Frankfurt am Main, Germany
Frankfurt am Main, Germany

The Goethe University Frankfurt is a university which was founded in 1914 as a Citizens' University, which means that, while it was a State university of Prussia, it had been founded and financed by the wealthy and active liberal citizenry of Frankfurt am Main, a unique feature in German university history. It was named in 1932 after one of the most famous natives of Frankfurt, the poet and writer Johann Wolfgang von Goethe. Today, the university has 46,000 students, on 4 major campuses within the city.Several Nobel Prize winners have been affiliated with the university, such as Max von Laue. The university is also affiliated with 11 winners of the Gottfried Wilhelm Leibniz Prize. Wikipedia.


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Ruckriegel A.,Goethe University Frankfurt | Kopietz P.,Goethe University Frankfurt
Physical Review B - Condensed Matter and Materials Physics | Year: 2017

In magnets with noncollinear spin configuration the expectation value of the conventionally defined spin current operator contains a contribution which renormalizes an external magnetic field and hence affects only the precessional motion of the spin polarization. This term, which has been named angular spin current by Sun and Xie [Phys. Rev. B 72, 245305 (2005)]PRBMDO1098-012110.1103/PhysRevB.72.245305, does not describe the translational motion of magnetic moments. We give a prescription for how to separate these two types of spin transport and show that the translational movement of the spin is always polarized along the direction of the local magnetization. We also show that at vanishing temperature the classical magnetic order parameter in magnetic insulators cannot carry a translational spin current and elucidate how this affects the interpretation of spin supercurrents. © 2017 American Physical Society.


Wiltschko R.,Goethe University Frankfurt
Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology | Year: 2017

Experiments with migrating birds displaced during autumn migration outside their normal migration corridor reveal two different navigational strategies: adult migrants compensate for the displacement, and head towards their traditional wintering areas, whereas young first-time migrants continue in their migratory direction. Young birds are guided to their still unknown goal by a genetically coded migration program that indicates duration and direction(s) of the migratory flight by controlling the amount of migratory restlessness and the compass course(s) with respect to the geomagnetic field and celestial rotation. Adult migrants that have already wintered and are familiar with the goal area approach the goal by true navigation, specifically heading towards it and changing their course correspondingly after displacement. During their first journey, young birds experience the distribution of potential navigational factors en route and in their winter home, which allows them to truly navigate on their next migrations. The navigational factors used appear to include magnetic intensity as a component in their multi-modal navigational ‘map’; olfactory input is also involved, even if it is not yet entirely clear in what way. The mechanisms of migratory birds for true navigation over long distances appear to be in principle similar to those discussed for by homing pigeons. © 2017 Springer-Verlag Berlin Heidelberg


Ubiquitination controls a plethora of cellular processes. Modifications by linear polyubiquitin have so far been linked with acquired and innate immunity, lymphocyte development and genotoxic stress response. Until now, a single E3 ligase complex (LUBAC), one specific deubiquitinase (OTULIN) and a very few linear polyubiquitinated substrates have been identified. Current methods for studying lysine-based polyubiquitination are not suitable for the detection of linear polyubiquitin-modified proteins. Here, we present an approach to discovering linear polyubiquitin-modified substrates by combining a lysine-less internally tagged ubiquitin (INT-Ub.7KR) with SILAC-based mass spectrometry. We applied our approach in TNFα-stimulated T-REx HEK293T cells and validated several newly identified linear polyubiquitin targets. We demonstrated that linear polyubiquitination of the novel LUBAC substrate TRAF6 is essential for NFκB signaling. © 2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Coja-Oghlan A.,Goethe University Frankfurt
Journal of the ACM | Year: 2017

Let φ be a uniformly distributed random k-SAT formula with n variables and m clauses. Nonconstructive arguments show that φ is satisfiable for clause/variable ratios m/n ≤ rkSAT∼ 2k ln 2 with high probability. Yet no efficient algorithm is known to find a satisfying assignment beyond m/n ∼ 2k ln(k)/k with a nonvanishing probability. On the basis of deep but nonrigorous statistical mechanics ideas, a message passing algorithm called Belief Propagation Guided Decimation has been put forward (Mézard, Parisi, Zecchina: Science 2002; Braunstein, Mézard, Zecchina: Random Struc. Algorithm 2005). Experiments suggested that the algorithm might succeed for densities very close to rk-SAT for k = 3, 4, 5 (Kroc, Sabharwal, Selman: SAC 2009). Furnishing the first rigorous analysis of this algorithm on a nontrivial input distribution, in the present article we show that Belief Propagation Guided Decimation fails to solve random k-SAT formulas already for m/n = O(2k/k), almost a factor of k below the satisfiability threshold rk-SAT. Indeed, the proof refutes a key hypothesis on which Belief Propagation Guided Decimation hinges for such m/n. 2017 Copyright is held by the owner/author(s).ACM.


Dirkes A.,Goethe University Frankfurt
Classical and Quantum Gravity | Year: 2017

In this article we will modify the Einstein field equations by promoting Newton's constant G to a covariant differential operator Gλ(□g) composed of two terms which operate in different energy regimes (IR and UV). The IR term inside the covariant differential operator acts like a high-pass filter with a macroscopic distance filter scale √λ and effectively degravitates energy sources characterized by wavelengths larger than the filter scale. While this term is predominant for cosmological energy processes it is almost inessential on astrophysical scales where the UV contribution inside Gλ(□g) leads to much stronger deviations compared to GR. In the context of this particular theory of gravity we work out the effective relaxed Einstein equations, the effective 1.5 post-Newtonian near zone mass for n-body systems as well as the IR and UV modified Schwarzschild metrics. We use these results in the context of the Double Pulsar binary system and observe that we recover, in the limit of vanishing UV-IR modification parameters, the corresponding general relativistic results. © 2017 IOP Publishing Ltd.


Hegen M.,Goethe University Frankfurt
Pacific Asia Conference on Information Systems, PACIS 2016 - Proceedings | Year: 2016

Consumers' Food Choice has been researched in the past, but as a result of advances in mobile technologies such as barcode scanning, new possibilities of obtaining additional product information emerged. As a result, present day consumers use their mobile devices to reduce information asymmetries and make more informed choices by supporting their buying decisions with additional information at the Point of Sale (PoS). This raises the question about the impact of Mobile Product Information Systems (MPIS) on consumers' food choices. Since most MPIS are not provided by producers of the food themselves, there is a risk that consumers no longer base their decisions on information provided on the product packaging, but instead on mobile information of third party service providers. To gain empirical insights about consumers' information seeking behaviour a research model is proposed and tested in a within-subject experiment with repeated-measures design with 665 participants. The results reveal that MPIS impact consumers' perceived food quality and perceived price in both directions, positive and negative, dependent on the presented information. However, purchase intention is only affected negatively confirming a risk for food producing companies by MPIS of third party providers.


Janze C.,Goethe University Frankfurt
Pacific Asia Conference on Information Systems, PACIS 2016 - Proceedings | Year: 2016

User-generated online reviews are an important decision aid for consumers affecting purchase probabilities and sales figures. However, little is known about factors influencing the review generation process. Thus, this paper empirically examines the impact of cross-organizational spillover effects on user-generated online service reviews. Specifically, we study how the overall perception of consumers towards a service provider expressed in online reviews is affected by upstream service providers in interdependent service chains (ISCs). Based on the Treatment-By-Association (TBA) phenomenon, we design a research model to study both the existence and evolvement of cross-organizational spillover effects in online reviews of ISCs. Utilizing every airline and airport review posted over 13 years on www.AirlineQuality.com, we show that both positive and negative spillover effects exist: Increased (decreased) overall ratings of an upstream service node are associated with increased (decreased) ratings of the directly following service node in the ISC. In addition, we show that this is not true for more distantly arranged service nodes. We contribute to the IS research stream of online reviews by shedding light on spillover effects and by providing evidence for the proposed TBA. Furthermore, suggestions how practitioners could manage and utilize spillover effects to improve their customer experience are provided.


Financial market manipulations represent a major threat to trust and market integrity in capital markets. Manipulations contribute to mispricing, market imperfections and an increase in transaction costs for market participants and in costs of capital for issuers. Manipulations are facilitated by increased transaction velocity, speculative trading and abusive usage of new trading technologies, i.e., they are directly linked to financial sector changes that drive financialization. Research at the intersection of financialization and IS might support regulatory authorities and market operators in improving market surveillance and helping to detect fraudulent activities. However, confusing terminology is prevalent on financial markets with respect to different manipulation techniques and their characteristics, which hampers efficient fraud detection. Furthermore, recognizing manipulations is challenging given the large number of information sources and the vast number of trades occurring not least because of high-frequency traders. Therefore, automated market surveillance tools require a comprehensive taxonomy of financial market manipulations as a basis for appropriate configuration. Based on a cluster analysis of SEC litigation releases, a review of the latest market abuse regulation and academic studies, we develop a taxonomy of manipulations that structures and details existing manipulation techniques and reveals how these techniques differ along several dimensions. In a case study, we show how the taxonomy can be utilized to guide the development of appropriate decision support systems for fraud detection. © 2017 Palgrave Macmillan UK


Dernbecher S.,Goethe University Frankfurt
European Journal of Information Systems | Year: 2017

The concept of mindfulness has garnered increasing attention during the last decade. Initially proposed within the scope of information systems (IS) research as a means of creating a deeper knowledge foundation for decision making regarding information technology (IT) innovations, it soon became broadly applied throughout IS research. To gain a better understanding of the evolved diversity of this concept, this paper reviews and analyzes extant IS research by means of (a) the investigated IS themes, (b) the purpose of using the concept, (c) the level of application of the concept, and (d) the tendency to focus either on mindfulness, mindlessness, or both. By synthesizing research findings, we derive a high-level IS mindfulness theory. We then propose future research opportunities, such as the explanation of the relationships between different levels of mindfulness, applying mindfulness to bridge the different phases of the software development process, and the identification of guidelines for designing information systems that facilitate mindfulness. As the first review on the application of mindfulness in IS research, we contribute to the overall understanding of mindfulness and address the four abovementioned dimensions from which mindfulness emerges in order to demonstrate that mindfulness provides a meaningful platform for generating knowledge. © 2017 Palgrave Macmillan UK


Toia A.,Goethe University Frankfurt
Journal of Physics: Conference Series | Year: 2017

Proton-nucleus collisions provide a reference for heavy ion-collisions, to study the signatures deriving from the presence of a complex nuclear structure in the initial state, which confirm that the suppression of high-p Thadron production observed in heavy-ion collisions is a genuine effect of the hot deconfined QGP. However, several measurements of particle production in the low and intermediate momentum region indicate the presence of coherent and collective effects, already in small systems, such as the ones produced in p-Pb collisions. Measurements from proton-lead collisions at √sNN = 5.02 TeV obtained by the ALICE experiment at the CERN LHC will be presented and compared to p-p, A-A and d-A experimental results at different collision energies and to the available theoretical model predictions. © Published under licence by IOP Publishing Ltd.


Drozhzhova T.,Goethe University Frankfurt
Journal of Physics: Conference Series | Year: 2017

Investigation of physical phenomena in heavy-ion collisions requires knowledge about collision geometry, which is characterized by the energy distribution in the overlap region of the colliding nuclei and of the collision spectators. Both the event-by-event distributions of produced particles and the spectator nucleons can be used to estimate the collision geometry. Due to the pressure gradients, the spatial anisotropy of initial state geometry is converted during the system evolution to an anisotropy in momentum space. The event-planes of this anisotropy can be estimated via measured azimuthal distributions of particles produced in the collision. We report on the performance of the ALICE experiment at the LHC for the centrality and the event-plane determination for different harmonics using measured distribution of produced particles at central and forward rapidity, and the energy distribution of the spectator neutrons at beam rapidity. © Published under licence by IOP Publishing Ltd.


Huhn P.,Goethe University Frankfurt
Journal of Physics: Conference Series | Year: 2017

The ALICE experiment at the LHC is designed to study the properties of the Quark-Gluon Plasma (QGP) based on high energy pp, p-Pb and Pb-Pb collisions. Certain properties of these collisions can be studied by measuring the production of charged particles. A suppression of the yield of charged particles was observed at high pT by comparing central Pb-Pb events scaled by the number of binary collisions to pp collisions, in terms of the nuclear modification factor RAA. This suppression can be an effect of the energy loss of partons as they propagate in a hot and dense QCD medium (QGP). In the end of 2015, pp and Pb-Pb collisions at √sNN = 5.02 TeV were measured by ALICE. Here, transverse momentum distributions of inclusive charged particles in pp and Pb-Pb collisions at √sNN = 5.02 TeV as well as the nuclear modification factor in six centrality classes are presented and compared with model predictions. © Published under licence by IOP Publishing Ltd.


Philipsen O.,Goethe University Frankfurt
EPJ Web of Conferences | Year: 2017

The properties of matter at finite baryon densities play an important role for the astrophysics of compact stars as well as for heavy ion collisions or the description of nuclear matter. Because of the sign problem of the quark determinant, lattice QCD cannot be simulated by standard Monte Carlo at finite baryon densities. I review alternative attempts to treat dense QCD with an effective lattice theory derived by analytic strong coupling and hopping expansions, which close to the continuum is valid for heavy quarks only, but shows all qualitative features of nuclear physics emerging from QCD. In particular, the nuclear liquid gas transition and an equation of state for baryons can be calculated directly from QCD. A second effective theory based on strong coupling methods permits studies of the phase diagram in the chiral limit on coarse lattices. © The Authors, published by EDP Sciences, 2017.


Yang S.,Goethe University Frankfurt
Pacific Asia Conference on Information Systems, PACIS 2015 - Proceedings | Year: 2015

In our digital and hyperconnected society, social networking sites such as Facebook or Instagram facilitated information sharing in the Web and it becomes an integral part of many people's daily life. Consequently, the amount of personal data available online is significantly increasing and concurrently, it is easy to find personal data in the Web. As a result of availability and uncomplicated retrieval of published personal data, creating comprehensive online profiles becomes effortless and also eases the derivation of implicit information for various purposes. Such information forms an online reputation and is used to make a judgment about a person (Farmer & Glass 2010). Although first studies show that individuals perceive their online reputation as important (Komisarjevsky 2012), their endeavor to manage their online reputation is on a low level (Brackenbury & Wong 2012; Madden & Smith 2010). In order to understand why individuals consider their online reputation as important but do not take action to manage it we conducted a grounded theory based on 22 qualitative interviews with digital natives to reveal the underlying motivation. Thereby, we contribute a new facet to the general understanding of online reputation management, its obstacles, and explanations for the lack of motivation.


Strobele H.,Goethe University Frankfurt
Journal of Physics: Conference Series | Year: 2017

The research programme of the NA61 collaboration covers a wide range of hadronic physics in the CERN SPS energy range. It encompasses measurements of hadron-hadron, hadron-nucleus as well as nucleus-nucleus collisions. The latter are analyzed to better understand the properties of hot and dense nuclear matter. In this contribution we present results on production in proton-proton interactions at beam energies of 40 and 158 GeV/c. © Published under licence by IOP Publishing Ltd.


Efthymiou C.,Goethe University Frankfurt
SIAM Journal on Computing | Year: 2016

Approximate random k-coloring of a graph G is a well-studied problem in computer science and statistical physics. It amounts to constructing a k-coloring of G which is distributed close to the Gibbs distribution in polynomial time. Here, we deal with the problem when the underlying graph is an instance of the Erdös-Rényi random graph G(n,d/n), where d is a sufficiently large constant. We propose a novel efficient algorithm for approximate random k-coloring G(n, d/n) for any k ≥ (1 + ϵ)d. To be more specific, with probability at least 1 - n-ω (1) over the input instances G(n,d/n) and for k ≥ (1 + ϵ)d, the algorithm returns a k-coloring which is distributed within total variation distance n-ω (1) from the Gibbs distribution of the input graph instance. The algorithm we propose is neither Markov chain Monte Carlo nor inspired by the message-passing algorithms proposed by statistical physicists. Roughly, the idea is as follows. Initially we remove sufficiently many edges of the input graph. This results in a "simple graph" which can be k-colored randomly efficiently. The algorithm colors randomly this simple graph. Then it puts back the removed edges one by one. Every time a new edge is put back the algorithm updates the coloring of the graph so that the coloring remains random. The performance of the algorithm depends heavily on certain spatial correlation decay properties of the Gibbs distribution. © 2016 Society for Industrial and Applied Mathematics.


RATIONALE:: Cell-based therapies are a promising option in patients with chronic post-infarction heart failure (ICM). However, the responses following intracoronary infusion of autologous bone marrow-derived mononuclear cells (BMC) are heterogeneous, which may be related to impaired cell retention in patients with ICM. Ischemic injury is associated with upregulation of prototypical chemoattractant cytokines mediating retention and homing of circulating cells. The development of ultrasensitive tests to measure troponin-T serum levels (hs-TnT) revealed the presence of ongoing minute myocardial injury even in patients with stable ICM. OBJECTIVE:: To test the hypothesis that serum levels of hs-TnT correlate with cell retention and determine the response to intracoronary BMC application in patients with ICM. METHODS AND RESULTS:: 157 patients with stable ICM and no substantial impairment of kidney function received intracoronary BMC administration. Immediately prior to cell application, hs-TnT levels to measure myocardial injury, and NT-proBNP levels as marker of left ventricular wall stress were determined.Patients with elevated hs-TnT were older and had more severe heart failure. Importantly, only patients with elevated baseline hs-TnT≥15.19 pg/ml (upper tertile) demonstrated a significant (p=0.04) reduction in NT-proBNP serum levels (-250[-1465;33]pg/ml; relative reduction -24%) 4 months after BMC administration, whereas NT-proBNP levels remained unchanged in patients in the two lower hs-TnT tertiles. The absolute decrease in NT-proBNP at 4 months was inversely correlated with baseline hs-TnT (r=-0.27, p=0.001). Finally, retention of intracoronarily infused, Indium-labelled cells within the heart was closely associated with hs-TnT levels in patients with chronic ischemic heart failure (p=0.0008, n=10, triple measurements). CONCLUSIONS:: The extent of ongoing myocardial injury as measured by serum levels of hs-TnT predicts the reduction of NT-proBNP serum levels at 4 months after intracoronary BMC administration in patients with ICM, suggesting that beneficial effects of BMC application on LV remodelling and wall stress are confined to patients with ongoing minute myocardial injury. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov. NCT00962364 © 2017 American Heart Association, Inc.


Smyrek I.,Goethe University Frankfurt | Stelzer E.H.K.,Goethe University Frankfurt
Biomedical Optics Express | Year: 2017

Three-dimensional cell biology and histology of tissue sections strongly benefit from advanced light microscopy and optimized staining procedures to gather the full three-dimensional information. In particular, the combination of optical clearing with light sheet-based fluorescence microscopy simplifies fast high-quality imaging of thick biological specimens. However, verified in toto immunostaining protocols for large multicellular spheroids or for tissue sections have not been published. We present a method for the verification of immunostaining in three-dimensional spheroids. The analysis relies on three criteria to evaluate the immunostaining quality: quality of the antibody stain specificity, signal intensity achieved by the staining procedure and the correlation of the signal intensity with that of a homogeneously dispersed fluorescent dye. We optimized and investigated variations of five immunostaining protocols for three-dimensional cell biology. Our method is an important contribution to three-dimensional cell biology and the histology of tissues since it allows to evaluate the efficiency of immunostaining protocols for large three-dimensional specimens, and to study the distribution of protein expression and cell types within spheroids and spheroid-specific morphological structures without the need of physical sectioning. © 2017 Optical Society of America.


News Article | April 21, 2017
Site: www.eurekalert.org

The rising demand for increasingly sophisticated smartphones, tablets and home cinemas is a growing challenge for display technology. At present, organic materials are the most effective way to master this challenge. In particular molecules from the class of materials known as polycyclic aromatic hydrocarbons (PAHs) can be used to produce large and mechanically flexible flat screens. They unite brilliant colours with high resolution and are at the same time low in energy consumption. Chemists at Goethe University Frankfurt are currently working on new types of organic luminescent materials which owe their particularly promising properties to the introduction of boron atoms into the PAH scaffold. To date, the syntheses required have been extremely complex and time-consuming. A recently developed screening process, which makes a wide variety of boron-doped PAHs quickly and easily accessible, could in future alleviate this situation. The technique makes it possible to evaluate their potential as OLED materials. Only the most promising candidates will be examined more extensively in the next stage. As the research group led by Professor Matthias Wagner at the Institute of Inorganic and Analytical Chemistry of Goethe University Frankfurt reports in the scientific journal "Angewandte Chemie", the method is based on a three-component reaction: Two components remain unchanged in all reactions whilst the third is chosen from a broad range of cheaply available PAHs. The reactive boron-containing starting material plays an important role in the assembly of the molecular scaffold. In addition, it gives the compounds obtained the desired optoelectronic properties by increasing luminescence and improving the materials' electrical conductivity. "For a long time, it has mostly been pharmaceutical research which has profited from screening processes", says doctoral researcher Alexandra John. "Yet it makes sense precisely in the dynamic and growing field of organic materials to use similar strategies to achieve results in a cost-efficient and resource-friendly way". Professor Matthias Wagner adds: "Our development's market relevance can also be seen by the fact that the Federal Ministry for Economic Affairs and Energy is giving our research work generous financial support." The funding instrument behind it -- WIPANO -- supports the transfer of knowledge and technology through patents and norms and aims to ensure the commercial exploitation of innovative ideas and inventions generated by public-funded research by safeguarding and utilizing intellectual property. Wagner and John have already filed a patent for their process.


News Article | April 21, 2017
Site: phys.org

A new screening process means that promising OLED lighting materials can be identified more efficiently. Credit: AG Matthias Wagner The rising demand for increasingly sophisticated smartphones, tablets and home cinemas is a growing challenge for display technology. At present, organic materials are the most effective way to master this challenge. In particular molecules from the class of materials known as polycyclic aromatic hydrocarbons (PAHs) can be used to produce large and mechanically flexible flat screens. They unite brilliant colours with high resolution and are at the same time low in energy consumption. Chemists at Goethe University Frankfurt are currently working on new types of organic luminescent materials which owe their particularly promising properties to the introduction of boron atoms into the PAH scaffold. To date, the syntheses required have been extremely complex and time-consuming. A recently developed screening process, which makes a wide variety of boron-doped PAHs quickly and easily accessible, could in future alleviate this situation. The technique makes it possible to evaluate their potential as OLED materials. Only the most promising candidates will be examined more extensively in the next stage. As the research group led by Professor Matthias Wagner at the Institute of Inorganic and Analytical Chemistry of Goethe University Frankfurt reports in the scientific journal Angewandte Chemie, the method is based on a three-component reaction: Two components remain unchanged in all reactions whilst the third is chosen from a broad range of cheaply available PAHs. The reactive boron-containing starting material plays an important role in the assembly of the molecular scaffold. In addition, it gives the compounds obtained the desired optoelectronic properties by increasing luminescence and improving the materials' electrical conductivity. "For a long time, it has mostly been pharmaceutical research which has profited from screening processes", says doctoral researcher Alexandra John. "Yet it makes sense precisely in the dynamic and growing field of organic materials to use similar strategies to achieve results in a cost-efficient and resource-friendly way". Professor Matthias Wagner adds: "Our development's market relevance can also be seen by the fact that the Federal Ministry for Economic Affairs and Energy is giving our research work generous financial support." The funding instrument behind it—WIPANO—supports the transfer of knowledge and technology through patents and norms and aims to ensure the commercial exploitation of innovative ideas and inventions generated by public-funded research by safeguarding and utilizing intellectual property. Wagner and John have already filed a patent for their process. Explore further: New boron compounds for organic light-emitting diodes


News Article | April 17, 2017
Site: www.eurekalert.org

The international Event Horizon Telescope (EHT) Collaboration, which is imaging for the first time the black-hole candidate at the center of our Milky Way, has a major research focus in Germany. A significant contribution to this experiment is part of "BlackHoleCam", a German-Dutch experiment founded in 2014. The research group of Prof. Rezzolla at the Institute for Theoretical Physics at the Goethe University Frankfurt is part of the collaboration. BlackHoleCam is supported by the European Research Council via an ERC Synergy Grant of 14 Million Euros. Due to the strong pull of gravity, not even light can escape from black holes, whose surface, i.e., the event horizon, cannot be observed directly. However, the boundary which separates photons that are trapped from those that can escape from the incredible gravitational pull is called the black-hole "shadow", because it would appear as a shadow against a bright lit background. It is such a shadow that is the target of series of observations presently ongoing of Sgr A*, the name of the black-hole candidate in our Milky Way. During the observations, the researchers will analyze the radio emission emitted by Sgr A*, whose mass is 4.5 million times that of our Sun and whose shadow is about half of the size of the distance between the Sun and the Earth. Despite being so massive, Sgr A* is also very far from us, at a 26,000 light years, making the angular size of the shadow extremely small. Measuring the emission from this surface is therefore equivalent to imaging an apple on the surface of the Moon. To accomplish this ambitious project several radio telescopes across the globe are connected and thus form a virtual telescope with a diameter comparable to the Earth. This technique is called Long Baseline Interferometry (VLBI). The work of BlackHoleCam is lead by Prof. Luciano Rezzolla (ITP, Frankfurt), Prof. Michael Kramer (Max Planck Institute for Radio Astronomy, Bonn), and by Prof. Heino Falcke (Radboud-University Nijmegen, Netherlands); all of them are important contributors of the EHT collaboration. In the current observations of Sgr A*, network of radiotelescopes from Europe, the United States of America, Middle- and South America, and the South Pole telescope are participating at the same time. During the observations, each telescope records the data on hard disks which are shipped after the end of the campaign to one of the high-performance computer centers in the US or to Bonn. In these centers the individual data of the telescopes are combined by supercomputers and an image can be reconstructed. This shadow image can be regarded as the starting point for the theoretical research of Prof. Rezzolla's group. Besides predicting theoretically what type of image scientists is expected to observe, the group in Frankfurt is also working on determining whether it will be possible to establish if Einstein's theory of general relativity is the correct theory of gravity. There are several other theories of gravity besides the well-known one by Einstein and the observations of the black-hole shadow may help to identify the true one. Because of this, scientists in Frankfurt analyze the size and the geometry of the shadow and compare them to synthetic images generated on supercomputers which model accretion flows onto black holes.. These images are computed by solving the equations of relativistic magneto-hydrodynamics and tracing the orbit of photons around black holes in different theories of gravity using state-of-the art numerical tools developed in the group of Prof. Rezzolla. Comparing the synthetic shadow to the observed one may shed light on the existence of one of the most extreme predictions of Einstein's theory of gravity: the existence of black holes. However, as Prof. Rezzolla remarks, "These observations represent a major step forward in the international attempt of understanding the nature of the dark and compact object at the centre of our Galaxy. However, they are just the first step and it is likely that many more observations of increasing precision will be necessary for finally settling this fundamental issue".


News Article | May 4, 2017
Site: www.eurekalert.org

Professor Ute Hellmich of Johannes Gutenberg University Mainz (JGU) has received a Fulbright-Cottrell Award, the most important transatlantic prize recognizing excellence in research and teaching. It is awarded by the German-American Fulbright Commission. This year's two recipients -- Professor Steffen Schumann of Georg-August-Universität Göttingen has been honored alongside Hellmich -- will each receive EUR 63,000 from the German Federal Ministry of Education and Research (BMBF) for a three-year teaching and research project and be given the opportunity to participate in the annual Cottrell Scholars Conferences in the USA. The official award presentation took place during a ceremony organized by the Fulbright Commission in Berlin. The award recognizes the combined research and teaching achievements of young German researchers who undertake teaching assignments in connection with Bachelor degree programs in the fields of chemistry, physics, astronomy, and biochemistry. The corresponding Cottrell Scholar Award has been presented annually in the USA since 1994. "The public image of a researcher is decisively influenced by his or her achievements in the field of research although a major part of our everyday work actually involves teaching and supervising students and doctoral candidates," emphasized Hellmich. "The Fulbright-Cottrell Award is unique as it recognizes not only accomplishments in research but also explicitly teaching achievements and thus I feel deeply honored by this award." It was Hellmich's proposed project "From local alterations to global changes: ABC transporters to study molecular determinants of protein function and dynamics" that convinced the jury. The project focuses on the molecular dynamics of membrane proteins and how the tiny machines in the membrane of our body cells control the uptake or release of substances such as nutrients and toxins. "Membrane proteins need to move in a very controlled manner to achieve the correct directional movement; it is as if they were a sluice that can only be opened on one side at a particular time," explained Hellmich. "We want to understand how these machines work and, using these machines as an example, reveal to our students how wonderful biochemistry can be and how satisfying a field of study it is." Ute Hellmich, born in 1981 in Heidelberg, studied Biochemistry at Goethe University Frankfurt and subsequently earned her doctorate with a thesis on the interaction between membrane proteins and lipids. She also spent periods abroad at the University of Cambridge and Harvard University. Hellmich was appointed Junior Professor of Membrane Biochemistry at Johannes Gutenberg University Mainz in January 2015. Her professorship is sponsored by the Carl Zeiss Foundation. The biochemist is also a Guest Scientist at the Center for Biomolecular Magnetic Resonance (BMRZ) at Goethe University Frankfurt. Her team currently investigates the functional dynamics of multi-substance transporters and ion channels in parasites.


Bauchle B.,Frankfurt Institute for Advanced Studies | Bleicher M.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2010

Direct photon emission in heavy-ion collisions is calculated within a relativistic micro + macro hybrid model and compared to the microscopic transport model, the Ultra-relativistic Quantum Molecular Dynamics model. In the hybrid approach, the high-density part of the evolution is replaced by an ideal three-dimensional hydrodynamic calculation. This allows the effects of viscosity and full local thermalization, in comparison with the transport model of the ideal fluid dynamics, to be examined. The origin of high-p photons as well as the impact of elementary high-√s collisions is studied. The contribution of different production channels and nonthermal radiation to the spectrum of direct photons is further explored. Detailed comparisons to the measurements by the WA98 Collaboration are also undertaken. © 2010 The American Physical Society.


Huang X.-G.,Frankfurt Institute for Advanced Studies | Huang X.-G.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2010

By adopting a T-matrix-based method within the G0G approximation for the pair susceptibility, we studied the effects of pairing fluctuation on the BCS-BEC crossover in symmetric nuclear matter. The pairing fluctuation induces a pseudogap in the excitation spectrum of a nucleon in both superfluid and normal phases. The critical temperature of the superfluid transition was calculated. It differs from the BCS result remarkably when density is low. We also computed the specific heat, which shows a nearly ideal BEC-type temperature dependence at low density, but a BCS-type behavior at high density. This qualitative change of the temperature dependence of specific heat may serve as a thermodynamic signal for the BCS-BEC crossover. © 2010 The American Physical Society.


Hofmann S.,Helmholtz Center for Heavy Ion Research | Hofmann S.,Goethe University Frankfurt
Radiochimica Acta | Year: 2011

The new elements from Z = 107 to 112 were synthesized in cold fusion reactions based on targets of lead and bismuth. The principle physical concepts are presented which led to the application of this reaction type in search experiments for new elements. Described are the technical developments from early mechanical devices to experiments with recoil separators. An overview is given of present experiments which use cold fusion for systematic studies and synthesis of new isotopes. Perspectives are also presented for the application of cold fusion reactions in synthesis of elements beyond element 113, the so far heaviest element produced in a cold fusion reaction. Further, the transition of hot fusion to cold fusion is pointed out, which occurs in reactions for synthesis of elements near Z = 126 using actinide targets and beams of neutron rich isotopes of elements from iron to germanium. © by Oldenbourg Wissenschaftsverlag, München.


Qin S.-X.,Goethe University Frankfurt | Rischke D.H.,Goethe University Frankfurt | Rischke D.H.,Frankfurt Institute for Advanced Studies
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The maximum entropy method is used to compute the quark spectral function at nonzero temperature. We solve the gap equation of quantum chromodynamics (QCD) self-consistently, employing a rainbow kernel which phenomenologically models results from Dyson-Schwinger equations and lattice QCD. We use the criterion of positivity restoration of the spectral function as a signal for deconfinement. Our calculation indicates that the critical temperature of deconfinement Td is slightly smaller than the one of chiral symmetry restoration Tc: Td∼94%Tc in the chiral limit and Td∼96%Tc with physical light quark masses. Since these deviations are within the systematic error of our approach, it is reasonable to conclude that chiral symmetry restoration and deconfinement coincide at zero chemical potential. © 2013 American Physical Society.


Iwata Y.,Helmholtz Center for Heavy Ion Research | Maruhn J.A.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2011

The tensor and spin-orbit forces contribute essentially to the formation of the spin mean field, and give rise to the same dynamical effect, namely spin polarization. In this paper, based on time-dependent density functional calculations, we show that the tensor force, which usually acts like a small correction to the spin-orbit force, becomes more important in heavy-ion reactions and the effect increases with the mass of the system. © 2011 American Physical Society.


Scharf K.-D.,Goethe University Frankfurt | Berberich T.,Biodiversity and Climate Research Center | Ebersberger I.,University of Veterinary Medicine Vienna | Nover L.,Goethe University Frankfurt
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2012

Ten years after the first overview of a complete plant Hsf family was presented for Arabidopsis thaliana by Nover et al. [1], we compiled data for 252 Hsfs from nine plant species (five eudicots and four monocots) with complete or almost complete genome sequences. The new data set provides interesting insights into phylogenetic relationships within the Hsf family in plants and allows the refinement of their classification into distinct groups. Numerous publications over the last decade document the diversification and functional interaction of Hsfs as well as their integration into the complex stress signaling and response networks of plants. This article is part of a Special Issue entitled: Plant gene regulation in response to abiotic stress. © 2011 Elsevier B.V.


Deng W.-T.,Frankfurt Institute for Advanced Studies | Huang X.-G.,Frankfurt Institute for Advanced Studies | Huang X.-G.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2012

We compute the electromagnetic fields generated in heavy-ion collisions by using the HIJING model. Although after averaging over many events only the magnetic field perpendicular to the reaction plane is sizable, we find very strong electric and magnetic fields both parallel and perpendicular to the reaction plane on the event-by-event basis. We study the time evolution and the spatial distribution of these fields. In particular, the electromagnetic response of the quark-gluon plasma can give nontrivial evolution of the electromagnetic fields. The implications of the strong electromagnetic fields on the hadronic observables are also discussed. © 2012 American Physical Society.


Dimmeler S.,Goethe University Frankfurt
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2011

MicroRNAs (miRs) are small, noncoding RNAs that posttranscriptionally control gene expression by inhibiting protein translation or inducing target mRNA destabilization. Besides their intracellular function, recent studies demonstrate that miRs can be exported or released by cells and circulate with the blood in a remarkably stable form. The discovery of circulating miRs opens up intriguing possibilities to use the circulating miR patterns as biomarker for cardiovascular diseases. Cardiac injury as it occurs after acute myocardial infarction increases the circulating levels of several myocardial-derived miRs (eg, miR-1, miR-133, miR-499, miR-208), whereas patients with coronary artery disease or diabetes showed reduced levels of endothelial-enriched miRs, such as miR-126. This review article summarizes the current clinical and experimental studies addressing the role of circulating miRs as a diagnostic or prognostic biomarker in cardiovascular disease. In addition, the mechanisms by which miRs are released and their putative function as long-distance communicators are discussed. © 2011 American Heart Association. All rights reserved.


Litvinova E.V.,Helmholtz Center for Heavy Ion Research | Litvinova E.V.,Goethe University Frankfurt | Afanasjev A.V.,Mississippi State University
Physical Review C - Nuclear Physics | Year: 2011

The impact of particle-vibration coupling and polarization effects due to deformation and time-odd mean fields on single-particle spectra is studied systematically in doubly magic nuclei from low-mass Ni56 up to superheavy ones. Particle-vibration coupling is treated fully self-consistently within the framework of the relativistic particle-vibration coupling model. Polarization effects due to deformation and time-odd mean field induced by odd particle are computed within covariant density functional theory. It has been found that among these contributions the coupling to vibrations makes a major impact on the single-particle structure. The impact of particle-vibration coupling and polarization effects on calculated single-particle spectra, the size of the shell gaps, the spin-orbit splittings and the energy splittings in pseudospin doublets is discussed in detail; these physical observables are compared with experiment. Particle-vibration coupling has to be taken into account when model calculations are compared with experiment since this coupling is responsible for observed fragmentation of experimental levels; experimental spectroscopic factors are reasonably well described in model calculations. © 2011 American Physical Society.


Weis B.L.,Goethe University Frankfurt | Schleiff E.,Goethe University Frankfurt | Zerges W.,Concordia University at Montréal
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013

Cells have complex membranous organelles for the compartmentalization and regulation of most intracellular processes. Organelle biogenesis and maintenance requires newly synthesized proteins, each of which needs to go from the ribosome translating its mRNA to the correct membrane for insertion or translocation to an organellar subcompartment. Decades of research have revealed how proteins are targeted to the correct organelle and translocated across one or more organelle membranes to the compartment where they function. The paradigm examples involve interactions between a peptide sequence in the protein, localization factors, and various membrane-embedded translocation machineries. Membrane translocation is either cotranslational or posttranslational depending on the protein and target organelle. Meanwhile, research in embryos, neurons and yeast revealed an alternative targeting mechanism in which the mRNA is localized and only then translated to synthesize the protein in the correct location. In these cases, the targeting information is encoded by cis-acting sequences in the mRNA ("Zipcodes") that interact with localization factors and, in many cases, are transported by molecular motors on cytoskeletal filaments. Recently, evidence has been found for this "mRNA-based" mechanism in organelle protein targeting to endoplasmic reticulum, mitochondria, and the photosynthetic membranes within chloroplasts. Here we review known and potential roles of mRNA localization in protein targeting to and within organelles. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. © 2012 Elsevier B.V.


Figge M.T.,Leibniz Institute for Natural Product Research and Infection Biology | Osiewacz H.D.,Goethe University Frankfurt | Reichert A.S.,Goethe University Frankfurt
BioEssays | Year: 2013

Maintenance of functional mitochondria is essential in order to prevent degenerative processes leading to disease and aging. Mitochondrial dynamics plays a crucial role in ensuring mitochondrial quality but may also generate and spread molecular damage through a population of mitochondria. Computational simulations suggest that this dynamics is advantageous when mitochondria are not or only marginally damaged. In contrast, at a higher degree of damage, mitochondrial dynamics may be disadvantageous. Deceleration of fusion-fission cycles could be one way to adapt to this situation and to delay a further decline in mitochondrial quality. However, this adaptive response makes the mitochondrial network more vulnerable to additional molecular damage. The "mitochondrial infectious damage adaptation" (MIDA) model explains a number of inconsistent and counterintuitive data such as the "clonal expansion" of mutant mitochondrial DNA. We propose that mitochondrial dynamics is a double-edged sword and suggest ways to test this experimentally. © 2013 WILEY Periodicals, Inc.


Ridding M.C.,University of Adelaide | Ziemann U.,Goethe University Frankfurt
Journal of Physiology | Year: 2010

The ability to induce cortical plasticity with non-invasive brain stimulation (NBS) techniques has provided novel and exciting opportunities for examining the role of the human cortex during a variety of behaviours. Additionally, and importantly, the induction of lasting changes in cortical excitability can, under some conditions, reversibly modify behaviour and interact with normal learning. Such findings have driven a large number of recent studies examining whether by using such approaches it might be possible to induce functionally significant changes in patients with a large variety of neurological and psychiatric conditions including stroke, Parkinson's disease and depression. However, even in neurologically normal subjects the variability in the neurophysiological and behavioural response to such brain stimulation techniques is high. This variability at present limits the therapeutic usefulness of these techniques. The cause of this variability is multifactorial and to some degree still unknown. However, a number of factors that can influence the induction of plasticity have been identified. This review will summarise what is known about the causes of variability in healthy subjects and propose additional factors that are likely to be important determinants. A greater understanding of these determinants is critical for optimising the therapeutic applications of non-invasive brain stimulation techniques. © 2010 The Authors. Journal compilation © 2010 The Physiological Society.


Deng H.,University of Michigan | Haug H.,Goethe University Frankfurt | Yamamoto Y.,Stanford University | Yamamoto Y.,Chiyoda Corporation | Yamamoto Y.,Nippon Telegraph and Telephone
Reviews of Modern Physics | Year: 2010

In the past decade, a two-dimensional matter-light system called the microcavity exciton-polariton has emerged as a new promising candidate of Bose-Einstein condensation (BEC) in solids. Many pieces of important evidence of polariton BEC have been established recently in GaAs and CdTe microcavities at the liquid helium temperature, opening a door to rich many-body physics inaccessible in experiments before. Technological progress also made polariton BEC at room temperatures promising. In parallel with experimental progresses, theoretical frameworks and numerical simulations are developed, and our understanding of the system has greatly advanced. In this article, recent experiments and corresponding theoretical pictures based on the Gross-Pitaevskii equations and the Boltzmann kinetic simulations for a finite-size BEC of polaritons are reviewed. © 2010 The American Physical Society.


Korfiatis N.,Goethe University Frankfurt | Poulos M.,Ionian University
Expert Systems with Applications | Year: 2013

Online consumer reviews play an important role in the decision to purchase services online, mainly due to the rich information source they provide to consumers in terms of evaluating "experience"-type products and services that can be booked using the Internet, with online travel services being a significant example. However, different types of travelers assess each quality indicator differently, depending on the type of travel they engage in, and not necessarily their cultural or age background (e.g. solo travelers, young couples with children etc.). In this study, we present architecture for a demographic recommendation system, based on a user-defined hierarchy of service quality indicator importance, and classification of traveler types. We use an algebraic approach to ascertain preferences from a large dataset that we obtained from the popular travel website Booking.com using a web crawler and compared with the customer-constructed preference matrix. Interestingly, the architecture of the evaluated recommendation system takes into account already defined demand characteristics of the hotels (such as the number of reviews of specific consumer types compared to the total number of reviews) in order to provide an example architecture for a recommendation system based on user-defined preference criteria. © 2013 Elsevier Ltd. All rights reserved.


Struckmeier J.,Helmholtz Center for Heavy Ion Research | Struckmeier J.,Goethe University Frankfurt
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

It is widely accepted that the fundamental geometrical law of nature should follow from an action principle. The particular subset of transformations of a system's dynamical variables that maintain the form of the action principle comprises the group of canonical transformations. In the context of canonical field theory, the adjective "extended" signifies that not only the fields but also the space-time geometry is subject to transformation. Thus, in order to be physical, the transition to another, possibly noninertial frame of reference must necessarily constitute an extended canonical transformation that defines the general mapping of the connection coefficients, hence the quantities that determine the space-time curvature and torsion of the respective reference frame. The canonical transformation formalism defines simultaneously the transformation rules for the conjugates of the connection coefficients and for the Hamiltonian. As will be shown, this yields unambiguously a particular Hamiltonian that is form-invariant under the canonical transformation of the connection coefficients and thus satisfies the general principle of relativity. This Hamiltonian turns out to be a quadratic function of the curvature tensor. Its Legendre-transformed counterpart then establishes a unique Lagrangian description of the dynamics of space-time that is not postulated but derived from basic principles, namely the action principle and the general principle of relativity. Moreover, the resulting theory satisfies the principle of scale invariance and is renormalizable. © 2015 American Physical Society.


Wu P.F.,University of Surrey | Korfiatis N.,Goethe University Frankfurt
Journal of the American Society for Information Science and Technology | Year: 2013

Taking a structuration perspective and integrating reciprocity research in economics, this study examines the dynamics of reciprocal interactions in social question & answer communities. We postulate that individual users of social Q&A constantly adjust their kindness in the direction of the observed benefit and effort of others. Collective reciprocity emerges from this pattern of conditional strategy of reciprocation and helps form a structure that guides the very interactions that give birth to the structure. Based on a large sample of data from Yahoo! Answers, our empirical analysis supports the collective reciprocity premise, showing that the more effort (relative to benefit) an asker contributes to the community, the more likely the community will return the favor. On the other hand, the more benefit (relative to effort) the asker takes from the community, the less likely the community will cooperate in terms of providing answers. We conclude that a structuration view of reciprocity sheds light on the duality of social norms in online communities. © 2013 ASIS&T.


