society in both industry and health care. Currently, however, we understand little about how these bio-films form and, more importantly, how they can be prevented. This lack of understanding means that patients often suffer unnecessary and painful infections following the formation of such films on surgical implants and catheters. With the growing problem of MRSA and C. difficile in hospitals, and the cost of policing and hygiene measures, an understanding of how to prevent bacterial persistence in the hospital environment is critical to the sustainability of European healthcare. A multi-disciplinary group of European experts have the common aim to understand exactly how bacteria attach to, and persist on both biological and inert surfaces. We will use a range of biological and physio-chemical techniques to study several fundamental aspects of bacterial attachment. We will employ new molecular microbiology techniques to understand the genetic components governing the interaction of a bacterial biotic cell surface with the novel antimicrobial surfaces we create. Second, we will be using new nano-scale material science and physical chemistry techniques to create and understand these antimicrobial surfaces. This duel systems approach will allow us to theoretically model the processes of bacterial attachment and survival, which in turn will allow us to improve these surfaces in an iterative approach. We will generate intellectual property around the coatings and treatments used to derive the surfaces and develop these in collaboration with industry. The solutions will be designed specifically for the industrial partners participating in the project but can, with a minimum effort be adapted for applications in other areas through the iterative steps within the WPs.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.4.2-9-3 | Award Amount: 8.67M | Year: 2011

Assessment of repeated dose toxicity is a standard requirement in human safety evaluation and relies on animal testing as no alternatives are currently accepted for regulatory purposes. An integrated research strategy for the replacement of animal tests needs to comprise the development of biomarkers of long-term toxicity in human target cells. To this aim, the DETECTIVE project will set up a screening pipeline of high content, high throughput as well as classical functional and -omics technologies to identify and investigate human biomarkers in cellular models for repeated dose in vitro testing. In view of industrial use in automated high throughput systems, essential questions of repeated dose toxicity such as stability and robustness of readouts will be investigated in a first phase. This will be the foundation for innovative biomarker development based on integration of multiple data streams derived from -omics readouts with traditional toxicological and histopathological endpoint evaluation. Toxicity pathways identified in -omics readouts can thus be further investigated by the functional readouts. DETECTIVE will initially use human hepatic, cardiac and renal models as common target organs of repeated dose toxicity. Ultimately, the strategy for establishing biomarkers will also be applicable to other organs or organ systems affected by systemic toxicants. It is also expected that DETECTIVE will be able to define human toxicity pathways relevant for all organs. Based on integrative statistical analysis, systematic verification and correlation with in vivo data, the most relevant, highly specific, sensitive and predictive biomarkers will be selected. Within DETECTIVE, partners from academia, industry and research will hence generate pathway- and evidence-based understanding of toxic effects, moving toxicology beyond descriptive science towards mechanism-based prediction.


Grant
Agency: Cordis | Branch: H2020 | Program: ERC-STG | Phase: ERC-StG-2014 | Award Amount: 1.44M | Year: 2015

Enhancers control the correct spatio-temporal activation of gene expression. A comprehensive characterization of the properties and regulatory activities of enhancers as well as their target genes is therefore crucial to understand the regulation and dysregulation of differentiation, homeostasis and cell type specificity. Genome-wide chromatin assays have provided insight into the properties and complex architectures by which enhancers regulate genes, but the understanding of their mechanisms is fragmented and their regulatory targets are mostly unknown. Several factors may confound the inference and interpretation of regulatory enhancer activity. There are likely many kinds of regulatory architectures with distinct levels of output and flexibility. Despite this, most state-of-the-art genome-wide studies only consider a single model. In addition, chromatin-based analysis alone does not provide clear insight into function or activity. This project aims to systematically characterize enhancer architectures and delineate what determines their: (1) restricted spatio-temporal activity; (2) robustness to regulatory genetic variation; and (3) dynamic activities over time. My work has shown enhancer transcription to be the most accurate classifier of enhancer activity to date. This data permits unprecedented modeling of regulatory architectures via enhancer-promoter co-expression linking. Careful computational analysis of such data from appropriate experimental systems has a great potential for distinguishing the different modes of regulation and their functional impact. The outcomes have great potential for providing us with new insights into mechanisms of transcriptional regulation. The results will be particularly relevant to interpretation of regulatory genetic variations. Ultimately, knowing the characteristics and conformations of enhancer architectures will increase our ability to link variation in non-coding DNA to phenotypic outcomes like disease susceptibility.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP-2009-2.1-1 | Award Amount: 4.88M | Year: 2011

The semiconductor industry has been able to improve the performance of electronic system by making ever-smaller devices. However, this approach will soon encounter both scientific and technical limits, which is why the industry is exploring alternative device technologies. Carbon-based nano-electronic is currently investigated. Discovered recently, the graphene is rapidly raising star on the horizon of materials science and condensed-matter physics. Its exceptional properties make it a promising material for applications in future nanoelectronic circuits and a number of graphene based devices have been proposed theoretically or already tested. However, the current performances are still below that what expected from this magic layer. Indeed, the alternative graphene synthesis, its manipulation and its interaction with neighboring environment impact drastically its structural properties considering intrinsic or generated defects. In this context, the key objective of GRENADA proposal is to tailor the graphenes properties and morphologies to provide high quality layers through different scalable deposition technologies. GRENADA consortium will work on graphene material development and properties investigation that be used as a final point in proof concept by operating basic systems to measure the graphene performances. Prior to that, a strong focus will be made on defects that are crucial regarding graphene properties and they will be, then, considered through their formation, evolution and their specific impact on integrated graphene properties. The consortium includes internationally renowned experimental and theoretical groups from academic and industry in advanced elaboration, modelling, characterization and industrialization methods that have a significant potential for graphene nanomaterials. That will ensure a tight focus on the exploitation of the project results for European industry.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.1.2-5 | Award Amount: 3.96M | Year: 2008

Inflammation is a complex biochemical and cellular response essential for the viability of higher organisms because of its requirement in anti-microbial defence and protection from the consequences of tissue injury. However, uncontrolled or sustained inflammation leads to several diseases with a huge social impact, ranging from autoimmune diseases to septic shock and cancer. While the requirement for specific transcription factors (TF) in inflammatory gene transcription is known, quantitative models describing how their interactions with genomic sequences leads to normal or pathological outcomes are not available. Unravelling how genomic organization underlies the orchestrated expression of inflammatory genes is crucial to understand how to pharmacologically tune pathological inflammatory responses. Now is the right moment to tackle this question as for the first time we have genomic technologies and computational abilities to generate the necessary quantitative data and to build computational models describing spatiotemporal coordination of transcription of hundreds of inflammatory genes by multiple TFs. To implement this objective, we have assembled a consortium of top-level scientists in the European Research Area who reached documented excellence in complementary aspects of transcriptional control, namely quantitative measurement of TF-DNA interactions, in vitro and in vivo analysis of chromatin organization, manipulation of genomic sequences by homologous recombination, computational and systems biology applied to transcriptional circuits. The network provides the critical mass required to generate ample quantitative and complementary datasets describing the minimal transcriptional regulatory blocks relevant for inflammation, thus enabling the integration of their coordinated activities via systems approaches. Each research group complements the other participants and the whole projects, and as such this proposal can not be carried out on any individual level.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH-2007-2.4.1-5 | Award Amount: 3.22M | Year: 2008

The project aims to explore, share and collate existing knowledge and practice in each of the key themes identified within the work programme. It aims to reach consensus (based on current practice and available research evidence) on the optimum care to be delivered in the last days of life and gaps in the knowledge base. In addition, it aims to develop innovative ways of addressing gaps in knowledge with the specific aim of improving care for cancer patients in the last days of life. Clearly, such improvements would also impact positively on their informal carers and health professionals delivering the care. Importantly, it aims to do this systematically and collaboratively across Europe and beyond to integrate knowledge from a range of healthcare enviroments and cultures and to avoid duplication of resource and effort.


The overall aim of ENORASIS is to develop an intelligent, integrated Decision Support System (ENORASIS Service Platform and Components) for environmentally optimized and, thus, sustainable irrigation management by farmers and water management organizations. ENORASIS system will actually target to motivate irrigation farmers to optimize the use of water, whereas it will also provide to (irrigation) water management organizations intelligent tools and services to effectively forecast and manage irrigation water resources, cover irrigation demand and charge customers (farmers) on the basis of an intelligent system of motives and incentives that exploits irrigation demand side fluctuations. To achieve so, ENORASIS will develop and integrate a bouquet of advanced technologies, methodologies and models in the fields of: (i) weather prediction systems that exploit satellite observations; (ii) irrigation optimization techniques and (iii) smart irrigation systems in order to arrive at a solution that will be easy to use for farmers and that will be flexible and robust enough for its use by irrigation water management organizations; and (iv) wireless sensor networks (functioning with solar energy) as key enabling technology for field measurements and monitoring conditions. Such an intelligent irrigation management and charging system is expected to have a major impact towards the adoption of more sustainable irrigation water management practices in agriculture and thus, increased environmental protection and costs savings for all stakeholders involved in agricultural economy. Finally, the ENORASIS project will be implemented over a period of 36 months by a multi-disciplinary and well-balanced consortium of 13 partners, including academic partners, research centers & institutes, SMEs as well as end-users (water management organization).


