Freiburg, Germany

The University of Freiburg , sometimes referred to with its full title, the Albert Ludwig University of Freiburg, is a public research university located in Freiburg im Breisgau, Baden-Württemberg, Germany.The university was founded in 1457 by the Habsburg dynasty as the second university in Austrian-Habsburg territory after the University of Vienna. Today, Freiburg is the fifth-oldest university in Germany, with a long tradition of teaching the humanities, social science and natural science. The university is made up of 11 faculties and attracts students from across Germany as well as from over 120 other countries. Foreign students constitute about 16% of total student numbers.Named as one of elite universities of Germany by academics, political representatives and the media, the University of Freiburg stands amongst Europe's top research and teaching institutions. With its long-standing reputation of excellence, the university looks both to the past, to maintain its historic academic and cultural heritage, and to the future, developing new methods and opportunities to meet the needs of a changing world. The University of Freiburg has been home to some of the greatest minds of the Western tradition, including such eminent figures as Martin Heidegger, Hannah Arendt, Rudolf Carnap, David Daube, Johann Eck, Hans-Georg Gadamer, Friedrich Hayek, Edmund Husserl, Friedrich Meinecke, and Max Weber. In addition, 19 Nobel laureates are affiliated with the University of Freiburg and 15 academics have been honored with the highest German research prize, the Gottfried Wilhelm Leibniz Prize, while working at the University of Freiburg. Wikipedia.


Time filter

Source Type

Patent
Kineticor, University of Hawaii at Manoa and Albert Ludwigs University of Freiburg | Date: 2016-07-28

The systems, methods, and devices described herein generally relate to achieving accurate and robust motion correction by detecting and accounting for false movements in motion correction systems used in conjunction with medical imaging and/or therapeutic systems. In other words, in some embodiments of the systems, methods, and devices described herein can be configured to detect false movements for motion correction during a medical imaging scan and/or therapeutic procedure, and thereby ensure that such false movements are not accounted for in the motion correction process. Upon detection of false movements, the imaging or therapeutic system can be configured to transiently suppress and/or subsequently repeat acquisitions.


Ziletti A.,Boston University | Carvalho A.,National University of Singapore | Campbell D.K.,Boston University | Coker D.F.,Boston University | And 3 more authors.
Physical Review Letters | Year: 2015

Surface reactions with oxygen are a fundamental cause of the degradation of phosphorene. Using first-principles calculations, we show that for each oxygen atom adsorbed onto phosphorene there is an energy release of about 2 eV. Although the most stable oxygen adsorbed forms are electrically inactive and lead only to minor distortions of the lattice, there are low energy metastable forms which introduce deep donor and/or acceptor levels in the gap. We also propose a mechanism for phosphorene oxidation involving reactive dangling oxygen atoms and we suggest that dangling oxygen atoms increase the hydrophilicity of phosphorene. © 2015 American Physical Society.


Muro-Pastor A.M.,University of Seville | Hess W.R.,Albert Ludwigs University of Freiburg
Trends in Microbiology | Year: 2012

There are several instances of cellular differentiation in prokaryotes, including the formation of spores in Bacillus, the fruiting bodies of Myxococcus, and the stalked cells of Caulobacter. The vegetative cells of particular filamentous cyanobacteria can differentiate into three different cell types: N2-fixing heterocysts, spore-like akinetes, and motile hormogonia. Heterocysts are crucial for the ability of these photosynthetic bacteria to fix N2 because they keep the oxygen-labile nitrogenase away from the photosynthetically produced O2. Heterocysts are morphologically and functionally distinct from vegetative cells in the filament. Their differentiation relies on sophisticated intercellular communication and is tightly regulated. Analyzed by classical mutagenesis for decades, heterocyst differentiation is now being approached by large-scale methodologies, leading to the identification of new elements that might be important in the process. © 2012 Elsevier Ltd.


Vashist S.K.,Institute For Mikro Und Informationstechnik | Vashist S.K.,Albert Ludwigs University of Freiburg | Lam E.,National Research Council Canada | Hrapovic S.,National Research Council Canada | And 2 more authors.
Chemical Reviews | Year: 2014

Biosensing and diagnostic platforms with high sensitivity, specificity, and fast response time are based on immobilized biomolecules such as antibodies (Abs), aptamers, enzymes, nucleic acids, receptors, and whole cells for the detection of target analytes. Such sensing biomolecules should be bound to the surface of a signal transducer with a required specific chemical, electrical, or optical property. The biological recognition event generates a quantifiable signal, which is equated to the amount or concentration of the analyte. APTES can be deposited on solid materials, electrode materials, nanomaterials, and nanocomposites under variable conditions of concentration, solvent, temperature, and time. In addition, curing conditions such as air/heat drying might be necessary depending upon the intended application. Pertinent information on the thickness, morphology, and conformation of the APTES layer reported in the literature is often different and conflicting.


Granacher U.,University of Potsdam | Gollhofer A.,Albert Ludwigs University of Freiburg | Hortobagyi T.,University of Groningen | Kressig R.W.,University of Basel | Muehlbauer T.,University of Potsdam
Sports Medicine | Year: 2013

Background: The aging process results in a number of functional (e.g., deficits in balance and strength/power performance), neural (e.g., loss of sensory/motor neurons), muscular (e.g., atrophy of type-II muscle fibers in particular), and bone-related (e.g., osteoporosis) deteriorations. Traditionally, balance and/or lower extremity resistance training were used to mitigate these age-related deficits. However, the effects of resistance training are limited and poorly translate into improvements in balance, functional tasks, activities of daily living, and fall rates. Thus, it is necessary to develop and design new intervention programs that are specifically tailored to counteract age-related weaknesses. Recent studies indicate that measures of trunk muscle strength (TMS) are associated with variables of static/dynamic balance, functional performance, and falls (i.e., occurrence, fear, rate, and/or risk of falls). Further, there is preliminary evidence in the literature that core strength training (CST) and Pilates exercise training (PET) have a positive influence on measures of strength, balance, functional performance, and falls in older adults. Objective: The objectives of this systematic literature review are: (a) to report potential associations between TMS/trunk muscle composition and balance, functional performance, and falls in old adults, and (b) to describe and discuss the effects of CST/PET on measures of TMS, balance, functional performance, and falls in seniors. Data Sources: A systematic approach was employed to capture all articles related to TMS/trunk muscle composition, balance, functional performance, and falls in seniors that were identified using the electronic databases PubMed and Web of Science (1972 to February 2013). Study Selection: A systematic approach was used to evaluate the 582 articles identified for initial review. Cross-sectional (i.e., relationship) or longitudinal (i.e., intervention) studies were included if they investigated TMS and an outcome-related measure of balance, functional performance, and/or falls. In total, 20 studies met the inclusionary criteria for review. Study Appraisal and Synthesis Methods: Longitudinal studies were evaluated using the Physiotherapy Evidence Database (PEDro) scale. Effect sizes (ES) were calculated whenever possible. For ease of discussion, the 20 articles were separated into three groups [i.e., cross-sectional (n = 6), CST (n = 9), PET (n = 5)]. Results: The cross-sectional studies reported small-to-medium correlations between TMS/trunk muscle composition and balance, functional performance, and falls in older adults. Further, CST and/or PET proved to be feasible exercise programs for seniors with high-adherence rates. Age-related deficits in measures of TMS, balance, functional performance, and falls can be mitigated by CST (mean strength gain = 30 %, mean effect size = 0.99; mean balance/functional performance gain = 23 %, mean ES = 0.88) and by PET (mean strength gain = 12 %, mean ES = 0.52; mean balance/functional performance gain = 18 %, mean ES = 0.71). Limitations: Given that the mean PEDro quality score did not reach the predetermined cut-off of ≥6 for the intervention studies, there is a need for more high-quality studies to explicitly identify the relevance of CST and PET to the elderly population. Conclusions: Core strength training and/or PET can be used as an adjunct or even alternative to traditional balance and/or resistance training programs for old adults. Further, CST and PET are easy to administer in a group setting or in individual fall preventive or rehabilitative intervention programs because little equipment and space is needed to perform such exercises. © 2013 Springer International Publishing Switzerland.


Medina H.R.,University of Seville | Cerda-Olmedo E.,University of Seville | Al-Babili S.,Albert Ludwigs University of Freiburg
Molecular Microbiology | Year: 2011

Mixed cultures of strains of opposite sex of the Mucorales produce trisporic acids and other compounds arising from cleavage of β-carotene, some of which act as signals in the mating process. The genome of Phycomyces blakesleeanus contains five sequences akin to those of verified carotenoid cleavage oxygenases. All five are transcribed, three of them have the sequence traits that are considered essential for activity, and we have discovered the reactions catalysed by the products of two of them, genes carS and acaA. The transcripts of carS became more abundant in the course of mating, and its expression in β-carotene-producing Escherichia coli cells led to the formation of β-apo-12'-carotenal, a C 25 cleavage product of β-carotene. Joint expression of both genes in the same in vivo system resulted in the production of β-apo-13-carotenone, a C 18 fragment. In vitro, AcaA cleaved β-apo-12'-carotenal into β-apo-13-carotenone and was active on other apocarotenoid substrates. According to these and other results, the first reactions in the apocarotenoid pathway of Phycomyces are the cleavage of β-carotene at its C11'-C12' double bond by CarS and the cleavage of the resulting C 25-fragment at its C13-14 double bond by AcaA. © 2011 Blackwell Publishing Ltd.


Tallaksen L.M.,University of Oslo | Stahl K.,Albert Ludwigs University of Freiburg
Geophysical Research Letters | Year: 2014

This study explores the performance of a suite of off-line, global (hydrological and land surface) models in mapping spatial and temporal patterns of large-scale hydrological droughts in Europe from simulated runoff in the period 1963-2000. Consistent model behavior was found for annual variability in mean drought area, whereas high model dispersion was revealed in the weekly evolution of contiguous area in drought and its annual maximum. Comparison with nearly three hundred catchment-scale streamflow observations showed an overall tendency to overestimate the number of drought events and hence underestimate drought duration, whereas persistence in drought-affected area (weekly mean) was underestimated, noticeable for one group of models. The high model dispersion in temporal and spatial persistence of drought identified implies that care should be taken when analyzing drought characteristics from only one or a limited number of models unless validated specifically for hydrological drought. ©2014. The Authors.


Marzolino U.,University of Ljubljana | Buchleitner A.,Albert Ludwigs University of Freiburg
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2015

We study teleportation with identical massive particles. Indistinguishability imposes that the relevant degrees of freedom to be teleported are not particles, but rather addressable orthogonal modes. We discuss the performances of teleportation under the constraint of conservation of the total number of particles. The latter inevitably decreases the teleportation fidelity. Moreover, even though a phase reference, given by the coupling to a reservoir, circumvents the constraint, it does not restore perfect deterministic teleportation. The latter is only achievable with some special resource entangled states and when the number of particles tends to infinity. Interestingly, some of such states are the many-particle atomic coherent states and the ground state of cold atoms loaded into a double well potential, which are routinely prepared in experiments. © 2015 American Physical Society.


Grant
Agency: Cordis | Branch: FP7 | Program: CPCSA | Phase: ICT-2013.9.9 | Award Amount: 74.61M | Year: 2013

This Flagship aims to take graphene and related layered materials from a state of raw potential to a point where they can revolutionize multiple industries from flexible, wearable and transparent electronics, to new energy applications and novel functional composites.\nOur main scientific and technological objectives in the different tiers of the value chain are to develop material technologies for ICT and beyond, identify new device concepts enabled by graphene and other layered materials, and integrate them to systems that provide new functionalities and open new application areas.\nThese objectives are supported by operative targets to bring together a large core consortium of European academic and industrial partners and to create a highly effective technology transfer highway, allowing industry to rapidly absorb and exploit new discoveries.\nThe Flagship will be aligned with European and national priorities to guarantee its successful long term operation and maximal impact on the national industrial and research communities.\nTogether, the scientific and technological objectives and operative targets will allow us to reach our societal goals: the Flagship will contribute to sustainable development by introducing new energy efficient and environmentally friendly products based on carbon and other abundant, safe and recyclable natural resources, and boost economic growth in Europe by creating new jobs and investment opportunities.


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

This project is the second in the series of EC-financed parts of the Graphene Flagship. The Graphene Flagship is a 10 year research and innovation endeavour with a total project cost of 1,000,000,000 euros, funded jointly by the European Commission and member states and associated countries. The first part of the Flagship was a 30-month Collaborative Project, Coordination and Support Action (CP-CSA) under the 7th framework program (2013-2016), while this and the following parts are implemented as Core Projects under the Horizon 2020 framework. The mission of the Graphene Flagship is to take graphene and related layered materials from a state of raw potential to a point where they can revolutionise multiple industries. This will bring a new dimension to future technology a faster, thinner, stronger, flexible, and broadband revolution. Our program will put Europe firmly at the heart of the process, with a manifold return on the EU investment, both in terms of technological innovation and economic growth. To realise this vision, we have brought together a larger European consortium with about 150 partners in 23 countries. The partners represent academia, research institutes and industries, which work closely together in 15 technical work packages and five supporting work packages covering the entire value chain from materials to components and systems. As time progresses, the centre of gravity of the Flagship moves towards applications, which is reflected in the increasing importance of the higher - system - levels of the value chain. In this first core project the main focus is on components and initial system level tasks. The first core project is divided into 4 divisions, which in turn comprise 3 to 5 work packages on related topics. A fifth, external division acts as a link to the parts of the Flagship that are funded by the member states and associated countries, or by other funding sources. This creates a collaborative framework for the entire Flagship.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.3.2 | Award Amount: 3.81M | Year: 2012

The project aims to develop a fully integrated, automated and user-friendly platform for infectious disease diagnosis. Malaria can be treated in just 48 hours, but delayed or false diagnosis or missing a relevant alternative cause of fever may be lethal. Therefore, other diseases with similar clinical symptoms will be investigated too. DiscoGnosis will integrate micro, nano, and bio components into a multi-functional point-of-care platform, performing simultaneously protein and genetic analysis to timely and accurately identify major pathogenic causes of fever, enabling proper treatment. A foil-based centrifugal microfluidic lab-on-a-chip cartridge, core of the platform, will integrate monolithically all necessary unit operations for raw sample treatment (blood-to-result regime), from sample collection and injection, to plasma separation, DNA extraction and purification. Low-cost production, scalable from prototype to batch fabrication (with proper quality control, calibration and standards specifications) will render the platform affordable to end users, even in developing countries; high sensitivity detection and multiplexity will rely on magnetic microparticles and quantum dot technologies, supported by dedicated optics development; rapid analysis (~30 min) will be achieved via isothermal DNA amplification protocols. The entire system will be validated in a controlled field test with standardized samples and by end-users in high-risk developing countries through partners established contacts. Data management will be implemented to allow rational organization in the field and to reinforce the shield of Europe against such diseases, as more than 30,000 malaria cases are reported annually among returning European tourists. This generic point-of-care platform can be applied to many diseases (eg, cancer, cardiovascular, Alzheimer) by only changing its bio-components. The strong SME participation indicates the high commercialization potential of the project.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2008-1-2-06 | Award Amount: 4.06M | Year: 2009

1. The effect of climate change on forest biodiversity will be evaluated through better understanding of the ecological processes that shape species composition and are particularly sensitive to climate conditions. Forest species composition will correspond to the assemblage of tree species and both symbiotic and antagonistic species that can drive tree species composition. Climate conditions will include both average and extreme values of climatic variables (e.g. temperature, humidity and wind). 2. The relationships between forest biodiversity and functioning will be deciphered through better understanding of the respective role of tree species richness and composition and by focussing on the biotic interactions between species. As the fundamental ecological hypothesis behind the diversity productivity relationship is the optimal use of resources, we will analyse the energy flow (i.e. resources production and consumption) across different trophic levels (trees and symbiotic organisms as producers, herbivores and pathogens as consumers). 3. In a final step we will aggregate the information from the first two steps to predict the effect of climate change on forest productivity through changes in tree species composition. The prediction will be expressed as a risk of dysfunction, in particular the risk of forest productivity loss. Traditionally, the risk for a given system is a function of hazard probability and system vulnerability to this hazard. In this case, hazards will be changes in average and extreme climatic conditions. Vulnerability will be the vulnerability to climate change of forest species that both shape forest composition and are the main drivers of forest biomass productivity. In each step, we will focus on fundamental ecological processes at work so that to deliver more generic scientific outcomes that will allow easier generalization to diverse types of European forest or forest managers expectations than a case by case approach.


Most cognitive functions are based on computations that take place in the cerebral cortex, composed of a larger number of areas, each with a complex anatomical structure, with neurons of different types and in different layers interacting according to a precise scheme. The anatomical organization of cortical areas is similar, with some modulation according to its sensory, motor or associative function. Several areas have a columnar organization, but in all areas a similar vertical organization of cortical modules is repeated, suggesting that the same fundamental computation scheme is carried out. Despite the large amount of available data, this processing capability of the cortical module is still poorly understood. Two key technological advances to explore cortical computation have been ensemble electrophysiology, the use of multiple electrodes to record groups of neurons, and optogenetics. However, the optogenetic tools are still critically lacking in layer and cell-type specificity, and the recording techniques still do not attain the yields necessary to properly characterize the cortical microcircuit. To overcome these limitations, we propose a new probe that dramatically increases the density of electrodes providing an unprecedented view of currents in the extracellular medium. This will be complemented with an optical stimulator, capable of activating excitatory and inhibitory channelrhodopsins with a 100 m resolution. We will take full advantage of the rich data that can be obtained with these new devices by producing new strategies for signal classification, to locate cells in cortical layers and assign them to a cell type based on the spatiotemporal fingerprint generated at each action potential. We will analyze cortical function at multiple scales in a number of contexts, from memory formation, to ongoing processing during decision making, and to sensorimotor integration for actions, advancing our understanding of cortical representations.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.2.1 | Award Amount: 8.85M | Year: 2008

The challenge laid out in this call is to understand the principles according to which cognitive\nsystems should be built if they are to handle novelty, situations unforeseen by their designers, and\nopen-ended, challenging environments with uncertainty and change. Our aim is to meet this challenge by creating a theory -- evaluated in robots -- of how a cognitive system can model its own knowledge; use this to cope with uncertainty and novelty during task execution; extend its own abilities and knowledge; and extend its own understanding of those abilities. Imagine a cognitive system that models not only the environment, but its own understanding of the environment and how this understanding changes under action. It identifies gaps in its own understanding and then plans how to fill those gaps so as to deal with novelty and uncertainty in task execution, gather information necessary to complete its tasks, and to extend its abilities and knowledge so as to perform future tasks more efficiently.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: FoF.ICT.2010.10.1 | Award Amount: 5.18M | Year: 2010

Todays automation and logistics paradigms make it difficult, time consuming, and costly to change the type of the product manufactured and to scale the production up and down in response to market volatility. Consequently, and with the increasing market uncertainties, it becomes more and more difficult to justify new automation lines. To keep production in Europe instead of shifting it to low-wage countries, this project will break new ground in robot-based automation and logistics as the backbone of a transformable factory of the future, enabling an economic production regardless of changes in volumes and product type.TAPAS pioneers the following tasks in real production environments: mobile robots with manipulation arms will make logistic tasks more flexible and more complete by not only transporting, but also collecting the parts needed and delivering them right to the place were needed. Since moving parts around the shop floor does not create value by itself, TAPAS robots go even beyond: they will automate assistive tasks that naturally extend the logistic tasks, such as preparatory and post-processing works, e.g., pre-assembly or machine tending with inherent quality control. Through this additional creation of value and by a faster adaptation to changes with new levels of robustness, availability, and completeness of jobs TAPAS robots promise to yield an earlier return of investment.To reach the objectives, the TAPAS consortium will iteratively test and validate the developments with two pilot installations of increasing complexity and scale. The drivers behind TAPAS are a robot manufacturer and a system integrator, providing both their production environments for intensive testing and validation, and a software technology provider. Teaming up with three excellent research partners they will develop logistic and assistive robotic solutions for transformable automation that are generally applicable and scalable.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.00M | Year: 2015

The height of conventional wind turbines is limited by the enormous stresses on the structure. The idea of the Airborne Wind Energy (AWE) is to replace the most efficient part of a conventional wind turbine, the tip of the turbine blade, with a fast flying high efficiency kite, and to replace the rest of the structure by a tether which anchors the kite to the ground. Power is generated either by periodically pulling a ground based generator via a winch, or by small wind turbines mounted on the kite that exploit its fast cross wind motion. While the concept is highly promising, major academic and industrial research is still needed to achieve the performance required for industrial deployment. This can best be done by innovative junior researchers in a closely cooperating consortium of academic and industrial partners. The ITN AWESCO combines six interdisciplinary academic and four industrial network partners with seven associated partners, all selected on the basis of excellence and complementarity. All partners work already intensively on AWE systems, several with prototypes, and they are committed to create synergies via the cooperation in AWESCO. The main task is to train fourteen Early Stage Researchers (ESRs) in training-by-research and to create a closely connected new generation of leading European scientists that are ready to push the frontiers of airborne wind energy. AWESCO is the first major cooperation effort of the most important European actors in the field and will help Europe to gain a leading role in a possibly huge emerging renewable energy market, and to meet its ambitious CO2 targets. In addition, the AWESCO early stage researchers will be trained in cutting-edge simulation, design, sensing, and control technologies that are needed in many branches of engineering.


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

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


Grant
Agency: Cordis | Branch: H2020 | Program: FCH2-RIA | Phase: FCH-01.1-2015 | Award Amount: 6.88M | Year: 2016

The objective is to develop and integrate the most advanced critical PEMFC stack components, many from recent FCH JU programmes, into an automotive stack showing BOL performance of 1.5 W/cm2 at 0.6V, <10% power degradation after 6,000 hours, with a technical and economic assessment showing a cost of less than 50/kW at a 50,000 annual production scale. This will be achieved by leading industrial and academic partners with expertise in the design and manufacture of PEMFC stacks, their components and materials. They will select and build on components which can achieve key target metrics, e.g. catalyst materials showing mass activities of 0.44 A/mg Pt. There will be focus on integration of the key components and optimisation of the interfaces regarding the electrochemistry, mass and heat transport, and mechanical interactions. Several iterations of an advanced stack design will be evaluated. Work is organised to optimise the flow of development, which begins with catalysts being advanced and down-selected, scaled then fed into the design and development of catalyst layers, integration with membranes and the demonstration of CCM performance. The CCMs feed into stack component development where they will be integrated with GDLs to form MEAs; and where bipolar plates will be designed and developed and supplied with the MEAs for iterative stack design, assembly and testing. All mandatory and optional objectives of the FCH 2 JU Work Plan are addressed. Performance and durability are evaluated from small single cell to stack level using standardised test protocols. Degradation is addressed by stability testing, structural visualisation and modelling. Interfaces and specification alignment is an important focus, being integrated with the evaluation of new architectures and synthesis methods and informing balance of plant component specifications. Dismantling and recycling for the recovery and re-use of all critical MEA components is included in the costing evaluation.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: NMP-2007-3.5-2 | Award Amount: 8.47M | Year: 2008

The objective of the project COTECH is to investigate new approaches of -manufacturing based on advanced technology convergence processes and to propose hybrid solutions for high added value cost effective -manufacturing emerging applications. The main goals of COTECH are to develop: (1) -replication technologies underpinned by emerging tool-making technologies for processing multi-material components and creating: a) 3D -components using high throughput multi-material -injection moulding with sub-m resolution; b) 2D -components using direct multi-material hot or UV embossing with a sub-200nm resolution. (2) Radically new replication convergent technologies combining the capabilities of -injection or embossing to a complementary activation step to create intelligent devices in a single process step: a) Hybrid processes based on -injection moulding using modules of e.g coating and compression injection moulding, to provide functionality to -devices, such as active coatings and combination of micro and nano features in a single step; b) Ultimately the hybrid processes based on -injection with embossing will be validated. This will offer a very high throughput multimaterial -injection that will enable the fabrication of 3D high aspect ratio -parts, complemented by an embossing step to allow ultra precise 2D features. (3) Global process chains with increased MTBF (50%) and fabrication of high quality products. This requires innovative non-destructive inspection solutions and simulation models. (4) High added value -devices with advanced functionalities. COTECH proposes to validate industrially the new technology convergence processes with 8 demonstrators representing the most emergent industrial sectors (transport, biomedical, energy). The expected market for the industry exceeds 1 Billion . COTECH will also address the problem of knowledge fragmentation by activating a polymer -manufacturing sub-platform as support to MINAM.


Grant
Agency: Cordis | Branch: H2020 | Program: BBI-RIA | Phase: BBI.VC2.R5-2015 | Award Amount: 5.26M | Year: 2016

The project focuses on increasing access to wood resources through more efficient silviculture and a better understanding of the business models governing the procurement of forest operations services. The project further considers increasing efficiency in forest harvesting and collection, and the reduction of soil impact from forest operations, and puts forward ways of making this a measurable and integrated part of operational efficiency. TECH4EFFECT offers the potential to revolutionize forest operations with a state-of-the-art knowledge-based efficiency development system, providing easily accessible decision support exploiting the large amount of data available in modern industrial forest management. The ambition of TECH4EFFECT is to implement such as management tool, enhanced through 4 years of intensive R&D in close cooperation with the end-users of the Efficiency Portal in 5 participating countries. It is the projects hope that implementation will result in such obvious benefits amongst the industrial partners that its application will become widespread within the European forest sector.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: SPA.2010.1.1-04 | Award Amount: 3.60M | Year: 2010

ReCover project will develop beyond state-of-the-art service capabilities to support fighting deforestation and forest degradation in the tropical region. The pilot service capabilities mean provision of a monitoring system of forest cover and forest cover changes and biomass including a robust accuracy assessment. The capabilities are based on utilizing mainly space-borne earth observation data and in-situ data. The service development is controlled by specific user requirements that are expressed through Service Level Agreements (SLA) between the ReCover consortium and six users. The services prepare particularly for the implementation of the post-Kyoto climate treaty and the REDD\. Service roll-out and expansion to the community outside the project and present pilot users is a key activity of ReCover. The outside community includes but is not restricted to TREES-3 project, GSE Forest Monitoring Extension, FRA, and GEO. The scientific viewpoint that reaches beyond the state-of-the-art techniques is the leading baseline of the study. The main research focus in ReCover is to develop a sound statistical concept and validation procedure in the production, apply very high resolution image data to improve result reliability, estimate biomass and degradation as well as their change, define the role of radar data in REDD related services, and build standardized service system with a capacity building concept. The consortium consists of nine leading research and industrial partners of which one is an SME. Three partners are from REDD eligible countries. The high impact value of ReCover is achieved by working directly for and with the customers and with local research partners, creating novel, trustworthy and standardized but affordable services and applying them in INSPIRE compatible service environment. The long-term service sustainability is concerned including evaluation of the potential of new missions such as the Sentinels.


A method for the precise measuring operating of a micro-mechanical rotation rate sensor, including at least one seismic mass, at least one drive device for driving the seismic mass in the primary mode (q_(1)) and at least three trimming electrode elements which are jointly associated directly or indirectly with the seismic mass. An electric trimming voltage (u_(1), u_(2), u_(3), u_(4)) is set respectively between the trimming electrode elements and the seismic mass. Each of the electric trimming voltages (u_(1), u_(2), u_(3), u_(4)) are adjusted in accordance with a resonance frequency variable (_(T), _(T,0)), a quadrature variable (_(c), _(C,0)) and a restoring variable (_(S)).


Patent
Forschungsverbund Berlin E.V. and Albert Ludwigs University of Freiburg | Date: 2013-10-25

An optical element includes a structured carrier layer having a macrostructure at a main surface and a layer of cured material. The layer of cured material includes an optically smooth surface facing away from the main surface, a macrostructure surface of the surface being dependent on the macrostructure of the carrier layer and on a layer thickness profile of the layer.


Runkel E.D.,Albert Ludwigs University of Freiburg | Liu S.,Albert Ludwigs University of Freiburg | Liu S.,Deutsches Zentrum fur Neurodegenerative Erkrankungen e.V. DZNE | Baumeister R.,Albert Ludwigs University of Freiburg | Schulze E.,Albert Ludwigs University of Freiburg
PLoS Genetics | Year: 2013

Disturbance of cellular functions results in the activation of stress-signaling pathways that aim at restoring homeostasis. We performed a genome-wide screen to identify components of the signal transduction of the mitochondrial unfolded protein response (UPRmt) to a nuclear chaperone promoter. We used the ROS generating complex I inhibitor paraquat to induce the UPRmt, and we employed RNAi exposure post-embryonically to allow testing genes whose knockdown results in embryonic lethality. We identified 54 novel regulators of the ROS-induced UPRmt. Activation of the UPRmt, but not of other stress-signaling pathways, failed when homeostasis of basic cellular mechanisms such as translation and protein transport were impaired. These mechanisms are monitored by a recently discovered surveillance system that interprets interruption of these processes as pathogen attack and depends on signaling through the JNK-like MAP-kinase KGB-1. Mutation of kgb-1 abrogated the inhibition of ROS-induced UPRmt, suggesting that surveillance-activated defenses specifically inhibit the UPRmt but do not compromise activation of the heat shock response, the UPR of the endoplasmic reticulum, or the SKN-1/Nrf2 mediated response to cytosolic stress. In addition, we identified PIFK-1, the orthologue of the Drosophila PI 4-kinase four wheel drive (FWD), and found that it is the only known factor so far that is essential for the unfolded protein responses of both mitochondria and endoplasmic reticulum. This suggests that both UPRs may share a common membrane associated mechanism. © 2013 Runkel et al.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.1.2-01 | Award Amount: 4.36M | Year: 2012

INFRES aims to accelerate the technological development and open new paths to EUs renewable targets by producing research based knowledge, technological solutions and service innovations for forest residue feedstock supply. INFRES aims at high efficiency and precise deliveries of woody feedstock to heat, power and biorefining industries by: Producing technological and logistic innovations for developing new harvesting, transport and storage technology for forest fuel procurement, Demonstrating new solutions in full supply chains from harvesting to transport and storage in real operational environment Spotting the technological, economic, regulatory and other bottlenecks in the innovation structures for the forest energy sector, Assessing the environmental, economical and social sustainability for the developed logistics including scenarios for different fuel sources, methods, technologies and transport distances and Disseminating the outcomes of research and demonstrations to the practices. Project consortium has 23 partners including 9 leading forest energy research organizations of accompanied with 14 SME along the biomass supply chain. SMEs include manufacturers of harvesting technology, chippers, feedstock supply enterprises, forest harvesting and transport providers, truck technology and IT service provider to manage fleet and storages. During the project INFRES develops and demonstrates technological and logistical solutions that decrease the fossil energy input in the biomass supply by 20% and reduces the raw material losses by 15%. The cost of supply can be reduced by 10-20% and precision of supply improves the economic outcome of CHP production by 10%. The CO2 emissions of feedstock supply will diminish by 10%. With the novel technologies and efficient transfer of best practices between the countries in the consortium and other countries with similar natural conditions the volume of forest energy supply in EU27 by 2015 will be 30% higher than today.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP-2009-1.2-3 | Award Amount: 2.22M | Year: 2009

Surface Acoustic Wave (SAW) technology has been applied for more than 20 years to develop sensors exhibiting unique capabilities with limited ageing effects resulting in long term stability properties. During the 90s, they have proved their capability to be wirelessly operated without any on-board power supply. In parallel, the long term development of advanced material, particularly in Russia, has yielded a new class of material, namely Langasite and its variant forms, that can be substituted to quartz and lithium niobate particularly when operating at high temperature. Our project will demonstrate wireless SAW sensors operating in an unprecedented temperature range. This sets extreme challenges to all parts of the sensor system since the developed wireless system will be suitable to operate in harsh environments. The great progress brought by the project takes advantage of a consortium involving complementary major academics and industrial actors of SAW-sensor-based systems capable to successfully face the challenges of implementing a whole system allowing for physical metrology in harsh conditions. Substantial improvements will be provided for sensing physical parameters in a wide temperature range (-20C to \650C), in monitoring a nano-based production process and other applications. Significant knowledge will be generated in nano-sciences and nano-technologies linked to SAW physical sensors and materials for industrial applications. Demonstration of the system will be achieved at an industrial level for monitoring physical parameters under high pressures and high temperatures. The SAWHOT project consortium is set up on the basis of a bilateral Russian-European partnership generating a unique workforce cooperating within the FP7 framework to address this challenge. Finally, this project will bring on sustainable high-tech socio economic prospects : new markets and standards, improved cooperation between EU and Russian organizations.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 4.09M | Year: 2009

Velocity map imaging (VMI) has enabled a number of remarkable advances in the field of molecular dynamics over the past few years. Owing to the robustness of VMI, exciting new applications are anticipated. ICONIC will link 15 European partners using and improving VMI in a four year program spanning several areas of experimental physics and chemistry and underpinning technologies in lasers, imaging detectors, high-speed electronics and mass spectrometric methods. We will pursue the following scientific objectives: 1. To develop novel imaging technology for detection of ions and electrons. 2. To apply this new technology in studies of time- and/or quantum- resolved molecular dynamics, with an emphasis on ion-molecule reactions, reactive scattering, and photochemical processes in amino-acids and bio-mimic molecules. 3. To develop novel mass spectrometric imaging applications for use in analytical chemistry by implementing state-of-the-art imaging detection techniques. 4. To integrate imaging techniques with ultrafast pulse-shaping, coincidence detectors, and molecular state preparation methods in order to create mechanisms for quantum control of molecular dynamics. We will provide high quality integrated training for ESRs (540 training months) and ERs (96 training months) which will expose them to a wide range of instrumental methods and applications and set broad horizons for their future career paths. Training of an individual ESR (or ER) will be the responsibility of the local primary supervisor, supported by two secondary supervisors one in the host institution, and a mentor from another node within the Network and the oversight of the network training coordinator (NTC), Prof. M. Ashfold (BRI). Training elements available to all ESRs will include workshops in Bristol on networking, communication and presentation, business, entrepreneurial and IP skills; along with scientific training via graduate schools and inter-lab secondments.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.1-4 | Award Amount: 4.15M | Year: 2008

Cancer accounts for nearly one-quarter of deaths in the developed world, exceeded only by heart diseases. One of the key strategies in cancer prevention is early diagnosis through cancer screening programs. Estimates of the premature deaths that could have been avoided through cancer screening vary from 3% to 35%, depending on a variety of assumptions. Beyond the potential to reduce mortality, screening may reduce cancer morbidity since treatment for earlier-stage cancers is often less aggressive than that for more advanced-stage cancers. Currently many of these screening programs, have issues with false negative results, long time delays to obtaining the results, which increase patient anxiety and delays in starting treatments. In this project we will develop a novel rapid real time PCR/probe technology, in a microarray biochip format with the corresponding automated instrumentation for use as a rapid point of care diagnostic device. Cervical cancer and its associated virus, human papilloma virus is the model system which will be used to develop this novel automated cancer screening technology. The novel real time PCR technology will permit detection of panels of multiple biomarkers in a single PCR reaction. The partners have already developed prototype technology which partly demonstrates a microarray approach to real time PCR. The project will build on this, providing the innovation needed to transform a promising technology to an integrated system suitable for practical use at point-of-care setting. The consortium includes four research institutes and two SMEs, who have extensive experience with real time PCR and microarray technologies, and are motivated to commercialise results. In addition partners 7 will act as end user, validating the system in a clinical setting.


Grant
Agency: Cordis | 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: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.3.6 | Award Amount: 4.76M | Year: 2008

Amputation of a limb is a surgical intervention used as a last resort to remove irreparably damaged, diseased, or congenitally malformed limbs where retention of the limb is a threat to the well-being of the individual. The procedure traumatically alters the body image, but often leaves sensations that refer to the missing body part, the phantom limb. In 50-80% of cases, these sensations are painful and currently, there are no effective treatment modalities. Given sufficient control over a large number of nerve fibers, a neural interface may be able to artificially evoke sensations of touch, or counteract the phantom limb pain. The application of Micro/nano technologies with functional electrical micro stimulation can not only pave the road towards a treatment, but also also provide amputees a means to sense virtual environments directly. The ultimate aim of this project is to develop this novel Human Machine Interface (HMI). A novel microfabricated neural interface, the Thin-film Intrafascicular Multichannel Electrode array, and implantable multichannel stimulator system will form the key core technological developments in the project. The work is structured in 10 work packages in three phases. The technological development phase will model, design, manufacture and characterize the multi-channel electrode (TIME) and design, manufacture and test an implantable, multi-channel stimulator. In vivo characterization phase will evaluate the TIME electrodes for biocompatibility, stability and chronic safety in animals and develop a psychophysical test platform for system integration. Finally, pre-clinical evaluation will test the system in short-term implants in amputee subjects. The work will provide direct contribution to the next-generation smart systems in the ICT-2007.3.6 Nano/Micro priority, strengthen Europes leading position in advanced electronic systems/biomedical applications, and improve the quality of life for amputees with phantom limb pain


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.3.1 | Award Amount: 2.65M | Year: 2008

Wafer handling in semiconductor manufacturing introduces microcracks at the wafer edge. During thermal processing, some of these grow into slip bands; on rapid thermal processing some of these grow into cracks, shattering the wafer and disrupting manufacture. Dense slip bands also lead to yield loss by locally increasing diffusion rates. Breakage losses alone were of the order of 2.5M p.a. for a single fab line at the 90 nm node. Microcracks and slip bands are visible through X-ray Diffraction Imaging (XRDI); but it is unknown which of the many defects imaged are those that will result in yield loss and breakage. We aim to discover how to derive quantitative, predictive information from XRDI, enabling a breakthrough metrology of wafer inspection. The project will comprise quantification of the XRDI images, modelling of the stresses introduced by the controlled defects, modelling the influence of thermal gradients in RTA upon the defects, and experimental confirmation of the conclusions. The outcome of this research will offer a competitive advantage at several levels to those members of the European Semiconductor Industry who agree to join the Industrial Advisory Board. European wafer manufacturers will have early access to a technique that reveals the nature of the defects in the wafers and their relevance to semiconductor device fabrication. This could provide Europe with a competitive advantage in the development of both 450mm and thin silicon wafers. European wafer and equipment manufacturers will have early access to a unique and specifically developed body of open knowledge to aid them in the evaluation of risk of breakage during their processes. They will have a choice of access to off-line characterization of defects by XRDI at ANKA or an in-line wafer inspection tool commercialized by Bede plc. The knowledge and tools developed will contribute to maintaining Europes leading position in semiconductor x-ray metrology.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: ENERGY-2007-3.7-01 | Award Amount: 2.82M | Year: 2008

The objective of the project is to harmonise biomass resource assessments, focusing on the availability of biomass for energy in Europe and its neighbouring regions. This harmonisation will improve the consistency, accuracy and reliability of biomass assessments, which can serve the planning of a transition to renewable energy in the European Union. The project activities will include (i) the analysis of recently conducted biomass resource assessments, (ii) the analysis of policy backgrounds, sustainability criteria and user requirements, (iii) the analysis of currently applied methodologies, (iv) an inventory of data sources and ongoing activities aimed at improved data quality and accessibility, (v) a proposal for a harmonised biomass potential assessment methodology, (vi) an illustration and validation of the developed approach in case studies at EU-27, the Pan-European level and for select countries, (vii) an evaluation of the harmonised approach and if necessary the identification of priorities for further development. The major focus will be (1) on methodological and dataset harmonisations fostered by ongoing research of a multidisciplinary team of project participants and (2) on the opportunities of utilising both earth observation and terrestrial data for biomass assessments and the integration of multiple data sources. The relevant sectors that will be investigated are forestry, energy crops and residues from traditional agriculture and waste. The consortium will build on its complementary sectorial expertise, which will allow the production of sector-overarching studies, taking competitive and economic aspects into account. Intensive scientific cooperation and dissemination will comprise the discussion of its objectives, interim and final results with stakeholders including the EC DGs, EEA, Eurostat, UN/ECE, research, industry, national ministries and associated authorities and sectorial organisations (ren. energy, agriculture, forestry, waste)


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.3.2-02 | Award Amount: 11.97M | Year: 2012

Marine microorganisms form an almost untapped resource of biotechnological potential. However, its use is hindered by the low success rate of isolation of novel microorganisms and often by poor growth efficiency. Hence, the vast majority of marine microorganisms has not been cultivated and is often considered as unculturable. MaCuMBA aims at improving the isolation rate and growth efficiency of marine microorganisms from conventional and extreme habitats, by applying innovative methods, and the use of automated high throughput procedures. The approaches include the co-cultivation of interdependent microorganisms, as well as gradient cultures and other methods mimicking the natural environment, and the exploitation of cell-to-cell communication. Signaling molecules produced by microorganisms may be necessary for stimulating growth of the same or other species, or may prevent their growth. Signaling molecules also represent an interesting and marketable product. MaCuMBA will make use of high throughput platforms such Cocagne, using gel micro-droplet technology, or MicroDish in which many thousands of cultures are grown simultaneously. Various single-cell isolation methods, such as optical tweezers, will aid the isolation of specific target cells. Isolated microorganisms as well as their genomes will be screened for a wide range of bioactive products and other properties of biotechnological interest, such as genetic transformability. Growth efficiency and expression of silent genes of selected strains will be increased also by using the clues obtained from genomic information. MaCuMBA is targeted to SMEs and industry and they make a significant part of the consortium, ensuring that the project focuses on the interests of these partners. Moreover, MaCuMBA has adopted a comprehensive and professional exploitation, dissemination, implementation, and education strategy, ensuring that MaCuMBAs results and products will be directed to end-users and stakeholders.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: ICT-24-2015 | Award Amount: 6.35M | Year: 2016

The TrimBot2020 project will research the robotics and vision technologies to prototype the first outdoor garden trimming robot. The robot will navigate over varying terrain, approach rose bushes, hedges and boxwood topiary, to trim them to an ideal shape. The robot will be based on a modified Bosch Indego robot lawnmower, which will navigate using a user-defined garden map and 3D scene analysis, and then visually servo a novel electric plant cutter. Achieving this will require a combination of robotics and 3D computer vision research and innovation activities. Original developments will be required for 3D sensing of semi-regular surfaces with physical texture (overgrown plant surfaces), coping with outdoor lighting variations, self-localising and navigating over real terrain and around obstacles, visual servoing to align the vehicle with potentially moving target plants, visual servoing to align leaf and branch cutters to a compliant surface, and innovative engineering to deliver all this on a small battery-powered consumer-grade vehicle. Development of these capabilities aligns closely with the Robotics Strategic Research Agenda and Multi-Annual Roadmap aspirations. This project falls clearly in the consumer market domain. It will develop service robotics, advanced perceptual capabilities, mobile manipulation, and flexible and reactive autonomy. As a novel robotics application, the current TRL is 1/2, but the project aims to achieve TRL 5/6. Bosch expects to exploit the projects results to extend its current automated lawnmower product. This exciting project will extend generic robotics and computer vision technologies, explore a new robot application, has an explicit route to market exploitation by an experienced manufacturer, and has a great team with experienced plant roboticists and world-leading computer vision researchers, led by an experienced EC project coordinator.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: REGIONS-2009-1 | Award Amount: 2.29M | Year: 2010

RoK-FOR aims to create a region of knowledge in the forestry sector in Europe, and will significantly contribute to forest sector supporting sustainable use of natural resources, renewable energy, sustainable construction materials and biobased products, without jeopardizing the environment. RoK-FOR is a Coordination Action of five regional research-driven clusters from six European countries: Germany (Baden-Wrttemberg); Finland (North Karelia); Spain (Catalonia), and the cross-border clusters from Croatia-Serbia and France-Spain (Aquitaine-Basque). These regional research-driven clusters collectively form a European level meta-cluster that will be working together to increase the coherence and address the needs of the three Lead Market Initiatives (renewable energy, sustainable construction, and bio-based products) under the umbrella of the sustainable forest management in an innovative and competitive manner. The RoK-FOR work programme is divided into seven interconnected and state of the art work packages which will be instrumental in fulfilling the objectives of the project in a three year period. The project will analyse the regional R&D needs, capacities and policies of the participating clusters, and will integrate them in regional research agendas and a Joint Action Plan to be developed in the course of the project. RoK-FOR will also take measures towards implementing the Joint Action Plan, including business plans and R&D design. RoK-FOR will address the European need of capacity building of the clustersin contributing to regional strategies in the central theme of the project, will support integration of SMEs in RTD, and has a specific Work Package for mentoring the cross-border region of Croatia-Serbia.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2009-1-2-07 | Award Amount: 4.24M | Year: 2009

A number of studies indicate that the market demand for wood will lead to strong competition between the different wood industry branches. This is especially true in view of a globalised wood market, in which production is characterised by fast structural changes and concentration processes. Competition between different wood industries and the development towards large production units, as well as an often highly diversified forest owner structure, demands a flexible delivery of varying wood quantities and quality. This leads to high cost, which weakens the position of the European wood industry within a global market. In addition, hazardous environmental events, such as wind throws, forest fires or beetle attacks, have increased during the past years. There is strong evidence that hazardous environmental events will become even more frequent, leading to unforeseeable damage in forests and to excessive felling. Increased competition, natural risks and political and economical disturbances within a global market undermine the concept of a steady and predictable long term development of the forest sector. The challenge is to improve existing processes of the wood supply chain to the needs of wood industry under these changing conditions. In order to meet the market demands of an improved and flexible wood supply chain, novel logistic concepts must provide better information assessment on wood resources and enhance optimisation models. The proposed project would provide a better and faster response to the demands of the different wood industry branches, which will lead to an increase in value recovery.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.1.2-06 | Award Amount: 7.49M | Year: 2012

Europe has set a clear and ambitious strategy (Europe 2020 Strategy) to base its economy on a smart, sustainable and inclusive growth. Part of this concept is to initiate the development towards an innovative, resource efficient and bio-based (bio-economy) European economy. Such development should contribute to economic growth and the creation of jobs, while mitigating climate change effects and providing effective responses to address the need for carbon neutral energy. In this context, European forests and the forest-based sector play an increasingly important role in fostering smart, sustainable and inclusive growth in Europe based on the production of eco-services and eco-efficient products from wood and non-wood-based products. Up to now the forest-based sector has been mainly build around wood based products. However, also multipurpose trees and non-wood forest products and services can significantly contribute to the achievement of the set goals. The objective of the STAR TREE project is to provide better understanding, knowledge, guidance and tools to support relevant stakeholders (e.g., forest owners, resource managers, enterprises, decision makers, other public and private entities) in optimising the management of multi-purpose trees and developing innovative approaches for increasing the marketability and profitability of NWFP for a more competitive rural economy. The overall impacts of the project are in the long term to support a sustainable rural development through a stronger utilisation of business opportunities based on non-wood forest products and multipurpose trees. This will particularly benefit the rural population as much as land owners and companies through a more competitive and robust rural economy and a better quality of life.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.4.1-12 | Award Amount: 16.04M | Year: 2009

Recent research suggests that the hypoxic micro-environment of tumours is one of the major drivers of metastatic spread of cancer. Furthermore, hypoxic tumour micro-environments may result in treatment resistance of cancer cells, therefore causing a double effect of reducing the potential of a successful treatment of the cancer patient. This project seeks to clarify the roles and functions of the hypoxic tumour micro-environment in relation to the survival of solid tumours likely to metastasise. We will gain new knowledge about molecular mechanisms behind hypoxia-driven metastasis, like the epithelial-mesenchymal transition (EMT) by several routes: (a): mechanisms related to cell growth- and cell proliferation (UPR, mTOR, CA9, HIF, Notch, and VHL), (b): angiogenesis and lymphangiogenesis, (c): metabolism and pH-regulation (d): the handling of reactive oxygen species (ROS). We will generate animal models for the study of the role of hypoxia in metastases and develop a bio-bank of tumour and blood samples for molecular diagnostic studies. We will identify and develop advanced imaging techniques and biomarkers and identify micro-metastases in bone marrow of patients to assist in the selection of appropriate stratification of the actual primary tumours and metastases micro-environmental conditions. We will also create a machine-learning based classifier of tumour hypoxia. The consortium has the necessary expertise to perform proof-of-principle clinical testing of new treatment strategies. We will thus perform clinical tests of new drugs developed to attack the regulatory mechanisms selected from the pre-clinical work and possible synergisms of combined treatments. We will also test new radiotherapy strategies for treatment of primary as well as metastatic tumours. Cancer types chosen for clinical studies are non-small-cell lung carcinoma, squamous cell carcinoma of the larynx, prostate cancer, primary breast cancer and rectal cancer.