Grant
Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: INFRA-2010-1.2.3 | Award Amount: 2.43M | Year: 2010

Structural biology and life sciences in general, and NMR in particular, have always been associated with advanced computing. The current challenges in the post-genomic era, with their focus on biomolecular interactions, call for virtual research platforms that provide the worldwide research community with both user-friendly tools, platforms for data analysis and exchange, and an underlying e-infrastructure.\n\nThe WeNMR project will group different research teams into a virtual research community at a worldwide level. It builds on the established eNMR e-Infrastructure tightly integrated into the EGEE and its steadily growing virtual organization currently representing the second largest VO in the life science area. WeNMR will consolidate the operation of the current services and provide an e-Infrastucture platform and structural biology Science Gateway towards EGI for the users of existing infrastructures. It will involve researchers from around the world and will build bridges to other areas of structural biology. Integration with a rapidly growing and highly complementary method, SAXS, is directly included in WeNMR, but links will also be established to related cryo-EM and X-ray crystallography initiatives. WeNMR will serve all relevant INSTRUCT communities in line with the ESFRI roadmap.\n\nFrom an e-infrastructure viewpoint, WeNMR will strengthen the European ties with National Grid Initiatives, the new EGI and PRACE initiatives toward an effective sharing of the offered service. Collaborations will be established with the Asian, South-African, South- and North-American GRID initiatives, in close contact with the existing EC projects, to extend and open the WeNMR Life-Science Gateway at global level. WeNMR will establish and promote best practices in life sciences and offers (virtual) training services to worldwide researchers. It will work with all stakeholders, including an industry panel, to ensure its sustainability.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.2.1-7 | Award Amount: 10.33M | Year: 2009

Mitochondrial dysfunction is a major hallmark of various neurodegenerative disorders including Alzheimers disease, Parkinsons disease, Huntingtons diseases or Amyotrophic Lateral Sclerosis (ALS). However linking mitochondrial dysfunction to the pathogenesis of some of these diseases still needs to be elucidated. Furthermore, in pathologies where this link is already established, the question remains whether specific targets or mechanisms involved in mitochondrial dysfunction will be amenable to therapeutic intervention. MitoTarget is an ambitious project aimed at providing solid data to better understand and exploit the circumstantial evidence linking mitochondrial dysfunction with neuronal dysfunction culminating in neurodegenerative disease. A 36 months translational research program will bring together a unique partnership between basic scientists, a seasoned team of clinical investigators and a SME that has identified a first-in-class compound, TRO19622, that targets mitochondria and has powerful neuroprotective and neuroregenerative activities. In parallel, and orchestrated by the SME that is the coordinator of the project, MitoTarget will bring together a more comprehensive insight into the mechanisms leading to mitochondrial impairments and establish their clinical relevance in a severe orphan neurodegenerative disease, ALS. If successful, it is expected that from this proof of principle a new class of therapeutic agents targeting the underlying mitochondrial dysfunction in neurons or their supporting cells will emerge. Results of the project have the potential to create a new paradigm for the drug discovery for neurodegenerative diseases.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.1.4 | Award Amount: 13.06M | Year: 2010

The number of transactions performed electronically is rising fast. Every day people use the Internet for purposes ranging from accessing information to electronic commerce and e-banking, to interactions with government bodies. As securing these transactions requires strong authentication, electronic authentication tokens and mechanisms become common. These mechanisms unfortunately use unique identifiers that link all transactions to users, thus seriously threatening their privacy.In several application areas, unique identification is inappropriate, making privacy-preserving attribute-based authentication desirable. However, some applications require both accountability and anonymity: e.g. voting, opinion surveys, or services restricted depending on age, citizenship, or other attributes. Other applications only require the ability to link to natural persons under very exceptional circumstances (e.g. criminal prosecution) and should otherwise make such linkage impossible. Over the past few years Attribute-based Credential (ABC) systems have emerged to support userids that can be trusted yet protect privacy at the same time.A position paper issued in 2009-02 by ENISA on Privacy Features of European eID Card Specifications underlines the need for privacy-respecting use of unique identifiers in emerging eID cards, and explicitly refers to ABC technologies as having significant potential in this area. None of these technologies has been successfully deployed so far for lack of architectural guidance and practical experience.ABC4Trusts objective is (1) to define a common, unified architecture for ABC systems to allow comparing their respective features and combining them on common platforms, and (2) to deliver open reference implementations of selected ABC systems and deploy them in actual production pilots allowing provably accredited members of restricted communities to provide anonymous feedback on their community or its members.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.91M | Year: 2015

Attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are frequent, chronic and highly heritable neurodevelopmental disorders. Despite their societal importance, progress in understanding disease biology has been slow and no curative treatment options are available. The pan-European training network MiND aims to educate a new generation of researchers in the field of neurodevelopmental disorders, through innovation-oriented research combined with highly interdisciplinary and intersectoral international training. Research and training in MiND span state-of-the-art topics in the fields of ADHD, ASD and their yet un-investigated overlap. We combine advanced (epi-)genetics approaches with bioinformatics and develop novel cell and animal models of increasing complexity to understand pathomechanisms. Integrated with research in large human DNA-neuroimaging-cognition data sets, we push forward the understanding of the biology leading from gene to cognition and disease. Our mechanistic work is embedded in a framework exploring alternative disease definitions for ADHD and ASD across the lifespan and working towards improved treatment: we use novel cognitive assessments, we probe the microbiome for dietary interventions reducing symptoms and evaluate mindfulness training as non-pharmacological treatment options, in addition to developing new compounds for pharmacological treatment optimization and individualization. The strategic collaboration of world-leading academic groups, research-intensive commercial enterprises and patient organisations will deliver 15 young, scientifically excellent researchers which are optimally prepared for private sector and academic careers. MiND can be expected to impact patients and society by improving our understanding of disease biology, by developing novel diagnostic and treatment strategies, and by raising awareness for the necessity of research of neurodevelopmental disorders from childhood to adulthood.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2011.5.2 | Award Amount: 5.47M | Year: 2013

The Go-Smart project will build a generic open-source software simulation environment for planning of image guided percutaneous Minimally Invasive Cancer Treatment (MICT). MICT includes radiofrequency ablation (RFA), cryoablation, microwave ablation (MW), transarterial chemoembolisation (TACE), brachytherapy (BT), and prospectively, irreversible electroporation (IRE). Beside of TACE each type of MICT uses needles that are inserted into the tumour tissue and the tissue is destroyed through heating, cooling, and application of an electric field or radiation. These treatments are often combined with TACE. The commonalities between the different procedures allow for the development of a generic, reusable, robust simulation environment with the relevant physics and physiology needed to correctly predict the result of MICT in terms of lesion size and shape. The environment will incorporate patient data and appropriate physiological models to simulate tissue response to heat, cooling, hypoxia, radiation, or electrical pulses. The models will account for multi-scale physiological dependencies between a full organ, its anatomical structures and tissue properties down to the cellular level. The software environment will be open-ended with extendable interfaces to allow clinicians to add further patient data collected before, during and after MICTs. This data will be used by the research community to refine the existing physiological tissue models thus transforming the environment into a user-driven growing info-structure. The Go-Smart environment will allow the Interventional Radiologists (IR) to select an optimal type of MICT by simulating the personalised result of the different treatments and medical protocols in patient specific conditions. Bringing different MICTs into a unified simulation environment is a unique approach and will promote their systematic comparison and establish much needed common standards and protocols for MICT in Europe.


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

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


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.1.1-5 | Award Amount: 15.72M | Year: 2008

The European Drug Initiative on Channels and Transporters, EDICT, allies for the first time, partners with world-class expertise in both the structural and functional characterisation of membrane channels and transporters. State-of-the-art facilities and personnel for X-ray crystallography, Electron Microscopy and Nuclear Magnetic Resonance and the latest throughput technology, will provide infrastructure for scientists characterising channel and transport functions in man and pathogenic microorganisms. Our experts in the analyses of all the databases of these membrane proteins and molecular modelling will work with our industrial partners on specific targets chosen for their potential to improve the health of European citizens, increase the competitiveness of European health-related industries and businesses and address global health issues. EDICT will increase knowledge of biological processes and mechanisms involved in normal health and in specific disease situations, and transpose this knowledge into clinical applications. By combining computational and experimental analyses, existing detailed molecular models of channel and transporter proteins, and novel structures derived by our partners, will be analysed to identify the critical regions constituting drug targets. These basic discoveries will be translated via in silico and experimental strategies with our industrial partners into the design of novel drugs that modify activities of the membrane proteins for the benefit of the patients. The range of human proteins covered includes potassium channels, anion and cation transporters, neurotransmitter transporters, cation-transporting ATPases and mitochondrial transporters. Structures of bacterial homologues to the human proteins are exploited to inform the studies of their human counterparts


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2011.1.4 | Award Amount: 13.48M | Year: 2012

Information security threats to organisations have changed completely over the last decade, due to the complexity and dynamic nature of infrastructures and attacks. Successful attacks cost society billions a year, impacting vital services and the economy. Examples include StuxNet, using infected USB sticks to sabotage nuclear plants, and the DigiNotar attack, using fake digital certificates to spy on website traffic. New attacks cleverly exploit multiple organisational vulnerabilities, involving physical security and human behaviour. Defenders need to make rapid decisions regarding which attacks to block, as both infrastructure and attacker knowledge change rapidly.\n\nCurrent risk management methods provide descriptive tools for assessing threats by systematic brainstorming. Attack opportunities will be identified and prevented only if people can conceive them. In todays dynamic attack landscape, this process is too slow and exceeds the limits of human imaginative capability. Emerging security risks demand tool support to predict, prioritise, and prevent complex attacks systematically. The TREsPASS project will make this possible, by building an attack navigator. This navigator makes it possible to say which attack opportunities are possible, which of them are the most urgent, and which countermeasures are most effective. To this end, the project combines knowledge from technical sciences (how vulnerable are protocols and software), social sciences (how likely are people to succumb to social engineering), and state-of-the-art industry processes and tools.\n\nBy integrating European expertise on socio-technical security into a widely applicable and standardised framework, TREsPASS will reduce security incidents in Europe, and allow organisations and their customers to make informed decisions about security investments. This increased resilience of European businesses both large and small is vital to safeguarding the social and economic prospects of Europe.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 2.83M | Year: 2012

The Marie Curie Initial Training Network SPOT-ITN will establish a multi-site network of early stage and experienced researchers at 9 partner institutions - including 3 from the private sector - in 4 European member countries and Israel to investigate fundamental and applied aspects of thermotolerance mechanisms contributing to the protection of pollen development at increased ambient temperatures. The envisioned joint research program is of broad commercial interest and will be an important contribution to the efforts undertaken world-wide to ensure future stability of food production in view of the prognosticated global climate change. Although the initial focus will be on tomato as an important agricultural crop, the results are expected to become applicable to other cultivated plants in the long run. Based on individual research projects of the young researchers, the main focus of the network will be to perform common, multidisciplinary experiments on a broad variety of heat-sensitive and heat-tolerant tomato genotypes and mutant lines at the molecular, cellular and organismic level with two major objectives: i) to describe the molecular basis of the striking sensitivity of pollen development at higher temperatures and regulation of pollen-specific heat stress response and thermotolerance mechanisms; and ii) to develop BIOMARKERS of POLLEN THERMOTOLERANCE usable in future screening programs to improve breeding of new heat-tolerant cultivars. Besides training of specific research tasks, the multi-disciplinary research program includes advanced methods and high-throughput technologies in plant genetics, molecular and cell biology, physiology, and bioinformatics. In addition, a multitude of opportunities are provided for training complementary skills to broaden the knowledge of the young researchers for developing their future career with comprehensive possibilities in a wide field of research areas in Life Sciences in both, the public and the private sector.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SiS.2011.2.2.3.1 | Award Amount: 1.99M | Year: 2011

Science and mathematics education is important for Europe. Creativity and innovation are equally recognised as important, and their strengthening in and through education as a vital priority. Importantly, also, creativity holds a strong position in early childhood. The Creative Little Scientists project constitutes a timely contribution to a better understanding, at the European level, of the potential available on the common ground that science and mathematics education in pre-school and early primary school can share with creativity. It provides a clear picture of existing and possible practices, as well as their implications and the related opportunities and challenges. Based on this, the project proposes guidelines, curricula and exemplary materials for relevant teacher training in the various European contexts. The research findings and outcomes are carefully disseminated, in easy to use formats, to all stakeholders at the European level. To achieve these, the Creative Little Scientists project brings together a consortium comprising expertise of the highest level and quality in the areas of science and mathematics education in early childhood, creativity in education, cognitive psychology, comparative educational studies, and teacher training. This consortium carries out research in a sample of nine European countries (Belgium, Finland, France, Germany, Greece, Malta, Portugal, Romania, and the UK) which have been selected to represent a wide spectrum of educational, economic, social and cultural contexts. In this way, the consortium will be able to extrapolate and exploit the findings from the nine sample countries, at the European level.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 4.68M | Year: 2009

Photoprotection against excess absorbed light energy is an essential and universal attribute of oxygenic photosynthetic organisms. This requirement has been a strong force in the evolution of plants and micro-organisms, and a diverse range of solutions have arisen. It has determined survival, productivity and habitat preference, and it determines the ceiling on the efficiency of energy conversion in photosynthesis in natural environment. Its investigation also provides insights into unique nanoscale switching processes. Understanding the molecular mechanisms of biological light adaptation will therefore have implication for many aspects of life, such as agriculture and food security, biodiversity and global climate change, biosolar energy and biofuels. This network brings together major high-quality EU centres with expertise in a wide range of disciplines from plant physiology to molecular biology, structural biology and photophysics and with great interest in interdisciplinary collaborative research. The network will thus provide a unique training opportunity for young researchers in key aspects of molecular biosciences and biophysical sciences in the context of practical applications in instrument development, agronomy, ecology and biotechnology. Researchers from within and outside this network will receive key research skills from several disciplines combined in a high-level and intrinsically collaborative research project, key transferable skills on information technology, written and oral communication and critical assessment, and key business and commercial skills on commercial exploitation and product development.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: ICT-06-2014 | Award Amount: 3.33M | Year: 2015

Never technology has penetrated so deeply and fast in society everyday life as Internet has done in the last decades and is expected to do in the future. The enormous flux of data transferred via wireless networks, increasing at exponential pace, makes todays state of the art networks soon outdated. Large parts of the society are deprived of adequate access to Internet due to the high costs, long deployment time of optical fibres and inadequate performance of wireless networks. This inequality will most likely pertain in the next years. Millimetre waves are the most promising solution to support the increasing data throughput and to be a credible fibre complement for the last miles. The TWEETHER aim is to realise the millimetre wave Point to multi Point segment to finally link fibre, and sub-6GHz distribution for a full three segment hybrid network, that is the most cost-effective architecture to reach mobile or fixed final individual client. The TWEETHER project responds to the call H2020-ICT6, to foster smart wireless network architecture for high capacity everywhere outdoor data distribution, in gigabit class, that other technologies cannot support, at low operating cost. High spectrum and energy efficient W-band (92-95GHz) technology will be developed. A powerful and compact transmission hub based on a novel traveling wave tube power amplifier with performance precluded to any other technology and an advanced chipset in a compact terminal will be realised. The TWEETHER system will be tested in a real operating environment. Integrated smart networks of backhaul for 4G and 5G small cells and of access for residential houses are the targeted market that benefits from the actual light regulation of W-band. A big company Thales Electron Devices, four SMEs, Bluwan, OMMIC, HFSE, Fibernova, and three top Universities, Lancaster, Goethe Frankfurt, Politecnica de Valencia, join their expertise to successfully tackle the formidable challenges of the TWEETHER project.


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

In the face of the increasing global consumption of fossil resources, photosynthetic organisms offer an attractive alternative that could meet our rising future needs as clean, renewable, sources of energy and for the production of fine chemicals. Key to the efficient exploitation of these organisms is to optimise the conversion of Solar Energy into Biomass (SE2B). The SE2B network deals with this optimisation in an interdisciplinary approach including molecular biology, biochemistry, biophysics and biotechnology. Regulation processes at the level of the photosynthetic membranes, integrating molecular processes within individual proteins up to flexible re-arrangements of the membranes, will be analysed as a dynamic network of interacting regulations. SE2B will yield information about the similarities and differences between cyanobacteria, green algae, diatoms and higher plants, the organisms most commonly employed in biotechnological approaches exploiting photosynthetic organisms, as well as in agriculture. The knowledge gained from understanding these phenomena will be directly transferred to increase the productivity of algal mass cultures for valuable products, and for the development of sophisticated analytic devices that are used to optimise this production. In future, the knowledge created can also be applicable to the design of synthetic cell factories with efficient light harvesting and energy conversion systems. The SE2B network will train young researchers to work at the forefront of innovations that shape the bio-based economy. SE2B will develop a training program based on individual and network-wide training on key research and transferable skills, and will furthermore disseminate these results by open online courses prepared by the young researchers themselves.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.4.3 | Award Amount: 4.59M | Year: 2010

The FIRST project provides a large-scale information extraction and integration infrastructure that supports non-ICT skilled end users for on-demand financial information access and execution of financial market analyses. Innovations in FIRST are: information extraction from unreliable semi-structured sources on a massive scale and in near real-time; automatic reuse of existing ontologies, large-scale ontology learning, and advanced decision models making use of semantic attributes.The FIRST Decision Support Infrastructure enables end-users to configure, deploy, and execute financial decision models with associated information channels. The FIRST Ontology Infrastructure provides tools for semi-automatically creating and maintaining domain knowledge models. The FIRST Semantic Information Extraction System addresses noise, uncertainty, and semantic interpretation of information sources. The FIRST Information Integration Infrastructure consolidates information from very large heterogeneous information sources.FIRST validates its innovations by three complementary use cases of market surveillance, investment management, and online retail banking and brokerage. The consortium comprises for each solution providers, data sources, and end users. FIRST implements a systematic strategy for scaling its methods and software infrastructure to the processing of massive amounts of information in real-time by three steps: (1) functional prototype, (2) scaling for non time-critical processing of massive historical data, and (3) scaling for massive live streams of structured feeds, textual news wire feeds, as well as semi-structured Web information in real-time.The impact is ensured through an active open source strategy which (1) bases all basic software components in the fields of ontology learning, information extraction, information integration, and decision support on existing open source software and (2) releases FIRST software as open source software.


Grant
Agency: European Commission | Branch: H2020 | Program: SGA-RIA | Phase: FETFLAGSHIP | Award Amount: 89.00M | Year: 2016

Understanding the human brain is one of the greatest scientific challenges of our time. Such an understanding can provide profound insights into our humanity, leading to fundamentally new computing technologies, and transforming the diagnosis and treatment of brain disorders. Modern ICT brings this prospect within reach. The HBP Flagship Initiative (HBP) thus proposes a unique strategy that uses ICT to integrate neuroscience data from around the world, to develop a unified multi-level understanding of the brain and diseases, and ultimately to emulate its computational capabilities. The goal is to catalyze a global collaborative effort. During the HBPs first Specific Grant Agreement (SGA1), the HBP Core Project will outline the basis for building and operating a tightly integrated Research Infrastructure, providing HBP researchers and the scientific Community with unique resources and capabilities. Partnering Projects will enable independent research groups to expand the capabilities of the HBP Platforms, in order to use them to address otherwise intractable problems in neuroscience, computing and medicine in the future. In addition, collaborations with other national, European and international initiatives will create synergies, maximizing returns on research investment. SGA1 covers the detailed steps that will be taken to move the HBP closer to achieving its ambitious Flagship Objectives.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.97M | Year: 2017

MMbio will bridge the classically separate disciplines of Chemistry and Biology by assembling leading experts from academia and non-academic partners (industry, technology transfer & science communication) to bring about systems designed to interfere therapeutically with gene expression in living cells. Expertise in nucleic acid synthesis, its molecular recognition and chemical reactivity is combined with drug delivery, cellular biology and experimental medicine. This project represents a concerted effort to make use of a basic and quantitative understanding of chemical interactions to develop and deliver oligonucleotide molecules of utility for therapy. Our chemical biology approach to this field is ambitious in its breadth and represents a unqiues opportunity to educate young scientists across sectorial and disciplinary barriers. Training will naturally encompass a wide range of skills, requiring a joint effort of chemists and biologists to introduce young researchers in a structured way to and array of research methodologies that no single research grouping could provide. The incorporation of early-stage and later stag ebiotechnology enterprises ensures that commercialisation of methodologies as well as the drug development process is covered in this ITN. We hope that MMBio will train scientists able to understand both the biological problem and the chemistry that holds the possible solution and develop original experimental approaches to stimulate European academic and commercial success in this area.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.19M | Year: 2016

Understanding mechanisms underlying comorbid disorders poses a challenge for developing precision medicine tools. Psychiatric disorders are highly comorbid, and are among the last areas of medicine, where classification is driven by phenomenology rather than pathophysiology. We will study comorbidity between the most frequent psychiatric conditions, ADHD, mood/anxiety, and substance use disorders, and a highly prevalent somatic disease, obesity. ADHD, a childhood-onset disorder, forms the entry into a lifelong negative trajectory characterized by these comorbidities. Common mechanisms underlying this course are unknown, despite their relevance for early detection, prevention, and treatment. Our interdisciplinary team of experts will integrate epidemiologic/genetic approaches with experimental designs to address those issues. We will determine disease burden of comorbidity, calculate its socioeconomic impact, and reveal risk factors. We will study biological pathways of comorbidity and derive biomarkers, prioritizing two candidate mechanisms (circadian rhythm and dopaminergic neurotransmission), but also leveraging large existing data sets to identify new ones. A pilot clinical trial to study non-pharmacologic, dopamine-based and chronobiological treatments will be performed, employing innovative mHealth to monitor and support patients daily life. Integration of findings will lead to prediction algorithms enhancing early diagnosis and prevention of comorbidity. Finally, we will screen to repurpose existing pharmacological compounds. Integrating complementary approaches based on large-scale, existing data and innovative data collection, we maximize value for money in this project, leading to insight into the mechanisms underlying this comorbidity triad with its huge burden for healthcare, economy, and society. This will facilitate early detection and non-invasive, scalable, and low-cost treatment, creating opportunities for substantial and immediate societal impact.


Potente M.,Max Planck Institute for Heart and Lung Research | Potente M.,Goethe University Frankfurt
Experimental Cell Research | Year: 2013

Phosphoinositide 3-kinases (PI3Ks) are an evolutionary conserved family of lipid kinases that control cell growth, metabolism and survival. By generating lipid second messengers that interact with specialized lipid-binding domains found in a wide spectrum of signaling molecules, PI3Ks instigate signaling through a network of downstream effector pathways. Genetic studies in zebrafish and mice revealed the critical importance of intact PI3K signaling in the endothelium and provided first insights into how individual PI3K isoforms are utilized to control vascular development and function. Here, we review the myriad roles of PI3Ks in the endothelium and the mechanisms through which they couple environmental signals with specific steps of angiogenic vessel growth. © 2013 Elsevier Inc.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-3 | Award Amount: 8.15M | Year: 2013

Aggression is a basic physiological trait with important roles throughout evolution, both in defence and predation. When expressed in humans in the wrong context, aggression leads to maladjustment, social impairment and crime. Despite this, knowledge about aggression aetiology is limited and current treatment strategies are insufficient. Contingent to a subdivision into impulsive and instrumental subtypes, we investigate the aetiology of maladaptive aggression in paediatric conduct disorders most strongly predisposing to pathological aggression, ADHD and conduct disorder, and in the general population. We employ highly innovative approaches in humans and animal models and maximize the output from the project by optimally balancing the use of large, existing data sets with new data acquisition. Through this, we build a knowledge chain from molecule to behaviour, investigating known and novel genes, gene-networks and their epigenetic interactions, and mapping their mode of action from the molecular via the cellular to the brain-circuit level. This is accompanied by highly powered analyses of the neural substrates of the aggression subtypes. Based on innovative bioinformatic multimodal data integration, our interdisciplinary research will lead to novel, accurate algorithms for reliable aggression prediction, which will be validated in existing longitudinal studies in children and tested for their predictive value in adult outcome. In addition to this approach towards prevention, we test promising non-pharmacological biofeedback for personalised treatment and prevention of overt aggression. For the identification of novel pharmacological compounds in aggression treatment, we introduce a new animal model, the zebrafish. The Aggressotype consortium is based on successful existing collaborations. It includes experts in childhood and adult psychiatry and research-intensive SMEs ensuring maximal dissemination, clinical implementation and business development opportunities.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.66M | Year: 2014

Cancer, the second most common form of death after cardiovascular disease, is a major European health concern. In 2006, 3.1 million new cases were diagnosed and 1.7 million deaths were attributed to cancer within Europe. The European Commission has a European Partnership for Action against Cancer (IP/09/1380) with the aim of reducing the number of cancer cases by 15% by 2020. A key challenge is to Develop a more coordinated approach to cancer-related research across Europe. Around 50% of patients receive radiotherapy as part of their cancer treatment and it is second only to surgery in its ability to cure cancer. However, radiotherapy is limited by the effects induced in the surrounding healthy tissues strongly, which very harmful for the patients. New approaches that enhance radiosensitivity within tumours have the potential to provide a major impact on the delivery of radiotherapy to patients. Two of the most promising approaches (hadron and nanoparticles-enhanced therapies) are driven by nanoscale phenomena. This proposal brings together world-leading researchers from the academic and private sectors aim at developing hadron and NP-enhanced therapies, united by the common purpose of optimising radiotherapy by understanding and exploiting nanoscale processes induced by radiation. Such an understanding will open a new era in which radiotherapy is revolutionised to provide more successful cancer treatment with subsequent economic and quality of life benefits for the EU population as a whole. The main objective of this intersectoral and multidisciplinary ITN is to create a new generation of researchers and experts able to create the platform on which next-generation cancer therapy will be built. The consortium aims to train a cohort of 13 ESRs to subsequently act as leaders and ambassadors in the field.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 5.80M | Year: 2008

Membrane proteins (MPs) are known to be key molecules in cellular communications, from signal transduction to transport of ions, metabolites and other molecules. They also participate in the synthesis of ATP, the import of soluble or MPs from the cytosol, and they protect living organisms from toxic factors. The proposal consists in a joint training effort involving the major biophysical methods that are -or soon will be- the major techniques used in the field of structural biology of MPs. A collaborative effort is essential for the training of the future generation of biologists dedicated to membrane proteins. It will pave the way to an integrative approach for the study of structure-function relationships of membranes. It will therefore open new strategies for structure-based drug design, in particular toward G-protein coupled receptors (GPCR), which are major drug targets (GPCRs represent 30% of current drug targets). The training proposed in this program will not only form high-level academic researchers but will also largely contribute in forming the main actors of the future developments in biotechnology and personalized medicine. This network combines 12 academic research groups and 3 industrial companies interested in collaborating with these groups and involved in drug discovery or scientific equipment for SBMP. These groups are internationally recognized for analysing the structure and dynamics of membrane proteins by a combination of experimental and theoretical approaches: in vivo and in vitro expressions systems, functional/biochemical/biophysical characterisation, X-Ray diffraction, electron microscopy (EM), atomic force microscopy (AFM), single-molecule force spectroscopy (SMFS), liquid and solid state NMR, numerical simulations. Seven partners from 6 different countries are involved: France, Poland, Portugal, Switzerland, Germany and the Netherlands.


Grant
Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: ICT-2013.9.9 | Award Amount: 72.73M | Year: 2013

Understanding the human brain is one of the greatest challenges facing 21st century science. If we can rise to the challenge, we can gain profound insights into what makes us human, develop new treatments for brain diseases and build revolutionary new computing technologies. Today, for the first time, modern ICT has brought these goals within sight. The goal of the Human Brain Project, part of the FET Flagship Programme, is to translate this vision into reality, using ICT as a catalyst for a global collaborative effort to understand the human brain and its diseases and ultimately to emulate its computational capabilities. The Human Brain Project will last ten years and will consist of a ramp-up phase (from month 1 to month 36) and subsequent operational phases.\nThis Grant Agreement covers the ramp-up phase. During this phase the strategic goals of the project will be to design, develop and deploy the first versions of six ICT platforms dedicated to Neuroinformatics, Brain Simulation, High Performance Computing, Medical Informatics, Neuromorphic Computing and Neurorobotics, and create a user community of research groups from within and outside the HBP, set up a European Institute for Theoretical Neuroscience, complete a set of pilot projects providing a first demonstration of the scientific value of the platforms and the Institute, develop the scientific and technological capabilities required by future versions of the platforms, implement a policy of Responsible Innovation, and a programme of transdisciplinary education, and develop a framework for collaboration that links the partners under strong scientific leadership and professional project management, providing a coherent European approach and ensuring effective alignment of regional, national and European research and programmes. The project work plan is organized in the form of thirteen subprojects, each dedicated to a specific area of activity.\nA significant part of the budget will be used for competitive calls to complement the collective skills of the Consortium with additional expertise.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2011-1.1.20. | Award Amount: 12.58M | Year: 2012

The Project promotes the access to five European Research Infrastructures, and it is structured into nine Networking Activities, plus the Management of the Consortium, and fourteen Joint Research Activities. The Project will profit of the success of the previous HadronPhysics project in FP6 and the current HadronPhysics2 in FP7, and originates from the initiative of more than 2.500 European scientists working in the field of hadron physics. Hadron physics deals with the study of strongly interacting particles, the hadrons. Hadrons are composed of quarks and gluons. Their interaction is described by Quantum Chromo Dynamics, the theory of the strong force. Hadrons form more complex systems, in particular atomic. Under extreme conditions of pressure and temperature, hadrons may loose their identity and dissolve into a new state of matter similar to the primordial matter of the early Universe. The Networking Activities are related to the organization of experimental and theoretical collaborative work concerning both ongoing activities at present Research Infrastructures and planned experiments at future facilities. In hadron physics the close interaction between experimentalists and theoreticians is of paramount importance. The Joint Research Activities concentrate on technological innovations for present and future experiments. Applications in material science, medicine, information, technology, etc., represent natural fall-outs. The main objective of this Integrating Activity is to optimize the use and development of the Research Infrastructures existing in Europe working in the field of hadron physics. The Project aims as well at structuring, on European scale, the way Research Infrastructures operate, and at fostering their joint development in terms of capacity and performance. The approach used is the bottom up approach, to respond to the needs of the scientific community in all fields of science and technology.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.1.1-2 | Award Amount: 15.99M | Year: 2011

PRIMES focuses on the role of protein interactions to assemble dynamic molecular machines that receive and process information to coordinate cellular responses. PRIMES investigates the following: (i) How do protein interactions contribute to the generation of biological specificity in signalling? (ii) How do pathogenetic perturbations affect protein interaction networks? (iii) How can we exploit protein interactions as therapeutic targets? We focus on the EGFR/ERBB signalling network and its role in colorectal cancer (CRC), the third most frequent cancer. The ERBB network is frequently altered in CRC either through overexpression or mutation of the receptors or downstream components. Network components have become important drug targets. Poor response rates and resistance demonstrate we lack sufficient insight to design efficacious therapies. Using proteomics, structural biology, advanced imaging and mathematical modelling we (i) map static and dynamic protein interactions in the ERBB network (ii) unravel the design principles and emergent network properties conferred by protein interactions; and (iii) validate these findings in genetic mouse models of CRC and human tissues. PRIMES aims to (i) enhance the functional pathogenetic understanding of CRC (ii) identify mechanisms of drug resistance and drug efficacy; and (iii) identify drugs that affect protein interactions to rationally manipulate network functions related to individual genetic mutations. Outcomes include (i) a dynamic, mechanistic flowchart of how protein interactions compute biochemical and biological specificity in signalling networks (ii) a functional protein interaction network of healthy and oncogenic ERBB signalling validated in mouse models of CRC and human tissues (iii) network level insights towards personalised CRC treatment based on genotype-phenotype relationships; and (iv) chemical compounds targeting protein interactions to restore normal ERBB network function or break oncogenic circuits.


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

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


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: SiS.2012.2.2.1-1 | Award Amount: 3.78M | Year: 2013

This project aims to promote a widespread use of inquiry-based science teaching (IBST) in primary and secondary schools. Our major innovation is to connect IBST in school with the world of work making science more meaningful for young European students and motivating their interest in careers in S & T. To this end, we will run training courses in which pre- and in-service teachers will learn about IBST supported by teachers from vocational education, representatives from industry and informal learning. They will develop inquiry tasks in vocational contexts, leading to a large European task repository. Teachers will experience IBST themselves and through iterative cycles of implementation followed by reflection integrate this into their practice. To ensure widespread participation we will use a pyramid model in which we will work with a small number of teachers first each of which will then work with further teachers. Additionally we will develop an innovative interactive e-learning platform. To profit from the international perspective offered by the project teachers will be connected with existing European networks and our own thematic network on IBST through (virtual) meetings, a forum and the task repository. We will adopt a systemic approach to dissemination working with teachers and additionally parents, students, school authorities and policy makers. National and European advisory panels will bring together stakeholders to advise partners throughout the project; dialogue with policy makers will be facilitated by workshops and policy papers. To ensure effectiveness our work will be informed by a detailed analysis of the educational systems in partner nations. We plan to reach more than 65.000 teachers directly and 800.000 teachers indirectly (via stakeholders, media). Throughout, our work will be subject to rigorous evaluation and measures of quality assurance that will be both summative and formative in informing the progress of the project.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: KBBE-2007-2-3-03 | Award Amount: 4.10M | Year: 2008

Functional foods provide a buoyant growth sector and the use of carotenoids is the most dynamic not only as colorants but as food additives. One issue with these products is their instability both on the shelf and upon digestion. Recently, gastric-stable bacterial-derived carotenoid preparations have been discovered by members of this consortium and these 2nd generation carotenoid preparations, and the bacteria that produce them will be studied. Existing prototypes will be developed as potential food additives but an extensive screen for new 2nd generation prototypes will also be made from marine environments. The consortium includes microbiologists, biochemists and food bio-technologists and will determine the identity of new carotenoid preparations and the bacteria that produce them. The nutritional value of these bacteria will be assessed and a risk-benefit assessment made using modern metabolomic technologies as well as traditional toxicology in order to designate the prototypes as QPS (ie, qualified presumption of safety). Bioprocessing of these bacterial carotenoid preparations will eliminate traditional chemical synthesis and the use of organic solvents. Also the delivery system will utilise a synergistic biological matrix making it a sustainable source. The use of these bacteria as colour-nutritional additives will be assessed by process optimisations, colour and texture analysis. The consortium includes 9 partners, including one ICPC and one associated country. Two IND partners, one an SME, will work together to exploit prototypes as additives, colourants and as functional foods. This will include patenting, licensing and the opening of new markets. Both IND partners are looking for new markets in the food additive/functional food sector and this project will enable them to identify new markets. The project will directly impact the food industry by developing new, natural as well as novel food additives and ingredients that can replace synthetic ones.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-3.2-1 | Award Amount: 3.42M | Year: 2009

Chronic health conditions that impose a heavy burden on society and account for a large share of health care costs. Better prevention and management could potentially decrease costs and improve quality of care and health outcomes. An important means of accomplishing these goals is through the use of disease management (DM) interventions that educate patients about prevention and health management strategies, while also providing guidance, behavioral modification techniques, and social and emotional support. DM also seeks to assist providers by informing them about best practices and treatment opportunities. The underlying assumption is that DM leads to better quality of care, more health-conscious behavior, and improved disease prevention and control. In the short run, disease management would decrease costs by optimizing utilization of medical care. In the long run, DM lead to improved health status among patients with chronic conditions, thereby avoiding medical expenditures and improving workplace productivity. Many health care systems in Europe and elsewhere are beginning to embrace DM programmes. Although the concept of disease management offers great promise, these programs ability to reduce cost and improve care has not yet been empirically demonstrated; more and more policymakers are demanding objective assessments of a programmes impact. Part of the problem is that there are no universally accepted evaluation methods to measure and report programme performance in a scientifically sound fashion that is also practicable for routine operations. This project seeks to bridge this gap. It will provide an overview of approaches to chronic care and DM methods across Europe and test and validate possible evaluation approaches. These include non-experimental and experimental evaluation designs and performance measures. Best practices will be identified and used to develop recommendations for policymakers, program operators and researchers.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE-2007-3-2-06 | Award Amount: 8.10M | Year: 2009

The NEMO project provides novel efficient enzymes and microbes for 2nd generation bioethanol production. It generates through metabolic engineering and mutagenesis & screening approaches robust yeast strains that have a broad substrate range and can (co-)ferment C6 and C5 sugars to ethanol with high productivity (rate and yield), and that are significantly more stress tolerant, i.e. inhibitor, ethanol and thermotolerant than the current S.cerevisiae strains used in ethanol production. The NEMO project also identifies and improves enzymes for hydrolysis of biomasses relevant for Europe. Novel enzymes are identified and improved through various approaches, based on screening, broad comparative genomics analyses, and protein engineering. These efforts will generate more thermostable enzymes for high temperature hydrolysis, more efficient enzymes for hydrolysis of the resistant structures in lignocellulose such as crystalline cellulose and lignin-hemicellulose complexes, enzymes with reduced affinity on lignin, and efficient thermo and mesophilic enzyme mixtures that are optimised and tailor-made for the relevant biomasses for Europe and European industry. These novel biocatalysts are tested in an iterative manner in process relevant conditions, including also pilot-scale operations, which ensure that the novel enzymes and microbes will be superior in real process conditions. Furthermore, optimal enzyme, microbe and process regime combinations are identified, providing basis for the development of the most economic and ecoefficient overall processes. The impact of the NEMO project on 2nd generation bioethanol production is significant because it provides most realistic but widely applicable technologies that could be exploited broadly by European industry. Its impact goes also much beyond bioethanol because NEMO provides technology improvements that are directly applicable and crucial for efficient and economic production of also other biofuels and bulk chemicals.