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.61M | Year: 2017

A well-functioning locomotor system is essential for human well-being. This is an important consideration in our aging population with the increased associated costs of ensuring high quality of life. Many people suffer from diseases of the locomotor system, such as bone defects or osteoarthritis, for which current treatments are insufficient. To develop new treatments, CarBon includes 6 academic partners, 3 companies and 3 charitable foundations, working together to train 14 young scientists. We will combine knowledge from the fields of tissue engineering, cartilage and bone developmental biology and pathobiology using skills from the disciplines of cell biology, computational modelling, biotechnology (bioreactors, biomaterials) and drug discovery. In a multifactorial approach the network of young scientists will identify the biological and physical factors that determine the fate of cartilage. Understanding and controlling the dual character of cartilage is pivotal: insufficient transition impairs bone healing, and undesired transition to bone leads to osteoarthritis. State of the art in vitro, in silico and in vivo models will be uniquely combined to elucidate how this transition is orchestrated and how it can be modulated. The main objectives of CarBon are: - To establish a network of 14 highly skilled early stage researchers (ESRs) equipped with essential knowledge, scientific expertise, transferable skills and societal awareness as a foundation for their future careers. ESRs will be trained in cutting edge technology, communication, intellectual property and valorisation. - To understand cartilage to bone transition, to identify targets to develop novel functionalised biomaterials and to discover therapeutic drugs that either prevent or stimulate cartilage to bone transitions. This will lead to new treatment options for large bone defects and osteoarthritis.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SFS-03a-2014 | Award Amount: 7.00M | Year: 2015

Insects are the most diverse Class of life on earth, and different insects can be essential for, or highly damaging to, agriculture, horticulture and forestry. There is a pressing need, not just for new insecticides to combat resistance, but more specific, greener insecticides that target deleterious insects while sparing beneficial ones. This proposal aims to identify such insecticides by turning the insects own hormones against them, both by designing artificial neuropeptide mimetic analogs as candidate compounds, and by generating transgenic insects that carry deleterious neuropeptide payloads within them, that can propagate through a population and impact on survival at times of stress. We have assembled an international multi-actor consortium from EU member and associated member states, as well as a third country partner, with unparalleled experience in insect functional genomics, neuropeptide physiology, synthetic chemistry and synthetic biology, and in field-testing of candidates. Established links to agricultural, horticultural and forestry end-users, agencies/advisors and our SME partners ensure relevance to user need; and set out a pathway to exploitation and implementation of our results, for impact across three major economic sectors in the EU and globally. We will deliver novel, green neuropeptide-based insect pest biocontrol tools by: utilising beyond the State-of-the-Art technologies based on two approaches: rational design of neuropeptide hormone analogues; and development of genetically-encoded neuropeptides for translational insect synthetic biology in genetic pest management. bridging outstanding research and technology in neuroendocrinology and genetics to end user need, to ultimately produce neuropeptide hormone analogues and genetic pest management biocontrol tools. validating and demonstrating these novel insect biocontrol agents in laboratory, field and forest applications, based on user need and a market-driven approach.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-22-2015 | Award Amount: 7.09M | Year: 2016

As the number of older people in Europe grows, increasing healthy life years is a priority. Cognitive decline, dementia (e.g. Alzheimers disease, AD), sleep disturbances and depression, all related to psychological distress and anxiety, are significant drivers of reduced quality of life in older adults. This project builds on evidence that lifestyle factors and meditation practice have the potential to downregulate these adverse factors and positively impact mental and neurological conditions including AD. Our main objectives are i) to improve early AD detection and understanding of physiopathological mechanisms; and to investigate ii) the impact of internal/external (e.g. genetic and lifestyle) determinants and iii) the effect and mechanisms of action of meditation training, on mental health and wellbeing in older people. This will be achieved by using pre-existing databases from European partners and conducting two randomized controlled trials (Studies 1 and 2B) and one observational study (2A). STUDY 1 will assess the short-term effects of an 8-week meditation intervention (versus cognitive training) in patients with subjective cognitive decline at risk for AD on behavioural measures including anxiety and wellbeing. STUDY 2A will assess senior expert meditators to identify neural signatures of different meditation practices on attention and emotion regulation tasks. STUDY 2B will assess long-term effects of an 18-month meditation intervention (versus an active control) on behavioural and biological markers of mental health and wellbeing in cognitively intact elderly. The cognitive and affective regulatory mechanisms underlying these effects will be investigated using the neural signatures identified in the expert meditators. High public health relevance is likely: the proposed intervention targets the most common mental and neurological conditions in the elderly and it can be scaled up within preventive programmes at a population level.


Altland A.,University of Cologne | Egger R.,Heinrich Heine University Düsseldorf
Physical Review Letters | Year: 2013

We study multiple helical nanowires in proximity to a common mesoscopic superconducting island, where Majorana fermion bound states are formed. We show that a weak finite charging energy of the center island may dramatically affect the low-energy behavior of the system. While for strong charging interactions, the junction decouples the connecting wires, interactions lower than a nonuniversal threshold may trigger the flow towards an exotic Kondo fixed point. In either case, the ideally Andreev reflecting fixed point characteristic for infinite capacitance (grounded) devices gets destabilized by interactions. © 2013 American Physical Society.


Messing R.,Heinrich Heine University Düsseldorf | Schmidt A.M.,Heinrich Heine University Düsseldorf | Schmidt A.M.,University of Cologne
Polymer Chemistry | Year: 2011

Significant advances in the field of responsive hydrogels have been achieved by the combination of soft, gel-based matrices with the unique functions of inorganic or biological nanostructures. Like in many biological tissues, the components of such hybrid materials often have converse, yet complementary properties. The possibility of forming self-assembled and supramolecular morphologies from organic polymers in combination with inorganic nanoparticles or biological motifs is of interest for gels with new response properties. A variety of complex gel structures with unique chemical, physical, and biological properties have been engineered or discovered at the nanoscale. In this review, we highlight recent accomplishments and trends in the field of hybrid polymer hydrogels with a focus on approaches towards soft, yet tough shape-changing and actuating materials. We conclude with an outline on future directions and challenges that have to be faced in the design and application of hybrid hydrogels. © The Royal Society of Chemistry.


Ros R.,University of Valencia | Munoz-Bertomeu J.,University of Valencia | Munoz-Bertomeu J.,Institute Biologia Molecular Y Celular Of Plantas Ibmcp | Krueger S.,University of Cologne
Trends in Plant Science | Year: 2014

Serine (Ser) has a fundamental role in metabolism and signaling in living organisms. In plants, the existence of different pathways of Ser biosynthesis has complicated our understanding of this amino acid homeostasis. The photorespiratory glycolate pathway has been considered to be of major importance, whereas the nonphotorespiratory phosphorylated pathway has been relatively neglected. Recent advances indicate that the phosphorylated pathway has an important function in plant metabolism and development. Plants deficient in this pathway display developmental defects in embryos, male gametophytes, and roots. We propose that the phosphorylated pathway is more important than was initially thought because it is the only Ser source for specific cell types involved in developmental events. Here, we discuss its importance as a link between metabolism and development in plants. © 2014 Elsevier Ltd.


Zazunov A.,Heinrich Heine University Düsseldorf | Altland A.,University of Cologne | Egger R.,Heinrich Heine University Düsseldorf
New Journal of Physics | Year: 2014

We provide a comprehensive theoretical description of low-energy quantum transport for a Coulomb-Majorana junction, where several helical Luttinger liquid nanowires are coupled to a joint mesoscopic superconductor with finite charging energy. Including the Majorana bound states formed near the ends of superconducting wire parts, we derive and analyze the Keldysh phase action describing non-equilibrium charge transport properties of the junction. The low-energy physics corresponds to a two-channel Kondo model with symmetry group SO(M), where M is the number of leads connected to the superconductor. Transport observables, such as the conductance tensor or current noise correlations, display non-trivial temperature or voltage dependences reflecting non-Fermi liquid behavior. © 2014 IOP Publishing and Deutsche Physikalische Gesellschaft.


Hero B.,University of Cologne | Schleiermacher G.,University Pierre and Marie Curie
Neuropediatrics | Year: 2013

Opsoclonus myoclonus syndrome (dancing eye syndrome) is a rare paraneoplastic syndrome characterized by opsoclonus, myoclonus, and ataxia, usually accompanied by behavioral abnormalities. In adults, opsoclonus myoclonus syndrome has been reported in association with different types of cancer; whereas in children, the syndrome may be associated with neuroblastic tumors. Although a direct proof is lacking, the syndrome is assumed to be of autoimmune origin. The treatment is corticosteroid based with the addition of other immunosuppressive or immunomodulating drugs if intensification seems necessary. Because of the rarity of the disease, international collaborations as well on research as on therapeutic strategies are urgently needed. A European consortium just started a trial for this rare condition. © 2013 Georg Thieme Verlag KG Stuttgart.


