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Bonn, Germany

The University of Bonn is a public research university located in Bonn, Germany. Founded in its present form in 1818, as the linear successor of earlier academic institutions, the University of Bonn is today one of the leading universities in Germany. The University of Bonn offers a large number of undergraduate and graduate programs in a range of subjects. Its library holds more than two million volumes. The University of Bonn has 525 professors and 31,000 students. Among its notable alumni and faculty are seven Nobel Laureates, two Fields Medalists, twelve Gottfried Wilhelm Leibniz Prize winners, Prince Albert, Pope Benedict XVI, Frederick III, Karl Marx, Heinrich Heine, Friedrich Nietzsche, Konrad Adenauer, and Joseph Schumpeter. In the years 2010, 2011 and 2013, the Times Higher Education ranked the University of Bonn as one of the 200 best universities in the world. The University of Bonn is ranked 94th worldwide according to the ARWU University ranking. Wikipedia.

Novak N.,University of Bonn | Leung D.Y.M.,National Jewish Health
Current Opinion in Immunology | Year: 2011

Atopic dermatitis (AD) results from barrier defects combined with modified immune responses of the innate and the adaptive immune system to exogenous and endogenous factors. Recent research has continued to sort out the complex pathophysiologic puzzle of this frequent skin disease. However, the network of mechanisms leading to the manifestation of AD is far from being completely understood. © 2011 Elsevier Ltd.

Hoerauf A.,University of Bonn
The Lancet | Year: 2010

Lymphatic filariasis and onchocerciasis are parasitic helminth diseases that constitute a serious public health issue in tropical regions. The filarial nematodes that cause these diseases are transmitted by blood-feeding insects and produce chronic and long-term infection through suppression of host immunity. Disease pathogenesis is linked to host inflammation invoked by the death of the parasite, causing hydrocoele, lymphoedema, and elephantiasis in lymphatic filariasis, and skin disease and blindness in onchocerciasis. Most filarial species that infect people co-exist in mutualistic symbiosis with Wolbachia bacteria, which are essential for growth, development, and survival of their nematode hosts. These endosymbionts contribute to inflammatory disease pathogenesis and are a target for doxycycline therapy, which delivers macrofilaricidal activity, improves pathological outcomes, and is effective as monotherapy. Drugs to treat filariasis include diethylcarbamazine, ivermectin, and albendazole, which are used mostly in combination to reduce microfilariae in blood (lymphatic filariasis) and skin (onchocerciasis). Global programmes for control and elimination have been developed to provide sustained delivery of drugs to affected communities to interrupt transmission of disease and ultimately eliminate this burden on public health. © 2010 Elsevier Ltd.

Ohta S.,Kyoto University | Ohta S.,Max Planck Institute For Mathematik | Sturm K.-T.,University of Bonn
Archive for Rational Mechanics and Analysis | Year: 2012

We study contractivity properties of gradient flows for functions on normed spaces or, more generally, on Finsler manifolds. Contractivity of the flows turns out to be equivalent to a new notion of convexity for the functions. This is different from the usual convexity along geodesics in non-Riemannian Finsler manifolds. As an application, we show that the heat flow on Minkowski normed spaces other than inner product spaces is not contractive with respect to the quadratic Wasserstein distance. © 2012 Springer-Verlag.

Cristinziani M.,University of Bonn
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2010

Vertex detectors at future hadron colliders will need to cope with large particle fluences. Diamond is a particularly radiation hard material and exhibits further properties that makes it an attractive material for such detectors. Within the RD42 collaboration several chemical vapor deposition diamond samples are being studied in the form of strip and pixel detectors. While the quality of the poly-crystalline diamond samples is constantly increasing and the feasibility of producing wafers has been demonstrated, recently a single-crystal diamond pixel detector has been assembled and characterized in a 100 GeV particle beam at CERN. Results on performance, detection efficiency, spatial resolution and charge collection are reported here together with the latest radiation damage studies. © 2010 Elsevier B.V. All rights reserved.

Walter N.T.,University of Bonn
Psychosomatic Medicine | Year: 2011

Objective: To test the hypothesis that the interaction between the brain-derived neurotrophic factor (BDNF) and dopamine receptor D2 (DRD2)/ANKK1 gene contributes to individual differences in alexithymia. The personality construct of alexithymia refers to difficulties in emotional self-regulation and contributes as a risk factor to several mental disorders. Alexithymic individuals show an impoverished conscious experience of emotions but an intact autonomic emotional response. Persons with high alexithymia scores reportedly show a reduced activation of the anterior cingulate cortex (ACC) during the processing of emotional stimuli. An interaction between two polymorphisms on the BDNF and DRD2/ANKK1 gene has been recently associated with reduced gray matter volume in the ACC and higher trait anxiety. Methods: We conducted a genetic association study. A total of 664 healthy participants completed the Toronto Alexithymia Scale questionnaire and were genotyped for the BDNF Val66Met (rs6265) and the DRD2/ANKK1 Taq IA (rs1800497) polymorphisms. Results: Carriers of at least one BDNF 66Met and one DRD2/ANKK1 A1 allele showed the highest scores in the total Toronto Alexithymia Scale and in the subscale "Difficulties Identifying Feelings." CONCLUSION:: In line with recent studies investigating the role of BDNF Val66Met and DRD2/ANKK1 Taq IA polymorphisms on anxiety and gray matter volume in the ACC, our findings provide the first evidence for a genetic contribution to alexithymia. © 2011 by the American Psychosomatic Society.

Imhof L.A.,University of Bonn | Nowak M.A.,Harvard University
Proceedings of the Royal Society B: Biological Sciences | Year: 2010

Evolutionary game theory is the study of frequency-dependent selection. The success of an individual depends on the frequencies of strategies that are used in the population. We propose a new model for studying evolutionary dynamics in games with a continuous strategy space. The population size is finite. All members of the population use the same strategy. A mutant strategy is chosen from some distribution over the strategy space. The fixation probability of the mutant strategy in the resident population is calculated. The new mutant takes over the population with this probability. In this case, the mutant becomes the new resident. Otherwise, the existing resident remains. Then, another mutant is generated. These dynamics lead to a stationary distribution over the entire strategy space. Our new approach generalizes classical adaptive dynamics in three ways: (i) the population size is finite; (ii) mutants can be drawn non-locally and (iii) the dynamics are stochastic. We explore reactive strategies in the repeated Prisoner's Dilemma. We perform 'knock-out experiments' to study how various strategies affect the evolution of cooperation. We find that 'tit-for-tat' is a weak catalyst for the emergence of cooperation, while 'always cooperate' is a strong catalyst for the emergence of defection. Our analysis leads to a new understanding of the optimal level of forgiveness that is needed for the evolution of cooperation under direct reciprocity. © 2009 The Royal Society.

Haidenbauer J.,Julich Research Center | Meissner U.-G.,Julich Research Center | Meissner U.-G.,University of Bonn
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

We analyze the quark mass dependence of the binding energy of the H-dibaryon in the framework of chiral effective field theory. We show that the SU(3) breaking effects induced by the differences of the pertinent two-baryon thresholds (N σσ) have a very pronounced impact that need to be incorporated properly in future lattice QCD simulations. We also point out that if the H-dibaryon is a two-baryon bound state, its dominant component is N rather than which is a consequence of the approximate SU(3) flavor symmetry of the two-baryon interactions. © 2011 Elsevier B.V.

Engqvist L.,University of Groningen | Engqvist L.,University of Bonn
Behavioral Ecology | Year: 2011

In species with high male mating effort, there is a trade-off between mating effort spent in a current mating and resources left for future matings. Males are therefore expected to allocate resources prudently across successive matings. Attractive males that will have a high mating success might therefore be forced to decrease mating investment in comparison with less-attractive males. Furthermore, if there is genetic variation in attractiveness, one might expect to find a negative genetic correlation between attractiveness and mating investment. Here, this genetic prediction is tested using the scorpionfly Panorpa cognata (Insecta: Mecoptera). In this species, males offer costly salivary secretions as nuptial gifts to females. By producing large secretions, males increase copulation duration and sperm transfer, thus gaining an advantage in sperm competition. I used a full-sib breeding design and found that both attractiveness and mating investment showed considerable heritability. Most importantly, there was a significant negative genetic correlation between attractiveness and mating investment: In families with attractive individuals, males produced smaller salivary secretions than in those with less-attractive males. The results thus demonstrate an important evolutionary trade-off between mating success and sperm competition success. © 2011 The Author.

Allanach B.C.,University of Cambridge | Bernhard M.A.,University of Bonn
Computer Physics Communications | Year: 2010

Current publicly available computer programs calculate the spectrum and couplings of the minimal supersymmetric standard model under the assumption of R-parity conservation. Here, we describe an extension to the SOFTSUSY program which includes R-parity violating effects. The user provides a theoretical boundary condition upon the high-scale supersymmetry breaking R-parity violating couplings. Successful radiative electroweak symmetry breaking, electroweak and CKM matrix data are used as weak-scale boundary conditions. The renormalisation group equations are solved numerically between the weak scale and a high energy scale using a nested iterative algorithm. This paper serves as a manual to the R-parity violating mode of the program, detailing the approximations and conventions used. Program summary: Program title: SOFTSUSY v3.0. Catalogue identifier: ADPM_v2_0. Program summary URL: http://cpc.cs.qub.ac.uk/summaries/ADPM_v2_0.html. Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland. Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html. No. of lines in distributed program, including test data, etc.: 75 927. No. of bytes in distributed program, including test data, etc.: 570 916. Distribution format: tar.gz. Programming language: C++, Fortran. Computer: Personal computer. Operating system: Tested on Linux 4.x. Word size: 32 bits. Classification: 11.6. Catalogue identifier of previous version: ADPM_v1_0. Journal reference of previous version: Comput. Phys. Comm. 143 (2002) 305. Does the new version supersede the previous version?: Yes. Nature of problem: Calculating supersymmetric particle spectrum and mixing parameters in the R-parity violating minimal supersymmetric standard model. The solution to the renormalisation group equations must be consistent with a high-scale boundary condition on supersymmetry breaking parameters and Rp parameters, as well as a weak-scale boundary condition on gauge couplings, Yukawa couplings and the Higgs potential parameters. Solution method: Nested iterative algorithm. Reasons for new version: This is an extension to the SOFTSUSY program which includes R-parity violating effects. The user provides a theoretical boundary condition upon the high-scale supersymmetry breaking R-parity violating couplings. Successful radiative electroweak symmetry breaking, electroweak and CKM matrix data are used as weak-scale boundary conditions. The renormalisation group equations are solved numerically between the weak scale and a high energy scale using a nested iterative algorithm. The paper serves as a manual to the R-parity violating mode of the program, detailing the approximations and conventions used. Restrictions: SOFTSUSY3.0 will provide a solution only in the perturbative regime and it assumes that all couplings of the MSSM are real (i.e. CP-conserving). The iterative SOFTSUSY algorithm will not converge if parameters are too close to a boundary of successful electroweak symmetry breaking, but a warning flag will alert the user to this fact. Running time: A few seconds per parameter point. Crown Copyright © 2009.

Tauris T.M.,University of Bonn | Tauris T.M.,Max Planck Institute for Radio Astronomy | Van Den Heuvel E.P.J.,University of Amsterdam
Astrophysical Journal Letters | Year: 2014

The millisecond pulsar in a triple system (PSR J0337+1715, recently discovered by Ransom et al.) is an unusual neutron star with two orbiting white dwarfs. The existence of such a system in the Galactic field poses new challenges to stellar astrophysics for understanding evolution, interactions, and mass transfer in close multiple stellar systems. In addition, this system provides the first precise confirmation for a very wide-orbit system of the white dwarf mass-orbital period relation. Here, we present a self-consistent, semi-analytical solution to the formation of PSR J0337+1715. Our model constrains the peculiar velocity of the system to be less than 160 km s -1 and brings novel insight to, for example, common envelope evolution in a triple system, for which we find evidence for in-spiral of both outer stars. Finally, we briefly discuss our scenario in relation to alternative models. © 2014. The American Astronomical Society. All rights reserved..

Hornung V.,University of Bonn
Immunity | Year: 2014

The innate immune system has evolved sensors that can detect specific molecular fingerprints of non-self RNA or DNA. At the same time, some receptors respond to nucleic acids of both exogenous and endogenous origin, yet they are spatially segregated from endogenous nucleic acids. This SnapShot schematizes families and individual members of nucleic acid sensors with a focus on their ligands and the signaling pathways they employ. Copyright © 2014 Elsevier Inc. All rights reserved.

Perabo F.G.E.,University of Bonn
Drug Discovery Today: Therapeutic Strategies | Year: 2012

Lower urinary tract symptoms (LUTS) have long been an acknowledged complex of clinical manifestations related to a wide variety of urinary function. For a simplified way of addressing LUTS in a diagnostic and therapeutic approach, symptoms were brought into context of either prostate or the bladder pathology. However, current research and development of pharmaceutical agents requires understanding of the complex interaction of receptor pathways, and efferent and afferent signalling processes to successfully target the pathophysiological mechanisms that lead to clinical symptoms of LUTS. Drug development for this indication faces various challenges due to changing treatment paradigms and the evolved understanding of the disease. It is necessary to reflect this in the relationship to real-life clinical practice, bearing in mind patients' perspective, physicians' choices, cost-effectiveness, and the need to develop drugs in the context of what is driving care-seeking behaviour. © 2012 Elsevier Ltd. All rights reserved.

Moreno Mendez E.,National Autonomous University of Mexico | Moreno Mendez E.,University of Bonn
Astrophysical Journal | Year: 2014

Using binary evolution with Case-C mass transfer, the spins of several black holes (BHs) in X-ray binaries (XBs) have been predicted and confirmed (three cases) by observations. The rotational energy of these BHs is sufficient to power up long gamma-ray bursts (GRBs) and hypernovae (HNe) and still leave a Kerr BH behind. However, strong magnetic fields and/or dynamo effects in the interior of such stars deplete their cores from angular momentum preventing the formation of collapsars. Thus, even though binaries can produce Kerr BHs, most of their rotation is acquired from the stellar mantle, with a long delay between BH formation and spin up. Such binaries would not form GRBs. We study whether the conditions required to produce GRBs can be met by the progenitors of such BHs. Tidal-synchronization and Alfvén timescales are compared for magnetic fields of different intensities threading He stars. A search is made for a magnetic field range that allows tidal spin up all the way in to the stellar core but prevents its slow down during differential rotation phases. The energetics for producing a strong magnetic field during core collapse, which may allow for a GRB central engine, are also estimated. An observationally reasonable choice of parameters is found (B ≲ 102 G threading a slowly rotating He star) that allows Fe cores to retain substantial angular momentum. Thus, the Case-C mass-transfer binary channel is capable of explaining long GRBs. However, the progenitors must have low initial spin and low internal magnetic field throughout their H-burning and He-burning phases. © 2014. The American Astronomical Society. All rights reserved.

Guneysu B.,University of Bonn
Journal of Geometry and Physics | Year: 2010

Methods from stochastic analysis are combined with functional analytic methods in order to prove a Feynman-Kac formula för Schrödinger type operators with nonnegative locally square integrable potentials on vector bundles over complete Riemannian manifolds. In particular, we obtain a Feynman-Kac-Itô formula on manifolds for Schrödinger operators with magnetic fields. © 2010 Elsevier B.V.

Pawlowski M.S.,Case Western Reserve University | Kroupa P.,University of Bonn
Astrophysical Journal | Year: 2014

The satellite galaxies of the Milky Way (MW) align with and preferentially orbit in a vast polar structure (VPOS), which also contains globular clusters (GCs) and stellar and gaseous streams. Similar alignments have been discovered around several other host galaxies. We test whether recently discovered objects in the MW halo, the satellite galaxy/GC transition object named PSO J174.0675-10.8774 or Crater and three stellar streams, are part of the VPOS. Crater is situated close to the VPOS. Incorporating the new object in the VPOS-plane fit slightly improves the alignment of the plane with other features such as the Magellanic stream and the average orbital plane of the satellites co-orbiting in the VPOS. We predict Crater's proper motion by assuming that it, too, orbits in the VPOS. One of the three streams aligns well with the VPOS. Surprisingly, it appears to lie in the exact same orbital plane as the Palomar 5 stream and shares its distance, suggesting a direct connection between the two. The stream also crosses close to the Fornax dwarf galaxy and is oriented approximately along the galaxy's direction of motion. The two other streams cannot align closely with the VPOS because they were discovered in the direction of M31/M33, which is outside of the satellite structure. The VPOS thus attains two new members. This further emphasizes that the highly anisotropic and correlated distribution of satellite objects requires an explanation beyond the suggestion that the MW satellite system is an extreme statistical outlier of a ΛCDM sub-halo system. © 2014. The American Astronomical Society. All rights reserved..

Grosse-Brinkhaus C.,University of Bonn
Genetics, selection, evolution : GSE | Year: 2010

Quantitative trait loci (QTL) analyses in pig have revealed numerous individual QTL affecting growth, carcass composition, reproduction and meat quality, indicating a complex genetic architecture. In general, statistical QTL models consider only additive and dominance effects and identification of epistatic effects in livestock is not yet widespread. The aim of this study was to identify and characterize epistatic effects between common and novel QTL regions for carcass composition and meat quality traits in pig. Five hundred and eighty five F pigs from a Duroc × Pietrain resource population were genotyped using 131 genetic markers (microsatellites and SNP) spread over the 18 pig autosomes. Phenotypic information for 26 carcass composition and meat quality traits was available for all F animals. Linkage analysis was performed in a two-step procedure using a maximum likelihood approach implemented in the QxPak program. A number of interacting QTL was observed for different traits, leading to the identification of a variety of networks among chromosomal regions throughout the porcine genome. We distinguished 17 epistatic QTL pairs for carcass composition and 39 for meat quality traits. These interacting QTL pairs explained up to 8% of the phenotypic variance. Our findings demonstrate the significance of epistasis in pigs. We have revealed evidence for epistatic relationships between different chromosomal regions, confirmed known QTL loci and connected regions reported in other studies. Considering interactions between loci allowed us to identify several novel QTL and trait-specific relationships of loci within and across chromosomes.

Ferrari P.L.,University of Bonn
Journal of Statistical Mechanics: Theory and Experiment | Year: 2010

In this contribution we consider stochastic growth models in the Kardar-Parisi-Zhang universality class in 1 + 1 dimension. We discuss the large time distribution and processes and their dependence on the class of initial condition. This means that the scaling exponents do not uniquely determine the large time surface statistics, but one has to further divide into subclasses. Some of the fluctuation laws were first discovered in random matrix models. Moreover, the limit process for curved limit shape turned out to show up in a dynamical version of Hermitian random matrices, but this analogy does not extend to the case of symmetric matrices. Therefore the connection between growth models and random matrices is only partial. © 2010 IOP Publishing Ltd and SISSA.

Martin T.,University of Bonn
Journal of Vertebrate Paleontology | Year: 2013

Isolated bones of forelimb and pelvic girdle (two humeri, five ulnae, and an ilium) recovered from the Late Jurassic (Kimmeridgian) Guimarota coal mine in western central Portugal are attributed to the docodont Haldanodon exspectatus, dryolestoids, and a ?paulchoffatiid multituberculate. The larger of the two humeri is assigned to the dryolestid Dryolestes leiriensis based on size and shape. It clearly exhibits an incipient trochlea at the distal joint, suggesting that this derived character was well established among Late Jurassic dryolestidans, including Henkelotherium. Plesiomorphic characters are the prominent spherical radial condyle and the weakly developed ulnar condyle. An incipient medial keel is present in distal aspect of the humerus trochlea. The shallow olecranon fossa of the humerus corresponds to the small anconeal process of the radius. The smaller humerus with damaged distal joint is 50% smaller and cannot be assigned to a specific dryolestoid taxon. It is in the size range of the smaller Guimarota dryolestoids Krebsotherium, Drescheratherium, and Henkelotherium. One ulna differs from the dryolestoid ulnar shape by the nearly semicircular articular surface for the ulnar condyle of the humerus, the asymmetric olecranon with medial overhang, as well as the prominent anconeal process and is tentatively attributed to a paulchoffatiid multituberculate. © 2013 Copyright Taylor and Francis Group, LLC.

Franz J.,University of Bonn | Gianturco F.A.,University of Rome La Sapienza
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

In the present work we are reporting detailed quantum scattering calculations that describe the diffusion of a beam of low-energy positrons interacting with the pyrimidine target as a gas-phase partner. The calculations have employed an essentially ab initio model for the short-range correlation interaction and for the electrostatic interaction of an impinging positron and the electron+nuclear structure of the target molecule at its equilibrium geometry. The available experiments were also performed in the low-energy region below about 30 eV and have been reported by two different experimental groups cited in the main text. Those data include integral elastic plus rotationally and vibrationally summed cross sections, together with angular distributions over the same range of energies. The effects on the scattering observables which stem from the permanent dipole moment of the title molecule are carefully analyzed and computational corrections which ensure numerical convergence are introduced and discussed. The additional uncertainties introduced by the angular discrimination error present in the experiments are also discussed and analyzed, thereby providing a numerical procedure for correcting all available data. The final comparison between experimental angular distributions and the computed counterparts produced in the present work turns out to be very good. The same applies to the comparison in size and energy dependence of the integral cross sections, where we show that our calculated quantities and the corrected experiments are in very good agreement over the whole range of available energies. © 2013 American Physical Society.

Guo F.-K.,University of Bonn | Hidalgo-Duque C.,University of Valencia | Nieves J.,University of Valencia | Pavon Valderrama M.,University Paris - Sud
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Among the newly observed structures in the heavy-quarkonium mass region, some have been proposed to be hadronic molecules. We investigate the consequences of heavy-quark flavor symmetry on these heavy meson hadronic molecules. The symmetry allows us to predict new hadronic molecules on one hand, and test the hadronic molecular assumption of the observed structures on the other hand. We explore the consequences of the flavor symmetry assuming the X(3872) and Zb(10 610) as an isoscalar DD̄ * and isovector BB̄* hadronic molecule, respectively. A series of hadronic molecules composed of heavy mesons are predicted. In particular, there is an isoscalar 1++ BB ̄* bound state with a mass about 10 580 MeV which may be searched for in the Υ(1S,2S)π+π -π0 mass distribution; the isovector charmonium partners of the Zb(10 610) and the Zb(10 650) are also predicted, which probably corresponds to the very recently observed Zc(3900) and Zc(4025) resonances by the BESIII Collaboration. © 2013 American Physical Society.

Walter J.,University of Bonn
Molecular Medicine | Year: 2015

Alzheimer’s disease (AD) is characterized by progressive decline in cognitive functions associated with depositions of aggregated proteins in the form of extracellular plaques and neurofibrillary tangles in the brain. Extracellular plaques contain characteristic fibrils of amyloid β peptides (Aβ); tangles consist of paired helical filaments of the microtubuli-associated protein tau. Although AD manifests predominantly at ages above 65 years, rare cases show a much earlier onset of disease symptoms with very similar neuropathological characteristics. In 1995, two homologous genes were identified, in which mutations are associated with dominantly inherited familial forms of early onset AD. The genes therefore were dubbed presenilins (PS) and encode polytopic transmembrane proteins. At this time the role of these proteins in the pathogenesis of AD and their biological function in general were completely unknown. However, individuals carrying PS mutations showed alterations in the composition of different length variants of Aβ peptides in blood and cerebrospinal fluid, which indicated the potential involvement of presenilins in the metabolism of Aβ. After 20 years of intense research, the roles of presenilins in Aβ generation as well as important functions in biological processes have been identified. Presenilins represent the catalytic components of protease complexes that directly cleave the amyloid precursor protein (APP) but also many other proteins with important physiological functions. Here, the progress in presenilin research from basic characterization of their cellular functions to the targeting in clinical trials for AD therapy, and potential future directions, will be discussed. © 2015, Uninversity of Michigan. All rights reserved.

Kastenmuller W.,National Institute of Allergy and Infectious Diseases | Kastenmuller W.,University of Bonn | Brandes M.,National Institute of Allergy and Infectious Diseases | Wang Z.,National Institute of Allergy and Infectious Diseases | And 4 more authors.
Immunity | Year: 2013

After an infection, the immune system generates long-lived memory lymphocytes whose increased frequency and altered state of differentiation enhance host defense against reinfection. Recently, the spatial distribution of memory cells was found to contribute to their protective function. Effector memory CD8+ T cells reside in peripheral tissue sites of initial pathogen encounter, in apparent anticipation of reinfection. Here we show that within lymph nodes (LNs), memory CD8+ T cells were concentrated near peripheral entry portals of lymph-borne pathogens, promoting rapid engagement of infected sentinel macrophages. A feed-forward CXCL9-dependent circuit provided additional chemotactic cues that further increase local memory cell density. Memory CD8+ T cells also produced effector responses to local cytokine triggers, but their dynamic behavior differed from that seen after antigen recognition. These data reveal the distinct localization and dynamic behavior of naive versus memory T cells within LNs and how these differences contribute to host defense. © 2013 Elsevier Inc..

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.

Krauss M.E.,University of Wurzburg | Porod W.,University of Wurzburg | Staub F.,University of Bonn
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We consider a supersymmetric model motivated by a SO(10) grand unified theory: the gauge sector near the supersymmetry scale consists of SU(3) c×SU(2)L×U(1)R×U(1) B-L. We embed this model in minimal gauge mediation and incorporate neutrino data via an inverse seesaw mechanism. Also in this restricted model, the additional D terms can raise the light Higgs mass in a sizable way. Therefore, it is much easier to obtain mhâ‰125 GeV without the need to push the supersymmetry spectrum to extremely large values as it happens in models with minimal supersymmetric standard model particle content only. We show that this model predicts a diphoton rate of the Higgs equal to or smaller than the standard model expectation. We discuss briefly the collider phenomenology with a particular focus on the next to lightest supersymmetric particle in which this model offers the sneutrino as an additional possiblity. Moreover, we point out that, also in this model variant, supersymmetry can be discovered in Z′ decays even in scenarios in which the strongly interacting particles are too heavy to be produced at a sizable rate at the LHC with 14 TeV. In addition, we show that lepton flavor violating observables constrain the size of the neutrino Yukawa couplings for which, in particular, muon decays and μ-e conversion in heavy atoms are of particular importance. Once these constraints are fulfilled, the rates for τ decays are predicted to be below the reach of near-future experiments. © 2013 American Physical Society.

Bucker M.,TU Braunschweig | Bucker M.,University of Bonn | Hordt A.,TU Braunschweig
Geophysical Journal International | Year: 2013

Processes related to the membrane-like behaviour of pore throats are generally consideredrelevant for the induced polarization of granular media. A model to describe the impedanceof membrane polarization analytically was suggested previously for a 1-D system, consistingof a sequence of narrow and wide pores of different lengths. In that model, the membraneeffect is caused by different mobilities of the ion species, resulting in different ion transferencenumbers in the two pore types. We extend the model by explicitly including the properties of theelectrical double layer and the pore radii into the impedance calculation. Our basic assumptionis that in a cylindrical pore system, the ion concentrations in the direction perpendicular andparallel to the pore are independent of each other. We then obtain concentrations averaged overthe pore section from known theories of the charge distribution in a cylindrical pore. We alsoinclude the effect of the Stern layer in form of a partition coefficient. Our extension enables usto use the analytical expression of the impedance, but with an extended parametrization of thetransference numbers. We demonstrate the validity of our approach by comparing the resultsof our calculations with previously published numerical simulations for a particular model. The usefulness of our method is illustrated with parameter studies that illustrate the possibledependence of relaxation times on pore radii.© The Authors 2013.