Grant
Agency: GTR | Branch: BBSRC | Program: | Phase: Research Grant | Award Amount: 636.76K | Year: 2014

Great advances have been made in the development of proto-cells based on giant unilamellar vesicles (GUVs). However, one essential functional element of all living cells still to be incorporated into such systems is a glycocalyx. This coating of complex carbohydrates extends up to 100 nm from the cell membrane and provides an adhesive layer that mediates interactions between different cell types, viruses and signalling molecules. In most cases, these interactions involve specific carbohydrate-binding proteins (lectins) which may be either soluble or membrane-bound. For example, fertilisation is initiated by a specific carbohydrate on the surface of the egg adhering to a specific lectin on the head of the sperm. Protein-carbohydrate interactions also mediate the endocytosis of many bacteria, viruses and bacterial toxins which stick to specific glycolipids on the cell membrane. Protein-carbohydrate interactions thus present a general strategy for enabling cell adhesion and cell entry. In this project we will design and create a modular toolbox of synthetic glcocalyx components and engineered lectins that will be attached to lipid membranes to enable reversible proto-cell adhesion and incorporated into virus-like particles to mediate proto-cell entry. The methodology will be exemplified through the construction of proto-cells that contain proto-organelles and the assembly and remodelling of proto-tissues in which multiple types of proto-cells are brought together in a pre-defined fashion to create more complex systems.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2007-3-1-02 | Award Amount: 4.14M | Year: 2008

Green plants application is being promoted through different European directives, which aim to achieve 5.75% of liquid fuel supply by 2010 and 20% by 2020. Liquid fuels derived from cellulosic biomass offer an important alternative to conventional energy sources to reduce Europes dependence on fossil fuels. Trees are attractive dedicated energy crops because they display a wide range of growth habits and can be grown on marginal lands unsuited to other agricultural crops including energy grasses, with reduced input costs and optimised land management. ENERGYPOPLAR is designed to develop domesticated energy poplars having both desirable cell-wall traits and high biomass yield under sustainable low-input conditions to be used as a source of lignocellulosic feedstock for bioethanol. ENERGYPOPLAR will (i) Provide a better understanding of fundamental mechanisms determining optimised yield in Populus (ii) Understand mechanisms that regulate the synthesis of cell wall polysaccharides (iii) Provide a better understanding of lignocellulosic quality and in a particular the genetic and genomic basis of high cellulose trees linked to alterations in the quality and quantity of lignin (iv) Develop high thoughput assays for lignocellulosic quality and lignocellulose saccharification potential (v) Establish a platform for rapid genes discovery and testing using systems biology approaches to identify novel transcripts for traits of interest (vi) Develop a delivery pipeline for improved genotypes for ENERGYPOPLAR trees, with traits of interest and begin the process of commercialisation (vii) Establish a tool for environmental sustainability assessments of SRC Populus growing systems (viii) Disseminate the results and transfer technology to the energy industry, land-based sector and to appropriate policy makers


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: ENV.2008.4.1.1.1. | Award Amount: 7.91M | Year: 2009

EuroGEOSS demonstrates the added value to the scientific community and society of making existing systems and applications interoperable and used within the GEOSS and INSPIRE frameworks. The project will build an initial operating capacity for a European Environment Earth Observation System in the three strategic areas of Drought, Forestry and Biodiversity. It will then undertakes the research necessary to develop this further into and advanced operating capacity that provides access not just to data but also to analytical models made understandable and useable by scientists from different disciplinary domains. This concept of inter-disciplinary interoperability requires research in advanced modelling from multi-scale heterogeneous data sources, expressing models as workflows of geo-processing components reusable by other communities, and ability to use natural language to interface with the models. The extension of INSPIRE and GEOSS components with concepts emerging in the Web 2.0 communities in respect to user interactions and resource discovery, also supports the wider engagement of the scientific community with GEOSS as a powerful means to improve the scientific understanding of the complex mechanisms driving the changes that affect our planet.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-5 | Award Amount: 8.03M | Year: 2013

Amputation of a limb may result from trauma or surgical intervention. The amputation traumatically alters the body image, but often leaves sensations that refer to the missing body part. In 50-80% amputees, neuropathic pain develops, also called phantom limb pain (PLP). Both peripheral and central nervous system factors have been implicated as determinants of PLP. Also, PLP may be triggered by physical (changes in the weather) and psychological factors (emotional stress). Recent evidence suggests that PLP may be intricately related to neuroplastic changes in the cortex, and that these changes may modulated by providing sensory input to the stump or amputation zone. However, the understanding of why PLP occurs is still poor, the basic research results have not been tested on a large scale in the clinic, and there are no fully effective, long-term treatments readily available on the market. We aim to challenge the status-quo of PLP therapy by offering technological solutions that will invasively or non-invasively induce natural, meaningful sensations to the amputee to restore the neuroplastic changes in the cortex and thereby control and alleviate PLP. We will assess the effect of cortical neuroplastic, psychological and cognitive components of pain and integrate the knowledge into clinical guidelines. The proposed work directly targets the HEALTH.2013.2.2.1-5 topic. The consortium will build solutions based on existing technologies emerging from previous EU funded research which are presently only available in experimental settings. We believe that implementation of proposed work will be the cornerstone needed to exploit, validate and translate the basic research results into clinical applications and provide long-term, patient-specific solutions to a large group of patients suffering from PLP. The work will assist to improve the quality of life for amputees suffering from phantom limb pain and is of high socio-economic relevance to the EU.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: ENV.2011.2.1.6-1 | Award Amount: 8.85M | Year: 2011

The vital environmental and socio-economic role of European forests is well documented and acknowledged in policy documents of both the European Union and its member states. However, there are critical incoherencies within and between trans-national, national and local forest-related land use policies, the central issue being mismatches between the policies and their implementation at the landscape level. Hence, there is a need to improve existing policy and management approaches capable of delivering a better balance between multiple and conflicting demands for forest goods and services. Diminishing mismatches and providing a new policy and management approach that is sensitive to ecological, socioeconomic and political issues of are the main objectives of INTEGRAL. The objectives are achieved by following a research approach with 3 phases: diagnostic analysis of the status-quo (phase 1), participatory development and evaluation of scenarios (phase 2), and problem-solving oriented back-casting for policy development and evaluation (phase 3). The research design will be applied in a total of 20 landscapes in 10 European countries that differ in key characteristics, such as ownership, the importance of forestry and forest-based industries and the priorities of allocation and management of new and existing forest lands. The involvement of national and local stakeholder groups all the way through the project plays a decisive role in the project. The most important long term impact of INTEGRAL consists of the knowledge and competence base for integrating international, national and local levels in participatory decision and planning processes. This includes the development of manuals for how to conduct such processes, methods for utilizing quantitative decision support tools in the participatory process, and the establishment of a body of knowledge among those participating in the extensive case studies. Thus, the consistency of implemented forest policies can be enhanced.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: ENV.2011.1.3.2-2 | Award Amount: 4.19M | Year: 2011

The project will reduce future Europes vulnerability and risk to drought by innovative in-depth studies that combine drought investigations in six case study areas in water-stressed regions (river basin and national scale) with drought analyses at the pan-European scale. Knowledge transfer across these scales is paramount because vulnerability is context-specific (e.g. physical, environmental, socio-economic, cultural, legal, institutional), which requires analyses on detailed scales, whereas international policies and drought-generating climate drivers and land surface processes are operating on large scales. The project will adopt Science-Policy Interfacing at the various scales, by establishing Case Study Dialogue Fora and a pan-Europe Dialogue Forum, which will ensure that the research will be well integrated into the policy-making from the start of the project onwards. The study will foster a better understanding of past droughts (e.g. underlying processes, occurrences, environmental and socio-economic impacts, past responses), which then will contribute to the assessment of drought hazards and potential vulnerabilities in the 21th C. An innovative methodology for early drought warning at the pan-European scale will be developed, which will improve on the forecasting and a suite of interlinked physical and impact indicators. This will help to increase drought preparedness, and to indentify and implement appropriate Disaster Risk Reduction measures (along the lines of the UN/ISDR HFA). The project will lead through the combined drought studies at different scales to the identification of drought-sensitive regions and sectors across Europe and a more thorough implementation of the EU Water Framework Directive, particularly by further developing of methodologies for Drought Management Plans at different scales (incl. EU level). The work will be linked with the European Drought Centre ensuring that the outcome will be consolidated beyond the project lifetime.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: ENV.2010.2.1.4-1 | Award Amount: 9.23M | Year: 2010

FunDivEUROPE (FUNctional significance of forest bioDIVersity in EUROPE) proposes to quantify the effects of forest biodiversity on ecosystem function and services in major European forest types in the main bioclimatic regions of Europe. FunDivEUROPE will be based on four scientific platforms and seven cross-cutting Work Packages. The project will combine a global network of tree diversity experiments (Experimental Platform) with a newly designed network of observational plots in six focal regions within Europe (Exploratory Platform). Additionally, the project will integrate an in-depth analysis of inventory-based datasets of existing forest monitoring networks to extend the scope to larger spatial and temporal scales (Inventory Platform). FunDivEUROPE will thus combine the strengths of various scientific approaches to explore and quantify the significance of forest biodiversity for a very large range of ecosystem processes and ecosystem services. Using modeling and state-of-the-art techniques for quantitative synthesis, the project will integrate information gained from the different platforms to assess the performance of pure and mixed species stands under changing climate. In addition to the three research platforms, FunDivEUROPE will set up a Knowledge Transfer Platform in order to foster communication, aggregation and synthesis of individual findings in the Work Packages and communication with stakeholders, policy makers and the wider public. The information gained should thus enable forest owners, forest managers and forest policy makers to adapt policies and management for sustainable use of forest ecosystems in a changing environment, capitalizing on the potential effects of biodiversity for ecosystem functioning. The experiences gained within FunDivEUROPE will finally allow contributing to the development of the European Long-Term Ecosystem Research Network, complementing existing forest observation and monitoring networks.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: ISIB-04a-2014 | Award Amount: 5.00M | Year: 2015

Europes bioeconomy is expected to foster economic growth and to tackle significant societal challenges with less harmful environmental effects through innovative, sustainable and inclusive use of European forest resources. Increasing demand for biomass and other ecosystem goods and services calls for changes in forest-related policies at different levels and across different sectors. Accordingly, the recent Forest Strategy provides clear signals towards the need for harmonised information for mapping and assessing the dynamic state of forest ecosystems and their services. Building upon scientific advances in COST E4, 39, 43, USEWOOD, FORSYS, ORCHESTRA; the networks ENFIN, EFFIS, SOSIN; the FP7 EUFODOS, S2BIOM, INTEGRAL, SIMWOOD, FIRE PARADOX the project DIABOLO aims to: i) strengthen the methodological framework towards more accurate, harmonised and timely forest information, e.g. on growing stock and stock changes, biomass, carbon, NWFP; enable the analysis of sustainable biomass supply derived from multipurpose and multisource national forest inventories; and facilitate near real-time forest disturbance monitoring, e.g. on forest fires, storm, drought, insect outbreaks; ii) support EU policy processes, international reporting obligations, forest administration and forest planning entities with new methodologies and EU-wide consistent forest information; iii) make innovative use of existing field-collected data and EC space-based applications of EO and satellite positioning systems with reference to INSPIRE and GEOSS, and global monitoring systems such as REDD\, FLEGT and UNFF. To deliver high impact, beyond state-of-the-art work within the ecological and socio-economic diversity in Europe, the trans-disciplinary DIABOLO involves experts in quantitative modelling, policy science and NFIs, from 26 European countries, committed to provide new methodologies and information for various end-uses, including EFDAC (FISE) at JRC, GLOBIOM at IIASA and work at FAO/UNECE.


Grant
Agency: Cordis | Branch: H2020 | Program: IA | Phase: BIOTEC-3-2014 | Award Amount: 9.25M | Year: 2015

C-C bond forming reactions are at the heart of industrial organic synthesis, but remain largely unexplored due to long development timelines and the lack of broad biocatalytic reaction platforms. CARBAZYMES addresses these challenges by assembling an interdisciplinary and intersectoral consortium as a powerful synergistic tool to promote innovation in the field of biocatalytic C-C bond formation at large scale, and thus the global competitiveness of the European chemical and pharmaceutical industry. The proposed consortium, with 50% industrial participation, represents academia but also commercial interests in different stages of the research-to-market process. This top-down approach, together with a life-cycle innovation approach ensures an industrial drive to the project. Clearly aligned with the scope of topic BIOTEC3-2014, CARBAZYMES will pursue the biocatalytic synthesis (spanning TRLs 5-7) of 4 APIs and 3 bulk chemicals corresponding to market needs detected by the industrial partners in the Consortium. This will be accomplished through an inter-disciplinary approach which includes: i) a broad platform of 4 types of unique C-C bond-forming enzymes, mostly lyases; ii) the capacity to rapidly evolve enzymes to operate under industrial conditions by means of novel enzyme panels and massive screening methods; iii) application of microreactor technology for bioprocess characterization; iv) demonstration actions comprising technical (up to 100L) and economic viability studies carried out by industrial partners. CARBAZYMES unmistakably aims to have social and economic impact by addressing markets worth bn , developing enzyme evolution technologies beyond the state of the art and creating qualified jobs and technical-scale facilities at the industrial partners sites. CARBAZYMES will also achieve an environmental impact by enforcing that the developed processes replace more energy and resource intensive processes, thus leading to reduced environmental footprints.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.1.2-2 | Award Amount: 14.64M | Year: 2008

T-cell activation, whether induced by pathogens or auto-antigens, is a complex process relying on multiple layers of tightly controlled intracellular signalling modules that form an intricate network. Defects in this network can cause severe and chronic disorders such as autoimmune diseases. Although 5% of the population suffer from these diseases, only a few therapeutic treatments are available. To a large extent this is attributed to the lack of systems-level insights, which would provide concepts of how to modulate T-cell activation. The SYBILLA project groups 14 partners from 9 different EU countries, including 3 SMEs. Through a multidisciplinary effort it aims to understand at the systems level, how T-cells discriminate foreign from auto-antigens. Towards this goal, a transgenic mouse system will be used as a tractable physiological model. Data will be validated in human T-cells and a humanised mouse model for multiple sclerosis. SYBILLA will develop technological and mathematical tools to generate and integrate high-density quantitative data describing T-cell activation. Proteomics, transcriptomics, metabolomics, imaging and multiplexed biochemical techniques will be applied to obtain holistic maps of T-cell signalling networks and to achieve a quantitative understanding of the network and its regulation in response to different inputs. Building upon our existing network model, constant iterations will be used to develop more robust dynamic models to describe the networks response to perturbations. This will culminate in the generation of a Virtual T-Cell, allowing computer simulation to refine the predictability of physiological and pathophysiological reactions. SYBILLAs impact on EU biopharmaceutical competitiveness will be enormous through identification of new pharmacologic targets, optimised prediction of immunomodulatory drug efficacy, discovery of new concerted biomarkers and improvement of personalised medication for treating autoimmune diseases.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: ENV.2008.2.1.6.1. | Award Amount: 9.07M | Year: 2009

The project MOdels for AdapTIVE forest Management (MOTIVE) will evaluate the consequences of the intensified competition for forest resources given climate and land use change. The project focuses on a wide range of European forest types under different intensities of forest management. In particular, MOTIVE examines impacts with respect to the disturbance regimes determining forest dynamics. MOTIVE seeks to develop and evaluate strategies that can adapt forest management practices to balance multiple objectives under changing environmental conditions. The evaluation of different adaptive management systems will take place within a scenario analysis and a regional landscape framework. A wide range of possible scenarios will be taken into account on different time scales. The main forest types in Europe for the most important bioclimatic regions will be covered and the most important goods and services delivered by Eurpean forests will be assessed using the most up to date models. The ultimate objective of the MOTIVE project is to provide insights, data and tools to improve policymaking and adaptive forest resource management in the face of rapidly changing climatic and land-use conditions. In order to reach its objectives, MOTIVE is organized into six scientific work packages in addition to a management-oriented work package : Baseline trends and possible futures for the EU. Development of improved models for Adaptive Forest Management. Testing and evaluating management options and risks. Evaluating and selecting good adaptive forest management strategies. Improved decision support in adaptive forest management. Stakeholder/Decision maker interaction and Dissemination. One of the main deliverables of MOTIVE will be an Adaptive Forest Management toolbox. The toolbox will provide up-to-date methods for planning and decision making in AFM to the decision maker (forest resource manager, policy maker) for actual use in strategic and tactical forest management planning


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2013.2.1 | Award Amount: 8.48M | Year: 2014

Clutter in an open world is a challenge for many aspects of robotic systems, especially for autonomous robots deployed in unstructured domestic settings, affecting navigation, manipulation, vision, human robot interaction and planning.SQUIRREL addresses these issues by actively controlling clutter and incrementally learning to extend the robots capabilities while doing so. We term this the B3 (bit by bit) approach, as the robot tackles clutter one bit at a time and also extends its knowledge continuously as new bits of information become available.SQUIRREL is inspired by a user driven scenario, that exhibits all the rich complexity required to convincingly drive research, but allows tractable solutions with high potential for exploitation. We propose a toy cleaning scenario, where a robot learns to collect toys scattered in loose clumps or tangled heaps on the floor in a childs room, and to stow them in designated target locations.We will advance science w.r.t. manipulation, where we will incrementally learn grasp affordances with a dexterous hand; segmenting and learning objects and object category models from a cluttered scene; localisation and navigation in a crowded and changing scene based on incrementally built 3D environment models; iterative task planning in an open world; and engaging with multiple users in a dynamic collaborative task.Progress will be measured in scenarios of increasing complexity, starting with known object classes, via incremental learning of objects and grasp affordances to the full system with failure recovery and active control of clutter, instantiated on two different robot platforms.Systems will be evaluated at an end user site where children in nurseries teach the robot how to clean up, and will be exploited by an industrial partner with a strong market presence in advanced robotic toys, who will take up project outcomes to be integrated in their current line of developments.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.1.2-1 | Award Amount: 3.14M | Year: 2012

Currently cervical histology is the gold standard procedure in the field. However, there is a need for alternative approaches and specific biomarkers to aid objective CIN lesion grading and to identify true high grade cervical disease, especially in the advent of primary HPV screening and widespread HPV vaccination. Panel of mRNA markers has been developed using systems biology and datamining tools and has demonstrated high specificity [93%] and sensitivity [88%] for detecting CIN 2-3 lesions. Clinical data supports its application as a cervical cancer grading biomarker as well. Our goal is to ascertain the utility of this novel panel and extend it using systems biology approaches with experimentally and computationally derived proteomic biomarkers in cervical pre cancer and cancer disease, for more accurate diagnosis of CIN disease. Toward that goal we establish a general framework for validation of proteomic biomarkers. This will be achieved by combining advanced technologies in a robust and time-effective way, including DNA array to protein array copying, Human Combinatorial Antibody Library of phage display and iRIfS, imaging Reflectometric Interference Spectroscopy technology. Systems biology approached would focus on both the existing and new markers and will use this framework rapid validation. Systems biology exploration of some specific pathways is justified by our previous data, that the CIN1/CIN2\ discrimination could be related to some given pathways. The proposed approach potentially reduce costs of cervical clinical studies providing a reliable, quantitative, multi-content diagnostic approaches and results in reducing the number of colposcopic events. Cytology specimens will be of greater clinical utility and will result in earlier detection of disease. Molecular characterization of CIN lesions provides a basis for re-definition of histological categories.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2013.2.2 | Award Amount: 6.28M | Year: 2013

Part handling during the assembly stages in the automotive industry is the only task with automation levels below 30% due to the variability of the production and to the diversity of suppliers and parts. The full automation of such task will not only have a huge impact in the automotive industry but will also act as a cornerstone in the development of advanced mobile robotic manipulators capable of dealing with unstructured environments, thus opening new possibilities in general for manufacturing SMEs. The STAMINA project will use a holistic approach by partnering with experts in each necessary key fields, thus building on previous R&D to develop a fleet of autonomous and mobile industrial robots with different sensory, planning and physical capabilities for jointly solving three logistic and handling tasks: De-palletizing, Bin-Picking and Kitting. The robot and orchestration systems will be developed in a lean manner using an iterative series of development and validation testes that will not only assess the performance and usability of the system but also allow goal-driven research. STAMINA will give special attention to the system integration promoting and assessing the development of a sustainable and scalable robotic system to ensure a clear path for the future exploitation of the developed technologies. In addition to the technological outcome, STAMINA will allow to give an impression on how a sharing of work and workspace between humans and robots could look in the future.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ENERGY.2013.3.7.1 | Award Amount: 5.16M | Year: 2013

The main aim of this project is to support the sustainable delivery of non-food biomass feedstock at local, regional and pan European level through developing strategies, and roadmaps that will be informed by a computerized and easy to use toolset (and respective databases) with update harmonized datasets at local, regional, national and pan European level for EU27, western Balkans, Turkey and Ukraine. It will do so by comparing and making use of the most recent relevant information from recent and ongoing EU projects by a set of carefully selected validation case studies and in concise collaboration with key stakeholders from policy, industry and markets.The project fits under the overall umbrella of the Europe 2020 strategy for the building of a bioeconomy, as well as the targets for deployment of renewable energies and reduction of greenhouse gas emissions.The project will build up a concise knowledge base both for the sustainable supply and logistics of nonfood biomass (quantities, costs, technological pathway options for 2020 and beyond), for the development of technology and market strategies to support the development of a resource efficient Bioeconomy for Europe. This includes industrial processes (i.e. bio-based industries) for manufacturing biomass-derived goods/products as well as energy conversion, both for large scale and small scale units.The research work will be organized in three individual but strongly interrelated Themes: Theme 1 will focus on methodological approaches, data collection and estimation of sustainable biomass potentials, resource efficient pathways and optimal logistical supply routes as well as will develop the computerized toolset. Theme 2 will make use of the findings of Theme 1 and develop a Vision, Strategies and an R&D roadmap for the sustainable delivery of non-food biomass feedstock at local, regional and pan European level. Theme 3 will validate the findings from Themes 1 and 2 and ensure the project outreach


Grant
Agency: Cordis | 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.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.93M | Year: 2014

TEMPO addresses the needs of European companies and society for embedded control technology, through training on cutting edge research in the rapidly emerging inter-disciplinary field of embedded predictive control and optimization. The key objectives are: - to expand the scientific and technical knowledge platform for Embedded Predictive Control and Optimization in Europe; - to exploit this platform to train a new generation of world class researchers and professionals that are highly attractive for employment by the European industry; - to establish structures for long-term cooperation and strengthen the relations among the leading universities and industry in Europe in this field, to continuously develop the research training platform that European industry relies on. To achieve the objectives listed above, the main tasks of TEMPO are: - to attract and train 14 Early Stage Researchers in embedded MPC and optimization via a joint academic/industrial program of cutting edge training-by-research, high quality supervision, complementary and transferable skills training, inter-network secondments, and workshops; - to create a closely connected group of leading European scientists that are highly sought after by European industry, and ready to push forward embedded MPC and optimization into new innovative products, industries and services; - to build a solid foundation for long-term European excellence in this field by disseminating the research and training outcomes and best practice of TEMPO into the doctoral schools of the partners, and by fostering long-term partnerships and collaboration mechanisms that will outlast the ITN; - to disseminate the know-how of the participants to each other and to external groups via networking activities, inter-sectoral exposure, secondments, workshops, demonstrations, sharing of learning material, public engagement and outreach activities, and open source public domain software outcomes.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ENV.2013.6.2-7 | Award Amount: 3.90M | Year: 2013

European cultural landscapes are valued as everyday living environment, countryside, heritage, scenery with aesthetic and recreational qualities and unique biodiversity, and as a source of ecosystem services that they provide to society. Cultural landscapes, however, are undergoing rapid and fundamental transformations across Europe, mainly as a result of an on-going polarization of land use, with abandonment and rural exodus on the one hand, and intensification and (peri-) urbanisation on the other. So far, substantial challenges have inhibited the design of effective responses to safeguard cultural landscape values. The proposed HERCULES project strives for the empowerment of public and private actors to protect, manage, and plan for sustainable landscapes of significant cultural, historical, and archaeological value at local, national, and pan-European scales. By applying and developing innovative technologies and tools for assessing and mapping cultural landscapes, the project will (a) synthesise existing knowledge on drivers, patterns, and outcomes of persistence and change in Europes cultural landscapes; (b) perform targeted case studies to develop in-depth insights on dynamics and values of cultural landscapes; (c) develop a typology of cultural landscapes and scale-up case study insights using observations and landscape modelling; (d) develop visions for re-coupling social and ecological components in cultural landscapes and translate them into policy and management options; and (e) design and implement a community-based Knowledge Hub for Good Landscape Practice and demonstrate it with land users, agencies, SMEs, and citizen associations. HERCULES comprises European universities, SMEs, NGOs, and a research institute that are leaders in landscape science and practice. The project follows the European Landscape Conventions call for transdisciplinary research and involves all actors with stakes in cultural landscapes of historical and archaeological value.


Rodriguez A.,Albert Ludwigs University of Freiburg | Chakrabarti A.,Kalyani University | Romer R.A.,University of Warwick
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

We describe how to engineer wave-function delocalization in disordered systems modeled by tight-binding Hamiltonians in d1 dimensions. We show analytically that a simple product structure for the random on-site potential energies, together with suitably chosen hopping strengths, allows a resonant scattering process leading to ballistic transport along one direction, and a controlled coexistence of extended Bloch states and anisotropically localized states in the spectrum. We demonstrate that these features persist in the thermodynamic limit for a continuous range of the system parameters. Numerical results support these findings and highlight the robustness of the extended regime with respect to deviations from the exact resonance condition for finite systems. The localization and transport properties of the system can be engineered almost at will and independently in each direction. This study gives rise to the possibility of designing disordered potentials that work as switching devices and band-pass filters for quantum waves, such as matter waves in optical lattices. © 2012 American Physical Society.


Butz M.,Jülich Research Center | Steenbuck I.D.,Albert Ludwigs University of Freiburg | Van Ooyen A.,VU University Amsterdam
Frontiers in Synaptic Neuroscience | Year: 2014

In networks with small-world topology, which are characterized by a high clustering coefficient and a short characteristic path length, information can be transmitted efficiently and at relatively low costs. The brain is composed of small-world networks, and evolution may have optimized brain connectivity for efficient information processing. Despite many studies on the impact of topology on information processing in neuronal networks, little is known about the development of network topology and the emergence of efficient small-world networks. We investigated how a simple growth process that favors short-range connections over long-range connections in combination with a synapse formation rule that generates homeostasis in post-synaptic firing rates shapes neuronal network topology. Interestingly, we found that small-world networks benefited from homeostasis by an increase in efficiency, defined as the averaged inverse of the shortest paths through the network. Efficiency particularly increased as small-world networks approached the desired level of electrical activity. Ultimately, homeostatic small-world networks became almost as efficient as random networks. The increase in efficiency was caused by the emergent property of the homeostatic growth process that neurons started forming more long-range connections, albeit at a low rate, when their electrical activity was close to the homeostatic set-point. Although global network topology continued to change when neuronal activities were around the homeostatic equilibrium, the small-world property of the network was maintained over the entire course of development. Our results may help understand how complex systems such as the brain could set up an efficient network topology in a self-organizing manner. Insights from our work may also lead to novel techniques for constructing large-scale neuronal networks by self-organization. © 2014 Butz, Steenbuck and van Ooyen.


Carrera M.,Albert Ludwigs University of Freiburg | Giulini D.,Leibniz University of Hanover | Giulini D.,University of Bremen
Reviews of Modern Physics | Year: 2010

Attempts to estimate the influence of global cosmological expansion on local systems are reviewed. Here "local" is taken to mean that the sizes of the considered systems are much smaller than cosmologically relevant scales. For example, such influences can affect orbital motions as well as configurations of compact objects, like black holes. Also discussed are how measurements based on the exchange of electromagnetic signals of distances, velocities, etc. of moving objects are influenced. As an application, orders of magnitude of such effects are compared with the scale set by the apparently anomalous acceleration of the Pioneer 10 and 11 spacecrafts, which is 10 -9/s2. There is no reason to believe that the latter is of cosmological origin. However, the general problem of gaining a qualitative and quantitative understanding of how the cosmological dynamics influences local systems remains challenging, with only partial clues being so far provided by exact solutions to the field equations of general relativity. © 2010 The American Physical Society.


Taormina A.,Durham University | Wendland K.,Albert Ludwigs University of Freiburg
Journal of High Energy Physics | Year: 2013

In view of a potential interpretation of the role of the Mathieu group M 24 in the context of strings compactified on K3 surfaces, we develop techniques to combine groups of symmetries from different K3 surfaces to larger 'overarching' symmetry groups. We construct a bijection between the full integral homology lattice of K3 and the Niemeier lattice of type A 1 24, which is simultaneously compatible with the finite symplectic automorphism groups of all Kummer surfaces lying on an appropriate path in moduli space connecting the square and the tetrahedral Kummer surfaces. The Niemeier lattice serves to express all these symplectic automorphisms as elements of the Mathieu group M 24, generating the 'overarching finite symmetry group' (Z2)4 ∝ A 7 of Kummer surfaces. This group has order 40320, thus surpassing the size of the largest finite symplectic automorphism group of a K3 surface by orders of magnitude. For every Kummer surface this group contains the group of symplectic automorphisms leaving the Kähler class invariant which is induced from the underlying torus. Our results are in line with the existence proofs of Mukai and Kondo, that finite groups of symplectic automorphisms of K3 are subgroups of one of eleven subgroups of M 23, and we extend their techniques of lattice embeddings for all Kummer surfaces with Kähler class induced from the underlying torus. © 2013 SISSA, Trieste, Italy.


Hanewinkel M.,Swiss Federal Institute of forest | Hanewinkel M.,Albert Ludwigs University of Freiburg | Cullmann D.A.,Forest Research Institute of Baden Wuerttemberg | Schelhaas M.-J.,Wageningen University | And 2 more authors.
Nature Climate Change | Year: 2013

European forests, covering more than 2 million km2 or 32% of the land surface1, are to a large extent intensively managed and support an important timber industry. Climate change is expected to strongly affect tree species distribution within these forests2,3. Climate and land use are undergoing rapid changes at present4, with initial range shifts already visible5. However, discussions on the consequences of biome shifts have concentrated on ecological issues6. Here we show that forecasted changes in temperature and precipitation may have severe economic consequences. On the basis of our model results, the expected value of European forest land will decrease owing to the decline of economically valuable species in the absence of effective countermeasures. We found that by 2100 - depending on the interest rate and climate scenario applied - this loss varies between 14 and 50% (mean: 28% for an interest rate of 2%) of the present value of forest land in Europe, excluding Russia, and may total several hundred billion Euros. Our model shows that - depending on different realizations of three climate scenarios - by 2100, between 21 and 60% (mean: 34%) of European forest lands will be suitable only for a Mediterranean oak forest type with low economic returns for forest owners and the timber industry and reduced carbon sequestration. Copyright © 2013 Macmillan Publishers Limited.


Hills T.T.,University of Warwick | Kalff C.,Albert Ludwigs University of Freiburg | Wiener J.M.,Bournemouth University
PLoS ONE | Year: 2013

A considerable amount of research has claimed that animals' foraging behaviors display movement lengths with power-law distributed tails, characteristic of Lévy flights and Lévy walks. Though these claims have recently come into question, the proposal that many animals forage using Lévy processes nonetheless remains. A Lévy process does not consider when or where resources are encountered, and samples movement lengths independently of past experience. However, Lévy processes too have come into question based on the observation that in patchy resource environments resource-sensitive foraging strategies, like area-restricted search, perform better than Lévy flights yet can still generate heavy-tailed distributions of movement lengths. To investigate these questions further, we tracked humans as they searched for hidden resources in an open-field virtual environment, with either patchy or dispersed resource distributions. Supporting previous research, for both conditions logarithmic binning methods were consistent with Lévy flights and rank-frequency methods-comparing alternative distributions using maximum likelihood methods-showed the strongest support for bounded power-law distributions (truncated Lévy flights). However, goodness-of-fit tests found that even bounded power-law distributions only accurately characterized movement behavior for 4 (out of 32) participants. Moreover, paths in the patchy environment (but not the dispersed environment) showed a transition to intensive search following resource encounters, characteristic of area-restricted search. Transferring paths between environments revealed that paths generated in the patchy environment were adapted to that environment. Our results suggest that though power-law distributions do not accurately reflect human search, Lévy processes may still describe movement in dispersed environments, but not in patchy environments-where search was area-restricted. Furthermore, our results indicate that search strategies cannot be inferred without knowing how organisms respond to resources-as both patched and dispersed conditions led to similar Lévy-like movement distributions. © 2013 Hills et al.


Santiago-Alarcon D.,Institute Ecologia | Santiago-Alarcon D.,Albert Ludwigs University of Freiburg | Palinauskas V.,Institute of Ecology | Schaefer H.M.,Albert Ludwigs University of Freiburg
Biological Reviews | Year: 2012

Haemosporida is a large group of vector-borne intracellular parasites that infect amphibians, reptiles, birds, and mammals. This group includes the different malaria parasites (Plasmodium spp.) that infect humans around the world. Our knowledge on the full life cycle of these parasites is most complete for those parasites that infect humans and, to some extent, birds. However, our current knowledge on haemosporidian life cycles is characterized by a paucity of information concerning the vector species responsible for their transmission among vertebrates. Moreover, our taxonomic and systematic knowledge of haemosporidians is far from complete, in particular because of insufficient sampling in wild vertebrates and in tropical regions. Detailed experimental studies to identify avian haemosporidian vectors are uncommon, with only a few published during the last 25 years. As such, little knowledge has accumulated on haemosporidian life cycles during the last three decades, hindering progress in ecology, evolution, and systematic studies of these avian parasites. Nonetheless, recently developed molecular tools have facilitated advances in haemosporidian research. DNA can now be extracted from vectors' blood meals and the vertebrate host identified; if the blood meal is infected by haemosporidians, the parasite's genetic lineage can also be identified. While this molecular tool should help to identify putative vector species, detailed experimental studies on vector competence are still needed. Furthermore, molecular tools have helped to refine our knowledge on Haemosporida taxonomy and systematics. Herein we review studies conducted on Diptera vectors transmitting avian haemosporidians from the late 1800s to the present. We also review work on Haemosporida taxonomy and systematics since the first application of molecular techniques and provide recommendations and suggest future research directions. Because human encroachment on natural environments brings human populations into contact with novel parasite sources, we stress that the best way to avoid emergent and reemergent diseases is through a program encompassing ecological restoration, environmental education, and enhanced understanding of the value of ecosystem services. © 2012 The Authors. Biological Reviews © 2012 Cambridge Philosophical Society.


Beneke M.,Institute For Theoretische Teilchenphysik Und Kosmologie | Falgari P.,Durham University | Schwinn C.,Albert Ludwigs University of Freiburg
Nuclear Physics B | Year: 2011

We derive a factorization formula for the production of pairs of heavy coloured particles in hadronic collisions near the production threshold that establishes factorization of soft and Coulomb effects. This forms the basis for a combined resummation of Coulomb and soft corrections, including the non-trivial interference of the two effects. We develop a resummation formalism valid at NNLL accuracy using the momentum-space approach to soft gluon resummation. We present numerical results for the NLL resummed squark-antisquark production cross section at the LHC and Tevatron, including also the contribution of squark-antisquark bound states below threshold. The total correction on top of the next-to-leading order approximation is found to be sizeable, and amounts to (4-20)% in the squark mass region 200 GeV-3 TeV at the 14 TeV LHC. The scale dependence of the total cross section is also reduced. © 2010 Elsevier B.V.


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.