Barbui T.,Ospedale Papa Giovanni XXIII | Thiele J.,University of Cologne | Vannucchi A.M.,University of Florence | Tefferi A.,Mayo Medical School
Leukemia | Year: 2014

The aim of this review is to critically address the validity and clinical applicability of three major diagnostic classification systems for polycythemia vera (PV), that is, those proposed by the Polycythemia Vera Study Group (PVSG), the British Committee for Standards in Haematology (BCSH) and the World Health Organization (WHO). Special focus is on which one of the three red cell parameters (hemoglobin - HB, hematocrit - HCT and red cell mass - RCM) should be used as the diagnostic hallmark of PV. The revised BCSH employed a persistently raised HCT level as the first diagnostic criterion in combination with the presence of a JAK2V617F mutation. On the other hand, the WHO classification used a raised HB value as a surrogate for increased RCM in association with molecular markers and for the first time, the bone marrow (BM) morphology was included as a minor criterion. Ongoing controversy and discussion regards the use of certain threshold values for HCT and HB as surrogates for RCM as well as the existence of prodromal-latent disease, so-called masked PV (mPV). It has been shown that mPV can be recognized in patients not meeting the required HB or HCT threshold levels by both the WHO and BCSH criteria. These cases present with the same baseline clinical features as overt PV but present worsened survival. A critical reappraisal of the WHO criteria may suggest either to reduce the thresholds for HB or to consider HCT values as major diagnostic criterion, as in the BCSH, in association with JAK2V617F mutation. The clinical utility of using HCT as reference variable is supported also by results of clinical trials which explicitly recommend to use the HCT threshold for monitoring treatment. In questionable cases as in mPV, BM biopsy examinations should be mandated together with mutation analysis. © 2014 Macmillan Publishers Limited.


Saad S.,University of Cologne | Strassel V.,University of Cologne | Sauerland S.,Witten/Herdecke University
British Journal of Surgery | Year: 2013

Background: This three-armed randomized clinical trial, with blinding of patients and outcome assessors, tested the hypothesis that single-port (SP) and/or minilaparoscopic (ML) cholecystectomy are superior to conventional laparoscopic (CL) cholecystectomy. Methods: Patients eligible for elective laparoscopic cholecystectomy were randomized to SP, ML or CL procedures. The primary outcome was pain measured on a visual analogue scale twice daily during the blinded period. Secondary outcomes included duration of operation, technical performance score, complications, quality of life, cosmesis and patient satisfaction. Postoperative follow-up lasted 1 year. Results: A total of 105 patients were randomized, 35 in each group. One conversion from a SP to a CL technique was necessary in a patient with chronic cholecystitis. Pain intensity was similar in the three groups, both during the blinded period (day 0 to 3; P = 0·865) and over the whole 7-day evaluation period (P = 0·911). The presence of clinically relevant between-group differences was ruled out (95 per cent confidence interval + 1·0 to - 0·5 for difference in pain scores between SP and CL groups, and - 0·8 to + 0·6 between ML and CL groups). Operating time was significantly longer for SP and ML than for CL cholecystectomy (P = 0·001). Postoperative complications included injury to the diaphragm (1), choledocholithiasis (1), wound infection (5) and hernia (1), all after SP cholecystectomy (P = 0·001). Twelve-month follow-up was complete in 99 patients (94·3 per cent). Cosmesis as rated by patients was significantly better at 6 months after SP and ML procedures (P = 0·043), but no difference was observed at 12 months (P = 0·229). Conclusion: SP and ML cholecystectomy had no advantage over the CL approach in terms of postoperative outcome. Registration number: DRKS00000302 (German Registry of Clinical Trials). Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. No benefit from single-port cholecystectomy Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.


Manner H.,University of Cologne | Wunsch-Ziegler L.,Gesellschaft fur Innovative Marktforschung MbH
Accident Analysis and Prevention | Year: 2013

We study the severity of accidents on the German Autobahn in the state of North Rhine-Westphalia using data for the years 2009 until 2011. We use a multinomial logit model to identify statistically relevant factors explaining the severity of the most severe injury, which is classified into the four classes fatal, severe injury, light injury and property damage. Furthermore, to account for unobserved heterogeneity we use a random parameter model. We study the effect of a number of factors including traffic information, road conditions, type of accidents, speed limits, presence of intelligent traffic control systems, age and gender of the driver and location of the accident. Our findings are in line with studies in different settings and indicate that accidents during daylight and at interchanges or construction sites are less severe in general. Accidents caused by the collision with roadside objects, involving pedestrians and motorcycles, or caused by bad sight conditions tend to be more severe. We discuss the measures of the 2011 German traffic safety programm in the light of our results. © 2013 Elsevier Ltd.


Barbui T.,Ospedali Riuniti di Bergamo | Thiele J.,University of Cologne | Vannucchi A.M.,University of Florence | Tefferi A.,Mayo Medical School
Leukemia | Year: 2013

Reproducibility and clinical usefulness of the WHO classification of chronic myeloproliferative neoplasm (MPN) persist to be a controversial issue. Major arguments are focused on the critical impact of histopathology, particularly concerning the distinction between essential thrombocythemia (ET) versus early/prefibrotic primary myelofibrosis (PMF). Regarding bone marrow morphology, WHO guidelines strictly require the recognition of characteristic histological patterns based on standardized features and a consensus of clinical and molecular-genetic data. Molecular-genetic findings as JAK2V617F, may aid to exclude reactive thrombocytosis, although in ET and PMF only 50-60% of the cases show these aberrations. Considerable doubts over the existence of early/prefibrotic PMF have been expressed with the consequence to include this entity in the ET category. On the other hand, it has to be argued that some of the critical studies failed to adhere very strictly to the WHO guidelines. Contrasting this situation, recently published retrospective and prospective clinico-pathological studies featuring the WHO criteria provided an important information on disease outcomes supporting the existence of early/prefibrotic PMF as a distinct clinico-pathologic entity in patients presenting clinically with ET. Therefore, this controversy suggests a scientific project, including the community of pathologists and hematologists, for providing sound, objective and reproducible criteria for diagnosing early/prefibrotic PMF. © 2013 Macmillan Publishers Limited All rights reserved.


Bogershausen N.,University of Cologne | Bruford E.,European Bioinformatics Institute | Wollnik B.,University of Cologne
Clinical Genetics | Year: 2013

To unravel the system of epigenetic control of transcriptional regulation is a fascinating and important scientific pursuit. Surprisingly, recent successes in gene identification using high-throughput sequencing strategies showed that, despite their ubiquitous role in transcriptional control, dysfunction of chromatin-modifying enzymes can cause very specific human developmental phenotypes. An intriguing example is the identification of de novo dominant mutations in MLL2 as a cause of Kabuki syndrome, a well-known congenital syndrome that is associated with a very recognizable facial gestalt. However, the existing confusion in the nomenclature of the human and mouse MLL gene family impedes correct interpretation of scientific findings for these genes and their encoded proteins. This Review aims to point out this nomenclature pitfall, to explain its historical background, and to promote an unequivocal nomenclature system for chromatin-modifying enzymes as proposed by Allis et al. (2007). © 2012 John Wiley & Sons A/S.


Cheng M.,Microsoft | Cheng M.,University of Maryland University College | Becker M.,University of Cologne | Bauer B.,Microsoft | Lutchyn R.M.,Microsoft
Physical Review X | Year: 2014

We study the properties of a quantum dot coupled to a topological superconductor and a normal lead and discuss the interplay between Kondo-and Majorana-induced couplings in quantum dots. The latter appears due to the presence of Majorana zero-energy modes localized, for example, at the ends of the onedimensional superconductor. We investigate the phase diagram of the system as a function of Kondo and Majorana interactions using a renormalization-group analysis, a slave-boson mean-field theory, and numerical simulations using the density-matrix renormalization-group method. We show that, in addition to the well-known Kondo fixed point, the system may flow to a new fixed point controlled by the Majoranainduced coupling, which is characterized by nontrivial correlations between a localized spin on the dot and the fermion parity of the topological superconductor and the normal lead. We compute several measurable quantities, such as differential tunneling conductance and impurity-spin susceptibility, which highlight some peculiar features characteristic to the Majorana fixed point.


Bilal A.,French National Center for Scientific Research | Ferrari F.,Solvay Group | Klevtsov S.,University of Cologne
Nuclear Physics B | Year: 2014

We study a new two-dimensional quantum gravity theory, based on a gravitational action containing both the familiar Liouville term and the Mabuchi functional, which has been shown to be related to the coupling of non-conformal matter to gravity. We compute the one-loop string susceptibility from a first-principle, path integral approach in the Kähler parameterization of the metrics and discuss the particularities that arise in the case of the pure Mabuchi theory. While we mainly use the most convenient spectral cutoff regularization to perform our calculations, we also discuss the interesting subtleties associated with the multiplicative anomaly in the familiar ζ-function scheme, which turns out to have a genuine physical effect for our calculations. In particular, we derive and use a general multiplicative anomaly formula for Laplace-type operators on arbitrary compact Riemann surfaces. © 2014 The Authors.