Miller S.A.,University of Bonn
Advances in Geophysics | Year: 2013

Fluids play an integral role in the geodynamical system, from consumption through serpentinization at mid-ocean ridges and outer rises, to release through dehydration and decarbonization within subduction zones and beyond. Fluids affect a number of critical elements of the tectonic cycle, including weakening plate boundaries and catalyzing mantle wedge melting for feeding volcanic arcs. This review paper summarizes the vast topic of the hydrogeological cycle of the solid earth, and how fluids affect, and are affected by, tectonic processes. Ultimately these fluids must either remain trapped in the mantle or return to the surface at high pressure via ductile processes or fracture networks. High pressure fluids returning to the surface may get trapped at the base of the brittle crust, where they can contribute to earthquake nucleation and genesis. Evidence suggests that high pressure fluids are active participants in tectonic earthquakes, and the relatively recent discovery of slow slip earthquakes and non-volcanic tremor phenomena all point to trapped, over-pressured fluids as an underlying mechanical cause. Fluids play an integral role in lithospheric geodynamics, which provides for some speculations about fluids and earthquakes in a general sense. One such speculation is that spatial aftershock patterns reflect fluid pathways taken by the release of high pressure fluids triggered by the earthquake mainshock. Some of these patterns are shown, and I introduce the term " Zen Trees" to describe them because of their aesthetic form and their resemblance to Eastern calligraphy. I hypothesize that earthquakes that do not spawn significant aftershock sequences indicate little if any trapped high pressure fluids at depth, while earthquakes producing long-lived aftershock sequences point to large reservoirs of trapped high pressure fluids. Although the viscous mantle is the ultimate geophysical fluid, the focus in this paper is limited to fluids in the lithosphere because this boundary, typically treated as a thermal boundary layer, is controlled by complex dynamical interactions between fracture, deformation, dissolution/precipitation, and fluid flow. © 2013 Elsevier Inc.

Hujo W.,University of Munster | Grimme S.,University of Bonn
Journal of Chemical Theory and Computation | Year: 2013

The nonlocal, electron density dependent dispersion correction of Vydrov and Van Voorhis (Vydrov, O. A.; Van Voorhis, T. J. Chem. Phys.2010, 133, 244103), termed VV10 or DFT-NL, has been implemented for structural optimizations of molecules. It is tested in combination with the four (hybrid)GGA density functionals TPSS, TPSS0, B3LYP, and revPBE38 for inter- and intramolecular noncovalent interactions (NCI) and compared to results from atom-pairwise dispersion corrected DFT-D3. The methods are applied to a wide range of different problems, namely the S22 and S66 test sets, large transition metal complexes, water hexamer clusters, hexahelicene, and four other difficult cases of intramolecular NCI. Critical interatomic distances are computed remarkably accurately by both dispersion corrections compared to theoretical or experimental reference data and inter- and intramolecular interactions are treated on equal footing. The methods can be recommended as reliable and robust tools for geometry optimizations of large systems in which long-range dispersion forces are crucial. © 2012 American Chemical Society.

Forstner W.,University of Bonn
International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences - ISPRS Archives | Year: 2010

The paper presents a method for automatically and optimally determining the vanishing points of a single image, and in case the interior orientation is given, the rotation of an image with respect to the intrinsic coordinate system of a lego land scene. We perform rigorous testing and estimation in order to be as independent on control parameters as possible. This refers to (1) estimating vanishing points from line segments and the rotation matrix, (2) to testing during RANSAC and during boosting lines and (3) to classifying the line segments w. r. t. their vanishing point. Spherically normalized homogeneous coordinates are used for line segments and especially for vanishing points to allow for points at infinity. We propose a minimal representation for the uncertainty of homogeneous coordinates of 2D points and 2D lines and rotations to avoid the use of singular covariance matrices of observed line segments. This at the same time allows to estimate the parameters with a minimal representation. The vanishing point detection method is experimentally validated on a set of 292 images.

Staub F.,University of Bonn
Computer Physics Communications | Year: 2013

SARAH is a Mathematica package optimized for the fast, efficient and precise study of supersymmetric models beyond the MSSM: a new model can be defined in a short form and all vertices are derived. This allows SARAH to create model files for FeynArts/FormCalc, CalcHep/CompHep and WHIZARD/O'Mega. The newest version of SARAH now provides the possibility to create model files in the UFO format which is supported by MadGraph 5, MadAnalysis 5, GoSam, and soon by Herwig++. Furthermore, SARAH also calculates the mass matrices, RGEs and 1-loop corrections to the mass spectrum. This information is used to write source code for SPheno in order to create a precision spectrum generator for the given model. This spectrum-generator-generator functionality as well as the output of WHIZARD and CalcHep model files has seen further improvement in this version. Also models including Dirac gauginos are supported with the new version of SARAH, and additional checks for the consistency of the implementation of new models have been created. Program summary: Program title:SARAH Catalogue identifier: AEIB-v2-0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ AEIB-v2-0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 3 22 411 No. of bytes in distributed program, including test data, etc.: 3 629 206 Distribution format: tar.gz Programming language: Mathematica. Computer: All for which Mathematica is available. Operating system: All for which Mathematica is available. Classification: 11.1, 11.6. Catalogue identifier of previous version: AEIB-v1-0 Journal reference of previous version: Comput. Phys. Comm. 182 (2011) 808 Does the new version supersede the previous version?: Yes, the new version includes all known features of the previous version but also provides the new features mentioned below. Nature of problem: To use Madgraph for new models it is necessary to provide the corresponding model files which include all information about the interactions of the model. However, the derivation of the vertices for a given model and putting those into model files which can be used with Madgraph is usually very time consuming. Dirac gauginos are not present in the minimal supersymmetric standard model (MSSM) or many extensions of it. Dirac mass terms for vector superfields lead to new structures in the supersymmetric (SUSY) Lagrangian (bilinear mass term between gaugino and matter fermion as well as new D-terms) and modify also the SUSY renormalization group equations (RGEs). The Dirac character of gauginos can change the collider phenomenology. In addition, they come with an extended Higgs sector for which a precise calculation of the 1-loop masses has not happened so far. Solution method: SARAH calculates the complete Lagrangian for a given model whose gauge sector can be any direct product of SU(N) gauge groups. The chiral superfields can transform as any, irreducible representation with respect to these gauge groups and it is possible to handle an arbitrary number of symmetry breakings or particle rotations. Also the gauge fixing is automatically added. Using this information, SARAH derives all vertices for a model. These vertices can be exported to model files in the UFO which is supported by Madgraph and other codes like GoSam, MadAnalysis or ALOHA. The user can also study models with Dirac gauginos. In that case SARAH includes all possible terms in the Lagrangian stemming from the new structures and can also calculate the RGEs. The entire impact of these terms is then taken into account in the output of SARAH to UFO, CalcHep, WHIZARD, FeynArts and SPheno. Reasons for new version: SARAH provides, with this version, the possibility of creating model files in the UFO format. The UFO format is supposed to become a standard format for model files which should be supported by many different tools in the future. Also models with Dirac gauginos were not supported in earlier versions. Summary of revisions: Support of models with Dirac gauginos. Output of model files in the UFO format, speed improvement in the output of WHIZARD model files, CalcHep output supports the internal diagonalization of mass matrices, output of control files for LHPC spectrum plotter, support of generalized PDG numbering scheme PDG.IX, improvement of the calculation of the decay widths and branching ratios with SPheno, the calculation of new low energy observables are added to the SPheno output, the handling of gauge fixing terms has been significantly simplified. Restrictions: SARAH can only derive the Lagrangian in an automatized way for N=1 SUSY models, but not for those with more SUSY generators. Furthermore, SARAH supports only renormalizable operators in the output of model files in the UFO format and also for CalcHep, FeynArts and WHIZARD. Also color sextets are not yet included in the model files for Monte Carlo tools. Dimension 5 operators are only supported in the calculation of the RGEs and mass matrices. Unusual features: SARAH does not need the Lagrangian of a model as input to calculate the vertices. The gauge structure, particle and content and superpotential as well as rotations stemming from gauge symmetry breaking are sufficient. All further information is derived by SARAH on its own. Therefore, the model files are very short and the implementation of new models is fast and easy. In addition, the implementation of a model can be checked for physical and formal consistency. In addition, SARAH can generate Fortran code for a full 1-loop analysis of the mass spectrum in the context for Dirac gauginos. Running time: Measured CPU time for the evaluation of the MSSM using a Lenovo Thinkpad X220 with i7 processor (2.53 GHz). Calculating the complete Lagrangian: 9 s. Calculating all vertices: 51 s. Output of the UFO model files: 49 s. © 2013 Elsevier B.V. All rights reserved.

Koschorreck M.,University of Cambridge | Pertot D.,University of Cambridge | Vogt E.,University of Cambridge | Kohl M.,University of Cambridge | Kohl M.,University of Bonn
Nature Physics | Year: 2013

Harnessing spins as information carriers has emerged as an elegant extension to the transport of electrical charges. The coherence of such spin transport in spintronic circuits is determined b. The lifetime of spin excitations and by spin diffusion. Fermionic quantum gases allo. The study of spin transport from first principles because interactions can be precisely tailored an. The dynamics is on directly observable timescales. In particular, at unitarity, spin transport is dictated by diffusion an. The spin diffusivity is expected to reach a universal, quantum-limited value of the order of the reduced Planck constant Ä§ divided b. The mass m. Here, we study a two-dimensional Fermi gas after a quench into a metastable, transversely polarized state. Usin. The spin-echo technique, for strong interactions, we measur. The lowest transverse spin diffusion constant so far 0.25(3) Ä§/m. For weak interactions, we observe a collective transverse spin-wave mode that exhibits mode softening when approachin. The strongly interacting regime. © 2013 Macmillan Publishers Limited. All rights reserved.

Orfanos Z.,University of York | Orfanos Z.,University of Bonn | Sparrow J.C.,University of York
Journal of Cell Science | Year: 2013

During muscle development myosin molecules form symmetrical thick filaments, which integrate with the thin filaments to produce the regular sarcomeric lattice. In Drosophila indirect flight muscles (IFMs) the details of this process can be studied using genetic approaches. The weeP26 transgenic line has a GFP-encoding exon inserted into the single Drosophila muscle myosin heavy chain gene, Mhc. The weeP26 IFM sarcomeres have a unique MHC-GFP-labelling pattern restricted to the sarcomere core, explained by nontranslation of the GFP exon following alternative splicing. Characterisation of wild-type IFM MHC mRNA confirmed the presence of an alternately spliced isoform, expressed earlier than the major IFM-specific isoform. The two wild-type IFM-specific MHC isoforms differ by the presence of a C-terminal 'tailpiece' in the minor isoform. The sequential expression and assembly of these two MHCs into developing thick filaments suggest a role for the tailpiece in initiating A-band formation. The restriction of the MHC-GFP sarcomeric pattern in weeP26 is lifted when the IFM lack the IFM-specific myosin binding protein flightin, suggesting that it limits myosin dissociation from thick filaments. Studies of flightin binding to developing thick filaments reveal a progressive binding at the growing thick filament tips and in a retrograde direction to earlier assembled, proximal filament regions. We propose that this flightin binding restricts myosin molecule incorporation/dissociation during thick filament assembly and explains the location of the early MHC isoform pattern in the IFM A-band. © 2013.

Kamper N.,University of Bonn
PloS one | Year: 2012

The human lymphocyte antigen (HLA) encoded BAT3/BAG6 recently attracted interest as a regulator of protein targeting and degradation, a function that could be exerted in the cytosol and in the nucleus. The BAT3 gene was described to consist of 25 exons. Diversity of transcripts can be generated by alternative RNA splicing, which may control subcellular distribution of BAT3. By cDNA sequencing we identified a novel alternatively spliced sequence of the BAT3 gene located between exons 11 and 12, which was designated as exon 11B. Using PCR and colony hybridization we identified six cDNA variants, which were produced by RNA splicing of BAT3 exons 5, 11B and 24. In four examined cell types the content of BAT3 splice variants was examined. Most of the cDNA clones from monocyte-derived dendritic cells contain exon 11B, whereas this sequence was almost absent in the B lymphoma Raji. Exon 5 was detected in most and exon 24 in approximately half of the cDNA clones. The subcellular distribution of endogenous BAT3 largely correlates with a cell type specific splicing pattern. In cells transfected with BAT3 variants, full-length and Δ24 BAT3 displayed nearly exclusive nuclear staining, whereas variants deleted of exon 11B showed substantial cytosolic expression. We show here that BAT3 is mainly expressed in the cytosol of Raji cells, while other cell types displayed both cytosolic and nuclear staining. Export of BAT3 from the nucleus to the cytosol is inhibited by treatment with leptomycin B, indicating that the Crm1 pathway is involved. Nuclear expression of BAT3 containing exon 11B suggests that this sequence plays a role for nuclear retention of the protein. Cell type-specific subcellular expression of BAT3 suggests distinct functions in the cytosol and in the nucleus. Differential expression of BAT3 variants may reconcile the multiple roles described for BAT3.

Fell J.,University of Bonn
Frontiers in Human Neuroscience | Year: 2013

The investigation of resting state activity has become an extremely busy topic in neurocognitive research. A recent pubmed search revealed more than 2000 entries for the terms "resting state" AND "fMRI". Several putative clinical applications have been suggested, such as the detection of early signs of Alzheimer's disease (e.g. Lustig et al., 2003) or risk of developing psychosis (e.g. Jukuri et al., 2013). However, the usefulness of resting state data is hampered by the fact, that up to now only very few investigations have tried to elucidate the mental processes occurring during these experiments. Without knowledge of these processes the purely physiologically based findings of altered activations and functional connectivities during resting state lack a meaningful neurocognitive interpretation. © 2013 Fell.

Dohrenbusch R.,University of Bonn
Versicherungsmedizin / herausgegeben von Verband der Lebensversicherungs-Unternehmen e.V. und Verband der Privaten Krankenversicherung e.V | Year: 2011

The consideration of response bias is essential in the assessment of mental and psychosomatic disorders. In forensic contexts, as compared to clinical evaluations, an elevated rate of response distortions must be expected. Assessment methods should be selected with respect to the risk of either malingering or defensiveness. The choice of assessment strategies and instruments depends on the legal context of the examination. It is recommended that the consistency and plausibility of data from different levels and sources should be systematically analysed. Psychological test results should be integrated in this analysis. If the purpose of a test is obvious to the patient, the test result should be interpreted with respect to results from additional validity scales or symptom validity tests. In civil forensic evaluations of mental and psychosomatic disorders, the use of criterion-based content analysis is expected to be of limited benefit for the validation of symptoms and disability.

Bieber T.,University of Bonn
Annals of Dermatology | Year: 2010

Atopic dermatitis (AD) is a chronic and relapsing disease affecting an increasing number of patients. Usually starting in early childhood, AD can be the initial step of the so-called atopic march, i.e. followed by allergic rhinitis and allergic asthma. AD is a paradigmatic genetically complex disease involving gene-gene and gene-environment interactions. Genetic linkage analysis as well as association studies have identified several candidate genes linked to either the epidermal barrier function or to the immune system. Stress, bacterial or viral infections, the exposure to aero- or food-allergens as well as hygienic factors are discussed to aggravate symptoms of AD. Athough generalized Th2deviated immune response is closely linked to the condition of AD, the skin disease itself is a biphasic inflammation with an initial Th2 phase and while chronic lesions harbour Th0/Th1 cells. Regulatory T cells have been shown to be altered in AD as well as the innate immune system in the skin. The main treatment-goals include the elimination of inflammation and infection, preserving and restoring the barrier function and controlling exacerbating factors. The overall future strategy in AD will be aimed to control skin inflammation by a more proactive management in order to potentially prevent the emergence of sensitization as well as to design customized management based on genetic and pathophysiologic information.

Zimmer A.,University of Bonn
Journal of Basic and Clinical Physiology and Pharmacology | Year: 2016

Investigations into the cellular and molecular mechanisms underlying the psychoactive effects of cannabis preparations have led to the discovery of the endocannabinoid system. Interest in the central nervous system effects was initially the main focus of the research, but it soon became evident that the endocannabinoid system affects virtually every organ. The research field has therefore experienced a tremendous growth over the last decade and is now truly interdisciplinary. This short review provides a personal account of an interdisciplinary collaboration between Itai Bab from the Hebrew University of Jerusalem and the author. It describes the discovery of the endocannabinoid system in bone and the analysis of its functions. I am summarising the role of CB1 signalling as a modulator of sympathetic inhibition of bone formation. Thus, activation of CB1 receptors on sympathetic nerve terminals in bone, presumably from endocannabinoids released from apposing osteoblasts, reduces the inhibition of bone formation of sympathetic norepinephrine. CB2 receptors on osteoblasts and osteoclasts also modulate the proliferation and functions of these cells. Thus, activation of CB2 stimulates bone formation and represses bone resorption, whereas the genetic disruption of CB2 results in an osteoporosis-like phenotype. This signalling mechanism is clinically relevant, as shown by the association of polymorphisms in the CB2 receptor gene, CNR2, with bone density and osteoporosis. Finally, the review provides a summary of the recently discovered role of endocannabinoid signalling in one elongation. This review will also discuss the benefits of interdisciplinary and international collaborations. © 2016 by De Gruyter.

Tamboli I.Y.,University of Bonn
Autophagy | Year: 2011

Recent work from our laboratory demonstrates that the accumulation of sphingolipids (SLs) decreases the capacity of cells to clear potentially amyloidogenic fragments of the amyloid precursor protein (APP) during autophagy. APP is a type I membrane protein and could undergo sequential proteolytic processing by β- and γ-secretase resulting in the generation of the amyloid β-peptide (Aβ). Genetic, molecular and biochemical evidence indicates that the accumulation of toxic Aβ aggregates plays a critical role in the degeneration of neurons during the pathogenesis of Alzheimer disease (AD). Thus, SL storage could promote the accumulation of Ab in endosomal and lysosomal compartments and thereby induce characteristic cytopathological changes of AD.

Filatov M.,University of Bonn
Journal of Chemical Theory and Computation | Year: 2013

A number of commonly available density functionals have been tested for their ability to describe the energetics and the geometry at conical intersections in connection with the spin-restricted ensemble referenced Kohn-Sham (REKS) method. The minimum energy conical intersections have been optimized for several molecular systems, which are widely used as paradigmatic models of photochemical rearrangements and models of biological chromophores. The results of the calculations are analyzed using the sign-change theorem of Longuet-Higgins and a method of elementary reaction coordinates of Haas et al. The latter approach helps to elucidate the differences between the geometries at conical intersections as predicted by the multireference wave function ab initio methods and by the density functional methods. Overall, the BH&HLYP density functional yields the best results for the conical intersection geometries and energetics. © 2013 American Chemical Society.

Kolter T.,University of Bonn
Chemistry and Physics of Lipids | Year: 2011

Sphingolipid and glycosphingolipid levels and expression of sphingolipid metabolizing enzymes are altered in a variety of diseases or in response to drug treatment. Inherited defects of enzymes and other proteins required for the lysosomal degradation of these lipids lead to human sphingolipidoses. Also genetic defects that affect sphingolipid biosynthesis are known. Although the molecular details are often far from clear, (glyco)sphingolipids have been implicated to play a role in atherosclerosis, insulin resistance, cancer, and infections by pathogens. More general aspects of selected diseases are discussed. © 2011 Elsevier Ireland Ltd.

Garschagen M.,University of Bonn
Natural Hazards | Year: 2013

Resilience theory has gained considerable prominence with regard to the management of social-ecological systems and more recently climate change adaptation. Yet, how resilience is precisely understood, how its institutionalisation works and how organisations can operationalise principles for achieving resilience often remains vague. Therefore, the paper explores how institutional and organisational theory can enhance the understanding on resilience. Linking organisational institutionalism to resilience theory, the paper analyses in particular how resilience thinking can diffuse and translate into organisational action, and which challenges and barriers may exist. Empirical research on formal urban climate change adaptation in Vietnam is used to explore the important role of distinctive institutional features in a given culture, region or sector for shaping this process. It is argued that such context-specific institutional framework conditions are often underemphasised, thereby, hampering the transferability as well as operationalisation and implementation of resilience propositions. Relevant aspects include epistemological, ontological and normative dimensions. Linking the case study to neoinstitutional theory, recommendations are developed for increasing the intercultural transferability of resilience thinking into organisational practices. © 2011 Springer Science+Business Media B.V.

Perrings C.,Arizona State University | Duraiappah A.,University of Bonn | Larigauderie A.,French Natural History Museum | Mooney H.,Stanford University
Science | Year: 2011

Assessments must provide conditional predictions of the consequences of specific policy options, at well-defined spatial and temporal scales.

Molderings G.J.,University of Bonn
Translational Research | Year: 2016

Systemic mast cell activation disease (MCAD) comprises disorders characterized by an enhanced release of mast cell mediators accompanied by a varying accumulation of dysfunctional mast cells. Within the last years, evidence has been presented that MCAD is a multifactorial polygenic determined disease with the KITD816V mutation and its induced functional consequences considered as special case. The respective genes encode proteins for various signaling pathways, epigenetic regulators, the RNA splicing machinery, and transcription factors. Transgenerational transmission of MCAD appears to be quite common. The basics of the molecular mechanisms underlying predisposition of the disease, that is, somatic and germline mutations and the contribution of epigenetic processes have become identifiable. The aim of the present review is to present and discuss available genetic, epigenetic and epidemiological findings, and to present a model of MCAD pathogenesis. © 2016 Elsevier Inc.

Kambeitz J.,Ludwig Maximilians University of Munich | Romanos M.,University of Wurzburg | Ettinger U.,University of Bonn
Pharmacogenomics Journal | Year: 2014

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent childhood-onset neuropsychiatric disorder. Treatment with methylphenidate, which blocks dopamine and noradrenaline transporters, is clinically efficacious in reducing the symptoms of ADHD. However, a considerable proportion of patients show no or only insufficient response to methylphenidate. Following a pharmacogenetic approach, a number of studies have suggested that heterogeneity in treatment response across subjects might to some extent be due to genetic factors. In particular, a variable number tandem repeat (VNTR) polymorphism in the 3′ untranslated region of the SLC6A3 gene, which codes for the dopamine transporter, has been considered as a predictor of treatment success. However, the literature has so far been inconsistent. Here we present results of a meta-analysis of studies investigating the moderating effect of the SLC6A3 VNTR on response to methylphenidate treatment in subjects with ADHD. Outcome measures from 16 studies including data from 1572 subjects were entered into a random-effects model. There was no significant summary effect for the SLC6A3 VNTR on the response to methylphenidate treatment (P>0.5) and no effect on specific symptom dimensions of hyperactivity/impulsivity and inattention (all P>0.2). However, in a subanalysis of naturalistic trials, we observed a significant effect of d=-0.36 (P=0.03), indicating that 10R homozygotes show less improvement in symptoms following treatment than the non-10/10 carriers. This meta-analysis indicates that SLC6A3 VNTR is not a reliable predictor of methylphenidate treatment success in ADHD. Our study leaves unanswered the question of whether other genetic polymorphisms or nongenetic factors may contribute to the observed heterogeneity in treatment response across ADHD subjects. © 2014 Macmillan Publishers Limited All rights reserved.

Stock I.,University of Bonn
Medizinische Monatsschrift fur Pharmazeuten | Year: 2014

Enterobacteriaceae species such as Escherichia coli and Klebsiella pneumoniae are among the most common human pathogens. They are responsible for a wide range of community-acquired and nosocomial diseases. Many of the illnesses caused by these bacteria could be treated with beta-lactams for several decades. The increasing use of carbapenems for the treatment of diseases caused by Enterobacteriaceae expressing extended spectrum beta-lactamases, however, lead to the selection and spread of carbapenemase-producing pathogens. Such bacteria are not only resistant to virtually all beta-lactams, but also to numerous other antibiotics such as quinolones, co-trimoxazole, nitrofurantoin, tetracyclines and most aminoglycosides. During the last years, carbapenemase-producing Enterobacteriaceae have spread into almost all regions of the world. Klebsiella pneumoniae carbapenemases (KPC, belonging to Ambler class A), OXA-48 enzymes and their derivatives (belonging to Ambler class D) as well as some metallo-beta-lactamases (Ambler class B) such as NDM, VIM and IMP are the most important carbapenemases produced by Enterobacteriaceae strains. In Germany, the metallo-carbapenemase GIM-1, which has never been proven in bacteria outside Germany, is also of clinical significance. There is no established antibacterial therapy for these difficult-to-treat diseases. For the treatment of severe diseases caused by carbapenemase-producing bacteria, fosfomycin, gentamicin and tigecycline, polymyxins such as polymyxin B or colistin as well as carbapenems, are frequently applied. Combination antibiotic treatment may be more effective than monotherapy for severe ill patients with serious diseases. The most promising new treatment options arise with the development of avibactam. This non-beta-lactam beta-lactamase inhibitor shows good activity against (nearly) all class A and class C beta-lactamases (including strains expressing class A carbapenemases and/or derepressed AmpC enzymes) as well as OXA-48 carbapenemases. It may be used successfully in combination with ceftazidime, ceftaroline or aztreonam. © Deutscher Apotheker Verlag.

Schultze J.L.,University of Bonn
EMBO Journal | Year: 2014

Inflammation is a hallmark of many common diseases ranging from arthritis, atherosclerosis, or obesity to Alzheimer's disease and cancer. Identifying anti-inflammatory mechanisms is therefore an important and timely task of modern biomedicine. In this issue of The EMBO Journal, a study conducted by Escolano and colleagues target a particular interaction site of calcineurin with NFAT in macrophages to elicit profound anti-inflammatory effects (Escolano et al, 2014). Peptide-based targeting of a unique calcineurin/NFAT interaction site in macrophages reveals anti-inflammatory potential for various major diseases. © 2014 The Author.

Muller C.E.,University of Bonn
Current Medicinal Chemistry | Year: 2014

P2X receptors are trimeric ligand-gated ion channels whose potential as novel drug targets for a number of diseases has been recognized. They are mainly involved in inflammatory processes, including neuroinflammation, and pain sensation. The orthosteric binding site is lined by basic amino acid residues that bind the negatively charged agonist ATP. Therefore it is not easy to develop orthosteric ligands that possess drug-like properties for such a highly polar binding site. However, ligand-gated ion channels offer multiple additional binding sites for allosteric ligands, positive or negative allosteric modulators enhancing or blocking receptor function. So far, the P2X3 (and P2X2/3), as well as the P2X7 receptor subtype have been the main focus of drug development efforts. A number of potent and selective allosteric antagonists have been developed to block these receptors. We start to see the development of novel allosteric ligands also for the other P2X receptor subtypes, P2X1, P2X2 and especially P2X4. The times when only poor, non-selective, non-drug-like tools for studying P2X receptor function were available have been overcome. The first clinical studies with allosteric P2X3 and P2X7 antagonists suggest that P2X therapeutics may soon become a reality. Copyright © 2015 Bentham Science Publishers.

Saravanan V.S.,University of Bonn
Environmental Science and Policy | Year: 2015

To steer the socio-political process of water management towards a desired institutional change, scholars have adopted distinctive approaches focusing either on deliberate 'designing' of institutions or by emphasizing on the ability of agents to craft institutions. Applying ecological institutionalism as an overarching framework, the paper takes a complementary perspective of designing and crafting by heuristically examining the agents and their negotiation of power as linked with the institutions through an ethnographic method of long-time observation. By focusing on agents in their everyday practice of water management, the paper identifies five different types of agents - goal-oriented agents, agents maintaining positions, opportunistic, reactive, and supportive agents. These agents integrate institutions through historic specificity and rationality to enter the decision-making arena, and use their logic of action to display their power to bring about institutional change. They play a crucial role that underpins effective trajectories of policy development and implementation. Applying new institutionalism offers insights into three significant areas of water management - significant role of institutions, ability of agents to integrate multilayered institutions, and diverse forms of power displayed in the arenas. These three elements help us to better comprehend the complementary between designing and crafting of institutions to facilitate desired change. © 2015 Elsevier Ltd.

Belke A.,University of Duisburg - Essen | Bordon I.G.,University of Duisburg - Essen | Volz U.,University of Bonn
World Development | Year: 2013

This article investigates the relationship between global liquidity and commodity and food prices applying a global cointegrated vector-autoregressive model. We use different measures of global liquidity and various indices of commodity and food prices for the period 1980-2011. Our results support the hypothesis that there is a positive long-run relation between global liquidity and the development of food and commodity prices, and that food and commodity prices adjust significantly to this cointegrating relation. Global liquidity, in contrast, does not adjust, it drives the relationship. © 2012 Elsevier Ltd.