Muller M.,Albert Ludwigs University of Freiburg | Sprenger G.A.,University of Stuttgart | Pohl M.,Jülich Research Center
Current Opinion in Chemical Biology | Year: 2013

The present review summarizes recent achievements in enzymatic thiamine catalysis during the past three years. With well-established enzymes such as BAL, PDC and TK new reactions have been identified and respective variants were prepared, which enable access to stereoisomeric products. Further we highlight recent progress with 'new' ThDP-dependent enzymes like MenD and PigD, which catalyze the Stetter-like 1,4 addition of aldehydes and YerE, which is the first known ThDP-dependent enzyme accepting ketones as acceptors. © 2013 Elsevier Ltd.


Hoche S.,SLAC | Krauss F.,Durham University | Schonherr M.,Durham University | Siegert F.,Albert Ludwigs University of Freiburg
Physical Review Letters | Year: 2013

For the first time, differential cross sections for the production of W bosons in conjunction with up to three jets, computed at next-to leading order in QCD and including parton shower corrections, are presented and compared to recent experimental data from the Large Hadron Collider. © 2013 American Physical Society.


Kuntsi J.,King's College London | Klein C.,Bangor University | Klein C.,Albert Ludwigs University of Freiburg
Current Topics in Behavioral Neurosciences | Year: 2012

Intraindividual variability (IIV) – reflecting short-term (within-session), within-person fluctuations in behavioral performance – and, specifically, reaction time (RT) variability, is strongly linked with attention-deficit hyperactivity disorder (ADHD) both at the phenotypic and genetic levels. Phenotypic case–control comparisons show a consistent and robust association between ADHD and RT variability across a broad range of cognitive tasks, samples, and age ranges (from childhood to adulthood). The association does not appear to be a nonspecific effect mediated by lower general cognitive ability. The finding from quantitative genetic studies of the shared genetic etiology between ADHD and RT variability is similarly robust, replicating across tasks, samples, and definitions of ADHD. Molecular genetic studies have produced intriguing initial findings: increasing sample sizes and replications across datasets remain priorities for future efforts. While the field has come a long way from considering increased RT variability in ADHD as the “noise” or “error” that we need to reduce in our data, the investigation of the causal pathways is only beginning. The neural basis of IIV is being investigated, with initial data pointing to a crucial role of fronto-striatal systems in controlling behavioral consistency. Several theories have been put forward to account for the observed IIV in ADHD, including accounts of arousal regulation, temporal processing and the “default-mode network.” For the wider implications of the IIV phenomenon to be fully realized, we need to learn further about the underlying processes, their developmental context, and about shared and unique causal pathways across disorders where high RT variability is observed. © Springer‐Verlag Berlin Heidelberg 2011.


Matzarakis A.,Albert Ludwigs University of Freiburg | Nastos P.T.,National and Kapodistrian University of Athens
Theoretical and Applied Climatology | Year: 2011

The goal of this study is the analysis of heat waves and their impact on humans, using human biometeorological indices, which are based on the energy balance of the human body. The implications for humans are not only described through the intensity of the heat waves, but also through their duration over consecutive days. Both intensity and duration were analyzed for the Greater Athens Area during the period 1955 to 2001. The analysis was carried out using the daily physiologically equivalent temperature and the daily minimum air temperature. Based on these two parameters, the results showed an increase in the average duration of heat waves. Furthermore, the use of the Gaussian filter revealed the intra-annual variation of heat stress conditions and their relevance to humans. The results could be used for the management of the negative consequences of heat waves in cities suffering from environmental pollution and also for climate impact studies. © 2010 Springer-Verlag.


Schneider C.,Max Planck Institute of Quantum Optics | Schneider C.,Albert Ludwigs University of Freiburg | Porras D.,Complutense University of Madrid | Schaetz T.,Max Planck Institute of Quantum Optics | Schaetz T.,Albert Ludwigs University of Freiburg
Reports on Progress in Physics | Year: 2012

Direct experimental access to some of the most intriguing quantum phenomena is not granted due to the lack of precise control of the relevant parameters in their naturally intricate environment. Their simulation on conventional computers is impossible, since quantum behaviour arising with superposition states or entanglement is not efficiently translatable into the classical language. However, one could gain deeper insight into complex quantum dynamics by experimentally simulating the quantum behaviour of interest in another quantum system, where the relevant parameters and interactions can be controlled and robust effects detected sufficiently well. Systems of trapped ions provide unique control of both the internal (electronic) and external (motional) degrees of freedom. The mutual Coulomb interaction between the ions allows for large interaction strengths at comparatively large mutual ion distances enabling individual control and readout. Systems of trapped ions therefore exhibit a prominent system in several physical disciplines, for example, quantum information processing or metrology. Here, we will give an overview of different trapping techniques of ions as well as implementations for coherent manipulation of their quantum states and discuss the related theoretical basics. We then report on the experimental and theoretical progress in simulating quantum many-body physics with trapped ions and present current approaches for scaling up to more ions and more-dimensional systems. © 2012 IOP Publishing Ltd.


Nastos P.T.,National and Kapodistrian University of Athens | Matzarakis A.,Albert Ludwigs University of Freiburg
Theoretical and Applied Climatology | Year: 2012

This paper investigates whether there is any association between the daily mortality for the wider region of Athens, Greece and the thermal conditions, for the 10-year period 1992-2001. The daily mortality datasets were acquired from the Hellenic Statistical Service and the daily meteorological datasets, concerning daily maximum and minimum air temperature, from the Hellinikon/Athens meteorological station, established at the headquarters of the Greek Meteorological Service. Besides, the daily values of the thermal indices Physiologically Equivalent Temperature (PET) and Universal Thermal Climate Index (UTCI) were evaluated in order to interpret the grade of physiological stress. The first step was the application of Pearson's χ 2 test to the compiled contingency tables, resulting in that the probability of independence is zero (p = 0. 000); namely, mortality is in close relation to the air temperature and PET/UTCI. Furthermore, the findings extracted by the generalized linear models showed that, statistically significant relationships (p < 0. 01) between air temperature, PET, UTCI and mortality exist on the same day. More concretely, on one hand during the cold period (October-March), a 10°C decrease in daily maximum air temperature, minimum air temperature, temperature range, PET and UTCI is related with an increase 13%, 15%, 2%, 7% and 6% of the probability having a death, respectively. On the other hand, during the warm period (April-September), a 10°C increase in daily maximum air temperature, minimum air temperature, temperature range, PET and UTCI is related with an increase 3%, 1%, 10%, 3% and 5% of the probability having a death, respectively. Taking into consideration the time lag effect of the examined parameters on mortality, it was found that significant effects of 3-day lag during the cold period appears against 1-day lag during the warm period. In spite of the general aspect that cold conditions seem to be favourable factors for daily mortality, the air temperature and PET/UTCI exceedances over specific thresholds depending on the distribution reveal that, very hot conditions are risk factors for the daily mortality. © 2011 Springer-Verlag.


Schamel W.W.A.,Albert Ludwigs University of Freiburg | Alarcon B.,Autonomous University of Madrid
Immunological Reviews | Year: 2013

Despite the low affinity of the T-cell antigen receptor (TCR) for its peptide/major histocompatibility complex (pMHC) ligand, T cells are very sensitive to their antigens. This paradox can be resolved if we consider that the TCR may be organized into pre-existing oligomers or nanoclusters. Such structures could improve antigen recognition by increasing the functional affinity (avidity) of the TCR-pMHC interaction and by allowing cooperativity between individual TCRs. Up to approximately 20 TCRs become tightly apposed in these nanoclusters, often in a linear manner, and such structures could reflect a relatively generalized phenomenon: the non-random concentration of membrane receptors in specific areas of the plasma membrane known as protein islands. The association of TCRs into nanoclusters can explain the enhanced kinetics of the pMHC-TCR interaction in two dimensional versus three dimensional systems, but also their existence calls for a revision of the TCR triggering models based on pMHC-induced TCR clustering. Interestingly, the B-cell receptor and the FcεRI have also been shown to form nanoclusters, suggesting that the formation of pre-existing receptor oligomers could be widely used in the immune system. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.


Banfi A.,Albert Ludwigs University of Freiburg | Dasgupta M.,University of Manchester | Marzani S.,Durham University | Tomlinson L.,University of Manchester
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

We make theoretical predictions for the recently introduced variable φ * corresponding to the azimuthal angle between leptons produced in the Drell-Yan process at the LHC. As a consequence of this work we are also able to generate results for the more commonly studied transverse momentum Q T of the lepton pair. Comparisons of these purely perturbative estimates for the Q T case yield good agreement with ATLAS and CMS data, as we demonstrate. We anticipate that this work will help stimulate measurements of φ * at the LHC. © 2012 Elsevier B.V.


Tromas A.,University Paris - Sud | Paponov I.,Albert Ludwigs University of Freiburg | Perrot-Rechenmann C.,University Paris - Sud
Trends in Plant Science | Year: 2010

In this review, we examine the role of AUXIN BINDING PROTEIN 1 (ABP1) in mediating growth and developmental responses. ABP1 is involved in a broad range of cellular responses to auxin, acting either as the main regulator of the response, such as seen for entry into cell division or, as a fine-tuning device as for the regulation of expression of early auxin response genes. Phylogenetic analysis has revealed that ABP1 is an ancient protein that was already present in various algae and has acquired a motif of retention in the endoplasmic reticulum only recently. An evaluation of the evidence for ABP1 function according to its cellular localization supports the plasma membrane as a starting point for ABP1-mediated auxin signaling. © 2010 Elsevier Ltd.


Grant
Agency: Cordis | Branch: H2020 | Program: ERC-COG | Phase: ERC-CoG-2014 | Award Amount: 2.00M | Year: 2015

Mitochondria are essential organelles with crucial roles in cellular energy metabolism, Fe-S cluster biogenesis, signaling and apoptosis. Mitochondrial dysfunction causes encephalomyopathy and neurodegenerative diseases. Mitochondria possess a remarkably high content of small proteins compared to other cellular compartments. About one third of the cellular proteins 15 kDa characterized to date are located in mitochondria. Functional examples of such small proteins cover the whole mitochondrial biology like cristae morphology, Fe-S cluster formation, metabolite transport, protein biogenesis and respiration. However, the intracellular localization and function of most small proteins is unknown. These small proteins constitute one third of the uncharacterized open reading frames and even three quarters of the dubious open reading frames in the model organism budding yeast. Taken together we predict that more than 10% of the mitochondrial proteome deserves to be discovered. In an initial study we demonstrated the mitochondrial localization of several uncharacterized small open reading frame (smORF) proteins. MITOsmORFs aims to identify over 100 novel small mitochondrial proteins. MITOsmORFs will determine the submitochondrial localization and the functional role of the novel mitochondrial proteins by genetic, proteomic, metabolomic and lipidomic analysis, including interaction mapping and characterization of mitochondrial activities in vivo and in organello to explore the unknown biology of smORF proteins localized to mitochondria.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.1.2-5 | Award Amount: 3.83M | Year: 2009

Background. Parkinson Disease is the second most common progressive neurodegenerative disorder. The selective degeneration of subsets of midbrain dopaminergic neurons is believed to be the primary cause for disruption of the ability to control movements. Objective. We propose to apply a highly interdisciplinary approach to construct complex networks consisting of protein coding genes, non-protein-coding genes and cis-regulatory elements within dopaminergic neurons in the brain across three chordate organisms (Mouse, Zebrafish and Ciona) to identify and compare gene regulatory networks in these neurons. This will be achieved by: Expression profiling of genes on single dopaminergic neurons via laser microdissection and transgenic lines in Mouse, Ciona and Zebrafish HT-Sequencing of microCAGE assays on dopaminergic neurons, providing TSS usage and transcript discovery Microscopy HTS of cis-regulatory elements siRNA and morpholino network perturbation experiments Innovative systems biology approaches to decipher and define molecular networks Data generated by microCAGE and microarray will define a set of key genes in dopaminergic neurons, in which cis-regulatory elements will be predicted and screened utilizing HTS in zebrafish. The data will aid network reconstruction, which will be validated by perturbation experiments. This project relies also on the availability of data produced through the many existing collaborations among consortium partners such as FP6 funded TRANSCODE project as well as the international Fantom3 consortium. Potential impact: The prevalence of PD in Europe today is ~2 million people. Within the next 50 years, the number is expected to rise to 5 million. Thus, the burden placed by dementia on the working-age population will rise dramatically. No treatments are known to slow the progression of the disease. Deciphering the basic networks of dopaminergic neurons will generate novel diagnostic and therapeutic candidates.


Patent
Albert Ludwigs University of Freiburg and Universitaetsklinikum Freiburg | Date: 2011-11-18

The present invention is directed to a bio-functionalized stimulus-responsive dissolvable PEG-hydrogel. This inventive stimulus-responsive dissolvable PEG-hydrogel comprises a matrix of PEG-polymers, which are modified to contain at least one multifunctional fusion protein, the multifunctional fusion protein preferably comprising as components a substrate binding peptide (SBP), preferably a repetitive RGD-binding peptide and/or a ZZ-binding domain, preferably a tag for purification, and at least one N- and/or C-terminal linker. The present invention is furthermore directed to the use of such inventive stimulus-responsive dissolvable PEG-hydrogels in the treatment of lesions, in surgical dressings, for wound treating, for soft and hard tissue regeneration, for the treatment of wounds in the oral cavity, in the field of ophthalmology, in the field of periodontal defects, etc. The invention also describes a method of treatment for such diseases. Additionally, the present invention provides a kit comprising the inventive stimulus-responsive dissolvable PEG-hydrogel and optionally further components.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.74M | Year: 2014

The main goal of the project is to provide excellent initial training to young researchers in the field of high energy particle physics, paving the road for new discoveries about the fundamental nature of the Universe at a time when new discoveries are expected, and when the new Standard Model of Particle Physics is going to be forged. The research goal of HiggsTools is the investigation of electroweak symmetry breaking. This question lies at the very frontier of knowledge of theoretical particle physics and phenomenology and, in fact, the primary goal of the Large Hadron Collider (LHC) at CERN is to unveil the mechanism of electroweak symmetry breaking. During the period of the network it is certain that the mechanism of electroweak symmetry breaking will be further decoded and that the theoretical ideas that date back to 1964 will either be confirmed or supplemented through the discovery of new additional particles that contribute to it. The experiments at the LHC have already made an impressive step forward in answering this question, by discovering a particle that is looking more and more like a Higgs boson. It remains an open question, however, whether this is the Higgs boson of the Standard Model of particle physics, or possibly the lightest of several bosons predicted in some theories that go beyond the Standard Model. Finding the answer to this question will take time. The outcome of the Higgs studies at the LHC will either carve our present understanding of electroweak interactions in stone or will be the beginning of a theoretical revolution. We will therefore create a cohort of 21 early-stage researchers (ESR) who will all be in the network for the same 36 month period and therefore be able to obtain the full benefit from the training provided by the network. We request 500 person-months for early-stage researchers (ESR) in accordance with the rules of the People FP7 Programme. The remaining 256 person-months will be funded from local sources.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.93M | Year: 2012

The generation of young biotechnologists is of paramount importance for Europes future. PHOTO.COMM will train primarily early stage researchers who have demonstrated high ambitions and talents in a unique platform based on emerging technology and science that would shape the forefront of future European biotechnology. PHOTO.COMM involves the utilization of microalgae for the conversion of carbon dioxide and water into chemicals and fuels, to directly replace finite fossil fuels and products. Although this is a rapidly growing industry, true societal impact cannot be expected until larger-scale production of low value end-products becomes a commercial reality. PHOTO.COMM has the primary objective of generating the next-generation scientists that will make a substantial and potentially game-changing contribution towards this global challenge. The young researchers will be trained in multidisciplinary science and innovation-based business creation to foster a new approach to microalgae based production and the use of synthetic photobiological communities. The researchers will also strengthen the core of photobiological metabolism by innovative approaches to enhance photosynthesis and carbon-assimilation and deliver new approaches to create valuable end-products. PHOTO.COMM will provide an exciting environment where the young researchers will absorb and implement state-of-the-art analytical methods, intellectual property and business principles and obtain extensive training and practical experience in close collaboration between universities and companies. Altogether, the educated next-generation scientists and their technologies are expected to make a strong contribution towards a future Europe in which both economically and environmentally sustainable photosynthetic biotechnology is a main supply of commodities and energy.


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

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


Patent
Albert Ludwigs University of Freiburg and Universitaetsklinikum Freiburg | Date: 2012-04-04

The present invention is directed to a biocompatible and preferably biodegradable gradient layer system comprising at least one set of layers comprising a biocompatible and preferably biodegradable cross-linked polymer and at least one biocompatible and preferably biodegradable support layer, wherein a gradient is preferably formed with respect to the mechanical and/or physical properties of one or more layers of the at least one set of layers comprising a biocompatible and biodegradable cross-linked polymer and/or the at least one biocompatible and preferably biodegradable support layer. The at least one support layer preferably comprises a biocompatible and preferably biodegradable meltable polymer and/or a biocompatible and incorporable material. This biocompatible and preferably biodegradable gradient layer system may be used as a biomaterial for regenerative medicine, particularly as a wound dressing or for tissue support. The present invention also provides means utilizing said inventive gradient layer system and methods for producing same.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: ENV.2009.5.1.0.2 | Award Amount: 1.14M | Year: 2010

Genetic biodiversity is recognised by the Convention on Biological Diversity and the EC Biodiversity Strategy as one of three essential elements of living diversity, yet it is poorly represented at the policy level, compared to the two other components, species and ecosystems. The CONGRESS consortium aims to rectify this situation by delivering dissemination tools which policy makers and conservation managers can conveniently use to incorporate genetic biodiversity into their policy framework. The six work packages of this project fall into two components. The first component comprises WPs 1 5 which will provide a one-stop, community-enabled web portal, including the following components. WP1 concerns web portal design and construction. WP2 will provide databases on academics and professional end-users, publications and genetic data for key European species of conservation concern. WP3 will provide a simulation tool for biodiversity managers to assess the power of genetic data to reveal processes which may result in genetic erosion. WP4 will provide a decision matrix module to allow end-users to establish optimal policy and management options given the genetic data which have been produced. WP5 will provide a knowledge pack and information leaflets, translated into the main European languages, which can be assembled into a manual. The second component is WP6, which comprises a series of dissemination and exchange workshops carried out across the European Union, including a transborder workshop and hands-on demonstration meeting in Eastern Europe. CONGRESS will integrate and enhance these work packages by using the workshops as forums to discuss the contents of the portal and will be guided by an end-user advisory group, who will oversee the development of these tools and ensure their utility for the community who will benefit from them.


Grant
Agency: Cordis | Branch: FP7 | Program: ERC-AG | Phase: ERC-AG-LS7 | Award Amount: 2.50M | Year: 2009

The proposal is aimed at the development of ultrafast Magnetic Resonance Imaging (MRI) for applications in neuroscience, neurology and oncology. The methodology used is based on the principle of one-voxel-one-coil acquisition in which the sensitive volumes of arrays containing a large number of small receiver coils is used as primary source of spatial localization. This allows to achieve acquisition speed >> 10 fps and opens up new windows of application for MRI. Within this proposal research will be aimed at two areas of application: For investigation of fast physiological events in the brain, applications based on the observation of fast spatiotemporal events by MR-encephalography (MREG) will be developed. MREG will be used for detailed quantitative measurement of differential cortical response during activation of cortical networks by complex stimuli. Primary areas of interest will be the investigation of spatiotemporal response in visual perception, visual and auditory cued tasks and during language processing. In addition to quantitative mapping of response, map functional connectivity with and without correlation with ECG will be investigated. For neurological applications we will use the very high sensitivity of MREG to detect arterial pulsatility in order to generate quantitative, three-dimensional maps of hemodynamic function. Clinical applications for examination of patients with stroke, ischemia, vascular disease and vascular pathologies will be developed. The principles of OVOC-measurements will also be applied in oncology for measurements of fast intrinsic and stimulated physiological events like dynamic measurements of blood flow, tissue permeability and oxygenation in tumors and metastasis. Spectroscopic OVOC-measurements will be developed to observe metabolic turnover. All experiments will be performed both in humans and animal models. Highly localized experiments will be performed using microcoil arrays currently under development.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.8.1 | Award Amount: 2.78M | Year: 2012

Embedded systems are the invisible electronics and corresponding software that bring intelligence to objects, processes and devices. The main challenge in engineering education for embedded systems at university level is a complex and multidisciplinary approach which includes understanding of various systems based on different technologies and system solution optimizations. The main idea behind the project is to provide a unified platform which will cover a complete process for embedded systems learning. A modular approach is considered for skills practice through supporting individualisation in learning. This platform shall facilitate a novel development of universal approach in creative learning environment and knowledge management that encourage use of ICT. New learning model is challenging the education of engineers in embedded systems design through real-time experiments that stimulate curiosity with ultimate goal to support students to understand and construct their personal conceptual knowledge based on experiments. In addition to the technological approach, the use of cognitive theories on how people learn will help students to achieve a stronger and smarter adaptation of the subject. Applied methodology will be evaluated from the scientific point of view in parallel with the implementation in order to feed back results to the R&D.\nAs a result, the proposed Embedded Computer Engineering Learning Platform will ensure a sufficient number of educated future engineers in Europe, capable of designing complex systems and maintaining a leadership in the area of embedded systems, thereby ensuring that our strongholds in automotive, avionics, industrial automation, mobile communications, telecoms and medical systems are able to develop. In such a manner, the E2LP intends to increase European competitiveness in the learning process of embedded computer engineering, ensuring further technological and methodological development of the educational approach in this field.


Grant
Agency: Cordis | Branch: FP7 | Program: JTI-CP-ARTEMIS | Phase: SP1-JTI-ARTEMIS-2012-AIPP1 | Award Amount: 81.51M | Year: 2013

CRYSTAL aims at fostering Europes leading edge position in embedded systems engineering in particular regarding quality and cost effectiveness of safety-critical embedded systems and architecture platforms. Its overall goal is to enable sustainable paths to speed up the maturation, integration, and cross-sectoral reusability of technological and methodological bricks of the factories for safety-critical embedded systems engineering in the areas of transportation (aerospace, automotive, and rail) and healthcare providing a critical mass of European technology providers. CRYSTAL perfectly fits to other ARTEMIS projects, sharing the concept of a reference technology platform (RTP) as a consistent set of integration principles and seamless technology interoperability standards. Based on the methodologies of a service-oriented architecture and the results of previous projects CRYSTAL focuses on an industry-driven approach using cross-domain user stories, domain-specific use cases, public use cases, and technology bricks. This shall have a significant impact to strengthen European competitiveness regarding new markets and societal applications. In building an overall interoperability domain embedded systems, CRYSTAL will contribute to establishing a standard for model-based systems engineering in a certification and safety context which is expected to have global impact. By bringing together large enterprises and various industrial domains CRYSTAL will setup a sustainable innovation eco-system. By harmonizing the demands in the development of safety-relevant embedded systems including multi-viewpoint engineering and variability management across different industrial domains, CRYSTAL will achieve a strong acceptance from both vendors and the open-source community. CRYSTAL will drive forward interoperability towards a de facto standard providing an interoperable European RTP. Approved by the JU on 20-03-2015


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: NMP.2013.2.1-1 | Award Amount: 8.60M | Year: 2014

More and more industrial sectors (e.g. automotive, wind energy, boatbuilding) are demanding lightweight and high-performance composite materials, which represent a strong driver to develop the carbon fibre (CF) industry. Today, almost 80% of CF available on the market are using PolyAcryloNitrile (PAN) as the starting raw material because of its superior properties compared to pitch based carbon fibres. However, CF produced from PAN are expensive which limit their application to premium industrial sectors looking for high-performance structural materials while accepting high material costs (e.g. aeronautics, military devices, and sport goods). The strategic objective of CARBOPREC is to develop low cost precursors from renewable materials widely available in Europe (lignin and cellulose) reinforced by carbon nanotube (CNT) to produce high performance CF for automotive and wind energy applications. To achieve this objective, two white fibre processes will be studied to produce continuous fibers: - wet spinning approach for the cellulose dissolved in phosphoric acid (H3PO4), - melt spinning by extrusion for the lignin. Moreover, the carbonization process as well as the different functionalisation steps will be deeply investigated to enhance significantly both, the carbonisation yield, and the added value brought by the developed carbon fibers in the final applications targeted. The CARBOPREC consortium led by ARKEMA gathers 14 partners coming from 6 different European countries and Russia. It covers the whole value chain needed to develop innovative carbon fibers from renewable materials.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: SEC-2007-1.3-01;SEC-2007-4.3-03 | Award Amount: 2.64M | Year: 2008

The proposal concerns the technology development for instruments with the following capabilities: (a) To make spectroscopic measurements with efficiency equivalent to that of NaI detectors and energy resolution close to that of HPGe devices but without using cryogenic systems. (b) To find the direction and the distance of the radioactive source. (c) To localize the source into a cargo and estimate the radioactive source activity taking information about the source environment (shielding, absorption in the surrounding materials) (d) To work at a wide range of absorbed dose rates by adjusting the effective volume of the detector. The above capabilities will improve the quality of the data gathered by the customs officers during the routine inspections at the boarders and will assist the first responders in case of a radiological or nuclear emergency to estimate the exact situation. Basic tasks of the project will be: (a) The growth of high purity, detector grade Cd(Zn)Te crystals. Their performance will be optimized by material purification, selection of right dopants and post-growth processing to obtain high resistivity, high transport properties and homogeneous distribution of these material properties in the grown crystals. The growth of crystals with a diameter up to 75 mm will be performed. (b) The fabrication of pixel detectors having structure of p-n and Schottky diodes. This will permit the application of bias voltage high enough to collect all the induced charge by both electrons and holes. (c) The design of pixel electronics capable for simultaneous imaging and spectroscopy. The electronics will be bump bonded to the pixel detectors. This is essential for the localization and the identification of the radioactive source. (d) The construction of a portable instrument having a stack of detecting elements. This will allow to exploit the Compton Effect for the localization of the radioactive source and also to have variable detection efficiency.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2008-3-2-03 | Award Amount: 3.95M | Year: 2009

There is a growing need for effective monitoring of the micro-organisms and bioprocesses used in the sustainable production of fuels, chemicals and pharmaceuticals. The NANOBE -consortium will develop a compact, flexible analysis tool for reaction monitoring applications in the industrial biotechnology industry. The result of the NANOBE project will be an integrated measurement platform for real-time monitoring of industrial bioprocesses. This versatile platform will enable simultaneous analysis of dozens of analytes, including individual cells, product profiles and intracellular biomarkers. The platform will be composed of multiple lab-on-chip modules. Together, these modules will measure a broad range of analyte types, including small molecules, proteins, enzymes, metabolites, specific mRNAs and entire cells. The measurement platform will be a significant improvement in terms of automation, analysis time, identification and sensitivity. The analysis platform will permit real-time feedback control of large-scale production processes, screening of production organisms and optimisation of reaction conditions. The tool will improve process productivity, product quality and accelerate development of production organisms for applications in industrial biotechnology. The platform is designed to be flexible so that it can be applied either as a multiplex platform system to monitoring multiple analytes, or as individual device components for analysis of specific compounds. The versatile measurement tool will require only a change in method (e.g. a change of reagents or analysis conditions) to enable the measurement of a new analyte. The NANOBE consortium combines world-class expertise in microfluidics, nano- and microfabrication techniques, photonics, electronics, sensor technologies, and biotechnology. The platform will exploit the scaling laws associated with microfluidic devices to reduce analysis time and sample volume.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SEC-2011.6.2-1 | Award Amount: 4.32M | Year: 2012

Urban security is a complex multi-dimensional process that results from the interaction of an increasingly diverse collection of stakeholders. Many factors influence urban security, from the physical layout to the social and economic makeup of urban zones, from the political and economic landscape on a national level to the daily practices of public services that are active in the area. Seemingly unrelated events may trigger sudden escalation of unrest in neighbourhoods that have been under social tension for a prolonged period of time. Europe has seen many severe instances of urban unrest in recent times, but also the rapid expansion of new urban environments, and new types of communities due to migration, economic tension and social developments. These developments demand a better understanding of urban security throughout Europe, and more sensible policy development to create safer urban environments, and prevent undesirable security scenarios. Policy makers need to know and understand which factors directly or indirectly impact urban security and safety. This includes an appreciation of security status (such as threat levels and potential for crime) as well as public perception of safety and security. A failure by policy makers to timely recognise and mitigate such threats may allow unrest to develop, and consequently affect the prosperity and functionality of the area. Policy makers need to become aware of the interdependency of factors, and define policy based on that comprehension. However, in reality, most decisions are made on the basis of local, long-standing best practices. Given the universal importance of urban security, it is vital to share knowledge and practices among stakeholders throughout Europe, and to jointly work on a common understanding of urban security. The project Best practice Enhancers for Security in Urban Regions (BESECURE) will work towards a better understanding of urban security through examination of different European urban areas. By examining 8 urban areas throughout Europe, BESECURE will build a comprehensive and pragmatic set of indicators, and a pragmatic risk assessment model that can provide cues about the development of certain scenarios. BESECURE will improve urban security policy making by sharing best practices that are in use throughout Europe, and by providing visualisation and assessment tools and guidelines that will help local policy makers to assess the impact of their practices, and improve their decision making.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2013.3.3 | Award Amount: 18.11M | Year: 2013

The concept of the MSP project is based on a multi-project wafer approach that enables the development of highly innovative components and sensors based on Key Enabling Technologies (KETs). The central objective of the MSP-project is the development of a technology and manufacturing platform for the 3D-integration of sophisticated components and sensors with CMOS technology being the sound foundation for cost efficient mass fabrication.\nThe MSP project is focused on the development of essential components and sensors that are required for the realization of miniaturized smart systems capable for indoor and outdoor environmental monitoring:\n\ Gas sensors for detection of potentially harmful or toxic gases\n\ Sensors for particulate matter and ultrafine particles\n\ Development of metamaterial based IR sensors for presence and fire detection\n\ Development of optimized IR detectors based on SOI thermopiles\n\ Development of highly efficient photovoltaics and piezoelectrics for energy harvesting\n\ Development of light sensor and UV-A/B sensors.\nThe rigorous employment of Through-Silicon-Via technology enables a highly flexible plug-and play 3D-integration of these components and sensors to miniaturized smart systems with significantly advanced functionalities. The goal of the MSP project is the development of a smart multi-sensor platform for distributed sensor networks in Smart Building Management, which are able to communicate with smart phones.\nThe MSP project covers the heterogeneous integration of KETs and contributes to reinforce European industrial leadership through miniaturization, performance increase and manufacturability of innovative smart systems. The MSP project is focused on emerging innovative technologies and processes for customer needs with a special emphasis on SMEs to enable their take up of KETs for competitive, highly performing product development.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.8.0 | Award Amount: 3.03M | Year: 2010

In the quest for the realization of quantum information processors, trapped ions occupy a prominent position. The challenge of realizing large-scale processors and quantum simulators based on ions will, however, require that one deals with more complex structures, which may include mesoscopic ordered ion ensembles, i.e., ion Coulomb crystals. In this regime, it is expected that the effect of noise will grow in importance and the control techniques, which have been so successfully applied to small numbers of ions, will be inefficient. This raises the timely issue of identifying novel and efficient strategies for controlling the quantum dynamics and manipulating the quantum state of ion Coulomb crystals.\n\nThe PICC proposal represents a joint theoretical and experimental effort whose aims are (i) to identify tools for controlling ion crystals as their size is scaled up, (ii) to develop strategies for implementing controlled quantum dynamics of mesoscopic ion Coulomb crystals in a noisy environment and (iii) to explore the capability of ion Coulomb crystals as quantum simulators. The long-term vision underlying this proposal is to engineer quantum correlations and entanglement in ion Coulomb crystals in order to exploit them for technological purposes of different kinds.\n\nIt is expected that this effort will pave the way for what could be the realization of the first specific-purpose, large scale quantum processors, complementing existing efforts with the alternative system of neutral atoms in optical lattices.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.5.2 | Award Amount: 4.33M | Year: 2008

Epilepsy is the commonest serious brain disorder in every country, and probably the most universal of all medical disorders. In Europe six million people currently have epilepsy and fifteen million will have epilepsy at some time of their lives. Currently nearly 30% of these people cannot be treated by therapeutics based on pharmacological anticonvulsive medication or resective surgery and are completely subjected to the sudden and unforeseen seizures strike that has a strong impact on their everyday life, with temporary impairments of motoricity, perception, speech, memory or conscience.\nEpilepsy costs the countries of Europe over 20 billion ECU every year, most of which related to the untreatable patients, an amount that could be significantly reduced with effective action.\nThe project intends to develop an intelligent alarming system, transportable by the patient, measuring the brain dynamical activity, capable of predicting the seizures, allowing the patient to assess the risk of his actual situation and improving his safety The system is based on multisignal information (EEG, ECG and others), intelligent data processing and wireless communications.\nThe project will develop knowledge (in data analysis), algorithms (of seizure prediction) and technologies (of data acquisition and wireless transmission) that integrated into an intelligent system will be an important step forward in economical affordable personal healthcare systems for neurological applications.\nA European Epilepsy Database, replicated in the three clinical partners, will also be built by the project, including all the available information about epileptic patients, allowing semantic mining based on multimodal, multisignal and multidimensional data.\nThe EPILEPSIA consortium consists of seven partners from 4 countries: 3 academic, 3 clinics, 1 industrial SME company, covering the whole value chain from theoretical conception to market products and final users.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-1.3-3 | Award Amount: 3.78M | Year: 2008

The goal of the OpenTox project is to develop a predictive toxicology framework with a unified access to toxicological data, (Q)SAR models and supporting information. It will provide tools for the integration of data from various sources (public and confidential), for the generation and validation of (Q)SAR models, libraries for the development and integration of new (Q)SAR algorithms, and validation routines. OpenTox will attract toxicological experts without (Q)SAR expertise as well as model and algorithm developers. It will move beyond existing attempts to solve individual research issues, by providing a flexible and user friendly framework that integrates existing solutions and new developments. OpenTox will be relevant for REACH as it gives risk assessors simple access to experimental data, (Q)SAR models and toxicological information that adheres to European and international regulatory requirements. OpenTox will be published as an open source project to allow a critical evaluation of its algorithms, to promote dissemination, and to attract external developers. Facilities for the inclusion of confidential in-house data and for accessing commercial prediction systems will be included. OpenTox will contain high-quality data and (Q)SAR models for chronic, genotoxic and carcinogenic effects. These are the endpoints with the greatest potential to reduce animal testing. The impact of OpenTox will however go beyond REACH and long-term effects, because it will be straightforward to create models for other endpoints (e.g,. sensitisation, liver-toxicity, cardio-toxicity, ecotoxicity). The proposed framework will support the development of new (Q)SAR models and algorithms by automating routine tasks, providing a testing and validation environment and allowing the easy addition of new data. For this reason we expect, that OpenTox will lead to (Q)SAR models for further toxic endpoints and generally improve the acceptance and reliability of (Q)SAR models.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.4-2 | Award Amount: 8.64M | Year: 2014

This proposal builds on the proven methodology developed in the SEtTReND FP7 project to develop inhibitors of schistosome HME as lead compounds for new drugs. We will employ a target-based strategy for the development of novel drug leads against schistosomiasis, leishmaniasis, Chagas disease and malaria by targeting histone modifying enzymes (HME), in particular those involved in acetylation/deacetylation and methylation/demethylation. The principal objectives of A-PARADDISE are: - The identification of HMEs from Leishmania sp. and Trypanosoma cruzi and the molecular characterization and functional characterization of selected potential targets, - Phenotypic screening of Leishmania, T. cruzi, S. mansoni and P. falciparum using HME class inhibitors, inhibitors developed specifically against S. mansoni and P. falciparum HMEs. This will permit us to obtain a comprehensive view of inhibitor classes and chemical scaffolds of interest, - Production of recombinant Leishmania and T. cruzi HME proteins, structural studies. Selected, validated target enzymes will be produced, crystallized and analysed by X-ray diffraction. Assays will be optimized to permit testing of inhibitors, - High-throughput and structure-based (in silico) screening of selected HMEs. Inhibitors selected will be further screened by phenotypic assays on the parasites in vitro, - Optimisation of inhibitor structures by chemical synthesis based on molecular modelling studies (inhibitors of all origins), - Transcriptomic analysis of drug-treated parasites to verify target specificity and mechanism of action (all parasites), - Pharmacological and toxicological studies (in vitro and in vivo) of selected inhibitors, in vivo testing of compounds in parasite-infected mice. The overall objective of the A-PARADDISE project is to develop optimized epigenetic inhibitors for further testing and optimisation as drug candidates against the four parasites studied.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: FETOPEN-1-2014 | Award Amount: 4.00M | Year: 2015

Diagnostic tests are essential to provide a targeted treatment of infectious diseases and to contain the further spread of multidrug resistant pathogens. Current methods are based either on cultivation or on PCR and have significant limitations concerning the clinical requirements to characterise pathogens including their resistance mechanisms within 3 hours. In MARA, we will develop and combine three radically novel technologies that will lead to substantial breakthroughs in science, medicine and industry and, as proof-of principle, use them to create a DNA-based molecular toolkit characterising pathogens. First, the detection of pathogen-associated antigens will be performed by Autonomous Detection Nucleic Acids (AUDENA) that are independent of any laboratory instruments and sophisticated processing. The realisation of the AUDENA concept will lead to an autonomous, stable, simple and very economic novel sensor class applicable for any water-soluble substances. The second revolutionary technology in MARA employs a novel approach in protein mimicry and creation of artificial enzymes, which represents a breakthrough in several disciplines, such as biotechnology, biomedical manufacturing and the energy sector. The third breakthrough in this project represents the development of a Molecular Robot (MORO) that can specifically identify target cells and destroy them. In MARA, the MORO will be used for the lysis of bacterial cells to release intracellular antibiotic resistance associated antigens, but the long-term vision anticipates an application as antibiotic replacement for infectious diseases and a therapeutic agent for cancer treatment, which would represent one of the most important breakthroughs in medicine in the recent years. To meet the highly ambitious objectives pointed out in this proposal, MARA is driven by a complementary, multidisciplinary team of leading experts, with a young, high-profile scientist in the lead.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SEC-2011.6.1-5 | Award Amount: 4.38M | Year: 2012

SURVEILLE systematically reviews the impacts of different surveillance systems, and also helps manufacturers and end-users better to develop and deploy these systems. It is a multidisciplinary project combining law, ethics, sociology and technology analysis in a small number of highly collaborative, cross-cutting work packages. SURVEILLE will assess surveillance technology for its actual effectiveness in fighting crime and terrorism, for its social and economic costs, and will survey perceptions of surveillance in the general public and certain identified target groups. The investigation of societal and ethical aspects will focus on undesired side effects of surveillance systems. SURVEILLE will address legal limitations on the use of surveillance technologies as well as ethical constraints. SURVEILLE will include analysis of the potential of privacy by design and privacy-enhancing technologies in the context of surveillance systems. It will interact with technology developers and manufacturers through a systematically delivered advisory service. The issues raised in the advisory service will in turn inform emphases in research deliverables. SURVEILLE will provide an interface with law enforcement officials to seek their feedback as results emerge from the research. The project aims at wide dissemination, including amongst European and national decision-makers. It will also contribute in the field of training of judges, prosecutors and the police. Partners within the SURVEILLE consortium strongly represent academic, commercial, law-enforcement and community actors connected with surveillance.


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

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


Patent
Albert Ludwigs University of Freiburg and Universitaetsklinikum Freiburg | Date: 2011-12-22

The present invention relates to substrates comprising covalently attached antimicrobial polymers, which act as synthetic mimics of antimicrobial peptides (SMAMPs) and are preferably obtained by ring opening metathesis polymerization (ROMP). The inventive antimicrobial polymers exhibit a molecular weight of more than 100,000 g mol^(1 )and are preferably covalently attached to the surface of a substrate, e.g. an implant, a medical device, medical equipment or a (tissue-supporting) biomaterial, etc. Covalent bonding may be carried out using a photoreactive crosslinker but also by grafting onto or grafting from. The present invention is also directed to uses of the inventive antimicrobial polymers as defined herein, e.g. for antimicrobially coating a surface of such a substrate with a layer of the inventive antimicrobial polymer.


Bauder M.,Albert Ludwigs University of Freiburg
International Journal of Tourism Research | Year: 2015

In this paper a new approach to determine spatial visitor behaviour using GPS-based measurement of tourists' velocity is given. I prove that GPS-based velocity measurement is valid and feasible, even in urban areas. Furthermore, I illustrate that the possibility to interpret spatial visitor behaviour, as well as the choice of transportation type, can be drawn out of the recorded data. The suggested procedure delivers several benefits for destination and tourism management, given that the knowledge of spatial visitor behaviour is central to a successful and sustainable destination management. As an example, two studies (Freiburg, Berlin) are presented in this paper. © 2014 John Wiley & Sons, Ltd.


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.


Bildl W.,Albert Ludwigs University of Freiburg
Molecular & cellular proteomics : MCP | Year: 2012

Affinity purification (AP) of protein complexes combined with LC-MS/MS analysis is the current method of choice for identification of protein-protein interactions. Their interpretation with respect to significance, specificity, and selectivity requires quantification methods coping with enrichment factors of more than 1000-fold, variable amounts of total protein, and low abundant, unlabeled samples. We used standardized samples (0.1-1000 fmol) measured on high resolution hybrid linear ion trap instruments (LTQ-FT/Orbitrap) to characterize and improve linearity and dynamic range of label-free approaches. Quantification based on spectral counts was limited by saturation and ion suppression effects with samples exceeding 100 ng of protein, depending on the instrument setup. In contrast, signal intensities of peptides (peak volumes) selected by a novel correlation-based method (TopCorr-PV) were linear over at least 4 orders of magnitude and allowed for accurate relative quantification of standard proteins spiked into a complex protein background. Application of this procedure to APs of the voltage-gated potassium channel Kv1.1 as a model membrane protein complex unambiguously identified the whole set of known interaction partners together with novel candidates. In addition to discriminating these proteins from background, we could determine efficiency, cross-reactivities, and selection biases of the used purification antibodies. The enhanced dynamic range of the developed quantification procedure appears well suited for sensitive identification of specific protein-protein interactions, detection of antibody-related artifacts, and optimization of AP conditions.