Angassa A.,Hawassa University | Angassa A.,University of Cologne
Land Degradation and Development | Year: 2014

Grazing intensity and bush encroachment are disturbance factors that may alter the floristic composition of herbaceous species. This paper investigates impacts of grazing (intensity) and bush encroachment on herbaceous species and rangeland conditions in Borana, southern Ethiopia. Herbaceous species richness and the abundance of each species were greater in the light- and moderate-grazed areas than heavy-grazed sampling plots. Similarly, herbaceous species richness was highest at an intermediate level of biomass and seems to decline as biomass increases. Among a total of 40 herbaceous species recorded, 20 per cent were tolerant of grazing, whereas the remaining 80 per cent were highly susceptible to heavy grazing. In both encroached and non-encroached sampling plots, species richness varied from three to six species 0.25m-2. Overall, herbaceous species richness and abundance, in relation to grazing gradient, might disclose a better picture of the effect of grazing on individual herbaceous species. As species richness seems to decline under heavy grazing intensity, low to intermediate grazing levels may promote and conserve key forage species in savanna grazing lands. © 2012 John Wiley & Sons, Ltd.


Kaufmann K.B.,Institute for Biomedical Research | Buning H.,University of Cologne | Galy A.,Genethon | Schambach A.,Hannover Medical School | And 2 more authors.
EMBO Molecular Medicine | Year: 2013

The first gene therapy clinical trials were initiated more than two decades ago. In the early days, gene therapy shared the fate of many experimental medicine approaches and was impeded by the occurrence of severe side effects in a few treated patients. The understanding of the molecular and cellular mechanisms leading to treatment- and/or vector-associated setbacks has resulted in the development of highly sophisticated gene transfer tools with improved safety and therapeutic efficacy. Employing these advanced tools, a series of Phase I/II trials were started in the past few years with excellent clinical results and no side effects reported so far. Moreover, highly efficient gene targeting strategies and site-directed gene editing technologies have been developed and applied clinically. With more than 1900 clinical trials to date, gene therapy has moved from a vision to clinical reality. This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene therapy as a powerful treatment option for the correction of monogenic disorders. © 2013 The Authors.


Vilchez D.,University of California at Berkeley | Vilchez D.,University of Cologne | Simic M.S.,University of California at Berkeley | Simic M.S.,University Pierre and Marie Curie | And 2 more authors.
Trends in Cell Biology | Year: 2014

The accumulation of misfolded or damaged proteins is an important determinant of the aging process. Mechanisms that promote the homeostasis of the proteome, or proteostasis, can slow aging and decrease the incidence of age-related diseases. Adult stem cell function declines during the aging process of an organism. This demise of somatic stem cell function could contribute to tissue degeneration and organismal aging. Accumulation of damaged proteins in embryonic stem cells (ESCs) may also have an impact on the aging process, because the passage of these proteins to progenitor cells during asymmetric division could compromise development and aging. Therefore, proteostasis maintenance in stem cells might have an important role in organismal aging. In this review, we discuss exciting new insights into stem cell aging and proteostasis and the questions raised by these findings. © 2013 Elsevier Ltd.


Christian Reinhardt H.,Massachusetts Institute of Technology | Christian Reinhardt H.,University of Cologne | Yaffe M.B.,Massachusetts Institute of Technology | Yaffe M.B.,Beth Israel Deaconess Medical Center
Nature Reviews Molecular Cell Biology | Year: 2013

Coordinated progression through the cell cycle is a complex challenge for eukaryotic cells. Following genotoxic stress, diverse molecular signals must be integrated to establish checkpoints specific for each cell cycle stage, allowing time for various types of DNA repair. Phospho-Ser/Thr-binding domains have emerged as crucial regulators of cell cycle progression and DNA damage signalling. Such domains include 14-3-3 proteins, WW domains, Polo-box domains (in PLK1), WD40 repeats (including those in the E3 ligase SCF βTrCP), BRCT domains (including those in BRCA1) and FHA domains (such as in CHK2 and MDC1). Progress has been made in our understanding of the motif (or motifs) that these phospho-Ser/Thr-binding domains connect with on their targets and how these interactions influence the cell cycle and DNA damage response. © 2013 Macmillan Publishers Limited. All rights reserved.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.2-5 | Award Amount: 3.57M | Year: 2009

A key problem in repair and functional regeneration following myocardial infarction is the inability of heart muscle tissue to regenerate itself and appropriate vascularization under conditions of increased strain caused by the reduced contractibility of the damaged heart. This frequently leads to continuous loss of functional cells, further increase of the infarct area and finally complete loss of heart function. We propose to explore possibilities for cell therapy using different procedures and sources of stem and progenitor cells. First, we will investigate factors stimulatory for stem/progenitor cell release from the bone marrow, their recruitment to the heart and the activation of resident heart stem cells. Second, we will evaluate adoptive transfer of stem/progenitor cells of different sources, from bone marrow, adult and cord blood, adipose tissue and heart tissue itself. The use of ex vivo cultured and differentiated cells including embryonic stem cells will be tested. Third, we will test genetic modification of these cells for improved differentiation, homing and tissue repair. Fourth, we will use a unique artificial scaffold material as a slow release device for factors and as a structural support material for providing the different cell preparations to the damaged areas. This scaffold will aso be used for tissue engineering in vitro followed by insertion of artficial tissue onto the infarct area. This project of high clinical importance is designed to further support the research and development needs of two SMEs, one is determined to become a supplier of growth factor cocktails for clinical stem cell culture, a second is based on the generation and supply of stem cells for clinical use. It will evaluate whether induction of repair by factors, adoptive transfer of stem/progenitor cells or engineered tissue has benefit for heart regeneration and has potential to become a future clinical standard therapy.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SPA.2012.2.1-01 | Award Amount: 2.64M | Year: 2013

Black holes provide a crucial link between Einsteins theory of gravity and real cosmic objects which astronomers can observe and study in the Universe. This project is oriented towards legacy of the cornerstone XMM-Newton X-ray satellite mission of European Space Agency (ESA) in synergy with relevant data in other spectral domains that are covered by ground-based infrared and radio interferometric techniques at European Southern Observatory (ESO) and elsewhere. Information in different wavelengths will be gathered and explored in order to understand radiation processes in places of strong gravity, near black holes. We will address outstanding questions of determining the black hole spin, measuring the location of the accretion disc inner rim, and revealing connections between inflows and outflows in these objects. To this end we will analyze and interpret multi-wavelength spectral and fast timing information on accreting black holes in compact binaries, in cores of active galactic nuclei, as well as other galaxies exhibiting low level of activity due to intermittent supply of gas from the cosmic environment or by switching to a radiatively inefficient regime. We will include valuable data from archives and complement them by performing new observations where needed. Our main objective is to use and enhance computational tools that the participating groups have been developing over two decades, and to join our effort in a dedicated program of data analysis and science interpretation of the most bizarre cosmic objects. We will rely on unprecedented combination of sensitivity and energy resolution of current X-ray missions of ESA, together with wide spectral coverage by ground-based observatories in ESO and elsewhere. The developed techniques will be highly relevant in the context of new missions. We will make our tools available to the entire scientific community. The research team includes experts from 7 leading research institutes and universities.


Patent
University of Regensburg and University of Cologne | Date: 2011-02-04

The present invention provides acyloxy- and phosphoryloxy-butadiene-Fe(CO)_(3 )complexes which can deliver carbon monoxide to a physiological target, wherein release of carbon monoxide can be enzymatically-triggered. The present invention also provides for methods of manufacturing the enzymatically-triggered carbon monoxide releasing molecules and methods for their use.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2013-IRSES | Award Amount: 207.00K | Year: 2013

Low-dimensional carbon structures such as graphene and carbon nanotubes have raised tremendous interest in recent years both from fundamental and technological perspectives. However, the tunability of the density of electronic states of graphene and carbon nanotubes remains a limiting factor for their implementation in modern nanotechnology. It has been recently shown that the energy bandgap of graphene-based materials can be tailored via chemical modification of the graphene surface, e.g. by fluorination. We focus our efforts on tuning the chemical and physical properties of nanocarbon materials using different fluorination techniques and varying the degree of fluorination. A multidisciplinary approach will be applied ranging from fundamental research in chemistry and physics to studying the materials properties for application in electronics, photonics, and biomedicine. It is anticipated that the final outcome of this project will be a novel nanocarbon-based material with specific advanced properties.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.3.2-2 | Award Amount: 3.96M | Year: 2008