Schluessel V.,University of Bonn
Animal Cognition | Year: 2015

Adaptation of brain structures, function and higher cognitive abilities most likely have contributed significantly to the evolutionary success of elasmobranchs, but these traits remain poorly studied when compared to other vertebrates, specifically mammals. While the pallium of non-mammalian vertebrates lacks the mammalian neocortical organization responsible for all cognitive abilities of mammals, several behavioural and neuroanatomical studies in recent years have clearly demonstrated that elasmobranchs, just like teleosts and other non-mammalian vertebrates, can nonetheless solve a multitude of cognitive tasks. Sharks and rays can learn and habituate, possess spatial memory; can orient according to different orientation strategies, remember spatial and discrimination tasks for extended periods of time, use tools; can imitate and learn from others, distinguish between conspecifics and heterospecifics, discriminate between either visual objects or electrical fields; can categorize visual objects and perceive illusory contours as well as bilateral symmetry. At least some neural correlates seem to be located in the telencephalon, with some pallial regions matching potentially homologous areas in other vertebrates where similar functions are being processed. Results of these studies indicate that the assessed cognitive abilities in elasmobranchs are as well developed as in teleosts or other vertebrates, aiding them in fundamental activities such as food retrieval, predator avoidance, mate choice and habitat selection. © 2014, Springer-Verlag Berlin Heidelberg.

Pye O.,University of Bonn
Journal of Peasant Studies | Year: 2010

The 10 percent mandatory target for 'renewable energy' adopted by the European Parliament in December 2008 is fuelling a frenzy of investment in palm oil across Southeast Asia, leading in turn to the emergence of new, transnational campaign alliances. The specific dynamics of alliance building, political strategies and impacts of palm oil activism are shaped by the key role of the Indonesian environmental and agrarian justice movement, the broadening and radicalisation of groups in Europe and the ways in which these are interconnected by transnational activists. Campaigning has been successful in creating a transnational political debate around palm oil and biofuels and in influencing public opinion in Europe. Peasant activists have played an important role by combining issues of biodiversity and climate change with food sovereignty and by embedding the critique of biofuels within the global movement for climate justice. However, discontented palm oil smallholders and plantation workers are conspicuously absent at the transnational level. Building alliances between agrarian movements and plantation workers could strengthen the movement against biofuels by tapping into the potential offered by the transnational social and economic spaces which characterise the palm oil industry. © 2010 Taylor & Francis.

Struzyna M.,University of Bonn
Proceedings -Design, Automation and Test in Europe, DATE | Year: 2011

This paper presents a new quadratic, partitioning-based placement algorithm which is able to handle non-convex and overlapping position constraints to subsets of cells, the movebounds. Our new flow-based partitioning (FBP) combines a global MinCostFlow model for computing directions with extremely fast and highly parallelizable local realization steps. Despite its global view, the size of the MinCostFlow instance is only linear in the number of partitioning regions and does not depend on the number of cells. We prove that our partitioning scheme finds a (fractional) solution for any given placement or decides in polynomial time that none exists. In practice, BonnPlace with FBP can place huge designs with almost 10 million cells and dozens of movebounds in 90 minutes of global placement. On instances with movebounds, the netlengths of our placements are more than 32% shorter than RQL's [25] and our tool is 9-20 times faster. Even without movebounds, the FBP improves the quality and runtime of BonnPlace significantly and our tool shows the currently best results on the latest placement benchmarks [16]. © 2011 EDAA.

Knief C.,University of Bonn
Frontiers in Microbiology | Year: 2015

Methane-oxidizing bacteria are characterized by their capability to grow on methane as sole source of carbon and energy. Cultivation-dependent and -independent methods have revealed that this functional guild of bacteria comprises a substantial diversity of organisms. In particular the use of cultivation-independent methods targeting a subunit of the particulate methane monooxygenase (pmoA) as functional marker for the detection of aerobic methanotrophs has resulted in thousands of sequences representing "unknown methanotrophic bacteria." This limits data interpretation due to restricted information about these uncultured methanotrophs. A few groups of uncultivated methanotrophs are assumed to play important roles in methane oxidation in specific habitats, while the biology behind other sequence clusters remains still largely unknown. The discovery of evolutionary related monooxygenases in non-methanotrophic bacteria and of pmoA paralogs in methanotrophs requires that sequence clusters of uncultivated organisms have to be interpreted with care. This review article describes the present diversity of cultivated and uncultivated aerobic methanotrophic bacteria based on pmoA gene sequence diversity. It summarizes current knowledge about cultivated and major clusters of uncultivated methanotrophic bacteria and evaluates habitat specificity of these bacteria at different levels of taxonomic resolution. Habitat specificity exists for diverse lineages and at different taxonomic levels. Methanotrophic genera such as Methylocystis and Methylocaldum are identified as generalists, but they harbor habitat specific methanotrophs at species level. This finding implies that future studies should consider these diverging preferences at different taxonomic levels when analyzing methanotrophic communities. © 2015 Knief.

Etzold B.,University of Bonn
Population, Space and Place | Year: 2016

In Bangladesh, Dhaka is migrants' most important destination and has itself been fundamentally transformed through migration. But there is 'no place' for many migrants in Dhaka. Poorer migrants live in slums and many encroach on public space to sustain their lives - the new urbanites are taking their 'right to the city'. In doing so, they not only draw on local resources. Their production of the urban space often relates directly to their migration trajectory, their translocal networks, and their simultaneous situatedness at multiple places. Migrants connect 'the rural' and 'the urban' and constitute translocal spaces, which contribute to re-making Dhaka from below. This paper integrates current debates on translocality, informal labour, and subaltern urbanism to address two key questions on transient urban spaces: How do migration trajectories and translocality structure the urban poor's lives? How do migrants make use of local networks and translocal social relations to find work and appropriate 'their place' in the city? Empirical research on street food vendors in Dhaka, almost all of whom are internal migrants, builds the basis for my argument. I show that 'translocal social capital' and home-bound identities can be important resources to gain access to urban labour markets and to appropriate one's place in the city. The paper argues that the poor use translocality for their livelihoods and thereby continuously re-shape the face of the megacity of Dhaka. © 2016 John Wiley & Sons, Ltd.

Stamminger R.,University of Bonn
Energy Efficiency | Year: 2011

Recent research allocates up to 80% of environmental impact in energy and CO2 terms to direct and indirect consumer activities. Various models discussed how this impact can be assigned to specific lifestyles, production and consumption systems, and psychological motives in order to be able to predict and influence these effects. In this work, another approach is followed by showing on the example of laundry and dish washing how well-known factors of the technical status, consumer practices and demographic data allow building up a model to predict the energy and water consumption for these processes. The results show a variation of a factor of 5 between a more sustainable and a more careless behaviour and allow thus to identify levers to influence it. As results can also be easily transformed into monetary values, this may allow influencing the consumer via this channel as he/she can easily understand what may need to be changed. © 2011 Springer Science+Business Media B.V.

Kim S.C.,University of Bonn
Journal of visualized experiments : JoVE | Year: 2012

Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ischemia and reperfusion. Immune response includes cytokine expression and release or secretion of endogenous ligands of innate immune receptors. Activation of innate immunity can potentially modulate infarct size. We have modified an existing murine closed-chest model using hanging weights which could be useful for studying myocardial pre- and postconditioning and the role of innate immunity in myocardial ischemia and reperfusion. This model allows animals to recover from surgical trauma before onset of myocardial ischemia. Volatile anesthetics have been intensely studied and their preconditioning effect for the ischemic heart is well known. However, this protective effect precludes its use in open chest models of coronary artery ligation. Thus, another advantage could be the use of the well controllable volatile anesthetics for instrumentation in a chronic closed-chest model, since their preconditioning effect lasts up to 72 hours. Chronic heart diseases with intermittent ischemia and multiple hit models are other possible applications of this model. For the chronic closed-chest model, intubated and ventilated mice undergo a lateral blunt thoracotomy via the 4th intercostal space. Following identification of the left anterior descending a ligature is passed underneath the vessel and both suture ends are threaded through an occluder. Then, both suture ends are passed through the chest wall, knotted to form a loop and left in the subcutaneous tissue. After chest closure and recovery for 5 days, mice are anesthetized again, chest skin is reopened and hanging weights are hooked up to the loop under ECG control. At the end of the ischemia/reperfusion protocol, hearts can be stained with TTC for infarct size assessment or undergo perfusion fixation to allow morphometric studies in addition to histology and immunohistochemistry.

Noeker M.,University of Bonn
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | Year: 2012

In Europe and North America, about 80% of all patients with cancer in childhood and adolescence survive their leukemia, lymphomas or tumors. Therefore, neuropsychological impairments, psychopathological comorbidity and health-related quality of life become relevant parameters for treatment evaluation and conceptualization of future therapy protocols. During the last decade, a number of patient registries, multicenter studies and meta-analyses have analyzed the interaction of disease- and treatment-associated risk factors with pre-existing socio-demograph-ic and psychosocial vulnerability factors. Brain tumors and treatment strategies including CNS surgery, cranial radiotherapy and intrathecal chemotherapy carry an increased risk for neurological and neuropsychological long-term outcomes, which in turn also threatens the patients' psychosocial and vocational participation. In the area of psychosocial adaptation, a wide range of developmental paths results, ranging from increased psychological comorbidity, to subclinical impairments in quality of life, to normal courses to resilient outcomes, even with a developmental benefit. A hypothetical model is presented to explain this enormous variance in outcomes. Protective cognitive-emotional schemata already established at the premorbid stage predispose patients to be able to cope successfully with cancer-related challenges and thus further enhance the patients' future adaptability. In contrast, dysfunctional schemata at the premorbid level increase risks of coping failure and thus intensify the long-term risk for psychopathological comorbidity in terms of post-traumatic stress disorder, anxiety disorder or depression. © Springer-Verlag 2012.

Exner M.,University of Bonn
International journal of hygiene and environmental health | Year: 2011

Among the 3rd Seminar for PhD students working on Water and Health which was held in Cannes on 27-29 June 2011, experts from a number of universities and research institutes took the opportunity to discuss the emergence of Escherichia coli O104:H4 in Europe. Especially, possible threats for European water suppliers were considered. The consensus is summarized in this report. The main conclusion was that E. coli O104:H4 would not pose a substantial risk to well managed water supplies, especially where regular monitoring of indicator E. coli is negative. However, this may not apply for small and very small water systems which are quite common in Europe. New strategies like the Water Safety Plan approach are needed to protect also small scale drinking water systems and private wells in Europe. Water used in the processing of foods likely to be eaten raw, especially sprouts, should be of drinking water quality.

Rockstroh J.K.,University of Bonn | Rockstroh J.K.,German Center for Infection Research
Liver International | Year: 2015

The development of direct acting antivirals (DAAs) against the hepatitis C virus (HCV) has revolutionized treatment paradigms for HCV in HIV co-infected subjects. In the era of DAAs, HIV/HCV co-infected patients have the same cure rates of over 90% with interferon (IFN)-free DAA combinations. Therefore, guidelines no longer separate mono- and co-infected subjects. Indications for HCV therapy and DAA drug selection have become the same for all patients. The only special consideration in HIV/HCV co-infected subjects is the need to check for drug-drug interactions between HIV and HCV drugs, especially HIV and HCV protease inhibitors which have a high risk of clinically significant drug interactions. Because of the faster progression of fibrosis and the higher risk of hepatic decompensation in co-infected subjects, even with combination antiretroviral (ART) therapy, the availability of modern HCV treatments needs to be extended and HCV therapy should be discussed in all co-infected patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hartmann M.,University of Bonn
European Review of Agricultural Economics | Year: 2011

Corporate social responsibility (CSR) is of high relevance for food companies as this sector has a strong impact and a high dependence on the economy, the environment and on society. CSRs threats and opportunities are increasingly shifting from the single-firm level to food supply chains and food networks. This induces substantial challenges for the future due to firm heterogeneity and the associated diversity in CSR approaches. © Oxford University Press and Foundation for the European Review of Agricultural Economics 2011; all rights reserved.

Muller P.L.,University of Bonn
Retina | Year: 2016

PURPOSE:: To investigate choroidal alterations in ABCA4-related retinopathy. METHODS:: Mean choroidal thickness and subfoveal choroidal thickness were measured in the right eyes of 40 patients with ABCA4-related retinopathy using enhanced-depth imaging optical coherence tomography. The right eyes of 65 age-matched healthy subjects were used for comparison. RESULTS:: Compared with controls, patients with ABCA4-related retinopathy revealed a reduced subfoveal choroidal thickness ([mean ± SEM] 347 ± 10 μm vs. 302 ± 12 μm; P = 0.006) and mean choroidal thickness (315 ± 9 μm vs. 275 ± 10 μm; P = 0.005). This difference was mainly due to choroidal thinning in eyes with reduced photopic and/or scotopic amplitudes on full-field electroretinography. Atrophy of the retinal pigment epithelium (RPE) was associated with a thinner choroid compared with eyes without RPE atrophy (subfoveal choroidal thickness: 277 ± 17 μm vs. 341 ± 16 μm; mean choroidal thickness: 252 ± 13 μm vs. 313 ± 13 μm; both, P ≤ 0.001), but choroidal thinning was not restricted to the area of RPE atrophy. Choroidal thickness was similar to controls when RPE atrophy and functional loss were limited to the central retina. There was no association between visual acuity and choroidal thickness. CONCLUSION:: The results indicate choroidal alterations in widespread ABCA4-related retinopathy, especially when associated with atrophy of the RPE. The absence of focal choroidal thinning in areas of RPE atrophy is suggestive for a diffusible factor from the RPE sustaining the choroidal structure. © 2016 by Ophthalmic Communications Society, Inc.

Hadizadeh D.R.,University of Bonn
RoFo Fortschritte auf dem Gebiet der Rontgenstrahlen und der Bildgebenden Verfahren | Year: 2014

In the first decade of the twenty-first century, whole-body magnetic resonance scanners with high field strengths (and thus potentially better signal-to-noise ratios) were developed. At the same time, parallel imaging and echo-sharing techniques were refined to allow for increasingly high spatial and temporal resolution in dynamic magnetic resonance angiography (time-resolved = TR-MRA). This technological progress facilitated tracking the passage of intra-venously administered contrast agent boluses as well as the acquisition of volume data sets at high image refresh rates (4D-MRA). This opened doors for many new applications in non-invasive vascular imaging, including simultaneous anatomic and functional analysis of many vascular pathologies including arterio-venous malformations. Different methods were established to acquire 4D-MRA using various strategies to acquire k-space trajectories over time in order to optimize imaging according to clinical needs. These include keyhole-based techniques (e. g. 4D-TRAK), TRICKS - both with and without projection - and HYPR-reconstruction, TREAT, and TWIST. Some of these techniques were first introduced in the 1980 s and 1990 s, were later enhanced and modified, and finally implemented in the products of major vendors. In the last decade, a large number of studies on the clinical applications of TR-MRA was published. This manuscript provides an overview of the development of TR-MRA methods and the 4D-MRA techniques as they are currently used in the diagnosis, treatment and follow-up of vascular diseases in various parts of the body. © Georg Thieme Verlag KG Stuttgart · New York.

Dirksen S.,University of Bonn
Foundations of Computational Mathematics | Year: 2015

We present a theory for Euclidean dimensionality reduction with subgaussian matrices which unifies several restricted isometry property and Johnson–Lindenstrauss-type results obtained earlier for specific datasets. In particular, we recover and, in several cases, improve results for sets of sparse and structured sparse vectors, low-rank matrices and tensors, and smooth manifolds. In addition, we establish a new Johnson–Lindenstrauss embedding for datasets taking the form of an infinite union of subspaces of a Hilbert space. © 2015 SFoCM

Chashei I.V.,RAS Lebedev Physical Institute | Fahr H.J.,University of Bonn
Solar Physics | Year: 2014

We study the temperature of electrons advected with the solar wind to large solar distances far beyond 1 AU. Almost nothing is known about the thermodynamics of these electrons from in-situ plasma observations at these distances, and usually it is tacitly assumed that electrons, due to adiabatic behaviour and vanishing heat conduction, rapidly cool off to very low temperatures at larger distances. In this article we show, however, that electrons on their way to large distances undergo non-adiabatic interactions with travelling shocks and solar-wind bulk-velocity jumps and thereby are appreciably heated. Examining this heating process on an average statistical basis, we find that solar-wind electrons first cool down to a temperature minimum, which depending on the occurrence frequency of bulk velocity jumps is located between 3 and 6 AU, but beyond this the lowest electron temperature again starts to increase with increasing solar distance, finally achieving temperatures of about 7×104 K to 7×105 K at the location of the termination shock. Hence these electrons are unexpectedly shown to play an important dynamical role in structuring this shock and in determining the downstream plasma properties. © 2013 Springer Science+Business Media Dordrecht.

Eldar Y.C.,Technion - Israel Institute of Technology | Rauhut H.,University of Bonn
IEEE Transactions on Information Theory | Year: 2010

This paper considers recovery of jointly sparse multichannel signals from incomplete measurements. Several approaches have been developed to recover the unknown sparse vectors from the given observations, including thresholding, simultaneous orthogonal matching pursuit (SOMP), and convex relaxation based on a mixed matrix norm. Typically, worst case analysis is carried out in order to analyze conditions under which the algorithms are able to recover any jointly sparse set of vectors. However, such an approach is not able to provide insights into why joint sparse recovery is superior to applying standard sparse reconstruction methods to each channel individually. Previous work considered an average case analysis of thresholding and SOMP by imposing a probability model on the measured signals. Here, the main focus is on analysis of convex relaxation techniques. In particular, the mixed ℓ 2, 1 approach to multichannel recovery is investigated. Under a very mild condition on the sparsity and on the dictionary characteristics, measured for example by the coherence, it is shown that the probability of recovery failure decays exponentially in the number of channels. This demonstrates that most of the time, multichannel sparse recovery is indeed superior to single channel methods. The probability bounds are valid and meaningful even for a small number of signals. Using the tools developed to analyze the convex relaxation technique, also previous bounds for thresholding and SOMP recovery are tightened. © 2009 IEEE.

Rottner K.,Helmholtz Center for Infection Research | Rottner K.,University of Bonn | Stradal T.E.B.,Helmholtz Center for Infection Research | Stradal T.E.B.,University of Munster
Current Opinion in Cell Biology | Year: 2011

Cell migration is a highly coordinated process involving a multitude of separable but intertwined phenomena traditionally studied in multiple cell types, tissues and model systems. In spite of the multitude of mechanisms and modes of motility described in all these different systems, the ability to dynamically reorganize the actin cytoskeleton is common to all of them. However, defining the key molecular players in motility and their precise molecular functions continues to be challenging, last not least owing to robustness and flexibility common to complex biological phenomena. Here we will draft the future steps essential for achieving true progress towards the goal to increase our understanding of actin cytoskeleton dynamics driving cell migration. © 2011 Elsevier Ltd.

Urbach H.,University of Bonn
Neuroimaging Clinics of North America | Year: 2012

Epileptogenic lesions are often subtle, do not change during life, and are easily overlooked, if spatial resolution and signal to noise ratio are inappropriate. 2D or more recently 3D-FLAIR sequences are best suited to detect small cortical dysplasias which are often located at the bottom of a sulcus. 3D-T1-weighted gradient echo sequences are used for multiplanar, curved surface reformations, and voxel-based analyses. 3 T MR imaging is currently the state-of-the-art imaging modality for patients with suspected structural epilepsies in which an epileptogenic lesion has not yet been found. © 2012 Elsevier Inc.

Schwab J.O.,University of Bonn
Fundamental and Clinical Pharmacology | Year: 2010

With the increasing numbers of patients with implantable cardioverter/defibrillators for primary prevention (PP), the topic of inappropriate therapy becomes more and more important. If a shock intervention, e.g. for rapidly conducted atrial fibrillation or fast VT (FVT), represents the first reminder of the implantable cardioverter/defibrillator (ICD), the adherence to the therapy will decrease. Moreover, anxiety to receive the next inappropriate ICD Rx is able to initiate a bad quality of life or depression. Starting with the PainFREE Rx II Trial results, the programming of antitachycardia pacing was able to terminate even fast ventricular arrhythmia, i.e. ≥188 bpm, in three of four episodes. Thereafter, several studies evaluated whether a prolongation in ventricular tachyarrhythmia (VT) detection is able to reduce unnecessary ICD Rx owing to nonsustained VT. The PREPARE trial evaluated this concept in a cohort of PP patients. This nonrandomized study compared a historical control group to patients with a prolonged detection interval. The results underline the idea that an extension in detection time leads to a significant decrease in ICD Rx for supra- as well as VT. The RELEVANT study investigated in a randomized fashion the outcome of an increase in detection time in nonischemic patients under CRT including an ICD. The findings clearly demonstrated a reduction in ICD Rx as well as hospital admissions, significantly. Currently, the ADVANCE III trial investigates a 30/40 interval detection compared to 18/24 for FVT in prospective randomized fashion in patients for primary or secondary prevention including all ICD devices. © 2010 Société Française de Pharmacologie et de Thérapeutique.

Kundt W.,University of Bonn
Advances in Mathematical Physics | Year: 2015

In this year (2015), black holes (BHs) celebrate their 100th birthday, if their birth is taken to be triggered by a handwritten letter from Martin Schwarzschild to Albert Einstein, in connection with his newly found spherically symmetric vacuum solution. © 2015 Wolfgang Kundt.

Exner M.,University of Bonn
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | Year: 2012

Ten years after the publication of the recommendation: "Outbreak management and structural proceedings in case of cumulative occurrence of nosocomial infections" of the federal commission of hospital hygiene, these recommendations are now being re-evaluated. To date, the recommendations have proven valid and have maintained their significance for an effective management. However, besides new hygienic-microbiological methods and an increased sensitivity of the perception of nosocomial outbreaks by the public, by politicians and by the press, it is necessary to consider new issues in this field. Outbreaks are tragic events placing an extraordinary burden on all persons involved, which can have significant consequences. Therefore, it is necessary to ensure prompt outbreak management by experienced professionals who must combine a systematic on-site inspection, hygienic-microbiological investigation and typing methods used with epidemiological approaches. To assure these requirements, the support of independent reference centres such as universal hygiene institutes should be guaranteed. Politicians should be involved only after a scientific evaluation of the details of the outbreak has been made. A national documentation centre, e.g. at the Robert Koch Institute, should be established, thereby making experiences with outbreaks widely available. © 2012 Springer-Verlag.

Rabe E.,University of Bonn | Pannier F.,University of Cologne
Phlebology | Year: 2012

The first CEAP (clinical, aetiological, anatomical and pathological elements) consensus document was published after a consensus conference of the American Venous Forum, held at the sixth annual meeting of the AVF in February 1994 in Maui, Hawaii. In the following years the CEAP classification was published in many international journals and books which has led to widespread international use of the CEAP classification since 1995. The aim of this paper is to review the benefits and limits of CEAP from the available literature. In an actual Medline analysis with the keywords 'CEAP' and 'venous insufficiency', 266 publications using the CEAP classification in venous diseases are available. The CEAP classification was accepted in the venous community and used in scientific publications, but in most of the cases only the clinical classification was used. Limitations of the first version including a lack of clear definition of clinical signs led to a revised version. The CEAP classification is the gold standard of classification of chronic venous disorders today. Nevertheless for proper use some facts have to be taken into account: the CEAP classification is not a severity classification, C2 summarizes all kinds of varicose veins, in C3 it may be difficult to separate venous and other reasons for oedema, and corona phlebectatica is not included in the classification. Further revisions of the CEAP classification may help to overcome the still-existing deficits.

Derrien D.,French National Institute for Agricultural Research | Amelung W.,University of Bonn
European Journal of Soil Science | Year: 2011

Soils contain the largest carbon (C) reservoir on Earth, but the mean residence time (MRT) of soil C is often poorly estimated, despite its importance for assessing the efficiency with which soils may serve as a sink for atmospheric C. The objective of this study was to evaluate how the structure of simple models of soil C dynamics affects the MRT determined from isotope-mixing experiments, using data from field studies with either artificial labelling (FACE) or C3/C4 vegetation change. We first highlighted theoretically how non-steady-state conditions and the model structure (one single, two successive, or two parallel C pools) can have an impact on the MRT assessment. We then tested these different model structures against published data on the dynamics of different soil organic matter separates and their constituents. Our findings indicated that many of the reviewed studies assumed wrongly that the system was at steady state or could be described by a single-pool approach. To select the correct model, exact knowledge of C input rates and several data points are needed from the beginning of the experiment. For steady-state conditions an apparent temporal change of MRT computed from a single-pool model is thus a clear indicator that a two-pool approach must be chosen. The errors made by the wrong choice of model varied with the length of the experiment and usually resulted in an over-estimate of MRT by a factor of 1.15 for some data published on physical size separates, but by a factor of up to 11 for individual microbial biomarkers such as muramic acid. © 2011 The Authors. Journal compilation © 2011 British Society of Soil Science.

Hoger S.,University of Bonn
Pure and Applied Chemistry | Year: 2010

Shape-persistent macrocycles based on the arylene-ethynylene backbone are synthetically challenging targets that can be obtained in good to high yields either by statistical or by template-supported oxidative Glaser coupling of the corresponding bisacetylenes. The macrocycles can be adsorbed on highly oriented pyrolytic graphite (HOPG) to form well-ordered monolayers as visualized by scanning tunneling microscopy (STM). Moreover, bithiophene- containing macrocycles are able to bind fullerenes at the electron-rich sites of the rings. One-dimensional tubular structures based on shape-persistent macrocycles can also be obtained by oxidative acetylene coupling. These contain intraannularly bound conjugated polymers and represent bichromophoric systems that allow an accumulation of excitation energy on the conjugated core. In the field of defined 2D objects we describe molecular spoked wheels with a lateral expansion of more than 5 nm. These compounds are highly rigid. In order to provide sufficient solubility, they contain peripheral substituents and additional substituents orthogonal to the plane of the molecules. © 2010 IUPAC.

Waldvogel S.R.,University of Bonn
Pure and Applied Chemistry | Year: 2010

The oxidative phenol coupling reaction of phenols with simple methyl substituents can be difficult due to several by-products. Such a challenging substrate is 2,4-dimethyl-phenol. We studied the electrochemical access to the ortho-coupled dehydrodimer. Anodic treatment in a basic electrolyte supports the formation of a molecular tricyclic architecture called Pummerer's ketone. Employing a two-step sequence involving anodic conversion of 2,4-dimethylphenol to a preliminary substrate and different workup protocols yield exclusively and diastereoselectively polycyclic architectures. The selective ortho-coupling reaction was achieved by two strategies: A tetraphenoxy borate can be used as template substrate which can be easily made in large scale. Due to the ionic nature of the borate, no supporting electrolyte is required. This methodology can be applied to several related phenolic substrates. The second route is described by the direct conversion of 2,4-dimethylphenol on boron-doped diamond anodes. Surprisingly, the electrochemical transformation does not destruct or mineralize the substrate. Fluorinated additives allow the conversion of a broad scope of substrates. © 2010 IUPAC.

Koch K.-R.,University of Bonn
Journal of Applied Geodesy | Year: 2014

Best invariant quadratic unbiased estimates (BIQUE) of the variance and covariance components for a nonlinear Gauss Helmert (GH) model are derived. To detect outliers, the expectation maximization (EM) algorithm based on the variance-inflation model and the mean-shift model is applied, which results in an iterative reweighting least squares. Each step of the iterations for the EM algorithm therefore includes first the iterations for linearizing the GH model and then the iterations for estimating the variance components. The method is applied to fit a surface in three-dimensional space to the three coordinates of points measured, for instance, by a laser scanner. The surface is represented by a polynomial of second degree and the variance components of the three coordinates are estimated. Outliers are detected by the EM algorithm based on the variance-inflation model and identified by the EM algorithm for the mean-shift model. © 2014 by Walter de Gruyter Berlin/Boston 2014.

Koch H.,University of Bonn
Nonlinearity | Year: 2015

We construct self-similar finite energy solutions to the slightly super-critical generalized Korteweg-de Vries (gKdV) equation. These self-similar solutions bifurcate as a function of p from the soliton at the L2 critical exponent p = 4. © 2015 IOP Publishing Ltd & London Mathematical Society.

