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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.

Grahammer F.,Albert Ludwigs University of Freiburg
Kidney International | Year: 2015

Slowly progressive renal fibrosis is the hallmark of chronic kidney disease, independent of its etiology. Transforming growth factor-β (TGF-β) has been found to be the main profibrotic renal cytokine. Li et al. identify mTORC2 as an important mediator of TGF-β signaling. Being upstream of the previously described profibrotic kinases AKT, SGK1, and PKC-α, mTORC2 represents a potentially interesting drug target. Yet, although the mouse genetic approach yielded convincing results, transition from bench to bedside will remain challenging. © 2015 International Society of Nephrology.

von Detten R.,Albert Ludwigs University of Freiburg
European Journal of Forest Research | Year: 2011

Forest management, which is the main focus of this paper, is facing fundamental paradoxes and dilemmas that cannot be addressed by long-term management strategies or management concepts, even where the intention of these strategies is to follow a sustainability path. On this basis, it is argued that sustainability is not a suitable future-oriented term but rather a term oriented towards the present. The more complex the relationships between the different social subsystems, the more rapid the social change of modern societies, the more confusing the present situation and the more unpredictable the future, the less suitable utopian, long-term strategies and the attitude and strategy of firm decisiveness are to address challenges. Several suggested management strategies and techniques such as incrementalism, adaptive management and scenario-analysis are critically discussed. The intention of these strategies is to cope with uncertainty and ignorance. With regard to their limitations, it can be concluded that strategic decisions in the face of uncertainty have to explicitly consider the reversibility of decisions and the awareness of their shortcomings in relation to various dimensions of risk, uncertainty and ignorance. It is therefore necessary to look for modes of planning that actively address uncertainty in organizing learning opportunities and permanent feedback control. © 2010 Springer-Verlag.

Butenko Y.,Tel Aviv University | Ohad N.,Tel Aviv University | Ohad N.,Albert Ludwigs University of Freiburg
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2011

Polycomb Group (PcG) proteins form an epigenetic "memory system", conserved in both plants and animals, controlling global gene expression during development via histone modifications. The role of PcG proteins in plants was primarily explored in Arabidopsis thaliana, where PcG regulation of developmental processes was demonstrated throughout the plant life cycle. Our knowledge about the PcG machinery in terrestrial plants other than Arabidopsis began to accumulate only in recent years. In this review we summarize recent emerging data on the evolution and diversification of PcG mechanisms in various phyla, from early-diverging plants, including members of the Chlorophyte algae, through bryophytes and flowering plants. We describe the compositions of the PcG gene families, their so-far studied expression profiles, and finally summarize commonalities vs. differences among PcG functions across the various species. This article is part of a Special Issue entitled: Epigenetic control of cellular and developmental processes in plants. © 2011 Elsevier B.V.

Wittwer-Backofen U.,Albert Ludwigs University of Freiburg
Methods in Molecular Biology | Year: 2012

In Forensic Anthropology age diagnosis of unidentified bodies significantly helps in the identification process. Among the set of established aging methods in anthropology tooth cementum annulation (TCA) is increasingly used due to its narrow error range which can reach 5 years of age in adult individuals at best. The rhythm of cementum appositions of seasonally different density provides a principal mechanism on which TCA is based. Using histological preparation techniques for hard tissues, transversal tooth root sections are produced which can be analyzed in transmitted light microscopy. Even though no standard TCA preparation protocol exists, several methodological validation studies recommend specific treatments depending on individual conditions of the teeth. Individual age is estimated by adding mean tooth eruption age to the number of microscopically detected dark layers which are separated by bright layers and stand for 1 year of age each. To assure a high reliability of the method, TCA age diagnosis has to be based on several teeth of one individual if possible and needs to be supported by different techniques in forensic cases. © 2012 Springer Science+Business Media, LLC.

Wiltschi B.,Albert Ludwigs University of Freiburg
Methods in Molecular Biology | Year: 2012

Techniques to manipulate cellular gene expression such that amino acid analogs not encoded by the genetic code are incorporated into a polypeptide chain have recently gained increasing interest. The so-called noncanonical amino acids often have unusual properties that can be translated into target proteins by reprogrammed ribosomal protein synthesis. Residue-specific substitution of a specific canonical amino acid by its analogs provokes global effects in the resulting protein congeners that include improved stability or catalytic activity, reduced redox sensitivity, as well as altered spectral properties. Thus, the approach holds great promise for the engineering of synthetic proteins. This contribution describes a protocol for the incorporation of a noncanonical amino acid into a target protein expressed in an appropriate amino acid auxotrophic E. coli strain. © 2012 Springer Science+Business Media, LLC.

Ohnesorge D.,Albert Ludwigs University of Freiburg
European Journal of Wood and Wood Products | Year: 2011

This paper describes an investigation into the shear strength of glued laminated timber (GLT) made from European beech. Special consideration was paid to the possible strength influence of a frequently occurring discolouration of the timber, termed red heartwood, which is inherent to the species. The beech lamellae were visually graded according to German hardwood grading standard DIN 4074-5. Grade LS13, conforming to European hardwood strength class D40, was split into two sub-grades LS13- and LS13+. Additionally, modulus of elasticity (MOE) was determined by ultrasound pulse, longitudinal vibration and static tension tests. Sub-grade LS13+ showed a mean density and MOE of 690 kg/m 3 and 14,800 N/mm 2, respectively. The GLT shear strength was evaluated by means of four-point bending tests on structural sized I-shaped beams with a depth of 0.6 m and a span to depth ratio of 5:1. The slightly inhomogeneous build-up of the cross-section conformed to glulam strength class GL42c. Two beam samples were investigated, each with seven specimens, where one grouping had no red heartwood and the other with a high red heartwood in the web laminations. Additionally block shear tests on bond line strength were performed with standardized small specimens according to EN 392. Neither the beam shear capacity tests nor the bond line block shear tests revealed an influence of the red heartwood discolouration on strength. The fifth-percentile value of shear strength of all beams was 3.5 N/mm 2. The results of the block shear tests indicate that the present requirements on minimum block shear strength are set too low in the European standard EN 386 with regard to beech GLT. © 2010 Springer-Verlag.

The friction and wear properties of a composite containing unsaturated polyester resin with polyester fiber fabric reinforcement and internal PTFE lubricants are described under reciprocating dry sliding in a cylinder-on-plate contact against steel. By taking into account the deformation, creep, thermal expansion and strain recovery, on-line measurements for diameter reduction by wear are in agreement with post-mortem weight loss measurements. However, it is most important to consider the effects of the maximum polymer surface temperatures. The sliding properties are controlled by mechanical shear and plasticization of the PTFE lubricants under mild sliding conditions with a transition into instable sliding at 75 °C correlating with curing of the matrix, and stable sliding at temperatures of 120 °C corresponding to thermally-controlled sliding of PTFE. © 2016 Elsevier Ltd

Nikkhah G.,Albert Ludwigs University of Freiburg
Acta neurochirurgica. Supplement | Year: 2013

New insights into the mechanism of dopaminergic (DA) nigrostriatal neuron degeneration and regeneration in experimental studies in animal models of Parkinson's disease (PD) have opened up the discussion about novel therapeutic strategies such as cell-based therapies and neuroprotection of DA neurons. These cellular and molecular approaches aim at preventing or slowing down the progressive degeneration of DA neurons and/or replacing the lost ones. Here, a brief overview of basic principles and current strategies of these novel restorative approaches is discussed in light of experimental results and possible clinical applications.

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.

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.

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.

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.

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.

Anderson R.,Albert Ludwigs University of Freiburg
Frontiers in bioscience (Elite edition) | Year: 2010

Sepsis is one of the leading causes of death in intensive care medicine in western countries. A strong body of evidence has been accumulated indicating that immediate resuscitation and restoration of tissue perfusion as well as early antibiotic treatment could significantly decrease the mortality in these patients. The clinical definitions of sepsis are basically nonspecific, often resulting in the delay of the diagnosis. Therefore, identification of specific clinical biomarkers may accelerate the diagnosis and thus improve sepsis treatment. During the last decade, a variety of different molecules have been proposed as clinical biomarkers in sepsis, most of which are still in the experimental stage. However, some have found their way into clinical practice and have evolved as valuable tools for diagnosis, therapy monitoring, and outcome prediction. This review will summarize the currently most important biomarkers and will discuss their clinical relevance.

Dunay I.R.,Albert Ludwigs University of Freiburg | Sibley L.D.,University of Washington
Current Opinion in Immunology | Year: 2010

Toxoplasma gondii is a widespread protozoan parasite that causes water and foodborne infections in humans. The parasite not only infects intestinal enterocytes but also spreads by migration across the epithelial layer and entry into the submucosa. Within the lamina propria, innate immune responses lead to initial parasite control, although the infection disseminates widely and persists chronically despite adaptive immunity. Inflammatory monocytes exit the bone marrow and home to the lamina propria where they express antimicrobial effector functions that control infection. Ablation of the signals for recruitment of inflammatory monocytes in the mouse results in uncontrolled parasite replication, extensive infiltration of neutrophils, intestinal necrosis, and rapid death. Inflammatory monocytes play a pivotal role in mucosal immunity against T. gondii, and likely other enteric pathogens. © 2010 Elsevier Ltd.

Liu H.,Washington State University | Laborie M.-P.G.,Albert Ludwigs University of Freiburg
Cellulose | Year: 2011

A series of resole-type phenolic resin-based nanocomposites, uniformly filled with cellulose nanowhiskers (CNWs), was successfully fabricated via direct solution mixing, then solvent-exchange with DMF and finally stepwise thermal curing. Dynamic mechanical analysis evidenced a moderate reinforcing effect with a minimum CNWs weight content of 5.0 wt% especially above the resin glass transition temperature (Tg). The Halpin-Kardos model provided a good description of the CNWs reinforcing effect, suggesting perhaps the contribution of whiskers/matrix interactions rather than that of whiskers/whiskers interactions. Differential scanning calorimetry (DSC) further indicated that the nanowhiskers enhanced the resin cure, resulting in a more extensive degree of cure. Finally, the CNWs were found to only slightly lower the thermal stability of PF resins. In spite of a modest reinforcing effect, it is proposed that CNWs are also interesting fillers for high modulus and high Tg thermosetting resins that require high temperature cure. © 2011 Springer Science+Business Media B.V.

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.

Mouillot D.,Montpellier University | Villeger S.,CNRS Biological Evolution and Diversity Laboratory | Scherer-Lorenzen M.,Albert Ludwigs University of Freiburg | Mason N.W.H.,Landcare Research
PLoS ONE | Year: 2011

The accelerating rate of change in biodiversity patterns, mediated by ever increasing human pressures and global warming, demands a better understanding of the relationship between the structure of biological communities and ecosystem functioning (BEF). Recent investigations suggest that the functional structure of communities, i.e. the composition and diversity of functional traits, is the main driver of ecological processes. However, the predictive power of BEF research is still low, the integration of all components of functional community structure as predictors is still lacking, and the multifunctionality of ecosystems (i.e. rates of multiple processes) must be considered. Here, using a multiple-processes framework from grassland biodiversity experiments, we show that functional identity of species and functional divergence among species, rather than species diversity per se, together promote the level of ecosystem multifunctionality with a predictive power of 80%. Our results suggest that primary productivity and decomposition rates, two key ecosystem processes upon which the global carbon cycle depends, are primarily sustained by specialist species, i.e. those that hold specialized combinations of traits and perform particular functions. Contrary to studies focusing on single ecosystem functions and considering species richness as the sole measure of biodiversity, we found a linear and non-saturating effect of the functional structure of communities on ecosystem multifunctionality. Thus, sustaining multiple ecological processes would require focusing on trait dominance and on the degree of community specialization, even in species-rich assemblages. © 2011 Mouillot et al.

Mergner T.,Albert Ludwigs University of Freiburg
Annual Reviews in Control | Year: 2010

During biped stance or locomotion, humans show remarkable skills in reactive balancing upon external disturbances. Mainly four types of external disturbances are relevant for stance: the field force gravity, contact forces such as a push or pull against the body, as well as body support surface rotation and translational acceleration. It is known from clinics that sensory loss severely impairs the balancing. Three sensory inputs are instrumental: vestibular, joint angle, and joint torque. System identification studies currently try to understand how humans are able to flexibly cope with changes in, and superposition of the disturbances. A solution is presented in this article. The article first describes the control problem and then reviews recent evidence for a PD (proportional-derivative) controller, for multisensory feedback, and for sensory reweighting as a key to understand the flexibility. On this basis, a recent disturbance estimation and compensation (DEC) model is introduced. It builds on two concepts from previous psychophysical studies of human self-motion perception. First, inputs from several sensory transducers are fused to establish sensors that provide explicit measures of the physical variables (sensor concept). Second, a processing level, interleaved between sensors and feedback (meta level), performs online sensory estimations of the external disturbances. These estimations are then fed into a local proprioceptive feedback loop, yielding corresponding disturbance rejections. Previous work on using the DEC model to describe human reactive balancing data is briefly reviewed. Then, novel work is presented, in which voluntary control over the reactive balancing is added to the DEC model. A prediction method for anticipating self-produced and external disturbances is suggested and corresponding software and hardware (robot) simulations are presented. The results serve as guidelines for future human experiments. Since the DEC model is very simple, we concluded that its behavioral flexibility and fault tolerance goes together with computational parsimony, an equally important biological constraint. © 2010 Elsevier Ltd. All rights reserved.

Lomascolo S.B.,University of Florida | Lomascolo S.B.,Albert Ludwigs University of Freiburg | Schaefer H.M.,Laboratorio Of Interacciones Ecologicas
Journal of Evolutionary Biology | Year: 2010

The Dispersal Syndrome hypothesis remains contentious, stating that apparently nonrandom associations of fruit characteristics result from selection by seed dispersers. We examine a key assumption under this hypothesis, i.e. that fruit traits can be used as reliable signals by frugivores. We first test this assumption by looking at whether fruit colour allows birds and primates to distinguish between fruits commonly dispersed by birds or primates. Second, we test whether the colours of fruits dispersed by primates are more contrasting to primates than the colours of bird-dispersed fruits, expected if fruit colour is an adaptation to facilitate the detection by seed dispersers. Third, we test whether fruit colour has converged in unrelated plant species dispersed by similar frugivores. We use vision models based on peak sensitivities of birds' and primates' cone cells. We base our analyses on the visual systems of two types of birds (violet and ultraviolet based) and three types of primates (trichromatic primates from the Old and the New Worlds, and a dichromatic New World monkey). Using a Discriminant Function Analysis, we find that all frugivore groups can reliably discriminate between bird- and primate-dispersed fruits. Fruit colour can be a reliable signal to different seed dispersers. However, the colours of primate-dispersed fruits are less contrasting to primates than those of bird-dispersed fruits. Fruit colour convergence in unrelated plants is independent of phylogeny and can be better explained by disperser type, which supports the hypothesis that frugivores are important in fruit evolution. We discuss adaptive and nonadaptive hypotheses that can potentially explain the pattern we found. © 2010 The Authors. Journal Compilation © 2010 European Society For Evolutionary Biology.

Furrer A.,Paul Scherrer Institute | Waldmann O.,Albert Ludwigs University of Freiburg
Reviews of Modern Physics | Year: 2013

Magnetic clusters, i.e., assemblies of a finite number (between two or three and several hundred) of interacting spin centers which are magnetically decoupled from their environment, can be found in many materials ranging from inorganic compounds and magnetic molecules to artificial metal structures formed on surfaces and metalloproteins. Their magnetic excitation spectra are determined by the nature of the spin centers and of the magnetic interactions, and the particular arrangement of the mutual interaction paths between the spin centers. Small clusters of up to four magnetic ions are ideal model systems in which to examine the fundamental magnetic interactions, which are usually dominated by Heisenberg exchange, but often complemented by anisotropic and/or higher-order interactions. In large magnetic clusters, which may potentially deal with a dozen or more spin centers, there is the possibility of novel many-body quantum states and quantum phenomena. In this review the necessary theoretical concepts and experimental techniques to study the magnetic cluster excitations and the resulting characteristic magnetic properties are introduced, followed by examples of small clusters, demonstrating the enormous amount of detailed physical information that can be retrieved. The current understanding of the excitations and their physical interpretation in the molecular nanomagnets which represent large magnetic clusters is then presented, with a section devoted to the subclass of single-molecule magnets, distinguished by displaying quantum tunneling of the magnetization. Finally, there is a summary of some quantum many-body states which evolve in magnetic insulators characterized by built-in or field-induced magnetic clusters. The review concludes by addressing future perspectives in the field of magnetic cluster excitations. © 2013 American Physical Society.

Tobis J.,Albert Ludwigs University of Freiburg | Tiller J.C.,TU Dortmund
Biotechnology Letters | Year: 2014

Lipase from Candida rugosa was loaded into an amphiphilic polymer co-network (APCN) composed of the chiral poly[(R)-N-(1-hydroxybutan-2-yl) acrylamide] [P-(R)-HBA] and P-(S)-HBA, respectively, linked by poly(dimethylsiloxane). The nanophase-separated amphiphilic morphology affords a 38,000-fold activation of the enzyme in the esterification of 1-phenylethanol with vinyl acetate. Further, the enantioselectivity of the entrapped lipase was influenced by the configuration of the chiral, hydrophilic polymer matrix. While the APCN with the (S)-configuration of the APCN affords 5.4 faster conversion of the (R)-phenylethanol compared to the respective (S)-enantiomer, the (R)-APCN allows an only a 2.8 faster conversion of the (R)-enantiomer of the alcohol. Permeation-experiments reveal that the enantioselectivity of the reaction is at least partially caused by specific interactions between the substrates and the APCN. © 2014 Springer Science+Business Media Dordrecht.

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.