We propose to extend an existing collection of DNA extracts from TB patients and their corresponding TB DNA to establish the worlds largest resource of extracts from a population of TB patients and 5000 ethnically matched healthly controls. The bank will comprise 5000 DNA host DNA extracts paired the DNA and cultures of the strain of Mycobacterium tuberculosis causing their disease. We will perform a genome-wide scan to discover human genes predisposing to TB. We will then localise causal variants and study their role in a case-control population TB sample from another high incidence country in Africa ,Ghana. We will extensively characterise TB strains from a population in Russia using spoligotyping, minisatellite analysis, and SNP analysis of genes putatively associated with virulence and analyse the host-pathogen interaction identifying mycobacterial genes affecting the course of TB, the innate response to TB and outcome at a genetic level. Based on the existing collection of matched host-pathogen DNA we will perform functional experiments of the role of identified mycobacterial factors such as PE variants and the effect of this variation on aspects of innate immunity as influenced by newly-identified TB-associated genes.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP.2012.1.1-1 | Award Amount: 3.91M | Year: 2013

The rising global interest in hydrogen as the fuel of future has prompted tremendous interest in the development of efficient hydrogen production technologies that may serve as economically viable solutions towards solar fuels. The project SOLARGENIX will investigate novel nanostructured photocatalysts starting from comprehensive theoretical and experimental investigations on visible-light active meta-oxides for photoelectrochemical splitting of water to target the environmental hydrogen production from saline water by sun illumination. For this purpose, efficient multi-functional photoactive nano-catalysts will be developed whereby underlying atomic understanding of elementary chemical reactions and electrochemical processes will guard the scope of the project. The development of efficient nano-catalysts will be mastered by novel material combinations and interfacial engineering in nano-hetrostructures. Furthermore the project will demonstrate the feasibility of this technology together with industrial partners to develop first module-sized demonstrators for testing under real operating conditions.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: INFRA-2011-3.2. | Award Amount: 923.93K | Year: 2011

Due to globalization and an enormous technological innovation cultures and languages are subject to extreme changes and many of them will become extinct in the coming decades and with them much knowledge about nature and history. Digital archives have been setup to preserve cultural and language materials for future generations, but also to serve as database for cross-linguistic research about how the human brain processes language. In parallel CLARIN has finished its preparatory phase in which many suggestions have been worked out for example for proper standards, for proper preservation and access, and in which a network of persistent centers with different types of language material as the backbone of an emerging research infrastructure has started of being established. INNET wants (1) to intensify and extend the existing worldwide archiving grid, (2) to revitalize the existing expert network and (3) to intensify the use of archives not only by researchers but also by schools and the public. The intention is (1) to give the CLARIN center network a worldwide extension and impact, (2) to use the expert network to disseminate the CLARIN achievements and (3) to create a larger user base that will make use of the data stored in the CLARIN center network.


Gouni-Berthold I.,University of Cologne | Berthold H.K.,Bielefeld Evangelical Hospital EvKB
Atherosclerosis Supplements | Year: 2015

Familial hypercholesterolemia (FH) is a disease associated with very high plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. It is difficult in these high risk patients, exposed lifelong to very high LDL-C, to reach target LDL-C concentrations, which require >50% LDL-C reduction, even when on maximally tolerated statin therapy and on apheresis if available. Therefore, there is an unmet need for new therapeutic options for these patients. In 2013 two new drugs were approved for the treatment of homozygous FH, namely the apolipoprotein B synthesis inhibitor mipomersen and the microsomal transfer protein inhibitor lomitapide. Objective of this narrative review is to discuss the available evidence on the safety and efficacy profile of these new drugs. © 2015 Elsevier Ireland Ltd.


Baker M.J.,University of Cologne | Lampe P.A.,University of Cologne | Stojanovski D.,University of Melbourne | Korwitz A.,University of Cologne | And 4 more authors.
EMBO Journal | Year: 2014

The dynamic network of mitochondria fragments under stress allowing the segregation of damaged mitochondria and, in case of persistent damage, their selective removal by mitophagy. Mitochondrial fragmentation upon depolarisation of mitochondria is brought about by the degradation of central components of the mitochondrial fusion machinery. The OMA1 peptidase mediates the degradation of long isoforms of the dynamin-like GTPase OPA1 in the inner membrane. Here, we demonstrate that OMA1-mediated degradation of OPA1 is a general cellular stress response. OMA1 is constitutively active but displays strongly enhanced activity in response to various stress insults. We identify an amino terminal stress-sensor domain of OMA1, which is only present in homologues of higher eukaryotes and which modulates OMA1 proteolysis and activation. OMA1 activation is associated with its autocatalyic degradation, which initiates from both termini of OMA1 and results in complete OMA1 turnover. Autocatalytic proteolysis of OMA1 ensures the reversibility of the response and allows OPA1-mediated mitochondrial fusion to resume upon alleviation of stress. This differentiated stress response maintains the functional integrity of mitochondria and contributes to cell survival. Synopsis A sensor domain for mitochondrial stress and a novel self-degradation mechanism enables the mitochondrial protease OMA1 to reversibly control mitochondrial fragmentation in response to various cellular stresses. Various cellular stress conditions activate OMA1 and induce OPA1 processing and mitochondrial fragmentation. A stress-sensor domain is present outside the conserved metallopeptidase domain in the amino terminal region of mammalian OMA1. OMA1 activation is accompanied by its autocatalytic turnover ensuring the reversibility of the response. A sensor domain for mitochondrial stress and a novel self-degradation mechanism enables the mitochondrial protease OMA1 to reversibly control mitochondrial fragmentation in response to various cellular stresses. © 2014 The Authors.


Eisenhauer N.,University of Minnesota | Cesarz S.,University of Gottingen | Koller R.,University of Cologne | Worm K.,University of Minnesota | Reich P.B.,University of Minnesota
Global Change Biology | Year: 2012

The world's ecosystems are subjected to various anthropogenic global change agents, such as enrichment of atmospheric CO 2 concentrations, nitrogen (N) deposition, and changes in precipitation regimes. Despite the increasing appreciation that the consequences of impending global change can be better understood if varying agents are studied in concert, there is a paucity of multi-factor long-term studies, particularly on belowground processes. Herein, we address this gap by examining the responses of soil food webs and biodiversity to enrichment of CO 2, elevated N, and summer drought in a long-term grassland study at Cedar Creek, Minnesota, USA (BioCON experiment). We use structural equation modeling (SEM), various abiotic and biotic explanatory variables, and data on soil microorganisms, protozoa, nematodes, and soil microarthropods to identify the impacts of multiple global change effects on drivers belowground. We found that long-term (13-year) changes in CO 2 and N availability resulted in modest alterations of soil biotic food webs and biodiversity via several mechanisms, encompassing soil water availability, plant productivity, and - most importantly - changes in rhizodeposition. Four years of manipulation of summer drought exerted surprisingly minor effects, only detrimentally affecting belowground herbivores and ciliate protists at elevated N. Elevated CO 2 increased microbial biomass and the density of ciliates, microarthropod detritivores, and gamasid mites, most likely by fueling soil food webs with labile C. Moreover, beneficial bottom-up effects of elevated CO 2 compensated for detrimental elevated N effects on soil microarthropod taxa richness. In contrast, nematode taxa richness was lowest at elevated CO 2 and elevated N. Thus, enrichment of atmospheric CO 2 concentrations and N deposition may result in taxonomically and functionally altered, potentially simplified, soil communities. Detrimental effects of N deposition on soil biodiversity underscore recent reports on plant community simplification. This is of particular concern, as soils house a considerable fraction of global biodiversity and ecosystem functions. © 2011 Blackwell Publishing Ltd.


Sinisalo J.,University of Helsinki | Sreeram N.,University of Cologne | Qureshi S.A.,Evelina Childrens Hospital
Catheterization and Cardiovascular Interventions | Year: 2013

We describe transcatheter closure of an acquired Gerbode defect (left ventricle to right atrium shunt) in four patients, ranging in age from 8 to 75 years. All of them had undergone previous surgery (VSD closure in 3, aortic valve replacement in 1), and either had persistent symptoms of heart failure, or developed new symptoms several months or years later. The diagnosis was made by one of several imaging modalities (transthoracic or transesophageal echocardiography, or MRI), and confirmed at cardiac catheterization. Device closure using a variety of devices was successful in all, with resolution of symptoms. One patient developed complete heart block, requiring permanent pacemaker implantation. Transcatheter closure is effective, and may replace surgery in the management of these defects. © 2013 Wiley Periodicals, Inc.