Bo L.,TTI Chicago | Sminchisescu C.,University of Bonn
International Journal of Computer Vision | Year: 2010

We describe twin Gaussian processes (TGP), a generic structured prediction method that uses Gaussian process (GP) priors on both covariates and responses, both multivariate, and estimates outputs by minimizing the Kullback-Leibler divergence between two GP modeled as normal distributions over finite index sets of training and testing examples, emphasizing the goal that similar inputs should produce similar percepts and this should hold, on average, between their marginal distributions. TGP captures not only the interdependencies between covariates, as in a typical GP, but also those between responses, so correlations among both inputs and outputs are accounted for. TGP is exemplified, with promising results, for the reconstruction of 3d human poses from monocular and multicamera video sequences in the recently introduced HumanEva benchmark, where we achieve 5 cm error on average per 3d marker for models trained jointly, using data from multiple people and multiple activities. The method is fast and automatic: it requires no hand-crafting of the initial pose, camera calibration parameters, or the availability of a 3d body model associated with human subjects used for training or testing. © 2009 Springer Science+Business Media, LLC.

Schmieden H.,University of Bonn
International Journal of Modern Physics E | Year: 2010

At the electron accelerator facility ELSA of the University of Bonn presently the new BGO-OpenDipole experiment is being setup. It is optimized for meson photoproduction final states of mixed charges. The detector combines hermetic coverage for photon detection through the BGO ball of the former GRAAL experiment with high resolution detection of forward going charged particles in the Open Dipole spectrometer. This setup is well suited for many different channels, including pseudoscalar, vectormeson and associated strangeness photoproduction. This contribution highlights the strangeness channels associated with the Λ and Σ ground states and the Λ(1405) excited state. © 2010 World Scientific Publishing Company.

Nilles H.P.,University of Bonn
European Physical Journal C | Year: 2014

String theory constructions towards the MSSM allow us to identify some general properties that could be relevant for tests at the LHC. They originate from the geometric structure of compactification and the location of fields in extra-dimensional space. Within the framework of the heterotic MiniLandscape we extract some generic lessons for supersymmetric model building. Among them is a specific pattern of SUSY breakdown based on mirage mediation and remnants of extended supersymmetry. This leads to a split spectrum with heavy scalars of the first two families of quarks and leptons and suppressed masses for gauginos, top partners and Higgs bosons. The models exhibit some specific form of hidden supersymmetry consistent with the high mass of the Higgs boson and all presently available experimental constraints. The most compelling picture is based on precision gauge coupling unification that might be in the kinematic reach of the LHC. © 2014 The Author(s).

Canullo L.,University of Bonn
The International journal of oral & maxillofacial implants | Year: 2011

This study sought to determine whether there was a correlation between bone resorption and individual bone patterns in patients treated with implants restored conventionally or using the platform-switching concept. Ten patients (24 implants) were randomly assigned to receive implants with different platform diameters (3.8, 4.3, 4.8, or 5.5 mm), all of which were restored with standard 3.8-mm-diameter abutments. Biopsy specimens were obtained prior to implant placement, and histologic and immunohistochemical analyses were performed. Standardized radiographs were made at each site after implant placement and at 36 months after prosthetic loading and bone levels were determined. One patient dropped out, resulting in a total of 9 patients and 22 implants. Mean bone resorption was 1.358 mm for non-platform-switched implants; mean resorption was 0.832, 0.486, and 0.375 mm for implant platforms of 4.3, 4.8, and 5.5 mm, respectively. After standardization of peri-implant bone remodeling values, a borderline direct correlation between peri-implant bone changes and levels of biglycans was found. At the same time, a borderline indirect correlation between bone changes and levels of tumor necrosis factor-a was found. Within the limit of this study, which was conducted in a small patient sample over a short observation period, an individual resorption trend was detected and paralleled by immunohistochemical findings. Individual local bone structure and quality seemed to be correlated to peri-implant bone resorption. Correlations between biglycan and tumor necrosis factor-a and bone resorption should be confirmed by a larger patient sample.

Brauman K.A.,University of Minnesota | Siebert S.,University of Bonn | Foley J.A.,University of Minnesota
Environmental Research Letters | Year: 2013

Irrigation consumes more water than any other human activity, and thus the challenges of water sustainability and food security are closely linked. To evaluate how water resources are used for food production, we examined global patterns of water productivity - food produced (kcal) per unit of water (l) consumed. We document considerable variability in crop water productivity globally, not only across different climatic zones but also within climatic zones. The least water productive systems are disproportionate freshwater consumers. On precipitation-limited croplands, we found that ∼40% of water consumption goes to production of just 20% of food calories. Because in many cases crop water productivity is well below optimal levels, in many cases farmers have substantial opportunities to improve water productivity. To demonstrate the potential impact of management interventions, we calculated that raising crop water productivity in precipitation-limited regions to the 20th percentile of productivity would increase annual production on rainfed cropland by enough to provide food for an estimated 110 million people, and water consumption on irrigated cropland would be reduced enough to meet the annual domestic water demands of nearly 1.4 billion people. © 2013 IOP Publishing Ltd.

Brenner U.,University of Bonn
Proceedings -Design, Automation and Test in Europe, DATE | Year: 2012

We present a new approach to VLSI placement legalization. Based on a minimum-cost flow algorithm that iteratively augments flows along paths, our algorithm ensures that only augmentations are considered that can be realized exactly by cell movements. Hence, the method avoids realization problems which are inherent to previous flow-based legalization algorithms. As a result, it combines the global perspective of minimum-cost flow approaches with the efficiency of local search algorithms. The tool is mainly designed to minimize total and maximum cell movement but it is flexible enough to optimize the effect on timing or netlength, too. We compare our approach to legalization tools from industry and academia by experiments on dense recent real-world designs and public benchmarks. The results show that we are much faster and produce significantly better results in terms of average (linear and quadratic) and maximum movement than any other tool. © 2012 EDAA.

Schmidt-Hoberg K.,CERN | Staub F.,University of Bonn | Winkler M.W.,German Electron Synchrotron
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

Light scalars appear in many well-motivated extensions of the Standard Model including supersymmetric models with additional gauge singlets. Such scalars could mediate the interactions between dark matter and nuclei, giving rise to the tentative signals observed by several dark matter direct detection experiments including CDMS-Si. In this Letter, we derive strong new limits on light scalar mediators by using the LHCb, Belle and BaBar searches for rare Υ{hooked} and B decays. These limits rule out significant parts of the parameter space favored by CDMS-Si. Nevertheless, as current searches are not optimized for investigating weakly coupled light scalars, a further increase in experimental sensitivity could be achieved by relaxing requirements in the event selection. © 2013 Elsevier B.V.

Li B.,CAS Nanjing Institute of Soil Science | Li G.,CAS Nanjing Institute of Soil Science | Kronzucker H.J.,University of Toronto | Baluska F.,University of Bonn | Shi W.,CAS Nanjing Institute of Soil Science
Trends in Plant Science | Year: 2014

Ammonium (NH4 +) toxicity is a significant ecological and agricultural issue, and an important phenomenon in cell biology. As a result of increasing soil nitrogen input and atmospheric deposition, plants have to deal with unprecedented NH4 + stress from sources below and above ground. In this review, we describe recent advances in elucidating the signaling pathways and identifying the main physiological targets and genetic loci involved in the effects of NH4 + stress in the roots and shoots of Arabidopsis thaliana. We outline new experimental approaches that are being used to study NH4 + toxicity in Arabidopsis and propose an integrated view of behavior and signaling in response to NH4 + stress in the Arabidopsis system. © 2013 Elsevier Ltd.

McSweeney K.,Ohio State University | Nielsen E.A.,Northern Arizona University | Taylor M.J.,University of Denver | Wrathall D.J.,University of Bonn | And 3 more authors.
Science | Year: 2014

Drug trafficking is taking a toll on Central America's biodiverse forests.

Koch K.-R.,University of Bonn
Journal of Geodesy | Year: 2015

The concept of reliability was introduced into geodesy by Baarda (A testing procedure for use in geodetic networks. Publications on Geodesy, vol. 2. Netherlands Geodetic Commission, Delft, 1968). It gives a measure for the ability of a parameter estimation to detect outliers and leads in case of one outlier to the MDB, the minimal detectable bias or outlier. The MDB depends on the non-centrality parameter of the χ2-distribution, as the variance factor of the linear model is assumed to be known, on the size of the outlier test of an individual observation which is set to 0.001 and on the power of the test which is generally chosen to be 0.80. Starting from an estimated variance factor, the F-distribution is applied here. Furthermore, the size of the test of the individual observation is a function of the number of outliers to keep the size of the test of all observations constant, say 0.05. The power of the test is set to 0.80. The MDBs for multiple outliers are derived here under these assumptions. The method is applied to the reconstruction of a bell-shaped surface measured by a laser scanner. The MDBs are introduced as outliers for the alternative hypotheses of the outlier tests. A Monte Carlo method reveals that due to the way of introducing the outliers, the false null hypotheses cannot be rejected on the average with a power of 0.80 if the MDBs are not enlarged by a factor. © 2015, Springer-Verlag Berlin Heidelberg.

Jessen F.,University of Bonn | Jessen F.,German Center for Neurodegenerative Diseases
European Archives of Psychiatry and Clinical Neuroscience | Year: 2014

Research on Alzheimer’s disease (AD) dementia prediction has moved from the mild cognitive impairment stage to the preclinical stage of AD. This has also extended the focus from the early clinical sign of cognitive impairment measured with neuropsychological tests to the purely subjective report of cognitive decline (SCD) in unimpaired elderly individuals. Epidemiological studies have shown that both objective impairment and SCD are independently predictive of AD dementia. Both are also associated with an increased likelihood of biomarker or neuroimaging evidence of AD. However, the relationship of objective and subjective cognitive performance along the axis of AD development and their role at different stages in prediction of AD dementia is not well explored. Refined knowledge about strengths and weaknesses of both aspects at different pre-dementia disease stages will be beneficial for dementia prediction. Both concepts and their interaction are introduced in this article. © 2014, Springer-Verlag Berlin Heidelberg.

Cendes F.,University of Campinas | Sakamoto A.C.,University of Sao Paulo | Spreafico R.,Experimental Neurophysiology Unit | Bingaman W.,Cleveland Clinic | Becker A.J.,University of Bonn
Acta Neuropathologica | Year: 2014

Hippocampal sclerosis (HS) is considered the most frequent neuropathological finding in patients with mesial temporal lobe epilepsy (MTLE). Hippocampal specimens of pharmacoresistant MTLE patients that underwent epilepsy surgery for seizure control reveal the characteristic pattern of segmental neuronal cell loss and concomitant astrogliosis. However, classification issues of hippocampal lesion patterns have been a matter of intense debate. International consensus classification has only recently provided significant progress for comparisons of neurosurgical and clinic-pathological series between different centers. The respective four-tiered classification system of the International League Against Epilepsy subdivides HS into three types and includes a term of "gliosis only, no-HS". Future studies will be necessary to investigate whether each of these subtypes of HS may be related to different etiological factors or with postoperative memory and seizure outcome. Molecular studies have provided potential deeper insights into the pathogenesis of HS and MTLE on the basis of epilepsy-surgical hippocampal specimens and corresponding animal models. These include channelopathies, activation of NMDA receptors, and other conditions related to Ca2+ influx into neurons, the imbalance of Ca2+-binding proteins, acquired channelopathies that increase neuronal excitability, paraneoplastic and non-paraneoplastic inflammatory events, and epigenetic regulation promoting or facilitating hippocampal epileptogenesis. Genetic predisposition for HS is clearly suggested by the high incidence of family history in patients with HS, and by familial MTLE with HS. So far, it is clear that HS is multifactorial and there is no individual pathogenic factor either necessary or sufficient to generate this intriguing histopathological condition. The obvious variety of pathogenetic combinations underlying HS may explain the multitude of clinical presentations, different responses to clinical and surgical treatment. We believe that the stratification of neuropathological patterns can help to characterize specific clinic-pathological entities and predict the postsurgical seizure control in an improved fashion. © 2014 Springer-Verlag.

van Assche K.,The Development Cloud | Djanibekov N.,University of Bonn
Land Use Policy | Year: 2012

We start out from the premise of a continued need for policy integration to address both economic and environmental issues in society, arguing that spatial planning is a privileged site to locate such endeavor. While policy integration in planning can acquire many forms, we understand those forms as ways to manage interdependencies between organizations. Spatial planning can contribute to the integration of policies in comprehensive visions, but a planning system, in the sense of a network of organizations, does not escape from the evolutionary rigidity introduced by interdependence and path-dependence. In a study of the evolutionary path of spatial governance in Uzbekistan, a former Soviet republic, we investigated the shifting patterns of policy integration that affected the organization of space. Policy integration in planning, it is found, is path-dependent, worked out positively and negatively, and necessarily relied on informal coordination mechanisms. Thus, a planning system striving to manage interdependence has to be highly reflexive, to understand the extent to which its transformation options are constrained by history and by present linkages between organizations. © 2011 Elsevier Ltd.

Golubnitschaja O.,University of Bonn | Costigliola V.,The European Association for Predictive
EPMA Journal | Year: 2015

Over the next 10-20 years, a pessimistic prognosis considers pandemic scenario for type 2 diabetes mellitus, neurodegenerative disorders and some types of cancer followed by the economic disaster of healthcare systems in a global scale. Well-recognised deficits of currently provided medical services result from the delayed 'disease care'. Herewith EPMA releases the long-term strategies for the effective promotion of predictive, preventive and personalised medicine (PPPM) considered as the medicine of the future. Under the EPMA-umbrella, an international forum of currently 45 countries is actively contributing to the development and implementation of the innovative PPPM concepts. EPMA is open for collaboration with other leading European and global professional networks relevant for the effective promotion of PPPM in sciences and practical implementation. © 2015 Golubnitschaja et al.

Benakli K.,CNRS Theoretical and High Energy Physics | Goodsell M.D.,Ecole Polytechnique - Palaiseau | Staub F.,University of Bonn
Journal of High Energy Physics | Year: 2013

We investigate the mass, production and branching ratios of a 125 GeV Higgs in models with Dirac gaugino masses. We give a discussion of naturalness, and describe how deviations from the Standard Model in the key Higgs search channels can be simply obtained. We then perform parameter scans using a SARAH package upgrade, which produces SPheno code that calculates all relevant quantities, including electroweak precision and flavour constraint data, to a level of accuracy previously impossible for this class of models. We study three different variations on the minimal Dirac gaugino extension of the (N)MSSM. © 2013 SISSA.

Magallon S.,National Autonomous University of Mexico | Hilu K.W.,Virginia Polytechnic Institute and State University | Quandt D.,University of Bonn
American Journal of Botany | Year: 2013

Premise of the study: Land plants play an essential role in the evolution of terrestrial life. Their time of origin and diversification is fundamental to understanding the evolution of life on land. We investigated the timing and the rate of molecular evolution of land plants, evaluating the effects of different types of molecular data, including temporal information from fossils, and using different molecular clock methods. Methods: Ages and absolute rates were estimated independently with two substitutionally different data sets: a highly conserved 4-gene data set and matK, a fast-evolving gene. The vascular plant backbone and the crown nodes of all major lineages were calibrated with fossil-derived ages. Dates and absolute rates were estimated while including or excluding the calibrations and using two relaxed clocks that differ in their implementation of temporal autocorrelation. Key results: Land plants diverged from streptophyte alga 912 (870-962) million years ago (Mya) but diversified into living lineages 475 (471-480) Mya. Ages estimated for all major land-plant lineages agree with their fossil record, except for angiosperms. Different genes estimated very similar ages and correlated absolute rates across the tree. Excluding calibrations resulted in the greatest age differences. Different relaxed clocks provided similar ages, but different and uncorrelated absolute rates. Conclusions: Whole-genome rate accelerations or decelerations may underlie the similar ages and correlated absolute rates estimated with different genes. We suggest that pronounced substitution rate changes around the angiosperm crown node may represent a challenge for relaxed clocks to model adequately. © 2013 Botanical Society of America.

Kavsek M.,University of Bonn
Vision Research | Year: 2013

The study investigated the early development of responsiveness to rivalrous gratings. Infants were tested weekly between 6 and 16. weeks of age for their ability to discriminate between interocularly identical (fusible) lines and interocularly orthogonal (unfusible, rivalrous) lines. The stimuli were presented on an autostereoscopic monitor equipped with a face-tracking device. Two psychophysical techniques, the forced-choice preferential looking (FPL) method and measurement of looking times, were employed. Contrary to earlier findings, infants at all ages avoided looking at the rivalrous gratings instead of showing a developmental shift from a relative preference for unfusible, rivalrous gratings to a relative preference for fusible gratings. Avoidance of the rivalrous gratings became significant at 8-9. weeks of age, suggesting that infants clearly exhibit binocular rivalry from that age onwards. Control experiments secured that the infants' preference for the fusible gratings was not governed by a natural preference for less over more complex line patterns. © 2012 Elsevier Ltd.

Noeker M.,University of Bonn | Petermann F.,University of Bremen
Kindheit und Entwicklung | Year: 2011

Terminology and concepts of dissociation and conversion have been deeply rooted in the psychoanalytical tradition for more than a century, while the empirically driven clinical psychology and child psychology have largely neglected this research field. Children have a lot of spontaneous dissociative experiences (e.g., daydreaming). They play an important role in emotion and affect regulationwhen confronted with stressors ranging from daily hassles to extremely challenging and traumatic experiences (e. g., traffic accidents, physical abuse, sexual violence). At least in the short run, dissociative coping mechanisms protect from sensory, cognitive and emotional overload. From a categorical perspective, dissociative disorders include both (psychoform) disorders of consciousness including amnesia, confusion, stupor, and disturbances of identity as well as conversion disorders including motor and sensory loss and nonepileptic seizures. Dissociative disorders have close ties to somatoform disorders, acute stress disorder, and posttraumatic stress disorder, as well as to emotionally instable and histrionic personality disorders. To date, the present therapeutic approaches are largely lacking an evidencebased foundation. In the future, dissociative disorders and mechanisms will not only deserve special research efforts from a psychopathological point of view but also from a therapeutic interventional perspective. The so-called third wave of behavior therapy and its various current mindfulness-based therapy approaches (acceptance and commitment therapy, meta-cognitive therapy, dialecticalbehavioral therapy, schema therapy) have begun to explore the psychotherapeutic potential inherent to therapeutically induced dissociation. Dissociative techniques can support the patient in observing threatening or traumatic content of consciousness from a safe dissociated distance, hence overcoming previous perceptual and cognitive avoidance behavior. © Hogrefe Verlag, Göttingen 2011.

Schmidt-Hoberg K.,CERN | Staub F.,University of Bonn | Winkler M.W.,German Electron Synchrotron
Journal of High Energy Physics | Year: 2013

We show that within MSSM singlet extensions the experimental hints beyond the standard model from the Fermi LAT telescope as well as from the LHC can be explained simultaneously while being consistent with all experimental constraints. In particular we present an example point which features a ∼ 130 GeV lightest neutralino with an annihilation cross section into photons consistent with the indication from the Fermi satellite with simultaneously the right relic abundance, a continuum photon spectrum consistent with observation, direct detection cross section below the experimental limits, electroweak observables consistent with experiment and a 125 GeV light Higgs boson with a slightly enhanced h → γγ rate. © 2013 SISSA.

Marinas C.,University of Bonn
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2013

An upgrade of the existing Japanese flavor factory (KEKB in Tsukuba, Japan) is under construction, and foreseen for commissioning by the end of 2014. This new e+e- machine ("SuperKEKB") will deliver an instantaneous luminosity of 8×1035 cm-2 s -1, which is 40 times higher than the world record set by KEKB. In order to be able to fully exploit the increased number of events and provide high precision measurements of the decay vertex of the B meson systems in such a harsh environment, the Belle detector will be upgraded ("Belle II") and a new silicon vertex detector, based on the DEPFET technology, will be designed and constructed. The new pixel detector, close to the interaction point, will consist on two layers of DEPFET active pixel sensors. This technology combines the detection together with the in-pixel amplification by the integration, on every pixel, of a field effect transistor into a fully depleted silicon bulk. In Belle II, DEPFET sensors thinned down to 75μm with low power consumption and low intrinsic noise will be used. © 2013 CERN.

Webster S.G.,Bangor University | Keller R.,University of Bonn | Dircksen H.,University of Stockholm
General and Comparative Endocrinology | Year: 2012

Apart from providing an up-to-date review of the literature, considerable emphasis was placed in this article on the historical development of the field of "crustacean eyestalk hormones" A role of the neurosecretory eyestalk structures of crustaceans in endocrine regulation was recognized about 80. years ago, but it took another half a century until the first peptide hormones were identified. Following the identification of crustacean hyperglycaemic hormone (CHH) and moult-inhibiting hormone (MIH), a large number of homologous peptides have been identified to this date. They comprise a family of multifunctional peptides which can be divided, according to sequences and precursor structure, into two subfamilies, type-I and -II. Recent results on peptide sequences, structure of genes and precursors are described here. The best studied biological activities include metabolic control, moulting, gonad maturation, ionic and osmotic regulation and methyl farnesoate synthesis in mandibular glands. Accordingly, the names CHH, MIH, and GIH/VIH (gonad/vitellogenesis-inhibiting hormone), MOIH (mandibular organ-inhibiting hormone) were coined. The identification of ITP (ion transport peptide) in insects showed, for the first time, that CHH-family peptides are not restricted to crustaceans, and data mining has recently inferred their occurrence in other ecdysozoan clades as well. The long-held tenet of exclusive association with the eyestalk X-organ-sinus gland tract has been challenged by the finding of several extra nervous system sites of expression of CHH-family peptides. Concerning mode of action and the question of target tissues, second messenger mechanisms are discussed, as well as binding sites and receptors. Future challenges are highlighted. © 2011.

Sohl G.,University of Bonn
BMC ophthalmology | Year: 2010

Gap junction channels allow direct metabolically and electrical coupling between adjacent cells in various mammalian tissues. Each channel is composed of 12 protein subunits, termed connexins (Cx). In the mouse retina, Cx43 could be localized mostly between astroglial cells whereas expression of Cx36, Cx45 and Cx57 genes has been detected in different neuronal subtypes. In the human retina, however, the expression pattern of connexin genes is largely unknown. Northern blot hybridizations, RT-PCR as well as immunofluorescence analyses helped to explore at least partially the expression pattern of the following human connexin genes GJD2 (hCx36), GJC1 (hCx45), GJA9 (hCx59) and GJA10 (hCx62) in the human retina. Here we report that Northern blot hybridization signals of the orthologuous hCx36 and hCx45 were found in human retinal RNA. Immunofluorescence signals for both connexins could be located in both inner and outer plexiform layer (IPL, OPL). Expression of a third connexin gene denoted as GJA10 (Cx62) was also detected after Northern blot hybridization in the human retina. Interestingly, its gene structure is similar to that of Gja10 (mCx57) being expressed in mouse horizontal cells. RT-PCR analysis suggested that an additional exon of about 25 kb further downstream, coding for 12 amino acid residues, is spliced to the nearly complete reading frame on exon2 of GJA10 (Cx62). Cx59 mRNA, however, with high sequence identity to zebrafish Cx55.5 was only weakly detectable by RT-PCR in cDNA of human retina. In contrast to the neuron-expressed connexin genes Gjd2 coding for mCx36, Gjc1 coding for mCx45 and Gja10 coding for mCx57 in the mouse, a subset of 4 connexin genes, including the unique GJA9 (Cx59) and GJA10 (Cx62), could be detected at least as transcript isoforms in the human retina. First immunofluorescence analyses revealed a staining pattern of hCx36 and hCx45 expression both in the IPL and OPL, partially reminiscent to that in the mouse, although additional post-mortem material is needed to further explore their sublamina-specific distribution. Appropriate antibodies against Cx59 and Cx62 protein will clarify expression of these proteins in future studies.

Kramer H.J.,University of Bonn
Frontiers in Endocrinology | Year: 2015

This brief review describes some representative methodological approaches to the isolation of putative endogenous inhibitors of epithelial sodium transport - i.e., as ouabain-like factors (OLF) that inhibit the sodium transport enzyme Na-K-ATPase or inhibit the epithelial sodium channel (ENaC). Gel chromatography and reverse-phase (RP)-high performance liquid chromatography (HPLC) of lyophilized and reconstituted 24 h-urine from salt-loaded healthy humans led to two active fractions, a hydrophilic OLF-1 and a lipophilic OLF-2, whose mass (Ms)-spectroscopic data indicate a Mr of 391 (1, 2). Further identification was attempted by Ms-, infrared (IR)-, ultraviolet (UV)-, and 1H-NMR-spectroscopy. OLF-1 and OLF-2 may be closely related if not identical to (di)ascorbic acid or its salts such as vanadium (V)-Vv-diascorbate with Mr 403 (3) and VIV-diascorbate. OLF-1 and Vv-diascorbate are about 10-fold stronger inhibitors of Na-K-ATPase than OLF-2 and VIV-diascorbate, respectively. In conscious rats, i.v. infusion of OLF-1 and OLF-2 resulted in a strong natriuresis. In a similar study, Cain et al. (4) isolated a sodium transport inhibitor from the urine of uremic patients by gel chromatography and RP-HPLC. In uremic rats, a natriuretic response to the injection of the active material was found. Xanthurenic acid 8-O-β-d-glucoside (Mr 368) and xanthurenic acid 8-O-sulfate (Mr 284) were identified as endogenous inhibitors of sodium transport acting, e.g., by ENaC blockade. No definite relation to blood pressure, body fluid volume, or sodium balance has been reported for any of these above factors, and further studies to identify the natriuretic and/or ouabain-like compound(s) or hormone(s) will be needed. © 2015 Kramer.

Hougardy S.,University of Bonn
Information Processing Letters | Year: 2010

The Floyd-Warshall algorithm is a simple and widely used algorithm to compute shortest paths between all pairs of vertices in an edge weighted directed graph. It can also be used to detect the presence of negative cycles. We will show that for this task many existing implementations of the Floyd-Warshall algorithm will fail because exponentially large numbers can appear during its execution. © 2010 Elsevier B.V. All rights reserved.

Greiner C.,University of Cologne | Sakdapolrak P.,University of Bonn
Population and Environment | Year: 2013

The nexus between migration dynamics and environmental change has drawn the attention of many researchers in the recent past. While the majority of studies focus on the impact of the environment on migration decisions, less emphasis has been placed on the feedback effect of migration on the environment in rural sending areas. This article provides a critical review of this relationship by focusing on the rich literature on rural-urban migration of smallholder households in Kenya and its effects on rural environments. The article argues that there are distinct relations between migration, agricultural change and the environment. These are mediated in varying degrees by flows of remittances, loss of labor, socioeconomic stratification, gender dynamics, and cultural factors. Overly generalizing assumptions about these relations, however, fail to grasp their complexity. We propose employing a translocal perspective to enrich future analysis and enhance the understanding of migration-environmental interactions. © 2012 Springer Science+Business Media, LLC.

Taubock G.,Vienna University of Technology | Hlawatsch F.,Vienna University of Technology | Eiwen D.,University of Vienna | Rauhut H.,University of Bonn
IEEE Journal on Selected Topics in Signal Processing | Year: 2010

We consider the application of compressed sensing (CS) to the estimation of doubly selective channels within pulse-shaping multicarrier systems (which include orthogonal frequency-division multiplexing (OFDM) systems as a special case). By exploiting sparsity in the delay-Doppler domain, CS-based channel estimation allows for an increase in spectral efficiency through a reduction of the number of pilot symbols. For combating leakage effects that limit the delay-Doppler sparsity, we propose a sparsity-enhancing basis expansion and a method for optimizing the basis with or without prior statistical information about the channel. We also present an alternative CS-based channel estimator for (potentially) strongly timefrequency dispersive channels, which is capable of estimating the off-diagonal channel coefficients characterizing intersymbol and intercarrier interference (ISI/ICI). For this estimator, we propose a basis construction combining Fourier (exponential) and prolate spheroidal sequences. Simulation results assess the performance gains achieved by the proposed sparsity-enhancing processing techniques and by explicit estimation of ISI/ICI channel coefficients. © IEEE.