Reinecke S.,Albert Ludwigs University of Freiburg
Environmental Science and Policy | Year: 2015

Environmental policies are broadly claimed to rely on sound scientific evidence because of the complexity, the uncertainty and the diverging political stakes that characterize issues like biodiversity decline or climate change. Classical advisory formats like assessments or standing advisory bodies have proliferated widely - especially at the global and national levels - yet exert only a limited influence on political decision-making, particularly in sub-national and local implementation contexts. Against this background, scholars have called for 'bottom-up' approaches to Science-policy interfaces that move from 'problem to policy'. In the area of climate change, numerous 'climate services' have evolved at national, sub-national and even local levels, with the promise of being more decision-oriented. Four climate services in three European countries (the United Kingdom, Germany and Switzerland) are investigated regarding whether and how they institutionalize and enact knowledge brokerage in a credible, salient and legitimate way. Focusing on the institutional and strategic design principles of this advisory setting in climate policy, insights are generated for the biodiversity policy field, where comparable settings are still broadly lacking. © 2015 Elsevier Ltd.


Wallmen B.,Albert Ludwigs University of Freiburg | Schrempp M.,Albert Ludwigs University of Freiburg | Hecht A.,Albert Ludwigs University of Freiburg
Nucleic Acids Research | Year: 2012

T-cell factor (Tcf)/lymphoid-enhancer factor (Lef) proteins are a structurally diverse family of deoxyribonucleic acid-binding proteins that have essential nuclear functions in Wnt/β-catenin signalling. Expression of Wnt/β-catenin target genes is highly dependent on context, but the precise role of Tcf/Lef family members in the generation and maintenance of cell-type-specific Wnt/β-catenin responses is unknown. Herein, we show that induction of a subset of Wnt/β-catenin targets in embryonic stem cells depends on Tcf1 and Tcf4, whereas other co-expressed Tcf/Lef family members cannot induce these targets. The Tcf1/Tcf4-dependent gene responses to Wnt are primarily if not exclusively mediated by C-clamp-containing Tcf1E and Tcf4E splice variants. A combined knockdown of Tcf1/Tcf4 abrogates Wnt-inducible transcription but does not affect the active chromatin conformation of their targets. Thus, the transcriptionally poised state of Wnt/β-catenin targets is maintained independent of Tcf/Lef proteins. Conversely, ectopically overexpressed Tcf1E cannot invade silent chromatin and fails to initiate expression of inactive Wnt/β-catenin targets even if repressive chromatin modifications are abolished. The observed non-redundant functions of Tcf1/Tcf4 isoforms in acute transcriptional activation demonstrated that the cell-type-specific complement of Tcf/Lef proteins is a critical determinant of context-dependent Wnt/β-catenin responses. Moreover, the apparent inability to cope with chromatin uncovers an intrinsic property of Tcf/Lef proteins that prevents false ectopic induction and ensures spatiotemporal stability of Wnt/β-catenin target gene expression. © 2012 The Author(s).


Dittmaier S.,Albert Ludwigs University of Freiburg | Huber M.,Max Planck Institute for Physics
Journal of High Energy Physics | Year: 2010

An adequate description of the neutral-current Drell-Yan process at the Tevatron and the LHC, in particular, requires the inclusion of electroweak radiative corrections. We extend earlier work in this direction in various ways. First, we define and numerically compare different methods to describe the Z-boson resonance including next-to-leading order electroweak corrections; moreover, we provide explicit analytical expressions for those. Second, we pay particular attention to contributions from γγ and γ-quark collisions, which involve photons in the initial state, and work out how their impact can be enhanced by selection cuts. Third, we supplement the O(α) corrections by universal electroweak effects of higher order, such as universal two-loop contributions from Δα and Δρ, and the leading two-loop corrections in the high-energy Sudakov regime as well as multi-photon radiation off muons in the structure-function approach. Finally, we present results on the complete next-to-leading order electroweak and QCD corrections within the minimal supersymmetric extension of the Standard Model.


Fahrbach F.O.,Albert Ludwigs University of Freiburg | Rohrbach A.,Albert Ludwigs University of Freiburg
Optics Express | Year: 2010

We recently demonstrated that Microscopy with Self-Reconstructing Beams (MISERB) increases both image quality and penetration depth of illumination beams in strongly scattering media. Based on the concept of line scanned light-sheet microscopy, we present an add-on module to a standard inverted microscope using a scanned beam that is shaped in phase and amplitude by a spatial light modulator. We explain technical details of the setup as well as of the holograms for the creation, positioning and scaling of static light-sheets, Gaussian beams and Bessel beams. The comparison of images from identical sample areas illuminated by different beams allows a precise assessment of the interconnection between beam shape and image quality. The superior propagation ability of Bessel beams through inhomogeneous media is demonstrated by measurements on various scattering media. © 2010 Optical Society of America.


Meerpohl J.J.,Albert Ludwigs University of Freiburg
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Sickle cell disease (SCD) is a group of genetic haemoglobin disorders. Increasingly, some people with SCD develop secondary iron overload due to occasional red blood cell transfusions or are on long-term transfusion programmes for e.g. secondary stroke prevention. Iron chelation therapy can prevent long-term complications.Deferoxamine and deferiprone have been found to be efficacious. However, questions exist about the effectiveness and safety of the new oral chelator deferasirox. OBJECTIVES: To assess the effectiveness and safety of oral deferasirox in people with SCD and secondary iron overload. SEARCH STRATEGY: We searched the Cystic Fibrosis & Genetic Disorders Group's Haemoglobinopathies Trials Register (06 April 2010).We searched MEDLINE, EMBASE, EBMR, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE and three trial registries: www.controlled-trials.com; www.clinicaltrials.gov; www.who.int./ictrp/en/. Most recent searches: 22 June 2009. SELECTION CRITERIA: Randomised controlled trials comparing deferasirox with no therapy or placebo or with another iron chelating treatment schedule. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. We contacted the study author for additional information. MAIN RESULTS: One study (203 people) was included comparing the efficacy and safety of deferasirox and deferoxamine after 12 months. Data were not available on mortality or end-organ damage. Using a pre-specified dosing algorithm serum ferritin reduction was similar in both groups, mean difference (MD) 375.00 microg/l in favour of deferoxamine; (95% confidence interval (CI) -106.08 to 856.08). Liver iron concentration measured by superconduction quantum interference device showed no difference for the overall group of patients adjusted for transfusion category, MD -0.20 mg Fe/g dry weight (95% CI -3.15 to 2.75).Mild stable increases in creatine were observed more often in people treated with deferasirox, risk ratio 1.64 (95% CI 0.98 to 2.74). Abdominal pain and diarrhoea occurred significantly more often in people treated with deferasirox. Rare adverse events (less than 5% increase) were not reported; long-term adverse events could not be measured in the included study (follow-up 52 weeks). Patient satisfaction with, and convenience of treatment were significantly better with deferasirox. AUTHORS' CONCLUSIONS: Deferasirox appears to be as effective as deferoxamine. However, only limited evidence is available assessing the efficacy regarding patient-important outcomes. The short-term safety of deferasirox seems to be acceptable, however, follow-up was too short to exclude long-term side effects and thus treatment with deferasirox cannot be judged completely safe. Future studies should assess long-term outcomes for safety and efficacy, and also evaluate rarer adverse effects.


Benadi G.,Albert Ludwigs University of Freiburg
Proceedings of the Royal Society B: Biological Sciences | Year: 2015

Plant–pollinator interactions are often thought to have been a decisive factor in the diversification of flowering plants, but to be of little or no importance for the maintenance of existing plant diversity. In a recent opinion paper, Pauw (2013 Trends Ecol. Evol. 28, 30–37. (doi:10.1016/j.tree.2012.07.019)) challenged this view by proposing a mechanism of diversity maintenance based on pollination niche partitioning. In this article, I investigate under which conditions the mechanism suggested by Pauw can promote plant coexistence, using a mathematical model of plant and pollinator population dynamics. Numerical simulations show that this mechanism is most effective when the costs of searching for flowers are low, pollinator populations are strongly limited by resources other than pollen and nectar, and plant–pollinator interactions are sufficiently specialized. I review the empirical literature on these three requirements, discuss additional factors that may be important for diversity maintenance through pollination niche partitioning, and provide recommendations on how to detect this coexistence mechanism in natural plant communities. © 2015 The Author(s) Published by the Royal Society. All rights reserved.


Ziegler C.,Albert Ludwigs University of Freiburg | Thiele S.,Albert Ludwigs University of Freiburg | Zengerle R.,Albert Ludwigs University of Freiburg
Journal of Power Sources | Year: 2011

The direct three-dimensional reconstruction of a polymer electrolyte fuel cell cathode catalyst layer from focused ion beam/scanning electron microscope (FIB/SEM) images is presented. The carbon and pore distribution is shown and quantitatively analysed. A new catalyst layer sample (Fumapem-F950/HiSpec13100) is sliced with FIB and a series of SEM images is taken. The images are registered, segmented and a three-dimensional stack is reconstructed. The three-dimensional carbon and pore distribution is shown. Based on the reconstruction the pore size distribution is evaluated. The total porosity and the unconnected pores space is analysed. The fully segmented 2D images are provided as supplemental material to this paper for future analysis and modeling work. © 2010 Elsevier B.V.


Uasuf A.,Albert Ludwigs University of Freiburg | Becker G.,Albert Ludwigs University of Freiburg
Biomass and Bioenergy | Year: 2011

The development of cleaner and renewable energy sources are needed in order to reduce dependency and global warming. Wood pellets are a clean renewable fuel and has been considered as one of the substitutes for fossil fuels. In Argentina, large quantities of sawmill residues are still unused and wood pellets production could be seen as both, as an environmental solution and an extra economical benefit. The general aim of this study was to determine the wood pellets production costs and energy consumption under different framework conditions in northeast Argentina. The specific costs of wood pellets for the different scenarios showed relative lower costs comparing to the ones reported in other studies, ranging from 35 to 47 /Mgpellets. Raw material costs represented the main cost factor in the calculation of the total pellets production costs. A lower specific production cost was observed when 50% of the raw material input was wood shavings. The specific electricity consumption per metric ton of pellet was lower in scenarios with higher production rate. Lower heat energy consumption was observed in scenarios that have a mixed raw material input. The most promising framework condition for Northeast Argentina, in terms of costs effectiveness and energy consumption could be acquired with production rates of 6 Mg/h with sawdust and wood shavings as raw material. However, simultaneous increment of the electricity by 50% and raw material price by 100% may increase the specific costs up to 50%. © 2010 Elsevier Ltd.


Schuh C.,Albert Ludwigs University of Freiburg | Ruhe J.,Albert Ludwigs University of Freiburg
Macromolecules | Year: 2011

We report on the reaction of surface-attached polymer brushes with polymer molecules, which are present in a contacting solution. More specifically, we synthesize copolymer brushes containing N-hydroxysuccinimide active ester groups and study their reaction with poly(ethylene glycol) molecules, which carry an amino group at one end. Qualitatively, highly "pegylated" surfaces are obtained with an equivalent thickness of the PEG layers of up to 200 nm. Yield and kinetics of the grafting reaction are studied as a function of size and concentration of the incoming molecules, brush graft density, and brush molecular weight. It is observed that the completion of the grafting reaction is surprisingly fast, the molecular weight of the incoming molecules has a strong, while graft density and molecular weight of the brush have only a weak influence on the extent of functionalization. We develop a model for the grafting reaction, where due to limited penetration of the brush by the incoming chains the reaction occurs only at the outer periphery of the surface-attached layer. Reactive groups present in the inner parts of the brush do not take part in the attachment reaction. In the outer parts of the brush, however, partial penetration is possible so that the attachment reaction is fast and essentially only governed by the details of the shape of the segment density distribution and the size of the incoming chains. © 2011 American Chemical Society.


Maio G.,Albert Ludwigs University of Freiburg
Zeitschrift fur Psychiatrie, Psychologie und Psychotherapie | Year: 2015

This paper wants to reflect the actual transformations of modern medicine. The implementation of the market into medicine is only possible by presupposing at least three implications: a. the patient as consumer, b. medical care as commodity, c.competitiveness as criteria for good medicine. All three implications seem to be inadequate if the core identity of medicine is considered. If medicine is regarded as a human service for suffering people it becomes clear that what medicine has to offer must be more than mere commodity. It is suggested to see medicine as a social institution which is linked to the obligation of the whole society to give medicine the possibility and the economic independence to in order to remain an institution of caritas which assures help for every man in need and which cannot be reduced to a mere enterprise. ©.2015 Verlag Hans Huber, Hogrefe AG, Bern


Boeker M.,Albert Ludwigs University of Freiburg | Vach W.,Albert Ludwigs University of Freiburg | Motschall E.,Albert Ludwigs University of Freiburg
BMC Medical Research Methodology | Year: 2013

Background: Recent research indicates a high recall in Google Scholar searches for systematic reviews. These reports raised high expectations of Google Scholar as a unified and easy to use search interface. However, studies on the coverage of Google Scholar rarely used the search interface in a realistic approach but instead merely checked for the existence of gold standard references. In addition, the severe limitations of the Google Search interface must be taken into consideration when comparing with professional literature retrieval tools.The objectives of this work are to measure the relative recall and precision of searches with Google Scholar under conditions which are derived from structured search procedures conventional in scientific literature retrieval; and to provide an overview of current advantages and disadvantages of the Google Scholar search interface in scientific literature retrieval. Methods. General and MEDLINE-specific search strategies were retrieved from 14 Cochrane systematic reviews. Cochrane systematic review search strategies were translated to Google Scholar search expression as good as possible under consideration of the original search semantics. The references of the included studies from the Cochrane reviews were checked for their inclusion in the result sets of the Google Scholar searches. Relative recall and precision were calculated. Results: We investigated Cochrane reviews with a number of included references between 11 and 70 with a total of 396 references. The Google Scholar searches resulted in sets between 4,320 and 67,800 and a total of 291,190 hits. The relative recall of the Google Scholar searches had a minimum of 76.2% and a maximum of 100% (7 searches). The precision of the Google Scholar searches had a minimum of 0.05% and a maximum of 0.92%. The overall relative recall for all searches was 92.9%, the overall precision was 0.13%. Conclusion: The reported relative recall must be interpreted with care. It is a quality indicator of Google Scholar confined to an experimental setting which is unavailable in systematic retrieval due to the severe limitations of the Google Scholar search interface. Currently, Google Scholar does not provide necessary elements for systematic scientific literature retrieval such as tools for incremental query optimization, export of a large number of references, a visual search builder or a history function. Google Scholar is not ready as a professional searching tool for tasks where structured retrieval methodology is necessary. © 2013 Boeker et al.; licensee BioMed Central Ltd.


Weigel M.,Albert Ludwigs University of Freiburg | Hennig J.,Albert Ludwigs University of Freiburg
Magnetic Resonance in Medicine | Year: 2012

This article introduces an effective b-factor bTSE for turbo spin echo (TSE) sequences to quantify their inherent diffusion sensitivity. bTSE is investigated for a broad variety of two-dimensional- and three-dimensional-TSE sequences using constant and varying flip angles (transitions between pseudo steady states, SPACE, VISTA, Cube, etc.). The inherent TSE diffusion sensitivity becomes important for high-resolution protocols, which can lead to subtle contrast modifications or even fluid suppressions in a clinical setting or animal imaging regime. The bTSE values obtained considerably depend on the relaxation times and diffusion coefficient and, thus, on the tissue under observation. The fractional b TSE contributions per TSE imaging encoding axis are highly anisotropic. Further noteworthy effects such as decreasing b-factors along a TSE train are pointed out and explained. The results are also discussed in combination with recent findings regarding contrast properties and possible diffusion sensitivity of TSE sequences. Identical but well more pronounced bTSE effects are observed in the animal imaging regime due to smaller field of view and higher resolutions. Copyright © 2012 Wiley Periodicals, Inc.


Baumdicker F.,Albert Ludwigs University of Freiburg | Hess W.R.,Albert Ludwigs University of Freiburg | Pfaffelhuber P.,Albert Ludwigs University of Freiburg
Genome Biology and Evolution | Year: 2012

The distributed genome hypothesis states that the gene pool of a bacterial taxon is much more complex than that found in a single individual genome. However, the possible fitness advantage, why such genomic diversity is maintained, whether this variation is largely adaptive or neutral, and why these distinct individuals can coexist, remains poorly understood. Here, we present the infinitely many genes (IMG) model, which is a quantitative, evolutionary model for the distributed genome. It is based on a genealogy of individual genomes and the possibility of gene gain (from an unbounded reservoir of novel genes, e.g., by horizontal gene transfer from distant taxa) and gene loss, for example, by pseudogenization and deletion of genes, during reproduction. By implementing these mechanisms, the IMG model differs from existing concepts for the distributed genome, which cannot differentiate between neutral evolution and adaptation as drivers of the observed genomic diversity. Using the IMG model, we tested whether the distributed genome of 22 full genomes of picocyanobacteria (Prochlorococcus and Synechococcus) shows signs of adaptation or neutrality. We calculated the effective population size of Prochlorococcus at 1.01 × 1011 and predicted 18 distinct clades for this population, only six of which have been isolated and cultured thus far. We predicted that the Prochlorococcus pangenome contains 57,792 genes and found that the evolution of the distributed genome of Prochlorococcus was possibly neutral, whereas that of Synechococcus and the combined sample shows a clear deviation from neutrality. © The Author(s) 2012.


Maier M.,Albert Ludwigs University of Freiburg | Schack-Kirchner H.,Albert Ludwigs University of Freiburg
Agricultural and Forest Meteorology | Year: 2014

Gas exchange between soil and atmosphere represents a major component of global greenhouse gas fluxes. Chamber methods and micro-meteorological methods are well-established techniques to measure gas fluxes. The gradient method is not as widely used, but it has gained increased attention during the last decade. In this review we provide an overview of the gradient method, from the concept over different aspects of the application to the limitations and challenges of the method. Assuming gas diffusion as the dominant transport mechanism, gas flux in porous media such as soil or snow can be calculated based on the profiles of gas concentrations and soil gas diffusivity. A variety of systems has been used to determine the vertical gas profile depending on the objective of the respective study. The estimation of soil gas diffusivity is a major source of uncertainty. Soil gas diffusivity can be derived using diffusivity models, laboratory measurements or in situ approaches, e.g. the Radon method. Choosing a diffusivity model has to be considered carefully, since flux estimates are directly affected. Different approaches to calculate the gas flux have been introduced, from direct simple calculations to analytical and numerical solutions. Flux estimation is highly sensitive to the calculation procedure. It is important therefore to consider the implicit assumptions of each calculation approach.Several studies compared flux estimates measured by the gradient method and other methods. Good agreement was found in studies of CO2 production and methane consumption in soils, particularly in studies using near-continuous measurements of CO2. The relation was not as strong for fluxes of CH4 and N2O. Deviations were attributed to the possible coexistence of production and consumption of methane and N2O in the top soil layer. © 2014 Elsevier B.V.


Kenkmann T.,Albert Ludwigs University of Freiburg | Poelchau M.H.,Albert Ludwigs University of Freiburg | Wulf G.,Albert Ludwigs University of Freiburg
Journal of Structural Geology | Year: 2014

The formation of impact craters is a highly dynamic and complex process that subjects the impacted target rocks to numerous types of deformation mechanisms. Understanding and interpreting these styles of micro-, meso- and macroscale deformation has proved itself challenging for the field of structural geology. In this paper, we give an overview of the structural inventory found in craters of all size ranges on Earth, and look into the structures of craters on other planetary bodies. Structural features are discussed here that are caused by i) extremely high pressures and temperatures that occur during the initial passage of the shock wave through the target rock and projectile, ii) the resulting flow field in the target that excavates and ejects rock materials, and iii) the gravitationally induced modification of the crater cavity into the final crater form. A special focus is put on the effects that low-angle impacting bodies have on crater formation. We hope that this review will help both planetary scientists and structural geologists understand the deformation processes and resulting structures generated by meteorite impact. © 2014.


Reiter G.,Albert Ludwigs University of Freiburg
Chemical Society Reviews | Year: 2014

Mono-lamellar single crystals in thin films provide suitable model systems for studying crystallisation of long chain polymers, making distinct differences with respect to small molecules visible. Due to the high viscosity of polymeric melts, transport toward the growth front is slow and the corresponding crystal growth can suitably be followed in time. Besides being able to investigate generic processes in controlling crystal morphology like epitaxial growth or growth front instabilities, thin film studies reveal unique features of polymer crystallisation. In particular, it is possible to observe a logarithmic spatio-temporal evolution of the lamellar crystal thickness, caused by continuous rearrangements leading to regions of differing degrees of meta-stability within polymer single crystals. As a consequence of the kinetically determined lamellar thickness and the corresponding variations in melting temperature, polymer crystals allow for self-seeding, i.e., crystals can be re-grown from a melt which contains a few thermodynamically stable remnants of pre-existing crystals acting as seeds. Hence, when a single crystal is molten, all remnants have a unique orientation and thus also the crystals re-grown from these seeds. The logarithmic time-dependence of the variation in crystal thickness is reflected in a number of seeds decreasing exponentially with increasing seeding temperature. Despite their molecular complexity and some unique features, polymers proved to be valuable systems for detailed studies of crystal growth, allowing testing of theoretical concepts of morphology development. This journal is © the Partner Organisations 2014.


Vlachos I.,Albert Ludwigs University of Freiburg | Aertsen A.,Albert Ludwigs University of Freiburg | Kumar A.,Albert Ludwigs University of Freiburg
PLoS Computational Biology | Year: 2012

It is a common and good practice in experimental sciences to assess the statistical significance of measured outcomes. For this, the probability of obtaining the actual results is estimated under the assumption of an appropriately chosen null-hypothesis. If this probability is smaller than some threshold, the results are deemed statistically significant and the researchers are content in having revealed, within their own experimental domain, a "surprising" anomaly, possibly indicative of a hitherto hidden fragment of the underlying "ground-truth". What is often neglected, though, is the actual importance of these experimental outcomes for understanding the system under investigation. We illustrate this point by giving practical and intuitive examples from the field of systems neuroscience. Specifically, we use the notion of embeddedness to quantify the impact of a neuron's activity on its downstream neurons in the network. We show that the network response strongly depends on the embeddedness of stimulated neurons and that embeddedness is a key determinant of the importance of neuronal activity on local and downstream processing. We extrapolate these results to other fields in which networks are used as a theoretical framework. © 2012 Vlachos et al.


van der Maaten E.,Albert Ludwigs University of Freiburg
Trees - Structure and Function | Year: 2012

The climate sensitivity of radial growth in European beech (Fagussylvatica L.) was analyzed within a narrow valley in the Swabian Alb (southwestern Germany). We collected stem disks from three aspects (NE, NW and SW) of trees belonging to different social classes. Common climatic factors limiting growth across the valley were identified using a principal component analysis (PCA). Further, we performed hierarchical cluster analysis (HCA), redundancy analysis (RDA) and bootstrapped correlation analysis to reveal differences in chronologies and climate-growth relationships between aspect and social class. Climatic variables considered in our analyses were monthly and seasonal data on temperature and precipitation, as well as a self-calibrating Palmer drought severity index (sc-PDSI). We identified drought in the period June-August as the most prominent factor limiting growth across the valley. Dominant and co-dominant trees at the NW and SW aspects were found to be particularly drought sensitive, whereas intermediate trees were less susceptible to drought. Underlying causes of established climate-growth relationships are discussed in the context of drought susceptibility, tree-size modulation and tree physiological processes. © 2011 Springer-Verlag.


Vuilleumier R.,Albert Ludwigs University of Freiburg
Fly | Year: 2011

Orchestration of spatial organization by signaling gradients--morphogen gradients--is a fundamental principle in animal development. Despite their importance in tissue patterning and growth, the exact mechanisms underlying the establishment and maintenance of morphogen gradients are poorly understood. Our recent work on BMP (bone morphogenetic protein) morphogen signaling during wing development identified a novel protein, Pentagone (Pent), as a critical regulator of morphogen activity. In the following, we discuss the properties of Pent and its role as a feed-back loop in morphogen gradient formation.


Breunig I.,Albert Ludwigs University of Freiburg
Laser and Photonics Reviews | Year: 2016

We review the progress in the development of frequency converters based on three-wave mixing in whispering gallery resonators (WGRs). The theoretical description, given in a unified notation for all basic processes, reveals that the phase-matching condition known from conventional devices is replaced by several selection rules and, furthermore, the fact that conversion efficiencies of more than 25% can be reached in the overcoupled regime only. Experimentally, the conversion efficiencies exceed 50% already at milliwatt input powers. This is achieved, however, so far in bulk resonators only since today the on-chip devices have two orders of magnitude lower quality factors. Regarding the stability of the conversion process, one has to consider impurities left from the crystal growth and material specific effects like photoconductivity, photorefractivity, and pyroelectricity. The impressive experimental progress paves the way that micrometer-sized frequency converters based on WGRs will find the way out of the lab into real-world applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA


Arant R.J.,University of California at Berkeley | Ulbrich M.H.,Albert Ludwigs University of Freiburg
ChemPhysChem | Year: 2014

The limit of subdiffraction imaging with fluorescent proteins currently lies at 20 nm, and therefore most protein complexes are too small (2-5 nm) to spatially resolve their individual subunits by optical means. However, the number and stoichiometry of subunits within an immobilized protein complex can be resolved by the observation of photobleaching steps of individual fluorophores or co-localization of single-molecule fluorescence emission in multiple colors. We give an overview of the proteins that have been investigated by this approach and the different techniques that can be used to immobilize and label the proteins. This minireview should serve as a guideline for scientists who want to employ single-molecule subunit counting for their research. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Roa-Garcia M.C.,University of British Columbia | Weiler M.,Albert Ludwigs University of Freiburg
Hydrology and Earth System Sciences | Year: 2010

We present a new modeling approach analyzing and predicting the Transit Time Distribution (TTD) and the Response Time Distribution (RTD) from hourly to annual time scales as two distinct hydrological processes. The model integrates Isotope Hydrograph Separation (IHS) and the Instantaneous Unit Hydrograph (IUH) approach as a tool to provide a more realistic description of transit and response time of water in catchments. Individual event simulations and parameterizations were combined with long-term baseflow simulation and parameterizations; this provides a comprehensive picture of the catchment response for a long time span for the hydraulic and isotopic processes. The proposed method was tested in three Andean headwater catchments to compare the effects of land use on hydrological response and solute transport. Results show that the characteristics of events and antecedent conditions have a significant influence on TTD and RTD, but in general the RTD of the grassland dominated catchment is concentrated in the shorter time spans and has a higher cumulative TTD, while the forest dominated catchment has a relatively higher response distribution and lower cumulative TTD. The catchment where wetlands concentrate shows a flashier response, but wetlands also appear to prolong transit time. © Author(s) 2010.


Himmel D.,Albert Ludwigs University of Freiburg | Krossing I.,Albert Ludwigs University of Freiburg | Schnepf A.,University of Tübingen
Angewandte Chemie - International Edition | Year: 2014

Risky business? The use of dative bonds to describe the electronic structure of main-group compounds has come into vogue in recent years. But where are the limits? When does the description as a dative bond make sense and when is this view misleading? This Essay develops the idea on the basis of current examples. © 2014 WILEY-VCH Verlag GmbH.


Forrester D.I.,Albert Ludwigs University of Freiburg
Forest Ecology and Management | Year: 2014

Mixed-species forests and plantations sometimes have greater levels of ecosystem functions and services, including productivity, than monocultures. However, this is not always the case and there are many examples where mixtures are not more productive. Whether or not mixtures are more productive depends on the net effects of different types of interactions, and these are dynamic, changing through space and time. Many studies have examined how species interactions influence the growth of mixtures, but few have examined how spatial and temporal differences in resource availability or climatic conditions can influence these interactions. This review examines these spatial and temporal dynamics. The processes driving the dynamics are discussed using the production ecology equation, where plant growth is a function of resource availability, multiplied by the fraction of resources that are captured by the trees, multiplied by the efficiency with which the resources are used. Relative complementary effects depended on the types of species interactions and how resource availability changed. Complementary effects increased as soil nitrogen or water availability decreased when mixtures contained nitrogen fixing species, or when interactions were assumed to reduce competition for water. In contrast, some studies found that complementary effects increased with increasing site qualities, however in those studies there were no measurements of soil resource availability or any complementarity mechanisms. In those studies it was assumed that as growing conditions improved, competition for light increased and complementary effects resulted from interactions that improved light absorption or light-use efficiency. Multiple types of interactions can occur simultaneously in mixtures (e.g. nitrogen fixation, increased light absorption, and increased water-use efficiency) and so different resource availability-complementarity patterns will probably occur for a given pair of species, depending on the resource being examined. Less than half of the studies actually measured variables of the production ecology equation to indicate the processes driving the patterns. Several questions are listed that cannot yet be answered with confidence. Finally, stand structural characteristics, such as density, have also been shown to strongly increase or decrease complementarity effects and these need to be taken into account when interpreting results, but the mechanisms driving these density patterns were rarely quantified. © 2013 Elsevier B.V.


Bakhtina N.A.,Albert Ludwigs University of Freiburg | Korvink J.G.,Albert Ludwigs University of Freiburg
RSC Advances | Year: 2014

The in vivo analysis of a small multicellular organism such as the nematode Caenorhabditis elegans, enables fundamental biomedical and environmental studies of a complete organism under normal physiological conditions. Continuous advancements in photonics, electronics, as well as the material sciences, are paving the way towards miniaturized bioanalytical systems, known as labs-on-a-chip (LOC). These microfluidic technologies facilitate the manipulation and study of nematodes in a precise, real-time, portable, and cost-effective manner, potentially for high throughput operation. In this paper we review all currently available "worm-on-a-chip" miniaturized systems that address the manipulation, detection, and study of the sensory response of C. elegans, and take a close look at their advantages, application challenges, and scientific potential. The paper aims to consolidate recent results of dedicated worm microsystems that target a better understanding of C. elegans. © 2014 The Royal Society of Chemistry.


Leipold S.,Albert Ludwigs University of Freiburg
Forest Policy and Economics | Year: 2014

There is a new trend in international forest policy science. Over the past decade the term "discourse" has entered the field. Discourse analytical approaches and methods have become increasingly popular among scholars dealing with forests and their governance. When consulting the growing literature, one quickly notes the inconsistent use of the terms "discourse" and "discourse analysis".On this basis, this paper will provide (1) an overview of discourse approaches in international social and political science literature on forests, (2) identify existing trends and gaps in the literature, and (3) critically assess deficits and opportunities of existing discursive perspectives on forests and their governance.The article is based on a comprehensive survey of sixty-six journal articles, book chapters, books and online publications referring to the terms "forest" and "discourse" in the title or key words. The results suggest that forest-related discourse research may benefit from a stronger emphasis on the politics of discourse. In particular, questions of "where" and "by whom" discourses are circulated and institutionalised could provide valuable insights into forest governance. In order to arrive at these insights, however, more theoretical and methodological rigour and innovation seem to be required. Consequently, this review suggests that forest-related discourse research would benefit from (1) relating new work to the most recent discourse research conducted in different disciplines and specialisations, (2) boldly testing different available discourse lenses from political science as well as other disciplines, and (3) getting creative in adjusting those lenses (theoretically and methodologically). © 2013 Elsevier B.V.


Prostate cancer is the most common malignancy, accounting for about 25% of all incident cases among men in industrialized countries. The human androgen-dependent prostate cancer cell line LNCaP, which is derived from a metastatic lesion of human prostatic adenocarcinoma, is frequently used to study prostate cancer associated signaling pathways in vitro. Recently it was described that Rho GTPase activation in these cells leads to apoptotic responses. We used the bacterial toxins CNFy and CNF1, which specifically and directly activate Rho GTPases by deamidation of a single glutamine. We asked whether these Rho activators could induce apoptosis in LNCaP cells. Our results indicate that RhoA activation, induced by CNFy, does lead to intrinsic apoptosis of the cells. Analysis of the underlying signaling pathway reveals that apoptosis induction requires the activity of Rho kinase (ROCK) and myosin activation, an apoptotic pathway previously identified in cancer stem cells.


Fritz G.,Albert Ludwigs University of Freiburg
Trends in Biochemical Sciences | Year: 2011

The receptor for advanced glycation end products (RAGE) is a central signaling molecule in the innate immune system and is involved in the onset and sustainment of the inflammatory response. RAGE belongs to a class of pattern recognition receptors that recognize common features rather than a specific ligand. Recent structural information on the extracellular portion (ectodomain) of RAGE shed new light on this unusual ability. X-ray crystallographic, NMR and biochemical data suggest that ligand binding is driven largely by electrostatic interactions between the positively charged surface of the ectodomain and negatively charged ligands. In this article, I propose a putative mechanism of RAGE ligand recognition of receptor activation. © 2011 Elsevier Ltd.


Hug M.J.,Albert Ludwigs University of Freiburg
Methods in molecular biology (Clifton, N.J.) | Year: 2011

Cystic fibrosis (CF) is caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR functions as an anion channel and is known to interact with a number of other cellular proteins involved in ion transport. To date more than 1,800 mutations are known, most of which result in various degrees of impaired transport function of the gene product. Due to the high inter-individual variability of disease onset and progression, CF still is a diagnostic challenge. Implemented almost 20 years ago, the measurement of electrolyte transport function of rectal biopsies is a useful ex vivo tool to diagnose CF. In this chapter we will review the different approaches to perform ion transport measurements and try to highlight the advantages and limitations of these techniques.


Onichtchouk D.,Albert Ludwigs University of Freiburg
Genesis | Year: 2012

Gastrulation in vertebrates is a conserved process, which involves transition from cellular pluripotency to early precursors of ectoderm, mesoderm, and endoderm. Pluripotency control during this stage is far from being understood. Recent genetic and transcriptomic studies in zebrafish suggest that the core pluripotency transcription factors (TFs) Pou5f1 and TFs of the SoxB1 group are critically involved in large-scale temporal coordination of gene expression during gastrulation. A significant number of evolutionary conserved target genes of Pou5f1 in zebrafish are also involved in stem-cell circuit in mammalian ES cell cultures. Here, I will review the roles of Pou5f1 in development and discuss the evolutionary conservation of Pou5f1 functions and their relation to pluripotency control. © 2011 Wiley Periodicals, Inc.


Bartos M.,Albert Ludwigs University of Freiburg | Elgueta C.,Albert Ludwigs University of Freiburg
Journal of Physiology | Year: 2012

Cortical neuronal network operations depend critically on the recruitment of GABAergic interneurons and the properties of their inhibitory output signals. Recent evidence indicates a marked difference in the signalling properties of two major types of perisomatic inhibitory interneurons, the parvalbumin- and the cholecystokinin-containing basket cells. Parvalbumin-expressing basket cells are rapidly recruited by excitatory synaptic inputs, generate high-frequency trains of action potentials, discharge single action potentials phase-locked to fast network oscillations and provide fast, stable and timed inhibitory output onto their target cells. In contrast, cholecystokinin-containing basket cells are recruited in a less reliable manner, discharge at moderate frequencies with single action potentials weakly coupled to the phases of fast network oscillations and generate an asynchronous, fluctuating and less timed inhibitory output. These signalling modes are based on cell type-dependent differences in the functional and plastic properties of excitatory input synapses, integrative qualities and in the kinetics and dynamics of inhibitory output synapses. Thus, the two perisomatic inhibitory interneuron types operate with different speed and precision and may therefore contribute differently to the operations of neuronal networks. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society.


van der Laan M.,Albert Ludwigs University of Freiburg | Bohnert M.,Albert Ludwigs University of Freiburg | Wiedemann N.,Albert Ludwigs University of Freiburg | Pfanner N.,Albert Ludwigs University of Freiburg
Trends in Cell Biology | Year: 2012

Mitochondria possess a complex architecture with two membranes. The inner membrane is divided into two domains: the inner boundary membrane, which is adjacent to the outer membrane, and membrane invaginations termed cristae. Both domains are connected by tubular openings, the crista junctions. Recent studies led to the identification of a large protein complex that is crucial for establishing inner-membrane architecture. This mitochondrial inner-membrane organizing system (MINOS) interacts with protein translocases of the outer membrane that are functionally connected to the endoplasmic reticulum (ER)-mitochondria encounter structure. Here, we propose that MINOS forms a central part of an ER-mitochondria organizing network (ERMIONE) that controls mitochondrial membrane architecture and biogenesis. © 2012 Elsevier Ltd.


Weber W.,Albert Ludwigs University of Freiburg | Fussenegger M.,ETH Zurich | Fussenegger M.,University of Basel
Nature Reviews Genetics | Year: 2012

Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications. © 2011 Macmillan Publishers Limited. All rights reserved.


Spittau B.,Albert Ludwigs University of Freiburg | Krieglstein K.,Albert Ludwigs University of Freiburg
Cell and Tissue Research | Year: 2012

Klf10 and Klf11 belong to the family of Sp1/Krüppel-like zinc finger transcription factors that play important roles in a variety of cell types and tissues. Although Klf10 and Klf11 were initially introduced as transforming growth factor-beta (TGF-beta)-inducible genes, several studies have described their upregulation by a plethora of growth factors, cytokines and hormones. Here, we review the current knowledge of the inductive cues for Klf10 and Klf11 and focus on their transcriptional regulation by members of the TGF-beta superfamily. We further summarize their involvement in the regulation of the TGF-beta signaling pathway and discuss their possible role as molecules mediating crosstalk between various signaling pathways. Finally, we provide an overview of the pro-apoptotic and anti-proliferative functions of Klf10 and Klf11. © Springer-Verlag 2011.


Beck K.,Albert Ludwigs University of Freiburg | Schachtrup C.,Albert Ludwigs University of Freiburg
Cell and Tissue Research | Year: 2012

The brain function depends on a continuous supply of blood. The blood-brain barrier (BBB), which is formed by vascular cells and glia, separates components of the circulating blood from neurons and maintains the precisely regulated brain milieu required for proper neuronal function. A compromised BBB alters the transport of molecules between the blood and brain and has been associated with or shown to precede neurodegenerative disease. Blood components immediately leak into the brain after mechanical damage or as a consequence of a compromised BBB in brain disease changing the extracellular environment at sites of vascular damage. It is intriguing how blood-derived components alter the cellular and molecular constituents of the neurovascular interface after BBB opening. We recently identified an unexpected role for the blood protein fibrinogen, which is deposited in the nervous system promptly after vascular damage, as an initial scar inducer by promoting the availability of active TGF-β. Fibrinogen-bound latent TGF-β interacts with astrocytes, leading to active TGF-β formation and activation of the TGF-β/Smad signaling pathway. Here, we discuss the pleiotropic effects of potentially vascularderived TGF-β on cells at the neurovascular interface and we speculate how these biological effects might contribute to degeneration and regeneration processes. Summarizing the effects of the components derived from the brain vascular system on nervous system regeneration might support the development of new therapeutic approaches. © Springer-Verlag 2011.


Reactive oxygen species (ROS) exhibit procarcinogenic effects at multiple stages during multistep oncogenesis. As a hallmark of the transformed state, extracellular superoxide anions generated by NADPH oxidase1 (NOX1) are centrally involved in the control of the transformed state. These pro-carcinogenic effects of ROS are counterbalanced by specific ROS-dependent apoptosis induction in malignant cells, based on four interconnected signaling pathways. Tumor progression selects for a phenotype characterized by resistance to ROS-dependent apoptotic signaling. Resistance is based on membrane-associated catalase in tumor cells, which therefore represents a promising and unique target for specific tumor therapy. Novel approache, developed in vitro, utilize antibody-mediated inhibition of catalase or ROS-driven singlet oxygen generation and subsequent inactivation of tumor cell catalase as initial steps. As a consecutive step, malignant cell-generated superoxide anions then drive apoptotic signaling with high selectivity for malignant cells. We propose to translate this complex but well-established ROS-dependent signaling chemistry into novel approaches for experimental therapy in vivo.


Brabletz T.,Albert Ludwigs University of Freiburg
Nature Reviews Cancer | Year: 2012

Why are many metastases differentiated? Invading and disseminating carcinoma cells can undergo an epithelialg-mesenchymal transition (EMT), which is associated with a gain of stem cell-like behaviour. Therefore, EMT has been linked to the cancer stem cell concept. However, it is a matter of debate how subsequent mesenchymalg-epithelial transition (MET) fits into the metastatic process and whether a MET is essential. In this Opinion article, I propose two principle types of metastatic progression: phenotypic plasticity involving transient EMTg-MET processes and intrinsic genetic alterations keeping cells in an EMT and stemness state. This simplified classification integrates clinically relevant aspects of dormancy, metastatic tropism and therapy resistance, and implies perspectives on treatment strategies against metastasis. © 2012 Macmillan Publishers Limited. All rights reserved.


Manukyan M.,Albert Ludwigs University of Freiburg | Singh P.B.,Charité - Medical University of Berlin
Genes to Cells | Year: 2012

Induced pluripotent stem (iPS) cells have provided a rational means of obtaining histo-compatible tissues for 'patient-specific' regenerative therapies (Hanna 2010; Yamanaka & Blau 2010). Despite the obvious potential of iPS cell-based therapies, there are certain problems that must be overcome before these therapies can become safe and routine (Ohi 2011; Pera 2011). As an alternative, we have recently explored the possibility of using 'epigenetic rejuvenation', where the specialized functions of an old cell are rejuvenated in the absence of any change in its differentiated state (Singh & Zacouto 2010). The mechanism(s) that underpin 'epigenetic rejuvenation' are unknown and here we discuss model systems, using key epigenetic modifiers, which might shed light on the processes involved. Epigenetic rejuvenation has advantages over iPS cell techniques that are currently being pursued. First, the genetic and epigenetic abnormalities that arise through the cycle of dedifferentiation of somatic cells to iPS cells followed by redifferentiation of iPS cells into the desired cell type are avoided (Gore 2011; Hussein 2011; Pera 2011): epigenetic rejuvenation does not require passage through the de-/redifferentiation cycle. Second, because the aim of epigenetic rejuvenation is to ensure that the differentiated cell type retains its specialized function it makes redundant the question of transcriptional memory that is inimical to iPS cell-based therapies (Ohi 2011). Third, to produce unrelated cell types using the iPS technology takes a long time, around three weeks, whereas epigenetic rejuvenation of old cells will take only a matter of days. Epigenetic rejuvenation provides the most safe, rapid and cheap route to successful regenerative medicine. © 2012 The Authors. Journal compilation © 2012 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.