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

Structural biology provides insight into the molecular architecture of cells up to atomic resolution, revealing the biological mechanisms that are fundamental to life. It is thus key to many innovations in chemistry, biotechnology and medicine such as engineered enzymes, new potent drugs, innovative vaccines and novel biomaterials. iNEXT (infrastructure for NMR, EM and X-rays for Translational research) will provide high-end structural biology instrumentation and expertise, facilitating expert and non-expert European users to translate their fundamental research into biomedical and biotechnological applications. iNEXT brings together leading European structural biology facilities under one interdisciplinary organizational umbrella and includes synchrotron sites for X-rays, NMR centers with ultra-high field instruments, and, for the first time, advanced electron microscopy and light imaging facilities. Together with key partners in biological and biomedical institutions, partners focusing on training and dissemination activities, and ESFRI projects (Instruct, Euro-BioImaging, EU-OPENSCREEN and future neutron-provider ESS), iNEXT forms an inclusive European network of world class. iNEXT joint research projects (fragment screening for drug development, membrane protein structure, and multimodal cellular imaging) and networking, training and transnational access activities will be important for SMEs, established industries and academics alike. In particular, iNEXT will provide novel access modes to attract new and non-expert users, which are often hindered from engaging in structural biology projects through lack of instrumentation and expertise: a Structural Audit procedure, whereby a sample is assessed for its suitability for structural studies; Enhanced Project Support, allowing users to get expert help in an iNEXT facility; and High-End Data Collection, enabling experienced users to take full benefit of the iNEXT state-of-the-art equipment.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.18M | Year: 2016

In the ASPIRE project, whose academic and industrial beneficiaries are world leading in their complementary fields of expertise, the overarching research goal is the measurement of photoelectron angular distributions (PADs) in the molecular frame (MF) of systems of biological relevance. These MF-PADs can be interpreted as electron diffraction patterns, achieved by illuminating the molecule from within, and enable the shapes and motions of individual molecules to be interrogated. Such knowledge is needed for the development of new medicines (the shapes of drug molecules dictate their function) and new materials (efficient solar cells can be constructed if energy dissipation processes in molecules are understood). Progress in this area is highly technologically driven, requiring high repetition rate, short wavelength light sources and fast detectors. The input of private sector beneficiaries is therefore critical to the scientific objectives, as well as to the enhanced training environment. Work packages on advanced light source and detector developments will feed into the overall goal through secondments, regular virtual meetings and face-to-face network meetings. The symbiosis of the developments that will take place in ASPIRE will create a research and training environment that is world-leading and optimally tailored to capitalise, for example, on the investment that has been made in the European XFEL facility. The ESRs will be trained in world-leading laboratories and will benefit from the exchange of best practice among beneficiaries and partners, and from unique training events. ASPIRE will therefore ensure that European research remains competitive in the global market, and that the trained researchers will be uniquely well-placed to contribute to the development of novel instrumentation in the future.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.07M | Year: 2015

The brain barriers function to protect the central nervous system (CNS) from neurotoxic compounds. By the same traits they unfortunately block delivery of drugs to the CNS thus hindering proper diagnosis and effective treatment of neurological disorders including Alzheimers disease and multiple sclerosis. The unusual complexity of the brain barriers has severely hampered progress in the market of CNS targeting therapeutics. BtRAIN bridges this gap by creating particular knowledge on vertebrate brain barrier signature genes and their specific roles in regulating brain barrier function in development, health, ageing and disease. Brain barrier signature genes will be identified by combining cross-species and cross-system brain barrier transcriptome analysis with dedicated bioinformatics. These data will be made available for brain barrier datamining in the userfriendly online platform BBBHub. Within BtRAIN, the side-by-side comparison of a unique and broad armamentarium of different vertebrate in vitro and in vivo brain barrier models will allow to develop and validate particular in vitro brain barrier models that are suited to reliably predict brain barrier function in vivo. Combined with an accompanying in depth analysis of the pathological alterations of the brain barriers during neurological disorders BtRAIN will create unique knowledge to overcome the unmet need for the development of diagnostic and therapeutic tools able to breach the brain barriers. In BtRAIN 12 academic, 6 non-academic partners and 1 European network will jointly train young researchers at unique interfaces of brain barrier research, bioinformatics, business development and science communication for an international research or entrepreneur career. To create this expert pool is the motivation for the involved partners as it will advance the Euopean capacity to bring innovative approaches to the untapped potential of the CNS therapeutic market.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.90M | Year: 2016

The European Pharma industry is a major contributor to EU well-being, both in public health and economic (sales >200 billion /year) terms. To maintain global leadership, it must respond to challenges from low-cost producers e.g. China by bringing new drug molecules to market in a streamlined, cost-effective manner. This strategy is underscored by recent initiatives of European regulators to expedite the approval of breakthrough drugs so patients can gain earlier access to life-saving drugs. To realise these goals, scientists with an integral understanding of drug development and regulatory approval processes are urgently needed. PEARRL will train 15 Early Stage Researchers (ESR) who can develop new bio-enabling formulations (better drugs), biorelevant and in silico methods to predict formulation performance in vivo (streamlined development) and serve as communication bridgers between research and regulatory science (accelerated approval), thus bringing Pharma and regulatory objectives to fruition. PEARRL brings a multi-sectorial team, comprising key European regulatory authorities, academic leaders in bio-enabling formulations and biopharmaceutics tools, and an array of Pharma companies with a wealth of combined experience in bringing molecules to market, together for the first time to deliver a unique research and training programme. Key PEARRL elements are individual research projects with synergistic output; exposure of all ESR to academia, industry and regulatory in secondments; and ongoing innovative learning via Online Portals, Science Slams and Boot Camps. Key PEARRL impacts will be availability of excellent pharmaceutical researchers; streamlined drug development with a higher success rate for the industrial partners; enriched academic research through cooperation with industry and regulatory; earlier availability of breakthrough medicines to patients; a competitive pharma industry in Europe and contributions to European public health interests.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: BIOTEC-03-2016 | Award Amount: 6.24M | Year: 2016

CHASSY will unlock the full potential of the yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus as cell factories for production of high value compounds which have applications in the cosmetic, nutraceutical and white biotechnology sectors. Current cell factory strains for these classes of product are restricted to proof-of-principle levels because of limited precursor supply, poor product tolerance and lack of versatility. CHASSY addresses these challenges by redesigning metabolic circuits and expanding the host range to include the oleaginous yeast, Y. lipolytica and the thermotolerant yeast, K. marxianus. The systems biology approach will integrate model-based design, construction and analysis of yeast strains, resulting in reconfigured metabolic networks optimised for the production of lipid and aromatic molecules. Construction of the chassis strains, using new and existing synthetic biology tools, will be directed by knowledge derived from a thorough systems biology comparison of the three yeast species, conducted using integrative data analysis and genome scale metabolic models. The chassis strains will be used to build cell factories to produce three specific high value products: the oleochemicals, Docosanol and Octanoic acid; and the aromatic molecule, Amorfrutin 1. These new cell factory strains will be evaluated under industrial conditions to produce data that will further improve the chassis platforms. The major outcomes of this project will be (1) a new set of chassis yeast strains that are widely applicable for development of industrial cell factories; (2) the knowledge and technology to readily build and evaluate new chassis tailored to specific applications; (3) prototype cell factory strains producing three high value metabolites for commercial exploitation; (4) a dissemination and exploitation strategy to ensure that European SMEs benefit from the knowledge base, platform chassis and resources generated in CHASSY.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-3 | Award Amount: 8.21M | Year: 2013

Conduct Disorder (CD) and Oppositional Defiant Disorder with symptoms of Conduct Disorder (which is included among the abbreviation CD throughout the proposal) has a highly negative impact for the affected individual as well as for families and society. Although the number of females exhibiting serious aggressive behaviours is growing, the majority of studies on aetiology and treatment of CD have focused on male subjects only, despite strong evidence for a differential neurobiological basis of female CD. The key aims of the FemNAT-CD consortium are to identify biomarkers and to study disease mechanisms from pre- to postpubertal female CD as well as new psychological and pharmacological treatment options for female adolescent CD targeting emotion processing abilities. With the present proposal, we aim at clarifying the phenomenology and neurobiology of female CD from pre-puberty to post-puberty. We will study the role of genetic and environmental risk factors on female CD, related psychopathology, brain structure and function, HPA axis and autonomic nervous system (ANS) disturbance to elicit CD specific endophenotypes and its biomarkers. We will describe the clinical, neuronal and neurocognitive phenotype of female CD from pre- to postpuberty and related neuroendocrine and ANS function as well as moderating, mediating and direct risk factors to identify distinct homogeneous subtypes to guide targeted future treatment approaches. We translate knowledge of neuropsychological and neurobiological characteristics into targeted intervention by performing a randomised controlled trial of an innovative 16-week DBT-CD-A psychological treatment program focussing on emotion processing. The effect oxytocin and serotonin on neural function underlying emotion processing and aggression will be studied in a female animal model and two proof of concept pharmaco-challenge studies. We also target several societal and education objectives. Our consortium brings together strong clinical and basic science expertise on paediatric CD, including a number of SMEs and a professional management company.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.4-2 | Award Amount: 7.92M | Year: 2013

The trypanosomatid diseases, leishmaniasis, Human African trypanosomiasis (HAT) and Chagas disease (CD), continue to impart a heavy toll on human health. The treatments available are limited and threatened by drug resistance with few newdrugs in the pipeline. The KINDReD consortium integrates five leading academic laboratories in Europe (Portugal, United Kingdom, and Switzerland), the USA (California) and South America (Brazil) with high throughput screening (HTS) facilities equally distributed between all three major kinetoplastid parasites. Intracellular amastigote screening will be employed as the most relevant for Leishmania spp and T cruzi. Compound libraries (focused, diversity oriented or natural) will be screened in these systems, as well as compound series devised through target screening and in silico approaches. For carefully chosen protein targets, all three kinetoplastid parasite homologs will be screened against the closest human homolog to establish selectivity. Promising lead compounds will be optimised for efficacy and tolerability in cell-based and animal disease models. Toxicological markers will be evaluated in human cell lines prior to toxicity (acute,subacute,chronic) testing in lower then higher mammals. In parallel, and in line with the FDAs Critical Path Initiative, several check point controls will be built into the pipeline to flag, identify and allow early correction of potential toxicity/efficacy issues. These will include (i) a systems biology approach to identify drug target and off-target interactions via activity-based chemoproteomics (ii) uptake and metabolismas potential modulators of drug efficacy and/or resistance and (iii) the establishment of a firm set of rules for drug efficacy and safety in kinetoplastid chemotherapy. Our goal is to strengthen the drug development pipeline in order to achieve at least one new Phase I clinical candidate for each trypanosomatid disease at or shortly after the project completion date.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2011-1.1.10.;INFRA-2011-1.1.11. | Award Amount: 10.44M | Year: 2011

InGOS will support and integrate the observing capacity of Europe for non-CO2 greenhouse gases (NCGHG: CH4, N2O, SF6, H2 and halocarbons). The emissions of these gases are very uncertain and it is unknown how future climate change will feedback into the land use coupled emissions of CH4 and N2O. The NCGHG atmospheric abundances will increase further in the future and the emissions of these gases are an attractive target for climate change mitigation policies. InGOS aims to improve the existing European observation system so that this will provide us insight into the concentration levels and European and extra-European emissions of the NCGHGs. The data from the network will enable to better constrain the emissions of NCGHGs within the EU and show whether emission reduction policies are effective. The data from the network is designed to allow to detect the spatial and temporal distribution (hotspots) of the sources and to detect changes in emissions due to mitigation and feedbacks with climate change. To strengthen the European observation system, the project has several objectives: Harmonize and standardize the measurements. Provide capacity building in new member states and countries with inadequate existing infrastructure. Support existing observation sites and transfer of selected sites into supersites. Integrate and further integrate marine observations of the NCGHGs with land-based observations Improve measurement methods by testing new innovative techniques and strategies. Test advanced isotope techniques for application in the network to enable attribution of the atmospheric fractions to source categories Integrate data for network evaluation by using inverse modeling and data-assimilation methods and developments in bottom up inventories Link the network to remote sensing data of column abundances from in-situ and satellite observations Prepare for the integration of the NCGHG network with the Integrated Carbon Observation System


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2010-1.1.32 | Award Amount: 11.03M | Year: 2010

ENSAR is the Integrating Activity of Nuclear Scientists from almost all European countries performing research in three of the major subfields of Nuclear Physics: Nuclear Structure, Nuclear Astrophysics and Applications of Nuclear Science. It proposes an optimised ensemble of Networking (NAs), Transnational Access and Joint Research Activities (JRAs), which will ensure qualitative and quantitative improvement of the access provided by the current seven 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 in Europe that can supply different ion beams and energies. We have made great efforts 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 in nuclear instrumentation to other research 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 socioeconomic 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. In addition, a key JRA aims at integrating the laboratories in Central and South-Eastern European countries with those elsewhere in Europe. The NAs of ENSAR have been set-up with specific actions to strengthen the communities coherence around certain research topics and to ensure a broad dissemination of results and stimulate multidisciplinary and application-oriented research at the Research Infrastructures.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENV.2013.6.1-2 | Award Amount: 11.46M | Year: 2013

Clouds are a very important, yet not well understood feedback factor in climate change and they contribute to the effective radiative forcing (ERF) from aerosol-cloud interactions (ACI). The uncertainty in ERFaci is larger than for any other forcing agent. Also, feedbacks between the terrestrial and marine biosphere and the atmosphere involving ACI are thought to play an important role in regulating climate change but their relevance remains poorly quantified. BACCHUS proposes to quantify key processes and feedbacks controlling ACI, by combining advanced measurements of cloud and aerosol properties with state-of-the-art numerical modelling. The analysis of contrasting environments will be the guiding strategy for BACCHUS. We will investigate the importance of biogenic versus anthropogenic emissions for ACI in regions that are key regulators of Earths climate (Amazonian rain forest) or are regarded as tipping elements in the climate system (Arctic). BACCHUS will generate a unique database linking long-term observations and field campaign data of aerosol, cloud condensation and ice nuclei and cloud microphysical properties; this will enable a better quantification of the natural aerosol concentrations and the anthropogenic aerosol effect. BACCHUS will advance the understanding of biosphere aerosol-cloud-climate feedbacks that occur via emission and transformation of biogenic volatile organic compounds, primary biological aerosols, secondary organic aerosols and dust. Integration of new fundamental understanding gained in BACCHUS in Earth Systems Models allows to reduce the uncertainty in future climate projections. This will have a direct impact on decision-making addressing climate change adaptation and mitigation. BACCHUS brings together a critical mass of experimentalists and modellers with the required scientific expertise to address these complex topics and a high commitment to communicate their findings in many ways in order to ensure a high-impact project.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.1.4 | Award Amount: 5.95M | Year: 2008

With the emergence of services for professional and private on-line collaboration via the Internet, many European citizens spend work and leisure time in on-line communities. Users consciously leave private information; they may also leave personalized traces they are unaware of. PICOS will develop and build a state-of-the-art platform for providing the trust, privacy and identity management aspects of community services and applications on the Internet and in mobile communication networks. The PICOS approach to trustworthy on-line community collaboration addresses these four questions: What are the Trust, Privacy and Identity issues in new context-rich mobile communication services, especially community-supporting services? How can information flows and privacy requirements be balanced in complex distributed service architectures (e.g., mash-ups)? How can these issues be solved in an acceptable, trustworthy, open, scalable, manner? Which supporting services and infrastructures do the stakeholders need? The PICOS consortium includes European industry and research communities. The project will first review contemporary research in relevant disciplines. Its platform design and prototype development work will then create interoperable, open, privacy-respecting identity and trust management tools that can be demonstrated to the public. These will be used to construct community application prototypes by leading industry partners; those will be trialled with selected on-line communities. PICOS will self-evaluate usability, ergonomics, legal issues, trust and privacy. Expected PICOS results are: - A set of interdisciplinary requirements for trustworthy, privacy-friendly community transactions, - A platform prototype that demonstrates the provision of state-of-the-art privacy and trust technology to community applications, - User-centric trials that validate its applicability, Publications and a final report will disseminate the PICOS results to the public.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.4-1 | Award Amount: 3.97M | Year: 2008

Autoimmune Addisons disease (AAD) is an endocrine disease resulting from the immune systems destruction of hormone producing cells in the adrenal cortex. Diagnosis is frequently first established after a life-threatening adrenal crisis, often resulting in untimely fatalities. The disease is rare, more common in women than in men, and also affects children. AAD very frequently occurs with other autoimmune diseases, such as type 1 diabetes mellitus, autoimmune thyroid disease and/or premature ovarian failure. Based on a European network of patient registry and biobanks, a translational approach using genetics, immunology, clinical management, and epidemiology, the project aims to unravel the pathogenesis and natural course of AAD, ultimately to improve diagnosis and treatment as well as to offer strategies for disease prevention. The consortium capitalises on the joint cutting edge expertise of leading European investigators covering all these fields. Exploiting these resources, we will describe the natural course of the disease with focus on factors limiting quality of life, and identify and characterise the disease-causing genes, using the corresponding disease in a spontaneous dog model and a gene targeted mouse model. In parallel, the cellular and molecular mechanisms of autoimmunity directed at the adrenal cortex will be unravelled both in humans with ADD and in the genetic mouse model. Together, these efforts will increase our still incomplete understanding of pathogenic pathways operational in AAD and pave the way for new therapies of this debilitating disorder. Moreover, clinical studies will be performed to evaluate more physiological and personalised treatment with cortisol also aimed at prevention. As an autoimmune model disease the results of the project will not only lead to the development of novel diagnostic and therapeutic interventions for Addison patients, but also increase our understanding of the pathogenesis of autoimmune diseases in general.


Grant
Agency: European Commission | Branch: FP7 | Program: ERC-SyG | Phase: ERC-2013-SyG | Award Amount: 13.98M | Year: 2014

Gravity is successfully described by Einsteins theory of general relativity (GR), governing the structure of our entire universe. Yet it remains the least understood of all forces in nature, resisting unification with quantum physics. One of the most fundamental predictions of GR are black holes (BHs). Their defining feature is the event horizon, the surface that light cannot escape and where time and space exchange their nature. However, while there are many convincing BH candidates in the universe, there is no experimental proof for the existence of an event horizon yet. So, does GR really hold in its most extreme limit? Do BHs exist or are alternatives needed? Here we propose to build a Black Hole Camera that for the first time will take an actual picture of a BH and image the shadow of its event horizon. We will do this by providing the equipment and software needed to turn a network of existing mm-wave radio telescopes into a global interferometer. This virtual telescope, when supplemented with the new Atacama Large Millimetre Array (ALMA), has the power to finally resolve the supermassive BH in the centre of our Milky Way the best-measured BH candidate we know of. In order to compare the image with the theoretical predictions we will need to perform numerical modelling and ray tracing in GR and alternative theories. In addition, we will need to determine accurately the two basic parameters of the BH: its mass and spin. This will become possible by precisely measuring orbits of stars with optical interferometry on ESOs VLTI. Moreover, our equipment at ALMA will allow for the first detection of pulsars around the BH. Already a single pulsar will independently determine the BHs mass to one part in a million and its spin to a few per cent. This unique combination will not only produce the first-ever image of a BH, but also turn our Galactic Centre into a fundamental-physics laboratory to measure the fabric of space and time with unprecedented precision.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SSH.2013.1.3-2 | Award Amount: 3.34M | Year: 2014

During the global financial crisis and ensuing Great Recession, economists at policy-making institutions had little choice but to augment macroeconomic models with ad-hoc assumptions and adjustments in order to provide analysis and advice for policy makers. Our consortiums proposal aims to move policy-focused macroeconomic modelling beyond this approach to the endogenous modelling of the dynamics resulting from financial risks and related decision making in banks, households, firms and public institutions. We bring together four broad lines of research to systematically develop new behavioural and institutional building blocks, integrating them in policy-focused macroeconomic models and using these models in a new framework for policy evaluation. In terms of building blocks, one line of research moves beyond the assumption of representative and homo-oeconomicus-type agents to incorporate micro-behavioural realism in decision making, while a second line of research advances the modelling of financial institutions, their fragility and the dynamics of systemic risk. The third line of research integrates these new building blocks (including a selection of those developed by researchers outside the consortium) in a new generation of policy-focused macroeconomic models. In parallel, in the fourth line of research new policy evaluation tools are developed, with a focus on robust tools aimed at containing financial contagion and boom-bust cycles, maintaining fiscal sustainability and coordinating monetary, fiscal and regulatory policies in normal and crisis regimes. The consortium comprises researchers with a strong track record in advancing the frontier on behavioural and institutional modelling, highly influential macroeconomic modellers as well as seasoned veterans of model-based monetary, fiscal, and regulatory policy evaluation and design. Consortium members have strong academic backgrounds as well as substantive practical experience at policy-making institutions.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.2.1-4 | Award Amount: 4.06M | Year: 2009

To maintain homeostasis of the central nervous system (CNS) the blood-brain barrier (BBB) prevents the free transcellular passage of hydrophilic molecules from the blood into the CNS. Because of this, the BBB is now recognised as the major obstacle to the treatment of most neurological disorders, as it hinders the delivery of many potentially important therapeutic and diagnostic substances to the CNS. Previous approaches in improving drug delivery across the BBB, which have primarily aimed at highjacking the transcellular transport machinery that is dedicated to the selective transport of specific molecules across the BBB, have had limited success, especially with regard to large molecular weight drugs. Lack of knowledge on the molecular composition and function of cerebrovascular cell-to-cell junctions has hampered the development of safe strategies for paracellular drug delivery across the BBB until recently. Members of the JUSTBRAIN consortium have accumulated knowledge on the structure and function of BBB cell-to-cell junctions, identified endothelial signals controlling the expression of individual junctional proteins and have begun to develop approaches, which may either open or close BBB junctions. Using in vitro and in vivo BBB models and animal models of neurological disorders, where BBB opening may be therapeutic, JUSTBRAIN is dedicated to translate this basic knowledge into identifying an entire novel platform of drugable molecular targets that could be functionally modulated thus allowing to bypass the BBB via the paracellular route. By these means JUSTBRAIN expects to improve efficient delivery of large molecules into the CNS and thus to expand on diagnostic and therapeutic possibilities for neurological disorders.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: NMP.2011.1.4-5 | Award Amount: 1.98M | Year: 2011

The goal of this project is to develop multiscale theoretical models of biocompatible metallic nanomaterials and apply them for the analysis, design and optimization of the materials. Two groups of titanium based nanomaterials are considered (while the methods developed should be applicable to other metallic materials as well): nanostructured commercially pure titanium and shape memory NiTi alloy. The multiscale model of nanostructured titanium (nTi) includes atomistic molecular dynamics (MD) discrete dislocation dynamic model (DDD) of the nucleation, interaction and movement of dislocations, crystal plasticity models mechanical behavior of Ti nano-grains, coupled texture and substructure evolution model for severe plastic deformation of polycrystalline Ti, micromechanical analysis of the grain sizes and microstructures on the mechanical properties. The atomistic and micromechechanical modeling of martensitic transformation (or reorientation) lattice strain of NiTi alloys is carried out. The biocompatibility of these two groups of materials (MD modeling of the interactions between metallic nanoparticles and biological molecules) is studied theoretically. The theoretical studies and recommendations are validated experimentally and in practice.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: SSH.2012.5.1-1 | Award Amount: 8.43M | Year: 2013

The European Court of Justice expects European citizenship to become the fundamental status of nationals of the Member States. It lies at the heart of the European integration process. The treaties, legislation, and case law have given Europeans an increasing number of rights. Yet the European Commission complains that these remain underused. Therefore, it has included in FP7 a call for a large-scale IP, identifying and analyzing barriers to exercising such European citizenship rights. Utrecht University is initiating a response to this call. In its project proposal it identifies research questions and several categories of potential hindrances as answers to some of them: contradictions between different rights, multilevel rights, and differences in priorities Member States accord these rights; differences in political, administrative, and legal institutions; financial restraints; lack of sufficient solidarity; administrative and bureaucratic hurdles; language problems; and other practical barriers to claiming and exercising rights - and related duties. Furthermore we distinguish citizenship rights by the types of rights - economic, social, political, and civil - and by the ascribed characteristics of the subjects of these rights: male and female, young and old, native and immigrant. We believe multidisciplinarity will help in identifying and analyzing barriers to the exercise of European citizenship. We can learn from other times and places; therefore we add a historical and comparative dimension to the analysis. And we aim to combine insights from the historical, legal, and social sciences. Overall we want to investigate the options for a multilayered citizenship true to the EUs motto In Varietate Concordia. The research questions and theoretically identified barriers will be investigated in 12 different work packages, each containing specific research objectives, tasks, roles of the participants, and deliverables


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SSH-2007-1.3-01 | Award Amount: 1.68M | Year: 2008

This project contributes to the evaluation of macroeconomic policy by advancing the analysis of optimal fiscal and monetary policy in monetary union such as the European one. This work will result in the addition of new numerical tools, specially designed for the computation of optimal policy in large macro-econometric models. Such multi-country models are necessary to take into account the diversity of the countries making now the European Union. These new tools for the computation of optimal policy will be added to DYNARE, a public domain platform for the simulation and estimation of dynamic stochastic general equilibrium models (DSGE), that is increasingly used in policy making institution and in academic research alike. New models are proposed to analyze the contribution of optimal policy to smooth shocks in a union of heterogeneous countries with rigidities in labor and financial markets. In that framework, special attention is given to the dynamics of public debt. Systematic models comparison is made possible thanks to a database of macroeconomic models currently in use in policy making institutions around the world. New numerical tools are added to DYNARE that provide the computation of optimal policy, either under commitment, in a timeless perspective or under discretion, for a general class of nonlinear models. Particular attention is given to correct linear quadratic approximation of these models. Extensions are proposed to deal with partial information. These tools shall also permit to perform Bayesian estimation of models under the assumption that the policies followed were optimal. Special emphasis is placed on the definition of priors. Given the complexity of the numerical computations, we stress speed of computation and the development of parallel algorithms. Altogether, this project should represent a very significant step forward towards better models and better tools for the formulation of macroeconomic policies.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.31M | Year: 2012

Aim of the CAFFEIN network is to provide 10 early stage researchers (ESRs) and 2 exprerienced researchers (ERs) with excellent training in an industry relevant area of cancer research, complementary skills required for pharmaceutical industry, and knowledge in setting up biomedical start-up companies. To this end, the network comprises two full industrial partners: the established pharmaceutical company Medimmune, a global leader in immunopharmaceuticals, and the small biotech company Gimmune, which used breakthrough results in nanotechnology to establish a new enterprise. The research focus of CAFFEIN, which stands for Cancer Associated Fibroblasts (CAF) Function in Tumor Expansion and Invasion, is to understand the mechanisms, how fibroblastoid cells support tumor progression and metastasis formation. CAF biology is therefore rather complex, but the research groups of the CAFFEIN network cover many different aspects of it, thus having a critical mass to provide relevant training in this area. Training in complementary skills important for work in the pharmaceutical industry is provided by the industrial partner MedImmune, where communication with management, industrial project planning, IPR, etc. will be taught. Entrepreneurial skills, business plans, funding by venture capitalists, and patentability of research findings are highlights of the training provided by the industrial partner Gimmune. All this training is transmitted to the ESRs/ERs by networkwide events, secondments and tight research collaboration. Taken together, the CAFFEIN research training network combines the acquisition of excellent scientific knowledge in an area highly attractive for pharmaceutical industry with special education in relevant complementary skills that increase employment chances of the trained researchers in industry and that encourage them to translate their scientific results into products, thus improving health and economic welfare of European citizens.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2010-1.1.8 | Award Amount: 10.93M | Year: 2010

In the past two decades spectacular insight into basic principles of life has been obtained from paradigmatic high-resolution structural investigations providing a rational basis for biological experiments. NMR is an indispensable enabling technology for determining such structures and their interactions in solution, the immobilized state and living cells. The power of NMR to link structural, dynamic, kinetic and thermodynamic information makes it an essential component of cutting edge research in medicine and biology. Bio-NMR pools pan-European resources of the most relevant bio-NMR infrastructures. Eleven partners will provide access to researchers involved in structural biology following the EU-NMR I3 project. This initiative successfully responded to the increasing demand for access since 1994. Seven other excellent partners, including the leading NMR manufacturer Bruker, are included in the new consortium. Jointly, they will develop methods aimed at pushing the frontiers of biological NMR and improving the quality of access to allow users to tackle ever more challenging goals in cellular structural biology. Finally, all nineteen partners, amongst them a company specialized in NMR technology dissemination, are involved in the networking activities. These include (1) knowledge transfer among consortium members, Bio-NMR users and other NMR researchers, (2) the demonstration to biologists of the potential of structural biology with NMR , and lowering the barriers to their becoming users, (3) interactions with industrial and medical communities, and (4) raising awareness of the impact of the results achieved through Bio-NMR among society, financing and governing bodies with the final aim of developing a business plan for self-sustainability. The overall project and its management have been conceived in coordination with INSTRUCT, which will contribute to the cultural frame and networking activities of Bio-NMR.


Grant
Agency: European Commission | Branch: FP7 | Program: ERC-AG | Phase: ERC-AG-PE8 | Award Amount: 3.47M | Year: 2011

The identification of degradation pathways relevant for organic micropollutants in biological wastewater treatment processes is currently a major gap, preventing a profound evaluation of the capability of biological wastewater treatment. By elucidating the responsible enzymatic reactions of mixed microbial populations this project will cover this gap and thereby allow finding technical solutions that harness the true potential of biological processes for an enhanced biodegradation and detoxification. Due to the multi-disciplinary approach Athene will have impacts on the fields of biological wastewater treatment, analytical and environmental chemistry, environmental microbiology, water and (eco)toxicity. The multi-disciplinary approach of the project requires the involvement of a co-investigator experienced in process engineering and microbiology in wastewater treatment. Athene will go far beyond state-of-the-art in the following fields: a) efficiency in chemical analysis and structure identification of transformation products at environmental relevant concentrations; b) identification of enzymatic pathways relevant for micropollutant degradation in biological wastewater treatment; c) designing innovative technical solutions to maximize biodegradation; d) map and model relevant enzymatic pathways for environmental concentrations. Furthermore, designing biological wastewater treatment processes by understanding enzymatic pathways relevant for organic micropollutants removal represents a paradigm shift for municipal wastewater treatment. In the context of the actual scientific discussion about the relevance of trace organics in the aquatic environment and in drinking water, this topic is deemed as highly innovative: for its potential of proposing new technical options as well as for the gain in understanding compound persistency. Finally enzymatic reactions as well as the treatment schemes will be assessed for there capability to reduce toxiciological effects.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SSH-2009-1.1.1. | Award Amount: 3.52M | Year: 2010

The GOETE project will analyse the role of school in re-conceptualising education in terms of lifelong learning by combining a life course and a governance perspective. In European knowledge societies adequacy of education means a balance of individual, social and economic aspects. This is operationalised by exploring how educational institutions conceptualise and organise individual educational trajectories. The study covers the period from transition into lower secondary education to transition into upper secondary education/vocational education and training, i.e. the age group between 10 and 16 years. Comparative analysis will focus on the regulation of access to education, of support measures for coping with education and of securing the relevance of education for social integration and the labour market. In 8 EU countries the mixed-method study involves surveys with students, parents and school principals; comparison of teacher training; case studies of local school spaces; discourse analysis; expert interviews with policy makers and stakeholders. On a scientific level, the comparison of the regulation of educational trajectories involves re-conceptualising the social aspects of learning and education under conditions of late modern knowledge societies. It reflects the need for formal education to be embedded in social life worlds, enabled by social support, and complemented by informal and non-formal learning. On a practice and policy level, it will provide information about alternative means of providing children and young people with access to education; of supporting them in coping with education and ensuring the relevance of education by communication and cooperation between school, labour market, other educational actors, students and parents. The communication of findings will include a dialogic model of educational policy planning at local level, training workshops with teachers, youth workers and policy makers, and a European policy seminar.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.07M | Year: 2013

The YEASTCELL ITN will train 11 Early Stage Researchers for productive careers as research scientists and leaders in the public or private yeast biotechnology sectors. Yeast biotechnology spans fundamental and applied research and is an area with an immediate need for highly trained researchers to advance knowledge and to develop new applications. The training consortium comprises 9 Public Sector (6 Universities, 3 Research Institutes) and 4 Private Sector (2 large companies and 2 SME) partners. A research training programme embracing the philosophy of use-inspired fundamental research has been designed to provide all 11 ESRs with interdisciplinary research training in both the public and private sectors. The research themes include yeast physiology and metabolism, metabolic engineering, mathematical modeling, genomics and bioinformatics, fermentation, synthetic biology and systems biology. In addition to training via collaborative research projects, ESRs will participate in courses at local and network levels to enhance their technical and academic skills. All ESRs will register for PhD degrees and will also take a separate postgraduate certificate course in commercialisation and entrepreneurship. Industry-led workshops, research secondments and site visits will provide specific training that prepares ESRs for research in the private sector. A comprehensive programme of advanced training in complementary topics and skills of relevance to both the public and private sectors is provided at the network level. As well as directly training 11 ESRs, the network training activities will provide opportunities for ~40 additional researchers and will promote long-term interactions between research groups at the partner Institutions. The major impact of YEASTCELL will be a cohort of highly-trained ESRs with excellent career prospects in the yeast biotechnology sector and a lasting European training and research collaboration between public and private sector partners.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: HEALTH-2007-3.1-3 | Award Amount: 2.76M | Year: 2009

There is a deficit in activity related to patient safety in primary care and the primary care/secondary care interface in Europe. This deficit relates to research, to sharing of information, to learning and to collaboration. This co-ordination action will specifically address issues addressed in the call through: (1)The development of a taxonomy of adverse events and errors. (2) Identifying best clinical practice and the way that it improves patient safety through an understanding of decision making and medication errors in primary care. (3) Achieve consensus on the measurement of safety culture and leadership in the primary care context and develop agreement on indicators which can be used to assess patient safety and improvements in safety culture. (4) Enhancing existing knowledge from quality improvement techniques which are widely used in the primary care setting and applying these to learning cycles for improvements in patient safety. (5) Develop a reporting system which can be used for identifying errors in primary care in countries where activities related to patient safety in primary care are in a nascent state and develop an accreditation framework for patient safety in these nascent organisations. (6) Identifying methods to involve patients in patient safety initiatives in primary care. (7) Identifying communication-related threats at the primary-secondary care interface and developing intervention strategies to overcome these. Building up an existing network of researchers into a pan European network, this co-ordination action will extend the current knowledge and experience from countries where the importance of patient safety is nationally recognised to countries where it is less developed, ensure that there is an appropriate focus on primary care and encourage co-operation and collaboration for future interventions through large scale trials. We aim to substantially increase the level of activity in relation to sharing information through workshops and seminars.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA | Phase: Fission-2013-4.1.2 | Award Amount: 9.33M | Year: 2013

The CHANDA project main objective is to address the challenges in the field of nuclear data for nuclear applications and its acronym stands for solving CHAllenges in Nuclear DAta The project will prepare a proposal for an organization that will coordinate the nuclear data research program, and the infrastructures and capabilities of the EU Member States in a stable structure, well integrated with R&D coordination tools (EERA, HORIZON 2020) , and with priorities aligned with the SET Plan and the SRAs of the EURATOM Technological Platforms, including the following general objectives: - to provide the nuclear data required for the safe and sustainable operation, and development, of existing and new reactors and nuclear fuel cycle facilities, - to prepare solutions for the challenges risen by the nuclear data measurements needed by nuclear systems, like the data for highly radioactive, short lived or rare materials, - to prepare tools that solve the challenges of quantifying and certifying the accuracy of the results of simulations based on available nuclear data and models (uncertainties), - to identify and promote synergies with other nuclear data applications. Using these tools will allow EU to upgrade the nuclear data up to the level needed by simulation codes to fulfill present requirements. In particular, the simulations should be able to: reduce the number of expensive experimental validations, to support the new tendencies in safety assessments to use best estimate codes to understand the limits of the plat safety towards extreme operational conditions, to optimize safety and performance of present and future reactors and other radioactive facilities. Other applications will benefit from this accuracy in nuclear data, notably in medical applications to optimize performance and minimize dose of radiation for diagnose and treatment.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 3.30M | Year: 2009

Storage research increasingly gains importance based on the tremendous need for storage capacity and I/O performance. Over the past years, several trends have considerably changed the design of storage systems, starting from new storage media over the widespread use of storage area networks, up to grid and cloud storage concepts. Furthermore, to achieve cost efficiency, storage systems are increasingly assembled from commodity components. Thus, we are in the middle of an evolution towards a new storage architecture made of many decentralized commodity components with increased processing and communication capabilities, which requires the introduction of new concepts to benefit from the resulting architectural opportunities. The consortium of this Marie Curie Initial Training Network (MCITN) SCALing by means of Ubiquitous Storage (SCALUS) aims at elevating education, research, and development inside this exciting area with a focus on cluster, grid, and cloud storage. The vision of this MCITN is to deliver the foundation for ubiquitous storage systems, which can be scaled in arbitrary directions (capacity, performance, distance, security) Providing ubiquitous storage will become a major demand for future IT systems and leadership in this area can have significant impact on European competitiveness in IT technology. To get this leadership, it is necessary to invest into storage education and research and to bridge the current gap between local storage, cluster storage, grid storage, and cloud storage. The consortium will proceed into the direction by building the first interdisciplinary teaching and research network on storage issues. It consists of top European institutes and companies in storage and cluster technology, building a demanding but rewarding interdisciplinary environment for young researchers.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2008-1.1.1 | Award Amount: 18.74M | Year: 2009

The Project promotes the access to five European Research Infrastructures, and it is structured intop eight Networking Activities, plus the Management of the Consortium, and fourteen Joint Research Activities. The Project represents the continuation of the successful HadronPhysics project in FP6 and originates from the initiative of more than 2.500 European scientists working in the field of hadron physics. Hadron physics deals with the study of strongly interacting particles, the hadrons. Hadrons are composed of quarks and gluons. Their interaction is described by Quantum Chromo Dynamics, the theory of the strong force. Hadrons form more complex systems, in particular atomic. Under extreme conditions of pressure and temperature, hadrons may loose their identity and dissolve into a new state of matter similar to the primordial matter of the early Universe. The Networking Activities are related to the organization of experimental and theoretical collaborative work concerning both ongoing activities at present Research Infrastructures and planned experiments at future facilities. In hadron physics the close interaction between experimentalists and theoreticians is of paramount importance. The Joint Research Activities concentrate on technological innovations for present and future experiments. Applications in material science, medicine, information, technology, etc., represent natural fall-outs. The main objective of this Integrating Activity is to optimize the use and development of the Research Infrastructures existing in Europe working in the field of hadron physics. The Project aims as well at structuring, on European scale, the way Research Infrastructures operate, and at fostering their joint development in terms of capacity and performance. The approach used is the bottom up approach, to respond to the needs of the scientific community in all fields of science and technology.


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

The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) today announced the winners of the second round of an ideas competition in international research marketing. Awards will go to the Humboldt University of Berlin, Goethe University Frankfurt and the GFZ German Research Centre for Geosciences in Potsdam. The three institutions will each receive prize money of 100,000 euros to implement their research marketing actions. In addition, a special start-up prize was offered for the first time this year, designed for recipients who want to establish research marketing at their institutions. This special award, worth 75,000 euros, will go to the Technical University of Kaiserslautern. The prizes are funded from special funds of the German Federal Ministry of Education and Research (BMBF). The award ceremony will be held in Potsdam on 16 February 2017. This year 19 universities and research institutions took part in the competition. The ideas competition is designed to promote activities that enhance the visibility and attractiveness of German research abroad and attract highly qualified researchers, either to participate in collaborative projects with German researchers or to visit Germany for research purposes. "We believe that the role of international research marketing at higher education institutions is more important now than ever before and that universities must be supported in developing structures to enhance this area," said DFG Secretary General Dorothee Dzwonnek. "The competition for the best minds is getting more difficult worldwide. It is becoming increasingly important to boost Germany's visibility as an outstanding place of research in the global research system and to attract highly qualified researchers to Germany. For this reason, strategic international research marketing will become more and more significant for German research institutions," Dzwonnek continued. The winning ideas impressed the international selection panel, consisting of research managers and experts in internationalisation, communication and marketing, through their bold approaches and successful focus on individual institutional competence. The proposed activities were found to be very tangible and represent genuine partnerships between research and administration within the universities and research institutions, strongly anchored at the leadership level. In addition, the actions no longer merely focus on individual institutions, but on regions and their core research areas: The focus of the research marketing proposal submitted by the Humboldt University of Berlin is a journalist-in-residence programme. Together with the Technical University of Berlin, the Charité and the Einstein Foundation Berlin and with the support of the Wissenschaft im Dialog initiative and Berlin Partner für Wirtschaft und Technologie GmbH, talented young journalists from North and South America and Asia - regions where the Humboldt University has strategically developed its international network - will be invited to visit Berlin. They will have the opportunity to get to know Berlin as a hub of research, including its clusters of excellence and graduate schools, and report on their impressions back home. The idea presented by Goethe University Frankfurt is based on the university's core research area in ubiquitin and autophagy research (UBAUT), which came about through the Collaborative Research Centre "Molecular and Functional Characterisation of Selective Autophagy". The aim is to network UBAUT research in the Rhine-Main region with leading universities in the San Francisco Bay Area and the Greater Boston area. To this end, a fellowship programme will be established and a convention for German and US researchers will be organised on the US West Coast. The joint research marketing idea designed by the GFZ German Research Centre for Geosciences and the Geo.X network focuses on two regions: Russia and the Middle East. This clear regional focus is intended to help maintain bilateral dialogue through research and promote scientific collaboration in regions where little has been done to date in this area. The GFZ will organise summer schools and workshops specifically for early career researchers. Networking opportunities will also be offered through "Geoscience Days" at the German embassies in the chosen regions. The special start-up prize, offered for the first time in 2016, will go to the Technical University of Kaiserslautern. Through a proposal entitled Kaiserslautern Research Matching (KAREMA), the university is taking its first systematic steps in international research marketing. It intends to recruit international postdoctoral researchers in the following core research areas: optics and material sciences; mathematical modelling in the engineering sciences; and biology and biotechnology. In the jury's view, this project could provide inspiration for other smaller institutions. The International Research Marketing project is a joint initiative of the DFG, the Alexander von Humboldt Foundation (AvH), the German Academic Exchange Service (DAAD) and the Fraunhofer-Gesellschaft (FhG). These organisations promote Germany as a place to carry out research through the "Research in Germany" brand. The project is funded by the German Federal Ministry of Education and Research as part of the initiative "Promote innovation and Research in Germany". For more information about the DFG ideas competition "International Research Marketing", visit: http://www. (only available in German)


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

FRANKFURT. Microbes are already used on a wide scale for the production of fuels and base chemicals, but for this most of them have to be "fed" with sugar. However, since sugar-based biotechnology finds itself in competition with food production, it is faced with increasingly fierce criticism. Carbon dioxide has meanwhile become the focus of attention as an alternative raw material for biotechnological processes. Goethe University Frankfurt has now taken charge of a collaborative European project, the aim of which is to advance the development of processes for microbial, CO2-based biotechnology. The project will be funded over the next three years with two million Euro. "This application-oriented work is the logical continuation of our successful endeavours over many years to understand the metabolism of CO2-reducing acetogenic bacteria. We can now start to steer their metabolism in such a way that they produce valuable substances and fuels which are interesting for mankind", says Professor Volker Müller, professor at the Institute of Molecular Biosciences of Goethe University Frankfurt. He is coordinating this transnational project in the framework of the "Industrial Biotechnology" European Research Area Network (ERA-NET), within which the German research groups are financed by the Federal Ministry of Education and Research. This means that Goethe University Frankfurt now plays a pivotal role in the development of a next-generation technology. The special group of acetogenic bacteria converts carbon dioxide (CO2) in a fermentation process which is independent of light and oxygen. The bacteria use hydrogen (H2) or carbon monoxide (CO) or a mix of both (synthesis gas) as a source of energy. However, the bacteria produce very little cellular energy in this metabolic process. This drastically limits the product range possible with gas fermentation, so that at present only acetic acid and ethanol can be manufactured on an industrial scale. That is why the collaborative European project has set itself the objective of genetically modifying suitable acetogenic bacteria in such a way that these energetic barriers can be overcome. Partners in the consortium are Goethe University Frankfurt as well as the universities in Ulm, Göttingen and La Coruna. ArcelorMittal, the largest steel manufacturer worldwide, is the industrial partner. This microbial, CO2-based biotechnology could in future be an environmentally friendly alternative for the reprocessing of industrial waste gases rich in energy and carbon and reduce our dependency on crude oil. The microbial fixation and transformation of CO2 into raw materials produced biologically additionally makes it possible to reduce greenhouse gas emissions. A diagram can be downloaded from: http://www. Acetogenic (acetic acid-producing) bacteria produce acetic acid or ethanol from H2 + CO2 or CO. Energy is released in the form of ATP (adenosine triphosphate) in the process. The synthesis of other products interesting for industry from the intermediate product acetyl-CoA, however, also uses up ATP. The aim of this project is to alter the energy balance of the bacteria by means of genetic modification in such a way that the production of such energy-consuming compounds will also be possible.


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

FRANKFURT. When new particles develop in the atmosphere, this influences cloud formation and with that the climate too. Since a few years, these complex processes have been reproduced in a large air chamber within the CLOUD experiment at CERN. Researchers have now used the results for the first time to calculate the production of aerosol particles in all the Earth's regions and at different heights. The study published in the journal Science, in which researchers from Goethe University Frankfurt were involved, deciphers the role of the various chemical systems which are responsible for particle formation. They also determined the influence of ions which develop through cosmic radiation. Soot particles, dust lifted up by the wind or sea spray account for only some of the particles in the atmosphere. Others develop from certain trace vapours, for example when individual sulphuric acid and water molecules cluster as tiny droplets. This formation of new particles is known as nucleation. Clouds are formed by water condensing on the larger aerosol particles or what are known as cloud condensation nuclei. The more cloud droplets develop, the more sunlight is reflected back into space. Climate models show that the additional particles caused by human activity produce a cooling effect which partially offsets the greenhouse effect. It is, however, less than previously assumed. The model calculations presented in "Science" prove that about half the cloud condensation nuclei in the atmosphere originate from nucleation. In the atmosphere today, particle formation is dominated almost everywhere by mechanisms where at least three chemical components must come together: apart from the two basic substances, i.e. sulphuric acid and water, these are either ammonia or specific organic compounds such as oxidation products from terpenes. Close to ground level, organic substances from natural sources are important, whilst ammonia plays a key role higher up in the troposphere. Ammonia and sulphur emissions have increased considerably over the past decades as a result of human activities. CLOUD has also investigated how the 11-year solar cycle influences the formation of aerosol particles in our present-day atmosphere. The model calculations show that the effects as a result of changes in ionisation through the sun are too small to make a significant contribution to cloud formation. Although the ions are originally involved in the development of almost one third of all newly formed particles, the concentration of the large cloud condensation nuclei in the course of the 11-year cycle changes by only 0.1 percent - not enough to have any sizeable influence on the climate. The CLOUD team has also presented first global model calculations for aerosol formation caused without the involvement of sulphuric acid and solely through extremely low volatile substances of biological origin (Gordon et al., PNAS). According to the findings, this process contributed significantly to particle formation above all in the pre-industrial atmosphere, since at that time far less sulphur components were released into the atmosphere. The number of particles in the pre-industrial atmosphere is now estimated to be far greater through the additional process than was shown in earlier calculations. The model calculations, which are based on data from the CLOUD experiment, reveal that the cooling effects of clouds are 27 percent less than in climate simulations without this effect as a result of additional particles caused by human activity: Instead of a radiative effect of -0.82 W/m2 the outcome is only -0.60 W/m2.


News Article | November 18, 2016
Site: www.eurekalert.org

FRANKFURT. The first Research Training Group ever with a focus on film studies will be established in the course of the coming year at Goethe University Frankfurt. This was announced by the German Research Foundation on the 14th of November. In the framework of the RTG with the title "Configurations of Film", twelve doctoral researchers and two post-docs will examine from 2017 onwards how film culture is changing in the context of advancing digitalisation in various areas. Contemporary film culture is often referred to as the "post-cinematographic era". Professor Vinzenz Hediger, scholar and film expert at the University who will also be the RTG's speaker, remarks: "Film has expanded its reach more and more beyond public screenings in the cinema. With the proliferation of digital platforms, new forms are developing and new patterns of cinematic experience emerge." At the same time, film serves increasingly as a creative template in theatre, fine arts and music. Hediger says: "As films circulate ever more widely, they affect other art forms and have a growing impact on other areas of life, including interpersonal communication. This increasing presence of filmic images and formats in all areas of life also constitutes a growing societal challenge." The "Configurations of Film" RTG of the German Research Foundation wants to take on this challenge by investigating the current transformations of film and their impact on other art forms and areas of life from an interdisciplinary perspective. The RTG combines an emphasis on historical research with systematic and comparative perspectives; in addition, the programme will use digital methods for film analysis and data mining on the internet, with which, for example, the proliferation of new film formats via platforms such as YouTube or Vimeo can be tracked. The Research Training Group will build on successful cooperation between Goethe University Frankfurt and the German Film Institute (Deutsches Filminstitut), which together run the Masters degree programme in "Film Culture: Archiving, Programming, Presentation", and profit from links to other cultural institutions in the Rhine-Main region. The RTG also builds on the interdisciplinary Masters degree programme in "Aesthetics", which is unique to Frankfurt and in which all the disciplines participating in the RTG are also involved. Twelve doctoral researchers and two post-docs, who can apply for a German Research Foundation scholarship in the framework of the Research Training Group, will start with their research in 2017. They will be supervised and mentored by 15 researchers from six universities: Goethe University Frankfurt, Offenbach University of Art and Design, Johannes Gutenberg University Mainz, the University of Mannheim and Philipps University Marburg. Alongside film studies and media studies, the disciplines involved include theatre studies, philosophy, musicology, literary studies and sociology. The RTG has an international focus and cooperates with the film studies programmes at Yale University (New Haven, USA) and Concordia University (Montreal, Canada). Funding amounts to about € 3.3 million for the first phase from 2017 to 2022. In the spirit of the "citizen's university", the study programme will include a series of public lectures and events, for example at b3, the Biennale of the Moving Image, and at the cinema of the German Film Museum (Deutsches Filmmuseum), in the framework of which the RTG's themes and research questions will be discussed in public and address a broader audience.