Warner K.,University of Bonn
Environment and Planning C: Government and Policy | Year: 2012

The first-time-ever agreed-upon text on migration, displacement, and planned relocation in the United Nations Framework Convention on Climate Change (UNFCCC) climate negotiations process was informed by recent empirical research, and will shape how human mobility is dealt with under adaptation. Migration, displacement, and planned relocation feature in the text of the Cancun Adaptation Framework as technical cooperation issues which highlight activities that help to guide adaptation funding. Human mobility in the UNFCCC context is distinct from other policy fora-like international protocols and expanding mandates of existing frameworks such as the 1951 Geneva Convention. Operationally oriented solutions and discussions are moving forward in a UNFCCC process through the Cancun Adaptation Framework [paragraph 14(f)], the Climate Finance and the Adaptation Committee, and the Subsidiary Body on Implementation's Work Program on Loss and Damage. These and other policy processes catalyze nationally and regionally driven work on the topics of migration, displacement, and planned relocation in the context of climate change.

Noeker M.,University of Bonn
Hormone Research in Paediatrics | Year: 2011

Living with idiopathic short stature (ISS) may entail significant risks to psychological functioning and quality of life. Apparent inconsistency among study findings can be resolved if methodological differences among study designs are taken into account (i.e., definition of particular endpoints, sample selection from clinic or population, source of report, specific or generic assessment instruments, statistical control of confounders). Some individuals fail and others succeed in mastering the challenges of ISS. The principles of multifinality and equifinality may explain the emergence of a broad variation of individuals with ISS as a result of an interaction of the individual medical and auxological features on the one side, and psychosocial risk and protective factors on the other. As a result, patients may show heterogeneous developmental outcomes ranging from clinical psychopathology to development of resilience. A taxonomy of four distinct pathways of adaptation to ISS is delineated as a basis for case formulation and treatment planning. Psychological intervention in ISS includes counseling, cognitive-behavioral therapy and assertiveness training to improve psychological functioning via enhancement of target coping behaviors for critical situations. Copyright © 2011 S. Karger AG, Basel.

Grimme S.,University of Bonn | Goerigk L.,University of Sydney | Fink R.F.,University of Tubingen
Wiley Interdisciplinary Reviews: Computational Molecular Science | Year: 2012

Spin-component-scaled (SCS) electron correlation methods for electronic structure theory are reviewed. The methods can be derived theoretically by applying special conditions to the underlying wave functions in perturbation theory. They are based on the insight that low-order wave function expansions treat the correlation effects of electron pairs with opposite spin (OS) and same spin (SS) differently because of their different treatment at the underlying Hartree-Fock level. Physically, this is related to the different average inter-electronic distances in the SS and OS electron pairs. The overview starts with the original SCS-MP2 method and discusses its strengths and weaknesses and various ways to parameterize the scaling factors. Extensions to coupled-cluster and excited state methods as well the connection to virtual-orbital dependent density functional approaches are highlighted. The performance of various SCS methods in large thermochemical benchmarks and for excitation energies is discussed in comparison with other common electronic structure methods. © 2012 John Wiley & Sons, Ltd.

Samanta R.C.,University of Munster | De Sarkar S.,University of Munster | Frohlich R.,University of Munster | Grimme S.,University of Bonn | Studer A.,University of Munster
Chemical Science | Year: 2013

This edge article reports the synthesis and full characterization including X-ray analysis of three different acylazolium ions. The reactivity of these acylazolium ions as acylating reagents of amines and alcohols is discussed. Whereas benzylamine slowly reacts with the acylazolium ions, benzyl alcohol acylation does not occur. However, upon activation of the alcohol with an N-heterocyclic carbene (NHC) as catalyst, efficient esterification is achieved. Importantly, benzylester formation is obtained in the presence of benzylamine upon selective alcohol activation by the NHC. High level DFT calculations reveal that alcohol activation occurs by strong H-bond formation between the NHC and the alcohol thereby increasing the nucleophilicity of the alcohol. For oxidatively generated acylazolium ions under NHC catalysis, the carbene has a dual role (cooperative catalysis): (a) the NHC is used for generation of the acylazolium ion and (b) the NHC is used for activation of the alcohol in the subsequent acylation step. NHC-catalyzed selective acylation of benzyl alcohol in the presence of benzylamine can also be achieved with trifluoroethyl and hexafluoroisopropylesters as acylation reagents. Moreover, an enol acetate also shows high O-selectivity as a chemoselective acetylation reagent. Kinetic and mechanistic studies are provided and some examples of the chemoselective acylation of amino alcohols are presented. © 2013 The Royal Society of Chemistry.

Hougardy S.,University of Bonn
Computational Geometry: Theory and Applications | Year: 2011

We prove that every set of squares with total area 1 can be packed into a rectangle of area at most 2867/2048=1.399⋯. This improves on the previous best bound of 1.53. Also, our proof yields a linear time algorithm for finding such a packing. © 2011 Elsevier B.V.

Koch K.-R.,University of Bonn
International Journal of Advanced Manufacturing Technology | Year: 2010

For reverse engineering, nonuniform rational B-spline (NURBS) surfaces expressed by the tensor product are fitted to measured coordinates of points. To estimate the unknown control points, the lofting or skinning method by cross-sectional curve fits leads to efficient computations. Its numerical complexity for estimating k 2 control points is O(k 3), while simultaneously estimating the control points possesses a complexity of O(k 6). Both methods give identical results. The lofting method is generalized here from a two-dimensional surface represented by the tensor product to a three-dimensional one. Such a surface is needed for a deformation analysis or for solving dynamical problems of reverse engineering, where surfaces change with time. It is shown that the numerical complexity to estimate k 3 control points for a three-dimensional surface is only O(k 4). It is also shown by an analytical proof and confirmed by a numerical example that the lofting method for estimating the control points and their simultaneous estimation give identical results. The numerical complexity increases from O(k 4) for the lofting method to O(k 9) for the simultaneous estimation of k 3 control points. Thus, the lofting method leads to an efficient way of estimating three-dimensional NURBS surfaces for time-depending problems. © 2009 Springer-Verlag London Limited.

Walstab J.,University of Heidelberg | Walstab J.,University of Bonn | Rappold G.,University of Heidelberg | Niesler B.,University of Heidelberg
Pharmacology and Therapeutics | Year: 2010

Serotonin type 3 (5-HT3) receptors are pentameric ion channels belonging to the superfamily of Cys-loop receptors. Receptor activation either leads to fast excitatory responses or modulation of neurotransmitter release depending on their neuronal localisation. 5-HT3 receptors are known to be expressed in the central nervous system in regions involved in the vomiting reflex, processing of pain, the reward system, cognition and anxiety control. In the periphery they are present on a variety of neurons and immune cells. 5-HT3 receptors are known to be involved in emesis, pain disorders, drug addiction, psychiatric and GI disorders. Progress in molecular genetics gives direction to personalised medical strategies for treating complex diseases such as psychiatric and functional GI disorders and unravelling individual drug responses in pharmacogenetic approaches. Here we discuss the molecular basis of 5-HT3 receptor diversity at the DNA and protein level, of which our knowledge has greatly extended in the last decade. We also evaluate their role in health and disease and describe specific case-control studies addressing the involvement of polymorphisms of 5-HT3 subunit genes in complex disorders and responses to drugs. Furthermore, we focus on the actual state of the pharmacological knowledge concerning not only classical 5-HT3 antagonists - the setrons - but also compounds of various substance classes targeting 5-HT3 receptors such as anaesthetics, opioids, cannabinoids, steroids, antidepressants and antipsychotics as well as natural compounds derived from plants. This shall point to alternative treatment options modulating the 5-HT3 receptor system and open new possibilities for drug development in the future. © 2010 Elsevier Inc.

Gieselmann V.,University of Bonn | Krageloh-Mann I.,University Childrens Hospital
Neuropediatrics | Year: 2010

Metachromatic leukodystrophy (MLD) is a rare lysosomal sphingolipid storage disorder, caused by a deficiency of arylsulfatase A (ASA). It is inherited in an autosomal recessive way, among Caucasians three causing alleles are frequent. Demyelination is the hallmark of MLD. Interest in the disease has increased as therapeutic options such as stem cell transplantation, enzyme replacement and gene therapy are topics of current research. A late-infantile (onset before 3 years of age), a juvenile form (onset before 16 years) and an adult form are usually distinguished. Rapid motor decline is typical for the first and also the second forms, the second may be preceded by cognitive and behavioural problems, which mainly characterize the adult form. There is evidence for a genotype-phenotype correlation: patients homozygous for alleles which do not allow the expression of any enzyme activity (null-allele) suffer from the late infantile form; heterozygosity for a null allele and a non-null allele are more associated with the juvenile form and homozygosity for non-null alleles is more frequent in the most attenuated adult onset form. © Georg Thieme Verlag KG Stuttgart New York.

Majer C.,University of Tubingen | Hochholdinger F.,University of Tubingen | Hochholdinger F.,University of Bonn
Trends in Plant Science | Year: 2011

The plant-specific LBD (Lateral Organ Boundaries Domain) gene family is essential in the regulation of plant lateral organ development and is involved in the regulation of anthocyanin and nitrogen metabolism. LBD proteins contain a characteristic LOB domain composed of a C-motif required for DNA-binding, a conserved glycine residue, and a leucine-zipper-like sequence required for protein-protein interactions. Recently, several LBD genes associated with mutant phenotypes related to almost all aspects of plant development, including embryo, root, leaf, and inflorescence development have been functionally characterized. These novel insights contribute to a better understanding of the molecular definition of boundaries between organs or boundaries between organs and meristems and the regulation of these processes by environmental cues and phytohormones. © 2010 Elsevier Ltd.

Boufounos P.,MItsubishi Electric | Kutyniok G.,University of Osnabruck | Rauhut H.,University of Bonn
IEEE Transactions on Information Theory | Year: 2011

Sparse representations have emerged as a powerful tool in signal and information processing, culminated by the success of new acquisition and processing techniques such as compressed sensing (CS). Fusion frames are very rich new signal representation methods that use collections of subspaces instead of vectors to represent signals. This work combines these exciting fields to introduce a new sparsity model for fusion frames. Signals that are sparse under the new model can be compressively sampled and uniquely reconstructed in ways similar to sparse signals using standard CS. The combination provides a promising new set of mathematical tools and signal models useful in a variety of applications. With the new model, a sparse signal has energy in very few of the subspaces of the fusion frame, although it does not need to be sparse within each of the subspaces it occupies. This sparsity model is captured using a mixed ℓ1/ℓ2 norm for fusion frames. A signal sparse in a fusion frame can be sampled using very few random projections and exactly reconstructed using a convex optimization that minimizes this mixed ℓ1/ℓ2 norm. The provided sampling conditions generalize coherence and RIP conditions used in standard CS theory. It is demonstrated that they are sufficient to guarantee sparse recovery of any signal sparse in our model. Moreover, a probabilistic analysis is provided using a stochastic model on the sparse signal that shows that under very mild conditions the probability of recovery failure decays exponentially with increasing dimension of the subspaces. © 2011 IEEE.

Schneider P.,University of Bonn
Astronomy and Astrophysics | Year: 2014

Strong gravitational lensing of sources with different redshifts has been used to determine cosmological distance ratios, which in turn depend on the expansion history. Hence, such systems are viewed as potential tools for constraining cosmological parameters. Here we show that in lens systems with two distinct source redshifts, of which the nearest one contributes to the light deflection toward the more distant one, there exists an invariance transformation that leaves all strong-lensing observables unchanged (except for the product of time delay and Hubble constant), generalizing the well-known mass-sheet transformation in single-plane lens systems. The transformation preserves the relative location of mass and light. All time delays (from sources on both planes) scale with the same factor-time-delay ratios are therefore invariant under the mass-sheet transformation. Changing cosmological parameters, and thus distance ratios, is essentially equivalent to such a mass-sheet transformation. As an example, we discuss the double-source plane system SDSSJ0946+1006, which has recently been studied by Collett and Auger, and show that variations of cosmological parameters within reasonable ranges lead to only a weak mass-sheet transformation in both lens planes. Hence, the ability to extract cosmological information from such systems depends heavily on the ability to break the mass-sheet degeneracy. © 2014 ESO.

Moriya T.J.,University of Bonn | Moriya T.J.,University of Tokyo
Astronomy and Astrophysics | Year: 2014

We present a novel mechanism for enhancing the mass-loss rates of massive stars shortly before their explosion. The neutrino luminosities of the stellar core of massive stars increase as they get closer to the time of the core collapse. As emitted neutrinos escape freely from the core, the core mass is significantly reduced when the neutrino luminosity is high. If a star is near the Eddington luminosity when the neutrino luminosity is high, the star can exceed the Eddington luminosity because of the core neutrino mass loss. We suggest that the stellar surface mass-loss rates due to the core neutrino emission can be higher than 10-4 M⊙ yr-1 from ~1 year before the core collapse. The mass-loss rates can exceed 10 -2 M⊙ yr-1 ~ 10 days before the core collapse. This mass-loss mechanism may be able to explain the enhanced mass loss observed in some supernova progenitors shortly before their explosion. Even if the star is not close enough to the Eddington luminosity to enhance the mass loss, the star can still expand because of the reduced gravitational force. This mechanism can be activated in Wolf-Rayet stars, and it can create the hydrogen-poor, as well as hydrogen-rich, dense circumstellar media observed in some supernovae. © 2014 ESO.

Conti S.,University of Bonn | Dolzmann G.,University of Regensburg
Archive for Rational Mechanics and Analysis | Year: 2015

We consider vectorial variational problems in nonlinear elasticity of the form $${I[u]=\int W(Du)\,{\rm d}x}$$I[u]=∫W(Du)dx, where W is continuous on matrices with a positive determinant and diverges to infinity along sequences of matrices whose determinant is positive and tends to zero. We show that, under suitable growth assumptions, the functional $${\int W^{\rm qc}(Du)\,{\rm d}x}$$∫Wqc(Du)dx is an upper bound on the relaxation of I, and coincides with the relaxation if the quasiconvex envelope Wqc of W is polyconvex and has p-growth from below with $${p\geqq n}$$p≧n. This includes several physically relevant examples. We also show how a constraint of incompressibility can be incorporated in our results. © 2014, Springer-Verlag Berlin Heidelberg.

Von Zur Gathen J.,University of Bonn
Finite Fields and their Applications | Year: 2014

Ritts Second Theorem deals with composition collisions g ̊ h=* ̊ * of univariate polynomials over a field, where degg=deg*. Joseph Fels Ritt (1922) presented two types of such decompositions. His main result here is that these comprise all possibilities, up to some linear transformations. We present a normal form for Ritts Second Theorem, which is unique in many cases, and clarify the relation between the two types of examples. This yields an exact count of the number of such collisions in the "tame case", where the characteristic of the (finite) ground field does not divide the degree of the composed polynomial. © 2013 Elsevier Inc.

Langer N.,University of Bonn | Kudritzki R.P.,University of Hawaii at Manoa | Kudritzki R.P.,Ludwig Maximilians University of Munich
Astronomy and Astrophysics | Year: 2014

Context. The Hertzsprung-Russell diagram is an essential diagnostic diagram for stellar structure and evolution, which has now been in use for more than 100 years. Aims. We introduce a new diagram based on the gravity-effective temperature diagram, which has various advantages. Methods. Our spectroscopic Hertzsprung-Russell (sHR) diagram shows the inverse of the flux-mean gravity versus the effective temperature. Observed stars whose spectra have been quantitatively analyzed can be entered in this diagram without the knowledge of the stellar distance or absolute brightness. Results. Observed stars can be as conveniently compared to stellar evolution calculations in the sHR diagram as in the Hertzsprung-Russell diagram. However, at the same time, our ordinate is proportional to the stellar mass-to-luminosity ratio, which can thus be directly determined. For intermediate-and low-mass star evolution at constant mass, we show that the shape of an evolutionary track in the sHR diagram is identical to that in the Hertzsprung-Russell diagram. We also demonstrate that for hot stars, their stellar Eddington factor can be directly read off the sHR diagram. For stars near their Eddington limit, we argue that a version of the sHR diagram may be useful where the gravity is exchanged by the effective gravity. Conclusions. We discuss the advantages and limitations of the sHR diagram, and show that it can be fruitfully applied to Galactic stars, but also to stars with known distance, e.g., in the LMC or in galaxies beyond the Local Group. © 2014 ESO.

Bendas G.,University of Bonn | Borsig L.,University of Zurich
International Journal of Cell Biology | Year: 2012

Cell adhesion molecules play a significant role in cancer progression and metastasis. Cell-cell interactions of cancer cells with endothelium determine the metastatic spread. In addition, direct tumor cell interactions with platelets, leukocytes, and soluble components significantly contribute to cancer cell adhesion, extravasation, and the establishment of metastatic lesions. Clinical evidence indicates that heparin, commonly used for treatment of thromboembolic events in cancer patients, is beneficial for their survival. Preclinical studies confirm that heparin possesses antimetastatic activities that lead to attenuation of metastasis in various animal models. Heparin contains several biological activities that may affect several steps in metastatic cascade. Here we focus on the role of cellular adhesion receptors in the metastatic cascade and discuss evidence for heparin as an inhibitor of cell adhesion. While P- and L-selectin facilitation of cellular contacts during hematogenous metastasis is being accepted as a potential target of heparin, here we propose that heparin may also interfere with integrin activity and thereby affect cancer progression. This review summarizes recent findings about potential mechanisms of tumor cell interactions in the vasculature and antimetastatic activities of heparin. Copyright 2012 Gerd Bendas and Lubor Borsig.

Folbergrova J.,Academy of Sciences of the Czech Republic | Kunz W.S.,University of Bonn
Mitochondrion | Year: 2012

Mitochondrial dysfunction has been identified as one potential cause of epileptic seizures. Impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon's horn sclerosis and of adult and immature animal models of epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca 2+ homeostasis and generation of reactive oxygen species, their dysfunction strongly affects neuronal excitability and synaptic transmission. Therefore, mitochondrial dysfunction is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant epilepsy. For this reason mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy. © 2011 Elsevier B.V. and Mitochondria Research Society.

Seppelt R.,Helmholtz Center for Environmental Research | Lautenbach S.,University of Bonn | Volk M.,Helmholtz Center for Environmental Research
Current Opinion in Environmental Sustainability | Year: 2013

Research on mitigating land use conflicts is characterized by a variety of projects from the global to various sub-global scales. These projects are aiming at disentangling feedbacks within changing socio-environmental systems to identify strategies for sustainable resource use. Our review shows that any global analysis benefits from systematic synthesis of sub-global research from various scales, while sub-global investigations require embedding in global scenarios. There is an urgent need for improved methods to identify trade-offs at all scales as scenario analysis frequently results in a discrete set of options. We argue that the use of optimization algorithms including Pareto-frontiers combined with scenario analysis can provide efficient options for sustainable land use from global to sub-global scales. © 2013 Elsevier B.V.

Tesfahunegn G.B.,University of Bonn
Land Degradation and Development | Year: 2013

Assessment of soil quality (SQ) indicators that detect soil degradation in different land use and soil management systems (LUSMS) is desirable to achieve sustainable management strategies. The LUSMS identified for evaluation included natural forest (LS1), plantation of protected area (LS2), grazed land (LS3), teff (Eragrostis tef)-faba bean (Vicia faba) rotation (LS4), teff-wheat (Triticum vulgare)/barley (Hordeum vulgare) rotation (LS5), teff mono-cropping (LS6), maize (Zea mays) mono-cropping (LS7), and uncultivated marginal land (LS8). The SQ indicators were significantly influenced (p≤0·05) by the LUSMS. The first four principal components with eigenvalue>1 explain about 88% of the SQ variability across the LUSMS. The final principal component chosen indicators that mainly influence SQ variability were organic carbon, total nitrogen, cation exchange capacity, total phosphorus, silt, bulk density, and iron. In this study, a higher SQ was found in LS1 followed by LS2, whereas a seriously degraded SQ was observed in LS8 followed by LS6. © 2013 John Wiley & Sons, Ltd.

Stover B.C.,University of Munster | Stover B.C.,University of Bonn | Muller K.F.,University of Munster
BMC Bioinformatics | Year: 2010

Background: Today it is common to apply multiple potentially conflicting data sources to a given phylogenetic problem. At the same time, several different inference techniques are routinely employed instead of relying on just one. In view of both trends it is becoming increasingly important to be able to efficiently compare different sets of statistical values supporting (or conflicting with) the nodes of a given tree topology, and merging this into a meaningful representation. A tree editor supporting this should also allow for flexible editing operations and be able to produce ready-to-publish figures.Results: We developed TreeGraph 2, a GUI-based graphical editor for phylogenetic trees (available from http://treegraph.bioinfweb.info). It allows automatically combining information from different phylogenetic analyses of a given dataset (or from different subsets of the dataset), and helps to identify and graphically present incongruences. The program features versatile editing and formatting options, such as automatically setting line widths or colors according to the value of any of the unlimited number of variables that can be assigned to each node or branch. These node/branch data can be imported from spread sheets or other trees, be calculated from each other by specified mathematical expressions, filtered, copied from and to other internal variables, be kept invisible or set visible and then be freely formatted (individually or across the whole tree). Beyond typical editing operations such as tree rerooting and ladderizing or moving and collapsing of nodes, whole clades can be copied from other files and be inserted (along with all node/branch data and legends), but can also be manually added and, thus, whole trees can quickly be manually constructed de novo. TreeGraph 2 outputs various graphic formats such as SVG, PDF, or PNG, useful for tree figures in both publications and presentations.Conclusion: TreeGraph 2 is a user-friendly, fully documented application to produce ready-to-publish trees. It can display any number of annotations in several ways, and permits easily importing and combining them. Additionally, a great number of editing- and formatting-operations is available. © 2010 Stöver and Müller; licensee BioMed Central Ltd.

Tambo J.A.,University of Bonn | Abdoulaye T.,International Institute Of Tropical Agriculture
Regional Environmental Change | Year: 2013

The savanna region of Africa is a potential breadbasket of the continent but is severely affected by climate change. Understanding farmers' perceptions of climate change and the types of adjustments they have made in their farming practices in response to these changes will offer some insights into necessary interventions to ensure a successful adaptation in the region. This paper explores how smallholder farmers in the Nigerian savanna perceive and adapt to climate change. It is based on a field survey carried out among 200 smallholder farm households selected from two agro-ecological zones. The results show that most of the farmers have noticed changes in climate and have consequently adjusted their farming practices to adapt. There are no large differences in the adaptation practices across the region, but farmers in Sudan savanna agro-ecological zone are more likely to adapt to changes in temperature than those in northern Guinea savanna. The main adaptation methods include varying planting dates, use of drought tolerant and early maturing varieties and tree planting. Some of the farmers are facing limitations in adapting because of lack of information on climate change and the suitable adaptation measures and lack of credit. The study then concludes that to ensure successful adaptation to climate change in the region, concerted efforts are needed to design and promote planned adaptation measures that fit into the local context and also to educate farmers on climate change and appropriate adaptation measures. © 2012 Springer-Verlag.

Pudasaini S.P.,University of Bonn
Acta Mechanica | Year: 2014

The general two-phase debris flow model proposed by Pudasaini (J. Geophys. Res. 117:F03010, 2012, doi: 10.1029/2011JF002186) is employed to simulate subaerial and submarine two-phase debris flows and the mechanics of complex wave generation and interactions between the solid and the fluid phases. This includes the fluid waves or the tsunami generated by the debris impact at reservoirs, lakes, and oceans. The analysis describes the generation, amplification, and propagation of super tsunami waves and run-ups along coastlines, debris slide and deposition at the bottom floor, and debris shock waves. Accurate and advance knowledge of the arrival of tsunami waves in the coastal regions is very important for the design of early warning strategies. Here, we show that the amount of solid grain in the fluid reservoir plays a significant role in controlling the overall dynamics of the submarine debris flow and the tsunami. For very small solid particle concentrations in the reservoir, the submarine debris flow moves significantly faster than the surface tsunami wave. As the solid volume fraction in the reservoir increases, the submarine debris speed slows down. For relatively large solid volume fractions in the reservoir, the speed of the submarine debris becomes slower than the surface tsunami wave. This information can be useful for early warning strategies in the coastal regions. The fast or slow speed of the submarine wave can be attributed to several dynamical aspects of the model including the generalized drag, basal traction, pressure gradient, virtual mass force, the non-Newtonian viscous stress, and the strong phase interaction between the solid and the fluid as they enhance or diminish the motion of the solid phase. Solid particle concentration in the reservoir dam also substantially influences the interaction between the submarine debris flow and the frontal wall of the dam, and the interaction between the tsunami and the submarine debris wave. The tsunami wave impact generates a largely amplified fluid level at the dam wall. Submarine debris shock waves are observed for small solid volume fractions in the reservoir. Another important aspect of the simulation is to investigate the complex interactions between the internal submarine debris wave and the surface tsunami wave. Three complex waves occur simultaneously: the subaerial debris flow in the upstream region, submarine debris flow in the reservoir basin, and a super tsunami wave on the surface of the reservoir. This helps to develop insight into the basic features of the complex nonlinear solid and fluid waves and their interactions. © 2014 Springer-Verlag Wien.

Kretschmer M.,University of Heidelberg | Menche D.,University of Bonn
Organic Letters | Year: 2012

A convergent synthesis of the central C8-C22 core of the potent macrolide antibiotic rhizopodin is reported. Notable features of the stereocontrolled approach include an asymmetric reverse prenylation of an alcohol using a method of Krische, a thiazolium catalyzed transformation of an epoxyaldehyde as described by Bode, and a late-stage oxazole formation from advanced intermediates. This route demonstrates the applicability of these methodologies in complex natural product synthesis. © 2011 American Chemical Society.

Struzyna M.,University of Bonn
Proceedings -Design, Automation and Test in Europe, DATE | Year: 2013

This paper presents a new flexible quadratic and partitioning-based global placement approach which is able to optimize a wide class of objective functions, including linear, sub-quadratic, and quadratic net lengths as well as positive linear combinations of them. Based on iteratively re-weighted quadratic optimization, our algorithm extends the previous linearization techniques. If l is the length of some connection, most placement algorithms try to optimize l1 or l2. We show that optimizing l p with 1 < p < 2 helps to improve even linear connection lengths. With this new objective, our new version of the flow-based partitioning placement tool BonnPlace [25] is able to outperform the state-of-the-art force-directed algorithms SimPL, RQL, ComPLx and closes the gap to MAPLE in terms of (linear) HPWL. © 2013 EDAA.

Grimm T.W.,Max Planck Institute for Physics | Vieira Lopes D.,University of Bonn
Nuclear Physics B | Year: 2012

We discuss the four-dimensional N=1 effective actions of single space-time filling D. p-branes in general Type IIA and Type IIB Calabi-Yau orientifold compactifications. The effective actions depend on an infinite number of normal deformations and gauge connection modes. For D6-branes the N=1 Kähler potential, the gauge-coupling function, the superpotential and the D-terms are determined as functions of these fields. They can be expressed as integrals over chains which end on the D-brane cycle and a reference cycle. The infinite deformation space will reduce to a finite dimensional moduli space of special Lagrangian submanifolds upon imposing F- and D-term supersymmetry conditions. We show that the Type IIA moduli space geometry is captured by three real functionals encoding the deformations of special Lagrangian submanifolds, holomorphic three-forms and Kähler two-forms of Calabi-Yau manifolds. These elegantly combine in the N=1 Kähler potential, which reduces after applying mirror symmetry to the results previously determined for space-time filling D3-, D5- and D7-branes. We also propose general chain integral expressions for the Kähler potentials of Type IIB D-branes. © 2011 Elsevier B.V..