Plessky V.P.,GVR Trade SA | Reindl L.M.,Albert Ludwigs University of Freiburg
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control | Year: 2010

SAW tags were invented more than 30 years ago, but only today are the conditions united for mass application of this technology. The devices in the 2.4-GHz ISM band can be routinely produced with optical lithography, high-resolution radar systems can be built up using highly sophisticated, but low-cost RF-chips, and the Internet is available for global access to the tag databases. The "Internet of Things," or I-o-T, will demand trillions of cheap tags and sensors. The SAW tags can overcome semiconductor-based analogs in many aspects: they can be read at a distance of a few meters with readers radiating power levels 2 to 3 orders lower, they are cheap, and they can operate in robust environments. Passive SAW tags are easily combined with sensors. Even the "anti-collision" problem (i.e., the simultaneous reading of many nearby tags) has adequate solutions for many practical applications. In this paper, we discuss the state-of-the-art in the development of SAW tags. The design approaches will be reviewed and optimal tag designs, as well as encoding methods, will be demonstrated. We discuss ways to reduce the size and cost of these devices. A few practical examples of tags using a timeposition coding with 106 different codes will be demonstrated. Phase-coded devices can additionally increase the number of codes at the expense of a reduction of reading distance. We also discuss new and exciting perspectives of using ultra wide band (UWB) technology for SAW-tag systems. The wide frequency band available for this standard provides a great opportunity for SAW tags to be radically reduced in size to about 1 × 1 mm2 while keeping a practically infinite number of possible different codes. Finally, the reader technology will be discussed, as well as detailed comparison made between SAW tags and IC-based semiconductor device. © 2006 IEEE.

Murphy R.F.,Carnegie Mellon University | Murphy R.F.,Albert Ludwigs University of Freiburg
Methods in Cell Biology | Year: 2012

This chapter describes approaches for learning models of subcellular organization from images. The primary utility of these models is expected to be from incorporation into complex simulations of cell behaviors. Most current cell simulations do not consider spatial organization of proteins at all, or treat each organelle type as a single, idealized compartment. The ability to build generative models for all proteins in a proteome and use them for spatially accurate simulations is expected to improve the accuracy of models of cell behaviors. A second use, of potentially equal importance, is expected to be in testing and comparing software for analyzing cell images. The complexity and sophistication of algorithms used in cell-image-based screens and assays (variously referred to as high-content screening, high-content analysis, or high-throughput microscopy) is continuously increasing, and generative models can be used to produce images for testing these algorithms in which the expected answer is known. © 2012 Elsevier Inc.

Voelxen N.,Albert Ludwigs University of Freiburg
Immunology and Cell Biology | Year: 2016

Persistent polyclonal B lymphocytosis (PPBL) is a benign hematological disorder characterized by a selective expansion of circulating polyclonal marginal zone (MZ)-like B cells. Previous reports demonstrated that cases of PPBL showed poor activation, proliferation and survival of B cells in vitro, yet the underlying defect remains unknown. Here we report for the first time an attenuated activation of the canonical NF-κB (nuclear factor of kappa light polypeptide gene enhancer in B cells) and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway after CD40 stimulation. This defect was selective, as alternative NF-κB signaling after CD40 stimulation and both B-cell receptor- and Toll-like receptor 9-mediated activation remained unaffected. Reduced canonical NF-κB activation resulted in decreased IκBα and CD40 expression in resting cells. In PPBL patients, expression of Bcl-xL in MZ-like B cells did not increase upon activation, consistent with the high apoptosis rates of PPBL-derived B cells that were observed in vitro. The B-cell phenotype of mice with selective knockouts of early components of the CD40 signaling pathway resembles PPBL, but sequencing corresponding genes in sorted MZ-like B cells of PPBL patients did not reveal relevant genetic alterations. Nevertheless, the frequently observed mutations in early signaling components of the NF-κB pathway in MZ lymphomas underline the relevance of our findings for the pathogenesis of PPBL.Immunology and Cell Biology advance online publication, 31 May 2016; doi:10.1038/icb.2016.46. © 2016 Australasian Society for Immunology Inc.

Ahrens I.,Albert Ludwigs University of Freiburg
Discovery medicine | Year: 2012

Two new classes of orally available anticoagulant drugs, the direct thrombin inhibitor (dabigatran etexilate) and direct factor Xa inhibitors (the -xabans), have been approved for various clinical indications, as alternatives to the vitamin K antagonists (e.g., warfarin). These include the prevention of venous thromboembolism after major orthopedic surgery, the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, and the secondary prevention and treatment of venous thromboembolism including pulmonary embolism. Other clinical indications including the add-on therapy to dual antiplatelet therapy in patients with acute coronary syndrome and extended prophylaxis of venous thromboembolism in acute medically ill patients are currently under clinical investigation. The clinical phase III development and indications of the currently clinically approved novel oral anticoagulants dabigatran etexilate, rivaroxaban, apixaban, and edoxaban are summarized and discussed.

Ahrens I.,Albert Ludwigs University of Freiburg
Discovery medicine | Year: 2012

Following the clinical approval of novel oral anticoagulants as alternatives to the vitamin K antagonists, many additional novel oral anticoagulant drugs are currently in early and advanced stages of clinical development. The majority of the drugs in development belong to the class of direct factor Xa inhibitors (the -xabans). These include betrixaban, letaxaban, darexaban, eribaxaban, and LY517717. Another representative of the class of orally available direct thrombin inhibitors (the -gatrans) is known as AZD0837. Furthermore other coagulation factors with central roles within the coagulation cascade are currently investigated as potential targets for the development of novel oral anticoagulant drugs. Among those, the first direct oral factor IXa inhibitor TTP889 has entered the clinical phase of development. A short summary of novel oral anticoagulant currently in earlier stages of clinical development is provided.

Horie M.,Albert Ludwigs University of Freiburg
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

Bornaviruses are the only animal RNA viruses that establish a persistent infection in their host cell nucleus. Studies of bornaviruses have provided unique information about viral replication strategies and virus-host interactions. Although bornaviruses do not integrate into the host genome during their replication cycle, we and others have recently reported that there are DNA sequences derived from the mRNAs of ancient bornaviruses in the genomes of vertebrates, including humans, and these have been designated endogenous borna-like (EBL) elements. Therefore, bornaviruses have been interacting with their hosts as driving forces in the evolution of host genomes in a previously unexpected way. Studies of EBL elements have provided new models for virology, evolutionary biology and general cell biology. In this review, we summarize the data on EBL elements including what we have newly identified in eukaryotes genomes, and discuss the biological significance of EBL elements, with a focus on EBL nucleoprotein elements in mammalian genomes. Surprisingly, EBL elements were detected in the genomes of invertebrates, suggesting that the host range of bornaviruses may be much wider than previously thought. We also review our new data on non-retroviral integration of Borna disease virus.

Accorsi R.,Albert Ludwigs University of Freiburg
Mathematical and Computer Modelling | Year: 2013

This paper presents BBox, a digital black box to provide for authentic archiving (and, consequently, forensic evidence) for remote auditing 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 keyword retrieval by authorized auditors. © 2012 Elsevier Ltd.

Schygulla J.,Albert Ludwigs University of Freiburg
Archive for Rational Mechanics and Analysis | Year: 2012

Motivated by a simple model for elastic cell membranes, we minimize the Willmore functional among two-dimensional spheres embedded in ℝ 3 with prescribed isoperimetric ratio. © 2011 Springer-Verlag.

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.

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.

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.

Speck T.,Albert Ludwigs University of Freiburg | Burgert I.,Max Planck Institute of Colloids and Interfaces
Annual Review of Materials Research | Year: 2011

Plant stems are one of nature's most impressive mechanical constructs. Their sophisticated hierarchical structure and multifunctionality allow trees to grow more than 100 m tall. This review highlights the advanced mechanical design of plant stems from the integral level of stem structures down to the fiber-reinforced-composite character of the cell walls. Thereby we intend not only to provide insight into structure-function relationships at the individual levels of hierarchy but to further discuss how growth forms and habits of plant stems are closely interrelated with the peculiarities of their tissue and cell structure and mechanics. This concept is extended to a further key feature of plants, namely, adaptive growth as a reaction to mechanical perturbation and/or changing environmental conditions. These mechanical design principles of plant stems can serve as concept generators for advanced biomimetic materials and may inspire materials and engineering sciences research. © 2011 by Annual Reviews. All rights reserved.

Holzwarth F.,University of Leipzig | Kahl A.,University of Leipzig | Bauhus J.,Albert Ludwigs University of Freiburg | Wirth C.,University of Leipzig
Journal of Ecology | Year: 2013

Partitioning of tree mortality into different modes of death allows the tracing and mechanistic modelling of individual key processes of forest dynamics each varying depending on site, species and individual risk factors. This, in turn, may improve long-term predictions of the development of old-growth forests. Six different individual tree mortality modes (uprooted and snapped (both with or without rot as a predisposing factor), standing dead and crushed by other trees) were analysed, and statistical models were derived for three tree species (European beech Fagus sylvatica, hornbeam Carpinus betulus and common ash Fraxinus excelsior) based on a repeated inventory of more than 13 000 trees in a 28 ha near-natural deciduous forest in Central Germany. The frequently described U-shaped curve of size-dependent mortality was observed in beech and hornbeam (but not ash) and could be explained by the joint operation of processes related to the six distinct mortality modes. The results for beech, the most abundant species, suggest that each mortality mode is prevalent in different life-history stages: small trees died mostly standing or being crushed, medium-sized trees had the highest chance of survival, and very large trees experienced increased rates of mortality, mainly by uprooting or snapping. Reduced growth as a predictor also played a role but only for standing dead, all other mortality modes showed no relationship to tree growth. Synthesis. Tree mortality can be partitioned into distinct processes, and species tend to differ in their susceptibility to one or more of them. This forms a fundamental basis for the understanding of forest dynamics in natural forests, and any mechanistic modelling of mortality in vegetation models could be improved by correctly addressing and formulating the various mortality processes. © 2012 The Authors. Journal of Ecology © 2012 British Ecological Society.

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.

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.

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.

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.

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.

Baumeister H.,Albert Ludwigs University of Freiburg | Baumeister H.,Black Dog Institute
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.

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.

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.

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.

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.

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.

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.

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..

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Ong A.C.M.,University of Sheffield | Ong A.C.M.,Sheffield Kidney Institute | Devuyst O.,University of Zurich | 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.

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.

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.

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.

Ren H.-P.,Xian 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.

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.

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.

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.

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.

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.

Conacci-Sorrell M.,Fred Hutchinson Cancer Research Center | Ngouenet C.,Fred Hutchinson Cancer Research Center | Anderson S.,Fred Hutchinson Cancer Research Center | Brabletz T.,Albert Ludwigs University of Freiburg | Eisenman R.N.,Fred Hutchinson Cancer Research Center
Genes and Development | Year: 2014

Evasion of apoptosis is critical in Myc-induced tumor progression. Here we report that cancer cells evade death under stress by activating calpain-mediated proteolysis of Myc. This generates Myc-nick, a cytoplasmic, transcriptionally inactive cleavage product of Myc. We found conversion of Myc into Myc-nick in cell lines and tissues derived from multiple cancers. In colon cancer, the production of Myc-nick is enhanced under stress conditions such as hypoxia and nutrient deprivation. Under these conditions, ectopic expression of Myc-nick promotes anchorage-independent growth and cell survival at least in part by promoting autophagy. Myc-nick also delays colon cancer cell death after treatment with chemotherapeutic drugs such as etoposide, cisplatin, and imatinib. Furthermore, colon cancer cells expressing a cleavage-resistant form of Myc undergo extensive apoptosis but are rescued by overexpression of Myc-nick. We also found that ectopic expression of Myc-nick results in the induction of the actin-bundling protein fascin, formation of filopodia, and increased cell motility-all mediators of tumor metastasis. Myc-nick-induced survival, autophagy, and motility require Myc box II (MBII), a region of Myc-nick that recruits acetyltransferases that in turn modify cytoplasmic proteins, including a-tubulin and ATG3. Our results suggest that Myc-nick-induced survival and motility contribute to colon cancer progression and metastasis. © 2014 Conacci-Sorrell et al.

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.

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.

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).

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.

Prinz M.,Albert Ludwigs University of Freiburg | Priller J.,Charite - 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Mei G.,Albert Ludwigs University of Freiburg
The Scientific World Journal | Year: 2014

Several key techniques in 3D geological modeling including planar mesh generation, spatial interpolation, and surface intersection are summarized in this paper. Note that these techniques are generic and widely used in various applications but play a key role in 3D geological modeling. There are two essential procedures in 3D geological modeling: the first is the simulation of geological interfaces using geometric surfaces and the second is the building of geological objects by means of various geometric computations such as the intersection of surfaces. Discrete geometric surfaces that represent geological interfaces can be generated by creating planar meshes first and then spatially interpolating; those surfaces intersect and then form volumes that represent three-dimensional geological objects such as rock bodies. In this paper, the most commonly used algorithms of the key techniques in 3D geological modeling are summarized. © 2014 Gang Mei.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

Manukyan M.,Albert Ludwigs University of Freiburg | Singh P.B.,Charite - 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.

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.

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.

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.

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.

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.

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.

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.

Mulhaupt R.,Albert Ludwigs University of Freiburg
Macromolecular Chemistry and Physics | Year: 2013

Dwindling fossil resources, surging energy demand and global warming stimulate growing demand for renewable polymer products with low carbon footprint. Going well beyond the limited scope of natural polymers, biomass conversion in biorefineries and chemical carbon dioxide fixation are teamed up with highly effective tailoring, processing and recycling of polymers. "Green monomers" from biorefineries, and "renewable oil", gained from plastics' and bio wastes, render synthetic polymers renewable without impairing their property profiles and recycling. In context of biofuel production, limitations of the green economy concepts are clearly visible. Dreams and reality of "green polymers" are highlighted. Regardless of their new greenish touch, highly versatile and cost-effective polymers play an essential role in sustainable development. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Berg I.A.,Albert Ludwigs University of Freiburg
Applied and Environmental Microbiology | Year: 2011

Autotrophic CO2 fixation represents the most important biosynthetic process in biology. Besides the wellknown Calvin-Benson cycle, five other totally different autotrophic mechanisms are known today. This minireview discusses the factors determining their distribution. As will be made clear, the observed diversity reflects the variety of the organisms and the ecological niches existing in nature. © 2011, American Society for Microbiology.

Fecher H.,Albert Ludwigs University of Freiburg
International Journal on Software Tools for Technology Transfer | Year: 2011

A key technique for the verification of programs is counterexample-guided abstraction-refinement (CEGAR). Grumberg et al. (LNCS, vol 3385, pp. 233-249. Springer, Berlin, 2005; Inf Comput 205(8):1130-1148, 2007) developed a CEGAR-based algorithm for the modal μ-calculus. There, every abstract state is split in a refinement step. In this paper, the work of Grumberg et al. is generalized by presenting a new CEGAR-based algorithm for the μ-calculus. It is based on a more expressive abstract model and applies refinement only locally (at a single abstract state), i. e., the lazy abstraction technique for safety properties is adapted to the μ-calculus. Furthermore, it separates refinement determination from the (3-valued based) model checking. Three different heuristics for refinement determination are presented and illustrated. © 2011 Springer-Verlag.

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

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

Stachon P.,Albert Ludwigs University of Freiburg
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2016

OBJECTIVE—: A solid body of evidence supports a role of extracellular ATP and its P2 receptors in innate and adaptive immunity. It promotes inflammation as a danger signal in various chronic inflammatory diseases. Thus, we hypothesize contribution of extracellular ATP and its receptor P2Y2 in vascular inflammation and atherosclerosis. APPROACH AND RESULTS—: Extracellular ATP induced leukocyte rolling, adhesion, and migration in vivo as assessed by intravital microscopy and in sterile peritonitis. To test the role of extracellular ATP in atherosclerosis, ATP or saline as control was injected intraperitoneally 3× a week in low-density lipoprotein receptor mice consuming high cholesterol diet. Atherosclerosis significantly increased after 16 weeks in ATP-treated mice (n=13; control group, 0.26 mm2; ATP group, 0.33 mm2; P=0.01). To gain into the role of ATP-receptor P2Y2 in ATP-induced leukocyte recruitment, ATP was administered systemically in P2Y2-deficient or P2Y2-competent mice. In P2Y2-deficient mice, the ATP-induced leukocyte adhesion was significantly reduced as assessed by intravital microscopy. P2Y2 expression in atherosclerosis was measured by real-time polymerase chain reaction and immunohistochemistry and demonstrates an increased expression mainly caused by influx of P2Y2-expressing macrophages. To investigate the functional role of P2Y2 in atherogenesis, P2Y2-deficient low-density lipoprotein receptor mice consumed high cholesterol diet. After 16 weeks, P2Y2-deficient mice showed significantly reduced atherosclerotic lesions with decreased macrophages compared with P2Y2-competent mice (n=11; aortic arch: control group, 0.25 mm; P2Y2-deficient, 0.14 mm2; P=0.04). Mechanistically, atherosclerotic lesions from P2Y2-deficient mice expressed less vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 RNA. CONCLUSIONS—: We show that extracellular ATP induces vascular inflammation and atherosclerosis via activation of P2Y2. © 2016 American Heart Association, Inc.

Portalupi S.,Albert Ludwigs University of Freiburg
Systematic reviews | Year: 2013

Methodological research has found that non-published studies often have different results than those that are published, a phenomenon known as publication bias. When results are not published, or are published selectively based on the direction or the strength of the findings, healthcare professionals and consumers of healthcare cannot base their decision-making on the full body of current evidence. As part of the OPEN project (http://www.open-project.eu) we will conduct a systematic review with the following objectives:1. To determine the proportion and/or rate of non-publication of studies by systematically reviewing methodological research projects that followed up a cohort of studies that a. received research ethics committee (REC) approval,b. were registered in trial registries, orc. were presented as abstracts at conferences.2. To assess the association of study characteristics (for example, direction and/or strength of findings) with likelihood of full publication.To identify reports of relevant methodological research projects we will conduct electronic database searches, check reference lists, and contact experts. Published and unpublished projects will be included. The inclusion criteria are as follows:a. RECs: methodological research projects that examined the subsequent proportion and/or rate of publication of studies that received approval from RECs;b. Trial registries: methodological research projects that examine the subsequent proportion and/or rate of publication of studies registered in trial registries;c. Conference abstracts: methodological research projects that examine the subsequent proportion and/or rate of full publication of studies which were initially presented at conferences as abstracts.Primary outcomes: Proportion/rate of published studies; time to full publication (mean/median; cumulative publication rate by time).Secondary outcomes: Association of study characteristics with full publication.The different questions (a, b, and c) will be investigated separately. Data synthesis will involve a combination of descriptive and statistical summaries of the included methodological research projects. Results are expected to be publicly available in mid 2013.

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.

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.

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.

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.