News Article | December 13, 2016
Site: www.eurekalert.org

FRANKFURT. Nature often produces a whole weaponry of active ingredients to ensure it is well prepared for any scenario that might occur. Pharmacists and medical experts have meanwhile learnt from this, since pathogens develop resistance more easily to single active drugs than to a combination therapy. The research group led by Professor Helge Bode has now discovered a whole class of new peptides with which bacteria are able to kill insect larvae. The peptides, known as rhabdopeptide/xenortide peptides (RXPs), are produced exclusively by the bacterial genera Photorhabdus and Xenorhabdus. They live in symbiosis with nematodes, together with which they infect and kill insect larvae. Since many RXPs are toxic for eukaryotic cells (including insect cells) and are produced by many different strains of Xenorhabdus and Photorhabdus, they presumably play a very important role during infection. One single strain of bacteria can produce up to 40 RXP derivates. As the research group, which is led by Professor Helge B. Bode, Merck Endowed Professor of Molecular Biotechnology at Goethe University Frankfurt, reported in the latest issue of Nature Chemistry, it was surprising to see that only a maximum of four enzymes is required for their production. Bode compares them with classic chemical catalysts for the formation of polymer chains. His group has successfully solved the mechanisms responsible for the production of the unusually high diversity of RXPs. Why do the bacteria produce a whole library of RXPs instead of single compounds? The researchers explain that the bacteria cannot control into which insect larvae they are delivered by their nematode host. However, in order to survive they must be able to kill any insect quickly and efficiently and direct the mixture of substances at perhaps completely different target sites in the insect cells at the same time. "Imagine shooting with a shotgun", explains Bode, "even if you're a poor marksman, there's a good chance that the spray of bullets will ensure that at least one hits the target!" Future work will focus on detecting the exact mode of action of the RXPs and identifying, by means of structure-activity analysis, particularly potent derivates, which can then be produced biotechnologically or chemically and perhaps used as insecticides. A picture can be downloaded from: http://www.


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

FRANKFURT. Translation of the genetic code in proteins is a central process in life and takes place in the ribosome, a giant molecule consisting of two subunits. This is where long chains of amino acids are formed like on an assembly line. An interdisciplinary research group from Goethe University Frankfurt, the EMBL in Heidelberg, and the Gene Center of the University of Munich (LMU) has now succeeded in solving the structure of a central player in this process bound to the small ribosomal subunit: the protein containing a unique iron-sulphur domain with the nickname "Iron Hammer" splits the two subunits of the ribosome when a protein chain is completed so that production of a new protein can begin. The two subunits of the ribosome have to be actively split once the protein chain is complete otherwise errors occur in mRNA translation: research ignored this fact for a long time. Central player in this "ribosome recycling" process is the essential and highly dynamic metalloenzyme ABCE1. The iron-sulphur domain of ABCE1, known as the "Iron Hammer", rotates and presses the ribosomal subunits apart like a lever. To uncover this, the research group led by Professor Robert Tampé at the Institute of Biochemistry at Goethe University Frankfurt isolated a complex of the small ribosomal subunit with ABCE1 (post-splitting complex) by means of an innovative preparation method. This complex was chemically fixed and cut into pieces, while the original distance information was preserved. At the EMBL in Heidelberg, the researchers used highly advanced mass spectrometry to analyse these small fragments and relate them to each other revealing their original distances on nanometre scale. The group in Munich then examined the reconstructed complex with a high-resolution cryogenic electron microscope and was able to reconstruct a 3D model of the post-splitting complex with tightly bound ABCE1 from a vast collection of single-particle images. Professor Robert Tampé summarizes the significance of these results: "We have forced the rebellious and aggressive multi-domain enzyme ABCE1 into a new, unexpected state on the ribosome and used the combined expertise of three institutes to enrich textbook knowledge for coming generations of students."


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: SSH.2011.1.2-1 | Award Amount: 10.37M | Year: 2012

The objective of this 4-year project is to provide the analytical basis for a socio-ecological transition in Europe: the change to a new growth path with smart, sustainable and inclusive growth as is envisaged in the EU 2020 strategy. In order to support the transition, we analyse the need, the feasibility and best practice for change, specifying the institutional changes needed at all policy levels to implement these options. The old and new challenges Europe is facing define the starting point: globalisation, new technologies and postindustrialisation, demographic change and ecology in the context of welfare systems that have come under stress due to high public deficits. The vision is that Europe will become a role model for a high road growth path which actively incorporates social and ecological goals, employment, gender and cultural aspects in an ambitious, forward looking way while continuing to be competitive in a globalised world. To achieve these objectives, the consortium will carry out and synthesise robust research in research areas covering the challenges to the welfare system, the biophysical dimension of socio-economic development, the identification of drivers towards socio-ecological transition, the role of governance and institutions on the European as well as the regional level. The consortium will benefit from ongoing dialogue with international experts in the form of expert panels and sounding boards, taking into account their views on the direction and feasibility for this new growth path. The project will be carried out by a consortium of 34 partners from universities and research institutes with international and interdisciplinary expertise. It represents 12 member states. High level Scientific and Policy Boards will monitor the analysis and the policy conclusions to guarantee the impact and dissemination of the results.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: SiS-2010-2.2.1.1 | Award Amount: 3.19M | Year: 2011

This project is about setting up a Europe-wide network for professionals and academics in the area of Primary Science Education. The aim is to provide training and professional support to teachers to help them use Inquiry based learning in Science in schools. The platform at European level will network professionals as well as support the organisation of training courses. It also recognises teachers and researchers achievements in implementing Inquiry-based learning in science, as well as provide an opportunity for teachers and academics to share their experiences and successes. The project will concurrently also take small projects in primary science education, and promote them on a larger scale in order to provide examples of Inquiry Based teaching approaches to have an impact at European level. The project includes several previous projects, mainly: using an already developed theoretical pedagogical model for the teaching of science at primary level for developing teaching resources (developed as part of Comenius 1 and 2 projects); utilising the European network for primary school teachers to provide training and professional development to primary science teacher trainers; as well as providing in-service training opportunities based on experience of partners in implementing ERASMUS intensive courses for primary school teachers on a national and international level. Pri_Sci_Net aims to establish a European community of primary science educators working within the Inquiry Based approach.


News Article | November 11, 2016
Site: phys.org

How can the enormous amounts of electricity generated through offshore wind power be temporarily stored on site? Until now there was no answer to this question. After several years' research work, the StEnSea project (Stored Energy in the Sea) funded by the Federal Ministry for Economic Affairs and Energy is now entering the test phase. In the framework of this project, IWES, the Fraunhofer institute in Kassel specialized in energy system technology, is now developing to application level the "marine egg" invented by two physics professors at Goethe University Frankfurt and Saarland University in Saarbrücken. A model on the scale of 1:10 with a diameter of about three meters was brought to the ferry terminal in Constance on 8.11.2016 and lowered on 9.11.2016 to a depth of 100 meters about 200 meters from the shore in Überlingen. It will now be tested for four weeks: "Pumped storage power plants installed on the seabed can use the high water pressure in very deep water to store electrical energy with the aid of hollow spheres", explains Horst Schmidt-Böcking, emeritus professor at Goethe University Frankfurt. To store energy water is pumped out of the sphere using an electric pump and to generate power water flows through a turbine into the empty sphere and produces electrical energy via a generator. Together with his colleague Dr. Gerhard Luther from Saarland University, Professor Schmidt-Böcking filed a patent for their principle for offshore energy storage in 2011, just a few days before the Fukushima disaster. The two inventors remember: "The rapid practical realization of our idea is actually thanks to a newspaper article in the FAZ. Georg Küffner, the technology editor, presented our idea for energy storage to the general public - as chance would have it on the 1st of April 2011. Lots of readers doubtlessly thought at first that it was an April Fool hoax, but experts at Hochtief Solutions AG in Frankfurt immediately recognized the idea's hidden possibilities. Within a couple of weeks we were able to set up a consortium for an initial feasibility study with Hochtief's specialists for concrete structures and the experts in marine power and energy storage at IWES in Kassel, the Fraunhofer Institute for Wind Energy and Energy System Technology", recall Schmidt-Böcking and Luther. Once the concept's feasibility had been proven, the Federal Ministry for Economic Affairs and Energy subsequently funded the StEnSea project so that the innovative pumped storage system could be further developed and tested on a model scale. It is now entering the test phase. Project Manager Matthias Puchta from Fraunhofer IWES summarizes the project's successes to date: "On the basis of our preliminary study, we carried out a detailed systems analysis with a design, construction and logistics concept for the pressure tank, developed a turbine-pump unit, examined how to connect the sphere to the electricity grid, calculated profitability and drew up a roadmap for the system's technical implementation." He continues: "The four-week model trials on the scale of 1:10 are starting now in Lake Constance. We will run various tests to check all the details concerning design, installation, configuration of the drivetrain and the electrical system, operation and control, condition monitoring as well as dynamic modeling and simulation of the system as a whole." IWES Head of Division Jochen Bard, who has been involved in marine power research for many years at both national and international level, explains: "With the results from the model trials, we want first of all to look more closely at suitable sites for a demonstration project in Europe. We are aiming at a sphere diameter of 30 meters for the demonstration-scale system. At the moment that's the most practical size in terms of engineering. What's already certain is that the system can only be used economically in the sea at depths of about 600-800 meters upwards. Storage capacity with the same volume increases linearly with the depth of the water and at 700 meters is about 20 megawatt hours (MWh) for a 30 m sphere." He continues: "There is great potential for the use of marine pumped storage systems in coastal areas, in particular near the coast in highly populated regions too, for example in Norway (Norwegian Trench). But Spain, the USA and Japan also have great potential. With a storage capacity of 20 MWh per sphere and standard technology available today, we can envisage a total electricity storage capacity of 893.000 MWh worldwide. This would make an important and inexpensive contribution to compensating fluctuations in electricity generation from wind and solar power."


News Article | November 11, 2016
Site: www.eurekalert.org

After several years' research work, the StEnSea project (Stored Energy in the Sea) funded by the Federal Ministry for Economic Affairs and Energy is now entering the test phase. In the framework of this project, IWES, the Fraunhofer institute in Kassel specialized in energy system technology, is now developing to application level the "marine egg" invented by two physics professors at Goethe University Frankfurt and Saarland University in Saarbrücken. A model on the scale of 1:10 with a diameter of about three meters was brought to the ferry terminal in Constance on 8.11.2016 and lowered on 9.11.2016 to a depth of 100 meters about 200 meters from the shore in Überlingen. It will now be tested for four weeks: "Pumped storage power plants installed on the seabed can use the high water pressure in very deep water to store electrical energy with the aid of hollow spheres", explains Horst Schmidt-Böcking, emeritus professor at Goethe University Frankfurt. To store energy water is pumped out of the sphere using an electric pump and to generate power water flows through a turbine into the empty sphere and produces electrical energy via a generator. Together with his colleague Dr. Gerhard Luther from Saarland University, Professor Schmidt-Böcking filed a patent for their principle for offshore energy storage in 2011, just a few days before the Fukushima disaster. The two inventors remember: "The rapid practical realization of our idea is actually thanks to a newspaper article in the FAZ. Georg Küffner, the technology editor, presented our idea for energy storage to the general public - as chance would have it on the 1st of April 2011. Lots of readers doubtlessly thought at first that it was an April Fool hoax, but experts at Hochtief Solutions AG in Frankfurt immediately recognized the idea's hidden possibilities. Within a couple of weeks we were able to set up a consortium for an initial feasibility study with Hochtief's specialists for concrete structures and the experts in marine power and energy storage at IWES in Kassel, the Fraunhofer Institute for Wind Energy and Energy System Technology", recall Schmidt-Böcking and Luther. Once the concept's feasibility had been proven, the Federal Ministry for Economic Affairs and Energy subsequently funded the StEnSea project so that the innovative pumped storage system could be further developed and tested on a model scale. It is now entering the test phase. Project Manager Matthias Puchta from Fraunhofer IWES summarizes the project's successes to date: "On the basis of our preliminary study, we carried out a detailed systems analysis with a design, construction and logistics concept for the pressure tank, developed a turbine-pump unit, examined how to connect the sphere to the electricity grid, calculated profitability and drew up a roadmap for the system's technical implementation." He continues: "The four-week model trials on the scale of 1:10 are starting now in Lake Constance. We will run various tests to check all the details concerning design, installation, configuration of the drivetrain and the electrical system, operation and control, condition monitoring as well as dynamic modeling and simulation of the system as a whole." IWES Head of Division Jochen Bard, who has been involved in marine power research for many years at both national and international level, explains: "With the results from the model trials, we want first of all to look more closely at suitable sites for a demonstration project in Europe. We are aiming at a sphere diameter of 30 meters for the demonstration-scale system. At the moment that's the most practical size in terms of engineering. What's already certain is that the system can only be used economically in the sea at depths of about 600-800 meters upwards. Storage capacity with the same volume increases linearly with the depth of the water and at 700 meters is about 20 megawatt hours (MWh) for a 30 m sphere." He continues: "There is great potential for the use of marine pumped storage systems in coastal areas, in particular near the coast in highly populated regions too, for example in Norway (Norwegian Trench). But Spain, the USA and Japan also have great potential. With a storage capacity of 20 MWh per sphere and standard technology available today, we can envisage a total electricity storage capacity of 893.000 MWh worldwide. This would make an important and inexpensive contribution to compensating fluctuations in electricity generation from wind and solar power."


News Article | October 11, 2016
Site: www.theenergycollective.com

The European Commission should set a target for retrofitting all of the continent’s existing buildings to a “Nearly Zero Energy” standard by 2050. That is the request in a letter to the Commission signed by the chief executives of 42 major building firms and six industry trade associations. The target would be enshrined in the upcoming revision of the Energy Performance of Building Directive and the Energy Efficiency Directive, which are currently under review. Arguing that “businesses, investors, citizens, governments, all need a clear 2050 vision to put the ambition level of the Paris Agreement into practice”, they state that doing so would provide an opportunity to create jobs and economic growth. The letter reads: “It is clear that the Paris commitment cannot be honoured without drastically reducing energy consumption in our buildings; the EU building stock emits over one-third of our CO2 emissions, three-quarters of our buildings are inefficient, and up to four-fifths will still be in use in 2050. We need EU wide action to drive the transformation of our inefficient building stock and make it a resilient component of the energy system of the 21st century.” It continues: “EU wide leadership and action in the construction and building sector will spur European jobs and growth (in particular for SMEs, which make up 90 per cent of the construction sector). A high level political commitment for renovation will give industry the much needed signal and certainty to unlock investments, in turn removing some of the market failures. “Most of all, making Europe’s buildings better through a mass EU-wide renovation movement will bring invaluable benefits to the whole of society by helping deliver something that every European citizen wants and deserves: a comfortable, safe and affordable home. This is a ‘win-win’ for Europe.” This target is in line with the aims of the World Green Building Council’s Advancing Net Zero project to make all the world’s buildings ‘net zero’ of emissions by 2050. It builds on a push to double efficiency by 2030. Launched in June, this program involves Green Building Councils from Australia, Brazil, Canada, Germany, India, Netherlands, South Africa and Sweden who will develop clear action plans, with an aim to launch a national net zero certification. Energy efficiency package postponed Despite the backing of the European Parliament, the European Commission appears reluctant to back energy efficiency. At the beginning of this week it was slammed by the Coalition on Energy Savings for its announcement that the energy efficiency package will not be launched before the end of the year. The package will define a target for energy efficiency for 2030 and extend the main elements of the Energy Efficiency Directive beyond 2020, as well as discuss buildings’ energy performance and financing. “This delay undermines the credibility of the European Commission to drive forward the EU with big and compelling projects like energy efficiency, which delivers benefits for people and business and which is the EU’s first action to fight climate change,” secretary general of the Coalition for Energy Savings Stefan Scheuer said. “European Commission president Jean-Claude Juncker must not hesitate to deliver on his promise to propose a more ambitious and binding energy efficiency target for 2030.” The European Parliament has repeatedly called for a binding 40 per cent energy reduction target by 2030 in line with the already identified cost-effective potential for implementing energy saving measures. The target is currently set at a reduction of 20 per cent in energy use by 2020. Energy efficiency mortgage scheme Further backing the increasing desire for making European buildings more energy efficient, a new financing initiative, that would potentially offer better borrowing rates on mortgages for homebuyers purchasing more energy-efficient homes or carrying out energy-saving retrofits within properties, was presented by energy and building sector professionals from across Europe last week. The European Energy Efficiency Mortgage was launched at the World Green Building Council’s “Build Upon” summit in Madrid by the European Mortgage Federation, which consists of the European Covered Bond Council with partners. See EU residents set to get cheaper home loans for energy efficient houses The scheme effectively creates a “pan-European mortgage financing system” in order to make energy efficiency measures more accessible and affordable for home-buyers. For banks and investors, the mortgage could allow for loans that represent a lower risk on the balance sheet and could therefore qualify for a better capital treatment. It could also ensure that banks are able to recognise “energy-efficient” assets in their risk-profiling, which would begin to help the market price-in the added value of energy-efficient real estate. The project is the first time a group of major banks and mortgage lenders have sat down with businesses and organisations from the building and energy industries to address the concept of energy efficient mortgages. Creating a private bank financing mechanism to encourage the energy efficient improvement of households would be a key means of helping the EU to meet its energy saving targets. Alongside the EMF-ECBC, the project partners are the Ca’Foscari University of Venice, RICS, European Regional Network of Green Building Councils, E.ON, and SAFE Goethe University Frankfurt. Over the coming months, they will begin a mapping exercise in relation to existing or past financing initiatives, energy efficiency indicators and valuation practices, with a view to identifying best practices with which to move the project forward. It will explore the link between energy efficiency and borrower’s reduced probability of default and the increase in value of energy efficient properties. The experts will meet again in Brussels in February 2017, followed by a public event at which the next stage will be decided. Europeans can also generate half their energy at home Continuing the news from Europe on energy and buildings, it also emerged last week that half of EU citizens – including local communities, schools and hospitals – could be producing their own renewable electricity by 2050. A study by Dutch consultancy firm CE Delft that evaluated the potential of decentralised power generation across the continent found that 264 million people in Europe could be producing their own renewable electricity by 2050 and meet 45 per cent of the EU’s energy demand, provided the right regulatory framework is put in place. Sweden looks like leading the way, with an estimated 79 per cent of the population being able to produce their own energy in 2050. Germany and other EU countries like the Netherlands already champion energy production by households, which can sell surplus electricity back to the grid at a guaranteed price. “But in Spain, there is a ‘sun tax’ which makes it very expensive to install solar panels on your roofs or have energy storage at home. And there is only a handful of cooperatives,” said Sebastian Mang, climate change and energy officer at Greenpeace EU, which is among the organisations behind the study. “Yet across Germany, you see solar panels on the roofs and hundreds of energy cooperatives flourishing.” The organisations are calling for the European Commission to enshrine so-called “energy citizens” at the centre of the EU’s Energy Union initiative. David Thorpe is the author of: Best Practices and Case Studies for Industrial Energy Efficiency Improvement (with Oung, K. and Fawkes, S. UNEP, 2016) A London Conversation: Business Briefing on Green Bonds (The Fifth Estate, 2015) The One Planet Life (Introduction: Jane Davidson. Routledge, 2015) Earthscan Expert Guide to Energy Management in Buildings (Earthscan, 2013) Earthscan Expert Guide to Energy Management in Industry (Earthscan, 2013) Earthscan Expert Guide to Solar Technology (Earthscan, 2011) Earthscan Expert Guide to Sustainable Home Refurbishment Photo Credit: Katherine Hodgson via Flickr Original Post


Kulic I.M.,Charles Sadron Institute | Kulic M.L.,Goethe University Frankfurt
Physical Review Letters | Year: 2013

From microscopic fluid clusters to macroscopic droplets, the structure of fluids is governed by the van der Waals force, a force that acts between polarizable objects. In this Letter, we derive a general theory that describes the nonequilibrium counterpart to the van der Waals force, which emerges in spatially coherently fluctuating electromagnetic fields. We describe the formation of a novel and complex hierarchy of self-organized morphologies in magnetic and dielectric colloid systems. Most striking among these morphologies are dipolar foams - colloidal superstructures that swell against gravity and display a high sensitivity to the applied field. We discuss the dominance of many-body forces and derive the equation of state for a material formed by the coherent van der Waals force. Our theory is applied to recent experiments in paramagnetic colloidal systems and a new experiment is suggested to test the theory. © 2013 American Physical Society.


Messerschmidt C.M.,Goethe University Frankfurt | Hinz O.,TU Darmstadt
Journal of Strategic Information Systems | Year: 2013

Grid computing can meet computational demands and offers a promising resource utilization approach. However, little research details the drivers of and obstacles to adoption of this technology. Institutional and organizational capability theory suggests an adoption model that accounts for inter- and intra-organizational influences. An empirical study with 233 high-ranking IT executives reveals that adoption results from social contagion, while organizational capabilities such as trust, firm innovativeness, tendency to outsource, and IT department size, influence adoption from an intra-organizational perspective. The findings show that mimetic pressures and trust play major roles in adoption processes, which differentiates grid computing from other inter-organizational systems. © 2013 Elsevier B.V. All rights reserved.


Halfon P.,Virological Departement Laboratoire Alphabio | Sarrazin C.,Goethe University Frankfurt
Liver International | Year: 2012

Recent advances in molecular biology have led to the development of novel small molecules that target specific viral proteins of the hepatitis C virus (HCV) life cycle. These drugs, collectively termed directly acting antivirals (DAA), include a range of non-structural (NS) 3/NS4A protease, NS5B polymerase and NS5A inhibitors at various stages of clinical development. Some others drugs called 'non DAA'or indirect inhibitors are not focused on one site of the life cycle target and are still in early pre-clinical and clinical phase I, II and III trials. The rapid replication rate of HCV, along with the low fidelity of its polymerase, results in a generation of mutations throughout the viral genome and sequence variation in the HCV population known as a quasispecies. The efficacy of DAA is limited by the presence of these mutations, resulting in amino acid substitutions within the targeted proteins which affect viral sensitivity to these compounds. Thus, attributable to the high genetic variability of HCV, variants with reduced susceptibility to DAA can occur naturally even before treatment begins, but usually at low levels. Thus it is not surprising that these changes are selected in patients that either breakthrough or do not respond to potent DAA treatment. Six major position mutations in the NS3 HCV Protease (36, 54, 155, 156, 168 and 170), fifteen in the NS5B polymerase (96, 282, 316, 365, 414, 419, 423, 448, 482, 494, 495, 496, 499, 554, 559) and five in the NS5 A region (28, 30, 31, 58 and 93) have now been reported in vitro or in vivo associated with different levels of resistance. The amino acid composition at several of the drug resistance sites can vary between the HCV genotypes/subtypes, resulting in different consensus amino acids leading to a reduction in replicative fitness as well as reduced DAA and non- DAA sensitivity. Information on patterns of resistance to and cross resistance between antiviral agents is increasingly available and may be important for decisions on how to combine drugs to achieve an optimum antiviral effect. This review debates the clinical relevance of resistance to direct and indirect inhibitors taking into account the future potential therapeutic strategies to help patients who do develop resistance to HCV inhibitors. Finally, this chapter treats two points of view: 'for' and 'against' the question of the importance of resistance. © 2012 John Wiley & Sons A/S.


Stangier U.,Goethe University Frankfurt | Schramm E.,Albert Ludwigs University of Freiburg | Heidenreich T.,Esslingen University of Applied Sciences | Berger M.,Albert Ludwigs University of Freiburg | Clark D.M.,King's College London
Archives of General Psychiatry | Year: 2011

Context: Cognitive therapy (CT) focuses on the modification of biased information processing and dysfunctional beliefs of social anxiety disorder (SAD). Interpersonal psychotherapy (IPT) aims to change problematic interpersonal behavior patterns thatmay have an important role in the maintenance of SAD. No direct comparisons of the treatments for SAD in an outpatient setting exist. Objective: To compare the efficacy of CT, IPT, and a waiting-list control (WLC) condition. Design: Randomized controlled trial. Setting: Two academic outpatient treatment sites. Patients: Of 254 potential participants screened, 117 had a primary diagnosis of SAD and were eligible for randomization; 106 participants completed the treatment or waiting phase. Interventions: Treatment comprised 16 individual sessions of either CT or IPT and 1 booster session. Twenty weeks after randomization, posttreatment assessment was conducted and participants in the WLC received 1 of the treatments. Main Outcome Measures: The primary outcome was treatment response on the Clinical Global Impression Improvement Scale as assessed by independent masked evaluators. The secondary outcome measures were independent assessor ratings using the Liebowitz Social Anxiety Scale, the Hamilton Rating Scale for Depression, and patient self-ratings of SAD symptoms. Results: At the posttreatment assessment, response rates were 65.8% for CT, 42.1% for IPT, and 7.3% for WLC. Regarding response rates and Liebowitz Social Anxiety Scale scores, CT performed significantly better than did IPT, and both treatments were superior to WLC. At 1-year follow-up, the differences between CT and IPT were largely maintained, with significantly higher response rates in the CT vs the IPT group (68.4% vs 31.6%) and better outcomes on the Liebowitz Social Anxiety Scale. No significant treatment X site interactions were noted. Conclusions: Cognitive therapy and IPT led to considerable improvements that were maintained 1 year after treatment; CT was more efficacious than was IPT in reducing social phobia symptoms. ©2011 American Medical Association. All rights reserved.


Fukushima K.,Kyoto University | Kharzeev D.E.,Brookhaven National Laboratory | Warringa H.J.,Goethe University Frankfurt
Physical Review Letters | Year: 2010

In quantum chromodynamics, a gauge field configuration with nonzero topological charge generates a difference between the number of left- and right-handed quarks. When a (electromagnetic) magnetic field is added to this configuration, an electromagnetic current is induced along the magnetic field; this is called the chiral magnetic effect. We compute this current in the presence of a color-flux tube possessing topological charge, with a magnetic field applied perpendicular to it. We argue that this situation is realized at the early stage of relativistic heavy-ion collisions. © 2010 The American Physical Society.


Huovinen P.,Goethe University Frankfurt | Petreczky P.,Brookhaven National Laboratory
Nuclear Physics A | Year: 2010

We compare the trace anomaly, strangeness and baryon number fluctuations calculated in lattice QCD with expectations based on hadron resonance gas model. We find that there is a significant discrepancy between the hadron resonance gas and the lattice data. This discrepancy is largely reduced if the hadron spectrum is modified to take into account the larger values of the quark mass used in lattice calculations as well as the finite lattice spacing errors. We also give a simple parametrization of QCD equation of state, which combines hadron resonance gas at low temperatures with lattice QCD at high temperatures. We compare this parametrization with other parametrizations of the equation of state used in hydrodynamical models and discuss differences in hydrodynamic flow for different equations of state. © 2010 Elsevier B.V.


Bokszczanin K.L.,GenXPro GmbH | Fragkostefanakis S.,Goethe University Frankfurt
Frontiers in Plant Science | Year: 2013

Global warming is a major threat for agriculture and food safety and in many cases the negative effects are already apparent. The current challenge of basic and applied plant science is to decipher the molecular mechanisms of heat stress response (HSR) and thermotolerance in detail and use this information to identify genotypes that will withstand unfavorable environmental conditions. Nowadays X-omics approaches complement the findings of previous targeted studies and highlight the complexity of HSR mechanisms giving information for so far unrecognized genes, proteins and metabolites as potential key players of thermotolerance. Even more, roles of epigenetic mechanisms and the involvement of small RNAs in thermotolerance are currently emerging and thus open new directions of yet unexplored areas of plant HSR. In parallel it is emerging that although the whole plant is vulnerable to heat, specific organs are particularly sensitive to elevated temperatures. This has redirected research from the vegetative to generative tissues. The sexual reproduction phase is considered as the most sensitive to heat and specifically pollen exhibits the highest sensitivity and frequently an elevation of the temperature just a few degrees above the optimum during pollen development can have detrimental effects for crop production. Compared to our knowledge on HSR of vegetative tissues, the information on pollen is still scarce. Nowadays, several techniques for high-throughput X-omics approaches provide major tools to explore the principles of pollen HSR and thermotolerance mechanisms in specific genotypes. The collection of such information will provide an excellent support for improvement of breeding programs to facilitate the development of tolerant cultivars. The review aims at describing the current knowledge of thermotolerance mechanisms and the technical advances which will foster new insights into this process. © 2013 Bokszczanin, Solanaceae Pollen Thermotolerance Initial Training Network (SPOT-ITN) Consortium and Fragkostefanakis.


Martinez M.,Goethe University Frankfurt | Strickland M.,Gettysburg College
Physical Review C - Nuclear Physics | Year: 2010

We demonstrate how to match pre-equilibrium dynamics of a 0+1-dimensional quark-gluon plasma to second-order viscous hydrodynamical evolution. The matching allows us to specify the initial values of the energy density and shear tensor at the initial time of hydrodynamical evolution as a function of the lifetime of the pre-equilibrium period. We compare two models for pre-equilibrium quark-gluon plasma, longitudinal free streaming and collisionally broadened longitudinal expansion, and present analytic formulas that can be used to fix the necessary components of the energy-momentum tensor. The resulting dynamical models can be used to assess the effect of pre-equilibrium dynamics on quark-gluon plasma observables. Additionally, we investigate the dependence of entropy production on pre-equilibrium dynamics and discuss the limitations of the standard definitions of nonequilibrium entropy. © 2010 The American Physical Society.


Popovic D.,Goethe University Frankfurt | Vucic D.,Genentech | Dikic I.,University of Split
Nature medicine | Year: 2014

Ubiquitination is crucial for a plethora of physiological processes, including cell survival and differentiation and innate and adaptive immunity. In recent years, considerable progress has been made in the understanding of the molecular action of ubiquitin in signaling pathways and how alterations in the ubiquitin system lead to the development of distinct human diseases. Here we describe the role of ubiquitination in the onset and progression of cancer, metabolic syndromes, neurodegenerative diseases, autoimmunity, inflammatory disorders, infection and muscle dystrophies. Moreover, we indicate how current knowledge could be exploited for the development of new clinical therapies.


Qin S.-X.,Goethe University Frankfurt | Roberts C.D.,Argonne National Laboratory | Schmidt S.M.,Jülich Research Center
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

The colour-singlet axial-vector vertex plays a pivotal role in understanding dynamical chiral symmetry breaking and numerous hadronic weak interactions, yet scant model-independent information is available. We therefore use longitudinal and transverse Ward-Green-Takahashi (WGT) identities, together with kinematic constraints, in order to ameliorate this situation and expose novel features of the axial vertex: amongst them, Ward-like identities for elements in the transverse piece of the vertex, which complement and shed new light on identities determined previously for components in its longitudinal part. Such algebraic results are verified via solutions of the Bethe-Salpeter equation for the axial vertex obtained using two materially different kernels for the relevant Dyson-Schwinger equations. The solutions also provide insights that suggest a practical Ansatz for the axial-vector vertex. © 2014.


Kim J.M.,University of California at San Francisco | Wu S.,University of California at San Francisco | Tomasiak T.M.,University of California at San Francisco | Mergel C.,Goethe University Frankfurt | And 7 more authors.
Nature | Year: 2015

ATP-binding cassette (ABC) transporters translocate substrates across cellmembranes, using energyharnessed fromATPbinding andhydrolysis at their nucleotide-bindingdomains1,2.ABCexporters are present both in prokaryotes and eukaryotes, with examples implicated in multidrug resistance of pathogens and cancer cells, aswell as inmany human diseases3,4.TmrABis a heterodimericABCexporter fromthe thermophilic Gram-negative eubacterium Thermus thermophilus; it is homologous to various multidrug transporters and contains one degenerate site with a non-catalytic residue next to the Walker B motif5. Here we report a subnanometre-resolution structure of detergent-solubilizedTmrABin a nucleotide-free, inward-facing conformation by single-particle electron cryomicroscopy. The reconstructions clearly resolve characteristic features ofABCtransporters, including helices in the transmembrane domain and nucleotidebinding domains. A cavity in the transmembrane domain is accessible laterally from the cytoplasmic side of the membrane as well as fromthe cytoplasm,indicating that the transporter lies in an inwardfacing open conformation. The two nucleotide-binding domains remain in contact via their carboxy-terminal helices. Furthermore, comparison between our structure and the crystal structures of other ABC transporters suggests a possible trajectory of conformational changes that involves a sliding and rotatingmotion between the two nucleotide-bindingdomains during the transition from the inwardfacing to outward-facing conformations. © 2015 Macmillan Publishers Limited. All rights reserved.


Dimmeler S.,Goethe University Frankfurt | Ding S.,University of California at San Francisco | Rando T.A.,Stanford University | Trounson A.,California Institute for Regenerative Medicine
Nature Medicine | Year: 2014

The scientific community is currently witnessing substantial strides in understanding stem cell biology in humans; however, major disappointments in translating this knowledge into medical therapies are flooding the field as well. Despite these setbacks, investigators are determined to better understand the caveats of regeneration, so that major pathways of repair and regrowth can be exploited in treating aged and diseased tissues. Last year, in an effort to contribute to this burgeoning field, Nature Medicine, in collaboration with the Volkswagen Foundation, organized a meeting with a panel of experts in regenerative medicine to identify the most pressing challenges, as well as the crucial strategies and stem cell concepts that can best help advance the translational regenerative field. Here some experts who participated in the meeting provide an outlook at some of those key issues and concepts. © 2014 Nature America, Inc.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: Fission-2010-2.3.1 | Award Amount: 4.95M | Year: 2011

The present FP-7 proposal MAX is subsequent to the recommendations of the Strategic Research Agenda of SNETP for ADS development in Europe. Its aim is to pursue the R&D required for a high power proton accelerator as specified by the MYRRHA project. There is especially a strong focus on all the aspects that pertain to the reliability and availability of this accelerator. This R&D effort builds on the large body of results and the clear conclusions that have been obtained during the consecutive FP5 project PDS-XADS and FP6 project EUROTRANS. MAX will further investigate the key issues of redundancy and fault-tolerance by real-world experience in making maximum use of already existing or to-be-built dedicated prototypes, both on the injector side and on the main superconducting linac side. At the end of the MAX project, it will be possible to generate an updated consolidated reference layout of the accelerator for MYRRHA with sufficient detail and adequate level of confidence in order to initiate its engineering design and subsequent construction phase.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: YOUNG-5a-2014 | Award Amount: 2.58M | Year: 2015

Existing research suggests that political participation and European orientation of young people depend on how they experience influence and involvement at local level. This reflects that individuals need the experience of self-efficacy to engage in wider communities. Research also reveals that only few young people engage in formalised participation (parties, trade unions, or youth councils) as these are not flexible enough for individualised concerns, biographies and life styles and they reflect patterns of social inequality. The project Spaces and Styles of Participation (PARTISPACE) starts from the assumption that all young people do participate while not all participation is recognised as such. The study asks for the different ways in which young people participate in decisions which concern them and, in general, the life of their communities. How do 15- and 30-year-olds engage with the public in formal, non-formal and informal settings and how is this supported or inhibited by local youth policies and youth work? The countries involved Bulgaria, France, Germany, Italy, Sweden, Switzerland, Turkey and the UK secure contrasting contexts of young peoples growing up as well as differing orientations towards Europe. The design of PARTISPACE includes: National research literature reviews and policy analysis; Analysis of European Social Survey data on young peoples participatory orientations; Local case studies in one major city per country including expert interviews, focus groups discussions, city walks and biographical interviews with young people, ethnographic case studies of formal, non-formal, and informal participatory spaces. Activating and supporting participatory action research by young people themselves. The analysis relates local constellations with national and European patterns and discourses of youth participation. Findings are constantly discussed with representatives of the youth sector at local and European level.


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

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


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-2 | Award Amount: 15.18M | Year: 2013

The ageing of the European population represents a rapidly rising social and economic challenge. Especially cardiovascular morbidity increases with age, but unfortunately, elderly patients are often difficult to diagnose due to confounding factors, leading to uncertainties in clinical decision making with huge impact on patients outcomes. Hence, there is an unmet need for novel biomarkers for more accurate diagnosis, risk assessment, and clinical outcome prediction for both acute and chronic cardiovascular diseases in the elderly. The BestAgeing consortium aims to improve this lack of diagnostic capabilities by developing and validating innovative omics-based biomarkers particularly for elderly patients supporting healthy ageing in Europe. Our study design addresses the most frequent and severe cardiovascular diseases of elderly patients by incorporating the appropriate disease cohorts and biomaterials from European populations. We aim to develop new omics-assays to diagnose cardiovascular disease, estimate risk, and monitor the response to treatment in elderly. This is envisaged to enable a more stratified and economic delivery of medicine. We expect that BestAgeing will generate novel European medical technologies that can improve the efficacy and efficiency of our care for elderly patients, which will also impact on socioeconomic wealth in Europe.


Grant
Agency: European Commission | Branch: H2020 | Program: IA | Phase: DS-02-2014 | Award Amount: 6.69M | Year: 2015

With increasing mobility and Internet usage, the demand for digital services increases and has reached critical and high assurance domains like e-Government, e-Health and e-Business. Those domains have high security and privacy requirements and hence will be harnessed with various novel mechanisms for secure access. Approaches for handling the resulting variety of authentication and authorisation mechanisms include the use of digital identity and access management systems (IAM). Like other technologies IAMs follow the trend of using cloud services. This allows abstracting over used resources and enables ubiquitous access to identity data which is stored and processed in the cloud, but also results in an additional degree of complexity for securely operating IAMs. The goal of CREDENTIAL is to develop, test and showcase innovative cloud based services for storing, managing, and sharing digital identity information and other critical personal data. The security of these services relies on the combination of strong hardware-based multi-factor authentication with end-to-end encryption representing a significant advantage over current password-based authentication schemes. The use of sophisticated proxy cryptography schemes will enable a secure and privacy preserving information sharing network for cloud-based identity information in which even the identity provider cannot access the data in plain-text and hence protect access to identity data. We focus not only on evaluating and applying novel crypto-approaches for IAMs but also on implementing them in an easy-to-use way to motivate secure handling of identity data. In order to also address security, privacy and trust issues related to the used cloud platforms and services we will investigate assurance and resilience approaches for enhancing underlying cloud services. To empirically evaluate our work and to produce outputs of a high technical readiness we will consider use cases from all three domains mentioned above.


Grant
Agency: European Commission | 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: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.31M | Year: 2011

The main objective of the international training network UPStream is the training of a novel generation of European scientist in a critical and complex field of modern biology: the understanding of the regulation of the UPS and its potential use for drug development. The importance of this process is illustrated by the imperious necessity to destroy certain proteins during several phases of the cell cycle in order to progress to the next phase. The biochemical process of ubiquitylation is an efficient way to label proteins that will be targeted to degradation by the proteasome at the right time and cellular compartment, according to the cell necessities. In addition, this post-translational modification also offers to the cell the possibility to control other processes related or not to proteolytic functions. Indeed, the attachment of ubiquitin (Ub) or ubiquitin-like (UBL) molecules such as SUMO and NEDD8 does not always result in proteolysis, but can induce conformational and/or interaction changes driving a large diversity of effects. Considering the interconnectivity among Ub and UBL molecules, we end up with an extremely complex system regulating protein activity and stability. Given the implications of the ubiquitin proteasome system (UPS) in many essential cellular processes, the technology required to study this system is very diverse. As part of the proposed network the latest technological developments (please see implementation) will be used to explore chemical, biochemical, molecular, developmental and genetic aspects of the UPS. This research area has become an area of investigation by itself, very attractive for fundamental scientists as well as for the pharmaceutical industry aiming to identify potential targets for drug development to be used in many diseases where this system has been shown to be vital.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-21-2016 | Award Amount: 4.26M | Year: 2017

Screening for vision and hearing disorders in children has shown to be highly effective. EU-directive 16620/11 invites EU-member states to give priority to such screening programmes. Early detection and treatment of a lazy eye (prevalence 3%) prevents lifelong visual impairment. Early detection and treatment of hearing impairment (prevalence 0.15%) prevents delayed speech and language development. Across Europe inequity exists in the provision of childhood vision and hearing screening programmes (VAHSPs). High-Income Countries (HICs) have VAHSPs, but they vary with regard to age and frequency of testing, tests used, uptake, screening professionals, referral pathway and funding. This makes it difficult for healthcare providers and policy makers to decide what VAHSP to implement in Low- to Middle-Income Countries (LMICs) and how. In this study, cost-optimised, evidence-based VAHSPs will be implemented in two LMICs, based on collated evidence from existing VAHSPs in Europe. Data on VAHSPs, demography, administration, general screening, screening professions, uptake and treatment availability will be gathered in an established network of professionals in 41 European countries and used in a disease/health system modelling framework to predict benefits and cost in the most optimal health system, taking regional diversity and organisational and resource requirements into account. Model-developed VAHSPs will be tested in the county of Cluj in Romania for vision, and in three counties in Albania for hearing screening. A generic strategy for implementation will be developed by detailed tracking, and from identified requirements, facilitators and barriers. The decision-analytic modelling framework and the strategy for implementation will be packed into a transferable TOOLKIT that will assist healthcare providers and policy makers worldwide in their decisions to introduce or modify VAHSPs, and increase effectiveness, efficiency and equity of child healthcare.


Grant
Agency: European Commission | Branch: FP7 | Program: ERC-SG | Phase: ERC-SG-PE6 | Award Amount: 1.10M | Year: 2011

This is a project in the area of Theoretical Computer Science, particularly discrete algorithms and computational complexity. Many Constraint Satisfaction Problems (`CSPs) such as Boolean satisfiability or graph coloring are well-known to be NP-hard, i.e., the worst-case computation time to solve these problems is exponential in the size of the problem instance. To illuminate the conceptual origins of the computational hardness of these problems, a major research effort over the past 30 years has been the study of Random instances of CSPs. Over the past decade, motivated by problems in statistical mechanics, physicists have developed stunningly detailed hypotheses on the structural and conceptual nature of random CSPs, based on ingenious but highly non-rigorous techniques. These hypotheses have led to a new class of Message Passing Algorithms, as well as to evidence that certain natural types of random CSPs may be computationally intractable. The goal of this project is to study these ideas rigorously and comprehensively from the perspective of the theory of computing.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA | Phase: ICT-2009.1.4 | Award Amount: 833.02K | Year: 2010

GINI-SA is a Support Action driven by the vision of a Personalized Identity Management ecosystem where people will control their own Individual Digital Identity (INDI) space. Individual persons will have the ability to establish and manage personalized digital identities which they will own, linking them to verifiable and authoritative national data registries. They will be able to present their chosen, verified digital identity to other physical persons or legal entities with which they wish to establish trust relationships in order to perform transactions for personal, business or official purposes. They will also be able to attach them to messages and profiles.\nGINI will address the individual persons requirements and preferences for different contexts of administrative, business and social use. Respect and enhancement of privacy will determine that identity data handling and storing must be conditional to the terms of the identity owner. Work will address how trust relationships can be managed through a dynamic interface, where differentiation of services is driven by the demand and individuals choices as to trust assurances. GINI will further examine the technological, legal, regulatory and privacy-related dimensions of the gap between the current state of the art and the vision for an INDI ecosystem beyond 2020.\nThe overall framework to be created will account for a market space capable of dynamically developing services for the handling and storage of identity data, based on the proportionality and minimization principles. Conditions for privacy will be greatly enhanced. The situation when identity retrieval is required by law, for fraud detection or conflict resolution, will require special considerations.\nGINI will provide crucial building blocks by developing a research and implementation Roadmap, forecasting developments and suggesting initiatives to be undertaken, mainly by the research community but driven by institutional stakeholders.\nINDI services will be developed by operators acting as professional and diversified Identity Service Providers. The development of such Operators, offering choice to individuals, will form a key part of the required infrastructure. GINI will study the legal and regulatory requirements for the establishment of such Operators in the EU and will make relevant recommendations in a White Paper.\nGINI-SA will devote significant effort to engagement and dissemination activities. It will consult with all relevant EU stakeholders in the research community, institutional actors in the EC and Member states, the industry, and grass-roots NGOs representing end-users. GINI will further act as a forum for constructive discussion and establishment of consensus on the content and priorities of the research and implementation agenda of the next 10-20 years, its findings representative of the wider constituency of the digital identity management domain.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.65M | Year: 2014

SNAL is a multidisciplinary programme specially designed to provide scientific and transferable skill training and career development for early stage researchers and experienced researchers in membrane research. Working in a multidisciplinary network will give the researchers a broad perspective on their research field as well as the basic ability of pursuing a research project from basic sciences to industrial applications. The broad aim is to train a new cohort of researchers with systemic thinking equipped with generic skills in combining experimental studies and computer simulations to prepare them for fruitful careers in academia and industry. One challenge for the project is the design and synthesis of novel biomaterials able to modify membrane properties. This requires deep understanding of the interactions of lipid membranes with nano-objects including functional biomimetic polymers, polymeric micelles, carbon nanotubes and polymer therapeutic complexes/conjugates to enable the intelligent design of novel materials with improved bilayer modifying properties. To achieve this goal we have assembled a highly interdisciplinary team of leading groups all having synergies in their established research interests in the field of lipid bilayer nano-objects interactions. The project combines computer simulations, chemical synthesis, clinical and industrial expertise, physical and biological experiments. The industry involvement in the project is very high with full participation of Unilever and Biopharma, the companies from different sectors. Complementarity of partner skills provides a logical basis for a collective training programme. The full cycle of the design process, from theoretical models to synthesis and experimental and clinical validation, is of particular importance for training of ESRs and their future career development.