Zwicknagl B.,University of Bonn
Archive for Rational Mechanics and Analysis | Year: 2014

For certain martensitic phase transformations, one observes a close relation between the width of the thermal hysteresis and the compatibility of two phases. This observation forms the basis of a theory of hysteresis that assigns an important role to the microstructures in the transition layer and their energetics (Zhang et al., Acta Mater 57(15), 4332-4352, 2009). We study microstructures for almost compatible phases in the context of nonlinear elasticity. Using a scalar valued ansatz we show that one expects a transition from uniform to branched patterns for various typical models of the surface energy. We subsequently consider needle-type transition layers and study quantitative differences between hard and soft austenite, and between twins of different martensitic variants. © 2014 Springer-Verlag Berlin Heidelberg.

Kurts C.,University of Bonn
Kidney International | Year: 2013

Knauf et al. demonstrate that prolonged activation of the intrarenal inflammasome is responsible for the loss of kidney function in oxalate crystal nephropathy. These findings suggest new therapeutic opportunities for patients suffering from severe hereditary kidney diseases such as primary hyperoxaluria, and reveal a previously unappreciated general mechanism of kidney disease progression that may also contribute to conditions other than crystal nephropathy. © 2013 International Society of Nephrology.

Tutken T.,University of Bonn
PloS one | Year: 2013

The equid Hippotherium primigenium, with moderately hypsodont cheek teeth, rapidly dispersed through Eurasia in the early late Miocene. This dispersal of hipparions into the Old World represents a major faunal event during the Neogene. The reasons for this fast dispersal of H. primigenium within Europe are still unclear. Based on its hypsodonty, a high specialization in grazing is assumed although the feeding ecology of the earliest European hipparionines within a pure C3 plant ecosystem remains to be investigated. A multi-proxy approach, combining carbon and oxygen isotopes from enamel as well as dental meso- and microwear analyses of cheek teeth, was used to characterize the diet of the earliest European H. primigenium populations from four early Late Miocene localities in Germany (Eppelsheim, Höwenegg), Switzerland (Charmoille), and France (Soblay). Enamel δ(13)C values indicate a pure C3 plant diet with small (<1.4‰) seasonal variations for all four H. primigenium populations. Dental wear and carbon isotope compositions are compatible with dietary differences. Except for the Höwenegg hipparionines, dental microwear data indicate a browse-dominated diet. By contrast, the tooth mesowear patterns of all populations range from low to high abrasion suggesting a wide spectrum of food resources. Combined dental wear and stable isotope analysis enables refined palaeodietary reconstructions in C3 ecosystems. Different H. primigenium populations in Europe had a large spectrum of feeding habits with a high browsing component. The combination of specialized phenotypes such as hypsodont cheek teeth with a wide spectrum of diet illustrates a new example of the Liem's paradox. This dietary flexibility associated with the capability to exploit abrasive food such as grasses probably contributed to the rapid dispersal of hipparionines from North America into Eurasia and the fast replacement of the brachydont equid Anchitherium by the hypsodont H. primigenium in Europe.

Eyerich K.,TU Munich | Novak N.,University of Bonn
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2013

Atopic eczema (AE) is a challenge for modern medicine, because it is prevalent, severely affects quality of life of patients and their families, and causes high socioeconomic costs. The pathogenesis of AE is complex. While initial studies suggested a Th2 deviation as primary reason for the disease, numerous studies addressed a genetically predetermined impaired epidermal barrier as leading cause in a subgroup of patients. Recently, immune changes beyond the initial Th2 concept were defined in AE, with a role for specialized dendritic cells as well as newly identified T helper cell subsets such as Th17 and Th22 cells. Furthermore, trigger factors are expanded beyond classical Th2 allergens such as pollen or house dust mites to microbial products as well as self-antigens. This review pieces together our current understanding of immune as well as barrier abnormalities into the pathogenesis mosaic of AE. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Grimme S.,University of Bonn
Journal of Chemical Theory and Computation | Year: 2014

A black-box type procedure is presented for the generation of molecule-specific, classical potential energy functions (force-field, FF) solely from quantum mechanically (QM) computed input data. The approach can treat covalently bound molecules and noncovalent complexes with almost arbitrary structure. The necessary QM information consists of the equilibrium structure and the corresponding Hessian matrix, atomic partial charges, and covalent bond orders. The FF fit is performed automatically without any further input and yields a specific (nontransferable) potential which very closely resembles the QM reference potential near the equilibrium. The resulting atomistic, fully flexible FF is anharmonic and allows smooth dissociation of covalent bonds into atoms. A newly proposed force-constant-bond-energy relation with little empiricism provides reasonably accurate (about 5-10% error) atomization energies for almost arbitrary diatomic and polyatomic molecules. Intra- and intermolecular noncovalent interactions are treated by using well established and accurate D3 dispersion coefficients, CM5 charges from small basis set QM calculations, and a new interatomic repulsion potential. Particular attention has been paid to the construction of the torsion potentials which are partially obtained from automatic QM-tight-binding calculations for model systems. Detailed benchmarks are presented for conformational energies, atomization energies, vibrational frequencies, gas phase structures of organic molecules, and transition metal complexes. Comparisons to results from standard FF or semiempirical methods reveal very good accuracy of the new potential. While further studies are necessary to validate the approach, the initial results suggest QMDFF as a routine tool for the computation of a wide range of properties and systems (e.g., for molecular dynamics of isolated molecules, explicit solvation, self-solvation (melting) or even for molecular crystals) in particular when standard parametrizations are unavailable. © 2014 American Chemical Society.

Bekeredjian-Ding I.,University of Bonn
Autoimmunity | Year: 2013

Autoantibodies directed against nuclear antigens often arise in autoimmune disease associated with the failure to clear apoptotic cells in a swift and timely manner. Nucleic acids present in apoptotic cells and in membranous microparticles derived thereof exert adjuvant activity in the immune response to apoptosis. The scope of this review is to provide an overview on the current knowledge on B cell responses to apoptotic cells and membranous microparticles. Although physiological B cell responses to apoptotic cells result in the release of IL-10 by B cells and immunosuppression, pathological responses lead to autoantibody formation. Toll-like receptors specific for nucleic acids are engaged in both types of responses. In this review we delineate the functional impact of nucleic acids on B cell responses in the context of apoptosis. © Informa UK, Ltd.

Anighoro A.,University of Modena and Reggio Emilia | Bajorath J.,University of Bonn | Rastelli G.,University of Modena and Reggio Emilia
Journal of Medicinal Chemistry | Year: 2014

At present, the legendary magic bullet, i.e., a drug with high potency and selectivity toward a specific biological target, shares the spotlight with an emerging and alternative polypharmacology approach. Polypharmacology suggests that more effective drugs can be developed by specifically modulating multiple targets. It is generally thought that complex diseases such as cancer and central nervous system diseases may require complex therapeutic approaches. In this respect, a drug that hits multiple sensitive nodes belonging to a network of interacting targets offers the potential for higher efficacy and may limit drawbacks generally arising from the use of a single-target drug or a combination of multiple drugs. In this review, we will compare advantages and disadvantages of multitarget versus combination therapies, discuss potential drug promiscuity arising from off-target effects, comment on drug repurposing, and introduce approaches to the computational design of multitarget drugs. © 2014 American Chemical Society.

Grimme S.,University of Bonn
Journal of Chemical Physics | Year: 2013

Two approximations in the Tamm-Dancoff density functional theory approach (TDA-DFT) to electronically excited states are proposed which allow routine computations for electronic ultraviolet (UV)- or circular dichroism (CD) spectra of molecules with 500-1000 atoms. Speed-ups compared to conventional time-dependent DFT (TD-DFT) treatments of about two to three orders of magnitude in the excited state part at only minor loss of accuracy are obtained. The method termed sTDA ("s" for simplified) employs atom-centered Löwdin-monopole based two-electron repulsion integrals with the asymptotically correct 1/R behavior and perturbative single excitation configuration selection. It is formulated generally for any standard global hybrid density functional with given Fock-exchange mixing parameter a x. The method performs well for two standard benchmark sets of vertical singlet-singlet excitations for values of ax in the range 0.2-0.6. The mean absolute deviations from reference data are only 0.2-0.3 eV and similar to those from standard TD-DFT. In three cases (two dyes and one polypeptide), good mutual agreement between the electronic spectra (up to 10-11 eV excitation energy) from the sTDA method and those from TD(A)-DFT is obtained. The computed UV- and CD-spectra of a few typical systems (e.g., C60, two transition metal complexes, [7]helicene, polyalanine, a supramolecular aggregate with 483 atoms and about 7000 basis functions) compare well with corresponding experimental data. The method is proposed together with medium-sized double- or triple-zeta type atomic-orbital basis sets as a quantum chemical tool to investigate the spectra of huge molecular systems at a reliable DFT level. © 2013 AIP Publishing LLC.

Haertle D.,University of Bonn
Journal of Optics A: Pure and Applied Optics | Year: 2010

Quasi-phase matching conditions for second-harmonic generation are analyzed for whispering-gallery modes. Several domain patterns, particularly those useful for resonators made of lithium niobate, are compared in terms of their effective nonlinear optical coefficients and spectral bandwidths. Only if the grating period at the circular surface of the resonator is monotonically increasing will the effective nonlinearity be independent of small variations of the properties of the resonator, such as the radius, and the offset between the domain pattern and the center of the resonator. © 2010 IOP Publishing Ltd.

Guenther U.,University of Bonn | Radtke F.M.,Klinik fur Anasthesiologie Mit Schwerpunkt Operative Intensivmedizin
Current Opinion in Anaesthesiology | Year: 2011

Purpose of Review: Delirium is an acute, potentially life-threatening organ dysfunction with an incidence reported to range from 10-70% after surgery. Postoperative delirium was found to be associated with persisting cognitive deficits, increased physical dependence and institutionalization, and increased mortality. It is a condition particularly relevant to patients with increasing age. Recent Findings: This study summarizes recent works of the past 2 years, giving a brief overview as well as background information with regard to risk factors, impact on outcome parameters, mechanisms of pathophysiology, current use of hospital medication, and prevention and treatment strategies of postoperative delirium. Summary: Delirium may have an impact on patients' outcomes beyond their stay in hospital, depending on preoperative comorbidities. Delirium can be devastating for activity of daily living, cognitive performance and survival. Predisposing factors should be recognized preoperatively; precipitating factors such as preoperative fasting, deep sedation and choice of psychotropic drugs, including sedatives, should be reconsidered. Regular structured delirium screening is the precondition for early detection and treatment. Treatment options include cognitive training programmes, anti-inflammatory measures and antipsychotic drugs. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Carretero R.,German Cancer Research Center | Sektioglu I.M.,German Cancer Research Center | Garbi N.,German Cancer Research Center | Garbi N.,University of Bonn | And 4 more authors.
Nature Immunology | Year: 2015

Tumor-associated eosinophilia is frequently observed in cancer. However, despite numerous studies of patients with cancer and mouse models of cancer, it has remained uncertain if eosinophils contribute to tumor immunity or are mere bystander cells. Here we report that activated eosinophils were essential for tumor rejection in the presence of tumor-specific CD8 + T cells. Tumor-homing eosinophils secreted chemoattractants that guided T cells into the tumor, which resulted in tumor eradication and survival. Activated eosinophils initiated substantial changes in the tumor microenvironment, including macrophage polarization and normalization of the tumor vasculature, which are known to promote tumor rejection. Thus, our study presents a new concept for eosinophils in cancer that may lead to novel therapeutic strategies.

Crunelli V.,University of Cardiff | Carmignoto G.,University of Padua | Steinhauser C.,University of Bonn
Neuroscientist | Year: 2015

During the last 20 years, it has been well established that a finely tuned, continuous crosstalk between neurons and astrocytes not only critically modulates physiological brain functions but also underlies many neurological diseases. In particular, this novel way of interpreting brain activity is markedly influencing our current knowledge of epilepsy, prompting a re-evaluation of old findings and guiding novel experimentation. Here, we review recent studies that have unraveled novel and unique contributions of astrocytes to the generation and spread of convulsive and nonconvulsive seizures and epileptiform activity. The emerging scenario advocates an overall framework in which a dynamic and reciprocal interplay among astrocytic and neuronal ensembles is fundamental for a fuller understanding of epilepsy. In turn, this offers novel astrocytic targets for the development of those really novel chemical entities for the control of convulsive and nonconvulsive seizures that have been acknowledged as a key priority in the management of epilepsy. © The Author(s) 2014.

Staub F.,University of Bonn
Computer Physics Communications | Year: 2014

We present the new version of the Mathematica package SARAH which provides the same features for a non-supersymmetric model as previous versions for supersymmetric models. This includes an easy and straightforward definition of the model, the calculation of all vertices, mass matrices, tadpole equations, and self-energies. Also the two-loop renormalization group equations for a general gauge theory are now included and have been validated with the independent Python code PyR@TE. Model files for FeynArts, CalcHep/CompHep, WHIZARD and in the UFO format can be written, and source code for SPheno for the calculation of the mass spectrum, a set of precision observables, and the decay widths and branching ratios of all states can be generated. Furthermore, the new version includes routines to output model files for Vevacious for both, supersymmetric and non-supersymmetric, models. Global symmetries are also supported with this version and by linking Susyno the handling of Lie groups has been improved and extended. Program summary Program title: SARAH Catalogue identifier: AEIB-v3-0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ AEIB-v3-0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 271 795 No. of bytes in distributed program, including test data, etc.: 2 612 867 Distribution format: tar.gz Programming language: Mathematica. Computer: All for which Mathematica is available. Operating system: All for which Mathematica is available. Classification: 11.1, 11.6. Catalogue identifier of previous version: AEIB-v2-1 Journal reference of previous version: Comput. Phys. Commun. 184 (2013) 2604 Does the new version supersede the previous version?: Yes, the new version includes all known features of the previous versions but also provides the new features mentioned below. Nature of problem: A supersymmetric model is usually characterized by the particle content, the gauge sector and the superpotential. It is a time consuming process to obtain all necessary information for phenomenological studies from these basic ingredients. Solution method: Non-supersymmetric models are supported by the new possibility to define not only chiral superfields but also component fields. The renormalization group equations (RGEs) for a non-supersymmetric models are calculated by using the generic formulae for a general quantum field theory. Reasons for new version: New features in the definition of models and a full support of non-supersymmetric models. New output for Vevacious. Summary of revisions: Support of non-supersymmetric models; calculation of renormalization group equations for a general gauge theory; link to Susyno for handling of non-SU(N) gauge groups; support of global symmetries; output of model files for Vevacious; support of aligned VEVs; calculation of gauge dependent parts of RGEs for VEVs in running of supersymmetric and non-supersymmetric models. Restrictions: Only renormalizable terms in the Lagrangian are supported. No support of fields with spin 2 or 3/2. Unusual features: Calculation of non-supersymmetric RGEs includes effects of kinetic mixing as well as gauge dependence of running vacuum expectation values. SARAH is the first tool which can automatically create model files for Vevacious. Fully automatized derivation of all terms in the Lagrangian which are fixed by gauge invariance. Running time: Loading the Standard Model: 1.6 s; calculation of all vertices: 11.8 s; calculation of all RGEs: 130.2 s; output for Vevacious model files: 0.1 s; output of model files in UFO format: 0.8 s; output of model files for FeynArts: 0.1 s; output of model files for CalcHep: 0.8 s; output of model files for WHIZARD: 3.5 s; writing of source code for SPheno: 34.5 s. All times measured on Lenovo X220 with Intel(R) Core(TM) i7-2620M CPU @ 2.70 GHz. © 2014 Elsevier B.V. All rights reserved.

Patrij K.,University of Bonn
German medical science : GMS e-journal | Year: 2011

We analyzed clinical outcome of patients with an isolated central nervous system lymphoma (CNSL) relapse after systemic non-Hodgkin's lymphoma (NHL). All 23 patients with an isolated secondary CNSL (SCNSL) treated at two institutions from 04/2003-12/2007 were included into this analysis. At cerebral relapse, 15/23 patients were treated with a regimen consisting of high-dose methotrexate (Bonn protocol). After a median follow-up of 6.5 months (range 1-68), 15/23 (65%) patients with SCNSL had relapsed or progressed. HD (high-dose)- methotrexate (MTX) chemotherapy according to the Bonn protocol is effective concerning response rates; however, overall survival of patients with SCNSL seems to be impaired in comparison to relapses in primary CNSL (PCNSL).

Ranathunge K.,University of Bonn
Plant science : an international journal of experimental plant biology | Year: 2011

Suberin is an apoplastic biopolymer with tissue-specific deposition in the cell walls of the endo- and exodermis of roots, of periderms including wound periderm and other border tissues. Suberised cell walls contain both polyaliphatic and polyaromatic domains which are supposedly cross-linked. The predominant aliphatic components are ω-hydroxyacids, α,ω-diacids, fatty acids and primary alcohols, whereas hydroxycinnamic acids, especially ferulic acid, are the main components of the polyaromatic domain. Although the monomeric composition of suberin has been known for decades, its biosynthesis and deposition has mainly been a subject of speculation. Only recently, significant progress elucidating suberin biosynthesis has been achieved using molecular genetic approaches, especially in the model species Arabidopsis. In parallel, the long-standing hypothesis that suberin functions as an apoplastic barrier has been corroborated by sophisticated, quantitative physiological studies in the past decade. These studies demonstrated that suberised cell walls could act as barriers, minimising the movement of water and nutrients, restricting pathogen invasion and impeding toxic gas diffusion. In addition, suberised cell walls provide a barrier to radial oxygen loss from roots to the anaerobic root substrate in wetland plants. The recent onset of multidisciplinary approaches combining genetic, analytical and physiological studies has begun to deliver further insights into the physiological importance of suberin depositions in plants. Copyright Â© 2010 Elsevier Ireland Ltd. All rights reserved.

Irani S.R.,University of Oxford | Bien C.G.,University of Bonn | Lang B.,University of Oxford
Current Opinion in Neurology | Year: 2011

Purpose of review: To review the recent literature describing the detection and clinical importance of serum antibodies in patients with various epilepsies and other seizure-related disorders. Recent findings: Auto-antibodies to the NMDA, GABAB and AMPA receptors and to LGI1, CASPR2 and Contactin-2, components of the voltage-gated potassium channel complex, have been detected in the serum of patients with seizures. These antigenic targets are ion channels, receptors and accessory proteins important in both cellular homeostasis and governing the electrical activity of the brain. Antibodies to glutamic acid decarboxylase (GAD) have been found in patients with temporal lobe epilepsy. Antibodies to LGI1 have been described in around 90% of patients with the newly described epileptic syndrome of faciobrachial dystonic seizures. Summary: An increasing number of antibodies have been described in the epilepsies and other seizure-related disorders. Evidence of direct pathogenicity comes from the extracellular domain targeted by all of these antibodies (other than GAD) and the often dramatic clinical and serological response to immunotherapies, when antiepileptic drugs may be ineffective. Definitive proof as to the pathological relevance of these antibodies will be achieved in the generation of an animal model that demonstrates the clinical phenotype of these antibody-mediated disorders. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Thal D.R.,University of Ulm | Walter J.,University of Bonn | Saido T.C.,RIKEN | Fandrich M.,University of Ulm
Acta Neuropathologica | Year: 2015

Alzheimer’s disease (AD) is characterized by β-amyloid plaques and intraneuronal τ aggregation usually associated with cerebral amyloid angiopathy (CAA). Both β-amyloid plaques and CAA deposits contain fibrillar aggregates of the amyloid β-peptide (Aβ). Aβ plaques and CAA develop first in neocortical areas of preclinical AD patients and, then, expand in a characteristic sequence into further brain regions with end-stage pathology in symptomatic AD patients. Aβ aggregates are not restricted to amyloid plaques and CAA. Soluble and several types of insoluble non-plaque- and non-CAA-associated Aβ aggregates have been described. Amyloid fibrils are products of a complex self-assembly process that involves different types of transient intermediates. Amongst these intermediate species are protofibrils and oligomers. Different variants of Aβ peptides may result from alternative processing or from mutations that lead to rare forms of familial AD. These variants can exhibit different self-assembly and aggregation properties. In addition, several post-translational modifications of Aβ have been described that result, for example, in the production of N-terminal truncated Aβ with pyroglutamate modification at position 3 (AβN3pE) or of Aβ phosphorylated at serine 8 (pSer8Aβ). Both AβN3pE and pSer8Aβ show enhanced aggregation into oligomers and fibrils. However, the earliest detectable soluble and insoluble Aβ aggregates in the human brain exhibit non-modified Aβ, whereas AβN3pE and pSer8Aβ are detected in later stages. This finding indicates the existence of different biochemical stages of Aβ aggregate maturation with pSer8Aβ being related mainly to cases with symptomatic AD. The conversion from preclinical to symptomatic AD could thereby be related to combined effects of increased Aβ concentration, maturation of aggregates and spread of deposits into additional brain regions. Thus, the inhibition of Aβ aggregation and maturation before entering the symptomatic stage of the disease as indicated by the accumulation of pSer8Aβ may represent an attractive treatment strategy for preventing disease progression. © 2014, Springer-Verlag Berlin Heidelberg.

Klockgether T.,University of Bonn
The Lancet Neurology | Year: 2010

In most patients with adult-onset progressive ataxia, the condition manifests without an obvious familial background. The classification and correct diagnosis of such patients remain a challenge, because almost the entire spectrum of non-genetic and genetic causes of ataxia has to be considered. A wide range of potential causes of acquired ataxia exist, including chronic alcohol use, various other toxic agents, immune-mediated inflammation, vitamin deficiency, chronic leptomeningeal deposition of iron leading to superficial siderosis, and chronic CNS infection. Mutations in single genes can also underlie sporadic ataxia in adults. Finally, patients might have a sporadic degenerative disease, such as multiple system atrophy of cerebellar type or sporadic adult-onset ataxia of unknown aetiology. The definition of clinical criteria and delineation of characteristic MRI features have greatly facilitated the early and correct recognition of sporadic ataxias. In addition, specific serological and genetic markers are available that allow a definite diagnosis in many cases. © 2010 Elsevier Ltd. All rights reserved.

Sauter T.,RWTH Aachen | Venema V.,University of Bonn
Journal of Climate | Year: 2011

The paper presents an approach for conditional airmass classification based on local precipitation rate distributions. The method seeks, within the potential region, three-dimensional atmospheric predictor domains with high impact on the local-scale phenomena. These predictor domains are derived by an algorithm consisting of a clustering method, namely, self-organizing maps, and a nonlinear optimization method, simulated annealing. The findings show that the resulting spatial structures can be attributed to well-known atmospheric processes. Since the optimized predictor domains probably contain relevant information for precipitation generation, these grid points may also be potential inputs for nonlinear downscaling methods. Based on this assumption, the potential of these optimized large-scale predictors for downscaling has been investigated by applying an artificial neural network as a nonparametric statistical downscaling model. Compared to preset local predictors, using the optimized predictors improves the accuracy of the downscaled time series, particularly in summer and autumn. However, optimizing predictors by a conditional classification does not guarantee that a predictor increases the explained variance of the downscaling model. To study the contribution of each predictor to the output variance, either individually or by interactions with other parameters, the sources of uncertainty have been estimated by global sensitivity analysis, which provides model-free sensitivity measures. It is shown that predictor interactions play an important part in the modeling process and should be taken into account in the predictor screening. © 2011 American Meteorological Society.

Hossain Mondal Md.A.,University of Bonn
Renewable Energy | Year: 2010

Bangladesh is richly endowed with solar energy. Solar Photovoltaic (PV) system seems to be an appropriate form of renewable energy despite the monsoon type of climate in Bangladesh. The most attractive use of solar home system (SHS) in Bangladesh is the lighting system. People in rural Bangladesh predominantly use kerosene oil based lamps for illuminating their homes at night. Dry cell batteries are used for radio and gradually car batteries are becoming popular for running TV near grid areas where the charging facilities are available. The cost of kerosene and charging cost of battery are quite high and solar home system can compete with them in this particular field. Six cases were analyzed to find out the economic sustainability of the solar home systems at selected villages in Gazipur district, Bangladesh during October 2004-December 2004 and also questionnaire survey method was followed to collect data. This study reveals that the solar home system is financially attractive for small rural business and household lighting with entertainment. Only for household lighting purpose the system is not financially and economically viable without considering social benefits. © 2009 Elsevier Ltd. All rights reserved.

Tutken T.,University of Bonn
Palaeogeography, Palaeoclimatology, Palaeoecology | Year: 2014

The Middle Eocene oil shale deposits of Messel are famous for their exceptionally well-preserved, articulated 47-Myr-old vertebrate fossils that often still display soft tissue preservation. The isotopic compositions (O, C, Sr, Nd) were analysed from skeletal remains of Messel's terrestrial and aquatic vertebrates to determine the condition of geochemical preservation. Authigenic phosphate minerals and siderite were also analysed to characterise the isotope compositions of diagenetic phases. In Messel, diagenetic end member values of the volcanically-influenced and (due to methanogenesis) 12C-depleted anoxic bottom water of the meromictic Eocene maar lake are isotopically very distinct from in vivo bioapatite values of terrestrial vertebrates. This unique taphonomic setting allows the assessment of the geochemical preservation of the vertebrate fossils. A combined multi-isotope approach demonstrates that enamel of fossil vertebrates from Messel is geochemically exceptionally well-preserved and still contains near-in vivo C, O, Sr and possibly even Nd isotope compositions while bone and dentine are diagenetically altered.Enamel of the hippomorph perissodactyl Propalaeotherium has low δ13C values (-9±0.7‰), typical for C3-plant-feeders. Dentine of the same teeth has δ13C values 15-17‰ higher, amongst the highest δ13Cbioapatite values reported for terrestrial vertebrates. This reflects diagenetic carbonate exchange with the strongly 12C-depleted anoxic lake bottom water. Enamel 87Sr/86Sr values (~0.711±0.001) are consistent with Propalaeotherium feeding on Palaeozoic bedrocks surrounding Lake Messel and suggests that the basaltic tuff ring around the maar was already eroded 640ka after its formation. Dentine has, however, much lower, volcanically influenced 87Sr/86Sr (~0.706) due to diagenetic Sr uptake from the lake water/oil shale. Enamel δ18Op values (~18±0.6‰) of Propalaeotherium are 2-3‰ lower than those of bones and scales of aquatic vertebrates that lived in the 18O-enriched lake water. Using transfer functions, a δ18OH2O value of -5±1‰ for meteoric water and a MAT of ~18±2.5°C were reconstructed for Messel. © 2014 Elsevier B.V.

Grubert C.,University of Bonn
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry | Year: 2011

Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) has antidepressant effects in patients suffering from treatment-resistant depression (TRD). However, limited information exists regarding the impact of NAcc-DBS on cognitive functioning. The aim of this study was to examine whether NAcc-DBS in patients with TRD has any cognitive effects. A comprehensive neuropsychological battery was administered to 10 patients with TRD before onset of bilateral NAcc-DBS and after 1 year of DBS stimulation. Neuropsychological testing covered the domains of attention, learning and memory, executive functions, visual perception, and language. Performance was analyzed at baseline and after 1 year of continuous DBS. No evidence was found for cognitive decline following NAcc-DBS comparing test results after 1 year of NAcc-DBS with baseline. However, significantly improved cognitive performance on tests of attention, learning and memory, executive functions and visual perception was found. In addition, there was a general trend towards cognitive enhancement from below average to average performance. These procognitive effects were independent of the antidepressant effects of NAcc-DBS or changes in NAcc-DBS parameters. These results not only support cognitive safety of NAcc-DBS but also stress its beneficial role in augmenting cognitive performance in patients with TRD.

Furletov S.,University of Bonn
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2011

The DEPFET pixel detector offers first stage in-pixel amplification by incorporating a field effect transistor in the high resistivity silicon substrate. In this concept, a very small input capacitance can be realized thus allowing for low noise measurements. This makes DEPFET sensors a favorable technology for tracking in particle physics. Therefore a system with a DEPFET pixel matrix was developed to test DEPFET performance for an application as a vertex detector for the Belle II experiment. The system features a current based, row-wise readout of a DEPFET pixel matrix with a designated readout chip, steering chips for matrix control, a FPGA based data acquisition board, and a dedicated software package. The system was successfully operated in both test beam and lab environment. In 2009 new DEPFET matrices have been characterized in a 120 GeV pion beam at the CERN SPS. The current status of the DEPFET system and test beam results are presented. © 2010 Elsevier B.V. All rights reserved.