Einsle O.,Albert Ludwigs University of Freiburg
Methods in Enzymology | Year: 2011

Cytochrome c nitrite reductase, NrfA, catalyzes the six-electron reduction of nitrite, NO 2 -, to ammonium, NH 4 +, as the final enzymatic step in the dissimilatory metabolic pathway of nitrite ammonification within the biogeochemical nitrogen cycle. NrfA is a 5565 kDa protein that binds five c-type heme groups via thioether bonds to the cysteines of conserved CXXCH heme attachment motifs. Four of these heme groups are considered to be electron transfer centers, with two histidine residues as axial ligands. The remaining heme group features an unusual CXXCK-binding motif, making lysine the proximal axial ligand and leaving the distal position for the substrate binding site located in a secluded binding pocket within the protein. The substrate nitrite is coordinated to the active site heme iron though the free electron pair at the nitrogen atom and is reduced in a consecutive series of electron and proton transfers to the final product, the ammonium ion. While no intermediates of the reaction are released, NrfA is able to reduce various other nitrogen oxides such as nitric oxide (NO), hydroxylamine (H 2NOH), and nitrous oxide (N 2O), but notably also sulfite, providing the only known direct link between the nitrogen and sulfur cycles. NrfA invariably forms stable homodimers, but there are at least two distinct electron transfer systems to the enzyme. In many enterobacterial species, NrfA is linked to the menaquinol pool in the cytoplasmic membrane through a soluble electron carrier, NrfB, that in turn interacts with a membrane-integral quinol dehydrogenase, NrfCD. In δ- and ε-proteobacteria, the dimeric NrfA forms a complex with a small quinol dehydrogenase of the NapC/NirT family, NrfH, allowing a more efficient electron transfer. © 2011 Elsevier Inc. All rights reserved.

Liu B.-H.,Hefei University of Technology | Li L.,Hefei University of Technology | Huang Y.-F.,Hefei University of Technology | Li C.-F.,Hefei University of Technology | And 4 more authors.
Nature Physics | Year: 2011

Realistic quantum mechanical systems are always exposed to an external environment. This often induces Markovian processes in which the system loses information to its surroundings. However, many quantum systems exhibit non-Markovian behaviour with a flow of information from the environment back to the system. The environment usually consists of large number of degrees of freedom which are difficult to control, but some sophisticated schemes for reservoir engineering have been developed. The control of open systems plays a decisive role, for example, in proposals for entanglement generation and dissipative quantum computation, for the design of quantum memories and in quantum metrology. Here we report an all-optical experiment which allows one to drive the open system from the Markovian to the non-Markovian regime, to control the information flow between the system and the environment, and to determine the degree of non-Markovianity by measurements on the open system. © 2011 Macmillan Publishers Limited. All rights reserved.

Renkl A.,Albert Ludwigs University of Freiburg
Cognitive Science | Year: 2014

Learning from examples is a very effective means of initial cognitive skill acquisition. There is an enormous body of research on the specifics of this learning method. This article presents an instructionally oriented theory of example-based learning that integrates theoretical assumptions and findings from three research areas: learning from worked examples, observational learning, and analogical reasoning. This theory has descriptive and prescriptive elements. The descriptive subtheory deals with (a) the relevance and effectiveness of examples, (b) phases of skill acquisition, and (c) learning processes. The prescriptive subtheory proposes instructional principles that make full exploitation of the potential of example-based learning possible. © 2013 Cognitive Science Society, Inc.

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.

Li Y.,Albert Ludwigs University of Freiburg
European Journal of Human Genetics | Year: 2016

Whole-exome sequencing allows for an unbiased and comprehensive mutation screening. Although successfully used to facilitate the diagnosis of single-gene disorders, the genetic cause(s) of a substantial proportion of presumed monogenic diseases remain to be identified. We used whole-exome sequencing to examine offspring from a consanguineous marriage featuring a novel combination of congenital hypothyroidism, hypomagnesemia and hypercholesterolemia. Rather than identifying one causative variant, we report the first instance in which three independent autosomal-recessive single-gene disorders were identified in one patient. Together, the causal variants give rise to a blended and seemingly novel phenotype: we experimentally characterized a novel splice variant in the thyroglobulin gene (c.638+5G>A), resulting in skipping of exon 5, and detected a pathogenic splice variant in the magnesium transporter gene TRPM6 (c.2667+1G>A), causing familial hypomagnesemia. Based on the third variant, a stop variant in ABCG5 (p.(Arg446*)), we established a diagnosis of sitosterolemia, confirmed by elevated blood plant sterol levels and successfully initiated targeted lipid-lowering treatment. We propose that blended phenotypes resulting from several concomitant single-gene disorders in the same patient likely account for a proportion of presumed monogenic disorders of currently unknown cause and contribute to variable genotype-phenotype correlations.European Journal of Human Genetics advance online publication, 27 January 2016; doi:10.1038/ejhg.2015.285. © 2016 Macmillan Publishers Limited

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.

Neumann-Haefelin C.,Albert Ludwigs University of Freiburg
Current Opinion in Rheumatology | Year: 2013

PURPOSE OF REVIEW: HLA-B27 is associated with low viral load and long-term nonprogression in HIV infection as well as spontaneous clearance of hepatitis C virus (HCV) infection. This review summarizes mechanisms that have been suggested to be involved in this protective effect of HLA-B27, and highlights possible lessons for the role of HLA-B27 in spondyloarthritis. RECENT FINDINGS: Recent studies linked protection by HLA-B27 in HIV and HCV infection to virological mechanisms such as a complicated pathways of viral escape from immunodominant HLA-B27-restricted virus-specific CD8+ T-cell epitopes. In addition, several immunological mechanisms have been proposed, including CD8+ T-cell polyfunctionality and functional avidity, thymic selection of CD8+ T-cell precursors, specific T-cell receptor repertoires and clonotypes, efficient antigen processing, and evasion from regulatory T-cell-mediated suppression. SUMMARY: Multiple virological and immunological mechanisms have been suggested to contribute to HLA-B27-mediated protection in HIV and HCV infection. Some of these mechanisms may also be involved in HLA-B27-associated pathogenesis in spondyloarthritis. © 2013 Wolters Kluwer Health / Lippincott Williams & Wilkins.

Schilling O.,Albert Ludwigs University of Freiburg | Huesgen P.F.,University of British Columbia | Barre O.,University of British Columbia | Auf Dem Keller U.,ETH Zurich | Overall C.M.,University of British Columbia
Nature Protocols | Year: 2011

To link cleaved substrates in complex systems with a specific protease, the protease active site specificity is required. Proteomic identification of cleavage sites (PICS) simultaneously determines both the prime- and non-prime-side specificities of individual proteases through identification of hundreds of individual cleavage sequences from biologically relevant, proteome-derived peptide libraries. PICS also identifies subsite cooperativity. To generate PICS peptide libraries, cellular proteomes are digested with a specific protease such as trypsin. Following protease inactivation, primary amines are protected. After incubation with a test protease, each prime-side cleavage fragment has a free newly formed N-terminus, which is biotinylated for affinity isolation and identification by liquid chromatographyg-tandem mass spectrometry. The corresponding non-prime sequences are derived bioinformatically. The step-by-step protocol also presents a web service for PICS data analysis, as well as introducing and validating PICS peptide libraries made from Escherichia coli. © 2010 Nature America, Inc. All rights reserved.

Jiang D.-E.,Oak Ridge National Laboratory | Walter M.,Albert Ludwigs University of Freiburg
Nanoscale | Year: 2012

Is it possible to replace all the thiolates in a thiolated gold nanocluster with halogens while still maintaining the geometry and the electronic structure? In this work, we show from density functional theory that such halogen analogs of thiolated gold nanoclusters are highly likely. Using Au 25X 18 - as an example, where X = F, Cl, Br, or I replaces -SR, we find that Au 25Cl 18 - demonstrates a high similarity to Au 25(SR) 18 - by showing Au-Cl distances, Cl-Au-Cl angles, band gap, and frontier orbitals similar to those in Au 25(SR) 18 -. DFT-based global minimization also indicates the energetic preference of staple formation for the Au 25Cl 18 - cluster. The similarity between Au m(SR) n and Au mX n could be exploited to make viable Au mX n clusters and to predict structures for Au m(SR) n. This journal is © 2012 The Royal Society of Chemistry.

Denner A.,Paul Scherrer Institute | Dittmaier S.,Albert Ludwigs University of Freiburg
Nuclear Physics B | Year: 2011

We provide a complete set of results for the scalar 4-point function appearing in one-loop calculations in QCD, QED, the electroweak Standard Model and popular extensions thereof. Complex internal masses, which are needed for calculations involving unstable particles, are supported throughout, whereas complex momenta are not supported. In particular, for the most general, regular case we present two independent results in terms of 72 and 32 dilogarithms. In addition we list explicit results for all soft- and/or collinear-singular cases in dimensional regularization, mass regularization, and in regularizations of mixed type. The exceptional case with a vanishing modified Cayley determinant, which hardly appears in applications, is not considered. © 2010 Elsevier B.V.

Spillmann L.,Albert Ludwigs University of Freiburg
Perception | Year: 2014

This paper traces the history of the visual receptive field (RF) from Hartline to Hubel and Wiesel. Hartline (1938, 1940) found that an isolated optic nerve fiber in the frog could be excited by light falling on a small circular area of the retina. He called this area the RF, using a term first introduced by Sherrington (1906) in the tactile domain. In 1953 Kuffler discovered the antagonistic center–surround organization of cat RFs, and Barlow, Fitzhugh, and Kuffler (1957) extended this work to stimulus size and state of adaptation. Shortly thereafter, Lettvin and colleagues (1959) in an iconic paper asked “what the frog’s eye tells the frog’s brain”. Meanwhile, Jung and colleagues (1952–1973) searched for the perceptual correlates of neuronal responses, and Jung and Spillmann (1970) proposed the term perceptive field (PF) as a psychophysical correlate of the RF. The Westheimer function (1967) enabled psychophysical measurements of the PF center and surround in human and monkey, which correlated closely with the underlying RF organization. The sixties and seventies were marked by rapid progress in RF research. Hubel and Wiesel (1959–1974), recording from neurons in the visual cortex of the cat and monkey, found elongated RFs selective for the shape, orientation, and position of the stimulus, as well as for movement direction and ocularity. These findings prompted the emergence in visual psychophysics of the concept of feature detectors selective for lines, bars, and edges, and contributed to a model of the RF in terms of difference of Gaussians (DOG) and Fourier channels. The distinction between simple, complex, and hypercomplex neurons followed. Although RF size increases towards the peripheral retina, its cortical representation remains constant due to the reciprocal relationship with the cortical magnification factor (M). This constitutes a uniform yardstick for M-scaled stimuli across the retina. Developmental studies have shown that RF properties are not fixed. RFs possess their full response inventory already at birth, but require the interaction with appropriate stimuli within a critical time window for refinement and consolidation. Taken together these findings paved the way for a better understanding of how objective properties of the external world are encoded to become subjective properties of the subjective, perceptual world. © 2014 a Pion publication.

Peano V.,Albert Ludwigs University of Freiburg | Thorwart M.,University of Hamburg
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

We analyze the driven resonantly coupled Jaynes-Cummings model in terms of a quasienergy approach by switching to a frame rotating with the external modulation frequency and by using the dressed atom picture. A quasienergy surface in phase space emerges whose level spacing is governed by a rescaled effective Planck constant. Moreover, the well-known multiphoton transitions can be reinterpreted as resonant tunneling transitions from the local maximum of the quasienergy surface. Most importantly, the driving defines a quasienergy well which is nonperturbative in nature. The quantum-mechanical quasienergy state localized at its bottom is squeezed. In the Purcell-limited regime, the potential well is metastable and the effective local temperature close to its minimum is uniquely determined by the squeezing factor. The activation occurs in this case via dressed spin-flip transitions rather than via quantum activation as in other driven nonlinear quantum systems such as the quantum Duffing oscillator. The local maximum is, in general, stable. However, in presence of resonant coherent or dissipative tunneling transitions the system can escape from it and a stationary state arises as a statistical mixture of quasienergy states being localized in the two basins of attraction. This gives rise to a resonant or an antiresonant nonlinear response of the cavity at multiphoton transitions. The model finds direct application in recent experiments with a driven superconducting circuit quantum electrodynamics setup. © 2010 The American Physical Society.

Kirschner J.,Albert Ludwigs University of Freiburg
Handbook of Clinical Neurology | Year: 2013

The congenital muscular dystrophies are a heterogeneous group of disorders in which weakness and dystrophic pattern on muscle biopsy are present at birth or during the first months of life. This chapter reviews the most common forms of congenital muscular dystrophies, including laminin α-2 (merosin) deficiency, Ullrich congenital muscular dystrophy, fukutin-related proteinopathy, rigid spine syndrome, and glycosylation disorders of α-dystroglycan. The latter group is often associated with neuronal migration defects including lissencephaly, pachygyria, cerebellar and brainstem abnormalities, and variable ocular anomalies. Typical clinical findings and underlying genetic defects are discussed to assist in the differential diagnosis and diagnostic work-up of patients with congenital muscular dystrophies. There are still no curative treatment options for patients with congenital muscular dystrophies but regular follow-up and symptomatic care by a multidisciplinary team considering the peculiarities of each disorder are important to maintain or improve patients' quality of life. © 2013 Elsevier B.V.

Korinthenberg R.,Albert Ludwigs University of Freiburg
Handbook of Clinical Neurology | Year: 2013

Guillain-Barré syndrome (GBS) is an acute, immune-mediated, postinfectious polyneuropathy with symmetrical ascending weakness, diminished deep tendon reflexes, and nonspecific sensory symptoms. CSF protein is raised with normal or only slightly elevated cell count. Based on electrophysiological and pathological findings, a demyelinating variant (acute inflammatory demyelinating polyneuropathy, AIDP) and an axonal variant (acute motor axonal neuropathy, AMAN) can be differentiated. Molecular mimicry with common epitopes between infective agents and peripheral nerves is discussed as an important pathophysiological principle. The symptoms progress for a mean of 10 days (up to 4 weeks) and after a plateau of 1-2 weeks remit spontaneously. At the height of the disease 60% of children are unable to walk and 10-15% need artificial ventilation. Treatment with plasmapheresis and intravenous immunoglobulins (IVIG) has been proven in placebo-controlled studies in adults with severe disease to speed up recovery significantly. In children, mostly open studies have shown similar treatment effects, although their spontaneous course is frequently less severe. Children with GBS should be treated with IVIG when they have lost the ability to walk, or when they are still deteriorating significantly and are expected to lose the ability to walk. The long-term prognosis is more favorable than that in adults. Whereas 25% of patients maintain mild neurological symptoms and signs, disability in the long term is very rare and usually due to complications such as myelitic involvement or chronic inflammatory demyelinating polyneuropathy (CIDP). © 2013 Elsevier B.V.

Protein crystals are of wide-spread interest because many of them allow structure analyses at atomic resolution. For soluble proteins, the packing density of such crystals is distributed according to the Matthews Graph. For integral membrane proteins, the respective graph is similar but at lower density and much broader. By visualizing the relative positions and orientations of membrane proteins in crystals, it has been suggested that the detergent micelles surrounding these proteins form sheets, filaments, or remain isolated in the crystal giving rise to three distinct packing density distributions that superimpose to form the observed broad distribution. This classification was indirect because detergent is not visible in X-ray crystallography. Given the extensive work involved in analyzing detergent structure directly by neutron diffraction, it seems unlikely that a statistically relevant number of them will be established in the near future. Therefore, the proposed classification is here scrutinized by a simulation in which an average detergent-carrying membrane protein was randomly packed to form crystals. The analysis reproduced the three types of detergent structures together with their packing density distributions and relative frequencies, which validates the previous classification. The simulation program was also run for crystals from soluble proteins using ellipsoids as reference shapes and defining a shape factor that quantifies the deviation from the nearest ellipsoid. This series reproduced and thus explained the Matthews Graph. Published by Wiley-Blackwell. © 2011 The Protein Society.

Schulz G.E.,Albert Ludwigs University of Freiburg
Journal of Molecular Biology | Year: 2011

Although being much smaller than the number of soluble proteins in the Protein Data Bank, the number of membrane proteins therein now approaches 700, and a statistical analysis becomes meaningful. Such an analysis showed that the conventional subdivision into monotopic, β-barrel and α-helical membrane proteins is appropriate but should be amended by a classification according to the detergent micelle structure in the crystal, which can be derived from the packing of the membrane-immersed parts of the proteins. The crystal packing density is specific for the three conventional types of membrane proteins and soluble proteins. It is also specific for three observed detergent arrangements that are micelle pockets, micelle filaments and micelle sheets, demonstrating that the detergent structure affects crystallization. The packing density distribution of crystals from integral membrane proteins has approximately the same shape as that of soluble proteins but is by a factor of two broader and shifted to lower density. It seems unlikely that the differences can be explained by a mere solvent expansion due to the required detergent. The crystallized membrane proteins were further analyzed with respect to protein mass, oligomerization and crystallographic asymmetric unit, space group, crystal ordering and symmetry. The results provide a new view on membrane proteins. © 2011 Elsevier Ltd. All rights reserved.

Bruckner-Tuderman L.,Albert Ludwigs University of Freiburg
Dermatologic Clinics | Year: 2010

Dystrophic epidermolysis bullosa (DEB) is relatively well understood. Potential therapies are in development. This article describes the pathogenesis and clinical features of DEB. It also describes therapeutic options and the future of molecular therapies. © 2010 Elsevier Inc. All rights reserved.

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.

Franca V.V.,Albert Ludwigs University of Freiburg | Vieira D.,Santa Catarina State University | Capelle K.,Federal University of ABC
New Journal of Physics | Year: 2012

Simple analytical parameterizations for the ground-state energy of the one-dimensional repulsive Hubbard model are developed. The charge dependence of energy is parameterized using exact results extracted from the Bethe-ansatz (BA). The resulting parameterization is shown to be in better agreement with highly precise data obtained from a fully numerical solution to the BA equations than previous expressions (Lima et al 2003 Phys. Rev. Lett. 90 146402). Unlike these earlier proposals, the present parameterization correctly predicts a positive Mott gap at half filling for any U > 0. The construction is extended to spin-dependent phenomena by parameterizing the magnetization dependence of the ground-state energy using further exact results and numerical benchmarking. Lastly, the parameterizations developed for the spatially uniform model are extended by means of a simple local-density-type approximation to spatially inhomogeneous models, e.g. in the presence of impurities, external fields or trapping potentials. The results are shown to be in excellent agreement with independent many-body calculations, at a fraction of the computational cost. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.