Solov'Yov I.A.,Goethe University Frankfurt | Mouritsen H.,University of Oldenburg | Schulten K.,University of Illinois at Urbana - Champaign
Biophysical Journal | Year: 2010

The magnetic compass of birds is embedded in the visual system and it has been hypothesized that the primary sensory mechanism is based on a radical pair reaction. Previous models of magnetoreception have assumed that the radical pair-forming molecules are rigidly fixed in space, and this assumption has been a major objection to the suggested hypothesis. In this article, we investigate theoretically how much disorder is permitted for the radical pair-forming, protein-based magnetic compass in the eye to remain functional. Our study shows that only one rotational degree of freedom of the radical pair-forming protein needs to be partially constrained, while the other two rotational degrees of freedom do not impact the magnetoreceptive properties of the protein. The result implies that any membrane-associated protein is sufficiently restricted in its motion to function as a radical pair-based magnetoreceptor. We relate our theoretical findings to the cryptochromes, currently considered the likeliest candidate to furnish radical pair-based magnetoreception. © 2010 by the Biophysical Society.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP-2010-4.0-1 | Award Amount: 13.81M | Year: 2011

SaveMe project will address current urgent needs for pancreatic cancer diagnosis and treatment by exploiting partners expertise and most recent research achievements for the design and development of novel modular nanosystems platform integrating new functionalized nano-core particles and active agents. The modular platform will enable the design of diverse active nanosystems per diagnostic or therapeutic application as defined by their active agent compositions. For diagnostics, superior tracers will be developed for molecular MR/PET and gamma camera imaging, enabling efficient diagnosis and guided surgery respectively. Novel functionalized nano-core systems will be conjugated with semi-confluent active shell layer. Three types of shell layers will be design: (1) novel iron oxide nanoparticles as advanced MRI contrast agents and/or (2) DOTA complexes for MRI (with Gd3\), or PET (with Ga-68), or gamma camera (with Ga-69); (3) Integrating within one tracer both iron oxide nanoparticles and DOTA-Ga-68 complexes for a sequential or simultaneous MR/PET imaging. For therapeutics, active nanosystems will be developed to deliver (1) therapeutic siRNAs or (2) anti-MP-inhibitory-scFVs. These non-classic anti-tumor drugs will be designed based on an extensive tumor degradome analysis for combining blockage of selective matrix MPs, thus preventing basic invasive and metastasis steps, with siRNA based neutralization of secondary molecular effects induced by the specific protease inhibition. Individualized degradome analysis will be developed for potential profiling of anti-MP and siRNAs based therapy per patient. To facilitate the above diagnostics and therapeutic effects, advanced tumor targeting and penetration active agents will be linked to nano-core functionalized groups, including a biocompatible PEG layer linked to tumor selective MMP substrate molecules and highly safe and potent novel somatostatin analogue peptides targeting SSTR overexpression.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-1.4-3 | Award Amount: 16.34M | Year: 2010

We propose to develop new strategies to mobilize skeletal muscle tissue-associated stem cells as a tool for efficient tissue repair. This will be combined with exploring novel approaches that limit tissue damage, and will focus on agents that modify muscle and muscle vasculature progenitor cells. These molecules include nitric oxide associated with non-steroidal anti-inflammatory drugs, HMGB1, Cripto, NAC, and present and improved deacetylase inhibitors. Three clinical trials will be run in tandem with efforts to dissect the underlying mechanisms of action. Importantly, we have already initiated a monocentric clinical trial that focuses on the efficacy of NO-donors plus NSAIDs in muscle pathologies. Our efforts will be complemented by novel biodelivery systems for effective targeting. Our efforts will be complemented by novel biodelivery systems for effective targeting. The most promising drugs, used alone or in combination, will be first validated in small and large animal models. Our project brings together leading investigators to examine how vascular and muscle progenitors participate in postnatal growth and muscle tissue repair. A key issue that this project addresses is the tissue environment in which endogenous stem cells are activated. We propose that muscle degeneration and fibrosis provokes altered vascularization and immune responses, which eventually affect negatively stem cell functions. Molecules that can be used to therapeutically target these key cells, and their communication with neighboring vascular, inflammatory and fibrotic cell types, will lead to more effective approaches to muscle regenerative medicine and to novel cures for degenerative diseases, including atherosclerosis, vascular damage in diabetes and in peripheral ischemic vascular disease.


Grant
Agency: GTR | Branch: NERC | Program: | Phase: Research Grant | Award Amount: 381.35K | Year: 2014

The sensitivity of global climate to increasing atmospheric carbon dioxide (CO2) levels is one of the biggest issues currently facing humanity. Quantifying the sensitivity of the Earths climate system to changes in CO2 levels in the geologic past is one way of reducing the uncertainty in future climate predictions. If man-made (anthropogenic) CO2 emissions to the atmosphere follow projected rates, by 2100 concentrations will reach values not seen on Earth since the Oligocene epoch ~23 to 34 million years ago (Ma). Back then, geologists infer that Earth was warmer than today, featuring a genuinely green Greenland and a waxing and waning East Antarctic Ice Sheet (EAIS) that drove high amplitude sea level change (~40 m). These startling observations provide a powerful incentive to improve our understanding of the workings of that past climate system. The focus of this proposal is on an important, but understudied, interval of time (~26 to 28 Ma) for which published palaeoclimate records indicate the biggest repeated (100 thousand-year time scale) changes in Antarctic ice volume and high-latitude temperatures of the entire Oligocene epoch. Our proposed study will generate geological data to both test this interpretation of Oligocene high-latitude climate instability and further elucidate the nature of ice-sheet and temperature variability. Validation of the existence of dynamic Antarctic ice sheets, however, would present a major scientific problem because numerical analysis of ice sheet behavior suggests that, in the absence of big changes in CO2 levels, a large Antarctic ice sheet should be stable once formed because of strong hysteresis properties associated with ice sheet geometry. Several important questions are therefore raised: 1. How resilient were the early Antarctic ice sheets to CO2 change? 2. Do the numerical models give a false sense of the stability of both the Oligocene and, by extension, present day East Antarctic Ice Sheet? 3. Was Oligocene CO2 variability much greater than indicated in existing reconstructions? 4. Is it possible that ice sheets existed beyond Antarctica during the Oligocene? The main factor that has limited progress in tackling these questions has been a lack of suitable sedimentary sections on which to work. We propose to exploit new deep-sea sediment archives recovered from the Antarctic and Newfoundland margins during Integrated Ocean Drilling Program Expeditions 318 and 342, respectively, on which our investigator team played significant roles (see Part 1, Case for Support). Our project will use (i) the Antarctic cores to test for the erosive products of dynamic behaviour (advance and retreat) on the East Antarctic margin, and (ii) the Newfoundland cores to test if high-latitude climatic conditions in the Northern Hemisphere were conducive to ice-sheet growth. Intriguingly, the drill cores from the Newfoundland margin contain abundant conspicuous angular sand sized lithic fragments that have been interpreted to be of ice-rafted origin-hinting at the presence of some form of nearby ice in the Oligocene. Our work will be accomplished through novel investigation of detrital isotope geochemistry on the Antarctic margin and application of organic geochemical temperature proxies in the high-latitude North Atlantic. Critical to our approach will be generation of high-resolution datasets that can be precisely dated and correlated to one another, as well as other high-resolution datasets around the globe.


Grant
Agency: European Commission | Branch: FP7 | Program: BSG-SME | Phase: SME-2011-1 | Award Amount: 1.52M | Year: 2011

Advances in micro-, nano-, and biotechnology put increasing demands on nanoscale microscopy and characterization. Atomic force microscopy (AFM) is one of the highest resolution microscopy methods used in this area. In this project, we will develop a new type of AFM sensor, which will significantly increase the performance of AFM and make it suitable for a much broader range of applications, especially in the life sciences. While traditional AFMs using optical detection of the cantilever sensor, yield very high resolution images, their imaging speed is low, they are difficult to automate and integration with other analysis techniques is limited due to the required optical components. This project aims at removing these limitations for a large area of attractive AFM-applications such as fast analysis in materials science and biological applications. The innovative concept is based on all electric bio cantilevers, ALBICAN. These cantilevers will use novel granular tunneling resistors (NTR), which are fabricated with a mask-less direct writing technique: focused electron beam induced deposited (FEBID). The AFM cantilever will be equipped with an NTR deflection sensor that directly measures the cantilever signal electrically, which removes the need for optical cantilever detection. Recent improvements in AFM cantilever technology have increased the imaging speed of AFM by up to two orders of magnitude by miniaturizing AFM cantilevers (SCL-Sensor.Tech., AMG-T). The unique approach in this proposal, which builds on new materials and fabrication processes (Nanoss), will allow the manufacturing of unprecedented small cantilever sensors with vastly superior performance in imaging speed and usability. These cantilevers will be compatible with a wide variety of existing AFMs and applications in materials and life science. Thereby providing a unique technological edge for the involved SMEs, and opening new avenues for the commercialization of their products and technologies.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE.2010.3.2-03 | Award Amount: 7.18M | Year: 2011

Microalgae are a highly promising resource for the sustainable production of a wide variety of biomaterials for a wide range of applications. Microalgae can transform solar energy at high efficiency directly into valuable biological products using marginal water resources, waste nutrients and exhaust CO2 without the needs for high value cropland. A wide variety of eukaryotic microalgae of high evolutionary diversity produce naturally valuable products like polyunsaturated fatty acids, carotenoids, medically active carbohydrates etc. Nevertheless only a few commercially viable algal products have entered the market. Algal cultivation and induction of high value product accumulation is a complex problem, algae grow in diluted solutions and require large areas and water volumes, causing high cultivation and harvesting costs and posing contamination problems and variable productivities due to climate variability. Genetic modifications to make microalgae better suit industrial applications are possible over a wide range of target mechanisms: stress tolerance, product accumulation pathways, cellular chlorophyll contents, novel metabolic pathways, resistance to pathogens and competition, etc. Due to the wide variability of algal strains under consideration, available techniques for genetic manipulations have to be adapted or developed for all algal strains of interest. Our consortium will adapt genetic engineering techniques to various algal strains of economic interest focusing on carotenoid and PUFA production and the overexpression of peptides of commercial value. In parallel we will develop cultivation technologies, harvesting and extraction methods for lipids, carotenoids and proteins using existing model algae strains that will then be adapted to suitable improved strains. Furthermore products will be tested for energy, pharmaceutical, nutritional or medical applications for economic evaluation of the production processes and their economic exploitation.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: ENV.2008.1.1.2.1. | Award Amount: 4.75M | Year: 2009

SHIVA aims to reduce uncertainties in present and future stratospheric halogen loading and ozone depletion resulting from climate feedbacks between emissions and transport of ozone depleting substances (ODS). Of particular relevance will be studies of short and very short-lived substances (VSLS) with climate-sensitive natural emissions. We will perform field studies of ODS production, emission and transport in understudied, but critical, regions of the tropics using ship, aircraft and ground-based instrumentation. We will parameterise potential climate sensitivities of emissions based on inter-dependencies derived from our own field studies, and surveys of ongoing work in this area. We will study the chemical transformation of ODS during transport from the surface to the tropical tropopause layer (TTL), and in the stratosphere, using a combination of aircraft and balloon observations together with process-oriented meso-scale modelling. These investigations will be corroborated by space-based remote sensing of marine phytoplankton biomass as a possible proxy for the ocean-atmosphere flux of ODS. From this a systematic emission inventory of VSLS ODS will be established to allow construction of future-climate scenarios. The impact of climate-sensitive feedbacks between transport and the delivery of ODS to the stratosphere, and their lifetime within it, will be studied using tracer observations and modelling. Further global modelling will assess the contribution of all ODS, including VSLS (which have hitherto normally been excluded from such models) to past, present and future ozone loss. Here, the sensitivity of natural ODS emissions to climate change parameters will be used in combination with standard IPCC climate model scenarios in order to drive measurement-calibrated chemical transport model (CTM) simulations for present and future stratospheric ozone; to better predict the rate, timing and climate-sensitivity of ozone-layer recovery.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.4.3-2 | Award Amount: 14.25M | Year: 2009

This proposal will pioneer the concept of tailored interventions with minimal immune system interference in new onset T1DM, leading to beta-cell protection and restoration, based on a solid understanding of the disease pathogenesis. This will enable experimental findings to be adopted for future clinical application. Four work packages are grouped around Reversal of autoimmunity, in which two key players of the immune system in beta-cell destruction will be targeted: the dendritic cell (WP1: Re-educating antigen-presenting cells) and the T-lymphocyte (WP2: Restoring the T-cell balance). In both cell types, interventions using steroid hormones (vitamin D and glucocorticoids) will be used to induce tolerance. Moreover, novel interventions using soluble T-cell receptors to target immune cells and beta-cells in an antigen-specific way (WP3: TCR-mediated immunotherapy) will be introduced. Novel mucosal interventions using probiotics and recombinant L. lactis as a carrier for specific peptides in combination with cytokines (WP4: Mucosal intervention for tolerance restoration) will be studied for their immune modulating potential. A full work package (WP5: Beta-cell protection and restoration the dialogue with the immune system) is dedicated to the beta-cell and its role in driving and amplifying the immune attack through communication between beta-cells and the immune system. The last scientific work package (WP6: Pharmacogenetics) will identify genetic profiles within patients that predict responsiveness to the steroid interventions proposed. WP7 and 8 are dedicated to training and management of the consortium. For this purpose, a multidisciplinary consortium of leading European diabetologists and immunologists from 11 academic research institutions, in co-operation with 3 SMEs developing novel technologies allowing translation of basic research results towards clinical applications, has been established.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.65M | Year: 2015

Endoplasmic reticulum (ER) stress is emerging as a common feature in the pathology of numerous diseases including cancer, neurodegenerative disorders, metabolic syndromes and inflammatory diseases. Thus ER stress represents a potential therapeutic intervention point to be exploited to develop novel therapies, diagnostic tools and markers for these diseases. However, exploitation is hampered by the shortage of scientists with interdisciplinary training that can navigate with ease between the academic, industrial and clinical sectors, and that have the scientific and complementary skills, together with an innovative outlook, to convert research findings into commercial and clinical applications. This proposal will bring young researchers together with world-leading academics, clinicians and industry personnel, who are united in (1) their goal of forming a network of excellence aimed at understanding the ER stress response mechanistically and quantitatively and (2) applying this understanding to identify and validate the most suitable intervention points in order to provide innovative knowledge-driven strategies for the treatment of ER stress-associated diseases. The TRAIN-ERS network will provide early stage researchers (ESRs) with high quality scientific and complementary skills training combined with international, intersectoral work experience. This will produce highly trained, innovative, creative and entrepreneurial ESRs with greatly enhanced career prospects, who will continue to advance the state of the art in the Biomedical field in their further careers, and will confidently navigate at the interface of academic, clinical and private sector research. The TRAIN-ERS research programme will provide the ESRs with the knowledge and the cutting edge scientific and technical skills that will drive our understanding and exploitation of the ER stress response for therapeutic and diagnostic purposes.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.96M | Year: 2015

NMR and MRI play unique roles in contemporary Science, from Physics, Chemistry and Biology, to clinical research and diagnosis. Despite its irreplaceable role, further progress in NMR and MRI is hampered by sensitivities that are much lower than those of alternatives such as mass-spec, or PET. The prospects of solving this problem by bigger machines are uncertain and of poor return, given the high maturity already achieved by NMR/MRI. This ETN challenges this status from an untapped perspective, combining NMR/MRI with nuclear hyperpolarization eliciting signals that surpass those currently available by up to 50,000x. Focus is placed on two particular approaches, dynamic nuclear polarization and para-hydrogen-driven polarization, exhibiting the highest potential for biophysical, metabolomic, pre-clinical and clinical research. To maximize these supersignals we assembled leading experts in the physics and engineering of magnetic resonance, in the synthetic chemistry essential for the success of these methods, in the uses of NMR to structural/cell biology, and in preclinical and clinical MRI applications. Guiding this assembling is the conception that only by teaming together key areas of expertise, can hyperpolarisations promises be realized. In addition to fostering synergies among experts from academia and industry, EUROPOL will provide frontier training for ESRs in all the topics underlying the advancement of MR. This will include advanced physics, new instruments and forms of exploiting NMR/MRIs hyperpolarisation, biophysical NMR, screening of healthy and diseased metabolomes, expanded portfolios of substrates to be targeted by in vivo MR, ancillary in cell and system biology explorations clarifying the nature of the metabolic phenomena, and in vivo hyperpolarisation strategies in MRI. This ETN is unparalleled in scope, breadth and potential for synergies.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.81M | Year: 2016

CELTA: Convergence of Electronics and Photonics Technologies for Enabling Terahertz Applications aims to produce the next generation of researchers who will enable Europe to take a leading role in the multidisciplinary area of utilizing Terahertz technology for applications involving components and complete systems for sensing, instrumentation, imaging, spectroscopy, and communications. All these technologies are key to tackle important solutions in a large number of focus areas relevant for the societal challenges identified in the Horizon2020 work programme. To achieve this objective, CELTA is comprised of eleven leading research institutions and assembled a comprehensive research training programme for all the fifteen early stage researchers (ESRs). CELTA integrates multidisciplinary scientific expertise, complementary skills, and experience working in academia and industry to empower ESRs to work in interdisciplinary teams, integrate their activities, share expertise, and promote a vision of a converged co-design and common engineering language between electronics and photonics for Terahertz technologies. Therefore, CELTA will introduce the strategy of converged electronics and photonics co-design in its research program and makes a special effort on establishing a common engineering language in its training program across the electronics, photonics and applications disciplines. We believe this common engineering language and converged co-design is mandatory to make the next logical step towards efficient and innovation solutions that can reach the market. The detailed compendium of lectures on state-of-the art technology, soft skills and entrepreneurship is accompanied by a research programme that focuses on THz key technologies. CELTA ESRs will develop three demonstrators: beam steering technology for communication applications, a photonic vector analyser for spectroscopy and materials characterization, and a THz imager for sensing applications.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: NFRP-09-2015 | Award Amount: 11.99M | Year: 2015

The Strategic Research Agenda of the EU Sustainable Nuclear Energy Technical platform requires new large infrastructures for its successful deployment. MYRRHA has been identified as a long term supporting research facility for all ESNII systems and as such put in the high-priority list of ESFRI. The goal of MYRTE is to perform the necessary research in order to demonstrate the feasibility of transmutation of high-level waste at industrial scale through the development of the MYRRHA research facility. Within MYRRHA as a large research facility, the demonstration of the technological performance of transmutation will be combined with the use for the production of radio-isotopes and as a material testing for nuclear fission and fusion applications. Numerical studies and experimental facilities are foreseen to reach this goal. Besides coordination, international collaboration and dissemination activities, the MYRTE proposal contains 5 technical work packages. The first and largest work-package is devoted to the realisation of the injector part of the MYRRHA accelerator to demonstrate the feasibility and required reliability of this non-semi-conducting part of the accelerator. The second work-package addresses the main outstanding technical issues in thermal hydraulics by numerical simulations and experimental validation. Pool thermal hydraulics and thermal hydraulics of the fuel assembly will be the focus of this WP. In the WP on LBE Chemistry, the evaporation from LBE, capture and deposition of Po and fission products will be studied in detail to complement the safety report. A small dedicated WP on experimental reactor physics is also foreseen to allow carrying out the necessary supplementary experiments at the GUINEVERE-facility to address the questions of the safety authorities. In a last WP, advanced studies on Americium-bearing oxide fuel are carried out to demonstrate the capability of developing minor actinide fuel for transmutation.


Kralj J.,Slovenian National Institute of Biology | Fuchs S.,Goethe University Frankfurt
Apidologie | Year: 2010

In this study we investigated whether the microsporidian Nosema sp. affects the flight behavior of forager bees. Bees released 6 and 10 m away from the colony took longer times to return. The proportion of bees that did not return was higher in the diseased bees compared to the healthy bees when released 30 m away from the colony. That diseased bees get lost from the colony was also supported by a considerably lower rate of infected bees among the returning foragers compared to departing foragers. In a hive entrance orientation test, diseased bees scored lower than healthy bees, indicating impaired orientation skills. These results are in line with previous results on foragers infested by the parasitic mite Varroa destructor. The similar influence of Nosema sp. and V. destructor on flight behavior, in that foragers might not return to the colony, can be interpreted as a general response of honey bees to diseases to decrease pathogen load within the colonies. © INRA/DIB-AGIB/EDP Sciences, 2009.


Grote P.,Goethe University Frankfurt | Herrmann B.G.,Max Planck Institute for Molecular Genetics | Herrmann B.G.,Charité - Medical University of Berlin
Trends in Genetics | Year: 2015

A large proportion of the cellular transcriptome of higher vertebrates consists of non-protein coding transcripts, among them the long noncoding RNAs (lncRNAs). Although lncRNAs are functionally extremely divergent, many ncRNAs have been shown to interact with chromatin modifying complexes and/or with transcriptional regulators. Via such interactions, many lncRNAs are involved in controlling the activity and expression level of target genes, including important regulators of embryonic processes, and thereby fine-tune gene regulatory networks controlling cell fate, lineage balance, and organogenesis. Intriguingly, an increase in organ complexity during evolution parallels a rise in lncRNA abundance. The current data suggest that lncRNAs support the generation of cell diversity and organ complexity during embryogenesis, and thereby have promoted the evolution of more complex organisms. © 2015 Elsevier Ltd.


Scheiter S.,Biodiversitat und Klima Forschungszentrum LOEWE BiK F | Langan L.,Goethe University Frankfurt | Higgins S.I.,Goethe University Frankfurt
New Phytologist | Year: 2013

Dynamic global vegetation models (DGVMs) are powerful tools to project past, current and future vegetation patterns and associated biogeochemical cycles. However, most models are limited by how they define vegetation and by their simplistic representation of competition. We discuss how concepts from community assembly theory and coexistence theory can help to improve vegetation models. We further present a trait- and individual-based vegetation model (aDGVM2) that allows individual plants to adopt a unique combination of trait values. These traits define how individual plants grow and compete. A genetic optimization algorithm is used to simulate trait inheritance and reproductive isolation between individuals. These model properties allow the assembly of plant communities that are adapted to a site's biotic and abiotic conditions. The aDGVM2 simulates how environmental conditions influence the trait spectra of plant communities; that fire selects for traits that enhance fire protection and reduces trait diversity; and the emergence of life-history strategies that are suggestive of colonization-competition trade-offs. The aDGVM2 deals with functional diversity and competition fundamentally differently from current DGVMs. This approach may yield novel insights as to how vegetation may respond to climate change and we believe it could foster collaborations between functional plant biologists and vegetation modellers. © 2013 New Phytologist Trust.


News Article | December 7, 2016
Site: www.eurekalert.org

FRANKFURT. Helium atoms are loners. Only if they are cooled down to an extremely low temperature do they form a very weakly bound molecule. In so doing, they can keep a tremendous distance from each other thanks to the quantum-mechanical tunnel effect. As atomic physicists in Frankfurt have now been able to confirm, over 75 percent of the time they are so far apart that their bond can be explained only by the quantum-mechanical tunnel effect. The binding energy in the helium molecule amounts to only about a billionth of the binding energy in everyday molecules such as oxygen or nitrogen. In addition, the molecule is so huge that small viruses or soot particles could fly between the atoms. This is due, physicists explain, to the quantum-mechanical "tunnel effect". They use a potential well to illustrate the bond in a conventional molecule. The atoms cannot move further away from each other than the "walls" of this well. However, in quantum mechanics the atoms can tunnel into the walls. "It's as if two people each dig a tunnel on their own side with no exit", explains Professor Reinhard Dörner of the Institute of Nuclear Physics at Goethe University Frankfurt. Dörner's research group has produced this helium molecule in the laboratory and studied it with the help of the COLTRIMS reaction microscope developed at the University. The researchers were able to determine the strength of the bond with a level of precision not previously achieved and measured the distance between the two atoms in the molecule. "The helium molecule is something of a touchstone for quantum-mechanical theories, as the value of the binding energy theoretically predicted is heavily dependent on how accurately all physical and quantum-mechanical effects were taken into account", explains Dörner. Even the theory of relativity, which is otherwise mainly required for astronomical calculations, had to be incorporated here. "If even just a small mistake occurs, the calculations produce major deviations or even indicate that a helium molecule cannot exist at all", says Dörner. The precision measurements performed by his research group will serve as a benchmark for future experiments. Dörner's research group began investigating the helium molecule back in 2009, when the German Research Foundation awarded him a Reinhart Koselleck Project and funding to the tune of € 1.25 million. "This type of funding is risk capital, as it were, with which the German Research Foundation supports experiments with a long lead time", explains Dörner. He was thus able to design and set up the first experiments with his group. Initial results were achieved by Dr. Jörg Voigtsberger in the framework of his doctoral dissertation. "In the search for atoms which 'live in the tunnel', Jörg Voigtsberger spent two years of his life in the cellar", recalls Dr. Till Jahnke, senior lecturer and Voigtberger's supervisor at the time. It is there, in the cellar, that the laser laboratory of the atomic physics group is housed. Stefan Zeller, the next doctoral researcher, considerably improved the equipment with the help of Dr. Maksim Kunitski and increased measurement precision still further. To do so, one of his tasks was to shoot at the very weakly bonded helium molecule with FLASH, the free-electron laser at the DESY research centre in Hamburg and the largest "photon canon" in Germany. "Stefan Zeller's work was remarkable. It was his untiring effort, his excellent experimental research skills and his ability not to be disheartened by temporary setbacks which made our success possible at all", remarks Professor Dörner, Zeller's doctoral supervisor. Already beforehand the results have attracted considerable interest at national and international level. They will now appear in the renowned journal "Proceedings of the National Academy of Sciences of the United States of America (PNAS)" and are also part of the research work for which the group was awarded the Helmholtz Prize 2016.


News Article | December 1, 2016
Site: www.eurekalert.org

The attachment of ubiquitin was long considered as giving the „kiss of death", labelling superfluous proteins for disposal within a cell. However, by now it has been well established that ubiquitin fulfils numerous additional duties in cellular signal transduction. A team of scientists under the lead of Ivan Dikic, Director of the Institute of Biochemistry II at Goethe University Frankfurt, has now discovered a novel mechanism of ubiquitination, by which Legionella bacteria can seize control over their host cells. Legionella causes deadly pneumonia in immunocompromised patients. According to the current understanding, the coordinated action of three enzymes is needed for attaching ubiquitin to other proteins. In April this year, U.S. scientists described an ubiquitination reaction that depends only on a single enzyme from Legionella bacteria. The Dikic team together with the group of Ivan Matic (Max Planck Institute for Biology of Ageing, Cologne, Germany) now elucidated the underlying molecular mechanism of its action and revealed a hitherto unknown type of chemical linkage between ubiquitin and target proteins. Their discovery breaks new ground in the field. Sagar Bhogaraju, researcher in the Dikic laboratory, comments: "Most exciting is of course the question if this unusual ubiquitination also occurs in human cells independently of bacterial infection and if there are similar, so far unknown enzymes in humans, which may have a profound influence on cellular processes." When studying the new mechanism in more detail, the Frankfurt scientists were very surprised to find that the Legionella enzyme does not only transfer ubiquitin onto target proteins, but also chemically manipulates the remaining pool of ubiquitin molecules. Modified ubiquitin almost completely inhibits the conventional ubiquitination system, thereby revealing a new role for this enzyme during Legionella infections. Several important cellular processes are affected by this shut-down of the ubiquitination system, which can also cause a rapid cell death. The Dikic team showed for example that modified ubiquitin prevents degradation of mitochondria (a process called mitophagy), affects transduction of inflammatory signals and constrains protein degradation. "Most likely, Legionella is not the only bacterium using this mechanism. We hope that our results help to identify new strategies for the development of antibacterial agents, which could complement conventional antibiotics by limiting cellular damage induced by bacterial enzymes", explains Dikic the high medical relevance of their discovery. The group of Ivan Dikic is located at both the Institute of Biochemistry II and the Buchmann Institute for Molecular Life Sciences at Goethe University Frankfurt and has previously contributed significantly to a paradigm change in the ubiquitin field. Ivan hypothesized early on that ubiquitin signals are recognized and translated by specialized domains in other proteins. He identified ubiquitin-binding domains in more than 200 ubiquitin receptors and was able to prove their role in diseases like cancer, amyotrophic lateral sclerosis and Parkinson's.


News Article | December 16, 2016
Site: www.eurekalert.org

Whether water freezes to ice, iron is demagnetized or a material becomes superconducting - for physicists there is always a phase transition behind it. They endeavour to understand these different phenomena by searching for universal properties. Researchers at Goethe University Frankfurt and Technische Universität Dresden have now made a pioneering discovery during their study of a phase transition from an electrical conductor to an insulator (Mott metal-insulator transition). According to Sir Nevill Francis Mott's prediction in 1937, the mutual repulsion of charged electrons, which are responsible for carrying electrical current, can cause a metal-insulator transition. Yet, contrary to common textbook opinion, according to which the phase transition is determined solely by the electrons, it is the interaction of the electrons with the atomic lattice of the solid which is the determinant factor. The researchers have reported this in the latest issue of the Science Advances journal. The research group, led by Professor Michael Lang of the Physics Institute at Goethe University Frankfurt, succeeded in making the discovery with the help of a homemade apparatus which is unique worldwide. It allows the measurement of length changes at low temperatures under variable external pressure with extremely high resolution. In this way, it was possible to prove experimentally for the first time that it is not just the electrons which play a significant role in the phase transition but also the atomic lattice - the solid's scaffold. "These experimental results will herald in a paradigm shift in our understanding of one of the key phenomena of current condensed matter research", says Professor Lang. The Mott metal-insulator transition is namely linked to unusual phenomena, such as high-temperature superconductivity in copper oxide-based materials. These offer tremendous potential for future technical applications. The theoretical analysis of the experimental findings is based on the fundamental notion that the many particles in a system close to a phase transition not only interact with their immediate neighbours but also "communicate" over long distances with all other particles. As a consequence, only overarching aspects are important, such as the system's symmetry. The identification of such universal properties is thus the key to understanding phase transitions. "These new insights open up a whole new perspective on the Mott metal-insulator transition and permit more sophisticated theoretical modelling of the phase transition", explains Dr. Markus Garst, Senior Lecturer at the Institute of Theoretical Physics of Technische Universität Dresden. The research work was funded by the German Research Foundation in the framework of the Collaborative Research Centre/Transregio "Condensed Matter Systems with Variable Many-Body Interactions" led by Professor Michael Lang.


News Article | November 11, 2016
Site: phys.org

Regulatory authorities around the world can in future instruct manufacturers of chemicals and drugs to check their products for harmful effects on reproduction by means of a new test with molluscs. After over 10 years of funding by the German Environment Agency in Dessau, a project coordinated by Goethe University Frankfurt has now resulted in an OECD guideline (Organisation for Economic Co-operation and Development) for global chemical testing. The test analyses in the laboratory the long-term effects of chemicals on reproduction in freshwater mudsnails (Potamopyrgus antipodarum). "Although this tiny creature is not an indigenous snail species, as what is known as a "model organism" its biological answers are also transferable to other molluscs, regardless of whether they stem from Europe, Asia or America", explains Professor Jörg Oehlmann, coordinator of the test development team and head of the Department of Aquatic Ecotoxicology at Goethe University Frankfurt. Potamopyrgus is a water dweller and was introduced to Europe in the mid 19th century on board ships from New Zealand. However, this alien species is meanwhile part of the normal landscape in many of Europe's watercourses. New chemicals which have not yet been approved and harm the mudsnail in OECD Test No. 242 in the laboratory would have the same effect on it and related species in the wild. Since molluscs, after insects and crustaceans, are the second most species-rich group in the animal kingdom, the loss of these organisms would be fatal for biodiversity and thus also for the correct functioning of the ecosystems. The development of the "snail test" therefore constitutes an important contribution to keeping our watercourses clean and healthy, since substances which show a toxic effect in this test for the snail can in future be identified and controlled prior to market introduction. In addition, the new snail test closes an existing gap in the environmental risk assessment of chemicals, since standardized tests with invertebrates to date focussed mainly on arthropods (insects and crustaceans). Snails had, however, in the past proven to be extraordinarily sensitive to a large number of harmful substances, including tributyltin compounds and other environmental chemicals which influence the hormone system. The work coordinated by Goethe University Frankfurt on the development and standardization of the snail test took place over a period of more than 10 years. Test conditions for the snails with regard to water and feedstuff quality, temperature, concentration and numerous other parameters were optimized in the framework of an extensive research programme. In the last six years, four final validation studies with six test substances were carried out in 16 laboratories in Europe and the USA which showed that the test protocol developed is robust and the test generates reproducible results, independent of in which laboratory it is implemented. For the test, female mudsnails are exposed to a concentration range of chemicals in ambient water. The organisms remain with the test substance in their test beakers for 28 days, after which the number of embryo amongst all surviving females is counted. "It's a process which is easy to use and also suitable for everyday use by water authorities", says Oehlmann. In their home country of New Zealand, both male and female mudsnails are found. In Europe, however, populations are composed solely of females which reproduce parthenogenetically. This makes using the test and analysing the results easier, all the more so since the tiny snail makes only modest demands on the laboratory. "The animal's small size has another advantage: in comparison to many other test procedures, this test can be miniaturized and doesn't take up much space", explains Oehlmann. That makes it possible to test a larger number of chemicals. More information: OECD guideline 242 for the testing of chemicals: dx.doi.org/10.1787/9789264264311-en


New model suggests testable hypotheses that could aid lab research toward novel treatment strategies Scientists have created the first validated mathematical model of an important cellular defense mechanism against the bacterium Salmonella, according to a new study in PLOS Computational Biology. Worldwide, Salmonella is responsible for millions of infections and thousands of deaths every year. When Salmonella enters a human cell under certain conditions, a process called xenophagy may target the bacterium for destruction. Understanding how cells defend against Salmonella is essential to develop new treatments, but xenophagy is not yet well-understood. In the new study, "wet lab" scientist Ivan Dikic and the bioinformatics team of Ina Koch at Goethe University Frankfurt used existing knowledge of molecular interactions, combined with a computer science technique called Petri nets, to build a mathematical model of xenophagy. To test the model, the researchers investigated what would happen when several proteins in the xenophagy process were virtually perturbed--a technique known as in silico knockout. The results of this computer-based perturbation were consistent with data from lab experiments in which the same proteins were perturbed, confirming that the model accurately reproduces known parts of the xenophagy process. The scientists also proposed a potential new mechanism for one of the proteins involved in the xenophagy process. This and other hypotheses suggested by further in silico knockout investigations could be tested in lab experiments. "The in silico knockouts formulate hypotheses for future experimental studies towards a better understanding of the cellular antibacterial defense and towards a better treatment of illnesses caused by Salmonella infection," says study first author Jennifer Scheidel. In your coverage please use this URL to provide access to the freely available article in PLOS Computational Biology: http://journals. Citation: Scheidel J, Amstein L, Ackermann J, Dikic I, Koch I (2016) In Silico Knockout Studies of Xenophagic Capturing of Salmonella. PLoS Comput Biol 12(12): e1005200. doi:10.1371/ journal.pcbi.1005200 Funding: This work was supported by the LOEWE program Ubiquitin Networks (Ub-Net) of the State of Hesse (Germany) (20120712/B4; https:/ ) and by the Cluster of Excellence `Macromolecular Complexes' of the Goethe University of Frankfurt (3212070002/TP2; http://www. ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.


Rapino F.,Goethe University Frankfurt | Jung M.,Albert Ludwigs University of Freiburg | Fulda S.,Goethe University Frankfurt
Oncogene | Year: 2014

Simultaneous inhibition of the two major constitutive protein quality control (PQC) pathways, that is, the ubiquitin-proteasome system (UPS) and the aggresome-autophagy system, has been suggested as a promising strategy to trigger cell death in cancer cells. However, we observed that one third of rhabdomyosarcoma (RMS) cells survives parallel inhibition of the UPS by Bortezomib and the aggresome-autophagy pathway by the cytoplasmic histone deacetylase 6 inhibitor ST80, and is able to regrow upon drug removal, thus pointing to the induction of compensatory pathways. Here, we identify Bcl-2-associated athanogene 3 (BAG3) as a critical mediator of inducible resistance in surviving cells after concomitant blockage of constitutive PQC pathways by mitigating ST80/Bortezomib-triggered proteotoxicity via selective autophagy. ST80/Bortezomib cotreatment upregulates BAG3 mRNA and protein levels in surviving cells in addition to triggering the accumulation of insoluble protein aggregates. Intriguingly, knockdown of BAG3 by RNA interference severely impairs clearance of protein aggregates, significantly increases cell death and reduces long-term survival and clonogenic growth during recovery after ST80/Bortezomib cotreatment. Similarly, inhibition of autophagy by inducible autophagy-related protein 7 knockdown prevents removal of protein aggregates and cell regrowth during recovery after ST80/Bortezomib cotreatment. Also, the inhibition of lysosomal degradation using the V-ATPase pump inhibitor Bafilomycin A1 enhances accumulation of protein aggregates, and completely abolishes regrowth after Bortezomib/ST80-induced proteotoxic stress. By identifying BAG3 as a key mediator of inducible resistance by mitigating proteotoxicity via selective autophagy after inhibition of constitutive PQC systems, our study provides new insights into the regulation of PQC pathways in cancer cells and identifies new targets for therapeutic intervention. © 2014 Macmillan Publishers Limited.


Lange C.M.,Goethe University Frankfurt | Jacobson I.M.,New York Medical College | Rice C.M.,Rockefeller University | Zeuzem S.,Goethe University Frankfurt
EMBO Molecular Medicine | Year: 2014

Opportunities to treat infection with hepatitis C virus (HCV) are evolving rapidly. From the introduction of interferon-α monotherapy in 1992 to the approval of telaprevir- and boceprevir-based triple therapies with pegylated interferon-α and ribavirin in 2011, the chances of curing patients infected with HCV genotype 1 have improved from <10% to approximately 70%. Significant further improvements are on the horizon, which may well cure virtually all hepatitis C patients with an all-oral, interferon-free regimen in the very near future. These exciting developments are reviewed in the present article. © 2013 The Authors.


Bicudo P.,University of Lisbon | Wagner M.,Goethe University Frankfurt
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Utilizing lattice QCD results for the potential of two static antiquarks and two dynamical quarks as well as quark model techniques for the dynamics of two heavy antiquarks in a cloud of two light quarks, we are provided with an accurate framework for the study of possibly existing heavy-heavy-light-light tetraquarks. Among the possible quantum numbers of such a system, we find binding in only one channel the scalar isosinglet. Solving the Schrödinger equation for the displacement of the heavy antiquarks and taking systematic errors into account, we find an antibottom-antibottom-light-light bound state with a confidence level of around 1.8σ-3.0σ and binding energy of approximately 30-57 MeV. © 2013 American Physical Society.


Koch J.,Paul Ehrlich Institute | Steinle A.,Goethe University Frankfurt | Watzl C.,Leibniz Research Center for Working Environment and Human Factors o | Mandelboim O.,Hebrew University of Jerusalem
Trends in Immunology | Year: 2013

Natural killer (NK) cells are central players in the vertebrate immune system that rapidly eliminate malignantly transformed or infected cells. The natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 are important mediators of NK cell cytotoxicity, which trigger an immune response on recognition of cognate cellular and viral ligands. Tumour and viral immune escape strategies targeting these receptor-ligand systems impair NK cell cytotoxicity and promote disease. Therefore, a molecular understanding of the function of the NCRs in immunosurveillance is instrumental to discovering novel access points to combat infections and cancer. © 2013 Elsevier Ltd.


Welsch C.,Goethe University Frankfurt | Jesudian A.,New York Medical College | Zeuzem S.,Goethe University Frankfurt | Jacobson I.,New York Medical College
Gut | Year: 2012

Until recently, the standard of care (SOC) for patients with chronic hepatitis C virus (HCV) infection has consisted of a combination of pegylated interferon- plus ribavirin, administered for 24- to 48-weeks depending on the HCV genotype. The sustained virologic response rate for this SOC has been only about 50% in patients infected with genotype 1 HCV, the most prevalent genotype in Europe and North America. HCV therapy has been revolutionised recently by the approval of two direct-acting antiviral agents (DAA) against the NS3/4A serine protease for use in genotype 1 HCV, the ketoamide inhibitors boceprevir and telaprevir. The novel SOC marks the beginning of an extraordinary new era in HCV therapy. We review this new SOC with an emphasis on practical issues related to protease inhibitors, e.g. prescribing guidelines, futility rules and management of adverse events. We also give a perspective on what to expect in the coming years. Newer DAA with simplified dosing regimens and/or minimal toxicity which, when used in combination, will lead to viral eradication in most if not all CHC patients who undergo treatment. The novel agents in clinical development are paving the way for future interferon-sparing regimens.


Hoelzer D.,ONKOLOGIKUM | Gokbuget N.,Goethe University Frankfurt
Blood Reviews | Year: 2012

ALL blast cells express a variety of specific antigens e.g. CD19, CD20, CD22, CD33, and CD52, which serve as targets for Monoclonal Antibodies (MoAbs). So far, the most experience is available for anti-CD20 (rituximab), which has been combined with chemotherapy for treatment of mature B-ALL/Burkitt's lymphoma. Studies with rituximab have also been completed in B-precursor ALL. Another antigen, CD19, is of great interest due to a very high rate of expression in ALL. It can be targeted by a bispecific monoclonal antibody, Blinatumomab, directed against CD19 and CD3. Smaller studies or case reports are also available for the anti CD52 antibody (Alemtuzumab), for anti CD22 (Epratuzumab) or anti CD33 (Gemtuzumab). Available data demonstrate that MoAb therapy in ALL is a highly promising targeted treatment. However, several details for an optimal treatment approach e.g. the required level of antigen expression, timing, schedule, dosage and stage of disease still need to be defined. © 2012.


Zickermann V.,Goethe University Frankfurt | Wirth C.,Albert Ludwigs University of Freiburg | Nasiri H.,University of Cambridge | Nasiri H.,Institute of Organic Chemistry and Chemical Biology | And 6 more authors.
Science | Year: 2015

Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complicated membrane protein complexes. The enzyme contributes substantially to oxidative energy conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders. We report the x-ray structure of mitochondrial complex I at a resolution of 3.6 to 3.9 angstroms, describing in detail the central subunits that execute the bioenergetic function. A continuous axis of basic and acidic residues running centrally through the membrane arm connects the ubiquinone reduction site in the hydrophilic arm to four putative proton-pumping units. The binding position for a substrate analogous inhibitor and blockage of the predicted ubiquinone binding site provide a model for the "deactive" form of the enzyme. The proposed transition into the active form is based on a concerted structural rearrangement at the ubiquinone reduction site, providing support for a two-state stabilization-change mechanism of proton pumping.