Luetkens J.A.,University of Bonn
RöFo : Fortschritte auf dem Gebiete der Röntgenstrahlen und der Nuklearmedizin | Year: 2015

PURPOSE: To investigate the effect of renal denervation on office-based and 24-h ambulatory blood pressure measurements (ABPM) in a highly selective patient population with drug-resistant hypertension.MATERIALS AND METHODS: Patients with drug resistant hypertension eligible for renal denervation were included in the study population. Office blood pressure and ABPM were assessed prior to and after renal denervation. To detect procedure related renal or renal artery damage, magnetic resonance imaging (MRI) and angiography (MRA) were performed pre-interventional, one day post-interventional, and one month after renal denervation.RESULTS: Mean follow-up time between renal denervation and blood pressure re-assessment was 9.5 ± 3.9 months. Between August 2011 and March 2013, 17 patients prospectively underwent renal denervation. Pre-interventional mean office blood pressure and ABPM were 177.3 ± 20.3/103.8 ± 20.4 mmHg and 155.2 ± 20.5/93.7 ± 14.5 mmHg, respectively. Post-interventional, office blood pressure was significantly reduced to 144.7 ± 14.9/89.5 ± 12.1 (p < 0.05). ABPM values remained unchanged (147.9 ± 20.3/90.3 ± 15.6, p > 0.05). The number of prescribed antihypertensive drugs was unchanged after renal denervation (4.7 ± 2.0 vs. 4.2 ± 1.2, p = 0.18). No renovascular complications were detected in follow-up MRI.CONCLUSION: After renal denervation, no significant decrease in ABPM was observed. These results may indicate a limited impact of renal denervation for drug resistant hypertension.KEY POINTS: • Renal denervation showed no significant effects on 24-h ambulatory blood pressure measurements. • A significant decrease in office blood pressure measurements may be explained by a potential detection bias. • Renal artery alterations were not observed on follow-up MRI scans. © Georg Thieme Verlag KG Stuttgart · New York.

Theis M.,University of Bonn | Giaume C.,College de France
Brain Research | Year: 2012

This review gives an overview of the current knowledge on connexin-mediated communication in astrocytes, covering gap junction and hemichannel functions mediated by connexins. Astroglia is the main brain cell type that expresses the largest amount of connexin and exhibits high level of gap junctional communication compared to neurons and oligodendrocytes. However, in certain developmental and regional situations, astrocytes are also coupled with oligodendrocytes and neurons. This heterotypic coupling is infrequent and minor in terms of extent of the coupling area, which does not mean that it is not important in terms of cell interaction. Here, we present an update on heterogeneity of connexin expression and function at the molecular, subcellular, cellular and networking levels. Interestingly, while astrocytes were initially considered as a homogenous population, there is now increasing evidence for morphological, developmental, molecular and physiological heterogeneity of astrocytes. Consequently, the specificity of gap junction channel- and hemichannel-mediated communication, which tends to synchronize cell populations, is also a parameter to take into account when neuroglial interactions are investigated. This article is part of a Special Issue entitled Electrical Synapses. © 2012 Elsevier B.V.

Schwarzlander M.,University of Bonn | Finkemeier I.,Ludwig Maximilians University of Munich | Finkemeier I.,University of Oxford
Antioxidants and Redox Signaling | Year: 2013

Significance: For a plant to grow and develop, energy and appropriate building blocks are a fundamental requirement. Mitochondrial respiration is a vital source for both. The delicate redox processes that make up respiration are affected by the plant's changing environment. Therefore, mitochondrial regulation is critically important to maintain cellular homeostasis. This involves sensing signals from changes in mitochondrial physiology, transducing this information, and mounting tailored responses, by either adjusting mitochondrial and cellular functions directly or reprogramming gene expression. Recent Advances: Retrograde (RTG) signaling, by which mitochondrial signals control nuclear gene expression, has been a field of very active research in recent years. Nevertheless, no mitochondrial RTG-signaling pathway is yet understood in plants. This review summarizes recent advances toward elucidating redox processes and other bioenergetic factors as a part of RTG signaling of plant mitochondria. Critical Issues: Novel insights into mitochondrial physiology and redox-regulation provide a framework of upstream signaling. On the other end, downstream responses to modified mitochondrial function have become available, including transcriptomic data and mitochondrial phenotypes, revealing processes in the plant that are under mitochondrial control. Future Directions: Drawing parallels to chloroplast signaling and mitochondrial signaling in animal systems allows to bridge gaps in the current understanding and to deduce promising directions for future research. It is proposed that targeted usage of new technical approaches, such as quantitative in vivo imaging, will provide novel leverage to the dissection of plant mitochondrial signaling. © Copyright 2013, Mary Ann Liebert, Inc.

Teichmann L.L.,Yale University | Teichmann L.L.,University of Bonn | Schenten D.,Yale University | Medzhitov R.,Yale University | And 2 more authors.
Immunity | Year: 2013

Detection of self nucleic acids by Toll-like receptors (TLR) preciptates autoimmune diseases, including systemic lupus erythematosus (SLE). It remains unknown how TLR signals in specific cell types contribute to distinct manifestations of SLE. Here, we demonstrate that formation of anti-nuclear antibodies in MRL.Faslpr mice entirely depends on the TLR signaling adaptor MyD88 in B cells. Further, MyD88 deficiency in B cells ameliorated nephritis, including antibody-independent interstitial T cell infiltrates, suggesting that nucleic acid-specific B cells activate nephrotoxic T cells. Surprisingly, MyD88 deletion in dendritic cells (DCs) did not affect nephritis, despite the importance of DCs in renal inflammation. In contrast, MyD88 in DCs was critical for dermatitis, revealing a separate pathogenetic mechanism. DC-expressed MyD88 promoted interferon-α production by plasmacytoid DCs, which was associated with Death domain-associated protein 6 upregulation and B lymphopenia. Our findings thus reveal unique immunopathological consequences of MyD88 signaling in B cells and DCs in lupus. © 2013 Elsevier Inc.

Epelbaum E.,Ruhr University Bochum | Krebs H.,Ruhr University Bochum | Lee D.,North Carolina State University | Meissner U.-G.,University of Bonn | Meissner U.-G.,Julich Research Center
Physical Review Letters | Year: 2011

The Hoyle state plays a crucial role in the helium burning of stars heavier than our Sun and in the production of carbon and other elements necessary for life. This excited state of the carbon-12 nucleus was postulated by Hoyle as a necessary ingredient for the fusion of three alpha particles to produce carbon at stellar temperatures. Although the Hoyle state was seen experimentally more than a half century ago nuclear theorists have not yet uncovered the nature of this state from first principles. In this Letter we report the first abAAinitio calculation of the low-lying states of carbon-12 using supercomputer lattice simulations and a theoretical framework known as effective field theory. In addition to the ground state and excited spin-2 state, we find a resonance at -85(3)MeV with all of the properties of the Hoyle state and in agreement with the experimentally observed energy. © 2011 American Physical Society.

Yan Y.Y.,University of Nottingham | Gao N.,University of Nottingham | Barthlott W.,University of Bonn
Advances in Colloid and Interface Science | Year: 2011

A typical superhydrophobic (ultrahydrophobic) surface can repel water droplets from wetting itself, and the contact angle of a water droplet resting on a superhydrophobic surface is greater than 150°, which means extremely low wettability is achievable on superhydrophobic surfaces. Many superhydrophobic surfaces (both manmade and natural) normally exhibit micro- or nanosized roughness as well as hierarchical structure, which somehow can influence the surface's water repellence. As the research into superhydrophobic surfaces goes deeper and wider, it is becoming more important to both academic fields and industrial applications. In this work, the most recent progress in preparing manmade superhydrophobic surfaces through a variety of methodologies, particularly within the past several years, and the fundamental theories of wetting phenomena related to superhydrophobic surfaces are reviewed. We also discuss the perspective of natural superhydrophobic surfaces utilized as mimicking models. The discussion focuses on how the superhydrophobic property is promoted on solid surfaces and emphasizes the effect of surface roughness and structure in particular. This review aims to enable researchers to perceive the inner principles of wetting phenomena and employ suitable methods for creation and modification of superhydrophobic surfaces. © 2011 Elsevier B.V. All rights reserved.

Madea B.,University of Bonn
Handbook of Forensic Medicine | Year: 2014

Forensic Medicine encompasses all areas in which medicine and law interact. This book covers diverse aspects of forensic medicine including forensic pathology, traumatology and violent death, sudden and unexpected death, clinical forensic medicine, toxicology, traffic medicine, identification, haemogenetics and medical law. A knowledge of all these subdisciplines is necessary in order to solve routine as well as more unusual cases. Taking a comprehensive approach the book m.oves beyond a focus on forensic pathology to include clinical forensic medicine and forensic toxicology. All aspects of forensic medicine are covered to meet the specialist needs of daily casework. Aspects of routine analysis and quality control are addressed in each chapter. The book provides coverage of the latest developments in forensic molecular biology, forensic toxicology, molecular pathology and immunohistochemistry. A must-have reference for every specialist in the field this book is set to become the bench-mark for the international forensic medical community. © 2014 by John Wiley & Sons, Ltd. All rights reserved.

Simon D.,University of Bern | Bieber T.,University of Bonn
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Systemic therapy for atopic dermatitis (AD) is indicated in patients with severe disease refractory to adequate topical treatment. Currently available drugs aim to decrease inflammation by suppressing and/or modulating immune responses and thus may indirectly improve skin barrier function, resulting in a decrease in clinical signs and symptoms in particular pruritus. Before considering systemic treatment, patient adherence to topical treatment including skin care has to be ensured. The selection of the drug depends on the disease severity, localization, complications, concomitant diseases, and age of the patient, but also on their availability and costs as well as the doctor's experience. Bearing in mind the potential risk of resistance, systemic therapy with antibiotics should be exclusively considered in clinically manifest infections such as in children. Here, we review recently published clinical trials and case reports on systemic therapy of pediatric and adult patients with AD to draw conclusions for clinical practice. Although AD is a common disease, controlled clinical studies investigating the efficacy of systemic drugs are scarce, except for cyclosporine, which has been approved for the therapy of severe AD. © 2013 John Wiley & Sons A/S.

Brand-Miller J.,University of Sydney | Buyken A.E.,University of Bonn
Current Opinion in Lipidology | Year: 2012

Purpose of review: In recent years, many of the concerns surrounding the glycemic index have been addressed by methodological studies and clinical trials comparing diets carefully matched for other nutrients. These findings are reviewed together with new observational evidence for the role of the dietary glycemic index in the etiology of cardiovascular disease. Recent findings: The determination and classification of the glycemic index of a food product is now standardized by the International Standards Organization. Systematic studies using isoenergetic single and mixed meals have shown that glycemic index and/or glycemic load are stronger predictors of postprandial glycemia and insulinemia than carbohydrate content alone. In overweight individuals, a diet that combined modestly higher protein and lower glycemic index carbohydrates was the most effective diet for prevention of weight regain. New observational studies have reported increased risks of coronary heart disease associated with higher intakes of carbohydrates from high glycemic index foods. Epidemiological evidence has emerged linking dietary glycemic index to visceral fat and inflammatory disease mortality. Summary: There is growing recognition that replacing saturated fat with refined, high glycemic index carbohydrates increases postprandial glycemia and may be detrimental for weight control and predisposition to cardiovascular and inflammatory disease. In contrast, low glycemic index carbohydrates reduce risk. © 2012 Lippincott Williams & Wilkins.

Sander P.M.,University of Bonn
PloS one | Year: 2013

Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades ("Reproduction", "Feeding", "Head and neck", "Avian-style lung", and "Metabolism"). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait "Very high body mass". Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size.

Prolss G.W.,University of Bonn
Surveys in Geophysics | Year: 2011

The upper atmosphere constitutes the outer region of the terrestrial gas envelope above about 100 km altitude. The energy budget of this outer gas layer is partly controlled by the dissipation of solar wind energy. Since this energy input is largely irregular, the resulting density changes are considered as perturbations. The properties and physics of such density perturbations are reviewed here. Besides being an important link in the complex chain of solar-terrestrial relations, such disturbances are also of practical interest because they affect the orbits of satellites and space stations and are responsible for ionospheric disturbance effects. © 2010 Springer Science+Business Media B.V.

Wang Y.,Yangzhou University | Frei M.,University of Bonn
Agriculture, Ecosystems and Environment | Year: 2011

Abiotic environmental stresses negatively impact crop productivity and are major constraints to global food security. As a consequence of global change, certain stress factors such as heat, drought, salinity, tropospheric ozone, and excess UV radiation might become even more prevalent in the coming decades. While the negative impact of these stresses on crop yields is obvious, their effects on crop quality are less recognized. Exposure to environmental stress induces numerous physiological stress reactions in plants that can alter the chemical composition of crops and thus the quality of the harvested products. Literature on the impact of abiotic environmental stresses on crop quality falls into seven categories of quality parameters: protein, lipids, non-structural carbohydrates, minerals, antioxidants, feed value for ruminant herbivores, and physical/sensory traits. Apart from summarizing net effects on these quality parameters, this review intends to elucidate physiological mechanisms leading to the observed changes in crop quality. All categories of traits are significantly affected by abiotic environmental stresses, resulting in both positive and negative changes in crop quality. The overall effect of a certain stress factor is often dependent on numerous interacting factors such as the timing of stress application, the intensity of the stress, and the crop species. In spite of these confounding elements, this review identifies some common patterns of stress response, such as a tendency towards increasing concentrations in protein and antioxidants in stressed crops, and a loss in quality in terms of feed value, starch and lipid concentration, or physical/sensory traits. This information might help agronomists and crop breeders to develop strategies to produce higher quality crops in stress environments. © 2011 Elsevier B.V.

Molderings G.J.,University of Bonn
Critical Reviews in Oncology/Hematology | Year: 2015

Within the last decade, and in particular since 2012, research has greatly extended our understanding of the molecular basis of systemic mast cell activation disease (MCAD). Initial studies demonstrated that somatic mutations in the tyrosine kinase KIT led to the establishment of a clonal mast cell population. Recent studies, in particular those involving next generation sequencing analyses of advanced systemic mastocytosis, have revealed mutations in additional genes. The respective genes encode proteins for various signaling pathways, epigenetic regulators, the RNA splicing machinery, and transcription factors. Although almost all of the detected mutations are somatic in nature, transgenerational transmission of MCAD appears to be quite common. However, the molecular mechanisms underlying genetic predestination, e.g. germline mutations and the contribution of epigenetic processes, still await identification. The aim of the present review is to present and discuss available genetic findings, and to outline the relationship between adult-onset systemic MCAD and childhood-onset mastocytosis, often termed cutaneous mastocytosis, on the basis of current genetic data. Finally, the implications of increased knowledge of the molecular basis of MCAD in terms of diagnostics and therapy are discussed. © 2014 Elsevier Ireland Ltd.

Frintrop S.,University of Bonn
Proceedings - IEEE International Conference on Robotics and Automation | Year: 2010

In this paper, we present a component-based visual object tracker for mobile platforms. The core of the technique is a component-based descriptor that captures the structure and appearance of a target in a flexible way. This descriptor can be learned quickly from a single training image and is easily adaptable to different objects. The descriptor is integrated into the observation model of a visual tracker based on the well known Condensation algorithm. We show that the approach is applicable to a large variety of objects and in different environments with cluttered backgrounds and a moving camera. The method is robust to illumination and viewpoint changes and applicable to indoor as well as outdoor scenes. ©2010 IEEE.

Schneider C.,ETH Zurich | Schneider C.,Howard Hughes Medical Institute | Nobs S.P.,ETH Zurich | Kurrer M.,Pathology Institute | And 3 more authors.
Nature Immunology | Year: 2014

Tissue-resident macrophages constitute heterogeneous populations with unique functions and distinct gene-expression signatures. While it has been established that they originate mostly from embryonic progenitor cells, the signals that induce a characteristic tissue-specific differentiation program remain unknown. We found that the nuclear receptor PPAR-γ 3 determined the perinatal differentiation and identity of alveolar macrophages (AMs). In contrast, PPAR-γ 3 was dispensable for the development of macrophages located in the peritoneum, liver, brain, heart, kidneys, intestine and fat. Transcriptome analysis of the precursors of AMs from newborn mice showed that PPAR-γ 3 conferred a unique signature, including several transcription factors and genes associated with the differentiation and function of AMs. Expression of PPAR-γ 3 in fetal lung monocytes was dependent on the cytokine GM-CSF. Therefore, GM-CSF has a lung-specific role in the perinatal development of AMs through the induction of PPAR-γ 3 in fetal monocytes. © 2014 Nature America, Inc. All rights reserved.

Frohlich H.,University of Bonn
Bioinformatics | Year: 2015

In the last years there has been an increasing effort to computationally model and predict the influence of regulators (transcription factors, miRNAs) on gene expression. Here we introduce biRte as a computationally attractive approach combining Bayesian inference of regulator activities with network reverse engineering. biRte integrates target gene predictions with different omics data entities (e.g. miRNA and mRNA data) into a joint probabilistic framework. The utility of our method is tested in extensive simulation studies and demonstrated with applications from prostate cancer and Escherichia coli growth control. The resulting regulatory networks generally show a good agreement with the biological literature. © 2015 The Author.

Junt T.,Novartis | Barchet W.,University of Bonn
Nature Reviews Immunology | Year: 2015

Nucleic acid sensing by innate receptors initiates immune defences against viruses and other pathogens. A hallmark of this response is the release of interferons (IFNs), which promote protective immunity by inducing IFN-stimulated genes (ISGs). A similar ISG signature is found in autoinflammatory and autoimmune conditions, indicating that chronic activation of nucleic acid-sensing pathways may contribute to these diseases. Here, we review how nucleic acid-sensing pathways are currently being targeted pharmacologically with both agonists and antagonists. We discuss how an improved understanding of the biology of these pathways is leading to novel therapies for infections, cancer, and autoimmune and autoinflammatory disorders, and how new therapeutics will, in turn, generate a deeper understanding of these complex diseases. © 2015 Macmillan Publishers Limited.

Watrous A.J.,University of California at Davis | Watrous A.J.,University of Bonn | Ekstrom A.D.,University of California at Davis
Frontiers in Human Neuroscience | Year: 2014

The spectral fingerprint hypothesis, which posits that different frequencies of oscillations underlie different cognitive operations, provides one account for how interactions between brain regions support perceptual and attentive processes (Siegel et al., 2012). Here, we explore and extend this idea to the domain of human episodic memory encoding and retrieval. Incorporating findings from the synaptic to cognitive levels of organization, we argue that spectrally precise cross-frequency coupling and phase-synchronization promote the formation of hippocampal-neocortical cell assemblies that form the basis for episodic memory.We suggest that both cell assembly firing patterns as well as the global pattern of brain oscillatory activity within hippocampal-neocortical networks represents the contents of a particular memory. Drawing upon the ideas of context reinstatement and multiple trace theory, we argue that memory retrieval is driven by internal and/or external factors which recreate these frequency-specific oscillatory patterns which occur during episodic encoding.These ideas are synthesized into a novel model of episodic memory (the spectrocontextual encoding and retrieval theory, or "SCERT") that provides several testable predictions for future research. © 2014 Watrous and Ekstrom.

Dreiner H.K.,University of Bonn | Haber H.E.,University of California at Santa Cruz | Martin S.P.,Northern Illinois University | Martin S.P.,Fermi National Accelerator Laboratory
Physics Reports | Year: 2010

Two-component spinors are the basic ingredients for describing fermions in quantum field theory in . 3+1 spacetime dimensions. We develop and review the techniques of the two-component spinor formalism and provide a complete set of Feynman rules for fermions using two-component spinor notation. These rules are suitable for practical calculations of cross-sections, decay rates, and radiative corrections in the Standard Model and its extensions, including supersymmetry, and many explicit examples are provided. The unified treatment presented in this review applies to massless Weyl fermions and massive Dirac and Majorana fermions. We exhibit the relation between the two-component spinor formalism and the more traditional four-component spinor formalism, and indicate their connections to the spinor helicity method and techniques for the computation of helicity amplitudes. © 2010.

Kavsek M.,University of Bonn
Attention, Perception, and Psychophysics | Year: 2014

In a series of preferential-looking experiments, infants 5 to 6 months of age were tested for their responsiveness to crossed and uncrossed horizontal disparity. In Experiments 1 and 2, infants were presented with dynamic random dot stereograms displaying a square target defined by either a 0.5° crossed or a 0.5° uncrossed horizontal disparity and a square control target defined by a 0.5° vertical disparity. In Experiment 3, infants were presented with the crossed and the uncrossed horizontal disparity targets used in Experiments 1 and 2. According to the results, the participants looked more often at the crossed (Experiment 1), as well as the uncrossed (Experiment 2), horizontal disparity targets than at the vertical disparity target. These results suggest that the infants were sensitive to both crossed and uncrossed horizontal disparity information. Moreover, the participants exhibited a natural visual preference for the crossed over the uncrossed horizontal disparity (Experiment 3). Since prior research established natural looking and reaching preferences for the (apparently) nearer of two objects, this finding is consistent with the hypothesis that the infants were able to extract the depth relations specified by crossed (near) and uncrossed (far) horizontal disparity. © 2014 Psychonomic Society, Inc.

Muller M.,Max Planck Institute for Informatics | Ewert S.,University of Bonn
IEEE Transactions on Audio, Speech and Language Processing | Year: 2010

Chroma-based audio features are a well-established tool for analyzing and comparing harmony-based Western music that is based on the equal-tempered scale. By identifying spectral components that differ by a musical octave, chroma features possess a considerable amount of robustness to changes in timbre and instrumentation. In this paper, we describe a novel procedure that further enhances chroma features by significantly boosting the degree of timbre invariance without degrading the features' discriminative power. Our idea is based on the generally accepted observation that the lower mel-frequency cepstral coefficients (MFCCs) are closely related to timbre. Now, instead of keeping the lower coefficients, we discard them and only keep the upper coefficients. Furthermore, using a pitch scale instead of a mel scale allows us to project the remaining coefficients onto the 12 chroma bins. We present a series of experiments to demonstrate that the resulting chroma features outperform various state-of-the art features in the context of music matching and retrieval applications. As a final contribution, we give a detailed analysis of our enhancement procedure revealing the musical meaning of certain pitch-frequency cepstral coefficients. © 2006 IEEE.

Stein K.W.,University of Bonn
PloS one | Year: 2013

Osteocytes harbour much potential for paleobiological studies. Synchrotron radiation and spectroscopic analyses are providing fascinating data on osteocyte density, size and orientation in fossil taxa. However, such studies may be costly and time consuming. Here we describe an uncomplicated and inexpensive method to measure osteocyte lacunar densities in bone thin sections. We report on cell lacunar densities in the long bones of various extant and extinct tetrapods, with a focus on sauropodomorph dinosaurs, and how lacunar densities can help us understand bone formation rates in the iconic sauropod dinosaurs. Ordinary least square and phylogenetic generalized least square regressions suggest that sauropodomorphs have lacunar densities higher than scaled up or comparably sized mammals. We also found normal mammalian-like osteocyte densities for the extinct bovid Myotragus, questioning its crocodilian-like physiology. When accounting for body mass effects and phylogeny, growth rates are a main factor determining the density of the lacunocanalicular network. However, functional aspects most likely play an important role as well. Observed differences in cell strategies between mammals and dinosaurs likely illustrate the convergent nature of fast growing bone tissues in these groups.

Bett P.,University of Bonn
Monthly Notices of the Royal Astronomical Society | Year: 2012

We analyse the impact of galaxy-halo misalignment on the ability of weak lensing studies to constrain the shape of dark matter haloes, using a combination of the Millennium dark matter N-body simulation and different semi-analytic galaxy formation models, as well as simpler Monte Carlo tests. Since the distribution of galaxy-halo alignments is not known in detail, we test various alignment models, together with different methods of determining the halo shape. In addition to alignment, we examine the interplay of halo mass and shape, and galaxy colour and morphology with the resulting stacked projected halo shape. We find that only in the case where significant numbers of galaxy and halo minor axes are parallel does the stacked, projected halo axis ratio fall below 0.95. When using broader misalignment distributions, such as those found in recent simulations of galaxy formation, the halo ellipticity signal is washed out and would be extremely difficult to measure observationally. It is important to note that the spread in stacked halo axis ratio due to theoretical unknowns (differences between semi-analytic models and between alignment models) are much bigger than any statistical uncertainty. It is naïve to assume that, simply because Λ cold dark matter (ΛCDM) predicts aspherical haloes, the stacked projected shape will be elliptical. In fact, there is no robust ΛCDM prediction yet for this procedure, and the interpretation of any such elliptical halo signal from lensing in terms of physical halo properties will be extremely difficult. © 2012 The Author. Monthly Notices of the Royal Astronomical Society © 2012 RAS.

Lindenberg R.,Beth Israel Deaconess Medical Center | Zhu L.L.,Beth Israel Deaconess Medical Center | Ruber T.,Beth Israel Deaconess Medical Center | Ruber T.,University of Bonn | Schlaug G.,Beth Israel Deaconess Medical Center
Human Brain Mapping | Year: 2012

Electrophysiological and neuroimaging studies suggest that the integrity of ipsilesional and inter-hemispheric motor circuits is important for motor recovery after stroke. However, the extent to which each of these tracts contributes to the variance in outcome remains unclear. We examined whether diffusion tensor imaging (DTI)-derived measures of corticospinal and transcallosal tracts predict motor improvement in an experimental neurorehabilitation trial. 15 chronic stroke patients received bihemispheric transcranial direct current stimulation and simultaneous physical/occupational therapy for five consecutive days. Motor impairment was assessed prior to and after the intervention. At baseline, the patients underwent DTI; probabilistic fiber tracking was used to reconstruct the pyramidal tract (PT), alternate descending motor fibers (aMF), and transcallosal fibers connecting primary motor cortices (M1-M1). Ipsilesional corticospinal tracts (PT, aMF) and M1-M1 showed significantly decreased fractional anisotropy (FA) and increased directional diffusivities when compared to age-matched healthy controls. Partial correlations revealed that greater gains in motor function were related to higher FA values and lower directional diffusivities of transcallosal and ipsilesional corticospinal tracts. M1-M1 diffusivity had the greatest predictive value. An additional slice-by-slice analysis of FA values along the corticospinal tracts demonstrated that the more the ipsilesional FA profiles of patients resembled those of healthy controls, the greater their functional improvement. In conclusion, our study shows that DTI-derived measures can be used to predict functional potential for subsequent motor recovery in chronic stroke patients. Diffusivity parameters of individual tracts and tract combinations may help in assessing a patient's individual recovery potential and in determining optimal neurorehabilitative interventions. © 2011 Wiley-Liss, Inc.

Oldenburg J.,University of Bonn
Blood | Year: 2015

Prophylactic application of clotting factor concentrates is the basis of modern treatment of severe hemophilia A. In children, the early start of prophylaxis as primary or secondary prophylaxis has become the gold standard in most countries with adequate resources. In adults, prophylaxis is reasonably continued when started as primary or secondary prophylaxis in childhood to maintain healthy joint function. Initial data support that adult patients with already existing advanced joint arthropathy benefit from tertiary prophylaxis with significantly lowered number of bleeds, almost complete absence of target joints, and less time off from work. Current prophylactic regimens, although very effective, do not completely prevent joint disease in a long-term perspective. Joint arthropathy in primary prophylaxis develops over many years, sometimes over a decade or even longer time periods. The ankle joints are the first and most severely affected joints in those patients and thus may serve in outcome assessment as an indicator of early joint arthropathy when followed by ultrasound or magnetic resonance imaging. Optimized outcome and best use of available resources is expected from individualization of therapy regimens, which comprises the individual's bleeding pattern, condition of the musculoskeletal system, level of physical activity and the pharmacokinetic profile of the substituted coagulation factor, and most recently includes novel products with extended half-lives. © 2015 by The American Society of Hematology J.O. received reimbursement for attending symposia/congresses, and/or honoraria for speaking, and/ or honoraria for consulting, and/or funds for research from Baxter, Bayer, Biogen Idec, Biotest, CSL-Behring, Grifols, Novo Nordisk, Octapharma, Swedish Orphan Biovitrum, and Pfizer.