Choi Y.-H.,University of Cologne | Kurtz A.,Berlin Brandenburg Center for Regenerative Therapies | Kurtz A.,Charité - Medical University of Berlin | Stamm C.,Berlin Brandenburg Center for Regenerative Therapies
Human Gene Therapy | Year: 2011

Despite refinements of medical and surgical therapies, heart failure remains a fatal disease. Myocardial infarction is the most common cause of heart failure, and only palliative measures are available to relieve symptoms and prolong the patient's life span. Because mammalian cardiomyocytes irreversibly exit the cell cycle at about the time of birth, the heart has traditionally been considered to lack any regenerative capacity. This paradigm, however, is currently shifting, and the cellular composition of the myocardium is being targeted by various regeneration strategies. Adult progenitor and stem cell treatment of diseased human myocardium has been carried out for more than 10 years (Menasche et al., 2001; Stamm et al., 2003), and it has become clear that, in humans, the regenerative capacity of hematopoietic stem cells and endothelial progenitor cells, despite potent proangiogenic effects, is limited (Stamm et al., 2009). More recently, mesenchymal stem cells (MSCs) and related cell types are being evaluated in preclinical models of heart disease as well as in clinical trials (see Published Clinical Trials, below). MSCs have the capacity to self-renew and to differentiate into lineages that normally originate from the embryonic mesenchyme (connective tissues, blood vessels, blood-related organs) (Caplan, 1991; Prockop, 1997; Pittenger et al., 1999). The current definition of MSCs includes plastic adherence in cell culture, specific surface antigen expression (CD105 +/CD90 +/CD73 +, CD34 -/CD45 -/CD11b - or CD14 -/CD19 - or CD79α -/HLA-DR1 -), and multilineage in vitro differentiation potential (osteogenic, chondrogenic, and adipogenic) (Dominici et al., 2006). If those criteria are not met completely, the term "mesenchymal stromal cells" should be used for marrow-derived adherent cells, or other terms for MSC-like cells of different origin. For the purpose of this review, MSCs and related cells are discussed in general, and cell type-specific properties are indicated when appropriate. We first summarize the preclinical data on MSCs in models of heart disease, and then appraise the clinical experience with MSCs for cardiac cell therapy. © 2011 Mary Ann Liebert, Inc.


Gerdes F.,University of Cologne | Tatsuta T.,University of Cologne | Langer T.,University of Cologne | Langer T.,Max Planck Institute for Biology of Ageing
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2012

Mitochondrial AAA proteases play an important role in the maintenance of mitochondrial proteostasis. They regulate and promote biogenesis of mitochondrial proteins by acting as processing enzymes and ensuring the selective turnover of misfolded proteins. Impairment of AAA proteases causes pleiotropic defects in various organisms including neurodegeneration in humans. AAA proteases comprise ring-like hexameric complexes in the mitochondrial inner membrane and are functionally conserved from yeast to man, but variations are evident in the subunit composition of orthologous enzymes. Recent structural and biochemical studies revealed how AAA proteases degrade their substrates in an ATP dependent manner. Intersubunit coordination of the ATP hydrolysis leads to an ordered ATP hydrolysis within the AAA ring, which ensures efficient substrate dislocation from the membrane and translocation to the proteolytic chamber. In this review, we summarize recent findings on the molecular mechanisms underlying the versatile functions of mitochondrial AAA proteases and their relevance to those of the other AAA+ machines. This article is part of a Special Issue entitled: AAA ATPases: Structure and function. © 2011 Elsevier B.V.


Baker M.J.,University of Cologne | Tatsuta T.,University of Cologne | Langer T.,University of Cologne | Langer T.,Max Planck Institute for Biology of Ageing
Cold Spring Harbor Perspectives in Biology | Year: 2011

A decline in mitochondrial activity has been associated with aging and is a hallmark of many neurological diseases. Surveillance mechanisms acting at the molecular, organellar, and cellular level monitor mitochondrial integrity and ensure the maintenance of mitochondrial proteostasis. Herewe will reviewthe central role of mitochondrial chaperones and proteases, the cytosolic ubiquitin-proteasome system, and the mitochondrial unfolded response in this interconnected quality control network, highlighting the dual function of some proteases in protein quality control within the organelle and for the regulation of mitochondrial fusion and mitophagy. © 2011 Cold Spring Harbor Laboratory Press.


Von Papen M.,University of Cologne | Saur J.,University of Cologne | Alexandrova O.,LESIA
Journal of Geophysical Research: Space Physics | Year: 2014

We analyze the statistical properties of magnetic field fluctuations measured by the Cassini spacecraft inside Saturn's magnetosphere. We introduce Saturn's magnetosphere as a new laboratory for plasma turbulence, where background magnetic field is strong (1 nT = 0.07), and the ion plasma βi is smaller than one. We also show that the dissipation of these magnetic field fluctuations has important implications for the magnetosphere. In a case study of the second orbit of Cassini around Saturn we show that at MHD scales, the spectra and the nature of fluctuations are characterized by large-scale nonstationary processes. The spectral slope varies between -0.8 and -1.7. At higher frequencies we observe a steeper spectrum with nearly constant power law exponent. A spectral break correlating with ion scales separates the two frequency ranges. We carry out a statistical study of high-frequency range fluctuations using the first seven orbits of Cassini. We find that the energy density of raw frequency spectra depends on radial distance from Saturn and thermal and magnetic pressures. However, normalized spectra depend only on ion plasma βi. Closer to Saturn the spectral slope is about -2.3 and for radial distances r>9 Rs the average slope is -2.6. The fluctuations have probability density functions with increasingly non-Gaussian tails and a power law increase of flatness with frequency, which indicates intermittency. We estimate the total energy flux contained in the turbulent cascade as 60-100 GW, which is on the same order of magnitude as needed to heat an adiabatically expanding plasma to the temperatures measured in Saturn's magnetosphere. Key Points A kinetic range turbulent cascade is found throughout the middle magnetosphere Plasma heating through turbulence is important for magnetospheric energy budget The turbulent cascade is intermittent and rather strong with spectral index 2.6 ©2014. American Geophysical Union. All Rights Reserved.


Antebi A.,Max Planck Institute for Biology of Ageing | Antebi A.,University of Cologne | Antebi A.,Baylor College of Medicine
Current Topics in Developmental Biology | Year: 2013

Hormones play a critical role in driving major stage transitions and developmental timing events in many species. In the nematode C. elegans the steroid hormone receptor, DAF-12, works at the confluence of pathways regulating developmental timing, stage specification, and longevity. DAF-12 couples environmental and physiologic signals to life history regulation, and it is embedded in a rich architecture governing diverse processes. Here, we highlight the molecular insights, extraordinary circuitry, and signaling pathways governing life stage transitions in the worm and how they have yielded fundamental insights into steroid regulation of biological time. © 2013 Elsevier Inc.


Potting C.,University of Cologne | Tatsuta T.,University of Cologne | Konig T.,University of Cologne | Haag M.,University of Cologne | And 4 more authors.
Cell Metabolism | Year: 2013

Cardiolipin (CL), a mitochondria-specific glycerophospholipid, is required for diverse mitochondrial processes and orchestrates the function of various death-inducing proteins during apoptosis. Here, we identify a complex of the p53-regulated protein TRIAP1 (p53CSV) and PRELI in the mitochondrial intermembrane space (IMS), which ensures the accumulation of CL in mitochondria. TRIAP1/PRELI complexes exert lipid transfer activity in vitro and supply phosphatidic acid (PA) for CL synthesis in the inner membrane. Loss of TRIAP1 or PRELI impairs the accumulation of CL, facilitates the release of cytochrome c, and renders cells vulnerable to apoptosis upon intrinsic and extrinsic stimulation. Survival of TRIAP1- and PRELI-deficient cells is conferred by an excess of exogenously provided phosphatidylglycerol. Our results reveal a p53-dependent cell-survival pathway and highlight the importance of the CL content of mitochondrial membranes in apoptosis. © 2013 Elsevier Inc.


Dell'Anna L.,University of Trieste | Dell'Anna L.,University of Padua | De Martino A.,University of Cologne
Physical Review B - Condensed Matter and Materials Physics | Year: 2011

We study the band structure of graphene's Dirac-Weyl quasiparticles in a one-dimensional magnetic superlattice formed by a periodic sequence of alternating magnetic barriers. The spectrum and the nature of the states strongly depend on the conserved longitudinal momentum and on the barrier width. At the center of the superlattice Brillouin zone we find new Dirac points at finite energies where the dispersion is highly anisotropic, in contrast to the dispersion close to the neutrality point which remains isotropic. This finding suggests the possibility of collimating Dirac-Weyl quasiparticles by tuning the doping. © 2011 American Physical Society.


Rugarli E.I.,University of Cologne | Langer T.,University of Cologne | Langer T.,Max Planck Institute for Biology of Ageing
EMBO Journal | Year: 2012

Neuronal survival critically depends on the integrity and functionality of mitochondria. A hierarchical system of cellular surveillance mechanisms protects mitochondria against stress, monitors mitochondrial damage and ensures the selective removal of dysfunctional mitochondrial proteins or organelles. Mitochondrial proteases emerge as central regulators that coordinate different quality control (QC) pathways within an interconnected network of mechanisms. A failure of this system causes neuronal loss in a steadily increasing number of neurodegenerative disorders, which include Parkinson's disease, spinocerebellar ataxia, spastic paraplegia and peripheral neuropathies. Here, we will discuss the role of the mitochondrial QC network for neuronal survival and neurodegeneration. © 2012 European Molecular Biology Organization.