Onichtchouk D.,Albert Ludwigs University of Freiburg
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2016

PouV class transcription factor Oct4/Pou5f1 is a central regulator of indefinite pluripotency in mammalian embryonic stem cells (ESCs) but also participates in cell lineage specification in mouse embryos and in differentiating cell cultures. The molecular basis for this versatility, which is shared between Oct4 and its non-mammalian homologs Pou5f1 and Pou5f3, is not yet completely understood. Here, I review the current understanding of the evolution of PouV class transcription factors and discuss equivalent and diverse roles of Oct4 homologs in pluripotency, differentiation, and cell behavior in different vertebrate embryos. This article is part of a Special Issue entitled: The Oct Transcription Factor Family, edited by Dr. Dean Tantin. © 2016 Elsevier B.V.

Fearon K.,University of Edinburgh | Arends J.,Albert Ludwigs University of Freiburg | Baracos V.,University of Alberta
Nature Reviews Clinical Oncology | Year: 2013

Cancer cachexia is a metabolic syndrome that can be present even in the absence of weight loss ('precachexia'). Cachexia is often compounded by pre-existing muscle loss, and is exacerbated by cancer therapy. Furthermore, cachexia is frequently obscured by obesity, leading to under-diagnosis and excess mortality. Muscle wasting (the signal event in cachexia) is associated not only with reduced quality of life, but also markedly increased toxicity from chemotherapy. Many of the primary events driving cachexia are likely mediated via the central nervous system and include inflammation-related anorexia and hypoanabolism or hypercatabolism. Treatment of cachexia should be initiated early. In addition to active management of secondary causes of anorexia (such as pain and nausea), therapy should target reduced food intake (nutritional support), inflammation-related metabolic change (anti-inflammatory drugs or nutrients) and reduced physical activity (resistance exercise). Advances in the understanding of the molecular biology of the brain, immune system and skeletal muscle have provided novel targets for the treatment of cachexia. The combination of therapies into a standard multimodal package coupled with the development of novel therapeutics promises a new era in supportive oncology whereby quality of life and tolerance to cancer therapy could be improved considerably.

Domes G.,Albert Ludwigs University of Freiburg
Psychological medicine | Year: 2013

The neuropeptide oxytocin (OT) has positive effects on the processing of emotional stimuli such as facial expressions. To date, research has focused primarily on conditions of overt visual attention. We investigated whether a single intranasal dose of OT (24 IU) would modulate the allocation of attentional resources towards positive and negative facial expressions using a dot-probe paradigm in a sample of 69 healthy men. Attentional capacity for these facial cues was limited by presentation time (100 or 500 ms). In addition, we controlled for overt visual attention by recording eye movements using a remote eye tracker. Reaction times (RTs) in the dot-probe paradigm revealed a pronounced shift of attention towards happy facial expressions presented for 100 ms after OT administration, whereas there were no OT-induced effects for longer presentation times (500 ms). The results could not be attributed to modulations of overt visual attention as no substance effects on gazes towards the facial target were observed. The results suggest that OT increased covert attention to happy faces, thereby supporting the hypothesis that OT modulates early attentional processes that might promote prosocial behavior.

Gonik M.A.,Center for Material Researches Photon | Croll A.,Albert Ludwigs University of Freiburg
CrystEngComm | Year: 2013

An additional heater, similar to the axial heating process setup (AHP heater), was used in crystal growth of Si and its compound with 20% at Ge by the Floating Zone (FZ) method with the purpose of controlling both the shape of the melt-crystal interface and the thermal conditions at the interfaces during the run. The heater shapes the melt zone around itself by surface tension forces, being suspended between the growing crystal and feed rod. To protect the graphite casing of the heater against the aggressive action of molten silicon, the casing surface was coated with SiC having a special nano-crystalline structure. The range of the melt layer thickness, which one could establish as high as possible for the stability of the shaping process, was found to be up to 20 mm. Grown As- doped Si single crystals with a diameter of up to 15 mm was shown to have strong twinning directly caused by presence of the SiC inclusions revealed in the bulk of a crystal. The possibility of reducing the convexity and produce an interface close to a flat shape by means of the AHP heater was proved. Faceted growth of Si was found to be present in crystal growth on [111]-oriented seeds, with the faceted area occupying almost all of the cross section of the crystal under certain conditions. © 2013 The Royal Society of Chemistry.

Shastri V.P.,Albert Ludwigs University of Freiburg
MRS Bulletin | Year: 2015

Biomineralization is the process by which living organisms orchestrate the synthesis and organization of minerals (biominerals), and it may be viewed as an ancient process for accumulation of metal ions in living systems. The structure and properties of biominerals have yet to be rivaled by any synthetic effort by scientists to date. Therefore, deciphering the assembly algorithms and the components that initiate and promote hierarchical deposition of cations has signifi cant implications for the development of nanocomposites and nanotechnology as a whole. This issue of MRS Bulletin highlights some of the challenges in characterizing and replicating the biomineralization processes, and the role of non-collagenous proteins in the biomineralization process. © 2015 Materials Research Society.

Quax T.E.F.,Wageningen University | Quax T.E.F.,Albert Ludwigs University of Freiburg | Claassens N.J.,Wageningen University | Soll D.,Yale University | van der Oost J.,Wageningen University
Molecular Cell | Year: 2015

The redundancy of the genetic code implies that most amino acids are encoded by multiple synonymous codons. In all domains of life, a biased frequency of synonymous codons is observed at the genome level, in functionally related genes (e.g., in operons), and within single genes. Other codon bias variants include biased codon pairs and codon co-occurrence. Although translation initiation is the key step in protein synthesis, it is generally accepted that codon bias contributes to translation efficiency by tuning the elongation rate of the process. Moreover, codon bias plays an important role in controlling a multitude of cellular processes, ranging from differential protein production to protein folding. Here we review currently known types of codon bias and how they may influence translation. We discuss how understanding the principles of codon bias and translation can contribute to improved protein production and developments in synthetic biology. © 2015 Elsevier Inc.

Spath P.,Albert Ludwigs University of Freiburg
Sustainability | Year: 2012

Regional initiatives pursuing self-sufficiency through the use of renewable energy sources (RESS-initiatives) aim at contributing to broader transitions towards more sustainable energy systems. As such, they have raised high expectations among local activists and are increasingly supported by diverse funding schemes such as national programs. How can the social dynamics entangled in these initiatives be understood and assessed? A discourse analytical perspective, such as the Argumentative Discourse Analysis developed by Hajer, can bring valuable insights in this regard. This approach highlights the formation of discourse coalitions and processes of discourse structuration and institutionalization. In order to illustrate my conceptual and methodological considerations, I present an analysis of discursive dynamics observed in the alpine district of Murau, Austria, where the vision of reaching 'energy autarky' by the year 2015 has influenced regional development plans since 2003. The chosen discourse analytical approach has been very helpful in guiding the analysis of this case. Specific local conditions can explain why certain visions gained discursive hegemony. © 2012 by the author.

Lussi A.,University of Bern | Hellwig E.,Albert Ludwigs University of Freiburg
Monographs in Oral Science | Year: 2014

A prerequisite for preventive measures is to diagnose erosive tooth wear and to evaluate the different etiological factors in order to identify persons at risk. No diagnostic device is available for the assessment of erosive defects. Thus, they can only be detected clinically. Consequently, erosion not diagnosed at an early stage may render timely preventive measures difficult. In order to assess the risk factors, patients should record their dietary intake for a distinct period of time. Then a dentist can determine the erosive potential of the diet. A table with common beverages and foodstuffs is presented for judging the erosive potential. Particularly, patients with more than 4 dietary acid intakes have a higher risk for erosion when other risk factors are present. Regurgitation of gastric acids is a further important risk factor for the development of erosion which has to be taken into account. Based on these analyses, an individually tailored preventive program may be suggested to the patients. It may comprise dietary advice, use of calcium-enriched beverages, optimization of prophylactic regimes, stimulation of salivary flow rate, use of buffering medicaments and particular motivation for nondestructive toothbrushing habits with an erosive-protecting toothpaste as well as rinsing solutions. Since erosion and abrasion often occur simultaneously, all of the causative components must be taken into consideration when planning preventive strategies but only those important and feasible for an individual should be communicated to the patient. © 2014 S. Karger AG, Basel.

Niemeyer C.M.,Albert Ludwigs University of Freiburg
Nature genetics | Year: 2010

CBL encodes a member of the Cbl family of proteins, which functions as an E3 ubiquitin ligase. We describe a dominant developmental disorder resulting from germline missense CBL mutations, which is characterized by impaired growth, developmental delay, cryptorchidism and a predisposition to juvenile myelomonocytic leukemia (JMML). Some individuals experienced spontaneous regression of their JMML but developed vasculitis later in life. Importantly, JMML specimens from affected children show loss of the normal CBL allele through acquired isodisomy. Consistent with these genetic data, the common p.371Y>H altered Cbl protein induces cytokine-independent growth and constitutive phosphorylation of ERK, AKT and S6 only in hematopoietic cells in which normal Cbl expression is reduced by RNA interference. We conclude that germline CBL mutations have developmental, tumorigenic and functional consequences that resemble disorders that are caused by hyperactive Ras/Raf/MEK/ERK signaling and include neurofibromatosis type 1, Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome and Legius syndrome.

Breuer H.-P.,Albert Ludwigs University of Freiburg | Laine E.-M.,Aalto University | Laine E.-M.,University of Turku | Piilo J.,University of Turku | And 2 more authors.
Reviews of Modern Physics | Year: 2016

The dynamical behavior of open quantum systems plays a key role in many applications of quantum mechanics, examples ranging from fundamental problems, such as the environment-induced decay of quantum coherence and relaxation in many-body systems, to applications in condensed matter theory, quantum transport, quantum chemistry, and quantum information. In close analogy to a classical Markovian stochastic process, the interaction of an open quantum system with a noisy environment is often modeled phenomenologically by means of a dynamical semigroup with a corresponding time-independent generator in Lindblad form, which describes a memoryless dynamics of the open system typically leading to an irreversible loss of characteristic quantum features. However, in many applications open systems exhibit pronounced memory effects and a revival of genuine quantum properties such as quantum coherence, correlations, and entanglement. Here recent theoretical results on the rich non-Markovian quantum dynamics of open systems are discussed, paying particular attention to the rigorous mathematical definition, to the physical interpretation and classification, as well as to the quantification of quantum memory effects. The general theory is illustrated by a series of physical examples. The analysis reveals that memory effects of the open system dynamics reflect characteristic features of the environment which opens a new perspective for applications, namely, to exploit a small open system as a quantum probe signifying nontrivial features of the environment it is interacting with. This Colloquium further explores the various physical sources of non-Markovian quantum dynamics, such as structured environmental spectral densities, nonlocal correlations between environmental degrees of freedom, and correlations in the initial system-environment state, in addition to developing schemes for their local detection. Recent experiments addressing the detection, quantification, and control of non-Markovian quantum dynamics are also briefly discussed. © 2016 American Physical Society.

Knobeloch K.-P.,Albert Ludwigs University of Freiburg
Sub-Cellular Biochemistry | Year: 2010

This chapterrecapitulates our current knowledge aboutthe functions of the interferon stimulated gene 15 (ISG15) system in vivo with a specific focus on physiological aspects and the biological relevance of ISG15 conjugation and deconjugation. ISG15 contains two domains with structural similarity to ubiquitin and was the first ubiquitin like modifier (UBL) described. It can be conjugated to protein substrates in a process similar to ubiquitin modification termed ISGylation. Of all ubiquitin like modifications ISGylation exhibits the highest degree of interlace with the ubiquitin system and distinct ubiquitin ligases and isopeptidases can also mediate ISG15 linkage and deconjugation, respectively. The system is strongly induced by Type I interferons or microbial infections and studies based on gene targeted mice have shown that it plays an important role in antiviral defence. ©2010 Landes Bioscience and Springer Science+Business Media.

Valido A.,Integrative Ecology Group | Schaefer H.M.,Albert Ludwigs University of Freiburg | Jordano P.,Integrative Ecology Group
Journal of Evolutionary Biology | Year: 2011

The functional or structural linkage among traits [phenotypic integration (PI)] within complex structures can constrain the evolutionary response of individual traits. To analyse whether frugivores with distinct sensory ecology have shaped the patterns of fruit diversification differently, we compared PI values of fleshy fruits that are consumed by birds and mammals. We used phylogenetic comparative analyses of PI among 13 morphological, nutritional and visual fruit traits from 111 Mediterranean plant species. Results showed that morphological traits had higher PI values than nutritional and colour traits. Visual and nutritional traits show positive phylogenetic covariance, while negative covariation occurs between fruits size and nutrients. Importantly, fruits consumed by birds were relatively more integrated than fruits consumed partly or solely by mammals. Hence, we show that major groups of mutualistic frugivores can shape the covariance among some fruit traits differently and thereby influence fruit diversification. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

Stoffers J.M.,Albert Ludwigs University of Freiburg
Cochrane database of systematic reviews (Online) | Year: 2012

Psychotherapy is regarded as the first-line treatment for people with borderline personality disorder. In recent years, several disorder-specific interventions have been developed. This is an update of a review published in the Cochrane Database of Systematic Reviews in 2006. To assess the effects of psychological interventions for borderline personality disorder (BPD). We searched the following databases: CENTRAL 2010(3), MEDLINE (1950 to October 2010), EMBASE (1980 to 2010, week 39), ASSIA (1987 to November 2010), BIOSIS (1985 to October 2010), CINAHL (1982 to October 2010), Dissertation Abstracts International (31 January 2011), National Criminal Justice Reference Service Abstracts (15 October 2010), PsycINFO (1872 to October Week 1 2010), Science Citation Index (1970 to 10 October 2010), Social Science Citation Index (1970 to 10 October 2010), Sociological Abstracts (1963 to October 2010), ZETOC (15 October 2010) and the metaRegister of Controlled Trials (15 October 2010). In addition, we searched Dissertation Abstracts International in January 2011 and ICTRP in August 2011. Randomised studies with samples of patients with BPD comparing a specific psychotherapeutic intervention against a control intervention without any specific mode of action or against a comparative specific psychotherapeutic intervention. Outcomes included overall BPD severity, BPD symptoms (DSM-IV criteria), psychopathology associated with but not specific to BPD, attrition and adverse effects. Two review authors independently selected studies, assessed the risk of bias in the studies and extracted data. Twenty-eight studies involving a total of 1804 participants with BPD were included. Interventions were classified as comprehensive psychotherapies if they included individual psychotherapy as a substantial part of the treatment programme, or as non-comprehensive if they did not.Among comprehensive psychotherapies, dialectical behaviour therapy (DBT), mentalisation-based treatment in a partial hospitalisation setting (MBT-PH), outpatient MBT (MBT-out), transference-focused therapy (TFP), cognitive behavioural therapy (CBT), dynamic deconstructive psychotherapy (DDP), interpersonal psychotherapy (IPT) and interpersonal therapy for BPD (IPT-BPD) were tested against a control condition. Direct comparisons of comprehensive psychotherapies included DBT versus client-centered therapy (CCT); schema-focused therapy (SFT) versus TFP; SFT versus SFT plus telephone availability of therapist in case of crisis (SFT+TA); cognitive therapy (CT) versus CCT, and CT versus IPT.Non-comprehensive psychotherapeutic interventions comprised DBT-group skills training only (DBT-ST), emotion regulation group therapy (ERG), schema-focused group therapy (SFT-G), systems training for emotional predictability and problem solving for borderline personality disorder (STEPPS), STEPPS plus individual therapy (STEPPS+IT), manual-assisted cognitive treatment (MACT) and psychoeducation (PE).

Albers S.,Albert Ludwigs University of Freiburg
Algorithmica (New York) | Year: 2010

We study web caching with request reordering. The goal is to maintain a cache of web documents so that a sequence of requests can be served at low cost. To improve cache hit rates, a limited reordering of requests is allowed. Feder et al. (Proceedings of the 13th ACM-SIAM Symposium on Discrete Algorithms, pp. 104-105, 2002), who recently introduced this problem, considered caches of size 1, i.e. a cache can store one document. They presented an offline algorithm based on dynamic programming as well as online algorithms that achieve constant factor competitive ratios. For arbitrary cache sizes, Feder et al. (Theor. Comput. Sci. 324:201-218, 2004) gave online strategies that have nearly optimal competitive ratios in several cost models. In this paper we first present a deterministic online algorithm that achieves an optimal competitiveness, for the most general cost model and all cache sizes. We then investigate the offline problem, which is NP-hard in general. We develop the first polynomial time algorithms that can manage arbitrary cache sizes. Our strategies achieve small constant factor approximation ratios. The algorithms are based on a general technique that reduces web caching with request reordering to a problem of computing batched service schedules. Our approximation result for the Fault Model also improves upon the best previous approximation guarantee known for web caching without request reordering. We remark that, unlike Feder et al.; we assume that bypassing is allowed, i.e. referenced documents do not necessarily have to be brought into cache to serve their requests. © 2009 Springer Science+Business Media, LLC.

Pokalyuk C.,Albert Ludwigs University of Freiburg
Journal of Mathematical Biology | Year: 2012

A selective sweep describes the reduction of diversity due to strong positive selection. If the mutation rate to a selectively beneficial allele is sufficiently high, Pennings and Hermisson (Mol Biol Evol 23(5):1076-1084, 2006a) have shown, that it becomes likely, that a selective sweep is caused by several individuals. Such an event is called a soft sweep and the complementary event of a single origin of the beneficial allele, the classical case, a hard sweep. We give analytical expressions for the linkage disequilibrium (LD) between two neutral loci linked to the selected locus, depending on the recurrent mutation to the beneficial allele, measured by D and, a quantity introduced by Ohta and Kimura (Genetics 63(1):229-238, 1969), and conclude that the LD-pattern of a soft sweep differs substantially from that of a hard sweep due to haplotype structure. The analytical results are compared with simulations. © 2011 Springer-Verlag.