Brieke C.,Goethe University Frankfurt | Brieke C.,Max Planck Institute for Medical Research | Heckel A.,Goethe University Frankfurt
Chemistry - A European Journal | Year: 2013

A new design is presented for the incorporation of spiropyran photoswitches into nucleic acids by oligonucleotide solid phase synthesis. This design enables interaction of the 6-nitrospirobenzopyran (NitroBIPS) photoswitch with the adjacent nucleobases and leaves the photochemical properties of NitroBIPS intact. UV/Vis spectroscopy and HPLC revealed that NitroBIPS incorporated into DNA consists of up to 40 % merocyanine in its thermal equilibrium and undergoes reversible switching between the photoisomeric spiropyran (SP) and merocyanin (MC) state by alternating excitation using visible light or heat for at least fifteen switching cycles. Exchanging the chromene part of NitroBIPS on the DNA level gives access to differently substituted spiropyran derivatives allowing the screening for spiropyrans with suitable properties in a straightforward manner. Thus, by incorporating the highly hydrolysis-stable pyrido-spiropyran derivative PyBIPS pure light-triggered reversible switching of a spiropyran in DNA has been realized for the first time. Therefore, this design represents a new useful platform for investigating the photochromic behavior of different spiropyran photoswitches in a nucleic acid environment and for using spiropyrans to induce light- or heat-triggered changes in conformations or in fluorescence quenching properties of oligonucleotides. Yes, it does switch! With a new design strategy the photochemical properties of spiropyran photoswitches can be retained in DNA. Spiropyrans can be diversified on the DNA level enabling screening for spiropyrans with suitable properties in a straightforward manner (see scheme). By incorporating the highly stable spiropyran derivative PyBIPS, pure light-triggered reversible switching of a spiropyran in DNA has been realized for the first time. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Werner K.,University of Nantes | Bleicher M.,Goethe University Frankfurt | Guiot B.,University of Nantes | Karpenko I.,Goethe University Frankfurt | And 2 more authors.
Physical Review Letters | Year: 2014

We show that a fluid dynamical scenario, already well tested against identified particle pt spectra, describes quantitatively the observed mass splitting of the elliptical flow coefficients v2 for pions and protons. This provides a strong argument in favor of the existence of a fluid dynamical expansion in p-Pb collisions at 5.02 TeV. © 2014 American Physical Society.


Zhuang J.-L.,Goethe University Frankfurt | Ar D.,Goethe University Frankfurt | Yu X.-J.,Goethe University Frankfurt | Liu J.-X.,Karlsruhe Institute of Technology | Terfort A.,Goethe University Frankfurt
Advanced Materials | Year: 2013

Flexible in many aspects: inkjet printing of metal-organic frameworks permits their larger area, high-resolution deposition in any desired pattern, even in the form of gradients or shades. When flexible substrates are used, many applications can be envisioned, such as sensing and capture of hazardous gases for personal safety measures. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Campbell W.B.,Medical College of Wisconsin | Fleming I.,Goethe University Frankfurt
Pflugers Archiv European Journal of Physiology | Year: 2010

Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are produced by the vascular endothelium in response to agonists such as bradykinin and acetylcholine or physical stimuli such as shear stress or cyclic stretch. In the vasculature, the EETs have biological actions that are involved in the regulation of vascular tone, hemostasis, and inflammation. In preconstricted arteries in vitro, EETs activate calcium-activated potassium channels on vascular smooth muscle and the endothelium causing membrane hyperpolarization and relaxation. These effects are observed in a variety of arteries from experimental animals and humans; however, this is not a universal finding in all arteries. The mechanism of EET action may vary. In some arteries, EETs are released from the endothelium and are transferred to the smooth muscle where they cause potassium channel activation, hyperpolarization, and relaxation through a guanine nucleotide binding protein-coupled mechanism or transient receptor potential (TRP) channel activation. In other arteries, EETs activate TRP channels on the endothelium to cause endothelial hyperpolarization that is transferred to the smooth muscle by gap junctions or potassium ion. Some arteries use a combination of mechanisms. Acetylcholine and bradykinin increase blood flow in dogs and humans that is inhibited by potassium channel blockers and cytochrome P450 inhibitors. Thus, the EETs are endothelium-derived hyperpolarizing factors mediating a portion of the relaxations to acetylcholine, bradykinin, shear stress, and cyclic stretch and regulate vascular tone in vitro and in vivo. © 2010 Springer-Verlag.


Blennow K.,Sahlgrenska University Hospital | Hampel H.,Goethe University Frankfurt | Hampel H.,University of Belgrade | Zetterberg H.,Sahlgrenska University Hospital | Zetterberg H.,University College London
Neuropsychopharmacology | Year: 2014

Drug candidates directed against amyloid-β (Aβ) are mainstream in Alzheimer's disease (AD) drug development. Active and passive Aβ immunotherapy is the principle that has come furthest, both in number and in stage of clinical trials. However, an increasing number of reports on major difficulties in identifying any clinical benefit in phase II-III clinical trials on this type of anti-Aβ drug candidates have caused concern among researchers, pharmaceutical companies, and other stakeholders. This has provided critics of the amyloid cascade hypothesis with fire for their arguments that Aβ deposition may merely be a bystander, and not the cause, of the disease or that the amyloid hypothesis may only be valid for the familial form of AD. On the other hand, most researchers argue that it is the trial design that will need refinement to allow for identifying a positive clinical effect of anti-Aβ drugs. A consensus in the field is that future trials need to be performed in an earlier stage of the disease and that biomarkers are essential to guide and facilitate drug development. In this context, it is reassuring that, in contrast to most brain disorders, research advances in the AD field have led to both imaging (magnetic resonance imaging (MRI) and PET) and cerebrospinal fluid (CSF) biomarkers for the central pathogenic processes of the disease. AD biomarkers will have a central role in future clinical trials to enable early diagnosis, and Aβ biomarkers (CSF Aβ42 and amyloid PET) may be essential to allow for testing a drug on patients with evidence of brain Aβ pathology. Pharmacodynamic Aβ and amyloid precursor protein biomarkers will be of use to verify target engagement of a drug candidate in humans, thereby bridging the gap between mechanistic data from transgenic AD models (that may not be relevant to the neuropathology of human AD) and large and expensive phase III trials. Last, downstream biomarker evidence (CSF tau proteins and MRI volumetry) that the drug ameliorates neurodegeneration will, together with beneficial clinical effects on cognition and functioning, be essential for labeling an anti-Aβ drug as disease modifying. © 2014 American College of Neuropsychopharmacology.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: YOUNG-3-2015 | Award Amount: 2.50M | Year: 2016

Most European Lifelong Learning (LLL) policies have been designed to create economic growth and, at the same time, guarantee social inclusion (EC 2010). First, we will study how different LLL policies are compatible with each other in terms of their orientations and objectives and how each policy considers the needs of young adults. Second, we will research the intended and unintended effects of policies on young adults. In this regard, we will look into relevant social developments such as life course de-standardisation processes and into an emerging new political economy of skills. Third, we will generate new knowledge about regional and local policymaking, with particular attention to actors, dynamics, and trends. By focusing on their regional/local context, we will elucidate the interaction and complementarity of LLL policies with other sectors of society, thus contributing to a better understanding of current fragmentation and discrepancies, in order to set parameters for future decision-making support systems. The project will first contribute new knowledge of the impact of LLL policies on young adults life courses, yielding insights on the conditions, strategies, and necessities for policies to become effective. In addition, it will provide insights on the innovations and potentials they unlock, in particular with view to informal and non-formal learning to better address vulnerable groups. Second, the project contributes to a better understanding of the structural relationships and functional match between education/training and the labour market sectors. Third, the project will provide a thorough review of regional policies and initiatives in the countries studied, laying bare distinct dynamics and trends, but also mismatches and redundancies. In particular, the project aims at identifying successful programmes in terms of sustainable solutions in integrating labour market with, social inclusion as well as their transferability to other contexts.


Grant
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: INFRADEV-03-2016-2017 | Award Amount: 3.95M | Year: 2017

Instruct-Ultra aims to advance the scope and efficiency of implementation of Instruct and consolidate the foundations for long-term sustainability. This will be achieved through specific objectives: expand Instruct membership to new Member States and increase global links; engage new user communities; improve efficiencies in service delivery; improve data capture and management; adjust the scale and reliability of the infrastructure. Instruct-Ultra will deliver these alongside the transition to ERIC legal status and rapid developments in, and increased demand for, integrated structural biology infrastructure. These advances in the scale and speed of delivery will earn further trust within the life science community. One focus will to expand membership to Eastern European states and EFTA countries, integrating their structural biology communities into Instruct and providing new opportunities to support research excellence and raise standards. Opportunities for engaging with industrialised and developing countries outside the ERA will build on existing cooperative work between Instruct and Asian, African and South American countries to establish strong bilateral programmes of benefit to both parties, giving Instruct better engagement in emerging global challenges and positioning Instruct as a trusted global resource for high quality structural biology services. Starting from baseline operations four years ago Instruct has now identified key areas of service which should be expanded, new potential user groups, and opportunities for more reliable, efficient and sometimes remotely used workflows. Instruct-Ultra will therefore test new modes of access and pilot new service methods in high demand areas to accelerate access for more users. Instruct-Ultra will reinforce Instruct operations by updating and expanding the business plan and structural biology roadmap, whilst improving the interface with academia and industry as a strategy to sustainability.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2010-IRSES | Award Amount: 321.30K | Year: 2011

The project aims to facilitate the collaborative research towards theory, design, manufacture and experimental tests of high-quality periodically bent crystalline structures as well as theoretical and experimental studies of the radiation formed in crystalline undulators. The idea of the crystalline undulator is based on the channeling phenomenon. Its advantage is in extremely strong electrostatic fields inside a crystal which are able to steer the particles much more effectively than even the most advanced superconductive magnets. A crystal with periodically bent crystallographic planes or axes can force particles to move along nearly sinusoidal trajectories and radiate electromagnetic waves in hard X ray and gamma ray frequency range. This opens the prospect of creation of novel light sources that will find their application in technology, medicine and basic sciences: nuclear, solid state and plasma physics, molecular biology, etc. It is planed to combine within a common project utilization of state-of-the-art technologies: molecular beam epitaxy, laser ablation, low pressure chemical vapour deposition, low energy plasma enhanced chemical vapour deposition with advances theoretical methods aimed to quantitative understanding of the underlying physical processes which will allow to manufacture bent crystals with preassigned shape of channels. The quality of the manufactured crystals will be controlled by several advanced methods: X-ray diffraction studies, transmission electron microscopy, atomic force microscopy, scanning electron microscopy and optical profilometry. Accelerator test of the crystalline undulators will be complemented with extensive Monte-Carlo simulations of particle channeling and emission of the radiation.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.74M | Year: 2016

PDZnet will create an innovative European PhD training network focusing on unraveling PDZ domain-mediated signaling networks. The emphasis will be on signaling nodes essential for the development of cancer and diseases of the nervous system, conditions that affect millions of Europeans and are major societal challenges. PDZ domains are protein and lipid recognizing modules that play a central role in trafficking and organizing diverse cell signaling assemblies, thereby allowing information to be transmitted from receptors, ion channels and transporters in the cell membrane. PDZ domain mediated interactions are emerging as conceptually novel and promising drug targets, with exciting opportunities for the development of novel therapies, especially within cancer and brain diseases. We will establish a European multidisciplinary platform integrating a plethora of complementary life science disciplines that range from chemical development of inhibitors to studies in live animals. The network encompasses 8 academic and 2 industrial beneficiaries as well as one industrial and one academic partner, which are all committed to promote frontline research, innovation and educational activities within the study of PDZ domain-mediated signal transduction pathways related to brain diseases and cancer. This interdisciplinary network will establish an outstanding training opportunity for Early Stage Researchers, who will be integrated in projects unraveling intracellular PDZ domain interactomes to provide pertinent information for discovering drug-related interactions. In a comprehensive and integrated training effort, involving a combination of scientific and transferable skills, the students will receive an interdisciplinary, intersectoral and innovative doctoral training from experienced industrial and academic leaders in well-reputed European Institutions.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SEC-2012.3.4-5 | Award Amount: 4.74M | Year: 2013

Security checks at borders are required to be increasingly thorough and fast. There are currently two types of technologies available for this application: those that automatically detect objects concealed on a person, and those that rely on human operator analysis and interpretation in order to classify or identify body-borne threats. The objective of TeraSCREEN is to combine these two capabilities, thus providing automatic detection and classification of body-borne threats for security screening. This will significantly improve both efficiency and security at border checks. TeraSCREEN aims to develop passive and active operation at several Terahertz frequencies. The resulting multi-frequency, multi-mode images will be processed automatically in real-time to reveal the location of potentially harmful objects concealed on a person. Privacy Enhancing Technologies will be used: the information will be displayed to the operator on a generic computerised silhouette and no anatomical details will be shown or saved. Terahertz radiation is non-ionizing, and reliable studies have shown that active operation in this frequency band is harmless to humans. The automatic recognition of threats, in addition to removing privacy issues, reduces the level of attention required from the operator, which implies a reduction in the personnel necessary for continuous operation. The TeraSCREEN Prototype System will be demonstrated at a live control point in Bristol International Airport. The feedback from the End-User and Advisory Board members will facilitate, outside this project, the conversion of the prototype into an innovative security screening product that will significantly improve the security and efficiency at, and experience of, border checks. The consortium consists of 12 partners from academia, research and industry across Europe, who each play complementary roles in the project and are interested in exploiting the results together.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-14-2015 | Award Amount: 5.87M | Year: 2016

The main objective of the project is to provide a treatment of the neurological symptoms of patients with Ataxia Telangiectasia (AT), a rare progressively disabling and life-shortening genetic disease for which no therapy is currently available. To achieve this, a pivotal Phase III study will be conducted, to allow regulatory filing to obtain market authorization in EU and USA by 2019. EryDex is an innovative product, developed by EryDel, used to administer dexamethasone sodium phosphate by ex-vivo encapsulation in autologous erythrocytes, which are infused into the patient. EryDex provides long-term delivery of low doses of dexamethasone without the typical steroid side effects and has reached a successful Phase II trial conducted in AT patients. The phase III trial will be an international, multi-center, 1 year, randomized, prospective, double-blind, placebo-controlled, designed to assess the effect of 2 dose ranges of EryDex, administered monthly by IV infusion, on neurological symptoms of AT patients. The protocol of the trial and the regulatory path to registration has already been agreed upon with EMA and FDA. An international patient registry will also be set with the aim of establishing and maintaining a comprehensive clinical database of patients with AT and closely related conditions, enabling the monitoring of AT epidemiology, the development of an evidence-based natural history of the condition, identification of biomarkers as well as development of clinical guidelines. The AT NEST, the first scale to assess symptoms specific to AT patients, coordinated by the AT centre at the Johns Hopkins University, will be tested in the study and if validated will represent the 1st scale assessing chief areas of impairment specific to AT. In parallel to the clinical trial, investigations into the molecular mechanisms of action of EryDex will be performed with the objective to provide the validation of a new biomarker predictive of treatment efficacy.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-09-2016 | Award Amount: 6.20M | Year: 2017

Due to lack of targeted interventions, compliance issues, insufficient effect sizes and a high non-responder rate to currently available interventions, there is an urgent need to develop innovative and new interventions for chronic paediatric neuropsychiatric disorders, such as Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Transcranial direct current stimulation (tDCS) has been shown to be an innovative, effective and safe alternative treatment approach for neuropsychiatric disorders in adults. Here, for the first time, the effect of tDCS on core neurocognitive and behavioral outcomes will be proven in children and adolescents. First, effect sizes and safety of standard tDCS in the clinical setting targeting core brain regions and disorder specific cognitive tasks will be established by three phase-IIa randomized, double blind, sham-controlled studies in ADHD and ASD. Second, the impact of brain development and age-dependent anatomical / functional features on effects of tDCS will be studied systematically using methods of modern neurophysiology, neuroimaging and electric current modeling. This involves an additional phase-I clinical trial. Third, mechanisms of tDCS on brain function will be studied, and biomarkers will be developed in order to predict individual response to standard and individualized stimulation protocols. Finally, the applicability of tDCS in children and adolescents will be improved by developing an innovative personalized home-based treatment option in combination with a telemental health service, which will be tested by a fifth, phase-IIa clinical trial. Throughout the entire project, ethical concerns of the target population will be addressed. This project opens a new avenue for the application of tDCS as an alternative treatment for a great number of chronic neuropsychiatric disorders in children and adolescents and will allow flexible integration of tDCS in the daily routine of families.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: REGPOT-2007-3-01 | Award Amount: 1.06M | Year: 2008

The project RESTCA-TERCE-NIPMSS is aimed at reinforcing the S&T potential of two emerging research centers, which are dealing with study of natural and industrial solid pollutants: (1) Mineralogy-Crystallography and Petrology-Geochemistry Departments of the Faculty of Mining and Geology, Serbia (UB-FMG) and Department of Geochemistry and Environmental Geology, Geological Survey of Slovenia (GeoZS) - by establishing strategic partnership among each other and with the Institute of Geosciences, Division of Mineralogy, University of Frankfurt, Germany (GUF). The major project objectives are: (i) strengthening the international co-operation networking and partnership between the UB-FMG, GUF and GeoZS and setting-up a brain-gain environment, (ii) improving material research standards at the UB-FMG by renewal and upgrade of the facilities, (iii) exploiting the RTD results of the GeoZS and UB-FMG and promoting them to national/regional centers of excellence, (iv) networking among the institutions from the European region of convergence and Western Balkan, (v) promoting the ideas of the EU 7th Framework Program, and (vi) counterbalancing the effects of brain drain in Serbia. These objectives are to be achieved within 36 months during which support and management actions organized in six Work Packages will be undertaken. These actions include (i) staff mobility in order to mobilize and reinforce the quality of human resources, (ii) purchase and renewal of the equipment, (iii) organization of lectures, short seminars and thematic workshops, (iv) opening two post-Doc positions, and (v) various dissemination and management activities. The RESTCA-TERCE-NIPMSS goals are to generate real scientific progress in the targeted research centers in Serbia and Slovenia without creating strong dependence. This is a step forward in harmonizing the scientific system in EU and in setting-up research-intensive clusters across Europe.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.77M | Year: 2012

The aim of CLOUD-TRAIN is to establish a multi-site network of Early Stage Researchers (here predominantly PhD students) and Experienced Researchers at 10 partner institutions across Europe. The role of aerosol nucleation for atmospheric CCN levels, clouds and climate is investigated. The influence of various vapours and ions for aerosol nucleation, growth and cloud processes is studied to significantly improve our understanding of natural and anthropogenic climate forcing as well as feedback mechanisms. The major focus of the network will be three sets of common experiments on ternary nucleation (ion-induced and neutral) and ion-aerosol-cloud interaction carried out at CERN to which all trainees contribute. These experiments are conducted at the newly established unique aerosol chamber CLOUD that is exposed to a CERN ionizing particle beam where the effects of cosmic rays on aerosol and clouds can be efficiently simulated. At the CLOUD chamber nucleation experiments are performed at an unprecedented level of precision and completeness using highly innovative instrumentation. A comprehensive high quality training programme is set up for the fellows. Additional to the experiments at CERN, they are brought together for network training events such as annual summer schools and workshops for integral data analysis. Courses by world leading experts are taught spanning from general aerosol chemistry and physics to specialized sessions. The summer schools and workshops are specifically tailored to the needs of the trainees and are scheduled in addition to the national PhD programmes of their hosting institutions. Comprehensive transferable skills training is included (e.g. scientific writing, presenting talks, interaction with the media, entrepreneurship, IPR, management). Five network partners are from the private sector (2 full, 3 assoc.). Secondments are planned for each fellow to broaden the experience and to include exposure to another sector.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 2.54M | Year: 2010

Chemical Biology is a new, supradisciplinary field that unites the classically separate disciplines of Chemistry and Biology. This network is centred around understanding the central biological process of phosphate transfer and combines leading experts in synthetic chemistry, enzyme model building, kinetic analysis, protein chemistry and directed evolution in a concerted effort to gain a quantitative understanding of transition states that are key to understanding how biological systems can achieve phosphate transfer with unrivalled efficiency. The quantitative language (i.e. kinetic and molecular recognition studies) used to describe and improve natural enzymes unites all participants and provides the theme for our training programme on analysis of phosphate transfer catalysis. Training in this area is highly interdisciplinary in nature requiring a joint effort of chemists and biologists centred around mechanistic thinking, which is at the core of this proposal. Ultimately our understanding of this central bioreaction should lead to useful applications on the long term, e.g. as artificial nucleases, with potential roles in gene regulation, if efficient catalysis can be combined with selective recognition. This proposal is part of a long-term strategy aimed at developing reagents which act by binding or catalytically (thus as artificial enzymes) to interfere with the expression of specific genes. This can be achieved through selective binding eventually (but not necessarily) followed by cleaving the nucleic acid backbone. Crucially for therapeutic success these reagents have to be deliverd into the cell, which is why delivery issues are also addressed. The incorporation of industrial partners ensures that the full life-span of drug development is covered in this training programme.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2013.5.2 | Award Amount: 5.62M | Year: 2014

MR-guided Focused Ultrasound Surgery (MRgFUS) combines high intensity focused ultrasound for thermal ablation of diseased tissue with MR imaging to visualise the tumour and surrounding anatomy and to provide MR thermal feedback.\nHowever, MRgFUS treatment of the liver and other abdominal organs present tremendous technological challenges, including motion due to breathing and shielding of the target by the rib cage.\nTo tackle these challenges, the VPH project FUSIMO has set out to develop a planning system for MRgFUS capable to deal with moving abdominal organs.\nTRANS-FUSIMO will translate the FUSIMO demonstrator into a clinically applicable system spanning the full clinical workflow of planning, conduction and assessment as well as learning from the procedure:\n1) Extension of the FUSIMO demonstrator to support conduction and assessment of the intervention under breathing motion\n2) Interfacing state-of-the-art FUS hardware and imaging devices to build an integrated real-time-capable system for liver FUS\n3) Improving model components for optimized clinical workflow, real-time applicability and validated outcome prediction\n4) Allowing training and learning using the FUSIMO software system by building a case and result database\n5) Conduction of pre-clinical (phantoms, cadaver, animal) experiments of the FUSIMO system\nIn a clinical trial, the feasibility of using the integrated system for neoadjuvant MRgFUS to achieve prolonged survival will be investigated.\nAs a final project result, the integrated system will be close to certification status and subsequent commercialization. With such an integrated real-time system, FUS can become a commercially and clinically competitive alternative to current surgical and minimal-invasive oncological interventions, thus providing a non-invasive treatment, reducing side-effects, and healthcare costs.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: SPA.2009.2.2.01 | Award Amount: 2.00M | Year: 2010

Sub-millimetre wave or terahertz heterodyne receivers are key instruments for many space applications. For example, they are required for monitoring of the earths atmosphere or detection of molecules that might be tracers of life on other planets or moons. However, key components of these systems are currently supplied from outside Europe and performance as well as mass and power requirements often prohibit the implementation. The TeraComp project aims at developing European industrial level capability to design and manufacture terahertz front-end electronics based on high frequency Schottky diodes, Heterostructure Barrier Varactor (HBV) diodes and mHEMT MMICs for space and other applications. The prototype components will be integrated into a compact 557 GHz heterodyne receiver and evaluated for space instrument applications. The front-end demonstrator consists of a low noise 557 GHz subharmonic Schottky diode mixer, a 275 GHz Heterostructure Barrier Varactor frequency tripler and a 92 GHz mHEMT power amplifiers and a 15 to 92 GHz 6x multiplier as part of the local oscillator chain. This development will significantly contribute to mass and power reduction and it will improve the performance of terahertz heterodyne receivers. In addition, the dependence on critical technologies and capabilities from outside Europe for future space applications will be reduced.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.1.2-1 | Award Amount: 3.90M | Year: 2012

With the arrival of new colorectal cancer (CRC) therapeutics targeting specific cell signalling pathways, such as anti-EGFR therapy, personalised cancer treatment is at the door step of clinical practise. This progress in drug development contrasts strikingly with current clinical practice, where decision making depends largely on clinical factors such as tumour staging and age of patient, with the success of such treatments being largely unpredictable. 5-FU-based chemotherapy represents the main stay of CRC therapy. DNA damaging agents such as 5-FU and anti-EGFR therapy seek to induce tumour regression through induction of apoptosis or sensitization to apoptosis. Dysfunctional apoptosis is well recognized as a key contributing factor in chemotherapy resistance. The aim of the APODECIDE consortium is to develop systems medicine tools that predict treatment responses in CRC patients to 5-FU-based chemotherapy and anti-EGFR therapy, based on a systems analysis of apoptosis and EGFR signalling pathways. Based on previous clinical proof-of-concept studies that demonstrated the unique potential of such approaches in predicting tumour resistance, the APO-DECIDE consortium aims to deliver new clinical decision making tools that enable personalised medicine approaches and smart clinical trials design in the future. The SMEs will benefit from the project through the development of systems-based combinatorial biomarkers adapted to formalin fixed paraffin-embedded material, the routine material used in clinical histopathology, hence providing a unique opportunity for marketing and exploitation. SMEs and their academic partners will also develop computational whole body models reflecting drug pharmacodynamics and pharmacokinetics in patient cohorts, providing a unique market niche in the field clinical oncology.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: ENV.2009.2.1.3.2 | Award Amount: 4.53M | Year: 2010

UNDESERT aims at combatting desertification and land degradation in order to mitigate their impacts on ecosystem services, and following on human livelihoods. The West African region is central for understanding desertification and degradation processes, which are already severe and widespread as a consequence of climate change and human impact. An improved understanding of the effects of desertification and degradation processes is obtained on a local to regional scale by integrating remote sensing information with sound field data on biodiversity and soil as well as socioeconomic and climate data. On this basis decision support models and tools will be developed and introduced to natural resource managers. UNDESERT also includes two very practical aspects, 1) restoration through tree plantations, which will be certified for CO2 marketing as the first restoration site in West Africa, 2) ecosystem management based on scientific data and best practices developed in close collaboration between scientists and local communities. As a demand driven project, UNDESERT activities will be implemented by employing 17 young PhD students, who will receive training to enhance future capacities to manage risks and uncertainties in the frame of future demographic and climatic changes. The scientific results will be used to combat desertification and degradation directly and will be transferred to international programs in order to contribute to the implementation of relevant international strategies, initiatives and commitments of the EU and African countries.


A Europe-wide consortium of experimental biologists, biomathematicians, biostatisticians, computer scientists and clinical scientists will team up to approach cell death pathways in health and disease, placing particular emphasis on cancer and AIDS. The consortium will create a unique database integrating existing and accumulating knowledge on lethal signal transduction pathways leading to apoptosis or non-apoptotic (necrotic, autophagic, mitotic) cell death, perform data mining to integrate system-wide analyses on cell death (genome, epigenome, transcriptome, proteome, lipidome data), and use high-throughput methods (omics, CHiP-chip and genome-wide siRNA screens) for the experimental exploration of death pathways in human cell lines in vitro and in relevant disease models (in vitro in human cells and in vivo in mice and Drosophila). In addition, the consortium will establish mathematical models of lethal pathways to devise algorithms that predict apoptosis susceptibility and resistance, obtain data (genome, transcriptome, proteome, lipidome) on clinical samples (cancer cell lines, cancer tissues, serum, and blood samples) and perform biostatistical analyses on them in order to demonstrate the contribution of apoptotic process in human cancers and AIDS. Then, the consortium will integrate the knowledge into mathematical models for the optimal interpretation of clinical data, aiming at optimal diagnostic and prognostic performance as well as at the identification of possible therapeutic targets for the treatment of cancer and AIDS.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-1;HEALTH.2011.1.4-2 | Award Amount: 7.84M | Year: 2011

Although the long term prognosis of patients suffering acute myocardial infarction (AMI) has improved since the introduction of reperfusion therapies and primary angioplasty, the 1 year mortality of patients with AMI and resultant left ventricular systolic dysfunction (LVSD) is still as high as 13%. A major reason for the high morbidity and mortality is that the heart has an inadequate regenerative response to the myocardial necrosis sustained following AMI; cell death from the ischaemic damage can lead to progressive ventricular dilation and dysfunction through the processes of vascular remodelling. Despite the use of full conventional treatment, including ACE inhibitors, beta-blockers, aldosterone inhibitors and diuretics, yearly mortality rates of patients with post-infarction heart failure are still in the range of 13 % and rehospitalisation for worsening of heart failure occurs at a yearly rate of 68%. Clinical data now exists supporting the concept that autologous bone marrow derived cells can restore cardiac function following AMI. We plan to advance this research in the BAMI project and will: Develop a standardised method of bone marrow cell collection Develop a standardised method of optimising reparative potential of bone marrow derived cells Standardise bone marrow preparation procedure so that it can be universally applied Standardise method of bone marrow cell delivery post AMI Conduct the first large scale all course mortality clinical trial to test if the product and delivery method mentioned above can lead to a 25% reduction in mortality end-point at 2 years Our project will establish the therapeutic value of this approach to stem cell therapy. Success will demonstrate that transcoronary infusion of bone marrow-derived progenitor cells is safe and will reduce the mortality rate by 25% and reduce the rehospitalisation rate by 15%.


The attachment of ubiquitin was long considered as giving the "kiss of death", labelling superfluous proteins for disposal within a cell. However, by now it has been well established that ubiquitin fulfils numerous additional duties in cellular signal transduction. A team of scientists under the lead of Ivan Dikic, Director of the Institute of Biochemistry II at Goethe University Frankfurt, has now discovered a novel mechanism of ubiquitination, by which Legionella bacteria can seize control over their host cells. Legionella causes deadly pneumonia in immunocompromised patients. According to the current understanding, the coordinated action of three enzymes is needed for attaching ubiquitin to other proteins. In April this year, U.S. scientists described an ubiquitination reaction that depends only on a single enzyme from Legionella bacteria. The Dikic team together with the group of Ivan Matic (Max Planck Institute for Biology of Ageing, Cologne, Germany) now elucidated the underlying molecular mechanism of its action and revealed a hitherto unknown type of chemical linkage between ubiquitin and target proteins. Their discovery breaks new ground in the field. Sagar Bhogaraju, researcher in the Dikic laboratory, comments: "Most exciting is of course the question if this unusual ubiquitination also occurs in human cells independently of bacterial infection and if there are similar, so far unknown enzymes in humans, which may have a profound influence on cellular processes." When studying the new mechanism in more detail, the Frankfurt scientists were very surprised to find that the Legionella enzyme does not only transfer ubiquitin onto target proteins, but also chemically manipulates the remaining pool of ubiquitin molecules. Modified ubiquitin almost completely inhibits the conventional ubiquitination system, thereby revealing a new role for this enzyme during Legionella infections. Several important cellular processes are affected by this shut-down of the ubiquitination system, which can also cause a rapid cell death. The Dikic team showed for example that modified ubiquitin prevents degradation of mitochondria (a process called mitophagy), affects transduction of inflammatory signals and constrains protein degradation. "Most likely, Legionella is not the only bacterium using this mechanism. We hope that our results help to identify new strategies for the development of antibacterial agents, which could complement conventional antibiotics by limiting cellular damage induced by bacterial enzymes", explains Dikic the high medical relevance of their discovery. The group of Ivan Dikic is located at both the Institute of Biochemistry II and the Buchmann Institute for Molecular Life Sciences at Goethe University Frankfurt and has previously contributed significantly to a paradigm change in the ubiquitin field. Ivan hypothesized early on that ubiquitin signals are recognized and translated by specialized domains in other proteins. He identified ubiquitin-binding domains in more than 200 ubiquitin receptors and was able to prove their role in diseases like cancer, amyotrophic lateral sclerosis and Parkinson's.


News Article | December 16, 2016
Site: phys.org

Electrons embedded in the atomic lattice – the components of a solid. The mutual repulsion of the electrons prevents them from coming into close contact. This impedes the electron flow and the system can become an insulator. Credit: Dr. Ulrich Tutsch Whether water freezes to ice, iron is demagnetized or a material becomes superconducting – for physicists there is always a phase transition behind it. They endeavour to understand these different phenomena by searching for universal properties. Researchers at Goethe University Frankfurt and Technische Universität Dresden have now made a pioneering discovery during their study of a phase transition from an electrical conductor to an insulator (Mott metal-insulator transition). According to Sir Nevill Francis Mott's prediction in 1937, the mutual repulsion of charged electrons, which are responsible for carrying electrical current, can cause a metal-insulator transition. Yet, contrary to common textbook opinion, according to which the phase transition is determined solely by the electrons, it is the interaction of the electrons with the atomic lattice of the solid which is the determinant factor. The researchers have reported this in the latest issue of the Science Advances journal. The research group, led by Professor Michael Lang of the Physics Institute at Goethe University Frankfurt, succeeded in making the discovery with the help of a homemade apparatus which is unique worldwide. It allows the measurement of length changes at low temperatures under variable external pressure with extremely high resolution. In this way, it was possible to prove experimentally for the first time that it is not just the electrons which play a significant role in the phase transition but also the atomic lattice—the solid's scaffold. "These experimental results will herald in a paradigm shift in our understanding of one of the key phenomena of current condensed matter research," says Professor Lang. The Mott metal-insulator transition is namely linked to unusual phenomena, such as high-temperature superconductivity in copper oxide-based materials. These offer tremendous potential for future technical applications. The theoretical analysis of the experimental findings is based on the fundamental notion that the many particles in a system close to a phase transition not only interact with their immediate neighbours but also "communicate" over long distances with all other particles. As a consequence, only overarching aspects are important, such as the system's symmetry. The identification of such universal properties is thus the key to understanding phase transitions. "These new insights open up a whole new perspective on the Mott metal-insulator transition and permit more sophisticated theoretical modelling of the phase transition," explains Dr. Markus Garst, Senior Lecturer at the Institute of Theoretical Physics of Technische Universität Dresden. Explore further: The metal-insulator transition depends on the mass of the Dirac electrons More information: E. Gati et al. Breakdown of Hookes law of elasticity at the Mott critical endpoint in an organic conductor, Science Advances (2016). DOI: 10.1126/sciadv.1601646


A new approach based on cell-squeezing technology developed at MIT allows researchers to deliver fluorescent tags that are much less bulky, making this kind of protein imaging easier and more efficient. In 2013, the MIT team demonstrated that squeezing cells makes it possible to deliver a variety of molecules, including proteins, DNA, carbon nanotubes, and quantum dots, into the cells without damaging them. Researchers at Goethe University Frankfurt in Germany, working with their MIT colleagues, have now employed this approach to deliver relatively tiny fluorescent tags that can be targeted to specific proteins. Using regular confocal microscopes or super resolution microscopes, scientists can then track these proteins over time as they perform their normal functions. "It really opens up the door to watching protein interactions in live cells," says Armon Sharei, a former postdoc at MIT's Koch Institute for Integrative Cancer Research. "Proteins are the building blocks of cells and control all their functions, so it's exciting to be able to finally visualize them in a living cell, without genetic modifications." Sharei is an author of a paper describing the technique in Nature Communications. The paper's lead author is Alina Kollmannsperger, a graduate student at Goethe University, and the senior authors are Ralph Weineke and Robert Tampé of Goethe University. Robert Langer, the David H. Koch Institute Professor at MIT, and Klavs Jensen, the Warren K. Lewis Professor of Chemical Engineering at MIT, are also authors. "We are very excited about this latest application for our cell squeezing approach and its implications for protein labeling," says Langer, who is a member of MIT's Koch Institute for Integrative Cancer Research. In their 2013 study, the MIT team showed that squeezing cells through a constriction 30 to 80 percent smaller than the cells' diameter caused tiny, temporary holes to appear in the cell membranes, allowing any large molecules in the surrounding fluid to enter. The holes reseal quickly and the cells suffer no long-term damage. The researchers then began working with the Goethe University team to use this technique to label proteins with small fluorescent tags, which have previously been difficult to get into living cells. The Goethe team developed a tag called trisNTA that binds to any protein with a long string of histidine molecules (one of the 20 amino acids that form the building blocks of proteins). For this study, the researchers first used genetic engineering to attach the histidine sequence to several different proteins, including one found in the nucleus and another involved in processing foreign molecules that have entered the cell. Then, the cells were pushed through a microfluidic channel at a rate of 1 million cells per second, which squeezed them sufficiently to allow the trisNTA tag in. Until now, scientists have had to use protein tags, such as the bulky GFP, that can be genetically encoded in the cells' DNA, or to study proteins in nonliving cells because the process of getting other fluorescent tags into the cells requires destroying the cell membrane. "This study shows how microfluidic cell-squeezing together with specific chemical labeling can be exploited to hook various synthetic fluorophores to intracellular proteins with exquisite specificity. I foresee many applications for this approach and I have a very long list of probes that I would like to test immediately," says Kai Johnsson, a professor of chemical sciences and engineering at the École Polytechnique Fédérale de Lausanne in Switzerland, who was not involved in the research. With further work, including the development of new tags that target other proteins, this technique could help scientists learn much more about proteins' functions inside living cells. "Basically everything that happens in your cells is mediated by proteins," Sharei says. "You can start to learn a lot about the basic biology of how a cell works, how it divides, and what makes the cancer cell a cancer cell, as far as what mechanisms go awry and what proteins are responsible for that." The researchers believe that the cell squeezing technique should work with nearly any type of cell. So far, they have tried it successfully with more than 30 different types of mammalian cells. An added benefit is that when cells undergo the squeezing procedure, they show no changes in the genes they express. In contrast, when a jolt of electricity is applied to cells to make them more permeable—a technique commonly used to deliver DNA and RNA—more than 7,000 genes are affected. "It's possible to assume that a squeezed cell is probably going to behave more or less normally, which is critical when you're trying to study these kinds of processes," Sharei says. A company called SQZ Biotech, started by MIT researchers including Sharei, Langer, and Jensen, has licensed the cell squeezing technology and is now using it to engineer immune cells to improve their ability to attack cancer cells. Explore further: Chemists design new way to fluorescently label proteins More information: Alina Kollmannsperger et al. Live-cell protein labelling with nanometre precision by cell squeezing, Nature Communications (2016). DOI: 10.1038/ncomms10372


News Article | September 2, 2016
Site: phys.org

Can life be transplanted to planets outside our solar system that are not permanently inhabitable? This is the question with which Professor Dr. Claudius Gros from the Institute of Theoretical Physics at Goethe University Frankfurt is dealing in an essay that will appear in the scientific journal Astrophysics and Space Science.


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

The German Research Foundation (DFG) will be providing financial support to the Collaborative Research Center (CRC) 1080 on "Molecular and cellular mechanisms of neuronal homeostasis" for four more years. In addition to Johannes Gutenberg University Mainz (JGU), Goethe University Frankfurt as the CRC's speaker university, the Max Planck Institute for Brain Research, and the Mainz-based Institute of Molecular Biology (IMB) are participating in this research center. A total of some EUR 12 million is being made available in the new funding period that will commence on January 1, 2017. CRC 1080 was established on January 1, 2013 with Johannes Gutenberg University Mainz acting as the speaker university. With the commencement of the new funding phase, the speaker role will be transferred to Frankfurt University which, as a member of the Rhine-Main Neuroscience Network (rmn²), is participating in the CRC with its own research projects. The future coordinator of the CRC, Professor Amparo Acker-Palmer, heads up the Frankfurt Institute for Cell Biology and Neurosciences and is also a fellow of the Gutenberg Research College (GRC) at JGU. Professor Heiko Luhmann, Director of the Institute of Physiology at the Mainz University Medical Center, will take up the post of deputy coordinator. The purpose of the CRC on "Molecular and cellular mechanisms of neuronal homeostasis" is to study the molecular and cellular interactions that enable the brain to maintain a state of functional equilibrium, otherwise known as network homeostasis. New findings should contribute to understanding disease processes in the brain, thus providing insights in the development of innovative new therapies. This might even include the creation of new pharmaceutical agents that could be used to treat cerebral disorders in humans. Specifically, the researchers working at the CRC are investigating different classes of molecules, such as those involved in the control of cell-to-cell interactions and signaling processes. "The extension of funding of the Collaborative Research Center 1080, which studies aspects that offer great potential benefits to society, owes much to our very productive and collaborative research endeavors," pointed out the Chief Scientific Officer of the Mainz University Medical Center, Professor Ulrich Förstermann.


Ionov D.A.,Jean Monnet University | Ionov D.A.,CNRS Magmas and Volcanoes Laboratory | Ionov D.A.,Goethe University Frankfurt
Journal of Petrology | Year: 2010

Peridotite xenoliths in arc volcanoes are very rare, usually small and remain poorly studied. Much of the earlier work focused on peridotites affected by re-crystallization, metasomatism and veining that took place shortly before the eruption of the host magmas; such lithologies may not be widespread in the mantle wedge. This study reports petrographic, major and trace element data for 17 large, fresh peridotite xenoliths from the active Avacha volcano and discusses the origin of supra-subduction zone lithospheric mantle, in particular the role and characteristics of partial melting and metasomatism. The xenoliths are spinel harzburgites containing interstitial cpx (1·5-3%) and amphibole (≤1%). Nearly all are medium- to coarse-grained with protogranular to granoblastic microstructures; some have fine-grained domains and thin cross-cutting veins of secondary opx and olivine. Core-rim zoning and unmixing of cpx and spinel in coarse opx indicate long-term cooling to ≤900-1000°C; Cr#Sp and Al and Cr in opx are correlated with equilibration temperatures. The peridotites are highly refractory, with ≥44% MgO and very low Al2O3 and CaO (0·4-0·9%), TiO2 (≤0.01%), Na2O (≤0.03%), K2O and P2O5 (below detection) and REE in whole-rocks, ≤2·1% Al2O3 in opx and ≤0·1-0·3% Na2O in cpx. Comparisons of Mg, Al and Fe contents with melting experiments indicate 28-35% melt extraction at ≤1 to 2 GPa, in line with the absence of primary cpx and high Mg#Ol (0·907-0·918) and Cr#Sp (0·53-0·65). Bulk-rock Al2O3 is a more robust melt extraction index than Cr#Sp, Mg#Ol and Mg#WR. Forearc harzburgites and certain xenoliths from the Western Pacific share many of these characteristics with the Avacha suite and may have similar origins. A distinctive feature of the Avacha harzburgites is a combination of variable but commonly high modal opx (18-30%) with very low modal cpx. At a given olivine or MgO content, they have higher opx and SiO2, and lower cpx (as well as Al2O3 and CaO) than typical refractory peridotite xenoliths in continental basalts. These features may indicate fluid fluxing during melting in the mantle wedge. Alternatively, they could have been produced after partial melting by selective metasomatic enrichment in SiO2 by fluids to transform some olivine into opx, although the latter mechanism is hard to reconcile with the very low alkalis and REE contents and the absence of silica correlation with fluid-mobile elements. Bulk-rock enrichments in silica and opx are unrelated to the presence or abundance of late-stage, fine-grained materials and are due to an ancient event rather than recent re-crystallization and veining. © The Author 2010. Published by Oxford University Press.


Muller B.,University of Heidelberg | Heilemann M.,Goethe University Frankfurt | Heilemann M.,University of Heidelberg
Trends in Microbiology | Year: 2013

For more than 70 years electron microscopy (EM) techniques have played an important role in investigating structures of enveloped viruses. By contrast, use of fluorescence microscopy (FM) methods for this purpose was limited by the fact that the size of virus particles is generally around or below the diffraction limit of light microscopy. Various super-resolution (SR) fluorescence imaging techniques developed over the past two decades bypass the diffraction limit of light microscopy, allowing visualization of subviral details and bridging the gap between conventional FM and EM methods. We summarize here findings on human immunodeficiency virus (HIV-1) obtained using SR-FM techniques. Although the number of published studies is currently limited and some of the pioneering analyses also covered methodological or descriptive aspects, recent publications clearly indicate the potential to approach open questions in HIV-1 replication from a new angle. © 2013 Elsevier Ltd.


Iozzo R.V.,Thomas Jefferson University | Schaefer L.,Goethe University Frankfurt
Matrix Biology | Year: 2015

We provide a comprehensive classification of the proteoglycan gene families and respective protein cores. This updated nomenclature is based on three criteria: Cellular and subcellular location, overall gene/protein homology, and the utilization of specific protein modules within their respective protein cores. These three signatures were utilized to design four major classes of proteoglycans with distinct forms and functions: the intracellular, cell-surface, pericellular and extracellular proteoglycans. The proposed nomenclature encompasses forty-three distinct proteoglycan-encoding genes and many alternatively-spliced variants. The biological functions of these four proteoglycan families are critically assessed in development, cancer and angiogenesis, and in various acquired and genetic diseases where their expression is aberrant. © 2015.