Martin S.F.,Albert Ludwigs University of Freiburg
Experimental Dermatology | Year: 2012

Contact allergens are small reactive chemicals. They cause allergic contact dermatitis (ACD) by activating the innate and adaptive immune system. Contact allergens are very peculiar because of their built-in autoadjuvanticity that allows them to trigger sterile inflammation following skin penetration. The innate inflammatory response involves the triggering of pattern recognition receptors either by direct chemical interaction with such receptors or by induction of endogenous activators. I discuss here the recent findings regarding prevalence and predisposition, the identification of innate immune and stress response mechanisms relevant for sensitization and the orchestration of the innate and adaptive immune response to contact allergens. Despite still significant gaps of knowledge, recent advances in our understanding of the immunopathogenesis of ACD can now be used for the development of causative treatment strategies and of in vitro alternatives to animal testing for the identification of contact allergens in immunotoxicology. © 2012 John Wiley & Sons A/S.


Engelke R.,Albert Ludwigs University of Freiburg | Becker A.C.,Albert Ludwigs University of Freiburg | Dengjel J.,Albert Ludwigs University of Freiburg
Antioxidants and Redox Signaling | Year: 2012

Significance: Protein degradation has been identified as being deregulated in numerous human diseases. Hence, proteins involved in proteasomal as well as lysosomal degradation are regarded as interesting potential drug targets and are thoroughly investigated in clinical studies. Recent Advances: Technical advances in the field of quantitative mass spectrometry (MS)-based proteomics allow for detailed investigations of protein degradation dynamics and identifications of responsible protein-protein interaction networks enabling a systematic analysis of the degradative inventory of the cell and its underlying molecular mechanisms. Critical Issues: In the current review we outline recent technical advances and their limitations in MS-based proteomics and discuss their use for the analysis of protein dynamics involved in degradation processes. Future Directions: In the next years the analysis of crosstalk between different posttranslational modifications (PTMs) will be a major focus of MS-based proteomics studies. Increasing evidence highlights the complexity of PTMs with positive and negative feedbacks being discovered. In this regard, the generation of absolute quantitative proteomic data will be essential for theoretical scientists to construct predictive network models that constitute a valuable tool for fast hypothesis testing and for explaining underlying molecular mechanisms. Antioxid. Redox Signal. © 2012 Mary Ann Liebert, Inc.


Mossmann D.,Albert Ludwigs University of Freiburg | Meisinger C.,Albert Ludwigs University of Freiburg | Vogtle F.-N.,Albert Ludwigs University of Freiburg
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2012

Mitochondrial proteins are synthesized as precursor proteins on either cytosolic or mitochondrial ribosomes. The synthesized precursors from both translation origins possess targeting signals that guide the protein to its final destination in one of the four subcompartments of the organelle. The majority of nuclear-encoded mitochondrial precursors and also mitochondrial-encoded preproteins have an N-terminal presequence that serves as a targeting sequence. Specific presequence peptidases that are found in the matrix, inner membrane and intermembrane space of mitochondria proteolytically remove the signal sequence upon import or sorting. Besides the classical presequence peptidases MPP, IMP and Oct1, several novel proteases have recently been described to possess precursor processing activity, and analysis of their functional relevance revealed a tight connection between precursor processing, mitochondrial dynamics and protein quality control. This article is part of a Special Issue entitled: Mitochondrial Gene Expression. © 2011 Elsevier B.V.


Horner M.,Albert Ludwigs University of Freiburg | Weber W.,Albert Ludwigs University of Freiburg
FEBS Letters | Year: 2012

Molecular switches are the fundamental building blocks in the field of synthetic biology. The majority of these switches is based on protein-protein, protein-DNA or protein-RNA interactions that are responsive towards endogenous metabolites or external stimuli like small molecules or light. By the rational and predictive reassembling of multiple compatible molecular switches, complex synthetic signaling networks can be engineered. Here we review how these switches were used for the regulation of important cellular processes at every level of the signaling cascade. In the second part we review how these switches can be assembled to open- and closed-loop control signaling networks and how these networks can be applied to facilitate cattle reproduction, to treat diabetes or to autonomously detect and cure disease states like gouty arthritis or cancer. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Zi Z.,Albert Ludwigs University of Freiburg | Chapnick D.A.,University of Colorado at Boulder | Liu X.,University of Colorado at Boulder
FEBS Letters | Year: 2012

The physiological responses to TGF-β stimulation are diverse and vary amongst different cell types and environmental conditions. Even though the principal molecular components of the canonical and the non-canonical TGF-β signaling pathways have been largely identified, the mechanism that underlies the well-established context dependent physiological responses remains a mystery. Understanding how the components of TGF-β signaling function as a system and how this system functions in the context of the global cellular regulatory network requires a more quantitative and systematic approach. Here, we review the recent progress in understanding TGF-β biology using integration of mathematical modeling and quantitative experimental analysis. These studies reveal many interesting dynamics of TGF-β signaling and how cells quantitatively decode variable doses of TGF-β stimulation. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Alexandrov A.,Albert Ludwigs University of Freiburg
Communications in Mathematical Physics | Year: 2015

In this paper we establish relations between three enumerative geometry tau-functions, namely the Kontsevich–Witten, Hurwitz and Hodge tau-functions. The relations allow us to describe the tau-functions in terms of matrix integrals, Virasoro constraints and Kac–Schwarz operators. All constructed operators belong to the algebra (or group) of symmetries of the KP hierarchy. © 2015, Springer-Verlag Berlin Heidelberg.


Richter S.,Griffith University | Richter S.,NICTA | Westphal M.,Albert Ludwigs University of Freiburg
Journal of Artificial Intelligence Research | Year: 2010

LAMA is a classical planning system based on heuristic forward search. Its core feature is the use of a pseudo-heuristic derived from landmarks, propositional formulas that must be true in every solution of a planning task. LAMA builds on the Fast Downward planning system, using finite-domain rather than binary state variables and multi-heuristic search. The latter is employed to combine the landmark heuristic with a variant of the well-known FF heuristic. Both heuristics are cost-sensitive, focusing on high-quality solutions in the case where actions have non-uniform cost. A weighted A search is used with iteratively decreasing weights, so that the planner continues to search for plans of better quality until the search is terminated. LAMA showed best performance among all planners in the sequential satisficing track of the International Planning Competition 2008. In this paper we present the system in detail and investigate which features of LAMA are crucial for its performance. We present individual results for some of the domains used at the competition, demonstrating good and bad cases for the techniques implemented in LAMA. Overall, we find that using landmarks improves performance, whereas the incorporation of action costs into the heuristic estimators proves not to be beneficial. We show that in some domains a search that ignores cost solves far more problems, raising the question of how to deal with action costs more effectively in the future. The iterated weighted A* search greatly improves results, and shows synergy effects with the use of landmarks. © 2010 AI Access Foundation. All rights reserved.


Merfort I.,Albert Ludwigs University of Freiburg
Current Drug Targets | Year: 2011

Sesquiterpene lactones are a large group of secondary plant metabolites mostly known from the Asteraceae family. They exert a broad variety of different biological activities. This review attempts to critically summarise the knowledge on the anti-inflammatory and cytotoxic activity of SLs, with a special focus on parthenolide and helenalin. Recent advances on their molecular modes of action, allergic potential and also QSAR studies with SLs are presented. Therapeutic areas are highlighted in which SLs may play a role in the future. Thus, SLs may possess therapeutic relevance as single components for the local treatment of inflammation, such as rheumatoid complaints. In cancer therapy, SLs may be favourable in dual therapy or in the inhibition of leukaemia cell growth. In each case, native SLs serve as leads that have to be optimised in terms of their specificity, pharmacokinetics and absorption, distribution, metabolism and excretion (=ADME) properties. Finally, appropriate in vivo studies will decide whether SLs will become therapeutics or remain interesting research compounds. © 2011 Bentham Science Publishers.


Beneke M.,RWTH Aachen | Falgari P.,University Utrecht | Klein S.,RWTH Aachen | Schwinn C.,Albert Ludwigs University of Freiburg
Nuclear Physics B | Year: 2012

We compute the total top-quark pair production cross section at the Tevatron and LHC based on approximate NNLO results, and on the summation of threshold logarithms and Coulomb enhancements to all orders with next-to-next-to-leading logarithmic (NNLL) accuracy, including bound-state effects. We findσtt̄(Tevatron)=(7.22-0.47+0.31-0.55+0.71) pb,σtt̄(LHC,s=7 TeV)=(162.6-7.6+7.4-14.7+15.4) pb for mt=173.3 GeV. The implementation of joint soft and Coulomb resummation, its ambiguities, and the present theoretical uncertainty are discussed in detail. We further obtain new approximate results at N3LO. © 2011 Elsevier B.V..


Necker S.,Albert Ludwigs University of Freiburg | Necker S.,Walter Eucken Institute
Research Policy | Year: 2014

This study reports the results of a survey of professional, mostly academic economists about their research norms and scientific misbehavior. Behavior such as data fabrication or plagiarism are (almost) unanimously rejected and admitted by less than 4% of participants. Research practices that are often considered "questionable," e.g., strategic behavior while analyzing results or in the publication process, are rejected by at least 60%. Despite their low justifiability, these behaviors are widespread. Ninety-four percent report having engaged in at least one unaccepted research practice. Surveyed economists perceive strong pressure to publish. The level of justifiability assigned to different misdemeanors does not increase with the perception of pressure. However, perceived pressure is found to be positively related to the admission of being involved in several unaccepted research practices. Although the results cannot prove causality, they are consistent with the notion that the "publish or perish" culture motivates researchers to violate research norms. © 2014 Elsevier B.V. All rights reserved.


Yu Y.,Albert Ludwigs University of Freiburg | Zappe H.,Albert Ludwigs University of Freiburg
Optics Letters | Year: 2012

We utilize three diffraction theories to investigate the focal-shift phenomena of plasmonic lenses. By taking the Fresnel number into account, a better accuracy in predicting the relative focal shift can be achieved for low-Fresnel-number systems. On the basis of this focal-shift effect, we present a method to realize an active plasmonic lens. Two-dimensional finite-difference time-domain simulation is performed to verify the method proposed. © 2012 Optical Society of America.


Fauser S.,Albert Ludwigs University of Freiburg
Advances and technical standards in neurosurgery | Year: 2012

Approximately one third of epilepsy patients are not adequately treatable by antiepileptic medication. Curative resective epilepsy surgery can be performed in only a subgroup of these pharmacoresistent patients in whom the epileptogenic focus is localizable and does not overlap with eloquent brain areas. To the remaining patients (with bilateral or multiple epileptogenic foci, with epilepsy onset in eloquent areas, or with no identifiable epileptogenic focus) palliative epilepsy surgery can be offered if they suffer from disabling seizures. Standard palliative procedures currently comprise corpus callosotomy, multiple subpial transections, and vagus nerve stimulation. New approaches such as focus distant deep brain stimulation or direct stimulation of the hippocampus have gained the most interest. Feasibility studies, small pilot studies, and, recently, larger multicenter trials showed that direct brain stimulation shall be considered a potential helpful procedure in the field of palliative surgery. Moreover, with the increasing use of stereo-EEG in invasive video-EEG monitoring, stereo-EEG-guided thermocoagulation has the potential for a promising new treatment option in patients not amenable to resective epilepsy surgery. There is no general consensus on which palliative procedure is most effective in patients with difficult-to-treat epilepsy syndromes. The decision must be based on individual factors of a given patient. This review summarizes experience with palliative approaches collected in adult and pediatric patient series over the past decades and may help to thoroughly balance beneficial effects and risks of each procedure.


On the basis of 90 relevés, rock vegetation and succulent communities were analysed in SW Arabia on a transect between 14° and 16° n. l. to see 1) which communities and water strategy types occur along an altitudinal range from sea level to 2500 m and its climatic gradient? 2) whether the chasmophytic flora mirrors the shift from palaeotropical lowlands to afro-montane phytogeographical relations in mid altitudes? 3) whether the floristic patterns in SW Arabia confirm the observations in other areas that rocks are evolutionary traps, have an outstanding rate of stenochorous species, and shelter palaeo- and neoendemics? The saxicolous flora is highly diversified. Euphorbia, Kleinia, Caralluma and Aloe have evolved ecological and geographical vicariant species. Euphorbiaceae and Asclepiadaceae are substituted in high altitude by frost tolerant Crassulaceae. The different bioclimatic niches of diagnostic species result in a number of syntaxa, replacing each other in altitude. The Kleinio odorae-Carallumetea penicillatae cl. nov. are characterized by succulent Stapelieae, candelabrous Euphorbias, and by Kleinia and Cissus ssp. Classification results in three clusters (alliances) and a number of associations, some of them new. The Euphorbion cacti occurs in the lower submontane belt, the Euphorbion inarticulatae in the Tihama Foothills. Both alliances grow on lithosols, on run-off sites and in ruderalized habitats. They are embedded as pedoclimax in the climatic climax of open woodlands. The Euphorbion adenensis is the climatic climax in the arid Eastern High Plains. Most of the associations are endemic in SW Arabia. The higher syntaxa are of Eritreo-Arabian distribution and have equivalents at the Horn of Africa. Rocks in the upper montane zone are colonized by the Centaurothamno maximi-Aeonion leucoblephari. This new alliance typifies the Crassulo albae-Aeonietea cl. nov., a class of Arabo-Afro-montane distribution. Terrace walls and rock fissures shelter small succulents (Dorstenia), poikilohydric ferns (Actiniopteris, Cheilanthes, Asplenium) and spike mosses (Selaginella), e.g. the Cheilantho coriaceae-Actiniopteridetum semiflabellatae (Selaginello yemenensis-Actiniopteridion, Cheilantho-Actiniopteridetalia). This new order has floristic relations with fern communities in the Mediterranean, in SW Australia and in the Andean Cordillera. They can be summarized in a Sinopterido-Aspleniea-class group. The rock vegetation in SW Arabia confirms 1) the high degree of endemism in the chasmophytic flora, 2) the importance of cliffs a refugium for Palaeoendemics and the role of the rock habitats for allopatric speciation and genetic drift. Close floristic relations and disjunctions exist between SW Arabia, NE Africa and Macaronesia, to a lesser extent with SW Africa. Common taxa for the class groups Kleinio-Euphorbiea and Crassulo-Aloea are the name-giving genera. These similarities have a phylogeographic background, and the phenomenon of synvicariance is obvious. Clear differences can be stated in the niche of dwarfish succulents: Caralluma and other Stapelieae evolved and radiated in Arabia, the Aeonium clade on the Canary Islands, and Aizoaceae in the Capensis. Succulent vegetation in the New World (class group Agavo-Opuntiea) has a totally different floristic basis. © 2014 Gebrüder Borntraeger, 70176 Stuttgart, Germany.


Gorelick L.,University of Western Ontario | Schmidt F.R.,Albert Ludwigs University of Freiburg | Boykov Y.,University of Western Ontario
Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition | Year: 2013

Trust region is a well-known general iterative approach to optimization which offers many advantages over standard gradient descent techniques. In particular, it allows more accurate nonlinear approximation models. In each iteration this approach computes a global optimum of a suitable approximation model within a fixed radius around the current solution, a.k.a. trust region. In general, this approach can be used only when some efficient constrained optimization algorithm is available for the selected non-linear (more accurate) approximation model. In this paper we propose a Fast Trust Region (FTR) approach for optimization of segmentation energies with non-linear regional terms, which are known to be challenging for existing algorithms. These energies include, but are not limited to, KL divergence and Bhattacharyya distance between the observed and the target appearance distributions, volume constraint on segment size, and shape prior constraint in a form of L2 distance from target shape moments. Our method is 1-2 orders of magnitude faster than the existing state-of-the-art methods while converging to comparable or better solutions. © 2013 IEEE.


Heppt W.,Albert Ludwigs University of Freiburg
HNO | Year: 2013

Correction of the nasal dorsum ranks among the most common surgical procedures in rhinoplasty. Due to the involvement of nasal support structures such as septolateral cartilage and the K and scroll areas, these procedures have both aesthetic and functional impacts. In addition to spreader grafts and spreader flaps, the most important surgical methods currently include the split hump reduction technique, cartilage-fascia transplants and cartilage grafts from rib and ear. In addition to serving to correct deformities, the techniques described here help prevent complications such as inverted V, hourglass and saddle nose deformities, as well as nasal valve stenosis. The basic operative principle calls for reinforcement and reconstruction of the anatomical support structures, while avoiding overresection and mucosal lacerations. © 2013 Springer-Verlag Berlin Heidelberg.


Streuff J.,Albert Ludwigs University of Freiburg
Chemical Record | Year: 2014

The coupling of similarly polarized carbon fragments can be achieved by a reductive umpolung strategy. This gives access to compounds with functional groups in even bond distances, which are difficult to synthesize by other means. Low-valent titanium catalysts enable such couplings under mild conditions. This account covers the recent progress on this topic with a focus on the development of cross-selective coupling reactions and stereoselective examples. © 2014 The Chemical Society of Japan and Wiley-VCH, Weinheim.


Pritzius A.B.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Angewandte Chemie - International Edition | Year: 2015

A Z-selective rhodium-catalyzed hydrothiolation of 1,3-disubstituted allenes and subsequent oxidation towards the corresponding allylic sulfones is described. Using the bidentate 1,4-bis(diphenylphosphino)butane (dppb) ligand, Z/E-selectivities up to >99:1 were obtained. The highly atom-economic desymmetrization reaction tolerates functionalized aromatic and aliphatic thiols. Additionally, a variety of symmetric internal allenes, as well as unsymmetrically disubstituted substrates were well tolerated, thus resulting in high regioselectivities. Starting from chiral but racemic 1,3-disubstituted allenes a dynamic kinetic resolution (DKR) could be achieved by applying (S,S)-Me-DuPhos as the chiral ligand. The desired Z-allylic sulfones were obtained in high yields and enantioselectivities up to 96 % ee. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Hilgendorf I.,Albert Ludwigs University of Freiburg | Swirski F.K.,Massachusetts General Hospital | Robbins C.S.,University of Toronto
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2015

Monocytes and their descendant macrophages are essential to the development and exacerbation of atherosclerosis, a lipid-driven inflammatory disease. Lipid-laden macrophages, known as foam cells, reside in early lesions and advanced atheromata. Our understanding of how monocytes accumulate in the growing lesion, differentiate, ingest lipids, and contribute to disease has advanced substantially over the last several years. These cells' remarkable phenotypic and functional complexity is a therapeutic opportunity: in the future, treatment and prevention of cardiovascular disease and its complications may involve specific targeting of atherogenic monocytes/macrophages and their products. © 2014 American Heart Association, Inc.


Considering the vast variety of synthetic cannabinoids and herbal mixtures - commonly known as 'Spice' or 'K2' - on the market and the resulting increase of severe intoxications related to their consumption, there is a need in clinical and forensic toxicology for comprehensive up-to-date screening methods. The focus of this project aimed at developing and implementing an automated screening procedure for the detection of synthetic cannabinoids in serum using a liquid chromatography-ion trap-MS (LC-MS(n)) system and a spectra library-based approach, currently including 46 synthetic cannabinoids and 8 isotope labelled analogues. In the process of method development, a high-temperature ESI source (IonBooster(TM), Bruker Daltonik) and its effects on the ionization efficiency of the investigated synthetic cannabinoids were evaluated and compared to a conventional ESI source. Despite their structural diversity, all investigated synthetic cannabinoids benefitted from high-temperature ionization by showing remarkably higher MS intensities compared to conventional ESI. The employed search algorithm matches retention time, MS and MS(2)/MS(3) spectra. With the utilization of the ionBooster source, limits for the automated detection comparable to cut-off values of routine MRM methods were achieved for the majority of analytes. Even compounds not identified when using a conventional ESI source were detected using the ionBooster-source. LODs in serum range from 0.1 ng/ml to 0.5 ng/ml. The use of parent compounds as analytical targets offers the possibility of instantly adding new emerging compounds to the library and immediately applying the updated method to serum samples, allowing the rapid adaptation of the screening method to ongoing forensic or clinical requirements. The presented approach can also be applied to other specimens, such as oral fluid or hair, and herbal mixtures and was successfully applied to authentic serum samples. Quantitative MRM results of samples with analyte concentrations above the determined LOD were confirmed as positive findings by the presented method. Copyright © 2014 John Wiley & Sons, Ltd.


Kiritsi D.,Albert Ludwigs University of Freiburg | Has C.,Albert Ludwigs University of Freiburg | Bruckner-Tuderman L.,Albert Ludwigs University of Freiburg
Cell Adhesion and Migration | Year: 2013

Laminin 332 is an essential component of the dermalepidermal junction, a highly specialized basement membrane zone that attaches the epidermis to the dermis and thereby provides skin integrity and resistance to external mechanical forces. Mutations in the LAMA3, LAMB3 and LAMC2 genes that encode the three constituent polypeptide chains, α3, β3 and γ2, abrogate or perturb the functions of laminin 332. The phenotypic consequences are diminished dermal-epidermal adhesion and, as clinical symptoms, skin fragility and mechanically induced blistering. The disorder is designated as junctional epidermolysis bullosa (JEB). This article delineates the signs and symptoms of the different forms of JEB, the mutational spectrum, genotype-phenotype correlations as well as perspectives for future molecular therapies. © 2013 Landes Bioscience.


Granacher U.,Friedrich - Schiller University of Jena | Gollhofer A.,Albert Ludwigs University of Freiburg
Journal of Strength and Conditioning Research | Year: 2012

The risk of sustaining falls and sports-related injuries is particularly high in children. Deficits in balance and muscle strength represent 2 important intrinsic fall and injury-risk factors. Therefore, the purpose of this study was to investigate the relationship between variables of static and dynamic postural control and isometric and dynamic muscle strength and to find out whether there is an association between measures of postural control and muscle strength in prepubertal children. Thirty children participated in this study (age 6.7 6 0.5 years; body mass index 16.0 6 1.8 kg·m -2). Biomechanic tests included the measurements of maximal isometric torque and rate of force development (RFD) of the plantar flexors on an isokinetic device, jumping power and height (countermovement jump [CMJ]) on a force plate, and the assessment of static and dynamic posture during bipedal stance on a balance platform. The significance level was set at p < 0.05. No significant associations were observed between variables of static and dynamic postural control. Significant positive correlations were detected between the RFD of the plantar flexors and CMJ height (r = 0.425, p < 0.01). No statistically significant associations were found between measures of postural control and muscle strength. The nonsignificant correlations between static and dynamic postural control and muscle strength imply that primarily dynamic measures of postural control should be incorporated in fall and injury-risk assessment and that postural control and muscle strength appear to be independent of each other and may have to be trained in a complementary manner for fall and injury-preventive purposes. © 2012 National Strength and Conditioning Association.


Koschker P.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Accounts of Chemical Research | Year: 2016

ConspectusWe present a new and efficient strategy for the atom-economic transformation of both alkynes and allenes to allylic functionalized structures via a Rh-catalyzed isomerization/addition reaction which has been developed in our working group. Our methodology thus grants access to an important structural class valued in modern organic chemistry for both its versatility for further functionalization and the potential for asymmetric synthesis with the construction of a new stereogenic center. This new methodology, inspired by mechanistic investigations by Werner in the late 1980s and based on preliminary work by Yamamoto and Trost, offers an attractive alternative to other established methods for allylic functionalization such as allylic substitution or allylic oxidation. The main advantage of our methodology consists of the inherent atom economy in comparison to allylic oxidation or substitution, which both produce stoichiometric amounts of waste and, in case of the substitution reaction, require prefunctionalization of the starting material. Starting out with the discovery of a highly branched-selective coupling reaction of carboxylic acids with terminal alkynes using a Rh(I)/DPEphos complex as the catalyst system, over the past 5 years we were able to continuously expand upon this chemistry, introducing various (pro)nucleophiles for the selective C-O, C-S, C-N, and C-C functionalization of both alkynes and the double-bond isomeric allenes by choosing the appropriate rhodium/bidentate phosphine catalyst. Thus, valuable compounds such as branched allylic ethers, sulfones, amines, or γ,δ-unsaturated ketones were successfully synthesized in high yields and with a broad substrate scope. Beyond the branched selectivity inherent to rhodium, many of the presented methodologies display additional degrees of selectivity in regard to regio-, diastereo-, and enantioselective transformations, with one example even proceeding via a dynamic kinetic resolution. Many advances presented in this account were driven by detailed mechanistic investigations including DFT-calculations, ESI-MS and in situ IR experiments and enabled the application of our chemistry for target-oriented syntheses demonstrated by several examples shown herein. In general, this research topic has matured over the past years into a viable option when synthesizing chiral compounds, from small molecules such as quercus lactones to complex target structures such as Homolargazole or Clavosolide A. This demonstrates the importance and utility of these coupling reactions, especially considering the ease with which carbon-heteroatom bonds can be built stereoselectively, with many of the product classes displaying motifs common in modern APIs. © 2016 American Chemical Society.


Quemin E.R.J.,Institute Pasteur Paris | Quax T.E.F.,Albert Ludwigs University of Freiburg
Frontiers in Microbiology | Year: 2015

The cell envelope represents the main line of host defense that viruses encounter on their way from one cell to another. The cytoplasmic membrane in general is a physical barrier that needs to be crossed both upon viral entry and exit. Therefore, viruses from the three domains of life employ a wide range of strategies for perforation of the cell membrane, each adapted to the cell surface environment of their host. Here, we review recent insights on entry and egress mechanisms of viruses infecting archaea. Due to the unique nature of the archaeal cell envelope, these particular viruses exhibit novel and unexpected mechanisms to traverse the cellular membrane. © 2015 Quemin and Quax.


Prinz M.,Albert Ludwigs University of Freiburg | Priller J.,Charité - Medical University of Berlin
Journal of Neuroimmunology | Year: 2010

Myeloid cells are mediators of central nervous system (CNS) damage and recovery in neuroinflammatory and neurodegenerative disorders. Besides endogenous myelomonocytic cell populations that reside in the brain already during development, newly migrated leukocytes are considered as important disease modulators in the adult brain. Thus, understanding of myeloid cell recruitment is pivotal for manipulating immune cell entry into the CNS and potentially reducing disease burden. Before myeloid cells engraft in the brain, they first tether to and roll on the activated brain endothelium, then they firmly adhere and eventually transmigrate into the damaged brain where they execute effector functions and differentiate into cells with microglia-like features. These steps are mainly regulated by adhesion molecules and by chemokines and their cognate receptors. Due to recent advances in our understanding of monocyte heterogeneity, the interest in chemokine receptors has significantly increased. Among others, the presence of the chemokine receptors CCR2 and CX3CR1 is considered to be critical for both myeloid cell trafficking along inflamed vessels and subsequent accumulation in the brain. Therefore, these molecules present viable targets for therapeutic manipulations of myeloid cells destined for the CNS. © 2010 Elsevier B.V.


Heinrich S.P.,Albert Ludwigs University of Freiburg
Documenta Ophthalmologica | Year: 2010

Steady-state evoked potentials are popular due to their easy analysis in frequency space and the availability of methods for objective response detection. However, the interpretation of steady-state responses can be challenging due to their origin as a sequence of responses to single stimuli. In the present paper, issues of signal extinction and some characteristics of higher harmonics are illustrated based on simple model data for those readers who do not regularly hobnob with frequency-space representations of data. It is important to realize that the absence of a steady-state response does not prove the lack of neural activity. For the same underlying reasons, namely constructive and destructive superposition of individual responses, comparisons of amplitudes between experimental conditions are prone to inaccuracies. Thus, before inferring physiology from steady-state responses, one should consider an alternative explanation in terms of signal composition. © 2010 Springer-Verlag.


Sonnen A.F.-P.,Albert Ludwigs University of Freiburg | Henneke P.,Albert Ludwigs University of Freiburg
Sub-Cellular Biochemistry | Year: 2014

The complement system is an intricate network of serum proteins that mediates humoral innate immunity through an amplification cascade that ultimately leads to recruitment of inflammatory cells or opsonisation or killing of pathogens. One effector arm of this network is the terminal pathway of complement, which leads to the formation of the membrane attack complex (MAC) composed of complement components C5b, C6, C7, C8 and C9. Upon formation of C5 convertases via the classical or alternative pathways of complement activation, C5b is generated from C5 by proteolytic cleavage, nucleating a series of association and polymerisation reactions of the MAC-constituting complement components that culminate in pore formation of pathogenic membranes. Recent structures of MAC components and homologous proteins significantly increased our understanding of oligomerisation, membrane association and integration, shedding light onto the molecular mechanism of this important branch of the innate immune system. © Springer Science+Business Media Dordrecht 2014.


Ramirez F.,Max Planck Institute of Immunobiology and Epigenetics | Dundar F.,Max Planck Institute of Immunobiology and Epigenetics | Dundar F.,Albert Ludwigs University of Freiburg | Diehl S.,Max Planck Institute of Immunobiology and Epigenetics | And 2 more authors.
Nucleic Acids Research | Year: 2014

We present a Galaxy based web server for processing and visualizing deeply sequenced data. The web server's core functionality consists of a suite of newly developed tools, called deepTools, that enable users with little bioinformatic background to explore the results of their sequencing experiments in a standardized setting. Users can upload pre-processed files with continuous data in standard formats and generate heatmaps and summary plots in a straight-forward, yet highly customizable manner. In addition, we offer several tools for the analysis of files containing aligned reads and enable efficient and reproducible generation of normalized coverage files. As a modular and open-source platform, deepTools can easily be expanded and customized to future demands and developments. The deepTools webserver is freely available at http://deeptools.ie-freiburg.mpg.de and is accompanied by extensive documentation and tutorials aimed at conveying the principles of deep-sequencing data analysis. The web server can be used without registration. deepTools can be installed locally either stand-alone or as part of Galaxy. © 2014 The Author(s).


Lauber B.,Albert Ludwigs University of Freiburg | Keller M.,University of Fribourg
European Journal of Sport Science | Year: 2014

Augmented feedback (AF) can play an important role when learning or improving a motor skill. As research dealing with AF is broad and diverse, the purpose of this review is to provide the reader with an overview of the use of AF in exercise, motor learning and injury prevention research with respect to how it can be presented, its informational content and the limitations. The term 'augmented' feedback is used because additional information provided by an external source is added to the task-intrinsic feedback that originates from a person's sensory system. In recent decades, numerous studies from various fields within sport science (exercise science, sports medicine, motor control and learning, psychology etc.) have investigated the potential influence of AF on performance improvements. The first part of the review gives a theoretical background on feedback in general but particularly AF. The second part tries to highlight the differences between feedback that is given as knowledge of result and knowledge of performance. The third part introduces studies which have applied AF in exercise and prevention settings. Finally, the limitations of feedback research and the possible reasons for the diverging findings are discussed. The focus of this review lies mainly on the positive influence of AF on motor performance. Underlying neuronal adaptations and theoretical assumptions from learning theories are addressed briefly. © 2012 © 2012 European College of Sport Science.


Urbach H.,Albert Ludwigs University of Freiburg
Current Opinion in Neurology | Year: 2014

PURPOSE OF REVIEW: To illustrate clinical presentations, imaging findings, and diagnostic and therapeutic approaches associated with various conditions of intracranial hypotension. RECENT FINDINGS: Intracranial hypotension occurs spontaneously, following (lumbar) dural puncture, accidental dural opening, or excessive surgical cerebrospinal fluid drainage. The typical clinical manifestation - orthostatic headache - may be masqueraded by atypical clinical findings, including coma, frontotemporal dementia, leptomeningeal hemosiderosis-associated symptoms, and others. MRI signs are highly specific, but the imaging strategy to search for spinal cerebrospinal fluid leaks (none, computed tomography myelography, magnetic resonance myelography with gadolinium, digital subtraction myelography) is a matter of debate. The same is true for the mode of treatment (bed rest, blind, fluoroscopy or computed tomography-guided epidural blood patching, fibrin patching, surgery). SUMMARY: Clinical presentation as well as diagnostic and therapeutic approaches in intracranial hypotension are very heterogenous.Copyright © 2014 Wolters Kluwer Health.


Kanat M.,Albert Ludwigs University of Freiburg | Heinrichs M.,Albert Ludwigs University of Freiburg | Schwarzwald R.,Albert Ludwigs University of Freiburg | Domes G.,Albert Ludwigs University of Freiburg
Neuropsychopharmacology | Year: 2015

The neuropeptide oxytocin has recently been shown to modulate covert attention shifts to emotional face cues and to improve discrimination of masked facial emotions. These results suggest that oxytocin modulates facial emotion processing at early perceptual stages prior to full evaluation of the emotional expression. Here, we used functional magnetic resonance imaging to examine whether oxytocin alters neural responses to backwardly masked angry and happy faces while controlling for attention to the eye vs the mouth region. Intranasal oxytocin administration reduced amygdala reactivity to masked emotions when attending to salient facial features, ie, the eyes of angry faces and the mouth of happy faces. In addition, oxytocin decreased neural responses within the fusiform gyrus and brain stem areas, as well as functional coupling between the amygdala and the fusiform gyrus specifically for threat cues from the eyes. Effects of oxytocin on brain activity were not attributable to differences in behavioral performance, as oxytocin had no impact on mere emotion detection. Our results suggest that oxytocin attenuates neural correlates of early arousal by threat signals from the eye region. As reduced threat sensitivity may increase the likelihood of engaging in social interactions, our findings may have important implications for clinical states of social anxiety.


Giere R.,Albert Ludwigs University of Freiburg | Querol X.,CSIC - Institute of Environmental Assessment And Water Research
Elements | Year: 2010

Atmospheric particulates - tiny particles in the air - represent an exciting new research area for mineralogists and geochemists. Emitted directly into or formed within the atmosphere, these particles are generated by both natural processes and human activity. Although derived mostly from sources that are spatially and temporally confined, the particles are ubiquitous globally due to atmospheric circulation. Depending on their physical and chemical properties, these small particles have local- to planetary-scale environmental impacts, influencing the radiative properties of the atmosphere and the cryosphere, the nucleation of both warm and ice clouds, and the nutrient contents of oceans and soils. Because airborne particles can affect human health and transportation, mainly aviation, they have become a focus of government attention and regulation.


Rago L.,Max Planck Institute of Immunobiology and Epigenetics | Rago L.,Albert Ludwigs University of Freiburg | Beattie R.,University of Basel | Taylor V.,University of Basel | And 2 more authors.
EMBO Journal | Year: 2014

N-cadherin-mediated adhesion is essential for maintaining the tissue architecture and stem cell niche in the developing neocortex. N-cadherin expression level is precisely and dynamically controlled throughout development; however, the underlying regulatory mechanisms remain largely unknown. MicroRNAs (miRNAs) play an important role in the regulation of protein expression and subcellular localisation. In this study, we show that three miRNAs belonging to the miR379-410 cluster regulate N-cadherin expression levels in neural stem cells and migrating neurons. The overexpression of these three miRNAs in radial glial cells repressed N-cadherin expression and increased neural stem cell differentiation and neuronal migration. This phenotype was rescued when N-cadherin was expressed from a miRNA-insensitive construct. Transient abrogation of the miRNAs reduced stem cell differentiation and increased cell proliferation. The overexpression of these miRNAs specifically in newborn neurons delayed migration into the cortical plate, whereas the knockdown increased migration. Collectively, our results indicate a novel role for miRNAs of the miR379-410 cluster in the fine-tuning of N-cadherin expression level and in the regulation of neurogenesis and neuronal migration in the developing neocortex. Synopsis Members of the miR379-410 miRNA cluster control the proliferation and differentiation of radial glial cells (RGCs) and the migration of cortical neurons by reducing N-cadherin levels in the developing neocortex. miR369-3p, miR496 and miR543 are expressed in the mouse developing neocortex. miR369-3p, miR496 and miR543 regulate the proliferation and differentiation of RGCs into cortical neurons. miR369-3p, miR496 and miR543 control cortical neuron migration. miR369-3p, miR496 and miR543 exert their effects via reduction of N-cadherin expression in vitro and in vivo. Members of the miR379-410 miRNA cluster control the proliferation and differentiation of radial glial cells (RGCs) and the migration of cortical neurons by reducing N-cadherin levels in the developing neocortex. © 2014 The Authors.


Busch K.,German Cancer Research Center | Klapproth K.,German Cancer Research Center | Barile M.,German Cancer Research Center | Flossdorf M.,German Cancer Research Center | And 7 more authors.
Nature | Year: 2015

Haematopoietic stem cells (HSCs) are widely studied by HSC transplantation into immune- and blood-cell-depleted recipients. Single HSCs can rebuild the system after transplantation. Chromosomal marking, viral integration and barcoding of transplanted HSCs suggest that very low numbers of HSCs perpetuate a continuous stream of differentiating cells. However, the numbers of productive HSCs during normal haematopoiesis, and the flux of differentiating progeny remain unknown. Here we devise a mouse model allowing inducible genetic labelling of the most primitive Tie2+ HSCs in bone marrow, and quantify label progression along haematopoietic development by limiting dilution analysis and data-driven modelling. During maintenance of the haematopoietic system, at least 30% or ∼5,000 HSCs are productive in the adult mouse after label induction. However, the time to approach equilibrium between labelled HSCs and their progeny is surprisingly long, a time scale that would exceed the mouse's life. Indeed, we find that adult haematopoiesis is largely sustained by previously designated "short-term" stem cells downstream of HSCs that nearly fully self-renew, and receive rare but polyclonal HSC input. By contrast, in fetal and early postnatal life, HSCs are rapidly used to establish the immune and blood system. In the adult mouse, 5-fluoruracil-induced leukopenia enhances the output of HSCs and of downstream compartments, thus accelerating haematopoietic flux. Label tracing also identifies a strong lineage bias in adult mice, with several-hundred-fold larger myeloid than lymphoid output, which is only marginally accentuated with age. Finally, we show that transplantation imposes severe constraints on HSC engraftment, consistent with the previously observed oligoclonal HSC activity under these conditions. Thus, we uncover fundamental differences between the normal maintenance of the haematopoietic system, its regulation by challenge, and its re-establishment after transplantation. HSC fate mapping and its linked modelling provide a quantitative framework for studying in situ the regulation of haematopoiesis in health and disease. © 2015 Macmillan Publishers Limited. All rights reserved.


Lienkamp S.,Albert Ludwigs University of Freiburg | Ganner A.,Albert Ludwigs University of Freiburg | Walz G.,Albert Ludwigs University of Freiburg
Differentiation | Year: 2012

Mutations of the ankyrin-repeat protein Inversin, a member of a diverse family of more than 12 proteins, cause nephronophthisis (NPH), an autosomal recessive cystic kidney disease associated with extra-renal manifestations such as retinitis pigmentosa, cerebellar aplasia and situs inversus. Most NPH gene products (NPHPs) localize to the cilium, and appear to control the transport of cargo protein to the cilium by forming functional networks. Inversin interacts with NPHP1 and NPHP3, and shares with NPHP4 the ability to antagonize Dishevelled-stimulated canonical Wnt signaling, potentially through recruitment of the Anaphase Promoting Complex (APC/C). However, Dishevelled antagonism may be confined towards the basal body, thereby polarizing motile cilia on the cells of the ventral node and respiratory tract. Inversin is essential for recruiting Dishevelled to the plasma membrane in response to activated Frizzled, a crucial step in planar cell polarity signaling. During vertebrate pronephros development, the Inversin-mediated translocation of Dishevelled appears to orchestrate the migration of cells and differentiation of segments that correspond to the mammalian loop of Henle. Thus, defective tubule migration and elongation may contribute to concentration defects and cause cyst formation in patients with NPH. © 2011 International Society of Differentiation.


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

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


Rennenberg H.,Albert Ludwigs University of Freiburg | Herschbach C.,Albert Ludwigs University of Freiburg
Journal of Experimental Botany | Year: 2014

Understanding the dynamics of physiological process in the systems biology era requires approaches at the genome, transcriptome, proteome, and metabolome levels. In this context, metabolite flux experiments have been used in mapping metabolite pathways and analysing metabolic control. In the present review, sulphur metabolism was taken to illustrate current challenges of metabolic flux analyses. At the cellular level, restrictions in metabolite flux analyses originate from incomplete knowledge of the compartmentation network of metabolic pathways. Transport of metabolites through membranes is usually not considered in flux experiments but may be involved in controlling the whole pathway. Hence, steady-state and snapshot readings need to be expanded to time-course studies in combination with compartment-specific metabolite analyses. Because of species-specific differences, differences between tissues, and stress-related responses, the quantitative significance of different sulphur sinks has to be elucidated; this requires the development of methods for whole-sulphur metabolome approaches. Different cell types can contribute to metabolite fluxes to different extents at the tissue and organ level. Cell type-specific analyses are needed to characterize these contributions. Based on such approaches, metabolite flux analyses can be expanded to the whole-plant level by considering long-distance transport and, thus, the interaction of roots and the shoot in metabolite fluxes. However, whole-plant studies need detailed empirical and mathematical modelling that have to be validated by experimental analyses. © 2014 The Author.


Einsle O.,Albert Ludwigs University of Freiburg | Einsle O.,Center for Biological Signalling Studies
Journal of Biological Inorganic Chemistry | Year: 2014

The enzyme nitrogenase catalyzes the six-electron reduction of molecular dinitrogen to ammonium, concomitant with the reduction of protons to yield hydrogen gas. In the MoFe protein component of the nitrogenase system, the unique FeMo cofactor is the active site of catalysis, but its exact mechanism remains under debate. This review focuses on the history of the structure determination of FeMo cofactor, a process that extended over two decades and involved several iterations and corrections that are unusual and unexpected within the established field of X-ray crystallography. However, FeMo cofactor has defied expectations on several occasions, and besides being the largest single iron-sulfur cluster known to bioinorganic chemistry, this [Mo:7Fe:9S:C]:homocitrate moiety is unique in some aspects that have misled researchers several times. We have now arrived at a final and complete description of the atomic structure of FeMo cofactor, and yet many questions regarding various aspects of the catalytic mechanism of this enzyme remain to be answered. © 2014 SBIC.