Meerpohl J.J.,Albert Ludwigs University of Freiburg
Cochrane database of systematic reviews (Online) | Year: 2012

Thalassemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusion. Iron chelation therapy is needed to prevent long-term complications.Both deferoxamine and deferiprone have been found to be efficacious. However, a systematic review of the effectiveness and safety of the new oral chelator deferasirox in people with thalassaemia is needed. To assess the effectiveness and safety of oral deferasirox in people with thalassaemia and secondary iron overload. We searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We also 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/. Date of the most recent searches of these databases: 24 June 2010.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 03 November 2011. Randomised controlled trials comparing deferasirox with no therapy or placebo or with another iron chelating treatment. Two authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. Four studies met the inclusion criteria.Two studies compared deferasirox to placebo or standard therapy of deferoxamine (n = 47). The placebo-controlled studies, a pharmacokinetic and a dose escalation study, showed that deferasirox leads to net iron excretion in transfusion-dependent thalassaemia patients. In these studies, safety was acceptable and further investigation in phase II and phase III trials was warranted.Two studies, one phase II study (n = 71) and one phase III study (n = 586) compared deferasirox to standard treatment with deferoxamine. Data suggest that a similar efficacy can be achieved depending on the ratio of doses of deferoxamine and deferasirox being compared; in the phase III trial, similar or superior efficacy for surrogate parameters of ferritin and liver iron concentration could only be achieved in the highly iron-overloaded subgroup at a mean ratio of 1 mg of deferasirox to 1.8 mg of deferoxamine corresponding to a mean dose of 28.2 mg/d and 51.6 mg/d respectively. Data on safety at the presumably required doses for effective chelation therapy are limited. Patient satisfaction was significantly better with deferasirox, while rate of discontinuations was similar for both drugs. Deferasirox offers an important alternative line of treatment for people with thalassaemia and secondary iron overload. Based on the available data, deferasirox does not seem to be superior to deferoxamine at the usually recommended ratio of 1 mg of deferasirox to 2 mg of deferoxamine. However, similar efficacy seems to be achievable depending on the dose and ratio of deferasirox compared to deferoxamine. Whether this will result in similar efficacy in the long run and will translate to similar benefits as has been shown for deferoxamine, needs to be confirmed. Data on safety, particularly on rare toxicities and long-term safety, are still limited.Therefore, we think that deferasirox should be offered as an alternative to all patients with thalassaemia who either show intolerance to deferoxamine or poor compliance with deferoxamine. In our opinion, data are still too limited to support the general recommendation of deferasirox as first-line treatment instead of deferoxamine. If a strong preference for deferasirox is expressed, it could be offered as first-line option to individual patients after a detailed discussion of the potential benefits and risks.

Schneider R.,Albert Ludwigs University of Freiburg
Discrete and Computational Geometry | Year: 2010

In the random mosaic generated by a stationary Poisson hyperplane process in ℝd, we consider the typical k-face weighted by the j-dimensional volume of the j-skeleton (0≤j≤k≤d). We prove sharp lower and upper bounds for the expected number of its vertices. © 2010 Springer Science+Business Media, LLC.

Hiller J.,Technical University of Denmark | Reindl L.M.,Albert Ludwigs University of Freiburg
Measurement: Journal of the International Measurement Confederation | Year: 2012

The knowledge of measurement uncertainty is of great importance in conformance testing in production. The tolerance limit for production must be reduced by the amounts of measurement uncertainty to ensure that the parts are in fact within the tolerance. Over the last 5 years, industrial X-ray computed tomography (CT) has become an important technology for dimensional quality control. In this paper a computer simulation platform is presented which is able to investigate error sources in dimensional CT measurements. The typical workflow in industrial CT metrology is described and methods for estimating measurement uncertainties are briefly discussed. As we will show, the developed virtual CT (VCT) simulator can be adapted to various scanner systems, providing realistic CT data. Using the Monte Carlo method (MCM), measurement uncertainties for a given measuring task can be estimated, taking into account the main error sources for the measurement. This method has the potential to deal with all kinds of systematic and random errors that influence a dimensional CT measurement. A case study demonstrates the practical application of the VCT simulator using numerically generated CT data and statistical evaluation methods. © 2012 Elsevier Ltd. All rights reserved.

Schulz G.E.,Albert Ludwigs University of Freiburg
Journal of Molecular Biology | Year: 2010

The fact that aggregates of identical protein molecules are usually symmetric has remained an enigma. An idealized model of a soluble monomeric protein was constructed and accompanied through a simulated evolutionary process resulting in dimerization, in order to elucidate this peculiarity. The model showed that the probability of a symmetric association is by a factor of 100 or above higher than the probability of an asymmetric one. Unexpectedly, symmetry prevails in the dimer initiation phase much more than in the dimer improvement phase of evolution. The result is clear-cut and robust against a broad spectrum of model inadequacies. It rationalizes the predominance of symmetric homo-oligomers. © 2009 Elsevier Ltd. All rights reserved.

Happle R.,Albert Ludwigs University of Freiburg
Journal of the European Academy of Dermatology and Venereology | Year: 2015

The name capillary malformation has caused much confusion because it is presently used to designate numerous quite different disorders such as naevus flammeus, the salmon patch, the vascular naevus of the hereditary 'megalencephaly-capillary malformation syndrome' and the skin lesions of non-hereditary traits such as 'capillary malformation-arteriovenous malformation' and 'microcephaly-capillary malformation'. To avoid such bewilderment, the present review describes the distinguishing clinical and genetic criteria of 20 different capillary malformations, and a specific name is given to all of them. The group of capillary naevi includes naevus flammeus, port-wine naevus of the Proteus type, port-wine naevus of the CLOVES type, naevus roseus, rhodoid naevus, cutis marmorata telangiectatica congenita, congenital livedo reticularis, segmental angioma serpiginosum, naevus anaemicus, naevus vascularis mixtus and angiokeratoma circumscriptum. Capillary lesions that perhaps represent naevi are the mesotropic port-wine patch, Carter-Mirzaa macules, unilateral punctate telangiectasia and unilateral naevoid telangiectasia of the patchy type. Capillary malformations that do not represent naevi include X-linked angiokeratoma corporis diffusum (Fabry disease), autosomal dominant angiokeratoma corporis diffusum, hereditary haemorrhagic telangiectasia, hereditary angioma serpiginosusm and the salmon patch. In this way, we are able to discriminate between various non-hereditary capillary naevi such as naevus roseus and the hereditary rhodoid naevus and several hereditary traits that do not represent naevi such as angiokeratoma corporis diffusum and hereditary haemorrhagic telangiectasia; between four different types of port-wine stains, three of them being lateralized and one being mesotropic; between cutis marmorata telangiectatica congenita and congenital livedo reticularis; between telangiectatic naevi and the vasoconstrictive naevus anaemicus; and between two different types of angiokeratoma corporis diffusum. Finally, arguments are presented why the salmon patch ('stork bite', 'naevus simplex') cannot be categorized as a naevus. © 2015 European Academy of Dermatology and Venereology.

Bauer G.,Albert Ludwigs University of Freiburg
Journal of Physics: Conference Series | Year: 2011

Transformed cells are selectively removed by intercellular ROS-mediated induction of apoptosis. Signaling is based on the HOCl and the NO/peroxynitrite pathway (major pathways) and the nitryl chloride and the metal-catalyzed Haber-Weiss pathway (minor pathways). During tumor progression, resistance against intercellular induction of apoptosis is acquired through expression of membrane-associated catalase. Low dose radiation of nontransformed cells has been shown to enhance intercellular induction of apoptosis. The present study was performed to define the signaling components which are modulated by low dose gamma irradiation. Low dose radiation induced the release of peroxidase from nontransformed, transformed and tumor cells. Extracellular superoxide anion generation was strongly enhanced in the case of transformed cells and tumor cells, but not in nontransformed cells. Enhancement of peroxidase release and superoxide anion generation either increased intercellular induction of apoptosis of transformed cells, or caused a partial protection under specific signaling conditions. In tumor cells, low dose radiation enhanced the production of major signaling components, but this had no effect on apoptosis induction, due to the strong resistance mechanism of tumor cells. Our data specify the nature of low dose radiation-induced effects on specific signaling components of intercellular induction of apoptosis at defined stages of multistep carcinogenesis. © 2011 IOP Publishing Ltd.

Baumeister H.,Albert Ludwigs University of Freiburg
Cochrane database of systematic reviews (Online) | Year: 2012

Depression occurs frequently in patients with diabetes mellitus and is associated with a poor prognosis. To determine the effects of psychological and pharmacological interventions for depression in patients with diabetes and depression. Electronic databases were searched for records to December 2011. We searched CENTRAL in The Cochrane Library, MEDLINE, EMBASE, PsycINFO, ISRCTN Register and clinicaltrials.gov. We examined reference lists of included RCTs and contacted authors. We included randomised controlled trials (RCTs) investigating psychological and pharmacological interventions for depression in adults with diabetes and depression. Primary outcomes were depression and glycaemic control. Secondary outcomes were adherence to diabetic treatment regimens, diabetes complications, death from any cause, healthcare costs and health-related quality of life (HRQoL). Two review authors independently examined the identified publications for inclusion and extracted data from included studies. Random-effects model meta-analyses were performed to compute overall estimates of treatment outcomes. The database search identified 3963 references. Nineteen trials with 1592 participants were included. Psychological intervention studies (eight trials, 1122 participants, duration of therapy three weeks to 12 months, follow-up after treatment zero to six months) showed beneficial effects on short (i.e. end of treatment), medium (i.e. one to six months after treatment) and long-term (i.e. more than six months after treatment) depression severity (range of standardised mean differences (SMD) -1.47 to -0.14; eight trials). However, between-study heterogeneity was substantial and meta-analyses were not conducted. Short-term depression remission rates (OR 2.88; 95% confidence intervals (CI) 1.58 to 5.25; P = 0.0006; 647 participants; four trials) and medium-term depression remission rates (OR 2.49; 95% CI 1.44 to 4.32; P = 0.001; 296 participants; two trials) were increased in psychological interventions compared to usual care. Evidence regarding glycaemic control in psychological intervention trials was heterogeneous and inconclusive. QoL did not improve significantly based on the results of three psychological intervention trials compared to usual care. Healthcare costs and adherence to diabetes and depression medication were examined in only one study and reliable conclusions cannot be drawn. Diabetes complications and death from any cause have not been investigated in the included psychological intervention trials.With regards to the comparison of pharmacological interventions versus placebo (eight trials; 377 participants; duration of intervention three weeks to six months, no follow-up after treatment) there was a moderate beneficial effect of antidepressant medication on short-term depression severity (all studies: SMD -0.61; 95% CI -0.94 to -0.27; P = 0.0004; 306 participants; seven trials; selective serotonin reuptake inhibitors (SSRI): SMD -0.39; 95% CI -0.64 to -0.13; P = 0.003; 241 participants; five trials). Short-term depression remission was increased in antidepressant trials (OR 2.50; 95% CI 1.21 to 5.15; P = 0.01; 136 participants; three trials). Glycaemic control improved in the short term (mean difference (MD) for glycosylated haemoglobin A1c (HbA1c) -0.4%; 95% CI -0.6 to -0.1; P = 0.002; 238 participants; five trials). HRQoL and adherence were investigated in only one trial each showing no statistically significant differences. Medium- and long-term depression and glycaemic control outcomes as well as healthcare costs, diabetes complications and mortality have not been examined in pharmacological intervention trials. The comparison of pharmacological interventions versus other pharmacological interventions (three trials, 93 participants, duration of intervention 12 weeks, no follow-up after treatment) did not result in significant differences between the examined pharmacological agents, except for a significantly ameliorated glycaemic control in fluoxetine-treated patients (MD for HbA1c -1.0%; 95% CI -1.9 to -0.2; 40 participants) compared to citalopram in one trial. Psychological and pharmacological interventions have a moderate and clinically significant effect on depression outcomes in diabetes patients. Glycaemic control improved moderately in pharmacological trials, while the evidence is inconclusive for psychological interventions. Adherence to diabetic treatment regimens, diabetes complications, death from any cause, health economics and QoL have not been investigated sufficiently. Overall, the evidence is sparse and inconclusive due to several low-quality trials with substantial risk of bias and the heterogeneity of examined populations and interventions.

Sturman B.,Russian Academy of Sciences | Breunig I.,Albert Ludwigs University of Freiburg
Journal of the Optical Society of America B: Optical Physics | Year: 2011

Extending Yariv's generic approach to the description of optical microresonators, we describe the secondharmonic generation and the optical parametric oscillation in whispering-gallery resonators (WGRs). The output characteristics of these nonlinear processes are expressed in terms of conventional cavity/coupling parameters and nonlinear material coefficients. The found relations are relevant to the description and optimization of experiments with nonlinearly active WGRs at ultralow input light powers. © 2011 Optical Society of America.

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

Schmidt H.M.,Albert Ludwigs University of Freiburg
Cochrane database of systematic reviews (Online) | Year: 2012

Psychotropic drugs are associated with sexual dysfunction. Symptoms may concern penile erection, lubrication, orgasm, libido, retrograde ejaculation, sexual arousal, or overall sexual satisfaction. These are major aspects of tolerability and can highly affect patients' compliance. To determine the effects of different strategies (e.g. dose reduction, drug holidays, adjunctive medication, switching to another drug) for treatment of sexual dysfunction due to antipsychotic therapy. An updated search was performed in the Cochrane Schizophrenia Group's Trials Register (3 May 2012) and the references of all identified studies for further trials. We included all relevant randomised controlled trials involving people with schizophrenia and sexual dysfunction. We extracted data independently. For dichotomous data we calculated random effects risk ratios (RR) with 95% confidence intervals (CI), for crossover trials we calculated Odds Ratios (OR) with 95% CI. For continuous data, we calculated mean differences (MD) on the basis of a random-effects model. We analysed cross-over trials under consideration of correlation of paired measures. Currently this review includes four pioneering studies (total n = 138 , duration two weeks to four months), two of which are cross-over trials. One trial reported significantly more erections sufficient for penetration when receiving sildenafil compared with when receiving placebo (n = 32, MD 3.20 95% CI 1.83 to 4.57), a greater mean duration of erections (n = 32, MD 1.18 95% CI 0.52 to 1.84) and frequency of satisfactory intercourse (n = 32, MD 2.84 95% CI 1.61 to 4.07). The second trial found no evidence for selegiline as symptomatic treatment for antipsychotic-induced sexual dysfunction compared with placebo (n = 10, MD change on Aizenberg's sexual functioning scale -0.40 95% CI -3.95 to 3.15). No evidence was found for switching to quetiapine from risperidone to improve sexual functioning (n = 36, MD -2.02 95% CI -5.79 to 1.75). One trial reported significant improvement in sexual functioning when participants switched from risperidone or an typical antipsychotic to olanzapine (n = 54, MD -0.80 95% CI -1.55 to -0.05). We are not confident that cross-over studies are appropriate for this participant group as they are best for conditions that are stable and for interventions with no physiological and psychological carry-over. Sildenafil may be a useful option in the treatment of antipsychotic-induced sexual dysfunction in men with schizophrenia, but this conclusion is based only on one small short trial. Switching to olanzapine may improve sexual functioning in men and women, but the trial assessing this was a small, open label trial. Further well designed randomised control trials that are blinded and well conducted and reported, which investigate the effects of dose reduction, drug holidays, symptomatic therapy and switching antipsychotic on sexual function in people with antipsychotic-induced sexual dysfunction are urgently needed.

Baumeister H.,Albert Ludwigs University of Freiburg
Cochrane database of systematic reviews (Online) | Year: 2011

Depression occurs frequently in patients with coronary artery disease (CAD) and is associated with a poor prognosis. To determine the effects of psychological and pharmacological interventions for depression in CAD patients with comorbid depression. CENTRAL, DARE, HTA and EED on The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, ISRCTN Register and CardioSource Registry were searched. Reference lists of included randomised controlled trials (RCTs) were examined and primary authors contacted. No language restrictions were applied. RCTs investigating psychological and pharmacological interventions for depression in adults with CAD and comorbid depression were included. Primary outcomes were depression, mortality and cardiac events. Secondary outcomes were healthcare costs and health-related quality of life (QoL). Two reviewers independently examined the identified papers for inclusion and extracted data from included studies. Random effects model meta-analyses were performed to compute overall estimates of treatment outcomes. The database search identified 3,253 references. Sixteen trials fulfilled the inclusion criteria. Psychological interventions show a small beneficial effect on depression compared to usual care (range of SMD of depression scores across trials and time frames: -0.81;0.12). Based on one trial per outcome, no beneficial effects on mortality rates, cardiac events, cardiovascular hospitalizations and QoL were found, except for the psychosocial dimension of QoL. Furthermore, no differences on treatment outcomes were found between the varying psychological approaches. The review provides evidence of a small beneficial effect of pharmacological interventions with selective serotonin reuptake inhibitors (SSRIs) compared to placebo on depression outcomes (pooled SMD of short term depression change scores: -0.24 [-0.38,-0.09]; pooled OR of short term depression remission: 1.80 [1.18,2.74]). Based on one to three trials per outcome, no beneficial effects regarding mortality, cardiac events and QoL were found. Hospitalization rates (pooled OR of three trials: 0.58 [0.39,0.85] and emergency room visits (OR of one trial: 0.58 [0.34,1.00]) were reduced in trials of pharmacological interventions compared to placebo. No evidence of a superior effect of Paroxetine (SSRI) versus Nortriptyline (TCA) regarding depression outcomes was found in one trial. Psychological interventions and pharmacological interventions with SSRIs may have a small yet clinically meaningful effect on depression outcomes in CAD patients. No beneficial effects on the reduction of mortality rates and cardiac events were found. Overall, however, the evidence is sparse due to the low number of high quality trials per outcome and the heterogeneity of examined populations and interventions.

Sakurai Y.,The Texas Institute | Kolokoltsov A.A.,TheUniversity of Texas Medical Branch | Chen C.-C.,Ludwig Maximilians University of Munich | Tidwell M.W.,Southwest Research Institute | And 6 more authors.
Science | Year: 2015

Ebola virus causes sporadic outbreaks of lethal hemorrhagic fever in humans, but there is no currently approved therapy. Cells take up Ebola virus by macropinocytosis, followed by trafficking through endosomal vesicles. However, few factors controlling endosomal virus movement are known. Here we find that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). Disrupting TPC function by gene knockout, small interfering RNAs, or small-molecule inhibitors halted virus trafficking and prevented infection. Tetrandrine, the most potent small molecule that we tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficacy in mice. Therefore, TPC proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy. © 2015, American Association for the Advancement of Science. All rights reserved.

Arends J.,Albert Ludwigs University of Freiburg
Aktuelle Ernahrungsmedizin | Year: 2012

Malnutrition develops frequently in cancer patients. Weight loss in these patients is associated with impaired quality of life and physical performance and a reduced tolerance of anticancer treatments. Gastrointestinal defects, chronic pain, psycho-social tensions and tumor-associated inflammatory reactions, all contribute to appetite loss, reduced intake of nutrients and energy, fatigue, diminished mobility and further loss of weight and muscles. Major aims of the nutritional and metabolic care of oncologic patients are the following: the careful assessment of the relevant problems; the targeted treatment of all factors interfering with nutritional intake and utilization; ensuring the required supply of nutrients and energy; exercise training; as well as anti-inflammatory and anti-catabolic strategies. © Georg Thieme Verlag KG Stuttgart · New York.