Groll A.H.,University of Munster | Castagnola E.,Instituto Giannina Gaslini | Cesaro S.,Pediatric Hematology Oncology | Dalle J.-H.,University Paris Diderot | And 6 more authors.
The Lancet Oncology | Year: 2014

Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript. © 2014 Elsevier Ltd.


Sisourat N.,University of Heidelberg | Kryzhevoi N.V.,University of Heidelberg | Kolorenc P.,Charles University | Scheit S.,University of Tokyo | And 2 more authors.
Nature Physics | Year: 2010

When an atom is electronically excited, it relaxes by emitting a photon or an electron. These carry essential information on the electronic structure of their emitter. However, if an atom is embedded in a chemical environment, another ultrafast non-radiative decay process called interatomic Coulombic decay (ICD) can become operative. As ICD occurs only in the presence of neighbours, it is highly sensitive to that environment. Therefore, it has the potential to become a powerful spectroscopic method to probe the close environment of a system. ICD has been observed experimentally in van der Waals clusters as well as in hydrogen-bonded systems. A key feature of ICD is that the excited atom can transfer its excess energy to its neighbours over large distances. The giant extremely weakly bound helium dimer is a perfect candidate to investigate how far two atoms can exchange energy. We report here that the two helium atoms within the dimer can exchange energy by ICD over distances of more than 45 times their atomic radius. Moreover, we demonstrate that ICD spectroscopy can be used for imaging vibrational wavefunctions of the ionized-excited helium dimer. © 2010 Macmillan Publishers Limited. All rights reserved.


Noronha-Hostler J.,University of Sao Paulo | Noronha J.,University of Sao Paulo | Greiner C.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2012

Lattice calculations of the QCD trace anomaly at temperatures T<160 MeV have been shown to match hadron resonance gas model calculations, which include an exponentially rising hadron mass spectrum. In this paper we perform a more detailed comparison of the model calculations to lattice data that confirms the need for an exponentially increasing density of hadronic states. Also, we find that the lattice data is compatible with a hadron density of states that goes as ρ(m)∼m -aexp(m/T H) at large m with a>5/2 (where T H∼167 MeV). With this specific subleading contribution to the density of states, heavy resonances are most likely to undergo two-body decay (instead of multiparticle decay), which facilitates their inclusion into hadron transport codes. Moreover, estimates for the shear viscosity and the shear relaxation time coefficient of the hadron resonance model computed within the excluded volume approximation suggest that these transport coefficients are sensitive to the parameters that define the hadron mass spectrum. © 2012 American Physical Society.


Rodel C.,Goethe University Frankfurt | Hofheinz R.,University of Heidelberg | Liersch T.,University of Gottingen
Current Opinion in Oncology | Year: 2012

Purpose of review: To discuss the recent developments of multimodal treatment for patients with local advanced rectal cancer, including incorporation of new chemotherapeutic and targeted agents, and the optimal sequence and timing of treatment components. Recent findings: Five randomized trials have been completed to determine whether the addition of oxaliplatin to preoperative, fluorouracil-based chemoradiotherapy (CRT) offers an advantage compared to single-agent fluorouracil CRT. Early results from the ACCORD 12, STAR-01, and NSAPB R-04 trials did not confirm a significant improvement of early efficacy endpoints with the addition of oxaliplatin, whereas the German CAO/ARO/AIO-04 did. Most of the phase II trials incorporating cetuximab into CRT reported disappointingly low rates of pathologic complete response (pCR); the combination of CRT with VEGF inhibition showed encouraging pCR rates; however, it was associated with increased surgical complications. Novel clinical trials address the role of induction chemotherapy, of delayed, minimal or omitted surgery following CRT, or the omission of radiotherapy for selected patients. Summary: At this time, the use of oxaliplatin or targeted agents as component of multimodality treatment for rectal cancer outside of a clinical trial is not recommended. The inclusion of different treatment options, according to tumor stage, location, imaging features, and response, will render the multimodal treatment approach of rectal cancer more risk-adapted. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Moreth K.,Goethe University Frankfurt | Iozzo R.V.,Thomas Jefferson University | Schaefer L.,Goethe University Frankfurt
Cell Cycle | Year: 2012

Inflammation is not only a defensive mechanism against microbial invasion, but also frequently represents a critical response to tissue injury under sterile conditions. It is now well established that tissue injury leads to the release of endogenous molecules of intra- and extracellular origin acting as damage-associated molecular patterns (DAMPs). The small leucine-rich proteoglycans (SLRPs) can act as powerful DAMPs following their proteolytical release from the extracellular matrix. Recent investigations of SLRP signaling networks revealed new levels of complexity, showing that SLRPs can cluster different types of receptors and orchestrate a host of downstream signaling events. This review will summarize the evidence for the multifunctional proinflammatory signaling properties of the two archetypal SLRPs, biglycan and decorin. These secreted proteoglycans link the innate to the adaptive immune response and operate in a broad biological context, encompassing microbial defense, tumor growth and autoimmunity. © 2012 Landes Bioscience.


Pal S.,Tata Institute of Fundamental Research | Bleicher M.,Goethe University Frankfurt
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

Hadron production and their suppression in Pb+Pb collisions at LHC at a center-of-mass energy of √s NN=2.76 TeV are studied within a multiphase transport (AMPT) model whose initial conditions are obtained from the recently updated HIJING 2.0 model. The centrality dependence of charged hadron multiplicity dN ch/dη at midrapidity was found quite sensitive to the largely uncertain gluon shadowing parameter s g that determines the nuclear modification of the gluon distribution. We find final-state parton scatterings reduce considerably hadron yield at midrapidity and enforces a smaller gluon shadowing to be consistent with dN ch/dη data at LHC. With such a constrained parton shadowing, charged hadron and neutral pion production over a wide transverse momenta range are investigated in AMPT. Relative to nucleon-nucleon collisions, the particle yield in central heavy ion collisions is suppressed due to parton energy loss. While the calculated magnitude and pattern of suppression is found consistent with that measured in Au+Au collisions at √s NN=0.2 TeV at RHIC, at the LHC energy the suppression is overpredicted which may imply the medium formed at LHC is less opaque than expected from simple RHIC extrapolations. Reduction of the QCD coupling constant α s by ~30% in the higher temperature plasma formed at LHC as compared to that at RHIC was found to reproduce the measured suppression at LHC. © 2012 Elsevier B.V.


Fischer C.S.,Justus Liebig University | Luecker J.,University of Heidelberg | Luecker J.,Goethe University Frankfurt | Welzbacher C.A.,Justus Liebig University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

We investigate the phase structure of QCD at finite temperature and light-quark chemical potential. We improve upon earlier results for Nf=2+1 dynamical quark flavors and investigate the effects of charm quarks in an extension to Nf=2+1+1. We determine the quark condensate and the Polyakov loop potential using solutions of a coupled set of (truncated) Dyson-Schwinger equations for the quark and gluon propagators of Landau gauge QCD. At zero chemical potential we find excellent agreement with results from lattice-QCD. With input fixed from physical observables we find only a very small influence of the charm quark on the resulting phase diagram at finite chemical potential. We discuss the location of the emerging critical end point and compare with expectations from lattice gauge theory. © 2014 American Physical Society.


Neill T.,Thomas Jefferson University | Schaefer L.,Goethe University Frankfurt | Iozzo R.V.,Thomas Jefferson University
American Journal of Pathology | Year: 2014

Autophagy plays an essential role in maintaining an intricate balance between nutrient demands and energetic requirements during normal homeostasis. Autophagy recycles metabolic substrates from nonspecific bulk degradation of proteins and excess or damaged organelles. Recent work posits an active and dynamic signaling role for extracellular matrix-evoked autophagic regulation, that is, allosteric and independent of prevailing nutrient conditions. Several candidates, representing a diverse repertoire of matrix constituents (decorin, collagen VI, laminin α2, endostatin, endorepellin, and kringle V), can modulate autophagic signaling pathways. Importantly, a novel principle indicates that matrix constituents can differentially modulate autophagic induction and repression via interaction with specific receptors. Most of the matrix-derived factors described here appear to control autophagy in a canonical manner but independent of nutrient deprivation. Because the molecular composition and structure of the extracellular matrix are dynamically remodeled during various physiological and pathological conditions, we propose that matrix-regulated autophagy is key for maintaining proper tissue homeostasis and disease prevention, such as cancer progression and muscular dystrophies. © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.


Wahl H.-W.,University of Heidelberg | Iwarsson S.,Lund University | Oswald F.,Goethe University Frankfurt
Gerontologist | Year: 2012

Purpose of the Study: The effects of the physical-spatial-technical environment on aging well have been overlooked both conceptually and empirically. In the spirit of M. Powell Lawton's seminal work on aging and environment, this article attempts to rectify this situation by suggesting a new model of how older people interact with their environment. Design and Methods: Goals of the paper include (a) integration of the essential elements of the ecology and aging literature, particularly in regard to Lawton's research, (b) development of connections between traditional theories of ecology of aging and life span developmental models of aging well, (c) acknowledgment of the pronounced historical and cohort-related changes affecting the interactions of older people with their environment, and (d) discussion of the implications of this analysis for concepts and theories of aging well. Results: The model builds on a pair of concepts: environment as related to agency and belonging, founded in motivational psychology, and developmental science. Implications: After describing the model's key components, we discuss its heuristic potential in four propositions for future gerontological research and identify implications of the model for future empirical research. © The Author 2012.


Muranyi W.,University of Heidelberg | Malkusch S.,University of Würzburg | Muller B.,University of Heidelberg | Heilemann M.,Goethe University Frankfurt | And 2 more authors.
PLoS Pathogens | Year: 2013

The inner structural Gag proteins and the envelope (Env) glycoproteins of human immunodeficiency virus (HIV-1) traffic independently to the plasma membrane, where they assemble the nascent virion. HIV-1 carries a relatively low number of glycoproteins in its membrane, and the mechanism of Env recruitment and virus incorporation is incompletely understood. We employed dual-color super-resolution microscopy visualizing Gag assembly sites and HIV-1 Env proteins in virus-producing and in Env expressing cells. Distinctive HIV-1 Gag assembly sites were readily detected and were associated with Env clusters that always extended beyond the actual Gag assembly site and often showed enrichment at the periphery and surrounding the assembly site. Formation of these Env clusters depended on the presence of other HIV-1 proteins and on the long cytoplasmic tail (CT) of Env. CT deletion, a matrix mutation affecting Env incorporation or Env expression in the absence of other HIV-1 proteins led to much smaller Env clusters, which were not enriched at viral assembly sites. These results show that Env is recruited to HIV-1 assembly sites in a CT-dependent manner, while Env(ΔCT) appears to be randomly incorporated. The observed Env accumulation surrounding Gag assemblies, with a lower density on the actual bud, could facilitate viral spread in vivo. Keeping Env molecules on the nascent virus low may be important for escape from the humoral immune response, while cell-cell contacts mediated by surrounding Env molecules could promote HIV-1 transmission through the virological synapse. © 2013 Muranyi et al.


Sarrazin C.,Goethe University Frankfurt | Hezode C.,University Paris Est Creteil | Hezode C.,French Institute of Health and Medical Research | Zeuzem S.,Goethe University Frankfurt | And 2 more authors.
Journal of Hepatology | Year: 2012

Resolution of the three-dimensional structures of several hepatitis C virus (HCV) proteins, together with the development of replicative cell culture systems, has led to the identification of a number of potential targets for direct-acting antiviral (DAA) agents. Numerous families of drugs that potently inhibit the HCV lifecycle in vitro have been identified, and some of these molecules have reached early to late clinical development. Two NS3/4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with pegylated interferon (IFN)-α and ribavirin for the treatment of chronic hepatitis C related to HCV genotype 1, in both treatment-naïve and treatment-experienced patients. Sustained virological response rates in the range of 6675 and 5966 (2988 if the response to the first course of therapy is taken into account) have been achieved in these two patient populations, respectively, with treatment durations of 24 to 48 weeks. A number of other DAAs are at the clinical developmental stage in combination with pegylated IFN-α and ribavirin or with other DAAs in IFN-free regimens, with or without ribavirin. They include second-wave, first-generation, and second-generation NS3/4A protease inhibitors, nucleoside/nucleotide analogue inhibitors and non-nucleoside inhibitorsof HCVRNA-dependent RNA polymerase, inhibitors of nonstructural protein 5A (NS5A) and host-targeted compounds, such as cyclophilin inhibitors and silibinin. The proof of concept that IFN-free regimens may lead to HCV eradication has recently been brought. However, new drugs may be associated with troublesome side effects and drugdrug interactions, and the ideal IFN-free DAA combination remains to be found. © 2012 European Association for the Study of the Liver.


Denic V.,Harvard University | Dotsch V.,Goethe University Frankfurt | Sinning I.,University of Heidelberg
Cold Spring Harbor Perspectives in Biology | Year: 2013

Hundreds of eukaryotic membrane proteins are anchored to membranes by a single trans-membrane domain at their carboxyl terminus. Many of these tail-anchored (TA) proteins are posttranslationally targeted to the endoplasmic reticulum (ER) membrane for insertion by the guided-entry of TA protein insertion (GET) pathway. In recent years, most of the components of this conserved pathway have been biochemically and structurally characterized. Get3 is the pathway-targeting factor that uses nucleotide-linked conformational changes to mediate the delivery of TA proteins between the GET pretargeting machinery in the cytosol and the transmembrane pathway componentsinthe ER. Herewefocuson the mechanismof the yeast GET pathway and make a speculative analogy between its membrane insertion step and the ATPase-driven cycle of ABC transporters. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.


Tamura H.,Tohoku University | Burghardt I.,Goethe University Frankfurt
Journal of Physical Chemistry C | Year: 2013

The mechanism of electron-hole separation overcoming Coulomb attraction is one of the important open questions related to the efficiency of organic solar cells. In this work, we have theoretically predicted the potential curves for electron-hole separation from the bound charge-transfer (CT) state at donor-acceptor heterojunctions. The electron-hole potential was calculated considering an oligothiophene-fullerene donor-acceptor complex using the long-range-corrected density functional theory. The screening effect of the medium was taken into account by scaling with the dielectric constants of fullerene and polythiophene. The potential barrier was found to decrease as the π-conjugation length of the donor increased. We propose a simple analytical formula for the Coulomb potential between an electron localized at a fullerene molecule and a hole distributed along a π-conjugated chain. We also discuss the possible role of the excess energy due to the preceding exciton dissociation in facilitating the charge separation. © 2013 American Chemical Society.


Neill T.,Thomas Jefferson University | Schaefer L.,Goethe University Frankfurt | Iozzo R.V.,Thomas Jefferson University
American Journal of Pathology | Year: 2012

Decorin, an archetypal member of the small leucine-rich proteoglycan gene family, has a broad binding repertoire that encompasses matrix structural components, such as collagens, and growth factors, particularly those that belong to the transforming growth factor-β ligand superfamily. Within the tumor microenvironment, stromal decorin has an inherent proclivity to directly bind and down-regulate several receptor tyrosine kinases, which are often overexpressed in cancer cells. The decorin interactome commands a powerful antitumorigenic signal by potently repressing and attenuating tumor cell proliferation, survival, migration, and angiogenesis. This collection of interacting molecules also regulates key downstream signaling processes indirectly via the sequestration of growth factors or directly via the antagonism of receptor tyrosine kinases. We propose that decorin can be considered a "guardian from the matrix" because of its innate ability to oppose pro-tumorigenic cues. © 2012 American Society for Investigative Pathology.


Nastase M.V.,Goethe University Frankfurt | Iozzo R.V.,Thomas Jefferson University | Schaefer L.,Goethe University Frankfurt
Biochimica et Biophysica Acta - General Subjects | Year: 2014

Background Small leucine-rich proteoglycans (SLRPs) are molecules that have signaling roles in a multitude of biological processes. In this respect, SLRPs play key roles in the evolution of a variety of diseases throughout the human body. Scope of Review We will critically review current developments in the roles of SLRPs in several types of disease of the kidney and lungs. Particular emphasis will be given to the roles of decorin and biglycan, the best characterized members of the SLRP gene family. Major Conclusions In both renal and pulmonary disorders, SLRPs are essential elements that regulate several pathophysiological processes including fibrosis, inflammation and tumor progression. Decorin has remarkable antifibrotic and antitumorigenic properties and is considered a valuable potential treatment of these diseases. Biglycan can modulate inflammatory processes in lung and renal inflammation and is a potential target in the treatment of inflammatory conditions. General Significance SLRPs can serve as either treatment targets or as potential treatment in renal or lung disease. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. © 2014 Elsevier B.V.


Stiele R.,University of Heidelberg | Fraga E.S.,Goethe University Frankfurt | Fraga E.S.,Federal University of Rio de Janeiro | Schaffner-Bielich J.,Goethe University Frankfurt
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

We investigate the phase structure of strongly interacting matter at non-vanishing isospin before the onset of pion condensation in the framework of the unquenched Polyakov-Quark-Meson model with 2. +. 1 quark flavors. We show results for the order parameters and all relevant thermodynamic quantities. In particular, we obtain a moderate change of the pressure with isospin at vanishing baryon chemical potential, whereas the chiral condensate decreases more appreciably. We compare the effective model to recent lattice data for the decrease of the pseudo-critical temperature with the isospin chemical potential. We also demonstrate the major role played by the value of the pion mass in the curvature of the transition line, and the need for lattice results with a physical pion mass. Limitations of the model at nonzero chemical potential are also discussed. © 2014 The Authors.


Uphoff J.,Goethe University Frankfurt | Fochler O.,Goethe University Frankfurt | Xu Z.,Tsinghua University | Greiner C.,Goethe University Frankfurt
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

The space-time evolution of open heavy flavor is studied in Pb + Pb collisions at s=2.76TeV using the partonic transport model Boltzmann Approach to MultiParton Scatterings (BAMPS). An updated version of BAMPS is presented which allows interactions among all partons: gluons, light quarks and heavy quarks. Heavy quarks, in particular, interact with the rest of the medium via binary scatterings with a running coupling and a Debye screening which is matched by comparing to hard thermal loop calculations. The lack of radiative processes in the heavy flavor sector is accounted for by scaling the binary cross section with a phenomenological factor K=3.5, which describes well the elliptic flow v2 and nuclear modification factor R AA at RHIC. Within this framework we calculate in a comprehensive study the v2 and R AA of all interesting open heavy flavor particles at the LHC: electrons, muons, D mesons, and non-prompt J/ψ from B mesons. We compare to experimental data, where it is already available, or make predictions. To do this accurately next-to-leading order initial heavy quark distributions are employed which agree well with proton-proton data of heavy flavor at s=7TeV. © 2012 Elsevier B.V.


Gavin S.,Wayne State University | Moschelli G.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2012

We propose that flow fluctuations have the same origin as transverse momentum fluctuations. The common source of these fluctuations is the spatially inhomogeneous initial state that drives hydrodynamic flow. Longitudinal correlations from an early Glasma stage followed by hydrodynamic flow quantitatively account for many features of multiplicity and p t fluctuation data. We develop a framework for studying flow and its fluctuations in this picture. We then compute elliptic and triangular flow fluctuations and study their connections to the ridge. © 2012 American Physical Society.


Noronha-Hostler J.,University of Sao Paulo | Greiner C.,Goethe University Frankfurt
Nuclear Physics A | Year: 2014

Thermal fits have consistently reproduced the experimental particle yields of heavy ion collisions, however, the proton to pion ratio from ALICE Pb. +. Pb sNN=2.76 TeV is over-predicted by thermal models - known as the p/π puzzle. Here we test the relevance of the extended mass spectrum, i.e., include Hagedorn states (resonances that follow an exponential mass spectrum and have very short life times) on the p/π puzzle. We find that the extended mass spectrum is able to reproduce particle ratios at both RHIC and the LHC as well as is able to match the lower p/π ratio at the LHC through dynamical chemical equilibration. © 2014 Elsevier B.V.


Gavin S.,Wayne State University | Moschelli G.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2012

Correlation measurements imply that anisotropic flow in nuclear collisions includes an interesting triangular component along with the more familiar elliptic-flow contribution. Triangular flow has been attributed to eventwise fluctuations in the initial shape of the collision volume. The following two questions are asked. First, how do these shape fluctuations impact other event-by-event observables? Second, can fundamental information on the early time fluctuations be disentangled from the complex flow that results? Correlation and fluctuation observables are studied in a framework in which flux tubes in an early Glasma stage later produce hydrodynamic flow. The calculated collision-energy dependence of multiplicity and transverse momentum fluctuations is in good accord with data from 62.4 GeV Au + Au up to 2.76 TeV Pb + Pb. © 2012 American Physical Society.


Pawlotsky J.-M.,University Paris Est Creteil | Pawlotsky J.-M.,French Institute of Health and Medical Research | Feld J.J.,University of Toronto | Zeuzem S.,Goethe University Frankfurt | Hoofnagle J.H.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases
Journal of Hepatology | Year: 2015

The hepatitis C virus (HCV) was discovered in the late 1980s. Interferon (IFN)-α was proposed as an antiviral treatment for chronic hepatitis C at about the same time. Successive improvements in IFN-α-based therapy (dose finding, pegylation, addition of ribavirin) increased the rates of sustained virologic response, i.e. The rates of curing HCV infection. These rates were further improved by adding the first available direct-acting antiviral (DAA) drugs to the combination of pegylated IFN-α and ribavirin. An IFN-free era finally started in 2014, yielding rates of sustained virologic response over 90% in patients treated for 8 to 24 weeks with all-oral regimens. Major challenges however remain in implementation of these new treatment strategies, not only in low- to middle-income countries, but also in high-income countries where the price of these therapies is still prohibitive. Elimination of HCV infection through treatment in certain areas is possible but raises major public health issues. © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Tamura H.,Tohoku University | Burghardt I.,Goethe University Frankfurt
Journal of the American Chemical Society | Year: 2013

In organic photovoltaics, the mechanism by which free electrons and holes are generated, overcoming the Coulomb attraction, is a currently much debated topic. To elucidate this mechanism at a molecular level, we carried out a combined electronic structure and quantum dynamical analysis that captures the elementary events from the exciton dissociation to the free carrier generation at polymer/fullerene donor/acceptor heterojunctions. Our calculations show that experimentally observed efficient charge separations can be explained by a combination of two effects: First, the delocalization of charges which substantially reduces the Coulomb barrier, and second, the vibronically hot nature of the charge-transfer state which promotes charge dissociation beyond the barrier. These effects facilitate an ultrafast charge separation even at low-band-offset heterojunctions. © 2013 American Chemical Society.


Yurugi H.,Kyoto Sangyo University | Rajalingam K.,Goethe University Frankfurt
Science Signaling | Year: 2013

Prohibitin 1 (PHB1) and PHB2 are evolutionarily conserved, ubiquitously expressed, pleotropic proteins that control various fundamental cellular processes, including proliferation, migration, metabolism, and death. Studies have unveiled a crucial role for plasma membrane-associated PHBs in regulating tumor metastasis, viral entry, and immune cell activation. A study now identifi es a role for PHB1 in the activation of mast cells and allergic reactions mediated by immunoglobulin E (IgE). PHB1 was primarily localized in mast cell granules; however, in response to stimulation with antigen, PHB1 translocated to plasma membrane lipid rafts to form a ternary complex with the high-affi nity IgE receptor FcεRIγ and the nonreceptor tyrosine kinase Syk. Syk became activated, which led to the activation of downstream signaling that stimulated mast cell degranulation and the secretion of cytokines. PHB1 was phosphorylated by the Src family tyrosine kinase Lyn, and palmitoylation of PHB1 was required for its association with the plasma membrane. These observations unveil a previously uncharacterized facet of prohibitin biology and shed further light on the proximal events that drive the activation of FceRI by IgE in mast cells during allergic reactions. Copyright © 2008 by the American Association for the Advancement of Science.


Nuclear magnetic resonance (NMR) spectroscopy is a key technology for research in the modern Life Sciences, with an increasing impact on human health. This technology is unique in new areas of molecular systems biology providing detailed insight into protein-protein and protein-ligand interactions. NMR Research Infrastructures (RIs) are of primary importance here; they offer the resources necessary to conduct cutting-edge research and support a knowledge base among a broad group of European users. Europe has traditionally enjoyed a leadership role in NMR; to maintain this position in the face of increasing international competition, scientific and technological capabilities throughout the EU must be fully exploited. This requires the full mobilization of all European countries, including Eastern Europe, where NMR applications are sparse and tackling challenging scientific projects is less common. As a consequence, human resources are underused. Emerging technological and research frontiers must also continue to be addressed. The EAST-NMR project responds to the new challenges facing NMR and its RIs, based on the I3 model. The project will (i) provide transnational access to NMR instrumentation based in Eastern Europe by taking advantage of the experiences of another on-going European project (EU-NMR) and will provide access to solid-state NMR facilities, an emerging technology at the international level; (ii) educate and train researchers in NMRs potential and use, with special care for Eastern Europeans, and (iii) advance in sample preparation technologies especially of difficult to tackle membrane proteins through joint research activities. The project will impact research throughout the Life Sciences and pan-European potential for excellence in competitive sectors such as pharmaceuticals and biotechnology.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-1 | Award Amount: 8.30M | Year: 2012

This project is focused on the clinical development of a new orphan drug that can rapidly become a new treatment option for patients with the X-linked form of chronic granulomatous disease (X-CGD). This rare primary immune deficiency of phagocytes is caused by mutations in the gp91phox gene. Affected patients are highly-susceptible to infections and develop inflammatory granulomas. Several members of the Net4CGD consortium have already attempted hematopoietic gene correction of X-CGD using gp91 gammaretroviral gene transfer vectors. While functional correction and clinical benefit was initially achieved, problems arose, linked to insertional mutagenesis, vector silencing and lack of long-term engraftment. Net4CGD proposes future trials to achieve (i) effective transduction of hematopoietic cells, (ii) physiological expression of the transgene and (iii) long-term engraftment of gene modified cells. A new lentiviral vector (LV) was developed to express gp91phox in myeloid cells. Encouraging results obtained in preclinical studies and through the compassionate treatment of a patient, prompt us to test the LV in a multi-center study in several European centers expert in CGD, under the sponsorship of a rare disease specialist. The tasks include i) Manufacturing clinical grade vector to support clinical studies, ii) Conducting a multi-center phase I/II trial in eligible X-CGD patients, with LV gene-modified autologous hematopoietic stem cells to evaluate the safety and efficacy of the procedure iii) Ensuring high-quality and harmonization of products and procedures to facilitate future product registration iv) Obtaining state-of-the art information on biological efficacy and safety in patients by assessing immune restoration and large-scale integrome data. If positive, this study will be used to register the orphan drug. The treatment is expected to improve patients quality of life and will reduce the economical burden of CGD. Results should benefit other RD.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: HEALTH-2007-3.4-1;HEALTH-2007-3.4-3 | Award Amount: 962.24K | Year: 2009

European Centres of Expertise Networks for rare diseases have been identified by the European Commission as one important area of future activity in the attempt of achieving one of the main objectives across the EC endeavour of Optimising the delivery of health care to European Citizens. It is obvious that especially in rare diseases the joined forces of the experts networking throughout Europe are more likely than national services to meet the needs and expectations of patients. The construction and implementation of European networks of centres of expertise (ENCE) call for input from many different stakeholders: patients and doctors and other care team members, clinical researchers, health administration, and health insurers will have to be heard to come to a model of such networks that can easily be used as blueprint for most of the rare disorders. To achieve this goal first a mapping exercise of existing networks and elements needed for such networking has to be done. We plan to do so for three different rare entities, i.e. cystic fibrosis (CF), pulmonary lymphangioleiomyomatosis (LAM), and lung transplantation (LTX), having in common that they all comply with the EC definition of a rare disease. From the information gathered during this process the areas of activity and a detailed set of criteria for such European networks will be developed. These construction principles will be brought together in a blueprint to be used for other rare disorders. These criteria can then be used for certification, quality control, and funding of a European system of networks. Networking in this European sense will make the best possible use of resources already existing and remaining in the responsibility of the individual member states by interfacing and complementing these present and future elements. This will help the health care system partners to learn from the best and improve the quality of care to the best European level of expertise.


News Article | November 15, 2016
Site: www.sciencedaily.com

Translation of the genetic code in proteins is a central process in life and takes place in the ribosome, a giant molecule consisting of two subunits. This is where long chains of amino acids are formed like on an assembly line. An interdisciplinary research group from Goethe University Frankfurt, the EMBL in Heidelberg, and the Gene Center of the University of Munich (LMU) has now succeeded in solving the structure of a central player in this process bound to the small ribosomal subunit: the protein containing a unique iron-sulphur domain with the nickname "Iron Hammer" splits the two subunits of the ribosome when a protein chain is completed so that production of a new protein can begin. The two subunits of the ribosome have to be actively split once the protein chain is complete otherwise errors occur in mRNA translation: research ignored this fact for a long time. Central player in this "ribosome recycling" process is the essential and highly dynamic metalloenzyme ABCE1. The iron-sulphur domain of ABCE1, known as the "Iron Hammer," rotates and presses the ribosomal subunits apart like a lever. To uncover this, the research group led by Professor Robert Tampé at the Institute of Biochemistry at Goethe University Frankfurt isolated a complex of the small ribosomal subunit with ABCE1 (post-splitting complex) by means of an innovative preparation method. This complex was chemically fixed and cut into pieces, while the original distance information was preserved. At the EMBL in Heidelberg, the researchers used highly advanced mass spectrometry to analyse these small fragments and relate them to each other revealing their original distances on nanometre scale. The group in Munich then examined the reconstructed complex with a high-resolution cryogenic electron microscope and was able to reconstruct a 3D model of the post-splitting complex with tightly bound ABCE1 from a vast collection of single-particle images. Professor Robert Tampé summarizes the significance of these results: "We have forced the rebellious and aggressive multi-domain enzyme ABCE1 into a new, unexpected state on the ribosome and used the combined expertise of three institutes to enrich textbook knowledge for coming generations of students."


News Article | November 15, 2016
Site: phys.org

Translation of the genetic code in proteins is a central process in life and takes place in the ribosome, a giant molecule consisting of two subunits. This is where long chains of amino acids are formed like on an assembly line. An interdisciplinary research group from Goethe University Frankfurt, the EMBL in Heidelberg, and the Gene Center of the University of Munich (LMU) has now succeeded in solving the structure of a central player in this process bound to the small ribosomal subunit: the protein containing a unique iron-sulphur domain with the nickname "Iron Hammer" splits the two subunits of the ribosome when a protein chain is completed so that production of a new protein can begin. The two subunits of the ribosome have to be actively split once the protein chain is complete otherwise errors occur in mRNA translation: research ignored this fact for a long time. Central player in this "ribosome recycling" process is the essential and highly dynamic metalloenzyme ABCE1. The iron-sulphur domain of ABCE1, known as the "Iron Hammer", rotates and presses the ribosomal subunits apart like a lever. To uncover this, the research group led by Professor Robert Tampé at the Institute of Biochemistry at Goethe University Frankfurt isolated a complex of the small ribosomal subunit with ABCE1 (post-splitting complex) by means of an innovative preparation method. This complex was chemically fixed and cut into pieces, while the original distance information was preserved. At the EMBL in Heidelberg, the researchers used highly advanced mass spectrometry to analyse these small fragments and relate them to each other revealing their original distances on nanometre scale. The group in Munich then examined the reconstructed complex with a high-resolution cryogenic electron microscope and was able to reconstruct a 3D model of the post-splitting complex with tightly bound ABCE1 from a vast collection of single-particle images. Professor Robert Tampé summarizes the significance of these results: "We have forced the rebellious and aggressive multi-domain enzyme ABCE1 into a new, unexpected state on the ribosome and used the combined expertise of three institutes to enrich textbook knowledge for coming generations of students." Explore further: Biochemists gain new insights into biogenesis of ribosomes More information: Kristin Kiosze-Becker et al, Structure of the ribosome post-recycling complex probed by chemical cross-linking and mass spectrometry, Nature Communications (2016). DOI: 10.1038/NCOMMS13248


Worldwide, Salmonella is responsible for millions of infections and thousands of deaths every year. When Salmonella enters a human cell under certain conditions, a process called xenophagy may target the bacterium for destruction. Understanding how cells defend against Salmonella is essential to develop new treatments, but xenophagy is not yet well-understood. In the new study, "wet lab" scientist Ivan Dikic and the bioinformatics team of Ina Koch at Goethe University Frankfurt used existing knowledge of molecular interactions, combined with a computer science technique called Petri nets, to build a mathematical model of xenophagy. To test the model, the researchers investigated what would happen when several proteins in the xenophagy process were virtually perturbed—a technique known as in silico knockout. The results of this computer-based perturbation were consistent with data from lab experiments in which the same proteins were perturbed, confirming that the model accurately reproduces known parts of the xenophagy process. The scientists also proposed a potential new mechanism for one of the proteins involved in the xenophagy process. This and other hypotheses suggested by further in silico knockout investigations could be tested in lab experiments. "The in silico knockouts formulate hypotheses for future experimental studies towards a better understanding of the cellular antibacterial defense and towards a better treatment of illnesses caused by Salmonella infection," says study first author Jennifer Scheidel. Explore further: New chemistry of life: Novel ubiquitination mechanism explains pathogenic effects of Legionella infection More information: Scheidel J, Amstein L, Ackermann J, Dikic I, Koch I (2016) In Silico Knockout Studies of Xenophagic Capturing of Salmonella. PLoS Comput Biol 12(12): e1005200. DOI: 10.1371/journal.pcbi.1005200


Radmark O.,Karolinska Institutet | Werz O.,Friedrich - Schiller University of Jena | Steinhilber D.,Goethe University Frankfurt | Samuelsson B.,Karolinska Institutet
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2015

5-Lipoxygenase (5-LOX) catalyzes two steps in the biosynthesis of leukotrienes (LTs), lipid mediators of inflammation derived from arachidonic acid. In this review we focus on 5-LOX biochemistry including 5-LOX interacting proteins and regulation of enzyme activity. LTs function in normal host defense, and have roles in many disease states where acute or chronic inflammation is part of the pathophysiology, as briefly summarized at the end of this chapter. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance. © 2014 Elsevier B.V.All rights reserved.


Diener H.-C.,University of Duisburg - Essen | Foerch C.,Goethe University Frankfurt | Riess H.,University Medicine Berlin | Rother J.,Stroke Unit and Intensive Care Unit | And 3 more authors.
The Lancet Neurology | Year: 2013

Systemic thrombolysis with alteplase is the only approved medical treatment for patients with acute ischaemic stroke. Thrombectomy is also increasingly used to treat proximal occlusions of the cerebral arteries, but has not shown superiority over systemic thrombolysis with alteplase. Many patients with acute ischaemic stroke are pretreated with antiplatelet or anticoagulant drugs, which can increase the bleeding risk of thrombolysis or thrombectomy. Pretreatment with aspirin monotherapy increases the bleeding risk of alteplase in both observational and randomised trials with no effect on clinical outcome, and the risk of intracerebral haemorrhage is increased with the combination of aspirin and clopidogrel. Antiplatelet drugs should not be given in the first 24 h after alteplase treatment. Data from pooled randomised trials and a large observational study show that thrombolysis can probably be done safely in patients given vitamin-K antagonists if the international normalised ratio is less than 1·7, although bleeding risk is slightly raised. Almost no data are available for the safety of alteplase in patients with atrial fibrillation who have been given novel oral anticoagulants (NOAC) for stroke prevention. Some coagulation parameters could help to identify patients treated with NOAC who might be eligible for thrombolysis. Thrombectomy can be done in patients given antiplatelets and probably in those given anticoagulants; however, conclusions about anticoagulants are based on findings from observational studies with small patient numbers. © 2013 Elsevier Ltd.


Maltezou H.C.,U.S. Center for Disease Control and Prevention | Wicker S.,Goethe University Frankfurt
American Journal of Infection Control | Year: 2013

Despite the availability of an effective and safe vaccine for almost half a century, measles is re-emerging in several developed countries because of the insufficient vaccination coverage among specific subpopulations, the emerging anti-vaccination movement, and the increasing movement of humans across borders. In this context, health-care settings play a critical role in the transmission of infection and generation of numerous cases. Health-care-associated outbreaks may be associated with severe morbidity and mortality among specific groups of patients, disruption of health-care services, and considerable costs. Misdiagnosis or delayed diagnosis of a measles case and inadequate implementation of infection control measures are common in almost all events of nosocomial spread. Measles vaccination of health-care workers is an effective means of prevention of nosocomial measles outbreaks. Eliminating measles by 2010 has not been accomplished. Stronger recommendations and higher vaccination coverage against measles in health-care workers could contribute to eliminate measles in the general population. Copyright © 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.


Teschke R.,Goethe University Frankfurt | Wolff A.,Friedrich - Schiller University of Jena | Frenzel C.,University of Hamburg | Schulze J.,Goethe University Frankfurt
Alimentary Pharmacology and Therapeutics | Year: 2014

Background Although evidence for their therapeutic efficacy is limited, herbal traditional Chinese medicine (TCM) preparations increasingly gain popularity. In contrast to other herbal products, adverse effects by herbal TCM including liver toxicity were rarely reported. In recent years, more cases were published, providing new clinical challenges. Aim To summarise comprehensively the literature on herbal TCM hepatotoxicity since 2011. Methods PubMed was searched using key words related to TCM, the results were restricted to full English-language publications and abstracts published since 2011. In addition, the database of the National Institutes of Health (NIH) and LiverTox was accessed under the topic 'Drug record: Chinese and other Asian herbal medicines'. Results Since 2011, new case reports and case series provided evidence for herbal hepatotoxicity by TCM, focusing on nine TCM herbal mixtures and four individual TCM herbs with potential health hazards. These were the TCM products Ban Tu Wan, Chai Hu, Du Huo, Huang Qin, Jia Wei Xia Yao San, Jiguja, Kamishoyosan, Long Dan Xie Gan Tang, Lu Cha, Polygonum multiflorum products, Shan Chi, 'White flood' containing the herbal TCM Wu Zhu Yu and Qian Ceng Ta, and Xiao Chai Hu Tang. Other developments include the establishment of a new and early diagnostic serum marker for hepatotoxicity caused by pyrrolizidine alkaloids, assessed using ultra performance liquid chromatography-mass spectrometry analysis, and new regulatory details to improve herbal TCM product quality and safety. Conclusion Stringent evaluation of the risk/benefit ratio is essential to protect traditional Chinese medicines users from health hazards including liver injury. © 2014 John Wiley & Sons Ltd.


Szklarczyk R.,Maastricht University | Nooteboom M.,Radboud University Nijmegen | Osiewacz H.D.,Goethe University Frankfurt
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2014

Various molecular and cellular pathways are active in eukaryotes to control the quality and integrity of mitochondria. These pathways are involved in keeping a 'healthy' population of this essential organelle during the lifetime of the organism. Quality control (QC) systems counteract processes that lead to organellar dysfunction manifesting as degenerative diseases and ageing. We discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA repair and reorganization, regeneration of oxidized amino acids, refolding and degradation of severely damaged proteins, degradation of whole mitochondria by mitophagy and finally programmed cell death. The control of the integrity of mtDNA and regulation of its expression is essential to remodel single proteins as well as mitochondrial complexes that determine mitochondrial functions. The redundancy of components, such as proteases, and the hierarchies of the QC raise questions about crosstalk between systems and their precise regulation. The understanding of the underlying mechanisms on the genomic, proteomic, organellar and cellular levels holds the key for the development of interventions for mitochondrial dysfunctions, degenerative processes, ageing and age-related diseases resulting from impairments of mitochondria. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Yalachkov Y.,Goethe University Frankfurt | Naumer M.J.,Maastricht University
Journal of Neurophysiology | Year: 2011

The study of Wagner et al. (J Neurosci 31: 894-898, 2011) reveals the neural correlates of spontaneously activated action representations in smokers when subjects watch movie characters smoke. We stress the importance of differentiating how these representations are activated: while the anterior intraparietal sulcus and inferior frontal gyrus are part of the mirror neuron system of smokers, the middle frontal gyrus, premotor cortex, and superior parietal lobule represent the smokingrelated tool use skills and action knowledge activated by smoking paraphernalia. © 2011 the American Physiological Society.


Nicolini P.,Goethe University Frankfurt | Rinaldi M.,University of Geneva
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

In this Letter we study the radiation measured by an accelerated detector, coupled to a scalar field, in the presence of a fundamental minimal length. The latter is implemented by means of a modified momentum space Green's function. After calibrating the detector, we find that the net flux of field quanta is negligible, and that there is no Planckian spectrum. We discuss possible interpretations of this result, and we comment on experimental implications in heavy ion collisions and atomic systems. © 2010 Elsevier B.V.


Fraga E.S.,Goethe University Frankfurt | Fraga E.S.,Federal University of Rio de Janeiro | Mintz B.W.,State University of Rio de Janeiro | Schaffner-Bielich J.,Goethe University Frankfurt
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

We explore the parameter space of the two-flavor thermal quark-meson model and its Polyakov loop-extended version under the influence of a constant external magnetic field B. We investigate the behavior of the pseudo critical temperature for chiral symmetry breaking taking into account the likely dependence of two parameters on the magnetic field: the Yukawa quark-meson coupling and the parameter T0 of the Polyakov loop potential. Under the constraints that magnetic catalysis is realized at zero temperature and the chiral transition at B = 0 is a crossover, we find that the quark-meson model leads to thermal magnetic catalysis for the whole allowed parameter space, in contrast to the present picture stemming from lattice QCD. © 2014 The Authors.


Poloczek M.,Goethe University Frankfurt | Szegedy M.,Rutgers University
Proceedings - Annual IEEE Symposium on Foundations of Computer Science, FOCS | Year: 2012

It is a long-standing problem to lower bound the performance of randomized greedy algorithms for maximum matching. Aronson, Dyer, Frieze and Suen studied the modified randomized greedy (MRG) algorithm and proved that it approximates the maximum matching within a factor of at least 1/2 + 1/400,000. They use heavy combinatorial methods in their analysis. We introduce a new technique we call Contrast Analysis, and show a 1/2 + 1/256 performance lower bound for the MRG algorithm. The technique seems to be useful not only for the MRG, but also for other related algorithms. © 2012 IEEE.


He L.,Goethe University Frankfurt | Huang X.-G.,Indiana University Bloomington
Annals of Physics | Year: 2013

We present a theoretical study of the superfluidity and the corresponding collective modes in two-component atomic Fermi gases with s-wave attraction and synthetic Rashba spin-orbit coupling. The general effective action for the collective modes is derived from the functional path integral formalism. By tuning the spin-orbit coupling from weak to strong, the system undergoes a crossover from an ordinary BCS/BEC superfluid to a Bose-Einstein condensate of rashbons. We show that the properties of the superfluid density and the Anderson-Bogoliubov mode manifest this crossover. At large spin-orbit coupling, the superfluid density and the sound velocity become independent of the strength of the s-wave attraction. The two-body interaction among the rashbons is also determined. When a Zeeman field is turned on, the system undergoes quantum phase transitions to some exotic superfluid phases which are topologically nontrivial. For the two-dimensional system, the nonanalyticities of the thermodynamic functions and the sound velocity across the phase transition are related to the bulk gapless fermionic excitation which causes infrared singularities. The superfluid density and the sound velocity behave nonmonotonically: they are suppressed by the Zeeman field in the normal superfluid phase, but get enhanced in the topological superfluid phase. The three-dimensional system is also studied. © 2013 Elsevier Inc.


Furstenberg A.,University of Geneva | Heilemann M.,Goethe University Frankfurt
Physical Chemistry Chemical Physics | Year: 2013

Fluorescence imaging beyond the diffraction limit has grown into a method of choice to elucidate questions related to biological structure and organisation. Among super-resolution techniques, imaging based on the localization of individual photoswitchable fluorescent probes has become particularly popular due to its relative ease of implementation and the nature of qualitative and quantitative answers it can offer. We review the field of single-molecule localization microscopy (SMLM) by providing an overview of its underlying principles and of different categories of photoswitchable fluorophores. In addition to summarizing target-specific labelling strategies and presenting examples of successful applications of SMLM in fixed and living systems, we show how SMLM data offer unique opportunities for quantitative biomolecular counting and distribution analysis. © the Owner Societies 2013.