Kreuzwieser J.,Albert Ludwigs University of Freiburg | Rennenberg H.,Albert Ludwigs University of Freiburg
Plant, Cell and Environment | Year: 2014

One major effect of global climate change will be altered precipitation patterns in many regions of the world. This will cause a higher probability of long-term waterlogging in winter/spring and flash floods in summer because of extreme rainfall events. Particularly, trees not adapted at their natural site to such waterlogging stress can be impaired. Despite the enormous economic, ecological and social importance of forest ecosystems, the effect of waterlogging on trees is far less understood than the effect on many crops or the model plant Arabidopsis. There is only a handful of studies available investigating the transcriptome and metabolome of waterlogged trees. Main physiological responses of trees to waterlogging include the stimulation of fermentative pathways and an accelerated glycolytic flux. Many energy-consuming, anabolic processes are slowed down to overcome the energy crisis mediated by waterlogging. A crucial feature of waterlogging tolerance is the steady supply of glycolysis with carbohydrates, particularly in the roots; stress-sensitive trees fail to maintain sufficient carbohydrate availability resulting in the dieback of the stressed tissues. The present review summarizes physiological and molecular features of waterlogging tolerance of trees; the focus is on carbon metabolism in both, leaves and roots of trees. © 2014 John Wiley & Sons Ltd.


Reese C.,Albert Ludwigs University of Freiburg | Mittag O.,Albert Ludwigs University of Freiburg
International Journal of Rehabilitation Research | Year: 2013

The purpose of the article is to summarize evidence and recommendations for psychological interventions in the rehabilitation of patients with chronic low back pain. We carried out a systematic literature search in several databases and on the websites of professional associations to identify relevant reviews and guidelines. In addition to the electronic search, a handsearch was carried out. Eligible publications were selected. We extracted and summarized both evidence for psychological interventions and recommendations on psychological diagnostics and interventions. Six systematic reviews and 14 guidelines were included. We collected recommendations and partially restricted evidence on the following psychological interventions: behavioural therapy, fear-avoidance training, stress management, relaxation therapy, patient education and back school. Most available evidence for psychological interventions in the rehabilitation of patients with chronic low back pain is of moderate to low quality. In addition, some of the older evidence is inapplicable to modern interventions using a biopsychosocial approach. Thus, high quality and current evidence is needed. The summary of guidelines shows that multimodal, multidisciplinary programmes including psychological interventions have become standard in the rehabilitation of patients with chronic low back pain. In most guidelines, however, there are no recommendations on which (psychological) intervention should be considered for which specific problem (problem-treatment pairs). Suggestions for future research and future guidelines are made. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Trentowska M.,Albert Ludwigs University of Freiburg | Bender C.,Albert Ludwigs University of Freiburg | Tuschen-Caffier B.,Albert Ludwigs University of Freiburg
Behaviour Research and Therapy | Year: 2013

Mirror exposure is an efficient treatment for body image problems in eating disorders. Although habituation processes and cognitive changes are postulated to be underlying mechanisms, evidence is scarce, especially during repeated mirror exposure treatment. Fourteen participants with eating disorders not otherwise specified (EDNOS) and five with bulimia nervosa (BN) composed the bulimic group (BG), and 19 healthy women without any mental disorder composed the healthy controls group (HC). The participants were treated by four standardized mirror exposure sessions. Subjective distress was assessed five times during each session. Both negative and positive emotions and negative thoughts were assessed after each session. The patients in the BG reported significantly higher levels of negative emotions and cognitions than did those in the HC in all measures and across all sessions. In both groups, subjective distress increased significantly within each session and decreased toward the end of each session. Only in the subjects of the BG group did both distress and negative thoughts and emotions decrease significantly from session to session, whereas positive emotions increased. The patterns of change differed between the BG and the HC, suggesting that habituation between sessions occurred only in the BG. Our findings suggest that the additional underlying cognitive-affective processes merit further investigation. © 2012 Elsevier Ltd.


Brunner T.,Albert Ludwigs University of Freiburg | Roux F.S.,South African Council for Scientific and Industrial Research
New Journal of Physics | Year: 2013

The entangled quantum state of a photon pair propagating through atmospheric turbulence suffers decay of entanglement due to the scintillation it experiences. In this paper, we investigate the robustness against this decay for different qutrit states. An infinitesimal propagation equation is used to obtain the density matrix as a function of the propagation distance and the tangle is used to quantify the entanglement between a pair of qutrits. We consider the evolution of various initial states as they propagate through turbulence. Using optimization of the parameters that define the initial state, we obtain expressions for bipartite qutrit states that retain their initial entanglement longer than the initially maximally entangled states. © IOP Publishing and Deutsche Physikalische Gesellschaft.


Spahn C.,Albert Ludwigs University of Freiburg
Progress in Brain Research | Year: 2015

Music performance anxiety (MPA) regularly occurs when musicians present themselves before an audience in performance situations, and thus, it plays an important role in the careers of professional musicians. MPA is expressed on the emotional and physical level, as well as on the levels of thinking and behavior, and extends along a continuum of varying severity. Its performance-impairing, afflicting form is considered to be a specific type of social phobia, which requires therapy. There are different psychological theories, which contribute to the understanding of the phenomenon of MPA and provide basic principles for the various treatment approaches. Current "best practice," in our clinical experience, is a personal- and problem-oriented approach within a multimodal therapy model, including the range of psychoanalytic and cognitive behavioral therapies, body-oriented methods, and mental techniques. In order to avoid severe MPA, prevention in the field of music pedagogic is very important. Thus, the concepts of dealing positively with MPA should be implemented very early into the instrumental and vocal education of musicians. © 2015 Elsevier B.V.


Winkel G.,Albert Ludwigs University of Freiburg
Forest Policy and Economics | Year: 2012

In this paper, a review is conducted on the use of the concepts of Michel Foucault in forest policy analysis. In doing so, three major questions are posed: (1) how Foucauldian thinking has influenced the analysis of forest policy, (2) what has been excluded from the analysis, and (3) how a Foucauldian perspective contributes to an enhancement of the theoretical knowledge on forest policy as well as how it may be used in future analyses. Accordingly, in the first section, the Foucauldian concepts that have been the most influential to forest policy analysis, discourse, knowledge, and power as well as governmentality are introduced and summarized in a table aiming to outline a 'Foucauldian perspective'. Subsequently, thirty-nine papers on forest policy that draw on Foucauldian concepts are analyzed with regard to the following dimensions: author, academic background, research motivation, regional focuses, topics and time span covered by the analysis, disciplinary approach, frameworks, theoretical approach and Foucauldian concepts used, methods, main findings, and the conclusions drawn by the scholars about the value of using Foucault for their research. Additionally, the development of the studies over time is analyzed.It can be shown that Foucauldian thoughts have inspired the analysis of forest policy in two major ways: first, via post-structural political ecology studies and, second, via post-positivist discourse analysis. While nearly all of the papers were written by geographers, anthropologists, and policy analysts affiliated with European or North American universities, most of the studies analyzed forest policies in developing countries. Less frequently, conflicts about boreal forests were addressed. Consequently, two commonly found patterns were: an extension of the suppressive effects of colonial forest governmentalities into modern forest policies and discursive struggles about the use of forests. All of the papers shared some common elements, such as: a skeptical attitude towards claims of a single rationality and an objective truth and, in particular, toward central state and capitalist discourses; an interest in the suppressive effects of dominant types of language and knowledge; an understanding that language and knowledge need to be addressed as aspects of power; and an emancipatory motive and interest in broadening the available knowledge base and democratizing policy making. Finally, the results are discussed, and the initially posed questions are again addressed. It is recommended that the Foucauldian analysis of forest policy should literally escape from its own main discourse and address topics that were largely neglected until now. © 2010 Elsevier B.V.


Li C.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Journal of the American Chemical Society | Year: 2014

A rhodium-catalyzed chemo- and regioselective intermolecular decarboxylative addition of β-ketoacids to terminal allenes is reported. Using a Rh(I)/DPPF system, tertiary and quaternary carbon centers were formed with exclusively branched selectivity under mild conditions. Preliminary mechanism studies support that the carbon-carbon bond formation precedes the decarboxylation and the reaction occurs in an outer-sphere mechanism. © 2014 American Chemical Society.


Sotirov M.,Albert Ludwigs University of Freiburg | Memmler M.,Albert Ludwigs University of Freiburg
Forest Policy and Economics | Year: 2012

In this paper, we deal with the Advocacy Coalition Framework (ACF) which has been promoted as a promising theoretical approach of policy change and stability. After outlining the framework's main features and development over time, we review numerous ACF applications in natural resource policy studies and relate them to existing theoretical debates. The framework accounts for long-lasting policy debates between advocacy coalitions regarding value conflicts in multitude geographical domains and political systems. However, we identify several empirical anomalies and conceptual inconsistencies regarding advocacy coalition properties and causal paths to policy change. We draw on cultural theory and veto-player theory and the empirical evidence to theorize and propose several conceptual improvements and new hypotheses. By doing so, we address the ACF's concepts of belief systems, collective action, the role of and interdependencies among external events, political resources and institutions. Our theoretical proposals could provide for more detailed, dynamic and comprehensive look at the interactions among actors and their wider political and socioeconomic environment. These theoretical enhancements could mediate between the ACF propositions and the long-lasting theoretical critique directed to this framework and the divergent empirical evidence as regards to policy change analysis. We acknowledge that the further conceptual development of the framework will depend on the willingness of ACF theorists to integrate insights from rival research programs. © 2011 Elsevier B.V.


Martin S.F.,Albert Ludwigs University of Freiburg
Current Opinion in Allergy and Clinical Immunology | Year: 2015

Purpose of review Allergic contact dermatitis is a skin disease resulting from an adverse reaction of the immune system to low-molecular-weight organic chemicals or metal ions. This review summarizes recent findings that highlight new details of the complex orchestration of the cellular and molecular immune response to contact allergens.Recent findings Progress has been made in the characterization of the roles of natural killer T cells, natural killer cells, mast cells and neutrophils, as well as in the elucidation of signaling pathways triggered by contact allergens. Global technologies begin to reveal gene signatures for contact allergen identification and improved diagnostics.Summary Recent progress in contact allergy research has deepened our understanding of the molecular and cellular pathomechanisms, and opens new avenues towards improved diagnostics and treatments, as well as prevention and risk assessment strategies. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Bauer G.,Albert Ludwigs University of Freiburg
Anticancer Research | Year: 2014

Expression of membrane-associated NADPH oxidase (NOX1) represents a characteristic feature of malignant cells. NOX1-derived extracellular superoxide anions are the basis for autocrine stimulation of proliferation, but also drive the HOCl and the NO/peroxynitrite signaling pathways. This may cause the elimination of transformed cells. Tumor cells express membrane-associated catalase that efficiently protects the cells against apoptosis-inducing reactive oxygen species (ROS) signaling. Membrane-associated superoxide dismutase (SOD) plays a co-modulatory protective role that is functionally interrelated with the protective effect mediated by catalase. Due to the co-localization of NOX1, catalase and SOD on the outer membrane of tumor cells, specific inhibition of membrane-associated SOD causes superoxide anion-dependent inhibition of catalase. This establishes a strong apoptotic signaling through the NO/peroxynitrite pathway. In parallel, it causes a drastic decrease in the concentration of proliferation-stimulating H2O2. Knowledge of the biochemical network on the surface of tumor cells should, therefore, allow development of specific novel strategies for tumor therapy, based on the specific features of tumor cell-specific extracellular ROS interactions.


Muller K.,Albert Ludwigs University of Freiburg | Zurbriggen M.D.,Albert Ludwigs University of Freiburg | Weber W.,Albert Ludwigs University of Freiburg
Nature Protocols | Year: 2014

Light-triggered gene expression systems offer an unprecedented spatiotemporal resolution that cannot be achieved with classical chemically inducible genetic tools. Here we describe a protocol for red light-responsive gene expression in mammalian cells. This system can be toggled between stable ON and OFF states by short pulses of red and far-red light, respectively. In the protocol, CHO-K1 cells are transfected to allow red light-inducible expression of the secreted alkaline phosphatase (SEAP) reporter, and gene expression is tuned by illumination with light of increasing wavelengths. As a starting point for elaborate red light-responsive gene expression, we outline the reversible activation of gene expression and describe how a spatial pattern can be 'printed' on a monolayer of cells by using a photomask. The core protocol requires only 4 d from seeding of the cells to reporter quantification, and other than light-emitting diode (LED) illumination boxes no elaborate equipment is required. © 2014 Nature America, Inc.


Vautravers N.R.,Albert Ludwigs University of Freiburg | Regent D.D.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Chemical Communications | Year: 2011

Based on a conceptually innovative bifunctional P,N ligand, an efficient protocol for the rhodium-catalyzed inter- and intramolecular hydroacylation of alkenes has been developed. © 2011 The Royal Society of Chemistry.


Witt B.,Albert Ludwigs University of Freiburg | Mintert F.,Albert Ludwigs University of Freiburg
New Journal of Physics | Year: 2013

We examine the excitation transport across quantum networks that are continuously driven by a constant and incoherent source. In particular we investigate the coherence properties of incoherently driven networks by employing recent tools from entanglement theory that enable a rigorous interpretation of coherence in the site basis. With these tools at hand we identify coherent delocalization of excitations over several sites to be a crucial prerequisite for highly efficient transport across networks driven by an incoherent source. These results are set into context with the latest discussion of the occurrence of coherence in molecular complexes that are driven by incoherent sun light. © IOP Publishing and Deutsche Physikalische Gesellschaft.


Xu K.,Albert Ludwigs University of Freiburg | Khakyzadeh V.,Albert Ludwigs University of Freiburg | Bury T.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Journal of the American Chemical Society | Year: 2014

A new strategy for the transformation of terminal alkynes to branched allylic sulfones was developed. Using a Rh(I)/DPEphos/benzoic acid catalyst system, terminal alkynes react with sulfonyl hydrazides to produce branched allylic sulfones with good to excellent yields and selectivities in general. © 2014 American Chemical Society.


Basso L.,Albert Ludwigs University of Freiburg
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

The 1-loop renormalization group equations for the minimal Z' models encompassing a type-I seesaw mechanism are studied in the light of the 125 GeV Higgs boson observation. This model is taken as a benchmark for the general case of singlet extensions of the standard model. The most important result is that negative scalar mixing angles are favored with respect to positive values. Further, a minimum value for the latter exists, as well as a maximum value for the masses of the heavy neutrinos, depending on the vacuum expectation value of the singlet scalar. © 2013 Elsevier B.V.


Friedrich L.,Albert Ludwigs University of Freiburg | Rohrbach A.,Albert Ludwigs University of Freiburg
Optics Letters | Year: 2012

Backfocal plane (BFP) interferometry is a single particle tracking technique that allows one to measure minute displacements of a microscopic particle from the center of a beam's focus in three dimensions. In this Letter, we present a Fourier optics model to describe the interference effects that allow one to track the position of a particle moving along the optical axis. A detection numerical aperture is derived theoretically and confirmed experimentally, within which the interference intensity has a positive correlation with the axial position of the scatterer. For larger detection angles, the correlation is negative. The model helps to understand previously reported measurements and to optimize BFP interferometric tracking. © 2012 Optical Society of America.


Draper P.,University of California at Santa Barbara | Rzehak H.,Albert Ludwigs University of Freiburg | Rzehak H.,University of Southern Denmark
Physics Reports | Year: 2016

The discovery of the Higgs boson is both a milestone achievement for the Standard Model and an exciting probe of new physics beyond the SM. One of the most important properties of the Higgs is its mass, a number that has proven to be highly constraining for models of new physics, particularly those related to the electroweak hierarchy problem. Perhaps the most extensively studied examples are supersymmetric models, which, while capable of producing a 125 GeV Higgs boson with SM-like properties, do so in non-generic parts of their parameter spaces. We review the computation of the Higgs mass in the Minimal Supersymmetric Standard Model, in particular the large radiative corrections required to lift mh to 125 GeV and their calculation via Feynman-diagrammatic and effective field theory techniques. This review is intended as an entry point for readers new to the field, and as a summary of the current status, including the existing analytic calculations and publicly-available computer codes. © 2016 Elsevier B.V..


Schubert T.,Albert Ludwigs University of Freiburg | Romer W.,Albert Ludwigs University of Freiburg
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2015

Synthetic membrane systems, such as giant unilamellar vesicles and solid supported lipid bilayers, have widened our understanding of biological processes occurring at or through membranes. Artificial systems are particularly suited to study the inherent properties of membranes with regard to their components and characteristics. This review critically reflects the emerging molecular mechanism of lipid-driven endocytosis and the impact of model membrane systems in elucidating the complex interplay of biomolecules within this process. Lipid receptor clustering induced by binding of several toxins, viruses and bacteria to the plasma membrane leads to local membrane bending and formation of tubular membrane invaginations. Here, lipid shape, and protein structure and valency are the essential parameters in membrane deformation. Combining observations of complex cellular processes and their reconstitution on minimal systems seems to be a promising future approach to resolve basic underlying mechanisms. This article is part of a Special Issue entitled: Mechanobiology. © 2015 Elsevier B.V.


Ginhoux F.,Agency for Science, Technology and Research Singapore | Prinz M.,Albert Ludwigs University of Freiburg
Cold Spring Harbor Perspectives in Biology | Year: 2015

Microglia are the resident macrophages of the central nervous system (CNS), which sit in close proximity to neural structures and are intimately involved in brain homeostasis. The microglial population also plays fundamental roles during neuronal expansion and differentiation, as well as in the perinatal establishment of synaptic circuits. Any change in the normal brain environment results in microglial activation, which can be detrimental if not appropriately regulated. Aberrant microglial function has been linked to the development of several neurological and psychiatric diseases. However, microglia also possess potent immunoregulatory and regenerative capacities, making them attractive targets for therapeutic manipulation. Such rationale manipulations will, however, require in-depth knowledge of their origins and the molecular mechanisms underlying their homeostasis. Here, we discuss the latest advances in our understanding of the origin, differentiation, and homeostasis of microglial cells and their myelomonocytic relatives in the CNS. © 2015, Cold Spring Harbor Laboratory Press; all rights reserved.


Drayer B.,Albert Ludwigs University of Freiburg
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2011

In this paper we compare images based on the constellation of their interest points. The fundamental technique for this comparison is our matching algorithm, that is capable to model miss- and multi-matches, while enforcing one-to-one matches. We associate an energy function for the possible matchings. In order to find the matching with the lowest energy, we reformulate this energy function as Markov Random Field and determine the matching with the lowest energy by an efficient minimization strategy. In the experiments, we compare our algorithm against the normalized cross correlation and a naive forth-and-back best neighbor match algorithm. © 2011 Springer-Verlag.


Baumeister H.,Albert Ludwigs University of Freiburg | Hutter N.,Albert Ludwigs University of Freiburg | Bengel J.,Albert Ludwigs University of Freiburg
Diabetic Medicine | Year: 2014

Aims: To summarize and critically evaluate the effectiveness of psychological and pharmacological interventions for depression in patients with both diabetes and depression. Methods: Randomized controlled trials investigating psychological and pharmacological interventions for depression in adults with diabetes and depression were included. A comprehensive search of primary studies according to Cochrane were conducted. Primary outcomes were depression and glycaemic control. Further, treatment adherence, diabetes complications, mortality, healthcare costs and quality of life were investigated. Two reviewers identified primary studies and extracted data independently. Random-effects model meta-analyses were conducted to compute overall estimates of treatment outcomes. Results: The database search resulted in 3963 references, of which 19 trials were included. Randomized controlled trials of psychological interventions showed positive effects on short- and medium-term depression severity [standardized mean difference short-term range -1.47; -0.14, n = 7; medium-term standardized mean difference -0.42 (95% CI -0.70 to -0.14), n = 3] and depression remission [odds ratio short term 2.88 (95% CI 1.58-5.25), n = 4; odds ratio medium term 2.49 (95% CI 1.44-4.32), n = 2]. Effects on glycaemic control in psychological intervention trials varied substantially (standardized mean difference range -0.97 to 0.47, n = 4). Selective serotonin reuptake inhibitors showed a moderate beneficial effect on short-term depression severity [standardized mean difference -0.39 (95% CI -0.64 to -0.13], n = 5) and depression remission [odds ratio 2.52 (95% CI 1.11-5.75), n = 2]. Glycaemic control improved in randomized controlled trials comparing selective serotonin reuptake inhibitors with placebo at the end of treatment [standardized mean difference -0.38 (95% CI -0.64 to -0.12), n = 5]. Conclusions: Psychological and pharmacological interventions positively affect depression outcomes in patients with diabetes at the end of treatment. Furthermore, short-term glycaemic control improved moderately in pharmacological trials. Most outcomes have not been investigated sufficiently. Moreover, there is a lack of follow-up data for pharmacological trials limiting the evidence on the sustainability of treatment effects. © 2014 Diabetes UK.


Kloke A.,Albert Ludwigs University of Freiburg | Von Stetten F.,Albert Ludwigs University of Freiburg | Zengerle R.,Albert Ludwigs University of Freiburg | Kerzenmacher S.,Albert Ludwigs University of Freiburg
Advanced Materials | Year: 2011

Porous platinum is of high technological importance due to its various applications in fuel cells, sensors, stimulation electrodes, mechanical actuators and catalysis in general. Based on a discussion of the general principles behind the reduction of platinum salts and corresponding deposition processes this article discusses techniques available for platinum electrode fabrication. The numerous, different strategies available to fabricate platinum electrodes are reviewed and discussed in the context of their tuning parameters, strengths and weaknesses. These strategies comprise bottom-up approaches as well as top-down approaches. In bottom-up approaches nanoparticles are synthesized in a first step by chemical, photochemical or sonochemical means followed by an electrode formation step by e.g. thin film technology or network formation to create a contiguous and conducting solid electrode structure. In top-down approaches fabrication starts with an already conductive electrode substrate. Corresponding strategies enable the fabrication of substrate-based electrodes by e.g. electrodeposition or the fabrication of self-supporting electrodes by dealloying. As a further top-down strategy, this review describes methods to decorate porous metals other than platinum with a surface layer of platinum. This way, fabrication methods not performable with platinum can be applied to the fabrication of platinum electrodes with the special benefit of low platinum consumption. Porous platinum electrodes bringing together high catalytic activity and high surface area have become integral parts of various applications such as fuel cells or sensors. This article discusses strengths and weaknesses of fabrication techniques for substrate-based electrodes (e.g., by electrodeposition), self-supporting electrodes (e.g., by dealloying) as well as nanoparticle based fabrication and approaches for platinum decoration of other conducting porous materials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Baglioni C.,Albert Ludwigs University of Freiburg | Riemann D.,Albert Ludwigs University of Freiburg
Current Psychiatry Reports | Year: 2012

Insomnia has been found to be a clinical predictor of subsequent depression. Nevertheless the biological processes underlying this causal relationship are yet not fully understood. Both conditions share a common imbalance of the arousal system. Patients with insomnia present fragmented REM sleep, which probably interferes with basal processes of emotion regulation. The interaction between the arousal and the affective system with the persistence of the disorder could slowly alter also the cognitive system and lead to depression. Although preliminary results seem to support this hypothesis, data are still too few to make valid conclusions. © Springer Science+Business Media, LLC 2012.


Thiele S.,Albert Ludwigs University of Freiburg | Zengerle R.,Albert Ludwigs University of Freiburg | Ziegler C.,Albert Ludwigs University of Freiburg
Nano Research | Year: 2011

The oxygen reduction reaction (ORR) in the cathode catalyst layer (CCL) of polymer electrolyte fuel cells (PEFC) is one of the major causes of performance loss during operation. In addition, the CCL is the most expensive component due to the use of a Pt catalyst. Apart from the ORR itself, the species transport to and from the reactive sites determines the performance of the PEFC. The effective transport properties of the species in the CCL depend on its nanostructure. Therefore a three-dimensional reconstruction of the CCL is required. A series of two-dimensional images was obtained from focused ion beam - scanning electron microscope (FIB-SEM) imaging and a segmentation method for the two-dimensional images has been developed. The pore size distribution (PSD) was calculated for the three-dimensional geometry. The influence of the alignment and the anisotropic pixel size on the PSD has been investigated. Pores were found in the range between 5 nm and 205 nm. Evaluation of the Knudsen number showed that gas transport in the CCL is governed by the transition flow regime. The liquid water transport can be described within continuum hydrodynamics by including suitable slip flow boundary conditions. © 2011 Tsinghua University Press and Springer-Verlag Berlin Heidelberg.


Accorsi R.,Albert Ludwigs University of Freiburg
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2011

This paper presents BBox, a digital black box to provide for authentic archiving in distributed systems. Based upon public key cryptography and trusted computing platforms, the BBox employs standard primitives to ensure the authenticity of records during the transmission from devices to the collector, as well as during their storage on the collector and retrieval by auditors. Besides presenting the technical underpinnings of the BBox, this paper demonstrates the authenticity guarantees it ensures and reports on the preliminary deployment figures. © 2011 Springer-Verlag.


Fritz R.D.,University of Basel | Radziwill G.,Albert Ludwigs University of Freiburg
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2011

FoxO transcription factors mediate anti-proliferative and pro-apoptotic signals and act as tumor suppressors in cancer. Posttranslational modifications including phosphorylation and acetylation regulate FoxO activity by a cytoplasmicxnuclear shuttle mechanism. Scaffold proteins coordinating signaling pathways in time and space play a critical role in this process. CNK1 acts as a scaffold protein in several signaling pathways controlling the function of FoxO proteins. An understanding of CNK1 and other scaffolds in the FoxO signaling network will provide insights how to release the tumor suppressor function of FoxO as a possibility to block oncogenic pathways. This article is part of a Special Issue entitled: P13K-AKT-FoxO axis in cancer and aging. © 2011 Elsevier B.V.


Wasch R.,Albert Ludwigs University of Freiburg
Expert Opinion on Therapeutic Targets | Year: 2011

Several chemotherapeutic drugs interfere with assembly of the mitotic spindle of cancer cells, leading to mitotic arrest, mediated by the spindle assembly checkpoint (SAC). However, cancer cells may be SAC-deficient and survive such treatment, due to mitotic slippage. Sensing of defective spindle assembly by the SAC, causes inhibition of the anaphase-promoting complex or cyclosome (APC/C), and blocks mitotic exit, by stabilizing APC/C substrates, such as cyclin B. Mitotic slippage may occur due to residual APC/C activity and slow cyclin B degradation. Recent preclinical data suggests that targeting mitotic exit by blocking APC/C activity is a much more efficient therapeutic approach than disturbing mitotic spindle assembly. © 2011 Informa UK, Ltd.


Baumgartne T.,Albert Ludwigs University of Freiburg | Pahl-Wostl C.,University of Osnabrück
Ecology and Society | Year: 2013

UN-Water was established in 2003 to coordinate United Nations activities on water. There have been no scientific assessments about this coordination mechanism and, hence, we focus on the role of UN-Water in global water governance. We use an analytical framework to conceptualize relevant natural and social phenomena, actors, and institutions in the field of global water governance. This framework ultimately allows an assessment of UN-Water's role in this field. Our work draws upon official UN-Water documents, a formal external review of UN-Water, and semistructured expert interviews to assess UN-Water's influence on global water discourses, particularly on the discourses of water and climate change, and integrated water resources management. This helps to identify UN-Water's specific functions in the field of global water governance. The mechanism acts as a bridge between the expert-centered background and the political foreground of global water governance. © 2013 by the author(s).


Reising K.,Albert Ludwigs University of Freiburg
Acta chirurgiae orthopaedicae et traumatologiae Cechoslovaca | Year: 2011

Surgical techniques for the treatment of supracondylar fractures in children are repeatedly the subject of discussion. The aim of the present study was to compare experience with the technique of crossed Kirschner wires at our own hospital with current literature. In the period from 2000-2006 a total of 86 children aged 1.7 to 12.7 years were treated by means of crossed K-wire osteosynthesis. Follow up was conducted at an average of 32 months. Outcomes were evaluated based on von Laer's criteria. Reported complications were migration of the K-wires in 7% of cases and secondary dislocation and re-operation in 4% of cases. Lesion of the radial nerve was diagnosed postoperatively in two cases. Hospital stay was 1.5 days on average. Postoperative immobilization in an upper arm splint and implant removal after 6 weeks on average. 57% of the children received physiotherapy during the course of treatment. Slight varization was found in 11% of children and an unsatisfactory range of motion in 13%. Satisfactory outcomes were recorded for 83% of patients. K-wire osteosynthesis is associated with a low complication rate and continues to be a safe standard procedure for the stabilization of supracondylar humerus fractures. Key words: supracondylar humerus fracture, Kirschner wires, paediatric fractures.


Koppelkamm A.,Albert Ludwigs University of Freiburg
International journal of legal medicine | Year: 2010

Gene expression analyses based on messenger RNA (mRNA) profiling require accurate data normalisation. When using endogenous reference genes, these have to be validated carefully. Therefore, we examined the transcript stability of 10 potential reference genes using quantitative real-time polymerase chain reaction: beta actin, 18S rRNA, glyceraldehyde-3-phosphate dehydrogenase, TATA box-binding protein, hypoxanthine phosphoribosyl-transferase I, beta-2-microglobulin, hydroxymethylbilane synthase, succinate dehydrogenase complex, subunit A, cyclophilin A and ubiquitin C. The aim of the current study was to assess which reference genes show stable mRNA levels in human post mortem cardiac muscle, skeletal muscle and brain tissue. Considering cardiac muscle tissue, CYCA and TBP were identified as the most stable while in skeletal muscle tissue, SDHA and TBP, and in brain tissue, SDHA and HMBS turned out to be the most stable. Furthermore, we recommend a minimum of four carefully validated endogenous control genes for reliable data normalisation in human post mortem tissue. Parameters influencing the stability of transcript amounts were found to be mainly the post mortem interval in cardiac muscle and skeletal muscle tissue and the donor's cause of death in skeletal muscle and brain samples. Further parameters like gender, age at death and body mass index were found to influence mRNA quantities in skeletal muscle only. The set of stable control genes identified in this study may be used in further studies if the composition of the samples is similar to the one used here.


Veitch V.,University of Waterloo | Ferrie C.,University of Waterloo | Gross D.,Albert Ludwigs University of Freiburg | Emerson J.,University of Waterloo
New Journal of Physics | Year: 2012

A central problem in quantum information is to determine the minimal physical resources that are required for quantum computational speed-up and, in particular, for fault-tolerant quantum computation. We establish a remarkable connection between the potential for quantum speed-up and the onset of negative values in a distinguished quasi-probability representation, a discrete analogue of the Wigner function for quantum systems of odd dimension. This connection allows us to resolve an open question on the existence of bound states for magic state distillation: we prove that there exist mixed states outside the convex hull of stabilizer states that cannot be distilled to non-stabilizer target states using stabilizer operations. We also provide an efficient simulation protocol for Clifford circuits that extends to a large class of mixed states, including bound universal states. © IOP Publishing and Deutsche Physikalische Gesellschaft.


Spatzal T.,Howard Hughes Medical Institute | Perez K.A.,Howard Hughes Medical Institute | Einsle O.,Albert Ludwigs University of Freiburg | Einsle O.,0 Center for Biological Signalling Studies | And 3 more authors.
Science | Year: 2014

(D.C.R.). The mechanism of nitrogenase remains enigmatic, with a major unresolved issue concerning how inhibitors and substrates bind to the active site. We report a crystal structure of carbon monoxide (CO)-inhibited nitrogenase molybdenum-iron (MoFe)-protein at 1.50 angstrom resolution, which reveals a CO molecule bridging Fe2 and Fe6 of the FeMo-cofactor. The μ2binding geometry is achieved by replacing a belt-sulfur atom (S2B) and highlights the generation of a reactive iron species uncovered by the displacement of sulfur. The CO inhibition is fully reversible as established by regain of enzyme activity and reappearance of S2B in the 1.43 angstrom resolution structure of the reactivated enzyme. The substantial and reversible reorganization of the FeMo-cofactor accompanying CO binding was unanticipated and provides insights into a catalytically competent state of nitrogenase. © 2014 by the American Association for the Advancement of Science; all rights reserved.


Matzarakis A.,Albert Ludwigs University of Freiburg
Gefahrstoffe Reinhaltung der Luft | Year: 2013

The climate change is an issue for climate protection and also for quality of life of city dwellers which has to be addressed quickly. This requires quantitative information about the frequency and intensity of conditions with heat stress for people. These data should be based on thermal indices (e.g. physiologically equivalent temperature) which consider the energy balance of the human body and characterize thermal comfort or stress conditions. Measurements and simulations for current and future climatic conditions show that for cities in temperate climate regions an adaptation potential exists which can be easily realized by means of urban planning measures, e.g., reconstruction of urban surfaces and optimization of vegetation by suitable broad-leaved trees.


Mintert F.,Albert Ludwigs University of Freiburg
Journal of Physics A: Mathematical and Theoretical | Year: 2010

We establish a technique to find the states with most robust entanglement in dissipative quantum systems and explicitly construct those states for various environments. © 2010 IOP Publishing Ltd.


Kubo F.,Max Planck Institute of Neurobiology | Hablitzel B.,Albert Ludwigs University of Freiburg | DalMaschio M.,Max Planck Institute of Neurobiology | Driever W.,Albert Ludwigs University of Freiburg | And 2 more authors.
Neuron | Year: 2014

Animals respond to whole-field visual motion with compensatory eye and body movements in order to stabilize both their gaze and position with respect to their surroundings. In zebrafish, rotational stimuli need to be distinguished from translational stimuli to drive the optokinetic and the optomotor responses, respectively. Here, we systematically characterize the neural circuits responsible for these operations using a combination of optogenetic manipulation and invivo calcium imaging during optic flow stimulation. By recording the activity of thousands of neurons within the area pretectalis (APT), we find four bilateral pairs of clusters that process horizontal whole-field motion and functionally classify eleven prominent neuron types with highly selective response profiles. APT neurons are prevalently direction selective, either monocularly or binocularly driven, and hierarchically organized to distinguish between rotational and translational optic flow. Our data predict a wiring diagram of a neural circuit tailored to drive behavior that compensates for self-motion. © 2014 Elsevier Inc.


Deuquet J.,Ecole Polytechnique Federale de Lausanne | Lausch E.,Albert Ludwigs University of Freiburg | Superti-Furga A.,University of Lausanne | Van Der Goot F.G.,Ecole Polytechnique Federale de Lausanne
EMBO Journal | Year: 2012

Capillary morphogenesis gene 2 (CMG2) is a type I membrane protein involved in the homeostasis of the extracellular matrix. While it shares interesting similarities with integrins, its exact molecular role is unknown. The interest and knowledge about CMG2 largely stems from the fact that it is involved in two diseases, one infectious and one genetic. CMG2 is the main receptor of the anthrax toxin, and knocking out this gene in mice renders them insensitive to infection with Bacillus anthracis spores. On the other hand, mutations in CMG2 lead to a rare but severe autosomal recessive disorder in humans called Hyaline Fibromatosis Syndrome (HFS). We will here review what is known about the structure of CMG2 and its ability to mediate anthrax toxin entry into cell. We will then describe the limited knowledge available concerning the physiological role of CMG2. Finally, we will describe HFS and the consequences of HFS-associated mutations in CMG2 at the molecular and cellular level. © 2012 European Molecular Biology Organization | All Rights Reserved.


Glocker E.,Albert Ludwigs University of Freiburg | Grimbacher B.,Albert Ludwigs University of Freiburg | Grimbacher B.,University College London
Cellular and Molecular Life Sciences | Year: 2012

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease are chronic and relapsing conditions, characterized by abdominal pain, diarrhea, bleeding and malabsorption. IBD has been considered a hyperinflammatory state due to disturbed interactions between the immune system and the commensal bacterial flora of the gut. However, there is evidence that Crohn's disease might be the consequence of a reduced release of pro-inflammatory cytokines and an impaired acute inflammatory response, thereby suggesting that IBD might be an immunodeficiency rather than an excessive inflammatory reaction. This theory has been supported by observations in patients with primary immunodeficiencies such as the Wiskott-Aldrich syndrome and IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In contrary, defects in the anti-inflammatory down-regulation of the immune response as they are seen in patients with Mendelian defects in the IL10 signaling pathway support the hyper-inflammatory theory. In this review, we describe and discuss primary immunodeficiencies associated with IBD and show that the bowel is a highly sensitive indicator of dysregulations, making IBD a model disease to study and identify key regulators required to balance the human mucosal immune system. © 2011 Springer Basel AG.


Reichle M.A.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Angewandte Chemie - International Edition | Year: 2012

Tolerant: Alkylmagnesium reagents can be synthesized from alkenes through a sequence of hydroboration and subsequent boron-magnesium exchange using a method that tolerates different functional groups (see scheme). The resulting alkylmagnesium reagents can be used in carbon-carbon bond forming reactions, such as alkylation reactions or transition-metal-catalyzed cross-coupling reactions. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Steuber J.,University of Hohenheim | Vohl G.,Albert Ludwigs University of Freiburg | Casutt M.S.,Albert Ludwigs University of Freiburg | Vorburger T.,University of Hohenheim | And 2 more authors.
Nature | Year: 2014

NADH oxidation in the respiratory chain is coupled to ion translocation across the membrane to build up an electrochemical gradient. The sodium-translocating NADH:quinone oxidoreductase (Na+-NQR), a membrane protein complex widespread among pathogenic bacteria, consists of six subunits, NqrA, B, C, D, E and F. To our knowledge, no structural information on the Na+-NQR complex has been available until now. Here we present the crystal structure of the Na+-NQR complex at 3.5 Å resolution. The arrangement of cofactors both at the cytoplasmic and the periplasmic side of the complex, together with a hitherto unknown iron centre in the midst of the membrane-embedded part, reveals an electron transfer pathway from the NADH-oxidizing cytoplasmic NqrF subunit across the membrane to the periplasmic NqrC, and back to the quinone reduction site on NqrA located in the cytoplasm. A sodium channel was localized in subunit NqrB, which represents the largest membrane subunit of the Na+-NQR and is structurally related to urea and ammonia transporters. On the basis of the structure we propose a mechanism of redox-driven Na+ translocation where the change in redox state of the flavin mononucleotide cofactor in NqrB triggers the transport of Na+ through the observed channel. ©2014 Macmillan Publishers Limited. All rights reserved.


Manoli M.,Albert Ludwigs University of Freiburg | Driever W.,Albert Ludwigs University of Freiburg
Frontiers in Neuroanatomy | Year: 2014

During ventral forebrain development, orthologs of the homeodomain transcription factor Nkx2.1 control patterning of hypothalamus, preoptic region, and ventral telencephalon. However, the relative contributions of Nkx2.1 and Nkx2.4 to prosencephalon development are poorly understood. Therefore, we analyzed functions of the previously uncharacterized nkx2.4-like zgc:171531 as well as of the presumed nkx2.1 orthologs nkx2.1a and nkx2.1b in zebrafish forebrain development. Our results show that zgc:171531 and nkx2.1a display overlapping expression patterns and a high sequence similarity. Together with a high degree of synteny conservation, these findings indicate that both these genes indeed are paralogs of nkx2.4. As a result, we name zgc:171531 now nkx2.4a, and changed the name of nkx2.1a to nkx2.4b, and of nkx2.1b to nkx2.1. In nkx2.1, nkx2.4a, and nkx2.4b triple morpholino knockdown (nkx2TKD) embryos we observed a loss of the rostral part of prosomere 3 and its derivative posterior tubercular and hypothalamic structures. Furthermore, there was a loss of rostral and intermediate hypothalamus, while a residual preoptic region still develops. The reduction of the ventral diencephalon was accompanied by a ventral expansion of the dorsally expressed pax6, revealing a dorsalization of the basal hypothalamus. Within the telencephalon we observed a loss of pallidal markers, while striatum and pallium are forming. At the neuronal level, nkx2TKD morphants lacked several neurosecretory neuron types, including avp, crh, and pomc expressing cells in the hypothalamus, but still form oxt neurons in the preoptic region. Our data reveals that, while nkx2.1, nkx2.4a, and nkx2.4b genes act partially redundant in hypothalamic development, nkx2.1 is specifically involved in the development of rostral ventral forebrain including the pallidum and preoptic regions, whereas nkx2.4a and nkx2.4b control the intermediate and caudal hypothalamus. © 2014, Manoli and Driever.


Brunner T.B.,Albert Ludwigs University of Freiburg | Brunner T.B.,University of Oxford
Current Oncology Reports | Year: 2013

Although neoadjuvant chemoradiotherapy has been tested for more than two decades and can be safely delivered to patients with non-metastatic pancreatic cancer, no randomised trials have been reported until now. Here we provide an overview of the first randomised trial in patients with potentially resectable cancer and of the latest developments in neoadjuvant therapy for this group of patients. It is necessary to continue to perform clinical trials in this field to accurately identify the effect on survival and quality of life in patients with potentially resectable, borderline resectable and unresectable pancreatic cancer. Aspects of imaging for restaging and clinical prognostic factors are also discussed given they will be useful instruments for future trials. © 2013 Springer Science+Business Media New York.