Banfi A.,Albert Ludwigs University of Freiburg | Monni P.F.,University of Zurich | Salam G.P.,CERN | Salam G.P.,Princeton University | And 2 more authors.
Physical Review Letters | Year: 2012

We derive first next-to-next-to-leading logarithmic resummations for jet-veto efficiencies in Higgs and Z-boson production at hadron colliders. Matching with next-to-next-to-leading order results allows us to provide a range of phenomenological predictions for the LHC, including cross-section results, detailed uncertainty estimates, and comparisons to current widely used tools. © 2012 American Physical Society.

Spontaneous complete remission (CR) is a rare, poorly understood phenomenon in acute myeloid leukemia (AML). We describe the 10-year follow-up of a patient with MLL-AF9-positive AML (Müller et al. Eur J Haematol 73:62-66, 2004), including ex vivo antileukemic immune responses which may contribute to the long-lasting spontaneous CR (tantamount to cure). We could demonstrate strong in vitro cytotoxic activity mediated by the patient's serum (cryopreserved at diagnosis 2001) against myeloid cell lines. We also addressed cellular cytotoxic activity against myeloid leukemia cells. When the patient's natural killer (NK) cells (obtained in 2007) were tested against the K562 cell line, upregulation of CD107 occurred, implying that long-term CR in this patient could be due to NK cell-mediated disease control.

Kliesch M.,Free University of Berlin | Gross D.,Albert Ludwigs University of Freiburg | Eisert J.,Free University of Berlin
Physical Review Letters | Year: 2014

Tensor network states constitute an important variational set of quantum states for numerical studies of strongly correlated systems in condensed-matter physics, as well as in mathematical physics. This is specifically true for finitely correlated states or matrix-product operators, designed to capture mixed states of one-dimensional quantum systems. It is a well-known open problem to find an efficient algorithm that decides whether a given matrix-product operator actually represents a physical state that in particular has no negative eigenvalues. We address and answer this question by showing that the problem is provably undecidable in the thermodynamic limit and that the bounded version of the problem is NP-hard (nondeterministic-polynomial-time hard) in the system size. Furthermore, we discuss numerous connections between tensor network methods and (seemingly) different concepts treated before in the literature, such as hidden Markov models and tensor trains. © 2014 American Physical Society.

Hahn T.,Max Planck Institute for Physics | Heinemeyer S.,Institute Fisica Of Cantabria Csic Uc | Hollik W.,Max Planck Institute for Physics | Rzehak H.,Albert Ludwigs University of Freiburg | Weiglein G.,German Electron Synchrotron
Physical Review Letters | Year: 2014

For the interpretation of the signal discovered in the Higgs searches at the LHC it will be crucial in particular to discriminate between the minimal Higgs sector realized in the standard model (SM) and its most commonly studied extension, the minimal supersymmetric standard model (MSSM). The measured mass value, having already reached the level of a precision observable with an experimental accuracy of about 500 MeV, plays an important role in this context. In the MSSM the mass of the light CP-even Higgs boson, Mh, can directly be predicted from the other parameters of the model. The accuracy of this prediction should at least match the one of the experimental result. The relatively high mass value of about 126 GeV has led to many investigations where the scalar top quarks are in the multi-TeV range. We improve the prediction for Mh in the MSSM by combining the existing fixed-order result, comprising the full one-loop and leading and subleading two-loop corrections, with a resummation of the leading and subleading logarithmic contributions from the scalar top sector to all orders. In this way for the first time a high-precision prediction for the mass of the light CP-even Higgs boson in the MSSM is possible all the way up to the multi-TeV region of the relevant supersymmetric particles. The results are included in the code FeynHiggs. © 2014 American Physical Society.

Gies H.,Friedrich - Schiller University of Jena | Gneiting C.,Albert Ludwigs University of Freiburg | Sondenheimer R.,Friedrich - Schiller University of Jena
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

We study the functional renormalization group flow of a Higgs-Yukawa toy model mimicking the top-Higgs sector of the standard model. This approach allows for treating arbitrary bare couplings. For the class of standard bare potentials of 4 type at a given ultraviolet cutoff, we show that a finite infrared Higgs mass range emerges naturally from the renormalization group flow itself. Higgs masses outside the resulting bounds cannot be connected to any conceivable set of bare parameters in this standard model 4 class. By contrast, more general bare potentials allow us to diminish the lower bound considerably. We identify a simple renormalization group mechanism for this depletion of the lower bound. If this depletion is also active in the full standard model, Higgs masses smaller than the conventional infrared window do not necessarily require new physics at low scales or give rise to instability problems. © 2014 American Physical Society.

Blumenthal N.R.,Karolinska Institutet | Hermanson O.,Karolinska Institutet | Heimrich B.,Albert Ludwigs University of Freiburg | Shastri V.P.,Karolinska Institutet
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Extracellular soluble signals are known to play a critical role in maintaining neuronal function and homeostasis in the CNS. However, the CNS is also composed of extracellular matrix macromolecules and glia support cells, and the contribution of the physical attributes of these components in maintenance and regulation of neuronal function is not well understood. Because these components possess well-defined topography, we theorize a role for topography in neuronal development and we demonstrate that survival and function of hippocampal neurons and differentiation of telencephalic neural stem cells is modulated by nanoroughness. At roughnesses corresponding to that of healthy astrocytes, hippocampal neurons dissociated and survived independent from astrocytes and showed superior functional traits (increased polarity and calcium flux). Furthermore, telencephalic neural stem cells differentiated into neurons even under exogenous signals that favor astrocytic differentiation. The decoupling of neurons from astrocytes seemed to be triggered by changes to astrocyte apical-surface topography in response to nanoroughness. Blocking signaling through mechanosensing cation channels using GsMTx4 negated the ability of neurons to sense the nanoroughness and promoted decoupling of neurons from astrocytes, thus providing direct evidence for the role of nanotopography in neuron-astrocyte interactions.We extrapolate the role of topography to neurodegenerative conditions and show that regions of amyloid plaque buildup in brain tissue of Alzheimer's patients are accompanied by detrimental changes in tissue roughness. These findings suggest a role for astrocyte and ECM-induced topographical changes in neuronal pathologies and provide new insights for developing therapeutic targets and engineering of neural biomaterials.

Rohr J.C.,Netherlands Cancer Institute | Rohr J.C.,Albert Ludwigs University of Freiburg | Gerlach C.,Harvard University | Kok L.,Netherlands Cancer Institute | Schumacher T.N.,Netherlands Cancer Institute
Trends in Immunology | Year: 2014

Upon primary infection, naïve T cells that recognize their cognate antigen become activated, proliferate, and simultaneously differentiate into various subsets. A long-standing question in the field has been how this cellular diversification is achieved. Conceptually, diverse cellular output may either arise from every single cell or only from populations of naïve cells. Furthermore, such diversity may either be driven by cell-intrinsic heterogeneity or by external, niche-derived signals. In this review, we discuss how recently developed technologies have allowed the analysis of the mechanisms underlying T cell diversification at the single cell level. In addition, we outline the implications of this work on our understanding of the formation of immunological memory, and describe a number of unresolved key questions in this field. © 2014 Elsevier Ltd.

Aberg J.,Albert Ludwigs University of Freiburg
Physical Review Letters | Year: 2014

Because of conservation of energy we cannot directly turn a quantum system with a definite energy into a superposition of different energies. However, if we have access to an additional resource in terms of a system with a high degree of coherence, as for standard models of laser light, we can overcome this limitation. The question is to what extent coherence gets degraded when utilized. Here it is shown that coherence can be turned into a catalyst, meaning that we can use it repeatedly without ever diminishing its power to enable coherent operations. This finding stands in contrast to the degradation of other quantum resources and has direct consequences for quantum thermodynamics, as it shows that latent energy that may be locked into superpositions of energy eigenstates can be released catalytically. © 2014 American Physical Society.

Schmidt D.,Albert Ludwigs University of Freiburg
European Journal of Medical Research | Year: 2013

Background: Several general diseases cause blindness in patients with simultaneous combined retinal artery and vein occlusion. Methods/patients. We examined 14 patients with acute unilateral visual loss due to combined retinal artery and venous occlusions. All 14 patients presented at the Polyclinic over a period of about 3 years. Fluorescein angiography was carried out in 12 patients to confirm the diagnosis. Ten patients underwent Doppler sonography and 11 echocardiography. Results: Concerning systemic diseases, 11 of our 14 patients presented several cardiovascular risk factors, i.e., immunocytoma and arterial hypertension and hypercholesterolemia in one patient; another patient had chronic bronchitis, tachycardia and hypercholesterolemia. Six patients presented coagulation anomalies, and eight patients had arterial hypertension.Doppler sonography revealed normal carotid arteries in nine of ten patients. In 8 of 11 patients, echocardiography displayed no cardiac abnormalities.Ophthalmoscopy revealed no emboli in any of these patients. Conclusion: Unilateral simultaneous combined incomplete retinal artery and venous occlusions should be considered as one entity. Eleven of our patients presented comorbidities reflecting several cardiovascular risk factors. Immunological diseases, malignancies and coagulopathies can cause this ocular disorder, resulting in blindness. No emboli were found in any of these patients. Patients suffering from acute visual loss must be examined for the presence of systemic diseases to enable therapy at an early stage. © 2013 Schmidt; licensee BioMed Central Ltd.

Hohne J.,TU Berlin | Tangermann M.,Albert Ludwigs University of Freiburg
PLoS ONE | Year: 2014

Realizing the decoding of brain signals into control commands, brain-computer interfaces (BCI) aim to establish an alternative communication pathway for locked-in patients. In contrast to most visual BCI approaches which use event-related potentials (ERP) of the electroencephalogram, auditory BCI systems are challenged with ERP responses, which are less class-discriminant between attended and unattended stimuli. Furthermore, these auditory approaches have more complex interfaces which imposes a substantial workload on their users. Aiming for a maximally user-friendly spelling interface, this study introduces a novel auditory paradigm: "CharStreamer". The speller can be used with an instruction as simple as "please attend to what you want to spell". The stimuli of CharStreamer comprise 30 spoken sounds of letters and actions. As each of them is represented by the sound of itself and not by an artificial substitute, it can be selected in a one-step procedure. The mental mapping effort (sound stimuli to actions) is thus minimized. Usability is further accounted for by an alphabetical stimulus presentation: contrary to random presentation orders, the user can foresee the presentation time of the target letter sound. Healthy, normal hearing users (n = 10) of the CharStreamer paradigm displayed ERP responses that systematically differed between target and non-target sounds. Class-discriminant features, however, varied individually from the typical N1-P2 complex and P3 ERP components found in control conditions with random sequences. To fully exploit the sequential presentation structure of CharStreamer, novel data analysis approaches and classification methods were introduced. The results of online spelling tests showed that a competitive spelling speed can be achieved with CharStreamer. With respect to user rating, it clearly outperforms a control setup with random presentation sequences. © 2014 Höhne, Tangermann.

Berstel-Da Silva B.,Albert Ludwigs University of Freiburg
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012

Production systems are declarative, in that they do not explicitly specify the control flow. Yet, the concept of a production system does not include the definition of a given control strategy. The control between rules in a production rule program is, in practice, defined by each implementation of a production rule engine. Engines have traditionally been implemented using the Rete algorithm. Since the turn of the century, however, production systems have evolved into industrial products known as Business Rules Management Systems (BRMS). BRMS have introduced new compilation and execution schemes, which are often called sequential in contrast with the incremental behavior of Rete. This change in execution scheme came with a change in semantics for rule programs. In this paper, we propose a formal description of the execution of production rule programs. Existing descriptions either ignore the control strategy, or assume a Rete semantics. Ours isolates the handling of rule eligibility in the control strategy, which allows us to describe the sequential execution semantics of rule programs, as well as the Rete semantics, and others. © 2012 Springer-Verlag.

Mockenhaupt M.,Albert Ludwigs University of Freiburg
Seminars in Cutaneous Medicine and Surgery | Year: 2014

Severe cutaneous adverse reactions are associated with significant morbidity and mortality. They may be life-threatening for the affected patient and difficult to treat. Such conditions include toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis and drug reaction with eosinophilia and systemic symptoms. Due to the fact that prognosis, etiology and treatment of the various reactions differ, a clear diagnosis based on the specific clinical pattern is important. This review will focus on the clinical presentations, pathogenesis, and important diagnostic and therapeutic considerations in the management of SJS and TEN. © 2014 Frontline Medical Communications.

Markl M.,Northwestern University | Leupold J.,Albert Ludwigs University of Freiburg
Journal of Magnetic Resonance Imaging | Year: 2012

Magnetic resonance imaging (MRI) based on gradient echoes is used in a wide variety of imaging techniques and clinical applications. Gradient echo sequences form the basis for an essential group of imaging methods that find widespread use in clinical practice, particularly when fast imaging is important, as for example in cardiac MRI or contrast-enhanced MR angiography. However, the term "gradient echo sequence" is somewhat unspecific, as even images acquired with the most common sequences employing the gradient echo for data acquisition can significantly differ in signal, contrast, artifact behavior, and sensitivity to, eg, flow. This is due to the different use of sequence timing and basic sequence building blocks such as spoiler gradients or specific radiofrequency (RF) pulse phase patterns. In this article the basic principles of gradient echo formation compared to spin echo imaging are reviewed and the properties of gradient echo imaging in its simplest form (TR ≤laquo; T2) are described. Further, the most common three variants of fast gradient echo sequences (TR < T2), namely, unbalanced gradient echo, RF spoiled gradient echo, and balanced steady state free precession; are discussed. For each gradient echo sequence type, examples of applications exploiting the specific properties of the individual technique are presented. Copyright © 2012 Wiley Periodicals, Inc.

Genetically evoked deficiency of collagen VII causes dystrophic epidermolysis bullosa (DEB)—a debilitating disease characterized by chronic skin fragility and progressive fibrosis. Removal of exons carrying frame-disrupting mutations can reinstate protein expression in genetic diseases. The therapeutic potential of this approach is critically dependent on gene, protein, and disease intrinsic factors. Naturally occurring exon skipping in COL7A1, translating collagen VII, suggests that skipping of exons containing disease-causing mutations may be feasible for the treatment of DEB. However, despite a primarily in-frame arrangement of exons in the COL7A1 gene, no general conclusion of the aptitude of exon skipping for DEB can be drawn, since regulation of collagen VII functionality is complex involving folding, intra- and intermolecular interactions. To directly address this, we deleted two conceptually important exons located at both ends of COL7A1, exon 13, containing recurrent mutations, and exon 105, predicted to impact folding. The resulting recombinantly expressed proteins showed conserved functionality in biochemical and in vitro assays. Injected into DEB mice, the proteins promoted skin stability. By demonstrating functionality of internally deleted collagen VII variants, our study provides support of targeted exon deletion or skipping as a potential therapy to treat a large number of individuals with DEB.Molecular Therapy (2016); doi:10.1038/mt.2016.92. © 2016 American Society of Gene & Cell Therapy

Denner A.,University of Wurzburg | Dittmaier S.,Albert Ludwigs University of Freiburg | Kallweit S.,Paul Scherrer Institute | Pozzorini S.,University of Zurich
Physical Review Letters | Year: 2011

Top-antitop quark pairs belong to the most abundantly produced and precisely measurable heavy-particle signatures at hadron colliders and allow for crucial tests of the standard model and new physics searches. Here we report on the calculation of the next-to-leading order (NLO) QCD corrections to hadronic W+W-bb̄ production, which provides a complete NLO description of the production of top-antitop pairs and their subsequent decay into W bosons and bottom quarks, including interferences, off-shell effects, and nonresonant backgrounds. Numerical predictions for the Tevatron and the LHC are presented. © 2011 American Physical Society.

Kosyfaki P.,Albert Ludwigs University of Freiburg
Quintessence international (Berlin, Germany : 1985) | Year: 2010

Location of the crown margin, marginal fit, crown material, and crown contour all impact periodontal tissues. This literature review evaluated available data on their relationship with the periodontium and also examines whether any changes in established knowledge and/or perspectives have been published during the past 30 years. Electronic and manual searches conducted for in vivo investigations in the English and German literature for 1953 to 2009 provided 64 studies. Findings indicate that the supragingival location remains the most advantageous from the periodontal point of view; esthetic demands, however, dictated an intracrevicular location of the margin in the anterior zone. Metal-ceramic and all-ceramic crowns show a clinically acceptable marginal fit. Ceramic materials have the lowest plaque-retaining capacity, and a normal crown contour guarantees satisfactory periodontal health and esthetics. The accompanying data confirm the results reported in the literature, revealing that nothing has substantially changed, thereby supporting current approaches.

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.

Aschendorff A.,Albert Ludwigs University of Freiburg
Laryngo- Rhino- Otologie | Year: 2011

Imaging procedures are a mainstream tool in the daily ENT workflow. Cochlear Implant patients are representing a special population with specific demands for imaging. There are different imaging techniques available for pre-operative evaluation, surgery and postoperative controls with different indications and consequences. High-resolution computed tomography and magnetic resonance imaging are mainly used in the evaluation process. New procedures, as digital volume tomography, are increasingly used intra- and postoperatively. Especially the intracochlear positioning in malformations of the inner ear, eventually added with radiological assisted navigation, can be considered a standard of modern cochlear implant surgery. In addition, digital volume tomography may serve as a quality control tool focusing on the evaluation of the intracochlear electrode position. The range of applications, indications and current results are illustrated. © Georg Thieme Verlag KG Stuttgart · New York.

Ueda M.,Nara Institute of Science and Technology | Laux T.,Albert Ludwigs University of Freiburg
Current Opinion in Plant Biology | Year: 2012

During embryogenesis, the basic body plan of an organism develops from a unicellular zygote. In most flowering plants, the polar zygote divides asymmetrically, making visible the apical-basal axis in the early embryo. The molecular mechanisms governing how the zygote polarizes and how this polarity is linked to embryo axis formation have been obscure, mainly owing to the difficulties to access the zygote that is deeply embedded in the maternal tissue. In this review, we summarize recent findings identifying key regulators in Arabidopsis and developing novel approaches in various plant species, which altogether set the stage for unraveling embryo axis formation. © 2012 Elsevier Ltd.