Bewernick B.H.,University of Bonn | Kayser S.,University of Bonn | Sturm V.,University of Cologne | Schlaepfer T.E.,University of Bonn | Schlaepfer T.E.,Johns Hopkins University
Neuropsychopharmacology | Year: 2012

Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated with antidepressant, anxiolytic, and procognitive effects in a small sample of patients suffering from treatment-resistant depression (TRD), followed over 1 year. Results of long-term follow-up of up to 4 years of NAcc-DBS are described in a group of 11 patients. Clinical effects, quality of life (QoL), cognition, and safety are reported. Eleven patients were stimulated with DBS bilateral to the NAcc. Main outcome measures were clinical effect (Hamilton Depression Rating Scale, Montgomery-Asperg Rating Scale of Depression, and Hamilton Anxiety Scale) QoL (SF-36), cognition and safety at baseline, 12 months (n11), 24 months (n=10), and last follow-up (maximum 4 years, n=5). Analyses were performed in an intent-to-treat method with last observation carried forward, thus 11 patients contributed to each point in time. In all, 5 of 11 patients (45%) were classified as responders after 12 months and remained sustained responders without worsening of symptoms until last follow-up after 4 years. Both ratings of depression and anxiety were significantly reduced in the sample as a whole from first month of NAcc-DBS on. All patients improved in QoL measures. One non-responder committed suicide. No severe adverse events related to parameter change were reported. First-time, preliminary long-term data on NAcc-DBS have demonstrated a stable antidepressant and anxiolytic effect and an amelioration of QoL in this small sample of patients suffering from TRD. None of the responders of first year relapsed during the observational period (up to 4 years). © 2012 American College of Neuropsychopharmacology. All rights reserved.


Jordan S.D.,University of Cologne | Konner A.C.,University of Cologne | Bruning J.C.,University of Cologne | Bruning J.C.,Max Planck Institute for Biology of Ageing
Cellular and Molecular Life Sciences | Year: 2010

The central nervous system (CNS) is capable of gathering information on the body's nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus. © 2010 The Author(s).


Hunzelmann N.,University of Cologne | Brinckmann J.,University of Lübeck
Annals of the Rheumatic Diseases | Year: 2010

Systemic sclerosis (SSc) is a chronic inflammatory autoimmune disease involving the connective tissue of the skin and various internal organs. In recent years research on SSc has evolved to provide a better understanding of the interdependence of the three major systems involved-namely, the vascular system, the immune system and the connective tissue. Hypoxia is increasingly recognised as a decisive factor in modulating the inflammatory process in SSc, activating fibroblasts and changing their phenotype. In addition, several mediators synthesised by immune cells, including cytokines such as transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF), cooperate in inducing the activation of fibroblasts and their differentiation into myofibroblasts. Therefore, a variety of intracellular and extracellular strategies to inhibit the activity of TGFβ and PDGF are currently receiving intense investigation. To further improve our therapeutic strategies for this paradigmatic fibrotic disease, an improved understanding of connective tissue remodelling as it takes place in the different stages of SSc will be imperative.


Pereg-Barnea T.,California Institute of Technology | Weber H.,University of British Columbia | Weber H.,University of Cologne | Refael G.,California Institute of Technology | Franz M.,University of British Columbia
Nature Physics | Year: 2010

When a metal is subjected to a strong magnetic field B, nearly all measurable quantities show oscillations periodic in 1/B. Such quantum oscillations represent a canonical probe of the defining aspect of a metal, its Fermi surface. Recent breakthrough experiments demonstrating the existence of unambiguous quantum oscillations in a cuprate superconductor, YBa 2 Cu 3 O 6.51, contradict the well-established result of many angle resolved photoemission studies, which consistently indicate Fermi arcstruncated segments of a Fermi surfacein the normal state of the cuprates. In this study, with the goal of reconciling the above disagreement, we introduce a mechanism for quantum oscillations that requires only finite segments of a Fermi surface. We show that oscillations periodic in 1/B can occur if the Fermi surface segments are terminated by a pairing gap and present arguments that these oscillations are in fact occurring in the cuprates. © 2010 Macmillan Publishers Limited. All rights reserved.


Tokano T.,University of Cologne | Lorenz R.D.,Johns Hopkins University
Icarus | Year: 2016

Density-driven circulation in Titan's seas forced by solar heating and methane evaporation/precipitation is simulated by an ocean circulation model. If the sea is transparent to sunlight, solar heating can induce anti-clockwise gyres near the sea surface and clockwise gyres near the sea bottom. The gyres are in geostrophic balance between the radially symmetric pressure gradient force and Coriolis force. If instead the sea is turbid and most sunlight is absorbed near the sea surface, the sea gets stratified in warm seasons and the circulation remains weak. Precipitation causes compositional stratification of the sea to an extent that the sea surface temperature can be lower than the sea interior temperature without causing a convective overturning. Non-uniform precipitation can also generate a latitudinal gradient in the methane mole fraction and density, which drives a meridional overturning with equatorward currents near the sea surface and poleward currents near the sea bottom. However, gyres are more ubiquitous than meridional overturning. © 2015 Elsevier Inc.


Escobar-Henriques M.,University of Cologne | Langer T.,University of Cologne | Langer T.,Max Planck Institute for Biology of Ageing
EMBO Reports | Year: 2014

Ubiquitin is a post-translational modifier with proteolytic and non-proteolytic roles in many biological processes. At mitochondria, it performs regulatory homeostatic functions and contributes to mitochondrial quality control. Ubiquitin is essential for mitochondrial fusion, regulates mitochondria-ER contacts, and participates in maternal mtDNA inheritance. Under stress, mitochondrial dysfunction induces ubiquitin-dependent responses that involve mitochondrial proteome remodeling and culminate in organelle removal by mitophagy. In addition, many ubiquitin-dependent mechanisms have been shown to regulate innate immune responses and xenophagy. Here, we review the emerging roles of ubiquitin at mitochondria. © 2014 The Authors.


Antebi A.,Max Planck Institute for Biology of Ageing | Antebi A.,University of Cologne | Antebi A.,Baylor College of Medicine
Experimental Gerontology | Year: 2013

Pioneering work in model organisms reveals that the reproductive system is involved not only in propagation of the species but also regulates organismal metabolism and longevity. In C. elegans, prevention of germline stem cell proliferation results in a 60% extension of lifespan, termed gonadal longevity. Gonadal longevity relies on the transcriptional activities of steroid nuclear receptor DAF-12, the FOXO transcription factor homolog DAF-16, the FOXA transcription factor homolog PHA-4, and the HNF-4-like nuclear receptor NHR-80. These transcription factors work in an integrated transcriptional network to regulate fatty acid lipolysis, autophagy, stress resistance and other processes, which altogether enhance homeostasis and extend life. Because the reproductive system also regulates longevity in other species, studies in C. elegans may shed light on ancient mechanisms governing reproduction and survival. © 2012 Elsevier Inc.


Tatsuta T.,University of Cologne | Scharwey M.,University of Cologne | Langer T.,University of Cologne | Langer T.,Max Planck Institute for Biology of Ageing
Trends in Cell Biology | Year: 2014

Mitochondria are dynamic organelles surrounded by two membranes with a defined lipid composition. The majority of lipids are synthesized in the endoplasmic reticulum (ER) and transported to the mitochondria, but the synthesis of cardiolipin and phosphatidylethanolamine in the inner membrane of mitochondria highlights their general importance for cellular lipid metabolism. Extensive exchange of lipids and their precursors occurs between the ER and mitochondria as well as between mitochondrial membranes. The recent identification of membrane-tethering complexes and lipid-transfer proteins in mitochondria now provides the first insight into the mechanisms of these transport processes, which are of fundamental importance for mitochondrial activities and cell homeostasis. Here, we summarize the current understanding of lipid trafficking at the mitochondria and discuss emerging models for the mechanisms of lipid transfer. © 2013 Elsevier Ltd.


Hanisch F.-G.,Institute of Biochemistry II | Hanisch F.-G.,University of Cologne
Analytical Chemistry | Year: 2011

The sites of mucin-type O-glycosylation are largely unpredictable, making structural analysis by mass spectrometry (MS) indispensible. On the peptide level, a site localization and characterization of O-linked glycans in situ using tandem MS with electron-transfer dissociation or matrix-assisted laser desorption ionization (MALDI) MS with postsource decay have been reported. The top-down sequencing on the protein level by MALDI-MS is based on the in-source decay (ISD) of intact glycoproteins induced by hydrogen radical transfer from the matrix. It allows a ladder sequencing from both termini with assignment of O-glycosylation sites based on intense c-, y-, and z-type ions. The feasibility of ISD-MALDI-MS in the localization of O-glycosylation sites was demonstrated with synthetic O-glycopeptides, the tandem repeat domain of recombinant MUC1, and the natural bovine glycoproteins asialofetuin and desialylated κ-casein. Ladder sequencing of the 17-18.5 kD MUC1 hexarepeat domains revealed (1) cell-specific glycosylation site patterns on comparison of probes expressed in human HEK-293 or Drosophila S2 cells, and (2) a site-specific microheterogeneity at the Thr/Ser sites with variations of the glycan compositions from zero to four monosaccharides. Novel O-glycosylation sites in the C-terminal domains of fetuin (T334) and κ-caseinoglycopeptide (S154 and T156) were assigned, the former representing a sequence conflict with the published T154. © 2011 American Chemical Society.