Grunanger C.U.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Angewandte Chemie - International Edition | Year: 2010

(Figure Presented) Remote and reversible! Phosphinites serve as reversibly bound directing groups for the remote control of the regio- and diastereoselective hydroformylation of bishomoallylic alcohols (see scheme; r.r: regioisomer ratio). The distance between the double bond and the functional hydroxy group to which the directing group is reversibly bound is the longest ever reported. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Cooke M.L.,Albert Ludwigs University of Freiburg | Xu K.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Angewandte Chemie - International Edition | Year: 2012

Branching out: The rhodium-catalyzed enantioselective hydroamination of monosubstituted allenes with anilines permits the atom-economic synthesis of valuable branched allylic amines. In contrast to previous linear selective allene hydroaminations, a Rh I/Josiphos catalyst system (see scheme; cod=1,5-cyclooctadiene, DCE=1,2-dichloroethane) allows branched allylic amines to be obtained with perfect regioselectivity, high yield, and good enantioselectivity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Gellrich U.,Albert Ludwigs University of Freiburg | Seiche W.,Albert Ludwigs University of Freiburg | Keller M.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Angewandte Chemie - International Edition | Year: 2012

The structural integrity and flexibility provided by intermolecular hydrogen bonds leads to the outstanding properties of the 6- diphenylphosphinopyridin-(2H)-1-one ligand (see scheme) in the rhodium-catalyzed hydroformylation of terminal alkenes, as demonstrated by the combination of spectroscopic methods and DFT computations. Hydrogen bonds were also detected in a competent intermediate of the catalytic cycle. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Huang J.,Albert Ludwigs University of Freiburg | Voss B.,Albert Ludwigs University of Freiburg
BMC Bioinformatics | Year: 2014

Background: RNA molecules, especially non-coding RNAs, play vital roles in the cell and their biological functions are mostly determined by structural properties. Often, these properties are related to dynamic changes in the structure, as in the case of riboswitches, and thus the analysis of RNA folding kinetics is crucial for their study. Exact approaches to kinetic folding are computationally expensive and, thus, limited to short sequences. In a previous study, we introduced a position-specific abstraction based on helices which we termed helix index shapes (hishapes) and a hishape-based algorithm for near-optimal folding pathway computation, called HiPath. The combination of these approaches provides an abstract view of the folding space that offers information about the global features. Results: In this paper we present HiKinetics, an algorithm that can predict RNA folding kinetics for sequences up to several hundred nucleotides long. This algorithm is based on RNAHeliCes, which decomposes the folding space into abstract classes, namely hishapes, and an improved version of HiPath, namely HiPath2, which estimates plausible folding pathways that connect these classes. Furthermore, we analyse the relationship of hishapes to locally optimal structures, the results of which strengthen the use of the hishape abstraction for studying folding kinetics. Finally, we show the application of HiKinetics to the folding kinetics of two well-studied RNAs. Conclusions: HiKinetics can calculate kinetic folding based on a novel hishape decomposition. HiKinetics, together with HiPath2 and RNAHeliCes, is available for download at http://www.cyanolab.de/software/RNAHeliCes.htm. © 2014 Huang and Voß licensee BioMed Central Ltd.


Royston P.,University College London | Sauerbrei W.,Albert Ludwigs University of Freiburg
Statistics in Medicine | Year: 2013

Interactions between treatments and covariates in RCTs are a key topic. Standard methods for modelling treatment-covariate interactions with continuous covariates are categorisation or linear functions. Both approaches are easily criticised, but for different reasons. Multivariable fractional polynomial interactions, an approach based on fractional polynomials with the linear interaction model as the simplest special case, was proposed. Four variants of multivariable fractional polynomial interaction (FLEX1-FLEX4), allowing varying flexibility in functional form, were suggested. However, their properties are unknown, and comparisons with other procedures are unavailable. Additionally, we consider various methods based on categorisation and on cubic regression splines. We present the results of a simulation study to determine the significance level (probability of a type 1 error) of various tests for interaction between a binary covariate ('treatment effect') and a continuous covariate in univariate analysis. We consider a simplified setting in which the response variable is conditionally normally distributed, given the continuous covariate. We consider two main cases with the covariate distribution well behaved (approximately symmetric) or badly behaved (positively skewed). We construct nine scenarios with different functional forms for the main effect. In the well-behaved case, significance levels are in general acceptably close to nominal and are slightly better for the larger sample size (n=250 and 500 were investigated). In the badly behaved case, departures from nominal are more pronounced for several approaches. For a final assessment of these results and recommendations for practice, a study of power is needed. © 2013 John Wiley & Sons, Ltd.


Keller J.,Albert Ludwigs University of Freiburg | Zaitsev A.N.,Natural History Museum in London
Lithos | Year: 2012

The natrocarbonatites of Oldoinyo Lengai, Tanzania, are unique in magmatic petrology. The historical activity of Oldoinyo Lengai has seen changes from nephelinitic to natrocarbonatitic character of the emitted magmas. Since 1983 the activity was characterized by the effusion of fluid natrocarbonatite lava from which we have collected and analyzed fresh samples in the summit crater from 1988 to 2007. The available compositional data set forms the basis for presenting and discussing the typical composition and variation of natrocarbonatites and their relationship to the silicate magmas of Oldoinyo Lengai. The "type" natrocarbonatite major and trace element composition is derived for an average of 25 samples with low standard deviation. Oldoinyo Lengai carbonatites are unique in almost all aspects of their petrological and geochemical characteristics and are characterized as extremely alkali-rich, with Na 2O+K 2O generally about 40wt.%, and with high CaO contents of 14-18wt.%. This composition results from the presence of phenocrysts of nyerereite (Na,K) 2Ca(CO 3) 2 and gregoryite (Na,K,Ca x) 2-x(CO 3) dominating the highly porphyritic natrocarbonatite lavas, with sylvite and fluorite as main groundmass minerals. The significance of particular trace element concentrations and ratios of equally incompatible elements (REE, Ba, Sr, Th/U, Nb/Ta, Zr/Hf) is evaluated for models of liquid-liquid separation. In defining a "type" natrocarbonatite composition, we also distinguish special variations in chemical and/or mineralogical compositions as follows: (1) silicate-bearing natrocarbonatites, characterized by the occurrence of nephelinite spheroids, as in the 1993 and 2006 lavas; (2) residual melt compositions as described from the 1988 eruptive period as represented by the aphyric, filter-pressed interstitial melt of solidifying porphyritic lavas; (3) an interlude during 2000 when natrocarbonatites with sylvite and fluorite microcrysts were emitted. After 25years of mostly mild activity characterized by effusion and spattering of fluid natrocarbonatite lava, the paroxysmal ash eruptions of September 4, 2007, changed dramatically the crater morphology, eruptive dynamics and magma composition of Oldoinyo Lengai. Fresh natrocarbonatites - if present at the bottom of the deep crater pit formed during the 2007-2008 explosive activity - will possibly remain inaccessible for decades. © 2012 Elsevier B.V.


Ong A.C.M.,University of Sheffield | Ong A.C.M.,Sheffield Teaching Hospitals NHS Foundation Trust | Devuyst O.,University of Zürich | Devuyst O.,Catholic University of Louvain | And 2 more authors.
The Lancet | Year: 2015

Autosomal dominant polycystic kidney disease is the most common inherited kidney disease and accounts for 7-10% of all patients on renal replacement therapy worldwide. Although first reported 500 years ago, this disorder is still regarded as untreatable and its pathogenesis is poorly understood despite much study. During the past 40 years, however, remarkable advances have transformed our understanding of how the disease develops and have led to rapid changes in diagnosis, prognosis, and treatment, especially during the past decade. This Review will summarise the key findings, highlight recent developments, and look ahead to the changes in clinical practice that will likely arise from the adoption of a new management framework for this major kidney disease. © 2015 Elsevier Ltd.


Basso L.,Albert Ludwigs University of Freiburg | Staub F.,University of Bonn
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We discuss the impact on the stau masses of additional D terms in U(1)-extended minimal supersymmetric standard models. We show, explicitly for the B-L supersymmetric standard model, that these contributions can play a crucial role in the explanation of the enhanced diphoton decay rate of a standard-model-like Higgs particle around 125 GeV. Even in the most constrained scenario with universal scalar and gaugino masses, it is possible to obtain a sizable enhancement and, in addition, the correct relic density for the LSP. Furthermore, a lighter CP-even scalar that could fit the LEP excess at 98 GeV is viable. © 2013 American Physical Society.


Friedrich L.,Albert Ludwigs University of Freiburg | Rohrbach A.,Albert Ludwigs University of Freiburg
Optics Letters | Year: 2010

For most optical tweezer applications, precise and reliable tracking of the trapped particle is an important requirement. Backfocal-plane interferometry is the fastest and most accurate tracking technique if the particle displacements are limited to half of the focal width. Especially for positive axial displacements, the nonlinear detector response can lead to incorrect tracking results. Here we show how the linear detection range around the trap center can be extended by a factor of 2 to 4 in the axial direction using a second frequency-detuned tracking focus that is generated by the same laser as the optical trap. Additionally, we show how the noise in the axial signal can be decreased significantly using a second detector. © 2010 Optical Society of America.


Chaves R.,Albert Ludwigs University of Freiburg
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

The assumption of local realism, in a Bell locality scenario, imposes nontrivial conditions on the Shannon entropies of the associated probability distributions, expressed by linear entropic Bell inequalities. In principle, these entropic inequalities provide necessary but not sufficient criteria for the existence of a local hidden variable model reproducing the correlations, as, for example, the paradigmatic nonlocal Popescu-Rohrlich (PR) box is entropically not different from a classically correlated box. In this paper we show that for the n-cycle scenario, entropic inequalities completely characterize the set of local correlations. In particular, every nonsignaling box which violates the Clauser-Horne-Shimony-Holt (CHSH) inequality - including the PR box - can be locally modified so that it also violates the entropic version of CHSH inequality. As we show, any nonlocal probabilistic model when appropriately mixed with a local model, violates an entropic inequality, thus evidencing a very peculiar kind of nonlocality. As the n-cycle captures equally well both the notion of local realism introduced by Bell and that of noncontextuality presented by the Kochen-Specker theorem, the results are also valid for noncontextuality scenarios. © 2013 American Physical Society.


Passia N.,Albert Ludwigs University of Freiburg
The European journal of esthetic dentistry : official journal of the European Academy of Esthetic Dentistry | Year: 2011

The "smile line" is commonly used as a parameter to evaluate and categorize a person's smile. This systematic literature review assessed the existing evidence on the validity and universal applicability of this parameter. The latter was evaluated based on studies on smile perception by orthodontists, general clinicians, and laypeople. Methods: A review of the literature published between October 1973 and January 2010 was conducted with the electronic database Pubmed and the search terms "smile," "smile line," "smile arc," and "smile design." Results: The search yielded 309 articles, of which nine studies were included based on the selection criteria. The selected studies typically correlate the smile line with the position of the upper lip during a smile while, on average, 75 to 100% of the maxillary anterior teeth are exposed. A virtual line that connects the incisal edges of the maxillary anterior teeth commonly follows the upper border of the lower lip. Average and parallel smile lines are most common, influenced by the age and gender of a person. Orthodontists, general clinicians, and laypeople have similar preferences and rate average smile lines as most attractive. Conclusions: The smile line is a valid tool to assess the esthetic appearance of a smile. It can be applied universally as clinicians and laypersons perceive and judge it similarly.


Basso L.,Albert Ludwigs University of Freiburg | Fischer O.,Albert Ludwigs University of Freiburg | Van Der Bij J.J.,Albert Ludwigs University of Freiburg
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We consider a model for a Z′-boson coupled only to baryon minus lepton number and hypercharge. Besides the usual right-handed neutrinos, we add a pair of fermions with a fractional lepton charge, which we therefore call leptinos. One of the leptinos is taken to be odd under an additional Z 2 charge, the other even. This allows for a natural (inverse) seesaw mechanism for neutrino masses. The odd leptino is a candidate for dark matter, but has to be resonantly annihilated by the Z′-boson or the Higgs-boson responsible for giving mass to the former. Considering collider and cosmological bounds on the model, we find that the Z′-boson and/or the extra Higgs-boson can be seen at the LHC. With more pairs of leptinos leptogenesis is possible. © 2013 American Physical Society.


Schilling C.,ETH Zurich | Gross D.,Albert Ludwigs University of Freiburg | Christandl M.,ETH Zurich
Physical Review Letters | Year: 2013

The Pauli exclusion principle is a constraint on the natural occupation numbers of fermionic states. It has been suspected since at least the 1970s, and only proved very recently, that there is a multitude of further constraints on these numbers, generalizing the Pauli principle. Here, we provide the first analytic analysis of the physical relevance of these constraints. We compute the natural occupation numbers for the ground states of a family of interacting fermions in a harmonic potential. Intriguingly, we find that the occupation numbers are almost, but not exactly, pinned to the boundary of the allowed region (quasipinned). The result suggests that the physics behind the phenomenon is richer than previously appreciated. In particular, it shows that for some models, the generalized Pauli constraints play a role for the ground state, even though they do not limit the ground-state energy. Our findings suggest a generalization of the Hartree-Fock approximation. © 2013 American Physical Society.


Kaier K.,Albert Ludwigs University of Freiburg
Health Economics, Policy and Law | Year: 2013

The aim of the analysis was to determine whether demand in Germany for specific antimicrobial agents is driven by prices that drop considerably when generic substitutes become available. A time-series approach was therefore carried out to explore price elasticities of demand for two different classes of broad-spectrum antimicrobials (fluoroquinolones and cephalosporins) using data on ambulatory antibiotics prescribed on the German statutory health insurance scheme and data on in-hospital antibiotic use in a German teaching hospital. In short, we attempted to explain demand for different antibiotics based on changes in price and hospital-wide morbidity. The data indicate that patent expiration is followed by substantial decreases in the price of antibiotics. In the outpatient sector, all antibiotics included in the analysis showed significant negative own-price elasticities of demand. However, in the hospital settings, significant own-price elasticities were only determined for some antibiotics, although price decreases were stronger than in the outpatient sector. We conclude that price dependence of demand for antimicrobials is present both in the ambulatory and the hospital setting. However, this is especially surprising in the hospital setting because price differences among the antibiotics observed are particularly small compared with the overall cost of hospitalisation. © 2012 Cambridge University Press.


Verdeny A.,Albert Ludwigs University of Freiburg | Mielke A.,University of Heidelberg | Mintert F.,Albert Ludwigs University of Freiburg
Physical Review Letters | Year: 2013

We present a systematic construction of effective Hamiltonians of periodically driven quantum systems. Because of an equivalence between the time dependence of a Hamiltonian and an interaction in its Floquet operator, flow equations, that permit us to decouple interacting quantum systems, allow us to identify time-independent Hamiltonians for driven systems. With this approach, we explain the experimentally observed deviation of expected suppression of tunneling in ultracold atoms. © 2013 American Physical Society.


Ren H.-P.,Xi'an University of Technology | Ren H.-P.,University of Aberdeen | Baptista M.S.,University of Aberdeen | Grebogi C.,University of Aberdeen | Grebogi C.,Albert Ludwigs University of Freiburg
Physical Review Letters | Year: 2013

The modern world fully relies on wireless communication. Because of intrinsic physical constraints of the wireless physical media (multipath, damping, and filtering), signals carrying information are strongly modified, preventing information from being transmitted with a high bit rate. We show that, though a chaotic signal is strongly modified by the wireless physical media, its Lyapunov exponents remain unaltered, suggesting that the information transmitted is not modified by the channel. For some particular chaotic signals, we have indeed proved that the dynamic description of both the transmitted and the received signals is identical and shown that the capacity of the chaos-based wireless channel is unaffected by the multipath propagation of the physical media. These physical properties of chaotic signals warrant an effective chaos-based wireless communication system. © 2013 American Physical Society.


Bermudez A.,University of Ulm | Schaetz T.,Albert Ludwigs University of Freiburg | Plenio M.B.,University of Ulm
Physical Review Letters | Year: 2013

We introduce a scheme to perform dissipation-assisted quantum information processing in ion traps considering realistic decoherence rates, for example, due to motional heating. By means of continuous sympathetic cooling, we overcome the trap heating by showing that the damped vibrational excitations can still be exploited to mediate coherent interactions as well as collective dissipative effects. We describe how to control their relative strength experimentally, allowing for protocols of coherent or dissipative generation of entanglement. This scheme can be scaled to larger ion registers for coherent or dissipative many-body quantum simulations. © 2013 American Physical Society.


Groten J.,Albert Ludwigs University of Freiburg | Bunte C.,Albert Ludwigs University of Freiburg | Ruhe J.,Albert Ludwigs University of Freiburg
Langmuir | Year: 2012

We report on a method to generate surfaces whose wettability can be reversibly switched between a superhydrophobic and Wenzel state or a Wenzel and superwetting state just by a short UV or VIS irradiation. To achieve this, we generate a silicon surface with a nanoscale roughness ("black silicon") and attach a polymer monolayer to it. The polymer contains a fluorinated azobenzene moiety which can be switched between the cis and trans state depending on the wavelength of the light used during illumination. The surface energy of the polymer coating is carefully adjusted to the energy value which separates distinct wetting regimes of the nanorough surface. This coupling of light induced switching to a transition of the wetting regimes can cause changes in the water contact angle as high as Δθ = 140° in the advancing CA or more than 175° in the receding CA even when the surface energy is changed only in a rather small range. Short irradiation times with UV or VIS light are enough to change the roll-off angle from <5° to no roll off at all and back. We discuss the requirements necessary so that large changes in the contact angle occur during photoswitching processes on rough surfaces. © 2012 American Chemical Society.


Hisch T.,Vienna University of Technology | Liertzer M.,Vienna University of Technology | Pogany D.,Vienna University of Technology | Mintert F.,Albert Ludwigs University of Freiburg | Rotter S.,Vienna University of Technology
Physical Review Letters | Year: 2013

The angular emission pattern of a random laser is typically very irregular and difficult to tune. Here we show by detailed numerical calculations that one can overcome the lack of control over this emission pattern by actively shaping the spatial pump distribution. We demonstrate, in particular, how to obtain customized pump profiles to achieve highly directional emission. Going beyond the regime of strongly scattering media where localized modes with a given directionality can simply be selected by the pump, we present an optimization-based approach which shapes extended lasing modes in the weakly scattering regime according to any predetermined emission pattern. © 2013 American Physical Society.


Baumgratz T.,University of Ulm | Gross D.,Albert Ludwigs University of Freiburg | Cramer M.,University of Ulm | Plenio M.B.,University of Ulm
Physical Review Letters | Year: 2013

Recent contributions in the field of quantum state tomography have shown that, despite the exponential growth of Hilbert space with the number of subsystems, tomography of one-dimensional quantum systems may still be performed efficiently by tailored reconstruction schemes. Here, we discuss a scalable method to reconstruct mixed states that are well approximated by matrix product operators. The reconstruction scheme only requires local information about the state, giving rise to a reconstruction technique that is scalable in the system size. It is based on a constructive proof that generic matrix product operators are fully determined by their local reductions. We discuss applications of this scheme for simulated data and experimental data obtained in an ion trap experiment. © 2013 American Physical Society.


Levi F.,Albert Ludwigs University of Freiburg | Mintert F.,Albert Ludwigs University of Freiburg
Physical Review Letters | Year: 2013

We derive hierarchies of separability criteria that identify the different degrees of entanglement ranging from bipartite to genuine multipartite in mixed quantum states of arbitrary size. © 2013 American Physical Society.


Teshima T.,Hokkaido University | Reddy P.,University of Michigan | Zeiser R.,Albert Ludwigs University of Freiburg
Biology of Blood and Marrow Transplantation | Year: 2016

Graft-versus-host disease (GVHD) continues to be a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Recent insights into intestinal homeostasis and uncovering of new pathways and targets have greatly reconciled our understanding of GVHD pathophysiology and will reshape contemporary GVHD prophylaxis and treatment. Gastrointestinal (GI) GVHD is the major cause of mortality. Emerging data indicate that intestinal stem cells (ISCs) and their niche Paneth cells are targeted, resulting in dysregulation of the intestinal homeostasis and microbial ecology. The microbiota and their metabolites shape the immune system and intestinal homeostasis, and they may alter host susceptibility to GVHD. Protection of the ISC niche system and modification of the intestinal microbiota and metabolome to restore intestinal homeostasis may, thus, represent a novel approach to modulate GVHD and infection. Damage to the intestine plays a central role in amplifying systemic GVHD by propagating a proinflammatory cytokine milieu. Molecular targeting to inhibit kinase signaling may be a promising approach to treat GVHD, ideally via targeting the redundant effect of multiple cytokines on immune cells and enterocytes. In this review, we discuss insights on the biology of GI GVHD, interaction of microflora and metabolome with the hosts, identification of potential new target organs, and identification and targeting of novel T cell-signaling pathways. Better understanding of GVHD biology will, thus, pave a way to develop novel treatment strategies with great clinical benefits. © 2016 American Society for Blood and Marrow Transplantation.


Sauer S.,Albert Ludwigs University of Freiburg | Gneiting C.,Albert Ludwigs University of Freiburg | Buchleitner A.,Albert Ludwigs University of Freiburg
Physical Review Letters | Year: 2013

We study to what extent the detrimental impact of dissipation on quantum properties can be compensated by suitable coherent dynamics. To this end, we develop a general method to determine the control Hamiltonian that optimally counteracts a given dissipation mechanism, in order to sustain the desired property, and apply it to two exemplary target properties: the coherence of a decaying two-level system and the entanglement of two qubits in the presence of local dissipation. © 2013 American Physical Society.


Schmidt Y.,Albert Ludwigs University of Freiburg | Breit B.,Albert Ludwigs University of Freiburg
Organic Letters | Year: 2010

On the basis of the assignment of methylene proton signals in 1H NMR and determination of the chemical shift difference (Δδ), the relative configuration of 1,3,n-methyl-branched deoxypropionates can be determined directly. Comparison of the chemical shifts in the corresponding syn- and anti-configured compound pairs shows remarkable differences, while the absolute values depend on the presence and nature of adjacent functional groups. The determination of the Δδ values provides a reliable assessment of the relative configuration in 1,3,n-methyl-branched polypropionate chains and is even valid for macrocycles. © 2010 American Chemical Society.


Vach W.,Albert Ludwigs University of Freiburg
Journal of Clinical Epidemiology | Year: 2013

Objectives: Calibration is often thought to assess the bias of a clinical prediction rule. In particular, if the rule is based on a linear logistic model, it is often assumed that an overestimation of all coefficients results in a calibration slope less than 1 and an underestimation in a slope larger than 1. Study Design and Setting: We investigate the relation of the bias and the residual variation of clinical prediction rules with the typical behavior of calibration plots and calibration slopes, using some artificial examples. Results: Calibration is not only sensitive to the bias of the clinical prediction rule but also to the residual variation. In some circumstances, the effects may cancel out, resulting in a misleading perfect calibration. Conclusion: Poor calibration is a clear indication of limited usefulness of a clinical prediction rule. However, a perfect calibration should be interpreted with care as this may happen even for a biased prediction rule. © 2013 Elsevier Inc. All rights reserved.


Bartels B.,Albert Ludwigs University of Freiburg | Mintert F.,Albert Ludwigs University of Freiburg
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

This paper describes an approach to construct temporally shaped control pulses that drive a quantum system toward desired properties. A parametrization in terms of periodic functions with predefined frequencies permits us to realize a smooth, typically simple shape of the pulses; their optimization can be performed based on a variational analysis with Floquet theory. As we show with selected specific examples, this approach permits us to control the dynamics of interacting spins, such that gate operations and entanglement dynamics can be implemented with very high accuracy. © 2013 American Physical Society.


Royston P.,University College London | Sauerbrei W.,Albert Ludwigs University of Freiburg
Statistics in Medicine | Year: 2014

In a large simulation study reported in a companion paper, we investigated the significance levels of 21 methods for investigating interactions between binary treatment and a continuous covariate in a randomised controlled trial. Several of the methods were shown to have inflated type 1 errors. In the present paper, we report the second part of the simulation study in which we investigated the power of the interaction procedures for two sample sizes and with two distributions of the covariate (well and badly behaved). We studied several methods involving categorisation and others in which the covariate was kept continuous, including fractional polynomials and splines. We believe that the results provide sufficient evidence to recommend the multivariable fractional polynomial interaction procedure as a suitable approach to investigate interactions of treatment with a continuous variable. If subject-matter knowledge gives good arguments for a non-monotone treatment effect function, we propose to use a second-degree fractional polynomial approach, but otherwise a first-degree fractional polynomial (FP1) function with added flexibility (FLEX3) is the method of choice. The FP1 class includes the linear function, and the selected functions are simple, understandable, and transferable. Furthermore, software is available. We caution that investigation of interactions in one dataset can only be interpreted in a hypothesis-generating sense and needs validation in new data. © 2014 John Wiley & Sons, Ltd.


Bieser A.M.,Albert Ludwigs University of Freiburg | Tiller J.C.,TU Dortmund
Macromolecular Bioscience | Year: 2011

A series of N-alkyl-N,N-dimethyldeoxyammonium celluloses is synthesized by converting tosyl celluloses with DBA and DDA, respectively. Surface coatings with these water-insoluble derivatives contain well-defined densities of quaternary ammonium functions and nonactive hydrophobic and hydrophilic groups. It is shown that the antimicrobial activity of such surfaces against S. aureus requires a delicate balance between DDA, BDA, and hydrophobic groups. A mechanism is proposed that involves the selective adhesion of anionic phospholipids from the bacterial cell membrane. This so-called phospholipid sponge effect is supported by the fact that all coatings could be deactivated by treatment with SDS or negatively charged phospholipids, but not with neutral phospholipids. The present work strives to gain better insights in the mechanism of surface grafted antimicrobial groups. To this end a series of water-insoluble cellulose derivatives with well-defined ratios of different quaternary ammonium groups and hydrophobic substituents were synthesized and their films were investigated regarding their antimicrobial potential. From the results we propose a new mechanism for such surface grafted biocides, the "phospholipid sponge effect." © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Bauer G.,Albert Ludwigs University of Freiburg | Zarkovic N.,Ruder Boskovic Institute | Zarkovic N.,University of Applied science
Free Radical Biology and Medicine | Year: 2015

Tumor cells generate extracellular superoxide anions and are protected against superoxide anion-mediated intercellular apoptosis-inducing signaling by the expression of membrane-associated catalase. 4-Hydroxy-2-nonenal (4-HNE), a versatile second messenger generated during lipid peroxidation, has been shown to induce apoptosis selectively in malignant cells. The findings described in this paper reveal the strong, concentration-dependent potential of 4-HNE to specifically inactivate extracellular catalase of tumor cells both indirectly and directly and to consequently trigger apoptosis in malignant cells through superoxide anion-mediated intercellular apoptosis-inducing signaling. Namely, 4-HNE caused apoptosis selectively in NOX1-expressing tumor cells through inactivation of their membrane-associated catalase, thus reactivating subsequent intercellular signaling through the NO/peroxynitrite and HOCl pathways, followed by the mitochondrial pathway of apoptosis. Concentrations of 4-HNE of 1.2 μM and higher directly inactivated membrane-associated catalase of tumor cells, whereas at lower concentrations, 4-HNE triggered a complex amplificatory pathway based on initial singlet oxygen formation through H2O2 and peroxynitrite interaction. Singlet-oxygen-dependent activation of the FAS receptor and caspase-8 increased superoxide anion generation by NOX1 and amplification of singlet oxygen generation, which allowed singlet-oxygen-dependent inactivation of catalase. 4-HNE and singlet oxygen cooperate in complex autoamplificatory loops during this process. The finding of these novel anticancer pathways may be useful for understanding the role of 4-HNE in the control of malignant cells and for the optimization of ROS-dependent therapeutic approaches including antioxidant treatments. © 2015 Elsevier Inc. All rights reserved.


Manz B.,Albert Ludwigs University of Freiburg
Nature communications | Year: 2012

Infection of mammals by avian influenza viruses requires adaptive mutations to achieve high-level replication in the new host. However, the basic mechanism underlying this adaptation process is still unknown. Here we show that avian polymerases, lacking the human signature PB2-E627K, are incapable of generating usable complementary RNA templates in cultured human cells and therefore require adaptation. Characterization of the highly pathogenic human H5N1 isolate A/Thailand/1(KAN-1)/2004 that retained the avian PB2-E627 reveals that the defect in RNA replication is only partially compensated by mutations in the polymerase. Instead, mutations in the nuclear export protein are required for efficient polymerase activity. We demonstrate that adaptive mutations in nuclear export proteins of several human isolates enhance the polymerase activity of avian polymerases in human cultured cells. In conclusion, when crossing the species barrier, avian influenza viruses acquire adaptive mutations in nuclear export protein to escape restricted viral genome replication in mammalian cells.


Baumeister H.,Albert Ludwigs University of Freiburg | Baumeister H.,Prince of Wales Hospital
Journal of Affective Disorders | Year: 2012

Recent studies indicate that antidepressant drugs are largely ineffective in patients with subthreshold to mild depression when compared to placebo. In spite of this evidence, researchers continue to judge the prescription of antidepressant drugs to patients with subthreshold to mild depression as an adequate treatment, which in turn serves to further reinforce the undifferentiated treatment strategy adopted by clinicians. The present narrative review critically reflects on current research practice and highlights the need for a more differentiated, evidence-based clinical and research practice. © 2011 Elsevier B.V. All rights reserved.


Richter H.,Max Planck Institute for Terrestrial Microbiology | Zoephel J.,Max Planck Institute for Terrestrial Microbiology | Schermuly J.,Max Planck Institute for Terrestrial Microbiology | Maticzka D.,Albert Ludwigs University of Freiburg | And 2 more authors.
Nucleic Acids Research | Year: 2012

The CRISPR arrays found in many bacteria and most archaea are transcribed into a long precursor RNA that is processed into small clustered regularly interspaced short palindromic repeats (CRISPR) RNAs (crRNAs). These RNA molecules can contain fragments of viral genomes and mediate, together with a set of CRISPR-associated (Cas) proteins, the prokaryotic immunity against viral attacks. CRISPR/Cas systems are diverse and the Cas6 enzymes that process crRNAs vary between different subtypes. We analysed CRISPR/Cas subtype I-B and present the identification of novel Cas6 enzymes from the bacterial and archaeal model organisms Clostridium thermocellum and Methanococcus maripaludis C5. Methanococcus maripaludis Cas6b in vitro activity and specificity was determined. Two complementary catalytic histidine residues were identified. RNA-Seq analyses revealed in vivo crRNA processing sites, crRNA abundance and orientation of CRISPR transcription within these two organisms. Individual spacer sequences were identified with strong effects on transcription and processing patterns of a CRISPR cluster. These effects will need to be considered for the application of CRISPR clusters that are designed to produce synthetic crRNAs. © 2012 The Author(s).


Yu Q.,Albert Ludwigs University of Freiburg | Beyer P.,Albert Ludwigs University of Freiburg
FEBS Letters | Year: 2012

Lycopene cyclases responsible for the formation of -ionone rings (LCYe) mark a plant-specific bifurcation of carotenogenesis. We investigated purified rice LCYe (OsLCYe) in a liposome-based biphasic assay system. OsLCYe depends on reduced flavin cofactors stabilizing a transient state formed during the non-redox cyclization reaction. In contrast to OsLCYb, OsLCYe produces predominantly monocyclic products and monocyclic carotene intermediates are not suitable substrates. Determination of the OsLCYe reaction specificities and the combined use of OsLCYb allow the characterization of the reaction sequence leading to heterocyclic carotenoids. It was also found that 5-cis-lycopene, which was thought to be decisive for -cyclization, was not involved in the reaction, with OsLCYe acting as an exclusion filter for this naturally occurring isomer. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Matzarakis A.,Albert Ludwigs University of Freiburg | Endler C.,Albert Ludwigs University of Freiburg
International Journal of Biometeorology | Year: 2010

The concept of physiologically equivalent temperature (PET) has been applied to the analysis of thermal bioclimatic conditions in Freiburg, Germany, to show if days with extreme bioclimatic conditions will change and how extreme thermal conditions can be modified by changes in mean radiant temperature and wind speed. The results show that there will be an increase of days with heat stress (PET > 35°C) in the order of 5% (from 9.2% for 1961-1990) and a decrease of days with cold stress (PET < 0°C) from 16.4% to 3.8% per year. The conditions can be modified by measures modifying radiation and wind speed in the order of more than 10% of days per year by reducing global radiation in complex structures or urban areas. © 2010 ISB.


Ludemann T.,Albert Ludwigs University of Freiburg
Palaeogeography, Palaeoclimatology, Palaeoecology | Year: 2010

Results and perspectives of charcoal research in Central Europe are highlighted, with special regard to the dependence of past fuel economy on the tree species composition of the natural forest vegetation. The main topic is how analyses of archaeological macrocharcoals from sites of historical mining, archaeo-metallurgical processes and charcoal burning (kiln site anthracology) can provide answers to questions on vegetation history, geography and ecology at the landscape level. This paper primarily focusses on the spatial differentiation at the regional scale. A synoptic overview is given for a diversified pilot area in the western part of Central Europe, with special regard to the natural diversity of growth conditions, forest vegetation and tree species composition at the regional scale. It includes results of 876 historical sites in the Black Forest, the Vosges and neighbouring regions. The material analysed spreads over a time scale of 7000 years from the Neolithic period to Modern Times. Most samples have been selected from postmedieval charcoal burning in the Black Forest and the Vosges as well as from medieval mining in the western part of the Black Forest. Generally, no selection of distinct species for fuel wood use was made in the past. All of the tree taxa to be expected for the natural conditions were exploited. Moreover, their frequencies also reflect a natural situation. The tree species of the climax vegetation were mainly used and all other species were quantitatively unimportant. The individual sample sites showconsiderable differences in tree taxa composition and frequency, fromwhich regular spatial patterns of the past tree species distribution have been deduced on local and regional scales. Linking the results of charcoal analyses with those of recent site ecology and vegetation science, these patterns can be explained by regional and local differences in the ecological conditions of the exploited forests in the vicinity of the sites studied. A pronounced dependence of the fuel wood use on the natural site specific distribution of the tree species is discernible. Moreover, taxa composition and the diameter of the wood used often indicate the exploitation of close-to-nature non-degraded forest stands in the past. The local natural availability of wood and the restricted possibilities of wood transport were important criteria for past fuel wood exploitation. © 2009 Elsevier B.V. All rights reserved.


Feuerriegel S.,Albert Ludwigs University of Freiburg | Neumann D.,Albert Ludwigs University of Freiburg
Energy Policy | Year: 2014

Due to the integration of intermittent resources of power generation such as wind and solar, the amount of supplied electricity will exhibit unprecedented fluctuations. Electricity retailers can partially meet the challenge of matching demand and volatile supply by shifting power demand according to the fluctuating supply side. The necessary technology infrastructure such as Advanced Metering Infrastructures for this so-called Demand Response (DR) has advanced. However, little is known about the economic dimension and further effort is strongly needed to realistically quantify the financial impact. To succeed in this goal, we derive an optimization problem that minimizes procurement costs of an electricity retailer in order to control Demand Response usage. The evaluation with historic data shows that cost volatility can be reduced by 7.74%; peak costs drop by 14.35%; and expenditures of retailers can be significantly decreased by 3.52%. © 2013 Elsevier Ltd.


Bucher K.,Albert Ludwigs University of Freiburg | Stober I.,Albert Ludwigs University of Freiburg
Geofluids | Year: 2010

Geofluids (2010) 10, 241-253. The brittle upper continental crust predominantly consists of granite and gneiss. Fractures form an interconnected network of water-conducting structures with an appreciable permeability also providing substantial fluid-saturated fracture porosity. The chemical composition of fluids in the fracture porosity of granite and gneiss changes with depth. Near the surface Ca-Na-HCO3 waters dominate. With increasing depth, water contains increasing amounts of alkalis and sulfate and grade into chloride-rich waters at greater depth. Total dissolved solids (TDS) of 105 mg l-1 are common at 5-km depth in most basement rocks. All reported deep fluids from the upper crust contain predominantly NaCl and CaCl2. The brines vary from NaCl-rich in granites to CaCl2-rich in mafic reservoir rocks such as amphibolites and gabbros. In regions of the crust with strong topography, fluid flow is important and recharge water may have flushed the basement efficiently, thereby removing old brine components from the granites. Water samples from the new Gotthard Rail Base Tunnel of the Alps represent this type of basement fluid. Analyzed fluids from up to 2.5-km depth differ from basement fluids from areas with less-extreme topography in the following ways. Such waters have relatively low TDS of some 100 mg l-1 and are typically of the Na2CO3-Na2SO4 type. pH tends to be high and varies from 9 to more than 10. Low Ca and ultra-low Mg of such waters result from efficient deposition of secondary Ca-Mg minerals as coatings on fracture walls. Reduction of CO2 to CH4 provides the oxidation capacity for sulfate production from primary rock sulfides. The composition of fluids in fractured continental crust at depths below 1-2 km depends strongly on the topography of the erosion surface. In crust with rugged alpine topography fluids at this depth are low-TDS high-pH waters that derive its composition from fluid-rock interaction alone. In crust with low-to-moderate topography, basement fluids are normally near neutral high-TDS Na-Ca chloride brines that derive the solutes not only from the rock matrix but also from external sources. © 2010 Blackwell Publishing Ltd.


Georg J.,Albert Ludwigs University of Freiburg | Hess W.R.,Albert Ludwigs University of Freiburg
Microbiology and Molecular Biology Reviews | Year: 2011

A substantial amount of antisense transcription is a hallmark of gene expression in eukaryotes. However, antisense transcription was first demonstrated in bacteria almost 50 years ago. The transcriptomes of bacteria as different as Helicobacter pylori, Bacillus subtilis, Escherichia coli, Synechocystis sp. strain PCC6803, Mycoplasma pneumoniae, Sinorhizobium meliloti, Geobacter sulfurreducens, Vibrio cholerae, Chlamydia trachomatis, Pseudomonas syringae, and Staphylococcus aureus have now been reported to contain antisense RNA (asRNA) transcripts for a high percentage of genes. Bacterial asRNAs share functional similarities with trans-acting regulatory RNAs, but in addition, they use their own distinct mechanisms. Among their confirmed functional roles are transcription termination, codegradation, control of translation, transcriptional interference, and enhanced stability of their respective target transcripts. Here, we review recent publications indicating that asRNAs occur as frequently in simple unicellular bacteria as they do in higher organisms, and we provide a comprehensive overview of the experimentally confirmed characteristics of asRNA actions and intimately linked quantitative aspects. Emerging functional data suggest that asRNAs in bacteria mediate a plethora of effects and are involved in far more processes than were previously anticipated. Thus, the functional impact of asRNAs should be considered when developing new strategies against pathogenic bacteria and when optimizing bacterial strains for biotechnology. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


van der Bij J.J.,Albert Ludwigs University of Freiburg
General Relativity and Gravitation | Year: 2011

I present an argument, based on the topology of the universe, why there are three generations of fermions. The argument implies a preferred unified gauge group of SU(5), but with SO(10) representations of the fermions. The breaking pattern SU(5) → SU(3) × SU(2) × U(1) is preferred over the pattern SU(5) → SU(4) × U(1). On the basis of the argument one expects an asymmetry in the early universe microwave data, which might have been detected already. © 2010 Springer Science+Business Media, LLC.


Noninvasive diagnosis of atherosclerosis via single biomarkers has been attempted but remains elusive. However, a previous polymarker or pattern approach of urine polypeptides in humans reflected coronary artery disease with high accuracy. The aim of the current study is to use urine proteomics in ApoE(-/-) mice to discover proteins with pathophysiological roles in atherogenesis and to identify urinary polypeptide patterns reflecting early stages of atherosclerosis. Urine of ApoE(-/-) mice either on high fat diet (HFD) or chow diet was collected over 12 weeks; urine of wild type mice on HFD was used to exclude diet-related proteome changes. Capillary electrophoresis coupled to mass spectrometry (CE-MS) of samples identified 16 polypeptides specific for ApoE(-/-) mice on HFD. In a blinded test set, these polypeptides allowed identification of atherosclerosis at a sensitivity of 90% and specificity of 100%, as well as monitoring of disease progression. Sequencing of the discovered polypeptides identified fragments of α(1)-antitrypsin, epidermal growth factor (EGF), kidney androgen-regulated protein, and collagen. Using immunohistochemistry, α(1)-antitrypsin, EGF, and collagen type I were shown to be highly expressed in atherosclerotic plaques of ApoE(-/-) mice on HFD. Urinary excretion levels of collagen and α(1)-antitrypsin fragments also significantly correlated with intraplaque collagen and α(1)-antitrypsin content, mirroring plaque protein expression in the urine proteome. To provide further confirmation that the newly identified proteins are relevant in humans, the presence of collagen type I, α(1)-antitrypsin, and EGF was also confirmed in human atherosclerotic disease. Urine proteome analysis in mice exemplifies the potential of a novel multimarker approach for the noninvasive detection of atherosclerosis and monitoring of disease progression. Furthermore, this approach represents a novel discovery tool for the identification of proteins relevant in murine and human atherosclerosis and thus also defines potential novel therapeutic targets.


Storch S.,Albert Ludwigs University of Freiburg | Winkel G.,Albert Ludwigs University of Freiburg
Forest Policy and Economics | Year: 2013

Climate change may affect forest management not only through predicted ecological impacts on forests, but also by reframing perspectives on land use issues, and thus changing forest policies. In this paper, forest policy making in the light of climate change is analyzed in two German Laender, Bavaria and North Rhine Westphalia, drawing on the Multiple Streams Framework. Empirically, document analysis and expert interviews substantiate this analysis. The formation of climate change related forest policy occurred differently in both Laender. In Bavaria, several factors triggered a successful integration of climate change adaptation measures related to forests into one program, the "Bavarian Climate Programme 2020". These factors were, for instance, an early problematization of climate change by forest science, a 'condensation' of the problem into particular areas of high need for action, the possibility to rely on already available (in parts, implemented), well-proven, and applicable forest policy measures, and the coordinated and entrepreneurial activities of the forest sector as a whole. In North Rhine Westphalia, the political framework conditions for a formation of climate change related forest policy were less favorable, and, hence, no broader forest policy on the issue occurred. Recent political changes, however, may allow for new prospects.We conclude that the extent to which the issue of climate change is integrated into forest policy depends on the overall framing of climate policy and the opportunities for the forest sector to substantiate the necessity of such a link. The preparedness and activities of the latter are then needed in order to utilize possible policy windows and to receive resources for forest climate policy measures. Forest science plays an important role by influencing the agenda, indicating challenges and providing scientific criteria to determine and rationalize specific measures. © 2013 Elsevier B.V.


Weyerbrock A.,Albert Ludwigs University of Freiburg
Neurosurgery | Year: 2012

Glutathione S-transferases (GSTs) control multidrug resistance and are upregulated in many cancers, including malignant gliomas. The diazeniumdiolate JS-K generates nitric oxide (NO) on enzymatic activation by glutathione and GST, showing promising NO-based anticancer efficacy. To evaluate the role of NO-based antitumor therapy with JS-K in U87 gliomas in vitro and in vivo. U87 glioma cells and primary glioblastoma cell lines were exposed to JS-K and a variety of inhibitors to study cell death by necrosis, apoptosis, and other mechanisms. GST expression was evaluated by immunocytochemistry, polymerase chain reaction, and Western blot, and NO release from JS-K was studied with a NO assay. The growth-inhibitory effect of JS-K was studied in a U87 xenograft model in vivo. Dose-dependent inhibition of cell proliferation was observed in human U87 glioma cells and primary glioblastoma cells in vitro. Cell death was partially induced by caspase-dependent apoptosis, which could be blocked by Z-VAD-FMK and Q-VD-OPH. Inhibition of GST by sulfasalazine, cGMP inhibition by ODQ, and MEK1/2 inhibition by UO126 attenuated the antiproliferative effect of JS-K, suggesting the involvement of various intracellular death signaling pathways. Response to JS-K correlated with mRNA and protein expression of GST and the amount of NO released by the glioma cells. Growth of U87 xenografts was reduced significantly, with immunohistochemical evidence for increased necrosis and apoptosis and reduced proliferation. Our data show for the first time the potent antiproliferative effect of JS-K in gliomas in vitro and in vivo. These findings warrant further investigation of this novel NO-releasing prodrug in gliomas.