Reiter G.,Albert Ludwigs University of Freiburg | Napolitano S.,Catholic University of Leuven
Journal of Polymer Science, Part B: Polymer Physics | Year: 2010

The possible origin of thickness-dependent deviations from bulk properties of thin polymer films is discussed. The central process in obtaining a thin polymer film concerns the transition from a mostly dilute solution to a dry glassy state. The solvent evaporates rapidly (within seconds) and the polymer concentration increases about exponentially in time until the film solidifies in many cases of film preparation from solution. The conformations at the stage of solidification differ necessarily from the ones of an equilibrated melt. Annealing the films at temperatures above the glass transition temperature of the bulk polymer (Tg, bulk) for many hours reduces the effect of negative thermal expansivity, but does not eliminate it completely. A comprehensive understanding of behavior of thin polymer films requires relating macroscopically observed phenomena to molecular properties such as the conformational entropy and the entanglement density of polymers confined in thin films.

Akbar S.,University of Reading | Elliott J.M.,University of Reading | Rittman M.,Albert Ludwigs University of Freiburg | Squires A.M.,University of Reading
Advanced Materials | Year: 2013

Direct electrochemical templating is carried out using a thin layer of a self-assembled diamond phase (QII D) of phytantriol to create a platinum film with a novel nanostructure. Small-angle X-ray scattering shows that the nanostructured platinum films are asymmetrically templated and exhibit "single diamond" morphology with Fd3m symmetry. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Schumacher Y.O.,Albert Ludwigs University of Freiburg | D'Onofrio G.,Catholic University of the Sacred Heart
Clinical Chemistry | Year: 2012

Expert evaluation of biological data is a key component of the Athlete Biological Passport approach in the fight against doping. The evaluation consists of a longitudinal assessment of biological variables to determine the probability of the data being physiological on the basis of the athlete's on own previous values (performed by an automated software system using a Bayesian model) and a subjective evaluation of the results in view of possible causes (performed by experts). The role of the expert is therefore a key component in the process. Experts should be qualified to evaluate the data regarding possible explanations related to the influence of doping products and methods, analytical issues, and the influence of exercise or pathological conditions. The evaluation provides a scientific basis for the decision taken by a disciplinary panel. This evaluation should therefore encompass and balance all possible causes for a given blood profile and provide a likelihood for potential scenarios (pathology, normal variation, doping) that might have caused the pattern. It should comply with the standards for the evaluation of scientific evidence in forensics. On the basis of their evaluation of profiles, experts might provide assistance in planning appropriate target testing schemes. © 2012 American Association for Clinical Chemistry.

Meta-analyses are particularly vulnerable to the effects of publication bias. Despite methodologists' best efforts to locate all evidence for a given topic the most comprehensive searches are likely to miss unpublished studies and studies that are published in the gray literature only. If the results of the missing studies differ systematically from the published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention's effects.As part of the OPEN project (http://www.open-project.eu) we will conduct a systematic review with the following objectives: To assess the impact of studies that are not published or published in the gray literature on pooled effect estimates in meta-analyses (quantitative measure). To assess whether the inclusion of unpublished studies or studies published in the gray literature leads to different conclusions in meta-analyses (qualitative measure). Inclusion criteria: Methodological research projects of a cohort of meta-analyses which compare the effect of the inclusion or exclusion of unpublished studies or studies published in the gray literature.Literature search: To identify relevant research projects we will conduct electronic searches in Medline, Embase and The Cochrane Library; check reference lists; and contact experts.Outcomes: 1) The extent to which the effect estimate in a meta-analyses changes with the inclusion or exclusion of studies that were not published or published in the gray literature; and 2) the extent to which the inclusion of unpublished studies impacts the meta-analyses' conclusions.Data collection: Information will be collected on the area of health care; the number of meta-analyses included in the methodological research project; the number of studies included in the meta-analyses; the number of study participants; the number and type of unpublished studies; studies published in the gray literature and published studies; the sources used to retrieve studies that are unpublished, published in the gray literature, or commercially published; and the validity of the methodological research project.Data synthesis: Data synthesis will involve descriptive and statistical summaries of the findings of the included methodological research projects. Results are expected to be publicly available in the middle of 2013.

Wei F.,Albert Ludwigs University of Freiburg
Proceedings of the ACM SIGMOD International Conference on Management of Data | Year: 2010

Efficient shortest path query answering in large graphs is enjoying a growing number of applications, such as ranked keyword search in databases, social networks, ontology reasoning and bioinformatics. A shortest path query on a graph finds the shortest path for the given source and target vertices in the graph. Current techniques for efficient evaluation of such queries are based on the pre-computation of compressed Breadth First Search trees of the graph. However, they suffer from drawbacks of scalability. To address these problems, we propose TEDI, an indexing and query processing scheme for the shortest path query answering. TEDI is based on the tree decomposition methodology. The graph is first decomposed into a tree in which the node (a.k.a. bag) contains more than one vertex from the graph. The shortest paths are stored in such bags and these local paths together with the tree are the components of the index of the graph. Based on this index, a bottom-up operation can be executed to find the shortest path for any given source and target vertices. Our experimental results show that TEDI offers orders-of-magnitude performance improvement over existing approaches on the index construction time, the index size and the query answering. © 2010 ACM.

Klingele J.,Albert Ludwigs University of Freiburg
Coordination Chemistry Reviews | Year: 2015

Citing 120 references, this article gives an overview of low-melting cationically tagged coordination compounds of transition metal ions. In three sections, focussing on Werner-type complexes, carbonyls and ferrocenes, ammonium-, phosphonium- and imidazolium-tagged complexes that have Tfus<200°C are summarised. Many of these compounds are identified as Ionic Liquids. Influences of the ligand, the metal ion and the anionic counterion on the melting point of the complexes are discussed. Together about 220 coordination compounds of about 100 ligands are described and shown in 11 figures. © 2015 Elsevier B.V.

Broom M.,Albert Ludwigs University of Freiburg
Proceedings. Biological sciences / The Royal Society | Year: 2013

The central question in communication theory is whether communication is reliable, and if so, which mechanisms select for reliability. The primary approach in the past has been to attribute reliability to strategic costs associated with signalling as predicted by the handicap principle. Yet, reliability can arise through other mechanisms, such as signal verification; but the theoretical understanding of such mechanisms has received relatively little attention. Here, we model whether verification can lead to reliability in repeated interactions that typically characterize mutualisms. Specifically, we model whether fruit consumers that discriminate among poor- and good-quality fruits within a population can select for reliable fruit signals. In our model, plants either signal or they do not; costs associated with signalling are fixed and independent of plant quality. We find parameter combinations where discriminating fruit consumers can select for signal reliability by abandoning unprofitable plants more quickly. This self-serving behaviour imposes costs upon plants as a by-product, rendering it unprofitable for unrewarding plants to signal. Thus, strategic costs to signalling are not a prerequisite for reliable communication. We expect verification to more generally explain signal reliability in repeated consumer-resource interactions that typify mutualisms but also in antagonistic interactions such as mimicry and aposematism.

Schaefer H.M.,Albert Ludwigs University of Freiburg | Schaefer H.M.,EBD Group
Proceedings. Biological sciences / The Royal Society | Year: 2014

Communication is a characteristic of life, but its reliability and basic definition are hotly debated. Theory predicts that trade among mutualists requires high reliability. Here, we show that moderate reliability already allows mutualists to optimize their rewards. The colours of Mediterranean fleshy-fruits indicate lipid rewards (but not other nutrients) to avian seed dispersers on regional and local scales. On the regional scale, fruits with high lipid content were significantly darker and less chromatic than congeners with lower lipid content. On the local scale, two warbler species (Sylvia atricapilla and Sylvia borin) selected fruit colours that were less chromatic, and thereby maximized their intake of lipids-a critical resource during migration and wintering. Crucially, birds were able to maximize lipid rewards with moderate reliability from visual fruit colours (r(2) = 0.44-0.60). We suggest that mutualisms require only that any association between the quality and sensory aspects of signallers is learned through multiple, repeated interactions. Because these conditions are often fulfilled, also in social communication systems, we contend that selection on reliability is less intense than hitherto assumed. This may contribute to explaining the extraordinary diversity of signals, including that of plant reproductive displays.

Spatz H.-C.,Albert Ludwigs University of Freiburg | Theckes B.,Ecole Polytechnique - Palaiseau
Plant Science | Year: 2013

Oscillation damping is of vital importance for trees to withstand strong gusty winds. Tree adaptation to wind loading takes place over a long time and during a storm only passive damping mechanisms can reduce the impact of the wind on trunk and roots. Structural damping, a phenomenon, which is associated with the conspicuous movements of the branches relative to the trunk is of particular importance. Primary and higher order branches can be seen as multiple tuned mass dampers. Moreover, as the frequency bands overlap within branches and between primary branches and the entire tree, resonance energy transfer can distribute mechanical energy over the entire tree, such that it is dissipated more effectively than in a tree with stiff branches and not so much focused on the tree trunk and the roots.Theoretical studies using modal analysis and finite element methods have supported these assertions. Next to "multiple mass damping" and "multiple resonance damping", both characterized by linear coupling between the elements, a third non linear mode, operative at large amplitudes has been identified: "damping by branching". In all these not mutually exclusive concepts frequency tuning between the elements appears to be a fundamental requisite. © 2013 Elsevier Ireland Ltd.

Samyn P.,Albert Ludwigs University of Freiburg
Journal of Materials Science | Year: 2013

The use of papers in packaging and development of novel technological applications for paper substrates largely depends on the control of the hydrophilic properties of the cellulose fibres and improvement of the water-repellent properties. This review provides an actual summary of available literature on theoretical concepts and practical methods to improve the hydrophobicity of cellulose fibres and paper webs. In the first part, the interaction of water with cellulose fibres and paper webs is described at different levels ranging from the molecular scale over the micro- to macroscale fibre properties towards the interactions with porous substrates. The concepts for hydrophobicity and superhydrophobicity applied to cellulose fibres are reviewed, considering the surface chemistry and topographical features. In the second part, current techniques for hydrophobization based on sizing or direct fibre surface functionalization are described. Besides traditional sizing procedures, novelties in nanoparticle applications as hydrophobic sizing agent are reviewed. Novel trends in physical, chemical and nanotechnological fibre surface modifications or surface coatings are reviewed to turn the wetting properties into the superhydrophobic regime. The main future concern in controlling cellulose wettability lies in the development of sustainable modification techniques based on renewable resources such as biopolymers and green chemistry. © 2013 Springer Science+Business Media New York.

Huttel W.,Albert Ludwigs University of Freiburg
Chemie-Ingenieur-Technik | Year: 2013

Due to the low reactivity of CH bonds and often low regio-and stereoselectivities, CH activations rank among the most challenging reactions in synthetic organic chemistry. In contrast, in nature CH functionalizations are integral part of numerous biosyntheses, especially of secondary metabolites. In aerobic organisms these reactions are typically catalyzed by oxygenases, among which the cytochrome P450 monooxygenases are the most prominent. A second large group are the α-ketoglutarate-(αKG) dependent dioxygenases, whose enormous synthetic potential has been discovered only recently. Although the utilization of oxygenases for organic synthesis is most desirable, their technical application is limited, because they are usually difficult to process. With αKG-dependent dioxygenases some of the problems can be reduced or even avoided. In this article some prominent examples for approaches with αKG-dependent dioxygenases are reviewed and efforts to engineer a deacetoxycephalosporin synthase are discussed. In addition to the well-known P450 monooxygenases, α-ketoglutarate-dependent dioxygenases have a great potential for the catalysis of regio-and stereoselective CH-functionalizations even at the industrial scale. In this review the most important approaches for the application of this as yet scarcely employed group of enzymes are discussed. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hernandez-Morcillo M.,Berlin Brandenburg Academy of science and Humanities | Plieninger T.,Berlin Brandenburg Academy of science and Humanities | Bieling C.,Albert Ludwigs University of Freiburg
Ecological Indicators | Year: 2013

Over millennia human well-being has benefited from ecosystems, not only through tangible goods, but also through intangible assets known as cultural ecosystem services. Despite growing research over the last decade, cultural services assessment still remains arbitrary and is largely limited to marketable services such as tourism. Evident difficulties in standardizing definitions and measurements have challenged cultural services accounting in decision making processes. However, the imminent formation of the Intergovernmental Platform on Biodiversity and Ecosystem Services offers an opportunity to counterbalance this misrepresentation by establishing a scientific basis for consistently assessing cultural services. In that regard, the current review intends to facilitate discussion investigating the current state of cultural services accounting by offering an appraisal of existing evidence regarding cultural services indicator quality. The review builds on scientifically recognized frameworks to develop a holistic understanding of how cultural services indicators are conceived within ecosystem services research. Among the measures found, benefit indicators were most frequently used for assessing inspirational, educational and recreational services. A broad variety of methods for accounting cultural services was found, mainly due to the varied aims of the studies. Most of the cultural services indicators were deficient concerning their clarity of definitions, purposes and understanding of the processes to be measured and referring only marginally to tradeoffs and bundles with other services. Only 17% performed multitemporal assessments and 23% used spatially explicit information. It seems that indicator quality could be greatly enhanced by investing more effort toward involving relevant stakeholders in conceptualization and communication phases, using participatory mapping tools to enhance visibility. © 2013 Elsevier Ltd All rights reserved.

Weis J.,Albert Ludwigs University of Freiburg
Expert Review of Pharmacoeconomics and Outcomes Research | Year: 2011

Cancer-related fatigue (CRF) is one of the most common symptoms reported by patients and is defined as the feeling of extraordinary exhaustion associated with a high level of distress, disproportionate to the patients' activity, and is not relieved by sleep or rest. Prevalence rates range from 59 to nearly 100% depending on the clinical status of the cancer. Except for chemotherapy-induced anemia, the mechanisms responsible for CRF are not yet completely understood. Therefore, CRF may be influenced by multiple possible somatic and psychosocial factors. CRF has been shown as either a short-term side effect of adjuvant cancer therapy or a chronic long-term late effect. Compared with other symptoms, such as pain or nausea, CRF is more distressing and often long lasting, with a strong impact on daily living and quality of life. The concept of fatigue has been widely elaborated and operationalized in different dimensions within the last few decades and specific instruments assessing fatigue in cancer populations have been developed. To support patients and alleviate CRF symptoms various treatment strategies are discussed in this article, including information and counseling, enhancement of activities, exercise and sports therapy, psychosocial interventions as well as pharmacological treatment. In most Western countries, treatment of CRF has been identified as a priority for advancing cancer patient care. This article gives an overview of the concept of CRF, its pathogenesis, assessment and treatment strategies. © 2011 Expert Reviews Ltd.

Arends J.,Albert Ludwigs University of Freiburg
Forschende Komplementarmedizin | Year: 2011

The vitamin D system has been strongly conserved in evolution. It links sun exposure to a multitude of endocrine messages. In most body cells the active hormone calcitriol binds intracellularly to the vitamin D receptor and regulates the expression of specific gene products. Vitamin D deficiency is epidemic affecting some 1 billion people worldwide and is mainly caused by chronically inadequate sun exposure. This deficiency is associated with harmful effects on almost all tissues including a predisposition to cancer. In cancer patients vitamin D deficiency is associated with a worsening of the prognosis. The active hormone calcitriol has anti-tumor activity and is being investigated as an anticancer agent. There is general agreement that exposure to sunlight should be increased while carefully avoiding UV erythema. In addition, recent suggestions call for a health-promoting dietary intake of 25-100 μg (1,000-4,000 IU) of vitamin D3. While supplements of vitamin D improve musculoskeletal symptoms, proof is still lacking that these doses convey a protection from cancer. Interventional studies that administer vitamin D versus placebo in patients with cancer should be a high priority because of the hypothesized benefits and the low risk of supplementation with vitamin D. © 2011 S. Karger GmbH, Freiburg.

Schaefer H.M.,Albert Ludwigs University of Freiburg
Acta Oecologica | Year: 2011

The colours of fleshy fruits are usually attributed to attract seed dispersers to the plant. A cursory look at the gaudy colours of fleshy fruits on offer in a local fruit stall gives the impression that plants use primarily bright colours to attract fruit consumer. This impression is misleading; many small fruits 'go to the dark side' and become dark purple or black when ripe. Intermingled in foliage, these colours, which are produced by anthocyanins, can be fairly inconspicuous and are thus not easily reconciled with a signalling function to attract seed dispersers. In this review I therefore discuss complementary hypotheses on the function and evolution of fruit colouration. First, I focus on the evidence that fruit colours indeed function as signals to attract seed dispersers. I then show that anthocyanins, the most prevalent fruit pigments, are important dietary antioxidants that can be selected by blackcaps (Sylvia atricapilla) which are important avian seed dispersers of many European plants. Moreover, the consumption of anthocyanins increases the likelihood that blackcaps mount an immune response during immune challenges. As a next step, I review evidence that anthocyanins accumulate in fruit skin in response to abiotic factors, in particular high illumination coupled with low temperature favour the increase of anthocyanins. Finally, I show that anthocyanins can also be selected for by fruit antagonists, consumers that do not disperse seeds. In particular, high contents of anthocyanins strongly reduce fungal growth in fruit tissue. Taken together, there are various selective pressures which likely influence fruit colour evolution. Currently, the relative importance of each of these selective agents is unknown. There is consequently a need to develop a more encompassing framework on fruit colour evolution. © 2011 Elsevier Masson SAS.

Bugger H.,Albert Ludwigs University of Freiburg | Abel E.D.,University of Iowa
Diabetologia | Year: 2014

In recent years, diabetes mellitus has become an epidemic and now represents one of the most prevalent disorders. Cardiovascular complications are the major cause of mortality and morbidity in diabetic patients. While ischaemic events dominate the cardiac complications of diabetes, it is widely recognised that the risk for developing heart failure is also increased in the absence of overt myocardial ischaemia and hypertension or is accelerated in the presence of these comorbidities. These diabetes-associated changes in myocardial structure and function have been called diabetic cardiomyopathy. Numerous molecular mechanisms have been proposed to contribute to the development of diabetic cardiomyopathy following analysis of various animal models of type 1 or type 2 diabetes and in genetically modified mouse models. The steady increase in reports presenting novel mechanistic data on this subject expands the list of potential underlying mechanisms. The current review provides an update on molecular alterations that may contribute to the structural and functional alterations in the diabetic heart. © 2014 Springer-Verlag.

Li M.,French Institute of Health and Medical Research | Li M.,University of Strasbourg | Li M.,Albert Ludwigs University of Freiburg
European Respiratory Review | Year: 2014

It has long been observed that the development of asthma, allergic rhinitis and food allergy are frequently preceded by atopic dermatitis, a phenomenon known as the "atopic march". Clinical, genetic and experimental studies have supported the fact that atopic dermatitis could be the initial step of the atopic march, leading to the subsequent development of other atopic diseases. This brief review will focus on the current evidence showing that epidermal barrier dysfunction and the keratinocyte-derived cytokine thymic stromal lymphopoietin play critical roles in the onset of the atopic march. © ERS 2014.