Hansel R.,Goethe University Frankfurt | Lohr F.,Goethe University Frankfurt | Trantirek L.,University Utrecht | Trantirek L.,Masaryk University | Dotsch V.,Goethe University Frankfurt
Journal of the American Chemical Society | Year: 2013

NMR and fluorescence spectroscopy were used to address the effect of intracellular molecular crowding and related hydration on a model telomeric G-quadruplex (G4) DNA structure (d(AG3(TTAGGG)3)). d(AG3(TTAGGG)3) prevalently adopted the hybrid-1 conformation in vivo, ex vivo, and in dilute potassium-based solution, while it formed the parallel propeller fold in water-depleted potassium-based solution, a commonly used model system for studying intracellular molecular crowding. The dilute potassium-based solution appeared to imitate the properties of the cellular environment required for d(AG3(TTAGGG)3) folding under in vivo and ex vivo conditions. High-resolution NMR investigations of site-specifically 15N-labeled G4 units in native-like single-stranded telomeric DNA revealed that the 3′-terminal and internal G4 unit predominantly coexist in 2-tetrad antiparallel basket and hybrid-2 structures that are arranged in "beads-on-a-string"-like fashion. Our data provide the first high-resolution insight into the telomeric G-overhang architecture under essentially physiological conditions and identify the 2-tetrad antiparallel basket and hybrid-2 topologies as the structural targets for the development of telomere-specific G4 ligands. © 2013 American Chemical Society.


Huck P.,Central China Normal University | Huck P.,Goethe University Frankfurt | Huck P.,Lawrence Berkeley National Laboratory
Nuclear Physics A | Year: 2014

We present the energy-dependent study of dielectron production in 0-80% minimum-bias Au+Au collisions at √sNN of 19.6, 27, 39, and 62.4 GeV in STAR. Invariant mass (Mee) and transverse momentum (pT) differential measurements of dielectron yields are compared to cocktail simulations of known hadronic sources and semi-leptonic charmed decays. The enhancement (excess yield) prominent in the Low-Mass Region (LMR) over the cocktail at all energies, is further compared to calculations of ρ in-medium modifications. Within statistical and systematic uncertainties, we find that the model consistently describes this enhancement from SPS up to top RHIC energies in its Mee- as well as pT-dependence. Dielectron measurements drive the statistics for the future BES Phase-II program, which promises to improve our understanding of the LMR enhancement's trend with total baryon densities. © 2014 Elsevier B.V.


Frassino A.M.,Goethe University Frankfurt | Panella O.,National Institute of Nuclear Physics, Italy
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We study the corrections to the Casimir effect in the classical geometry of two parallel metallic plates, separated by a distance a, due to the presence of a minimal length (√β) arising from quantum mechanical models based on a generalized uncertainty principle (GUP). The approach for the quantization of the electromagnetic field is based on projecting onto the maximally localized states of a few specific GUP models and was previously developed to study the Casimir-Polder effect. For each model we compute the lowest order correction in the minimal length to the Casimir energy and find that it scales with the fifth power of the distance between the plates a -5 as opposed to the well known QED result which scales as a -3 and, contrary to previous claims, we find that it is always attractive. The various GUP models can be in principle differentiated by the strength of the correction to the Casimir energy as every model is characterized by a specific multiplicative numerical constant. © 2012 American Physical Society.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.4.2-2 | Award Amount: 16.03M | Year: 2009

Arrhythmias are common manifestations of heart disease which frequently cause sudden cardiac death (SCD) or other devastating health problems. In Europe, prevention of SCD by device and drug therapy is expensive and increasingly strains public health resources due to a growing population at risk. However, identification of patients at increased risk for SCD is ineffective, and SCD prevention strategies are not directed at the underlying risk mechanisms. To address this challenging situation, new insights into genetic and environmental modulators of SCD risk, arrhythmia initiating mechanisms (Triggers) and therapeutic strategies (Treatments) are urgently needed. The EUTrigTreat consortium proposes a translational project strategy based on interactive objectives (modules). Module 1 investigates novel genetic arrhythmia mechanisms in patients and is supported by Module 2 which investigates genetic and environmental SCD risk modulators in animals with arrhythmias. Module 3 elucidates common environmental arrhythmia risk mediators including obesity and diabetes. Module 4 applies molecular and biophysical imaging techniques to identify novel risk biomarkers. Module 5 translates experimental data through computer modeling and prediction analysis. Modules 6 develops new SCD risk identification strategies through combined patient and experimental studies. Module 7 develops and validates novel therapeutic drug compounds and a new form of anti-arrhythmic device therapy. The pre-clinical and clinical activities will potentially result in patents of diagnostic and therapeutic applications, licensing strategies, early clinical trials and a spin-off company. Module 8 manages, advises and reviews the project progress of EUTrigTreat. Ultimately, we aim to better understand and educate about arrhythmia initiating mechanisms and associated risk biomarkers. Such knowledge will provide strong rationales towards improved prevention and treatment of patients at risk for SCD.


Grant
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: REFLECTIVE-8-2015 | Award Amount: 979.44K | Year: 2016

Dandelion will promote the work done by inclusive, innovative and reflective societies projects on a local, regional and European level by developing and implementing a series of innovative and exciting communications activities aiming to inform, educate and entertain a wide cross section of the European population, policy makers, academics and media. By placing European economic and financial reform, the problems young people face in Europe, cultural heritage, European values and diversities, the EUs role as a global actor and the new forms of public sector innovation at the heart of these activities, by involving established science educators, by creating clear lines of communication between projects and named mass media and by utilising novel communications, Dandelion will ensure that inclusive, innovative and reflective societies ambitious philosophy is given the highest profile. By giving tools and guidelines to the dissemination managers towards general public, policy makers, academia and media Dandelion will guarantee an improved access to research projects data in the future.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-SICA | Phase: HEALTH-2007-2.3.4-3 | Award Amount: 3.40M | Year: 2009

The majority of compounds used to treat diseases come from a single group of organisms, the actinomycetes. This over-reliance on a single organism to produce the worlds drugs is a major problem for the development of compounds with alternative modes of action which can overcome and delay the onset of drug resistance. To address this problem we will form an international multi-disciplinary group of experts to bioprospect for biologically active natural products. The central aim of this programme is to start rapidly deriving novel drugs from non-actinomycete sources. We will isolate novel strains of the proven but not well-explored drug producers Xenorhabdus and Photorhabdus. These bacteria will be isolated from insect pathogenic nematodes and characterized taxonomically (WP1) and strains will be analyzed for the production of novel compounds (WP2). This library of compounds will then be tested against a broad set of targets including bacteria, fungi, protozoans, nematodes, insects, and mammalian cell cultures (WP3). The five most productive bacterial strains will then be fully sequenced and used to construct genomic libraries. These libraries will be used to generate recombinant clones in heterologous hosts, enabling fast and efficient biotechnological production of the bioactive compounds (WP4). To ensure efficient interactions and comparability of results, especially regarding the bioactivity data, training sessions will be organized with seminars and hands on experience for each of the groups at a central site (WP5). Robust patent stuctures will ensure efficient technology transfer to our industrial partners (WP6) and overall coordination of the scientific and training programs will be overseen by WP7.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: Fission-2010-4.2.1 | Award Amount: 1.11M | Year: 2010

Different concepts involving critical (fast) reactors or subcritical accelerator-driven systems are being studied in view of their transmutation capabilities. These design studies imply high demands on the underlying nuclear database. The need for improved nuclear data has been expressed in the Strategic Research Agenda of the SNE-TP ( Sustainable Nuclear Energy Technology Platform). The accurate knowledge of neutron and proton induced nuclear reactions in the fast, intermediate- and high- energy domains (En = 1keV to 500 MeV) is of crucial importance for predicting the capabilities of reducing the inventory of plutonium, minor actinides, and long-lived fission products. In the past, this energy domain was not investigated with high priority because of minor importance for conventional light-water reactors. An additional challenge is the tightening demand on the accuracy of the data, especially for assessing criticality safety aspects and designing fuels for very high burn-up. The ERINDA project aims for a coordination of European efforts to exploit up-to-date neutron beam technology for novel research on advanced concepts for nuclear fission reactors and the transmutation of radioactive waste. Such waste is already existing in appreciable quantity due to the year-long operation of existing nuclear reactors and it will eventually also be generated during the running of new reactor types albeit they can be optimized to produce much less of it. Research to the aim of finding techniques optimized for a strong reduction of nuclear waste can already be performed at existing nuclear facilities from the consortium proposed in this proposal. The main objective is to provide adequate transnational access to the infrastructures. The consortium will also provide funding for scientific support of experiments by short term visits of scientist to the participating facilities and foster the communication and disseminaton of the results by organising scientific workshops.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-EJD | Phase: MSCA-ITN-2015-EJD | Award Amount: 2.57M | Year: 2015

It has long been realised that metabolism is central to cellular development, proliferation and homeostasis. Collectively, aberrations in metabolism are now recognised as a major hallmark of cancer, opening new avenues for personalised medicine. As haematological malignancies are multi-factorial diseases, our main emphasis will be on the integration of biomedical multi-omics data and computational systems modelling with the ultimate aim to understand metabolic regulation in haematological cancers. HaemMetabolism is design to unravel the regulatory mechanisms that link cell cycle control and metabolism. For this we will screen a panel of haematological cancer cell lines for the metabolic phenotypes and against a library of inhibitors. Gene-function analyses will be performed using shRNA libraries directed against key metabolome regulators. Validation will occur in primary patient samples in vitro and in vivo in preclinical humanized niche xenograft mouse models. A systems biomedicine approach will be integrated build genome-scale transcriptional models that explain deregulated metabolic pathways relevant for the development of haematological malignancies. This work will not only open new avenues for drug discovery but will also provide a multi-disciplinary framework for student training in biomedical technologies.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.3.5 | Award Amount: 4.10M | Year: 2008

This proposal focuses on the development of an application-specific component that works in the Terahertz (THz) regime; in this context, we propose to realize a THz source with innovative features specific for monitoring systems for safety and security. Until now the use of THz monitoring system has been strongly limited due to the very low power and the large dimensions of the existing sources in the THz.The OPTHER project aims at solving this limitation with a breakthrough with respect to all the other solutions up to know available in Europe, U.S. and Asia. We plan to use available optical THz sources (such as Quantum Cascade Lasers (QCL) or photomixing systems) and boost their performances by designing and fabricating compact, efficient and reliable novel vacuum THz amplifier.\nThe breakthrough of this proposal is the enhancement of the performance of THz optical source by using vacuum THz amplifiers purposely designed and integrated with the optical driver. The novel THz amplifier will be based on field emitting carbon nanotubes (CNT) used as cold cathodes. Two alternative schemes will be employed for amplification.\n- In the first one (THz drive signal amplifier) the continuous wave electron beam emitted by the CNT cathode is modulated by the electric field in the interaction structure driven by a THz signal\n- In the second one (optically modulated beam THz amplifier) the emission of current is driven by the THz signal. With this second scheme the delivery of high power output should be facilitated.\nThe source output signal will be fully characterized using commercial broadband detectors such as Schottky diodes or bolometers. The composition of the consortium has been carefully arranged for including all the expertise necessary for a successful conclusion of the research activity. In fact, the present consortium is composed by 6 partners, with complementary research expertise and background: two universities, a research institute and three industries


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENV.2011.3.1.9-1 | Award Amount: 2.56M | Year: 2012

Human activities are associated with increasing amounts of waste that ultimately find their ways into European waters and have negative consequences on the environment. With the background of an aging population and increasing urbanization, wastewater treatment must specifically target pharmaceutical products (PPs) and endocrine disrupting chemicals (EDCs) so that these highly biologically-active compounds are eliminated from the water resource. If conventional treatment technologies are very efficient on a large number of compounds, some chemicals, such as pharmaceutical residues and endocrine disruptors, are recalcitrant and are not removed. The chronic exposure to these compounds is a topic of threat as the long term effects are so far unpredictable and undocumented. This issue has recently drawn the interest of many medical professionals, eco-toxicologists and environmental and health agencies. The global objective of the ENDETECH program is to develop a technology which aims at eliminating persistent pharmaceutical pollutants in wastewaters originating from drug manufacturing sites, households, hospitals and animal farms, thanks to an innovative ENzymatic DEcontamination TECHnology. The pharmaceutical pollutants targeted in priority during this project will be antibiotics, hormones and endocrine disruptors. The ENDETECH program is articulated around three main steps: (1) enzyme libraries will be screened to identify novel enzymes able to inactivate the selected pollutants; (2) the discovered enzymes will be immobilized on beads or membranes and subsequently (3) used in bioreactors to decontaminate waste effluents. The ENDETECH consortium includes all the needed and complementary skills for the project in the fields of enzyme screening, optimization and immobilization, bioreactor development & design and chemical & eco-toxicological analysis. The ENDETECH network is composed of 3 SMEs and 3 RTD organizations.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2009-IRSES | Award Amount: 439.20K | Year: 2010

and institutions specialised in all aspects of NMR spectroscopy in Europe with newly developed laboratories in five other countries. It builds on EU-funded infrastructures and will enable the creation of strategic and sustainable links with nine Partners from countries outside Europe. In return Third Country Partners will gain access to highly sophisticated NMR equipment. NMR spectroscopy is a broadly applicable technology relevant to all aspects of Life Science research, with major influence and impact on the biomedical industries. The specific objectives will be reached through mutually beneficial collaborations: SO1: Increasing awareness of the potential of NMR spectroscopy in essentially all areas of Life Sciences. Mutual advancement of the research portfolio of the Partners involved through global networking, training in advanced technologies and meetings to present cutting edge research projects. SO2: Building joint collaborative projects for liquid-state and solid-state NMR investigations by providing access to NMR instrumentation, focussed on investigations of drug targets such as kinases, phosphatases, metalloproteinases, bromo domains, membrane proteins and their complexes with agonists and antagonists. SO3: Learning and participating in training and application in the field of metabolomics research. Building a world-wide agenda for the role of metabolomics in diagnosis, predictive and individualised medicine supporting human health programmes and in fundamental research in the context of a mechanistic systems biology view to cellular function. This project will support and reinforce the collaborative interactions amongst the participants and help to establish long-term research co-operation. Most importantly, WW-NMR will enable Europe to lead the agenda for future NMR activities on an international platform.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: REGIONS-2012-2013-1 | Award Amount: 1.89M | Year: 2013

Data centres are the cornerstones which underpin the digital economy, and create the essential environment for both business and employment to flourish. It is becoming urgent for established data centre states to contribute to R&D, share and develop skills, define standards and promote strategies for network investment. All of these activities will lead to increased trust of new technology such as cloud computing and encourage collaboration and interoperability. EU states with a less established data centre industry and footprint, but with a need for it to grow can benefit greatly from the knowledge transfer, insight, experience and raised profile. Initial research and workshops held between industry leaders and academic institutions within UK, The Netherlands and Germany has confirmed that Europe would benefit greatly from the creation of a Pan-European Data Centre Research and Development Academy. Most data centre related standards, guidelines and research comes from the USA which often causes a confusing mix of conflicting information with little relevance to Europe. Therefore, many new innovations that promote energy efficiency and general improvements are misinterpreted, not taken up or developed. This is due to a perceived risk factor due to lack of testing, validation and education. The vision, which is shared by the vast majority of the data centre sector, is to build upon existing collaboration within the data centre industry via the DCA. The foundations of such a initiative and broad agreement has already been reached. The proposal is to establish and extend the facility to all European Union states encompassing both higher education and the wider data centre industry. This is in order to meet the challenges laid out within the Europes Digital Agenda.


Grant
Agency: European Commission | Branch: FP7 | Program: | Phase: | Award Amount: 2.77M | Year: 2007

NMR plays an important role in life sciences (bio-NMR), and structural biology in particular, at both European and international levels. An I3 initiative is operative in the field, which provides access to NMR instrumentation and pursues technical advancement (EU-NMR). In addition, the EC has funded a Coordination action (NMR-Life) aimed at the establishment of common experimental approaches and at the spreading of best experimental practices across Europe. Altogether, these two initiatives provide a reference point for the large majority of European scientists with an interest in bio-NMR. In parallel, European developments in the area of Research Infrastructures in the past years resulted in a leading edge high-speed research network covering all Europe and in a overlaying production Grid infrastructure, realized by projects as EGEE/EGEE II. This integrated network and processing/storage environment - e-Infrastructure - provides a platform for new methods of global collaborative research - e-Science. The main objective of this project is to optimise and extend the use of the NMR Research Infrastructures of EU-NMR through the implementation of an e-Infrastructure in order to provide the European bio-NMR user community with a platform integrating and streamlining the computational approaches necessary for bio-NMR data analysis (e-NMR). The e-NMR infrastructure will be based on the Grid infrastructure. The project will also tackle the following objectives: - establish a human collaboration network between the bio-NMR and the e-Infrastructure scientific communities; - assess the state-of-the-art of the computational aspects of bio-NMR; - implement and make available state-of-the-art computational methods. A broad range of networking activities will focus on monitoring, dissemination and outreach, training, hands-on workshops. The development and enforcement of operational and organizational schemes and policies will also be addressed.


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

Data on seawater composition since the start of the Phanerozoic eon ~540 million years ago provide essential information for understanding long-term chemical processes of socio-economic dimension like the evolution of life, land-ocean interaction, atmospheric chemistry, ecosystem adaptation to climate change, oceanic trace metal cycling, and for applied geological processes like the formation of submarine energy resources. Although partly known this knowledge is still limited pending new methodical prospects and innovative analytical techniques. Following this approach, the proposed ETN BASE-LiNE Earth will train early stage researchers (ESRs) who will extend the knowledge of the complex and long-term Phanerozoic seawater history by the determination of original proxy information preserved in reliable ancient geological archives using cutting edge technologies and experimental approaches. In order to amplify this process the ESRs will be exposed to academic and non-academic high-tech institutions linking biogeochemical research and training in biology, ecology, geochemistry as well as chemical analytics to engineering and cutting edge analytical instrumentation. Multi- and interdisciplinary environments will expose our ESRs to highly demanded transferable skills increasing their employability when it comes to job application. BASE-LiNE Earth will offer societally important deliverables like time series of past trace element and isotope cycling and models about ocean material fluxes in and out of the Phanerozoic Ocean. This will be shared in publications, reports and exhibitions. Interactive lecturing material will be offered for education in general and specifically for high school teachers. Through collaboration with high-tech companies the ETN will contribute to establish both, new approaches for the exploration of hydrocarbon reservoirs and innovative and sophisticated analytical instrumentation for trace element and isotope measurements.


A new high resolution method developed by an international team of scientists including Robert Tampé and Ralph Wieneke from Goethe University Frankfurt now allows for the first time precise identification and quantification of interactions of a receptor with two ligands simultaneously. Credit: GU Signalling processes in organisms are governed by specific extracellular and intracellular interactions and involve hundreds of different functionally highly versatile receptors situated in cell membranes. For scientists wishing to understand signalling processes the situation is made more complex by the receptors not only being unevenly distributed and often able to bind more than one ligand but also by the same type of receptor being able to bind a ligand strongly, weakly or not all. New methods that allow precise quantifications of such complex interactions are urgently required. A new high resolution method developed by an international team of scientists including Robert Tampé and Ralph Wieneke from Goethe University Frankfurt now allows for the first time precise identification and quantification of interactions of a receptor with two ligands simultaneously. The new method has been published in the latest edition of the journal Nature Communications. Atomic force microscopy (AFM) is a powerful technique for nanoscale characterization of surfaces. It makes use of a cantilever with an extremely fine tip. Force-distance curve-based atomic force microscopy (FD-based AFM) combines high-resolution imaging and single-molecule force spectroscopy. In studies using biological samples, the AFM tip approaches and retracts from the sample for each pixel. FD-based AFM methods use different coatings of the AFM tip as a toolbox and such methods have made impressive progress in recent years. For the detection of specific binding sites FD-based AFM requires tethering of a ligand to the AFM tip. While contouring protein complexes in a membrane such functionalized AFM tips can then measure the interactions of the tethered ligand to the protein. It had not been possible to image single membrane receptors and simultaneously detect their interactions with more than one ligand, but the new method has overcome this hurdle. For their proof of principle the scientists used the human protease-activated receptor 1 (PAR1), one of the large family of G-protein-coupled membrane receptors. GPCRs mediate most cellular responses to hormones and neurotransmitters, as well as being responsible for vision, olfaction and taste. GPCRs can coexist in different functional states in the cell membrane and can bind various ligands at different strength or affinity. The GPCR PAR1 is activated by the coagulation protease thrombin which triggers signalling cascades to initiate cellular responses that help orchestrate haemostasis, thrombosis, inflammation and possibly also tissue repair. With the aid of their new FD-based AFM method human PAR1 in proteoliposomes could be imaged while simultaneously detecting extracellular and intracellular interactions of PAR1 with two ligands. The surface chemistry and nanoscopic method developed are applicable to a range of biological systems in vitro and in vivo. More information: Moritz Pfreundschuh et al. Identifying and quantifying two ligand-binding sites while imaging native human membrane receptors by AFM, Nature Communications (2015). DOI: 10.1038/ncomms9857


News Article | November 23, 2016
Site: www.eurekalert.org

Frankfurt, 23 November 2016. To date, the bonuses paid out to executive board members in Germany have not been sufficiently linked to long-term corporate success. This is the conclusion reached in the new "Remuneration Report" by consultants PwC in cooperation with Goethe University Frankfurt. Whilst about 60 percent of overall remuneration for Dax and MDax board members is indeed made up of performance-related payments - of which in turn more than half are long-term - most of these payments, which are known as Long Term Incentives (LTIs), are in cash rather than based on share plans. That means: Bonuses are automatically decoupled from business development the moment they are paid out. "When compared at international level, Germany can thus be classed as a special case. In our view, it would be more advantageous if long-term bonuses were awarded in the shape of shares in the respective company and the board members were also bound by means of corresponding clauses actually to keep these securities for a longer period of time, if necessary even beyond their term of office. This would ensure that it is in board members' vested interest really to work towards the company's long-term success", says Remo Schmid, co-author of the report and partner at PwC in Germany responsible for remuneration issues. CEOs earn almost twice as much as their board colleagues For the report, PwC and Goethe University Frankfurt examined remuneration structures in Dax and MDax companies. The analysis shows that developments in executive board remuneration in 2015 differed in comparison to the previous year: On average, a Dax CEO earned € 5.6 million, a plus of a good 3 percent. Other board members earned € 2.9 million, which equates to a minus of 2 percent. CEOs in MDax companies earned € 2.5 million on average, whilst their board colleagues were paid € 1.3 million. In other words: On the Dax, the barometer for blue chip companies, top managers are paid more than twice as much as their counterparts in medium-sized enterprises on the MDax. What's more: The average CEO earns on average almost double the salary of a "normal" board member. According to the analysis, the percentage of women amongst top-level executives is rising at an astoundingly slow pace. At the end of 2015, a good 91 percent of all board positions in Dax companies were still occupied by men - whilst in MDax firms it was even 96 percent. The picture is far better, though still not good, in regulatory bodies: In Dax companies, 26 percent of all supervisory board members were female compared to 18 percent in MDax firms. "In many enterprises, cultural change in this respect would be highly desirable", says Professor Dr. Hans-Joachim Böcking, co-author of the report and professor at Goethe University Frankfurt. Still: "At least as far as the basic salary of executive and supervisory board members is concerned, no gender-specific differences were detected either in Dax or MDax companies", says Böcking. A chairman on the supervisory board of a Dax company received an average total remuneration in 2015 of € 311,000. Deputies earned € 230,000, other supervisory board members € 127,500. Pay scales in MDax firms were far lower. Here companies considered their main overseer to be worth an average of € 183,500, the deputy was paid € 121,500 and the other members received € 75,000. Worth noting: Whilst the fixed remuneration for supervisory board members increased on average by about 12 percent in Dax and MDax companies, variable remuneration is still on the decline: in 2014, four out of ten Dax companies still made some form of variable payment. In 2015 it was only three out of ten.


Home > Press > New nanoscopic tools to study ligand-binding of receptors and quantifying two ligand-binding sites while imaging membrane receptors Abstract: Signalling processes in organisms are governed by specific extracellular and intracellular interactions and involve hundreds of different functionally highly versatile receptors situated in cell membranes. For scientists wishing to understand signalling processes the situation is made more complex by the receptors not only being unevenly distributed and often able to bind more than one ligand but also by the same type of receptor being able to bind a ligand strongly, weakly or not all. New methods that allow precise quantifications of such complex interactions are urgently required. A new high resolution method developed by an international team of scientists including Robert Tampé and Ralph Wieneke from Goethe University Frankfurt now allows for the first time precise identification and quantification of interactions of a receptor with two ligands simultaneously. The new method has been published in the latest edition of the journal Nature Communications. Atomic force microscopy (AFM) is a powerful technique for nanoscale characterization of surfaces. It makes use of a cantilever with an extremely fine tip. Force-distance curve-based atomic force microscopy (FD-based AFM) combines high-resolution imaging and single-molecule force spectroscopy. In studies using biological samples, the AFM tip approaches and retracts from the sample for each pixel. FD-based AFM methods use different coatings of the AFM tip as a toolbox and such methods have made impressive progress in recent years. For the detection of specific binding sites FD-based AFM requires tethering of a ligand to the AFM tip. While contouring protein complexes in a membrane such functionalized AFM tips can then measure the interactions of the tethered ligand to the protein. It had not been possible to image single membrane receptors and simultaneously detect their interactions with more than one ligand, but the new method has overcome this hurdle. For their proof of principle the scientists used the human protease-activated receptor 1 (PAR1), one of the large family of G-protein-coupled membrane receptors. GPCRs mediate most cellular responses to hormones and neurotransmitters, as well as being responsible for vision, olfaction and taste. GPCRs can coexist in different functional states in the cell membrane and can bind various ligands at different strength or affinity. The GPCR PAR1 is activated by the coagulation protease thrombin which triggers signalling cascades to initiate cellular responses that help orchestrate haemostasis, thrombosis, inflammation and possibly also tissue repair. With the aid of their new FD-based AFM method human PAR1 in proteoliposomes could be imaged while simultaneously detecting extracellular and intracellular interactions of PAR1 with two ligands. The surface chemistry and nanoscopic method developed are applicable to a range of biological systems in vitro and in vivo. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article | November 17, 2015
Site: www.nanotech-now.com

Home > Press > New nanoscopic tools to study ligand-binding of receptors Abstract: Signalling processes in organisms are governed by specific extracellular and intracellular interactions and involve hundreds of different functionally highly versatile receptors situated in cell membranes. For scientists wishing to understand signalling processes the situation is made more complex by the receptors not only being unevenly distributed and often able to bind more than one ligand but also by the same type of receptor being able to bind a ligand strongly, weakly or not at all. New methods that allow precise quantifications of such complex interactions are urgently required. A new high resolution method developed by an international team of scientists including Robert Tampé and Ralph Wieneke from Goethe University Frankfurt now allows for the first time precise identification and quantification of interactions of a receptor with two ligands simultaneously. The new method has been published in the latest edition of the journal Nature Communications. Atomic force microscopy (AFM) is a powerful technique for nanoscale characterization of surfaces. It makes use of a cantilever with an extremely fine tip. Force-distance curve-based atomic force microscopy (FD-based AFM) combines high-resolution imaging and single-molecule force spectroscopy. In studies using biological samples, the AFM tip approaches and retracts from the sample for each pixel. FD-based AFM methods use different coatings of the AFM tip as a toolbox and such methods have made impressive progress in recent years. For the detection of specific binding sites FD-based AFM requires tethering of a ligand to the AFM tip. While contouring protein complexes in a membrane such functionalized AFM tips can then measure the interactions of the tethered ligand to the protein. It had not been possible to image single membrane receptors and simultaneously detect their interactions with more than one ligand, but the new method has overcome this hurdle. For their proof of principle the scientists used the human protease-activated receptor 1 (PAR1), one of the large family of G-protein-coupled membrane receptors. GPCRs mediate most cellular responses to hormones and neurotransmitters, as well as being responsible for vision, olfaction and taste. GPCRs can coexist in different functional states in the cell membrane and can bind various ligands at different strength or affinity. The GPCR PAR1 is activated by the coagulation protease thrombin which triggers signalling cascades to initiate cellular responses that help orchestrate haemostasis, thrombosis, inflammation and possibly also tissue repair. With the aid of their new FD-based AFM method human PAR1 in proteoliposomes could be imaged while simultaneously detecting extracellular and intracellular interactions of PAR1 with two ligands. The surface chemistry and nanoscopic method developed are applicable to a range of biological systems in vitro and in vivo. Full bibliographic information Identifying and quantifying two ligand-binding sites while imaging native human membrane receptors by AFM. Pfreundschuh M, Alsteens D, Wieneke R, Zhang C, Coughlin SR, Tampé R, Kobilka BK, Müller DJ. Nat Commun. 2015 Nov 12;6:8857. doi: 10.1038/ncomms9857. About Goethe-Universität Frankfurt am Main The Goethe University is an institution with particularly strong research capabilities based in the European financial metropolis of Frankfurt. It celebrates its 100th year of existence in 2014. The university was founded in 1914 through private means from liberally-orientated citizens of Frankfurt and has devoted itself to fulfilling its motto "Science for the Society" in its research and teaching activity right up to the present day. Many of the founding donors were of Jewish origin. During the last 100 years, the pioneering services offered by the Goethe University have impacted the fields of social, societal and economic sciences, chemistry, quantum physics, neurological research and labour law. On January 1st, 2008, it achieved an exceptional degree of independence as it returned to its historical roots as a privately funded university. Today it is one of the ten universities that are most successful in obtaining external research funding and one of the three largest universities in Germany with centres of excellence in medicine, life sciences and humanities. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article | November 11, 2016
Site: www.eurekalert.org

FRANKFURT. Regulatory authorities around the world can in future instruct manufacturers of chemicals and drugs to check their products for harmful effects on reproduction by means of a new test with molluscs. After over 10 years of funding by the German Environment Agency in Dessau, a project coordinated by Goethe University Frankfurt has now resulted in an OECD guideline (Organisation for Economic Co-operation and Development) for global chemical testing. The test analyses in the laboratory the long-term effects of chemicals on reproduction in freshwater mudsnails (Potamopyrgus antipodarum). "Although this tiny creature is not an indigenous snail species, as what is known as a "model organism" its biological answers are also transferable to other molluscs, regardless of whether they stem from Europe, Asia or America", explains Professor Jörg Oehlmann, coordinator of the test development team and head of the Department of Aquatic Ecotoxicology at Goethe University Frankfurt. Potamopyrgus is a water dweller and was introduced to Europe in the mid 19th century on board ships from New Zealand. However, this alien species is meanwhile part of the normal landscape in many of Europe's watercourses. New chemicals which have not yet been approved and harm the mudsnail in OECD Test No. 242 in the laboratory would have the same effect on it and related species in the wild. Since molluscs, after insects and crustaceans, are the second most species-rich group in the animal kingdom, the loss of these organisms would be fatal for biodiversity and thus also for the correct functioning of the ecosystems. The development of the "snail test" therefore constitutes an important contribution to keeping our watercourses clean and healthy, since substances which show a toxic effect in this test for the snail can in future be identified and controlled prior to market introduction. In addition, the new snail test closes an existing gap in the environmental risk assessment of chemicals, since standardized tests with invertebrates to date focussed mainly on arthropods (insects and crustaceans). Snails had, however, in the past proven to be extraordinarily sensitive to a large number of harmful substances, including tributyltin compounds and other environmental chemicals which influence the hormone system. The work coordinated by Goethe University Frankfurt on the development and standardization of the snail test took place over a period of more than 10 years. Test conditions for the snails with regard to water and feedstuff quality, temperature, concentration and numerous other parameters were optimized in the framework of an extensive research programme. In the last six years, four final validation studies with six test substances were carried out in 16 laboratories in Europe and the USA which showed that the test protocol developed is robust and the test generates reproducible results, independent of in which laboratory it is implemented. For the test, female mudsnails are exposed to a concentration range of chemicals in ambient water. The organisms remain with the test substance in their test beakers for 28 days, after which the number of embryo amongst all surviving females is counted. "It's a process which is easy to use and also suitable for everyday use by water authorities", says Oehlmann. In their home country of New Zealand, both male and female mudsnails are found. In Europe, however, populations are composed solely of females which reproduce parthenogenetically. This makes using the test and analysing the results easier, all the more so since the tiny snail makes only modest demands on the laboratory. "The animal's small size has another advantage: in comparison to many other test procedures, this test can be miniaturized and doesn't take up much space", explains Oehlmann. That makes it possible to test a larger number of chemicals. OECD guideline 242 for the testing of chemicals: http://dx. .


Nayak A.,Goethe University Frankfurt | Viale-Bouroncle S.,University of Regensburg | Morsczeck C.,University of Regensburg | Muller S.,Goethe University Frankfurt
Molecular Cell | Year: 2014

The ubiquitin-like SUMO system regulates gene expression, but the molecular insights into this process are incomplete. We show that the SUMO-specific isopeptidase SENP3 controls H3K4 methylation by regulating histone-modifying SET1/MLL complexes. SET1/MLL complexes are composed of a histone methyltransferase and the regulatory components WDR5, RbBP5, Ash2L, and DPY-30. MLL1/MLL2 complexes contain menin as additional component and are particularly important for the activation of HOX genes. We demonstrate that SENP3 is associated with MLL1/MLL2 complexes and catalyzes deSUMOylation of RbBP5. This is required for activation of a subset of HOX genes, including the developmental regulator DLX3. In the absence of SENP3, the association of menin and Ash2L with the DLX3 gene is impaired, leading to decreased H3K4 methylation and reduced recruitment of active RNA polymerase II. Importantly, the SENP3-DLX3 pathway dictates osteogenic differentiation of human stem cells, thus delineating the importance of balanced SUMOylation for epigenetic control of gene expression programs. © 2014 Elsevier Inc.


Zagrebaev V.I.,Joint Institute for Nuclear Research | Greiner W.,Goethe University Frankfurt
Nuclear Physics A | Year: 2015

Production and studying properties of superheavy (SH) nuclei meet significant experimental difficulties owing to extremely low cross sections of their formation in heavy ion fusion or multinucleon transfer reactions. Accurate predictions of these cross sections along with the corresponding excitation functions are quite desirable for planning and performing experiments of such kind. Study of these cross sections (their dependence on projectile-target combination and energy dependence) gives us an opportunity to investigate complicated dynamics of low-energy heavy ion collisions as well as decay properties of excited SH nuclei. © 2015 Elsevier B.V.


Coja-Oghlan A.,Goethe University Frankfurt | Vilenchik D.,Weizamnn Institute
Proceedings - Annual IEEE Symposium on Foundations of Computer Science, FOCS | Year: 2013

In this paper we establish a substantially improved lower bound on the k-colorability threshold of the random graph G(n,m) with n vertices and m edges. The new lower bound is ≈ 1.39 less than the 2k ln k-ln k first-moment upper bound (and ≈ 0.39 less than the 2k ln k - ln k - 1 physics conjecture). By comparison, the best previous bounds left a gap of about 2 + lnk, unbounded in terms of the number of colors [Achlioptas, Naor: STOC 2004]. Furthermore, we prove that, in a precise sense, our lower bound marks the so-called condensation phase transition predicted on the basis of physics arguments [Krzkala et al.: PNAS 2007]. Our proof technique is a novel approach to the second moment method, inspired by physics conjectures on the geometry of the set of k-colorings of the random graph. Copyright © 2013 by The Institute of Electrical and Electronics Engineers, Inc.


Zagrebaev V.I.,Joint Institute for Nuclear Research | Greiner W.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2013

Problems of production and study of new neutron-enriched heavy nuclei are discussed. Low-energy multinucleon transfer reactions are shown to be quite appropriate for this purpose. Reactions with actinide beams and targets are of special interest for synthesis of new neutron-enriched transfermium nuclei and not-yet-known nuclei with closed neutron shell N=126 having the largest impact on the astrophysical r-process. The estimated cross sections for the production of these nuclei look very promising for planning such experiments at currently available accelerators. These experiments, however, are rather expensive and difficult to perform because of low intensities of the massive projectile beams and problems of separating and detecting the heavy reaction products. Thus, realistic predictions of the corresponding cross sections for different projectile-target combinations are definitely required. Some uncertainty still remains in the values of several parameters used for describing the low-energy nuclear dynamics. This uncertainty does not allow one to perform very accurate predictions for the productions of new heavier-than-target (trans-target) nuclei in multinucleon transfer reactions. Most of these parameters (nucleon transfer rate, nuclear viscosity, and fission barriers) are fundamental characteristics of low-energy nuclear dynamics. Determination of the values of these parameters (as well as their temperature dependence) is of significance in its own right. The available experimental data on the production of heavy nuclei in low-energy multinucleon transfer reactions are still insufficient and fragmentary. Several new experiments are proposed, these include those in which the role of shell effects in reaction dynamics can be better clarified. © 2013 American Physical Society.


Kotz S.A.,University of Manchester | Kotz S.A.,Max Planck Institute for Human Cognitive and Brain Sciences | Schmidt-Kassow M.,Max Planck Institute for Human Cognitive and Brain Sciences | Schmidt-Kassow M.,Goethe University Frankfurt
Cortex | Year: 2015

The current work set out to answer three questions: (1) Are reported syntactic deficits in patients with structural damage to the basal ganglia (BG) in the cortico-striato-thalamo-cortical systems (CSTCS) the result of a syntax specific computational deficit or are they potentially a consequence of a generalized timing deficit? (2) Do BG patients suffer from a simple beat perception deficit in speech comparable to the one reported in music? (3) Can regular speech meter (i.e., a pattern of beats induced by the regular alteration of stressed and unstressed syllable accents) ameliorate the computation of syntactically marked information by making speech events temporally predictable and salient? The latter 'remediation' hypothesis would predict that when speech events (i.e., those that are syntactically marked) are metrically aligned to the syllabic accent structure, the computation of syntactic information is facilitated or in the case of patients ameliorated. During continuous EEG measurement nineteen patients with focal BG lesions and matched healthy controls listened to metrically regular and syntactically well-formed sentences and metrically well-formed sentences that either violated syntactic expectancy, metrical expectancy, or both. While healthy controls showed an expected P600 response in the event-related brain potential (ERP) to all expectancy violations, BG patients showed overall comparable P600 responses to all, but the metrical expectancy violation. These results confirm that (1) BG patients suffer from a simple beat perception deficit in speech and (2) regular speech meter ameliorates the computation of syntactically marked information in the speech signal. We propose that a domain general sensorimotor cerebello-thalamo-cortical system (CTCS), involved in event-based temporal processing, engages in the remediation of dysfunctional cortico-striato-thalamo-cortical timing that affects the timely computation of linguistic (i.e., syntax) information in the speech signal. © 2015 Elsevier Ltd.


Tkalcec B.J.,Goethe University Frankfurt | Golabek G.J.,Laboratoire Of Geologie | Golabek G.J.,ETH Zurich | Brenker F.E.,Goethe University Frankfurt
Nature Geoscience | Year: 2013

Diogenite meteorites are thought to represent mantle rocks that formed as cumulates in magma chambers on 4 Vesta or a similar differentiated asteroid. Northwest Africa 5480 is a harzburgitic diogenite, composed mainly of heterogeneously distributed olivine and orthopyroxene. Here we present a microstructural analysis of olivine grains from Northwest Africa 5480, using electron backscatter diffraction techniques to quantify any preferred orientation of crystallographic lattice. We find that the preferred orientation in the olivine-dominated zones can be explained neither by cumulate formation nor by impact reprocessing near the asteroid's surface. Rather, they represent high-temperature solid-state plastic deformation by the pencil-glide slip system. The detected type of preferred orientation is well known from dry ultramafic rocks on Earth, where it is typically formed by mantle shear at temperatures between 1,273 and 1,523 K. Numerical modelling indicates that our observations can be explained by large-scale downwelling inside the asteroid's mantle, within the first 50 million years after formation of calcium-aluminium-rich inclusions. The discovery of solid-state plastic deformation in an asteroidal ultramafic rock represents compelling evidence of dynamic planet-like processes in asteroids. We conclude that long-lasting enhanced mass exchange occurred in the dynamic interior of a differentiated asteroid such as Vesta, and enabled accelerated chemical, structural and thermal equilibration. © 2013 Macmillan Publishers Limited. All rights reserved.


Vogeli B.,ETH Zurich | Kazemi S.,Goethe University Frankfurt | Guntert P.,Goethe University Frankfurt | Guntert P.,Tokyo Metroplitan University | Riek R.,ETH Zurich
Nature Structural and Molecular Biology | Year: 2012

Proteins are inherently dynamic systems whose motions cover large ranges in both magnitude and timescale. Because of the omnipresence of motion, it is likely that dynamics have important roles in the function of biomolecules. For detailed understanding of a protein's function, the three-dimensional structure and description of its dynamics are therefore required. Structure determination methods are well established, and NMR-relaxation phenomena provide insights into local molecular dynamics; moreover, recently several attempts have been made to detect concerted motion. Here, we present an ensemble-based structure-determination protocol using ensemble-averaged distance restraints obtained from exact NOE rates. Application to the model protein GB3 establishes an ensemble of structures that reveals correlated motion across the β-sheet, concerted motion between the backbone and side chains localized in the structure core, and a lack of concerted conformational exchange between the β-sheet and the α-helix. © 2012 Nature America, Inc. All rights reserved.


Zagrebaev V.I.,Joint Institute for Nuclear Research | Karpov A.V.,Joint Institute for Nuclear Research | Greiner W.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2012

Background. In the "cold" fusion reactions based on the use of lead and bismuth targets, the proton-rich isotopes of superheavy (SH) elements up to Z=113 have been produced. More neutron-rich isotopes of SH elements (up to Z=118) have been synthesized in "hotter" fusion reactions of 48Ca with actinide targets. α-decay half-lives of different isotopes of the same SH elements (for example, 112) were found to vary by several orders of magnitude. This indicates strong shell effects in this area of the nuclear map. The understanding of these effects and other properties of SH nuclei is strongly impeded by the absence of experimental data on decay properties of the not-yet-synthesized isotopes of SH elements located between those produced in the "cold" fusion reactions and those produced in the "hot" fusion reactions and also by the yet missing neutron-enriched isotopes of these elements. Purpose. In this paper we search for the optimal fusion reactions which may be used to fill this gap of the nuclear map and significantly extend the area of known SH nuclei. Method. For the calculation of the cross sections we use the same approach which was employed earlier for successful predictions of all 48Ca induced fusion reactions.Results. Several fusion reactions of the stable projectiles 40Ar, 44Ca, and 48Ca with different isotopes of actinides (lighter and heavier than those that have been already utilized in the Dubna experiments) could be used for synthesis of new SH nuclei. Predicted cross sections for the production of new isotopes of SH nuclei were found to be quite large, and the corresponding experiments can be easily performed at existing facilities. For the first time a "narrow pathway" to the middle of the island of stability was found owing to possible β + decay of SH nuclei 291115 and 291114 which could be formed in ordinary fusion reactions. © 2012 American Physical Society.


Gregory R.W.,IESE Business School | Beck R.,Goethe University Frankfurt | Keil M.,Georgia State University
MIS Quarterly: Management Information Systems | Year: 2013

While much is known about selecting different types of control that can be exercised in information systems development projects, the control dynamics associated with ISD offshoring projects represent an important gap in our understanding. In this paper, we develop a substantive grounded theory of control balancing that addresses this theoretical gap. Based on a longitudinal case study of an ISD offshoring project in the financial services industry, we introduce a three-dimensional control configuration category that emerged from our data, suggesting that control type is only one dimension on which control configuration decisions need to be made. The other two dimensions that we identified are control degree (tight versus relaxed) and control style (unilateral versus bilateral). Furthermore, we illustrate that control execution during the life cycle of an ISD offshoring project is highly intertwined with the development of client-vendor shared understanding and that each influences the other. Based on these findings, we develop an integrative process model that explains how offshoring project managers make adjustments to the control configuration periodically to allow the ISD offshoring project and relationship to progress, yielding the iterative use of different three-dimensional control configurations that we conceptualize in the paper. Our process model of control balancing may trigger new ways of looking at control phenomena in temporary interfirm organizations such as client-vendor ISD offshoring projects. Implications for research on organizational control and ISD offshoring are discussed. In addition, guidelines for ISD offshoring practitioners are presented.


Pfeiffer A.N.,ETH Zurich | Cirelli C.,ETH Zurich | Smolarski M.,ETH Zurich |