Haller O.,Albert Ludwigs University of Freiburg | Kochs G.,Albert Ludwigs University of Freiburg
Journal of Interferon and Cytokine Research | Year: 2011

The human myxovirus resistance protein 1 (MxA) is a key mediator of the interferon-induced antiviral response against a wide range of viruses. MxA expression is tightly regulated by type I and type III interferons, requires signal transducer and activator of transcription 1 signaling, and is not inducible directly by viruses or other stimuli. MxA shares many properties with the dynamin superfamily of large GTPases. It consists of 3 domains, namely, an N-terminal GTPase domain that binds and hydrolyses GTP, a middle domain mediating self-assembly, and a carboxy-terminal GTPase effector domain. Like dynamin, MxA has the ability to self-assemble into highly ordered oligomers and to form ring-like structures around liposomes, inducing liposome tubulation. The structural details of MxA oligomerization have recently been elucidated, providing new insights into the antiviral mechanism of this mechanochemical enzyme. The structural and functional data suggest that MxA targets the nucleoprotein of MxA-sensitive viruses. Thus, MxA may form oligomeric rings around tubular nucleocapsid structures, thereby inhibiting their transcriptional and replicative function. Here we briefly review the most salient features of MxA expression and antiviral function. © Copyright 2011, Mary Ann Liebert, Inc. 2011.


Bunermann O.,University of Gottingen | Stienkemeier F.,Albert Ludwigs University of Freiburg
European Physical Journal D | Year: 2011

The doping process of helium nanodroplets with alkali atoms has been modeled in order to study deviations from the Poissonian statistics of measured pick-up statistics which are important for assigning cluster or complex sizes in many experimental studies. Several, formally unexplained findings are reproduced and their origin has been analyzed: derivations from the expected functional form of the initial incline, the suppression of the formation of lithium clusters, the influence of the functional form and width of droplet size distributions. Furthermore, the controversially discussed formation of high-spin alkali clusters on helium droplets has been calculated within the model. The selection of high-spin states comes out to depend strongly on the experimental conditions, and is in general not pronounced for cluster sizes 3. The enhancement factor of 50 of high-spin states reported in earlier experiments is reproduced when choosing the conditions of these experiments. © 2011 EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg.


Yu Y.,Albert Ludwigs University of Freiburg | Zappe H.,Albert Ludwigs University of Freiburg
Optics Express | Year: 2011

We present a detailed investigation of the effect of lens size on the focusing performance of plasmonic lenses based on metallic nanoslit arrays with variable widths. The performance parameters considered include the focal length, depth of focus (DOF), full-width half-maximum (FWHM) and the maximum intensity of the focal point. 2D FDTD simulation was utilized. The results show that all the lens parameters are greatly affected by the lens size. A larger lens size, with a total phase difference of at least 2π, will produce a better focusing behavior and a closer agreement with the design. The Fresnel number and diffraction theory can be used to explain the effect of lens size. Suggestions are provided for realization of a practical plasmonic lens using the existing nanofabrication techniques. © 2011 Optical Society of America.


van der Maaten E.,Albert Ludwigs University of Freiburg
Forest Ecology and Management | Year: 2013

Analyses of seasonal growth patterns of trees permit an increased understanding on growth responses to year-to-year weather variability and site-specific conditions. In this study, growth responses of European beech (Fagus sylvatica L.) to thinning were analyzed in a narrow valley in southwestern Germany over a six-year study period (2001-2006). We considered three thinning treatments (unthinned control, intermediate thinning and heavy thinning), two aspects (north-east and south-west) and three social classes (predominant, dominant and co-dominant).The growth of 72 beech trees was monitored using automatic point dendrometers. To obtain seasonal curve parameters for statistical analyses, we fitted cumulative Weibull functions to standardized annual dendrometer series. The scale and shape parameter of this function, T and m, were used as indicators of timing and duration of growth, respectively. Together with annual radial growth, ir, they were analyzed in linear mixed models. Temporal variability in growth reflected inter-annual weather fluctuations; with generally lower growth levels and shorter growth duration in dry years. Further, the extreme dry year 2003 showed a remarkable early growth onset, followed by a late onset in 2004. Effects of thinning treatment highlighted the importance of resource limitation, e.g., water availability, as lowest growth levels were found in trees subjected to high competition in control plots. In addition, results indicated growing season prolongation with thinning. Effects of tree social class and aspect upon ir, T and m were absent or of minor importance, respectively.For both wet and dry years, reduced competition through thinning was found to stimulate growth and to prolong growth duration. Hence, thinning may be suggested as an adaptive forest management tool that may reduce stand vulnerability to drought. Further, this study illustrates that comparable growth levels can be achieved through very different seasonal growth patterns, thereby stressing the importance of intra-annual studies to increase the understanding on growth determinism of beech. © 2013 Elsevier B.V.


Espinosa C.,Albert Ludwigs University of Freiburg
Forest Policy and Economics | Year: 2013

The preservation of the cultural and biological features of the Yasuní biosphere reserve in Ecuador has been historically in conflict with oil activities. Astonishingly, in 2006 the government announced that this area, encompassing one fifth of the country's confirmed oil reserves, would be left indefinitely untapped if the international community contributed at least half of the revenue that the extraction of this oil would generate. Given Ecuador's oil dependency, this seems to be a riddle. Using a case study approach, this article applies concepts of discourse research to examine how the Yasuní-ITT project came about. It is shown how discursive elements related to indigenous peoples' rights, biodiversity conservation and climate change were drawn together and triggered a discontinuity in the dominant tradition of oil extraction. The specific socio-historical context in which these interwoven story-lines were inserted into formal politics is examined. Finally, a discussion is presented assessing the underlying discursive mechanisms that contributed to gaining government support as well as the institutionalization difficulties faced by the oil-moratorium. © 2012.


Seebauer M.,Albert Ludwigs University of Freiburg
Environmental Research Letters | Year: 2014

The IPCC has compiled the best available scientific methods into published guidelines for estimating greenhouse gas emissions and emission removals from the land-use sector. In order to evaluate existing GHG quantification tools to comprehensively quantify GHG emissions and removals in smallholder conditions, farm scale quantification was tested with farm data from Western Kenya. After conducting a cluster analysis to identify different farm typologies GHG quantification was exercised using the VCS SALM methodology complemented with IPCC livestock emission factors and the cool farm tool. The emission profiles of four farm clusters representing the baseline conditions in the year 2009 are compared with 2011 where farmers adopted sustainable land management practices (SALM). The results demonstrate the variation in both the magnitude of the estimated GHG emissions per ha between different smallholder farm typologies and the emissions estimated by applying two different accounting tools. The farm scale quantification further shows that the adoption of SALM has a significant impact on emission reduction and removals and the mitigation benefits range between 4 and 6.5 tCO2 ha-1 yr-1 with significantly different mitigation benefits depending on typologies of the crop-livestock systems, their different agricultural practices, as well as adoption rates of improved practices. However, the inherent uncertainty related to the emission factors applied by accounting tools has substantial implications for reported agricultural emissions. With regard to uncertainty related to activity data, the assessment confirms the high variability within different farm types as well as between different parameters surveyed to comprehensively quantify GHG emissions within smallholder farms. © 2014 IOP Publishing Ltd.


Louis-Dit-Sully C.,Albert Ludwigs University of Freiburg
EXS | Year: 2014

Small chemical compounds and certain metal ions can activate T cells, resulting in drug hypersensitivity reactions that are a main problem in pharmacology. Mostly, the drugs generate new antigenic epitopes on peptide-major histocompatibility complex (MHC) molecules that are recognized by the T-cell antigen receptor (TCR). In this review we discuss the molecular mechanisms of how the drugs alter self-peptide-MHC, so that neo-antigens are produced. This includes (1) haptens covalently bound to peptides presented by MHC, (2) metal ions and drugs that non-covalently bridge self-pMHC to the TCR, and (3) drugs that allow self-peptides to be presented by MHCs that otherwise are not presented. We also briefly discuss how a second signal-next to the TCR-that naïve T cells require to become activated is generated in the drug hypersensitivity reactions.


Esser P.R.,Albert Ludwigs University of Freiburg
EXS | Year: 2014

Allergic contact dermatitis is a T cell-mediated skin disease. Many hundreds of organic chemicals and some metal ions are contact sensitizers. They induce an innate inflammatory immune response in the skin that results in the priming of contact sensitizer-specific T cells by dendritic cells in the draining lymph nodes. The factors that determine the strength of this T cell response and thereby define the potency of a contact sensitizer are largely unknown. This chapter highlights different variables such as precursor frequency of antigen-specific T cells, possible bystander activation, and T cell receptor diversity or avidity of the TCR/peptide-MHC interactions, which might impact the quality and strength of T cell responses to contact sensitizers. In addition, different methods available to determine both the frequency of antigen-specific T cells and T cell receptor repertoires are discussed. Identification of the factors determining potency may allow for the development of suitable in vitro assays for potency assessment of contact sensitizers.


Peschke F.,Albert Ludwigs University of Freiburg | Kretsch T.,Albert Ludwigs University of Freiburg
Plant Physiology | Year: 2011

Light is among the most important exogenous factors that regulate plant development. To sense light quality, intensity, direction, and duration, plants have evolved multiple photoreceptors that enable the detection of photons from the ultraviolet B (UV-B) to the far-red spectrum. To study the effect of different light qualities on early gene expression, dark-grown Arabidopsis (Arabidopsis thaliana) seedlings were either irradiated with continuous far-red, red, or blue light or received pulses of red, UV-A, or UV-A/B light. The expression profiles of seedlings harvested at 45 min and 4 h were determined on a full genome level and compared with the profiles of dark controls. Data were used to identify light-regulated genes and to group these genes according to their light responses. While most of the genes were regulated by more than one light quality, a considerable number of UV-B-specific gene expression responses were obtained. An extraordinarily high similarity in gene expression patterns was obtained for samples that perceived continuous irradiation with either far-red or blue light for 4 h. Mutant analyses hint that this coincidence is caused by a convergence of the signaling cascades that regulate gene expression downstream of cryptochrome blue light photoreceptors and phytochrome A. Whereas many early light-regulated genes exhibited uniform responses to all applied light treatments, highly divergent expression patterns developed at 4 h. These data clearly indicate that light signaling during early deetiolation undergoes a switch from a rapid, but unspecific, response mode to regulatory systems that measure the spectral composition and duration of incident light.


Graeber K.,Albert Ludwigs University of Freiburg | Linkies A.,Albert Ludwigs University of Freiburg | Wood A.T.A.,University of Nottingham | Leubner-Metzger G.,Albert Ludwigs University of Freiburg
Plant Cell | Year: 2011

Comparative biology includes the comparison of transcriptome and quantitative real-time RT-PCR (qRT-PCR) data sets in a range of species to detect evolutionarily conserved and divergent processes. Transcript abundance analysis of target genes by qRT-PCR requires a highly accurate and robust workflow. This includes reference genes with high expression stability (i.e., low intersample transcript abundance variation) for correct target gene normalization. Cross-species qRT-PCR for proper comparative transcript quantification requires reference genes suitable for different species. We addressed this issue using tissue-specific transcriptome data sets of germinating Lepidium sativum seeds to identify new candidate reference genes. We investigated their expression stability in germinating seeds of L. sativum and Arabidopsis thaliana by qRT-PCR, combined with in silico analysis of Arabidopsis and Brassica napus microarray data sets. This revealed that reference gene expression stability is higher for a given developmental process between distinct species than for distinct developmental processes within a given single species. The identified superior cross-species reference genes may be used for family-wide comparative qRT-PCR analysis of Brassicaceae seed germination. Furthermore, using germinating seeds, we exemplify optimization of the qRT-PCR workflow for challenging tissues regarding RNA quality, transcript stability, and tissue abundance. Our work therefore can serve as a guideline for moving beyond Arabidopsis by establishing high-quality cross-species qRT-PCR. © American Society of Plant Biologists. All rights reserved.


BACKGROUND: Inflammation and myocardial necrosis play important roles in ischemia/reperfusion injury after coronary artery occlusion and recanalization. The detection of inflammatory activity and the extent of myocardial necrosis itself are of great clinical and prognostic interest. We developed a dual, noninvasive imaging approach using molecular magnetic resonance imaging in an in vivo mouse model of myocardial ischemia and reperfusion.METHODS AND RESULTS: Ischemia/reperfusion injury was induced in 10-week-old C57BL/6N mice by temporary ligation of the left anterior descending coronary artery. Activated platelets were targeted with a contrast agent consisting of microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody directed against a ligand-induced binding site (LIBS) on activated glycoprotein IIb/IIIa (LIBS-MPIOs). After injection and imaging of LIBS-MPIOs, late gadolinium enhancement was used to depict myocardial necrosis; these imaging experiments were also performed in P2Y12 (-/-) mice. All imaging results were correlated to immunohistochemistry findings. Activated platelets were detectable by magnetic resonance imaging via a significant signal effect caused by LIBS-MPIOs in the area of left anterior descending coronary artery occlusion 2 hours after reperfusion. In parallel, late gadolinium enhancement identified the extent of myocardial necrosis. Immunohistochemistry confirmed that LIBS-MPIOs bound significantly to microthrombi in reperfused myocardium. Only background binding was found in P2Y12 (-/-) mice.CONCLUSIONS: Dual molecular imaging of myocardial ischemia/reperfusion injury allows characterization of platelet-driven inflammation by LIBS-MPIOs and myocardial necrosis by late gadolinium enhancement. This noninvasive imaging strategy is of clinical interest for both diagnostic and prognostic purposes and highlights the potential of molecular magnetic resonance imaging for characterizing ischemia/reperfusion injury. © 2014 American Heart Association, Inc.


Ifenthaler D.,University of Oklahoma | Seel N.M.,Albert Ludwigs University of Freiburg
Computers and Education | Year: 2012

In this paper, there will be a particular focus on mental models and their application to inductive reasoning within the realm of instruction. A basic assumption of this study is the observation that the construction of mental models and related reasoning is a slowly developing capability of cognitive systems that emerges effectively with proper contextual and social support. More specifically, we first will identify some key elements of the structure and function of mental models in contrast to schemas. Next, these key elements of modeling will be used to generate some conjectures about the foundations of model-based reasoning. In the next section, we will describe the learning-dependent progression of mental models as a suitable approach for understanding the basics of deductive and inductive reasoning based on models as "tools for thought." The rationale of mental models as tools for reasoning will be supported by empirical research to be described in a particular section of this paper. Finally, we will turn to the instructional implications of model-based reasoning by discussing appropriate instructional methods to affect the construction of mental models for performing deductive and inductive reasoning. © 2012 Elsevier Ltd. All rights reserved.


Eibel H.,Albert Ludwigs University of Freiburg
Current allergy and asthma reports | Year: 2014

In this review we summarize recent insights into the development of human B cells primarily by studying immunodeficiencies. Development and differentiation of B cells can be considered as a paradigm for many other developmental processes in cell biology. However, it differs from the development of many other cell types by phases of extremely rapid cell division and by defined series of somatic recombination and mutation events required to assemble and refine the B cell antigen receptors. Both somatic DNA alteration and proliferation phases take place in defined sites but in different organs. Thus, cell migration and timely arrival at defined sites are additional features of B cell development. By comparing experimental mouse models with insights gained from studying defined genetic defects leading to primary immunodeficiencies and hypogammaglobulinemia, we address important features that are characteristic for human B cells. We also summarize recent advances made by developing improved in vitro and in vivo systems allowing the development of human B cells from hematopoietic stem cells. Combined with genetic and functional studies of immunodeficiencies, these models will contribute not only to a better understanding of disease affecting the B lymphocyte compartment, but also to designing better and safer novel B cell-targeted therapies in autoimmunity and allergy.


Niklas K.J.,Cornell University | Spatz H.-C.,Albert Ludwigs University of Freiburg
American Journal of Botany | Year: 2010

Premise of the study: The density of wood is highly correlated with the ability of stems and roots to resist bending or twisting, which is important for evaluating the mechanical behavior of trees. It also provides a measure of carbon storage, which is an important variable in modeling ecosystem processes and tree construction costs. However, most measurements of the density and mechanical properties of wood have little direct bearing on understanding the biomechanics of living plants because they are based on kiln- or air-dried samples. Methods: Here, we present and analyze the relationships between four important mechanical properties (Young' s modulus, the modulus of rupture, and the maximum strength in shearing and in compression) and the density of green wood (i.e., wood at 50% moisture content) from a worldwide, taxonomically broad spectrum of 161 species. Key results: These data indicate that each of the mechanical properties disproportionately increases across species with increasing green wood density, i.e., stems composed of denser green wood are disproportionately stiffer and stronger than stems with equivalent cross-sections composed of less dense green wood. Conclusions: Although denser wood may have a higher carbon construction cost, the mechanical benefits of denser woods likely outweigh the extra cost. © 2010 Botanical Society of America.


Hindley C.,University of Cambridge | Hindley C.,Albert Ludwigs University of Freiburg | Philpott A.,University of Cambridge
Biochemical Journal | Year: 2012

During embryonic development, cells must divide to produce appropriate numbers, but later must exit the cell cycle to allow differentiation. How these processes of proliferation and differentiation are co-ordinated during embryonic development has been poorly understood until recently. However, a number of studies have now given an insight into how the cell cycle machinery, including cyclins, CDKs (cyclin-dependent kinases), CDK inhibitors and other cell cycle regulators directly influence mechanisms that control cell fate and differentiation. Conversely, examples are emerging of transcriptional regulators that are better known for their role in driving the differentiated phenotype, which also play complementary roles in controlling cell cycle progression. The present review will summarise our current understanding of the mechanisms co-ordinating the cell cycle and differentiation in the developing nervous system, where these links have been, perhaps, most extensively studied. © 2012 The Author(s).


Drews G.,Albert Ludwigs University of Freiburg
Journal of Molecular Microbiology and Biotechnology | Year: 2013

The growth of purple bacteria is supported either by a photosynthetic, light-dependent electron transfer system or by a respiratory electron transfer system. Both systems are localized in both a cytoplasmic and an intracytoplasmic membrane system. Formation of the functional complexes is regulated by the oxygen partial pressure and light intensity. The organization and the multistep process of assembly of their components will be described in this review. Most details about the assembly of the respiratory complexes are known. Copyright © 2013 S. Karger AG, Basel.


Jakes P.,Albert Ludwigs University of Freiburg | Erdem E.,Albert Ludwigs University of Freiburg
Physica Status Solidi - Rapid Research Letters | Year: 2011

ZnO nanoparticles were synthesized by solid coprecipitation method with consecutive high energy ball milling procedure. By reducing the particle size of ZnO to nano dimensions strong nano-size effects were observed. In order to characterize the ZnO defect structure, EPR has been applied. It was observed that below 50 nm the surface defects play a dominant role in the electronic properties of ZnO. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Kierdorf K.,Albert Ludwigs University of Freiburg | Fritz G.,Albert Ludwigs University of Freiburg
Journal of Leukocyte Biology | Year: 2013

RAGE is a key molecule in the onset and sustainment of the inflammatory response. New studies indicate that RAGE might represent a new link between the innate and adaptive immune system. RAGE belongs to the superfamily of Ig cell-surface receptors and is expressed on all types of leukocytes promoting activation, migration, or maturation of the different cells. RAGE expression is prominent on the activated endothelium, where it mediates leukocyte adhesion and transmigration. Moreover, proinflammatory molecules released from the inflamed or injured vascular system induce migration and proliferation of SMCs. RAGE binds a large number of different ligands and is therefore considered as a PRR, recognizing a structural motif rather than a specific ligand. In this review, we summarize the current knowledge about the signaling pathways activated in the different cell types and discuss a potential activation mechanism of RAGE, as well as putative options for therapeutic intervention. © Society for Leukocyte Biology.


Ladwein K.I.,Albert Ludwigs University of Freiburg | Jung M.,Albert Ludwigs University of Freiburg
Angewandte Chemie - International Edition | Year: 2011

DNA methyltransferases catalyze the transfer of methyl groups to cytosines within DNA. Afterwards, 5-methylcytosine is oxidized to 5-hydroxymethylcytosine. Two further cytosine derivatives, 5-formylcytosine and 5-carboxycytosine, have been discovered recently. The existence of the seventh and eighth nucleobase provides new hints for deciphering the process of active DNA demethylation (see scheme). © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Sanos S.L.,Albert Ludwigs University of Freiburg | Diefenbach A.,Bavarian Nordic
Immunology and Cell Biology | Year: 2013

Innate lymphoid cells (ILC) are a recently discovered group of innate lymphocytes found at mucosal surfaces. The transcriptional and effector programs of ILC strikingly resemble those of the various T-helper (Th) cell fates (that is, Th1, Th2, Th9, Th17, Th22). ILC are involved in protecting the mucosal borders by producing tissue protective factors. More recently, evidence has been provided that inappropriately activated ILC can be drivers of various inflammatory disorders. Here, we will highlight recent developments in our understanding of the transcriptional and developmental programs controlling ILC specification and fate decisions. We will also review the roles assigned to ILC in protecting barriers and in promoting inflammatory diseases. Finally, we will outline how the power of ILC may be harnessed for clinical application, and how interference with ILC function may be used as a new strategy to treat inflammatory diseases. © 2013 Australasian Society for Immunology Inc. All rights reserved.


Haller O.,Albert Ludwigs University of Freiburg
Cell Host and Microbe | Year: 2013

Human MxA (MX1) protein is an interferon-induced restriction factor for a diverse range of viruses, whereas the related MxB (MX2) protein was thought to lack such activity. Three recent papers, including one in this issue of Cell Host & Microbe, show that MxB inhibits human immunodeficiency virus type 1 (HIV-1) infection. © 2013 Elsevier Inc.


Unsicker K.,Albert Ludwigs University of Freiburg | Spittau B.,Albert Ludwigs University of Freiburg | Krieglstein K.,Albert Ludwigs University of Freiburg
Cytokine and Growth Factor Reviews | Year: 2013

GDF-15 (also MIC-1, NAG-1, PLAB, PTGFB) is a member of the TGF-β superfamily, which is widely distributed in mammalian tissues and has been shown to play multiple roles in various pathologies, including inflammation, cancer, cardiovascular diseases, and obesity. GDF-15 serum levels are a highly reliable predictor of disease progression. Both the anti-tumorigenic potential of GDF-15 and its capacity to promote metastasis have been documented for a large variety of cancers, yet its opposing functions, which are typical for members of the TGF-β superfamily, have only partly been resolved on the molecular level. Knowledge on physiological functions in the non-diseased organism is scarce. In the nervous system GDF-15 knockout analyses have revealed that GDF-15 is essential for the postnatal maintenance of various neuron populations. When applied exogenously GDF-15 is a powerful factor for promoting survival of developing and lesioned neurons in vitro and in vivo. Receptor activation by GDF-15 has only been partially resolved. © 2013 Elsevier Ltd.


Muhlbacher L.,Albert Ludwigs University of Freiburg | Kleinekathofer U.,Jacobs University Bremen
Journal of Physical Chemistry B | Year: 2012

Using numerically exact path integral Monte Carlo simulations, the excitation energy transfer in the Fenna-Matthews-Olson (FMO) complex is determined at room temperature. The employed system and environment parameters are based on previously reported atomistic simulations. When starting with excitations localized at specific chromophores, no coherence features can be observed. In contrast, when starting with delocalized excitations, traces of coherent motion become apparent. On the one hand, as experimental findings account for much stronger quantum coherent motion, these results suggest a reevaluation of the underlying spectral densities. On the other hand, the results emphasize that the initial preparation of the excitonic system needs to be taken into account carefully when attempting to reproduce the respective experiments. © 2012 American Chemical Society.


Riemann D.,Albert Ludwigs University of Freiburg | Nissen C.,Albert Ludwigs University of Freiburg | Palagini L.,University of Pisa | Otte A.,Offenburg University of Applied Sciences | And 2 more authors.
The Lancet Neurology | Year: 2015

Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep-wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions. © 2015 Elsevier Ltd.


Martin S.F.,Albert Ludwigs University of Freiburg
Contact Dermatitis | Year: 2015

Allergic contact dermatitis affects a worrying proportion of the general population. The mechanisms underlying this chemical-triggered delayed-type hypersensitivity are still not fully understood. In recent years, basic research has shown that the immune system reacts to contact allergens by activation of signalling pathways that are usually used to fight infections. Ongoing work is aimed at the elucidation of the path that leads from the chemistry of contact allergens to the inflammatory skin disease. The cellular players and their complex interactions are being characterized. Proteins are being identified whose chemical modification by contact allergens results in the activation of signalling pathways involved in pathogenesis. Pathway identification is supported by genomic and proteomic techniques. All of these efforts will yield a cellular and molecular understanding of the orchestration of the innate and adaptive immune response to contact allergens. This knowledge will help in the identification of gene and protein signatures for improved diagnostics, the identification of novel drug targets for targeted treatments, as well the development of in vitro assays for contact allergen identification. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Multi-frequency and pulsed electron paramagnetic resonance (EPR) provides a sensitive spectroscopic tool to elucidate the defect structure of transition-metal doped perovskite oxides, as well as to monitor dynamic processes of oxygen vacancies in these materials. In this regard, high-frequency EPR spectrometers and pulsed EPR techniques such as the hyperfine sublevel correlation experiment (HYSCORE) may now routinely be used for dedicated investigations, providing considerably more insight than the application of standard continuous-wave EPR. Recent results include the formation of defect complexes between acceptor-type transition-metal centers with either one or two oxygen vacancies for the reason of charge compensation. Furthermore, such defect complexes follow the domain switching upon poling ferroelectric compounds with correspondingly high electric fields. On the other hand, multi-valent manganese functional centers provide trapping centers for electronic and ionic charge carriers (e′,) such that valency altered acceptor states or defect complexes are formed. Additionally, the trapping of charge carriers at the intrinsic 'reduced' B-site ions, and, can be observed by means of EPR spectroscopy.


Gnann H.,Albert Ludwigs University of Freiburg | Weinmann W.,University of Bern | Thierauf A.,Albert Ludwigs University of Freiburg
Alcoholism: Clinical and Experimental Research | Year: 2012

Background: For almost 30 years, phosphatidylethanol (PEth) has been known as a direct marker of alcohol consumption. This marker stands for consumption in high amounts and for a longer time period, but it has been also detected after 1 high single intake of ethanol (EtOH). The aim of this study was to obtain further information about the formation and elimination of PEth 16:0/18:1 by simulating extensive drinking. Methods: After 3 weeks of alcohol abstinence, 11 test persons drank an amount of EtOH leading to an estimated blood ethanol concentration of 1 g/kg on each of 5 successive days. After the drinking episode, they stayed abstinent for 16 days with regular blood sampling. PEth 16:0/18:1 analysis was performed using liquid chromatography-tandem mass spectrometry (high-performance liquid chromatography 1100 system and QTrap 2000 triple quadrupole linear ion trap mass spectrometer. Values of blood alcohol were obtained using a standardized method with headspace gas chromatography flame ionization detector. Results: Maximum measured concentrations of EtOH were 0.99 to 1.83 g/kg (mean 1.32 g/kg). These values were reached 1 to 3 hours after the start of drinking (mean 1.9 hours). For comparison, 10 of 11 volunteers had detectable PEth 16:0/18:1 values 1 hour after the start of drinking, ranging from 45 to 138 ng/ml PEth 16:0/18:1. Over the following days, concentrations of PEth 16:0/18:1 increased continuously and reached the maximum concentrations of 74 to 237 ng/ml between days 3 and 6. Conclusions: This drinking experiment led to measurable PEth concentrations. However, PEth 16:0/18:1 concentrations stayed rather low compared with those of alcohol abusers from previous studies. © 2012 by the Research Society on Alcoholism.


Butterbach-Bahl K.,Karlsruhe Institute of Technology | Dannenmann M.,Albert Ludwigs University of Freiburg
Current Opinion in Environmental Sustainability | Year: 2011

Human activities have accelerated global nitrogen cycling by approx. a factor of two. Also under future environmental conditions, agricultural nitrogen use is expected to remain the leading cause of reactive nitrogen (Nr) release to the environment. The main process to remove Nr from the environment is microbial denitrification. Here we summarize potential mechanisms that may affect denitrification and associated nitrous oxide (N2O) emissions in/from agricultural systems under future environmental conditions. Though changes in climate, specifically in temperature and precipitation, are likely to directly affect denitrification rates and N2O emissions, we identified several indirect mechanisms of global change that may potentially override direct effects. Among these are a) landscape scale changes of hotspots of denitrification: while the importance of non-hydromorphic upland soils for denitrification may decrease owing to limitations in soil moisture the importance of riparian areas as denitrification hotspots may further increase owing to the increased likeliness of flooding events leading to more frequent occurrences of aerobic-anaerobic cycles in riparian areas and, thus, increased denitrification, b) increased provision of labile carbon substrates via plant root exudation in the rhizosphere under elevated atmospheric carbon dioxide (CO2) concentrations, leading to increased microbial activity and higher denitrification rates in agricultural subsoils, thereby potentially reducing rates of nitrate leaching from agricultural soils and c) increased ammonia (NH3) volatilization from agricultural systems leading to increased denitrification rates and N2O emissions downwind from NH3 emission sources. Obviously, under future environmental conditions the mentioned mechanisms would further strengthen the regional disjunction of areas of Nr application from those of Nr removal by denitrification, thereby calling for a reappraisal of the importance of indirect emissions of N2O from agricultural Nr use. It remains unclear, to which extent climate change mitigation options such as the introduction of no-till systems or the increasing use of slow release fertilizers in conjunction with nitrification inhibitors or the adaptations of agricultural management practices to climate change such as altered timing of cultivation, choice of crop varieties and adaptation of water saving production systems may finally override direct and indirect climate change effects on denitrification and N2O emissions from agricultural systems. © 2011 Elsevier B.V.


Nelson J.,Imperial College London | Nelson J.,Albert Ludwigs University of Freiburg
Materials Today | Year: 2011

The efficiency of solar cells made from a conjugated polymer blended with a fullerene derivative has risen from around 1 to over 9 in the last ten years, making organic photovoltaic technology a viable contender for commercialization. The efficiency increases have resulted from the development of new materials with lower optical gaps, new polymer:fullerene combinations with higher charge separated state energies, and new approaches to control the blend microstructure, all driven by a qualitative understanding of the principles governing organic solar cell operation. In parallel, a device physics framework has been developed that enables the rational design of device structures and materials for improved organic photovoltaic devices. We review developments in both materials science and device physics for organic photovoltaics. © 2011 Elsevier Ltd.


Weber W.,ETH Zurich | Weber W.,Albert Ludwigs University of Freiburg | Fussenegger M.,ETH Zurich | Fussenegger M.,University of Basel
Current Opinion in Chemical Biology | Year: 2011

The rapid development of synthetic biology is a paradigm of how the molecular diversity of naturally occurring gene control components can be used to design synthetic control devices and gene networks that provide precisely programmed transgene expression dynamics in space and time. Here we offer an overview on recent advances in the modular design of trigger-inducible mammalian expression devices that are either responsive by exogenous stimuli such as chemicals and physical cues or controlled by endogenous metabolites driving prosthetic circuits to treat metabolic disorders in a self-sufficient manner. Compatible genetic switches can also be assembled to synthetic gene networks that show highly complex expression dynamics such as temporally resolved band-detect functions or oscillating transgene expression profiles. The ongoing metagenomic discovery and characterization of the unexplored sequence space is constantly increasing the molecular diversity in fundamental control components that fuels the further development of synthetic biology. © 2011 Elsevier Ltd.


Majer K.,Albert Ludwigs University of Freiburg | Issendorff B.V.,Albert Ludwigs University of Freiburg
Physical Chemistry Chemical Physics | Year: 2012

Photoelectron spectra of low temperature silicon doped gold cluster anions Au nSi - with n = 2-56 and silver cluster anions Ag nSi - with n = 5-82 have been measured. Comparing the spectra as well as the general size dependence of the electron detachment energies to the results on undoped clusters shows that the silicon atom changes the apparent free electron count in the clusters. In the case of larger gold clusters (with more than about 30 gold atoms) the silicon atom seems to consistently delocalize all of its four valence electrons, while in the case of the silver clusters a less uniform behavior is observed. Here the silicon atoms act partly as electron donors, partly as electron acceptors, without following an obvious simple principle. Additionally some structural information can be obtained from the measured spectra: while Ag 54Si - seems to adopt an icosahedral structural motif, Au 54Si - seems to take on a low symmetry structure, much like the corresponding pure 55 atom clusters. This indicates that for such larger clusters the incorporation of a single silicon atom does not change the ground state geometry significantly. © 2012 the Owner Societies.


Hilbert A.,University of Marburg | Tuschen-Caffier B.,Albert Ludwigs University of Freiburg | Czaja J.,University of Marburg
American Journal of Clinical Nutrition | Year: 2010

Background: Loss of control (LOC) eating in children leads to excessive weight gain. However, few studies have investigated the eating behavior of children with LOC eating and psychological and familial factors that maintain the eating behavior. Objective: This study sought to measure food intake in children with LOC eating and to examine maintenance through negative mood and parent-child mealtime interactions. Design: Children with or without LOC eating (n = 120, aged 8-13 y) consumed a parent-child test meal and a child-only meal, consisting of snack food, after the induction of negative mood. Food intake, mood, sense of LOC, hunger, satiety, and mealtime interactions were assessed. Results: Regardless of mood induction, children with LOC eating showed a greater intake of energy, fat, and protein and a greater sense of LOC than did those without LOC in the child-only snack group, which was accounted for by greater baseline hunger and satiety. Independently, children with high recurrent LOC eating had a greater food intake at both test meals than did those with low recurrent LOC eating. Overall, mealtime interactions did not differ between groups, but parents of children with LOC eating expressed more weight-related critique than did parents of children without LOC eating outside negative mood induction. Predictors of food intake were greater antecedent hunger or less satiety, stronger antecedent sense of LOC, and more weight-related critique. Conclusions: The results showed objective abnormalities in the eating behavior of children with LOC eating that were mostly unrelated to negative mood or dysfunctional mealtime interactions. Further research is required to specify factors maintaining LOC eating. © 2010 American Society for Nutrition.


Korner M.,Albert Ludwigs University of Freiburg
Clinical Rehabilitation | Year: 2010

Objective: To compare multi-and interdisciplinary team approaches concerning team process (teamwork) and team effectiveness (team performance and staff satisfaction) in German medical rehabilitation clinics. Design: A cross-sectional study with a descriptive-explorative design. Setting: Eighteen medical rehabilitation clinics divided into two groups (somatic and psychosomatic indication fields). Subjects: The 18 head physicians or psychotherapists in the clinics and their complete rehabilitation teams (n = 824). Main measures: An interview guide was designed to determine the team approach in a telephone interview. A staff questionnaire for team members measured teamwork and team effectiveness with psychometrically validated questionnaires and self-administered items. Results: All 18 head physicians took part in the telephone interview. The response rate of the employee attitude survey averaged 46% (n = 378). Eight teams were categorized as multidisciplinary and seven teams as interdisciplinary. In three cases the results were ambiguous. These teams were not considered in the further study. As expected, the interdisciplinary team approach showed significantly better results for nearly all aspects of teamwork and team effectiveness in comparison with the multidisciplinary team approach. The differences between multi-and interdisciplinary approach concerning teamwork and team effectiveness were higher in the somatic (8 teams, n = 183) than in the psychosomatic indication fields (7 teams, n = 195). Conclusions: Teamwork and team effectiveness are higher in teams working with the interdisciplinary team approach. Therefore the interdisciplinary approach can be recommended, particularly for clinics in the somatic indication field. Team development can help to move from the multidisciplinary to the interdisciplinary approach. © The Author(s), 2010.


Grimm D.,Albert Ludwigs University of Freiburg | Heeg M.,Albert Ludwigs University of Freiburg | Thimme R.,Albert Ludwigs University of Freiburg
Clinical Science | Year: 2013

Owing to the major limitations of current antiviral therapies in HBV (hepatitis B virus) infection, there is a strong need for novel therapeutic approaches to this major health burden. Stimulation of the host's innate and adaptive immune responses in a way that results in the resolution of viral infection is a promising approach. A better understanding of the virus-host interaction in acute and chronic HBV infection revealed several possible novel targets for antiviral immunotherapy. In the present review, we will discuss the current state of the art in HBV immunology and illustrate how control of infection could be achieved by immunotherapeutic interventions. © 2013 Biochemical Society.


Schallner N.,Albert Ludwigs University of Freiburg | Goebel U.,Albert Ludwigs University of Freiburg
Current Opinion in Anaesthesiology | Year: 2013

PURPOSE OF REVIEW: Conflicting reports about adverse events following nitrous oxide (N2O) application have spurred a discussion whether N2O should be abandoned from clinical practice. Concurrently, N2O is increasingly used as a single anesthetic agent in medical procedures. This article reviews and discusses reports about the present use of N2O. RECENT FINDINGS: Multiple publications demonstrate an increasing use of N2O as a procedural analgesic and sedative. Results from the Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia trial have been contrasted by recent studies reporting no increased risk for perioperative complications, particularly related to the cardiovascular and cerebrovascular system. Recent studies show that electroencephalogram-based anesthesia depth monitoring is not compatible with the use of N2O because of its distinct influence on electroencephalogram wave patterns. The clinical relevance of the proposed neurotoxicity, immunosuppression and influence on methionine metabolism remains unclear. Recently, its acute and long-term analgesic potency has been proven. Occupational exposure might pose a relevant health hazard. SUMMARY: Based on the present literature, abolishment of N2O is controversial. When avoided in patients at risk for adverse events, N2O is still a valuable supplement to general anesthesia and a potent procedural analgesic drug. In the latter, its use by nonanesthesiologists should be discouraged. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Weisenberger T.,Albert Ludwigs University of Freiburg | Bucher K.,Albert Ludwigs University of Freiburg
Journal of Metamorphic Geology | Year: 2010

Six different Ca-zeolite minerals are widespread in various assemblages in late fissures and fractures in granites and gneisses of the Swiss Alps. The zeolites formed as a result of water-rock interaction at relatively low temperatures (<250 °C) in the continental upper crust. The zeolites typically overgrow earlier minerals of the fissure assemblages, but zeolites also occur as monomineralic fissure fillings. They represent the youngest fissure minerals formed during uplift and exhumation of the Alpine orogen. A systematic study of zeolite samples showed that the majority of finds originate from three regions particularity rich in zeolite-bearing fissures: (i) in the central and eastern part of the Aar- and Gotthard Massifs; (2) Gibelsbach/Fiesch, in a fissure breccia located at the boundary of Aar Massif and Permian sedimentary rocks; and (3) in Penninic gneisses of the Simano nappe at Arvigo (Val Calanca). Rail and road tunnel construction across the Aar- and Gotthard Massif provided excellent data on zeolite frequency in Alpine fissures. It was found that 32% (Gotthard NEAT rail base tunnel, Amsteg section) and 18% (Gotthard road tunnel) of all studied fissures are filled with zeolites. The number of different zeolites is limited to six species: laumontite, stilbite and scolecite are abundant and common, whereas heulandite, chabazite and epistilbite occur occasionally. Calcium is the dominant extra-framework cation, with minor K and Na. Heulandite and chabazite contain Sr up to 29 and 10 mol.% extra-framework cations respectively. Na and K contents in zeolites tend to increase during growth as a result of changes in fluid composition and/or temperature. The K enrichment of stilbite found in surface outcrops compared to subsurface samples may indicate late stage cation exchange with surface water. Texture data, relative age sequences derived from fissure assemblages and equilibrium calculations show that the Ca-dominated zeolites precipitated from fluid with decreasing temperature in the order (old to young = hot to cold): scolecite, laumontite, heulandite, chabazite and stilbite. The necessary components for zeolite formation are derived from dissolving primary granite and gneiss minerals. The nature of these minerals depends, among other factors, on the metamorphic history of the host rock. Zeolites in the Aar Massif derived from the dissolution of epidote, secondary calcite and albite that were originally formed during Alpine greenschist metamorphism from primary granite and gneiss assemblages. Zeolite fissures occur in areas of H2O-dominated fluids. This is consistent with equilibrium calculations that predict a low CO2 tolerance of zeolite assemblages, particularly at low temperature. © 2010 Blackwell Publishing Ltd.


Horvath S.D.,Albert Ludwigs University of Freiburg
The European journal of esthetic dentistry : official journal of the European Academy of Esthetic Dentistry | Year: 2012

This study examined the correlation between maxillary anterior tooth form and gender with three-dimensional data. Three-dimensional digital models of the area between the maxillary right central incisor and the maxillary right canine were obtained from 120 Caucasian subjects (60 males and 60 females) with healthy dentitions. Correlation between gender and tooth form was assessed applying logistic regression, with and without size standardization. Success rates were estimated using 10-fold cross-validation. Principal components that correlated with gender were evaluated with a Wald test. Values for the significance of the predictors were provided with a likelihood ratio test (P < 0.05). Significant correlation between gender and tooth shape was found for the maxillary central incisor (P = 0.003), lateral incisor (P ≤ 0.001), and canine individually (P ≤ 0.001), and for the three teeth combined (P ≤ 0.001) without size standardization. For the maximillary right lateral incisor (P=0.004), canine (P ≤ 0.001), and a correlation of the teeth (P ≤ 0.001), a correlation was also established after size standardization. Prediction of gender was not possible without information on tooth size for the maxillary right central incisor (P =0.15). maxillary anterior teeth have gender-specific differences. Differences in tooth size account for part of the correlation. However, tooth shapes are also gender specific.