Streuff J.,Albert Ludwigs University of Freiburg
Synthesis (Germany) | Year: 2013

Reductive umpolung reactions of saturated and unsaturated carbonyl compounds enable the direct synthesis of 1,2-, 1,4-, 1,6-, etc. substituted carbon frameworks that are difficult to access by other methodologies. Herein, the evolution from stoichiometric to catalytic processes with high chemo-, regio- and stereoselectivity is discussed for each carbon-carbon bond connection type. At certain points, summaries of the known reaction conditions and discussions of the underlying mechanisms are included. © Georg Thieme Verlag Stuttgart New York.

Kmmerer K.,Albert Ludwigs University of Freiburg
Annual Review of Environment and Resources | Year: 2010

Pharmaceuticals are chemicals that are used because of their biological activity. They are often excreted unchanged and can reach the environment. Throughout developed countries, the pharmaceutical concentrations in the aquatic environment are in the same range (μg L-1 and below); however, it is not clear whether this holds for less-developed countries too. The health risks of active pharmaceutical ingredients (APIs) remain poorly understood. Although there are no known short-term effects on humans, long-term effects cannot be ruled out until there is more research. The significance of metabolites and transformation products resulting from the parent APIs is not yet known. Awareness of the presence of pharmaceuticals in the environment, coupled with some evidence of effects, suggests that precautionary management action to reduce the release of pharmaceuticals to the environment should be considered. As for effluent treatment, no technology works well for all compounds. Advanced effluent treatment is not sustainable because of energy consumption, efficiency, and efficacy. Therefore, its appropriateness must be assessed on a case-by-case basis. Increased handling and use measures at the source and better biodegradable pharmaceuticals are necessary in the long run for the new paradigm called "sustainable pharmacy." Copyright © 2010 by Annual Reviews. All rights reserved.

Dormann C.F.,Albert Ludwigs University of Freiburg | Strauss R.,Technion - Israel Institute of Technology
Methods in Ecology and Evolution | Year: 2014

Summary: Ecological networks are often composed of different subcommunities (often referred to as modules). Identifying such modules has the potential to develop a better understanding of the assembly of ecological communities and to investigate functional overlap or specialization. The most informative form of networks are quantitative or weighted networks. Here, we introduce an algorithm to identify modules in quantitative bipartite (or two-mode) networks. It is based on the hierarchical random graphs concept of Clauset et al. (2008 Nature 453: 98-101) and is extended to include quantitative information and adapted to work with bipartite graphs. We define the algorithm, which we call QuanBiMo, sketch its performance on simulated data and illustrate its potential usefulness with a case study. Modules are detected with a higher accuracy in simulated quantitative networks than in their binary counterparts. Even at high levels of noise, QuanBiMo still classifies 70% of links correctly as within- or between-modules. Recursively applying the algorithm results in additional information of within-module organization of the network. The algorithm introduced here must be seen as a considerable improvement over the current standard of algorithms for binary networks. Due to its higher sensitivity, it is likely to lead to be useful for detecting modules in the typically noisy data of ecological networks. © 2013 British Ecological Society.

Schmitt C.B.,Albert Ludwigs University of Freiburg
Carbon Management | Year: 2013

For REDD+ to achieve synergies between climate and biodiversity objectives, the complex spatial pattern of forest biodiversity needs to be considered. Data on forest cover and species diversity in tropical and subtropical forest types could serve as biodiversity indicators for REDD+ on the global scale. The evaluation of existing global ecological classification systems, forest and land cover maps, and species data shows that diverging definitions of forest and forest types impede the comparison and collation of these datasets. The development of a common classification for (sub)tropical forests could facilitate the evaluation of global biodiversity carbon trade-offs and REDD+ management options, but requires enhanced collaboration between the international organizations involved in forest, carbon and biodiversity research and management. © 2013 Future Science Ltd.

Espinosa C.,Albert Ludwigs University of Freiburg
Journal of Environment and Development | Year: 2014

The proposal to adopt the Universal Declaration of the Rights of Mother Earth (UDRME) sought to challenge the hegemony of green economy at Rio+20. The essence of this proposal is the recognition of nature as a subject holding rights. Adopting a discourse analytical perspective, this article analyzes the advocacy activities for the UDRME at Rio+20 and critically reconstructs the arguments in favor of the Rights of Nature, which condense deliberations about value, humans’ role on Earth, the planet’s physical characteristics, indigenous and traditional people’s wisdom, and the evolution of legal systems. The most prominent aspects of this argumentative endeavor are discussed to assess how a previously unthinkable international environmental normative framework became conceivable. The article contends that connections with long-standing environmental discourses and the enactment of the indigenous speaker position by UDRME advocates are central for understanding how this proposal has become part of contemporary environmental politics. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Rohracher H.,Linkoping University | Spath P.,Albert Ludwigs University of Freiburg
Urban Studies | Year: 2014

The cities of Graz in Austria and Freiburg in Germany have been perceived as ecological model cities since the late 1980s.This is shown by various international awards, press coverage and many visitors from other municipal administrations. Both cities have been well known for their attempts to bring about transitions towards more sustainable and low-carbon energy systems. The comparison of Graz and Freiburg over a period of two decades enables us to study how differing contexts, actor constellations and historic developments shape the transformation of energy systems towards greater sustainability. It is argued that understanding the role of cities for energy transitions requires a detailed examination of the coupled dynamics of socio-technical interactions across the levels of niches, regimes and landscapes on the one hand, and multilevel systems of governance on the other. At these intersections new, although spatially confined, socio-technical constellations of sustainable energy provision may emerge and be stabilised. Nevertheless, empirical evidence shows that it is misleading to conclude that true socio-technical transitions are taking place in these cities, even though a number of foundations for long-term change processes have been laid. © 2013 Urban Studies Journal Limited.

Lee A.,University of Iowa | Fakler B.,Albert Ludwigs University of Freiburg | Kaczmarek L.K.,Yale University | Isom L.L.,University of Michigan
Journal of Neuroscience | Year: 2014

Voltage- and ligand-gated ion channels form the molecular basis of cellular excitability. With>400 members and accounting for∼1.5% of thehumangenome, ion channels are some of the most well studied of all proteins in heterologous expression systems. Yet, ion channels often exhibit unexpected properties in vivo because of their interaction with a variety of signaling/scaffolding proteins. Such interactions can influence the function and localization of ion channels, as well as their coupling to intracellular second messengers and pathways, thus increasing the signaling potential of these ion channels in neurons. Moreover, functions have been ascribed to ion channels that are largely independent of their ion-conducting roles. Molecular and functional dissection of the ion channel proteome/interactome has yielded new insights into the composition of ion channel complexes and how their dysregulation leads to human disease. © 2014 the authors.

Rothe A.,Albert Ludwigs University of Freiburg
Topics in Cognitive Science | Year: 2012

During the last decades, the cognitive sciences and cognitive anthropology have increasingly veered away from each other. Cognitive anthropologists have become so rare within the cognitive sciences that Beller, Bender, and Medin (this issue) even propose a division of the cognitive sciences and cognitive anthropology. However, such a divorce might be premature. This commentary tries to illustrate the benefits that cognitive anthropologists have to offer, not despite, but because of their combination of humanistic and scientific elements. It argues that the cognitive sciences (among others) profit from these benefits, as culture will become crucial for cognitive research. At the same time, problems within cognitive anthropology are discussed, including, for example, the responsibility of cognitive anthropologists to promote young academics. Finally, ideas are presented that might support future interdisciplinary collaboration. © 2012 Cognitive Science Society, Inc..

Winkel G.,Albert Ludwigs University of Freiburg
Global Environmental Change | Year: 2014

Since the 1980s, the US Pacific Northwest has been shattered by a major environmental policy conflict related to the management of Federal forests. These "timber wars" were similar to forest environmental policy conflicts in several other countries, but were particularly polarized. They resulted in a significant change in Federal forest policy from timber production orientation to biodiversity conservation. The change occurred suddenly and had significant economic and social consequences within the region and beyond, but was embedded in long-term societal and institutional trends.In this paper, I adopt an interpretive approach in order to, first, understand contemporary interpretations of the 1993 policy change and, second, to reconstruct the contemporary discursive 'landscape' of the Pacific Northwest including the major resource management paradigms and narratives that guide policy making in this region today. Empirically, my interpretation is mostly built on 37 qualitative interviews with policy stakeholders that were conducted in the summer of 2011.Based on this evidence, the paper argues that there are four narratives circulating amongst policy stakeholders that represent different conceptualizations of the 1993 policy change. Yet, all narratives highlight the importance of environmental strategy making that mobilized the socio-institutional setting in order to prepare and finally achieve the change.Current forest policy in the region is characterized by a policy stalemate resulting from the confluence of diverse institutional, context-related factors and the inability of stakeholders to create enough contradictions or crisis by combining these factors in order to promote change-enabling narratives. Four resource management paradigms compete in the region and, within these, narratives and counter narratives on physical and social events are developed. Current forest policy is dominated by an ecosystem management paradigm, but forest management practices aim to reconcile demands arising from the different paradigms to a certain degree, for instance via the concept of "ecological restoration". Yet, given that the material base that feeds such compromises is finite, a new crisis in Pacific Northwest forest policy in the future is likely.In conclusion, this paper offers an interpretation of Pacific Northwest forest policy (change) as a process in which social and physical events are 'discursively mobilized' by means of narratives that are produced against the background of major natural resources paradigms. This includes the art of 'discourse agents' in constructing problematizations and intervention logics to either defend the current policy state or to increase the likelihood of change. © 2014 Elsevier Ltd.

Streuff J.,Albert Ludwigs University of Freiburg
Chemistry - A European Journal | Year: 2011

Titanium does the job: 1,6-Difunctionalized alkyl units, which are traditionally hard to access, have been successfully obtained through a reductive cross-coupling of activated alkenes catalyzed by TiIII. A plausible reaction mechanism that proceeds through redox umpolung of the enone is briefly discussed (see scheme, Cp=cyclopentadiene). © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Begitt A.,University of Nottingham | Droescher M.,University of Nottingham | Knobeloch K.-P.,Albert Ludwigs University of Freiburg | Vinkemeier U.,University of Nottingham
Blood | Year: 2011

The biologic effects of IFNγ are mediated by the transcription factor STAT1. The activity of STAT1 is inhibited by small ubiquitin-like modifier (SUMO) conjugation. This occurs both directly through decreasing STAT1 tyrosine phosphorylation and indirectly by facilitating STAT1 dephosphorylation consequential to increased STAT1 solubility because of suppressed paracrystal assembly. However, the physiologic implications of SUMO conjugation have remained unclear. Here, we used fibroblasts and bone marrow-derived macrophages (BMMs) from knockin mice expressing SUMO-free STAT1 to explore the consequences of STAT1 sumoylation for IFNγ signaling. Our experiments demonstrated buffer property of paracrystals for activated STAT1, such that SUMO-mediated paracrystal dispersal profoundly reduced phosphorylation of STAT1, which affected both the activating tyrosine 701 and the transcription-enhancing serine 727. Accordingly, the curtailed STAT1 activity in the nucleus caused by SUMO conjugation resulted in diminished transcription of IFNγ- responsive genes; and increased the IFNγ concentration more than 100-fold required to trigger lipopolysaccharide-induced cytotoxicity in bone marrow-derived macrophages. These experiments identify SUMO conjugation of STAT1 as a mechanism to permanently attenuate the IFNγ sensitivity of cells, which prevents hyperresponsiveness to this cytokine and its potentially self-destructive consequences. This sets the mode of SUMO-mediated inhibition apart from the other negative STAT regulators known to date. © 2011 by The American Society of Hematology.

Dengjel J.,Albert Ludwigs University of Freiburg | Abeliovich H.,Hebrew University of Jerusalem
Autophagy | Year: 2014

Mitophagy, or the autophagic degradation of mitochondria, is thought to be important in mitochondrial quality control, and hence in cellular physiology. Defects in mitophagy correlate with late onset pathologies and aging. Here, we discuss recent results that shed light on the interrelationship between mitophagy and mitochondrial dynamics, based on proteomic analyses of protein dynamics in wild-type and mutant cells. These studies show that different mitochondrial matrix proteins undergo mitophagy at different rates, and that the rate differences are affected by mitochondrial dynamics. These results are consistent with models in which phase separation within the mitochondrial matrix leads to unequal segregation of proteins during mitochondrial fission. Repeated fusion and fission cycles may thus lead to "distillation" of components that are destined for degradation. © 2014 Landes Bioscience.

Forrester D.I.,Albert Ludwigs University of Freiburg | Albrecht A.T.,Forest Research Institute of Baden Wurttemberg
Forest Ecology and Management | Year: 2014

There is great interest in how species interactions change along spatial gradients in resource availability and climatic conditions. Many studies have shown that facilitation or complementary effects increase as growing conditions become harsher, however, several studies in forests have recently shown the opposite trend. Increasing complementary effects with improving growing conditions may result when species interactions influence light absorption or use. This hypothesis was tested in mixed-species forests of Abies alba Mill. and Picea abies (L.) Karst. in south-western Germany where complementary effects on growth increased as climatic conditions improved. The absorption of photosynthetically active radiation (APAR) by individual trees was predicted using a detailed light model. Light-use efficiency (LUE) of individual trees was estimated as basal area growth per unit APAR. APAR and LUE were modelled as functions of crown size, climatic variables and the species composition and density of the neighbourhood of individual trees. For a given tree size, APAR (for both species) and LUE (of A. alba trees) were greater for trees in mixed-species neighbourhoods than monospecific neighbourhoods and this complementary effect increased as climatic conditions improved and on sites with faster growing trees. Increases in APAR for A. alba probably resulted because shading from P. abies trees was less intense than that from other A. alba trees on the more productive site. The species composition of individual tree neighbourhoods did not influence relationships between stem diameter and crown diameter or height to the crown base, for either species. However, the height of each species, for a given stem diameter, increased as the proportion of a given tree's neighbourhood basal area that was composed of the same species increased. This change in crown architecture could also have contributed to the complementarity effects in these stands. Increasing complementary effects with improving growing conditions is consistent with the stress-gradient hypothesis if competition for light is considered to be the stressor. This study shows that such a spatial pattern in species interactions could be associated with increasing differences in APAR or LUE between mixtures and monocultures as climatic conditions become more favourable. © 2014 Elsevier B.V.

Oberlack C.,Albert Ludwigs University of Freiburg | Eisenack K.,Carl von Ossietzky University
Global Environmental Change | Year: 2014

International cooperation on climate change adaptation is regarded as one of the major avenues to reduce vulnerability in developing countries. Nevertheless, it remains unclear which design properties of international arrangements match with specific problems in local adaptation processes. This paper analyses conditions and institutional design options under which international cooperation can facilitate climate adaptation in urban areas in developing countries. We conduct a qualitative meta-analysis of empirical evidence from 23 cases. Using the archetype approach, we identify re-appearing barriers and change factors in urban squatter settlements and municipal public sectors in developing countries. We characterise five generic modes of international cooperation for climate adaptation based on UNFCCC documents, process observation, and literature review. Combining these analyses, we develop testable propositions that explain how specific design options of international arrangements can alleviate barriers and make use of change factors for urban adaptation in developing countries. We find, first, that international cooperation has the most potential to tackle adaptation barriers in squatter settlements if its institutional mechanisms support improvements of procedures and rights in localised state-society interactions. Second, national or regional centres of competence may foster endogenous dynamics in municipal public sectors. Third, national adaptation policies can enable and incentivise municipal adaptation. Fourth, flexible indicators of adaptation benefits are instruments to tailor international decision making and monitoring systems to local needs. We conclude that these insights, the archetypes approach, and a multi-level study design can be used to advance research on international cooperation, barriers, and success factors for climate change adaptation. © 2013 Elsevier Ltd.

Ruyter-Spira C.,Wageningen University | Ruyter-Spira C.,Business Unit Bioscience | Al-Babili S.,Albert Ludwigs University of Freiburg | Al-Babili S.,King Abdullah University of Science and Technology | And 4 more authors.
Trends in Plant Science | Year: 2013

The strigolactones are rhizosphere signaling molecules as well as a new class of plant hormones with a still increasing number of biological functions being uncovered. Here, we review a recent major breakthrough in our understanding of strigolactone biosynthesis, which has revealed the unexpected simplicity of the originally postulated complex pathway. Moreover, the discovery and localization of a strigolactone exporter sheds new light on putative strigolactone fluxes to the rhizosphere as well as within the plant. The combination of these data with information on the expression and regulation of strigolactone biosynthetic and downstream signaling genes provides new insights into how strigolactones control the many different aspects of plant development and how their rhizosphere signaling role may have evolved. © 2012 Elsevier Ltd.

Aakeroy C.B.,Kansas State University | Champness N.R.,University of Nottingham | Janiak C.,Albert Ludwigs University of Freiburg
CrystEngComm | Year: 2010

The articles published in the tenth anniversary issue of CrystEngComm are reviewed. The issue highlighted the state-of-the-art of crystal engineering and new trends and developing areas in crystal engineering. In particular, the following article emphasises developments in the areas of intermolecular interactions, notably hydrogen and halogen bonds; metal-organic frameworks or coordination polymers; polymorphism and solvates. © The Royal Society of Chemistry.

Boels R.H.,University of Hamburg | Schwinn C.,Albert Ludwigs University of Freiburg
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

The consequences of on-shell supersymmetry are studied for scattering amplitudes with massive particles in four dimensions. Using the massive version of the spinor-helicity formalism, the supersymmetry transformations relating products of on-shell states are derived directly from the on-shell supersymmetry algebra for any massive representation. Solutions to the resulting Ward identities can be constructed as functions on the on-shell superspaces that are obtained from the coherent-state method. In simple cases, it is shown that these superspaces allow one to construct explicitly supersymmetric scattering amplitudes. Supersymmetric on-shell recursion relations for tree-level superamplitudes with massive particles are introduced. As examples, simple supersymmetric amplitudes are constructed in Supersymmetric Quantum Chromodynamics (SQCD), the Abelian Higgs model, the Coulomb branch of N=4, QCD with an effective Higgs-gluon coupling and for massive vector-boson currents. © 2011 American Physical Society.

Eisenegger C.,University of Zurich | Naef M.,University of Zurich | Naef M.,University of London | Snozzi R.,University of Zurich