Gouni-Berthold I.,University of Cologne | Berthold H.K.,Bielefeld Evangelical Hospital EvKB
Current Pharmaceutical Design | Year: 2014

Familial hypercholesterolemia (FH) is a common genetic disorder that presents with robust increases in low-density lipoprotein cholesterol (LDL-C) and can lead to premature cardiovascular disease. There are heterozygous and homozygous forms. The diagnosis is usually made based on blood cholesterol levels, clinical signs and family history. Genetic testing can be used to confirm the diagnosis. Effective lowering of LDL-C in FH can prevent cardiovascular morbidity and mortality, however, the disease remains greatly underdiagnosed. The mainstay of pharmacologic therapy in FH patients is high-dose statins, which are often combined with other lipidlowering agents. The homozygous form is mainly treated with lipid apheresis. Guideline-recommended target levels of LDL-C are often not reached, making new treatment options desirable. Four classes of newer lipid-lowering drugs offer promising advances in treating FH, namely the apolipoprotein-B synthesis inhibitors (mipomersen), the microsomal transfer protein inhibitors (lomitapide), the cholesterol ester transfer protein inhibitors (anacetrapib, evacetrapib) and the proprotein convertase subtilisin/kexin type 9 inhibitors (evolocumab, alirocumab). In this review, the available evidence regarding the use of these drugs in patients with FH is discussed, with particular focus on their efficacy and safety. © 2014 Bentham Science Publishers.


Gouni-Berthold I.,University of Cologne | Berthold H.K.,Bielefeld Evangelical Hospital EvKB
Nutrients | Year: 2014

The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to lysosomes for intracellular degradation. This results in decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and remove them from the circulation and therefore to a subsequent increase in circulating LDL-cholesterol (LDL-C) plasma levels. Since 2003, when the role of PCSK9 in LDL-C metabolism was discovered, there have been major efforts to develop efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies against PCSK9 are the furthest in development, with multiple phase 3 trials already published and with cardiovascular endpoint trials currently underway. Two fully human monoclonal antibodies, evolocumab (AMG 145) and alirocumab (REGN727/SAR236553), have been extensively studied in a wide range of subjects, such as those with statin intolerance, as an add-on to statin therapy, as a monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies result in a consistent and robust decrease in LDL-C plasma levels ranging from 40% to 70%, either on top of statins or as a monotherapy. If the safety data from the on-going phase 3 trials remain as reassuring as the data available till now, PCSK9 antibodies will offer a novel, powerful therapeutic option to decrease LDL-C plasma levels and, hopefully, cardiovascular risk. © 2014, by the authors; licensee MDPI, Basel, Switzerland.


Anand R.,University of Cologne | Langer T.,University of Cologne | Langer T.,Max Planck Institute for Biology of Ageing | Baker M.J.,University of Cologne
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013

Mitochondrial proteostasis depends on a hierarchical system of tightly controlled quality surveillance mechanisms. Proteases within mitochondria take center stage in this network. They eliminate misfolded and damaged proteins and ensure the biogenesis and morphogenesis of mitochondria by processing or degrading short-lived regulatory proteins. Mitochondrial gene expression, the mitochondrial phospholipid metabolism and the fusion of mitochondrial membranes are under proteolytic control. Furthermore, in response to stress and mitochondrial dysfunction, proteolysis inhibits fusion and facilitates mitophagy and apoptosis. Defining these versatile activities of mitochondrial proteases will be pivotal for understanding the pathogenesis of various neurodegenerative disorders associated with defective mitochondria-associated proteolysis. This article is part of a Special Issue entitled: Mitochondrial dynamics and physiology. © 2012 Elsevier B.V.


Nourmohammad A.,Princeton University | Held T.,University of Cologne | Lassig M.,University of Cologne
Current Opinion in Genetics and Development | Year: 2013

Molecular traits, such as gene expression levels or protein binding affinities, are increasingly accessible to quantitative measurement by modern high-throughput techniques. Such traits measure molecular functions and, from an evolutionary point of view, are important as targets of natural selection. We review recent developments in evolutionary theory and experiments that are expected to become building blocks of a quantitative genetics of molecular traits. We focus on universal evolutionary characteristics: these are largely independent of a trait's genetic basis, which is often at least partially unknown. We show that universal measurements can be used to infer selection on a quantitative trait, which determines its evolutionary mode of conservation or adaptation. Furthermore, universality is closely linked to predictability of trait evolution across lineages. We argue that universal trait statistics extends over a range of cellular scales and opens new avenues of quantitative evolutionary systems biology. © 2013.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-SICA | Phase: HEALTH-2007-3.5-2 | Award Amount: 4.01M | Year: 2009

Two generations of top-down decisions on health financing systems have produced very modest results for poor people, poor countries or indeed for the major donors/funders. In most developing countries, including India, the lions share of health spending is made out of pocket. Impoverishment, low access especially for weaker segments of the population such as women and children and thus bad health status are consequences. Health insurance has the potential to remedy or at least reduce the severe consequences of unforeseen health care expenditures. Recently, a growing number of community based health insurance (CBHI) schemes emerge in India and other developing countries. It is expected that CBHI can (i) help mobilizing additional resources for health financing, (ii) provide financial protection and (iii) increase access to health care and hence ultimately the health status of the rural population. Community based health insurance represent the highest hope for extension of insurance amongst the poor, drawing on experience of many western countries and Japan. However, in order to make use of the scarce resources available and build systems offering value to the poor, it is important to have a detailed and evidence based understanding on how to build an efficient and responsive CBHI-system. This proposed project sets out to close the knowledge gap on aspects important for the successful implementation of CBHI. It does so through a set of controlled field experiments through which CBHI is implemented in villages of three states of India. Rigorous longitudinal research documents the learning and makes it available for replication elsewhere. We apply quantitative research along with in depth qualitative research and spatial data. It is the projects overall objective to: Use affordable, responsive and inclusive Community Based Health Insurance to increase: (i) Equitable access to healthcare and (ii) Financial protection.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.3.6 | Award Amount: 4.98M | Year: 2011

SCOOP is focussed on OLED technology, microdisplays based on the combination of OLED with CMOS technology, and innovative visualisation systems. OLED microdisplays are based on Above-IC integration with the principal value chain being located in Europe. SCOOP intends to improve the competitiveness of European industry by helping the industrial partners to maintain and improve their technological advance and to extend their market share by enabling new products. The project will also contribute to strengthen Europes scientific and technology base in the field of OLED and thin film encapsulation, which can be leveraged for a variety of applications through the institutional partners and the material supplier involved in the project. The project will also provide system integrators with components with outstanding features enabling innovative products like informative eyewear or augmented reality glasses. Technical focus is on the development of OLED materials and devices with high brightness and high reliability as well as corresponding thin film encapsulation stacks, in order to overcome current limitations of OLED microdisplays, in particular for high end applications like electronic viewfinders, Head Mounted Displays for augmented reality, CAD, or professional applications. Moreover, by developing a new approach producing colour subpixels without colour filter in a simplified process, we will extend the field of application of OLED microdisplays to systems that require higher luminance for readability even in bright sunlight, like e.g. augmented reality glasses for medical, sports, or logistics. The partners cover the whole value chain, from research, materials, components to systems. All industrial partners have their main manufacturing sites located in Europe. The outcomes of the project are not limited to microdisplay applications but can apply to many OLAE devices like biosensors, small to large size direct view displays, lighting devices, or solar cells


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.1.2-1 | Award Amount: 13.67M | Year: 2010

Stem cells are central to emerging concepts in health, medicine and therapy. The realization that specific cell reservoirs retain multipotency for tissue establishment and replenishment has implications for both the emerging field of regenerative therapy and the long standing problems of cancer, ageing and degenerative diseases. Recently the prospects for regenerative therapy have been boosted by the breakthrough finding that somatic cells can be reprogrammed into pluripotent embryonic stem (ES) cells upon expression of ES cell transcription factors. This astonishing finding further emphasizes the need to understand stem cell biology. Most of the information acquired on stem cells so far is empirical. Recent progress in systematic and computational methodologies, including seminal contributions by the applicants, permits a new approach to stem cell biology. We can now describe the systems biology of stem cells. This proposal is based on the importance of stem cells in future medicine and the need to understand the fundamental mechanisms that regulate their potential to differentiate towards specific lineages. We aim to gather the information required to understand the regulomes of key stem cells, particularly the transition between embryonic (ES) and neural (NS) cells. NS cells can be readily reprogrammed back to ES cells. We will systematically gather proteomic, transcriptomic, regulomic, live cell and cell cycle data to understand the ES NS axis comprehensively (in both directions). We will validate the regulatory data by functional interrogation using RNAi screens and tests, complemented by quantitative fluorescent read-outs. To broaden the fundamental and medical relevance of the insights, we will pursue selected studies on other stem cells (e.g. HSCs), and their differentiated products. Thereby we will acquire a broader grasp on stem cell issues and also significantly advance mammalian systems biology.

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