Guta D.D.,University of Bonn
Energy Policy | Year: 2012

It is well known that poor rural households in low-income economies are reliant on traditional fuels to meet basic domestic energy needs, but little is known about the specific underlying socio-economic drivers of residential fuel choices in Ethiopia. I used the linear approximation almost ideal demand system (LAAIDS) with normalized prices to compute expenditure elasticity and a multinomial logit model (MLM) to examine household fuel use. The LAAIDS model result showed that expenditure was elastic for modern fuels, but inelastic for traditional fuels. Regression results from the MLM indicated that fuel choice behaviour of rural households could be more accurately described as 'fuel stacking' behaviour as opposed to the 'energy ladder' hypothesis. In rural areas household fuel choice may be constrained by limited access to commercial fuels and efficient cook stoves, supply dependency and affordability, consumer preferences and a web of other intricate factors. Rural households had less incentive for fuel switching due to underlying factors and the availability of fuel wood without direct financial cost. With continued deforestation and receding forests, households are expected to develop inter fuel substitution and switching behaviour conditional on access to modern energy technologies. © 2012 Elsevier Ltd.

Guta D.D.,University of Bonn
International Journal of Renewable Energy Research | Year: 2012

In recent years, there has been renewed interest on renewable biomass based energies. This is due to growing environmental benign, energy security concern and spiraling price of fossil fuel. In the case of poor economies like Ethiopia quality of life and energy consumption are tidily conjoined. This article assessed biomass fuel resource potential of Ethiopia and also investigated strategies for its modern utilization, with particular emphasis on sourcing options for cleaner energies. With proper sourcing strategies, biomass supplies green and cleaner renewable energy for wider human, industrial and transportation services. There is, however, no systematic study on strategies for efficient use of biomass fuel resource in Ethiopia. Abundant and untapped availability, user as well as environmental friendliness, applicability for wider fuel need purposes, competitiveness in terms of cost of production, its rural poverty linkages and multitude of other factors make biomass based fuels prior energy source of Ethiopia. Hence, innovative investment on renewable biomass based fuels (e.g. biogas, bioethanol and biodiesel) and broad distribution of improved fuel stove technologies to rural and urban households, as well as energy conservation technologies for industries and service sector should be promising areas for policies targeting green growth. Hence, developing appropriate institutions and technologies for renewable energies sourcing from biomass is invaluable.

Synofzik M.,University of Tubingen | Schlaepfer T.E.,University of Bonn | Schlaepfer T.E.,Johns Hopkins University
Brain Stimulation | Year: 2011

Background: Deep brain stimulation (DBS) has been used for neuropsychiatric disorders in clinical and research settings for almost 50 years now. Recent evidence demonstrates some efficacy in treating obsessive-compulsive disorder and major depression in patients refractory to other treatment modalities beyond single case reports. This has led to a considerable surge of clinical and commercial interest in DBS for psychiatric indications. Because of the high vulnerability of psychiatric patients, the lack of extensive short- and long-term data about effectiveness and the rapid spread of questionable indications this new field in psychiatry requires ethical criteria that can be applied to both research and clinical decision-making. Objective and Methods: We here present an evidence-based systematic ethical analysis of psychiatric DBS using the criteria of beneficence, nonmaleficence, and autonomy. Results and Conclusions: The proposed criteria are helpful in analyzing empirical evidence, informing research investigations and guiding clinical decision-making. This will prepare the ground for ethically justified, empirically comprehensive DBS in this highly vulnerable population and allow stringent future societal discussions about its legitimation. © 2011 Elsevier Inc. All rights reserved.

Kircheis G.,Heinrich Heine University Dusseldorf | Hilger N.,University of Bonn | Haussinger D.,Heinrich Heine University Dusseldorf
Gastroenterology | Year: 2014

Background & Aims Critical flicker frequency (CFF) and psychometric hepatic encephalopathy score (PHES) analyses are widely used to diagnose hepatic encephalopathy (HE), but little is known about their value in the diagnosis of low-grade HE. Methods The diagnostic values of CFF and PHES were compared using a computerized test battery and West Haven criteria as reference. We performed CFF analysis on 559 patients with cirrhosis and 261 without (controls). Of these 820 patients, 448 were evaluated using a modified PHES system and 148 were also evaluated using the conventional PHES system. Results CFF distinguished between patients with overt HE and without minimal or overt HE in the entire study population with 98% sensitivity and 94% specificity and in the subgroup of patients who were evaluated by conventional PHES with 97% sensitivity and 100% specificity. Conventional PHES identified patients with overt HE with 73% sensitivity and 89% specificity. CFF distinguished between patients with and without minimal HE with only 37% sensitivity but 94% specificity (entire study population). In the subgroup of patients evaluated by conventional PHES, CFF distinguished between patients with and without minimal HE with 22% sensitivity and 100% specificity; these values were similar to those for conventional PHES (30% sensitivity and 89% specificity). The modified PHES distinguished between patients with and without minimal HE with 49% sensitivity and 74% specificity. The diagnostic agreement values between CFF and conventional or modified PHES in patients with minimal HE were only 54% or 47%, respectively. Conclusions In an analysis of patients with cirrhosis and controls, CFF distinguished between patients with overt HE and without minimal or overt HE. PHES testing produced a statistically significant difference among groups, but there was considerable overlap between controls and patients with overt HE. PHES, CFF, and a combination of PHES and CFF could not reliably distinguish patients with minimal HE from controls or those with overt HE. © 2014 by the AGA Institute.

Latz E.,University of Massachusetts Medical School | Latz E.,University of Bonn
Current Opinion in Immunology | Year: 2010

In response to injurious or infectious agents caspase-1 activating multiprotein complexes, termed inflammasomes, assemble in the cytoplasm of cells. Activated caspase-1 cleaves the proforms of the interleukin-1 cytokine family members leading to their activation and secretion. The IL-1 family cytokines have multiple proinflammatory activities implicating them in the pathogenesis of many inflammatory diseases. While defined ligands have been identified for the NLRP1, IPAF, and AIM2 inflammasomes, little is known about the activation mechanisms of the NLRP3 inflammasome. Numerous different molecular entities, such as various crystals, pore-forming toxins, or extracellular ATP can trigger the NLRP3 inflammasome. Recent work proposes that NLRP3 is activated indirectly by host factors that are generated in response to NLRP3 triggers. © 2009 Elsevier Ltd. All rights reserved.

Hugging F.,University of Bonn
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2011

The ATLAS Detector will be upgraded for higher intensity running of the LHC. A long shutdown is envisioned in 2016 prior to the so-called Phase I running. A new pixel layer, called the Insertable B-Layer (IBL), will be inserted at a radius of about 3.2 cm between the existing Pixel Detector and a new (smaller radius) beam-pipe. The IBL requires the development of several new technologies to cope with the increased radiation level and pixel occupancy, as well as to improve the physics performance of the existing Pixel Detector. The IBL project provides a test of technologies for the Phase II upgrade of the entire ATLAS tracker for luminosities around 1035 cm-2 s-1. An overview of the project with particular emphasis on the IBL layout and expected performance as well as the module development including hybridization technologies is presented. © 2010 Elsevier B.V. All rights reserved.

Wermes N.,University of Bonn
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2011

The Pixel 2010 conference focused on semiconductor pixel detectors for particle tracking/vertexing as well as for imaging, in particular for synchrotron light sources and XFELs. The big LHC hybrid pixel detectors have impressively started showing their capabilities. X-ray imaging detectors, also using the hybrid pixel technology, have greatly advanced the experimental possibilities for diffraction experiments. Monolithic or semi-monolithic devices like CMOS active pixels and DEPFET pixels have now reached a state such that complete vertex detectors for RHIC and superKEKB are being built with these technologies. Finally, new advances towards fully monolithic active pixel detectors, featuring full CMOS electronics merged with efficient signal charge collection, exploiting standard CMOS technologies, SOI and/or 3D integration, show the path for the future. This résumé attempts to extract the main statements of the results and developments presented at this conference. © 2010 Elsevier B.V. All rights reserved.

Grimme S.,University of Bonn
Angewandte Chemie - International Edition | Year: 2013

The routine calculation of EI mass spectra is based on a combination of fast quantum chemical methods, molecular dynamics, and the stochastic preparation of "hot" primary ions. All basic elementary processes are considered with minor empiricism and realistic potential free energy surfaces are employed. Reasonable spectra are generated along with detailed information on the corresponding decomposition and reaction mechanisms. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Forsbach R.,University of Bonn
Nervenarzt | Year: 2012

The psychiatrist Friedrich Panse (1899-1973) was a T4 assessor during the Nazi era who sent mentally disabled and mentally ill people to their deaths. In the German Armed Forces he used higher galvanic currents to cure "war neurotics" and expose "malingerers." As a National Socialist he was a committed teacher of racial hygiene. Nonetheless, after the end of the Nazi regime many supporters quickly surfaced who were prepared to exonerate Panse. Panse himself was not among those who indignantly repudiated the accusation of any contact with the Nazi Party. He did not deny that he had openly embraced the Nazi measures for preserving the genetic integrity of the populace, but he did let it be known that he had suffered incredibly under the heavy burden. The State Government of North Rhine-Westphalia refused to allow Panse to continue in his capacity as an extraordinary professor. Panse successfully contested this decision at the State Administrative Court in Düsseldorf. He became the Director of the Institution in Düsseldorf-Grafenberg, the Psychiatric Clinic in Düsseldorf, a member of the German Council of Medical Advisors for questions regarding care for war victims of the German Federal Ministry of Labor, and President of the German Society for Psychiatry and Neurology. © Springer-Verlag 2012.

Bauer R.,University of Bonn
Results and Problems in Cell Differentiation | Year: 2010

Energy homeostasis and growth require the coordinated regulation of lipid metabolism. The underlying molecular mechanisms are poorly understood. We are interested in identifying key regulators of lipid homeostasis and their functional mechanism. Recently, we identified the schlank gene as a major regulator of lipid homeostasis in Drosophila. Schlank encodes a conserved member of the Lass/CerS family of ceramide synthases , which contain a catalytic Lag1 motif and a homeobox transcription factor domain. Schlank mutant larvae, show decreased levels of sphingolipids and depleted fat stores due to an upregulation of triacylglycerol lipases and a downregulation of SREBP-dependent fatty acid synthesis. In addition, we have demonstrated that mammalian members of the conserved Lass/CerS family had also effects on lipid homeostasis. Therefore, we are currently interested to find how members of this family e.g., schlank may act as regulators coordinating cellular and organismic lipid homeostasis in animals mechanistically. We now address these issues by using a combination of genetics, biochemistry and integrative physiology. © 2011 Springer Berlin Heidelberg.

Steinberg J.S.,University of Bonn
Retina | Year: 2015

PURPOSE:: To evaluate the development of intraretinal cystoid lesions (ICLs) in eyes with intermediate age-related macular degeneration. METHODS:: Serial multimodal retinal imaging data of 105 eyes from 87 age-related macular degeneration subjects (median age of 75.0 years) with no late age-related macular degeneration at baseline from the prospective longitudinal natural history “molecular diagnostic of age-related macular degeneration-study” were included. The presence of ICLs—defined as lacunar hyporeflective areas within the neurosensory retina—was determined by spectral-domain optical coherence tomography at Month 24. Both baseline and further follow-up data were additionally evaluated. RESULTS:: At Month 24, ICLs were identified in 12 of 105 (11.7%) eyes of which 4 had developed signs of choroidal neovascularization since baseline. Intraretinal cystoid lesions in these four eyes with choroidal neovascularization were mostly found at the level of the outer nuclear layer. Intraretinal cystoid lesions in the remaining 8 eyes occurred mainly at the level of the inner nuclear layer, showed smaller horizontal and vertical dimensions, and were not spatially confined to an increase in retinal thickness. CONCLUSION:: The results indicate that ICLs may develop also in the absence of active neovascularization. Distinctive morphologic features and localization of ICLs may be indicative of different underlying pathogenetic mechanisms. If no manifest choroidal neovascularization can be established in the presence of ICLs, close monitoring as well as awareness and self-monitoring seem to be advisable. © 2015 by Ophthalmic Communications Society, Inc.

Lukasiuk K.,Nencki Institute of Experimental Biology | Becker A.J.,University of Bonn
Neurotherapeutics | Year: 2014

Epileptogenesis, a process leading to a reduced threshold for seizures after transient brain insults, as well as the mechanisms underlying the propensity to generate spontaneous epileptic seizures, are highly dynamic processes. Biomarkers-objective measures of biological processes-would be excellent tools for monitoring epileptogenesis and the dynamics of increased seizure propensity, as well as the potential to interfere, for example pharmacologically, with these key pathological aspects of epilepsy. Molecular biomarkers have revolutionized therapies, as well as response prediction and monitoring of therapies in other biomedical fields. However, high-impact molecular biomarkers are still not available in the context of epilepsy. Several factors, such as the large heterogeneity of epileptic syndromes and their underlying pathological patterns, as well as the limited availability of tissue samples, represent a particular challenge to the development of molecular biomarkers in epileptogenesis and epilepsy. However, substantial technical progress has been made recently with respect to biomarker characterization and monitoring by large throughput analysis on the genomic, mRNA, and proteomic levels, starting from minute amounts of brain tissue or body fluids, for example cerebrospinal fluid, blood, serum, or plasma. Given the substantial cellular- and network-level functional pathophysiology involved in epilepsy, it may be beneficial in the future to combine molecular analysis with other methods, such as imaging and electrophysiological biomarkers. © 2014 The Author(s).

Frohlich H.,University of Bonn
PLoS ONE | Year: 2011

Diagnostic and prognostic biomarkers for cancer based on gene expression profiles are viewed as a major step towards a better personalized medicine. Many studies using various computational approaches have been published in this direction during the last decade. However, when comparing different gene signatures for related clinical questions often only a small overlap is observed. This can have various reasons, such as technical differences of platforms, differences in biological samples or their treatment in lab, or statistical reasons because of the high dimensionality of the data combined with small sample size, leading to unstable selection of genes. In conclusion retrieved gene signatures are often hard to interpret from a biological point of view. We here demonstrate that it is possible to construct a consensus signature from a set of seemingly different gene signatures by mapping them on a protein interaction network. Common upstream proteins of close gene products, which we identified via our developed algorithm, show a very clear and significant functional interpretation in terms of overrepresented KEGG pathways, disease associated genes and known drug targets. Moreover, we show that such a consensus signature can serve as prior knowledge for predictive biomarker discovery in breast cancer. Evaluation on different datasets shows that signatures derived from the consensus signature reveal a much higher stability than signatures learned from all probesets on a microarray, while at the same time being at least as predictive. Furthermore, they are clearly interpretable in terms of enriched pathways, disease associated genes and known drug targets. In summary we thus believe that network based consensus signatures are not only a way to relate seemingly different gene signatures to each other in a functional manner, but also to establish prior knowledge for highly stable and interpretable predictive biomarkers. © 2011 Holger Fröhlich.

Bilkei-Gorzo A.,University of Bonn
Pharmacology and Therapeutics | Year: 2014

Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. © 2013 Elsevier Inc.

Kariko K.,University of Pennsylvania | Muramatsu H.,University of Pennsylvania | Ludwig J.,University of Bonn | Weissman D.,University of Pennsylvania
Nucleic Acids Research | Year: 2011

In vitro-transcribed mRNA has great therapeutic potential to transiently express the encoded protein without the adverse effects of viral and DNA-based constructs. Mammalian cells, however, contain RNA sensors of the innate immune system that must be considered in the generation of therapeutic RNA. Incorporation of modified nucleosides both reduces innate immune activation and increases translation of mRNA, but residual induction of type I interferons (IFNs) and proinflammatory cytokines remains. We identify that contaminants, including double-stranded RNA, in nucleoside-modified in vitro-transcribed RNA are responsible for innate immune activation and their removal by high performance liquid chromatography (HPLC) results in mRNA that does not induce IFNs and inflammatory cytokines and is translated at 10-to 1000-fold greater levels in primary cells. Although unmodified mRNAs were translated significantly better following purification, they still induced high levels of cytokine secretion. HPLC purified nucleoside-modified mRNA is a powerful vector for applications ranging from ex vivo stem cell generation to in vivo gene therapy. © 2011 The Author(s).

Ingiliz P.,Medical Center for Infectious Diseases Berlin | Rockstroh J.K.,University of Bonn
Liver International | Year: 2012

With the licensing of the first hepatitis C (HCV) protease inhibitors (PI), telaprevir (TVR) and boceprevir (BOC), cure rates for chronic HCV infection will substantially improve. Human immunodeficiency virus- chronic hepatitis C (HIV-HCV) co-infected patients are in urgent need for these new drugs, because they are facing both severe liver disease and lower response rates than HCV monoinfected patients. The currently available efficacy data are however, limited to two phase II trials. Fortunately, TVR and BOC appear to be able to improve cure rates in co-infected patients. A major challenge for clinicians will be the management of drug-drug interactions of antiretroviral drugs and new PI. As HCV PI are also metabolized by the cytochrome P450 3A4 system interactions are probable as well with non-nucleoside reverse transcriptase inhibitors as with HIV PI. To our knowledge, TVR can only be safely used with one protease inhibitor, boosted atazanavir, and also with efavirenz (EFV), although this combination requires TVR dose adjustments. Boceprevir should not be combined with HIV PI and should not be combined with EFV. The approval of TVR and BOC will create new chances of cure also for HIV-HCV co-infected patients. However, the decision who to treat or not has to be taken carefully on the basis of fibrosis stage and previous treatment outcomes. In addition, HIV therapy needs to be optimized according to the available drug-drug interaction data. © 2012 John Wiley & Sons A/S.

Lacombe K.,University Pierre and Marie Curie | Rockstroh J.,University of Bonn
Gut | Year: 2012

With a prevalence affecting over 30% of HIV infected patients, coinfection with hepatitis B (HBV) or C (HCV) virus remains one of the most frequent comorbidities in this population, with a significant impact in terms of morbidity and mortality associated with liver disease. Recent findings in the physiopathology of HIV in the liver have confirmed that it may contribute, along with hepatotoxicity of antiretrovirals and the burden of metabolic diseases, to a more rapid progression of liver fibrosis, especially when there is underlying chronic hepatitis coinfection. Both fields of research and clinical appraisal of HBV and HCV coinfection are rapidly evolving and prompt a change in the former paradigms of clinical care and management of chronic hepatic coinfection in the context of HIV. The advent of anti-HCV direct antiviral agents has indeed completely shaken up the treatment guidelines for HCV, and the tricky management of these new agents with antiretrovirals means referring patients to specialised centres. In HBV coinfection, therapeutic options have not changed recently but new challenges have emerged regarding the management of low replicating HBV-DNA in optimally treated patients and long term exposure to antivirals. Finally, the global increase in life expectancy in HIV infected patients has been accompanied in coinfected patients by a higher risk of emergence of end stage liver diseases for which access to orthotopic liver transplantation and innovative procedures such as targeted hepatocellular carcinoma therapies should be facilitated.

Giaume C.,College de France | Theis M.,University of Bonn
Brain Research Reviews | Year: 2010

This review gives an overview of connexin expression in glial cells of the central nervous system, the different modes of connexin action, including gap junctional channels and hemichannels, as well as the available methodologies to measure their activity. We summarize the strengths and limitations of current pharmacological and genetic approaches to interfere with connexin channel functions. We outline new avenues not only to study specific mechanisms by which connexins exert these functions but also to selectively investigate well-defined coupling compartments among glial networks. © 2009 Elsevier B.V.

Furletov S.,University of Bonn
Journal of Instrumentation | Year: 2012

SuperKEKB, an upgrade of KEKB is under construction, to increase the luminosity by two orders of magnitude during a three-year shutdown, with an ultimate goal of 8 × 1035cm-2s-1 luminosity. To exploit the increased luminosity, an upgrade of the Belle detector has been proposed. The physics goals of the planned Belle II experiment require a vertex detector with unprecedented performance. The main issues are a high spatial resolution of a few micrometers, a high granularity, and a fast readout speed to cope with the expected high hit occupancy. © 2012 IOP Publishing Ltd and SISSA.

Walter J.,University of Bonn
Current Alzheimer Research | Year: 2012

Genetic studies demonstrate that the ε4 allele of the apolipoprotein (apo) E is a risk factor for late onset Alzheimer's disease (AD). Apo E is the major component of lipoprotein particles in the brain that mediate transport of cholesterol and other lipids between neurons and glial cells, indicating an implication of cerebral lipid metabolism in the pathogenesis of AD. In addition, apo E is also involved in the metabolism and aggregation of the amyloid β-peptide (Aβ) that derives from proteolytic processing of the amyloid precursor protein (APP) and is found in plaques of AD brains. The generation of Aβ involves sequential cleavages of APP by proteases called β-and γ-secretase. γ-Secretase is a high molecular weight protein complex containing presenilins as catalytically active subunits. Importantly, mutations in the genes of APP and the two homologous PS proteins are a major cause of familial early onset AD, indicating that the metabolism of APP and generation of Aβ play critical roles in the initiation of the disease. This review focuses on the functional relation of γ-secretase complexes and the metabolism of lipoproteins in the brain. It is hypothesized that γ-secretase activity is critically involved in cellular lipid homeostasis and that impaired lipid metabolism contributes to the pathogenesis of AD. © 2012 Bentham Science Publishers.

Baluska F.,University of Bonn
Plant Signaling and Behavior | Year: 2010

Plant cells and neurons share several similarities, including non-centrosomal microtubules, motile post-Golgi organelles, separated both spatially/ structurally and functionally from the Golgi apparatus and involved in vesicular endocytic recycling, as well as cell-cell adhesion domains based on the actin/myosin cytoskeleton which serve for cell-cell communication. Tip-growing plant cells such as root hairs and pollen tubes also resemble neurons extending their axons. Recently, surprising discoveries have been made with respect to the molecular basis of neurodegenerative disorders known as Hereditary Spastic Paraplegias and tipgrowth of root hairs. All these advances are briefly discussed in the context of other similarities between plant cells and neurons. © 2010 Landes Bioscience.

Neenan J.M.,University of Zurich | Klein N.,University of Bonn | Scheyer T.M.,University of Zurich
Nature Communications | Year: 2013

Sauropterygia was the most successful marine reptile radiation in history, spanning almost the entire Mesozoic and exploiting a wide range of habitats and ecological niches. Here we report a new, exceptionally preserved skull of a juvenile stem placodont from the early Middle Triassic of the Netherlands, thus indicating a western Tethyan (European) origin for Placodontia, the most basal group of sauropterygians. A single row of teeth on an enlarged palatine supports this close relationship, although these are small and pointed instead of broad and flat, as is the case in placodonts, which demonstrate the strongest adaptation to a durophagous diet known in any reptile. Peg-like, slightly procumbent premaxillary teeth and an 'L-shaped' jugal also confirm a close relationship to basal placodonts. The new taxon provides insight into the evolution of placodont dentition, representing a transitional morphology between the plesiomorphic diapsid condition of palatal denticles and the specialized crushing teeth of placodonts. © 2013 Macmillan Publishers Limited. All rights reserved.

Luedtke F.,University of Bonn | Buse K.,Albert Ludwigs University of Freiburg | Buse K.,Fraunhofer Institute for Physical Measurement Techniques | Sturman B.,Russian Academy of Sciences
Physical Review Letters | Year: 2012

We show that a continuous-wave (cw) pump beam at a wavelength of 532 nm produces substantial light-induced (LI) absorption in the visible range in initially transparent undoped LiNbO 3 crystals. The LI absorption coefficient stays linear in the pump intensity I p up to Ipmax=48kW/cm2. Together with other features including long-term stretched-exponential relaxation of the LI absorption, it indicates that the present concept of LI electron processes in this important optical material must be revised: the amount of photoactive electrons increases already within the cw intensity range. A quantitative model is proposed that explains the experimental data and employs two-step excitations from filled localized states near the valence band via intermediate deep centers into the conduction band. The introduced localized states serve as a hidden reservoir of electrons. © 2012 American Physical Society.

Nettersheim D.,University of Bonn
British Journal of Cancer | Year: 2016

Background:Cancer/testis-antigens (CTAs) are specifically expressed in human malignancies and testis tissue, but their molecular functions are poorly understood. CTAs serve as regulators of gene expression, cell cycle and spermatogenesis, as well as targets for immune-based therapies. The CTA PRAME is expressed in various cancers, antagonises retinoic acid signalling and is regulated by DNA methylation and histone acetylation.Methods:We analysed the molecular function of the CTA PRAME in primordial germ cells (PGC) and testicular germ cell cancers (GCC). GCCs arise from a common precursor lesion termed germ cell neoplasia in situ (GCNIS), which itself is thought to originate from a defective PGC. GCNIS cells eventually develop into unipotent seminomas or totipotent embryonal carcinomas (ECs), which are capable of differentiation into teratomas, yolk-sac tumours and choriocarcinomas.Results:PRAME is, like the master regulator of PGCs SOX17 expressed in human PGCs, GCNIS and seminomas but absent in ECs. shRNA-mediated knockdown of PRAME in seminomatous TCam-2 cells left SOX17 levels unchanged, but resulted in downregulation of pluripotency- and PGC-related genes (LIN28, PRDM14, ZSCAN10), whereas somatic and germ cell differentiation markers were upregulated. So, PRAME seems to act downstream of SOX17 by mediating the regulation of the germ cell differentiation and pluripotency programme. Endoderm differentiation is triggered in somatic cells by SOX17, suggesting that in PGCs, PRAME represses this programme and modulates SOX17 to function as a PGC-master regulator. Surprisingly, knockdown of PRAME in TCam-2 cells did not render the cells sensitive towards retinoic acid, despite the fact that PRAME has been described to antagonise retinoic acid signalling. Finally, we demonstrate that in non-seminomas PRAME expression is silenced by DNA methylation, which can be activated by formation of euchromatin via histone-deacetylase-inhibitors.Conclusions:We identified the CTA PRAME as a downstream factor of SOX17 and LIN28 in regulating pluripotency and suppressing somatic/germ cell differentiation in PGC, GCNIS and seminomas.British Journal of Cancer advance online publication, 21 July 2016; doi:10.1038/bjc.2016.187 www.bjcancer.com. © 2016 Cancer Research UK

Grunwald F.,University Hospital Frankfurt | Ezziddin S.,University of Bonn
Seminars in Nuclear Medicine | Year: 2010

Treatment with 131I-metaiodobenzylguanidine (MIBG) has been introduced to the management of neuroendocrine tumors (NET) nearly 30 years ago. It provides efficient internal radiotherapy of chromaffin tumors (neuroblastoma, pheochromocytoma, and paraganglioma), but also of carcinoid and other less frequent tumors. Although for various NET types the role of this treatment form decreased by the emergence of peptide receptor radionuclide therapy, 131I-MIBG still remains the primary radiopharmaceutical for targeting chromaffin tumors with outstanding efficiency. Results in neuroblastoma with overall response rates around 30% in refractory or recurrent diseases have been improved by combinations with chemotherapy, radiosensitizers, and autologous stem cell support. For adult chromaffin tumors, that is, pheochromocytoma and/or paraganglioma, 131I-MIBG therapy is currently the most efficient nonsurgical therapeutic modality and applies for inoperable, disseminated disease. The antisecretory effect with powerful palliation of symptomatic disease (response rate: 75%-90%) should also be considered when judging treatment benefit. The results in carcinoid tumors are less pronounced, primarily achieving arrest of tumor growth, and most importantly effective functional control. With the presence of peptide receptor radionuclide therapy, 131I-MIBG remains the alternative radionuclide in this tumor entity, for example, for patients with renal impairment. Another worthwhile mentioning indication-although less prevalent-are metastatic medullary thyroid carcinomas, especially if functioning. These patients are good candidates for this treatment form in the absence of reasonable surgical options and presence of diagnostic MIBG uptake. This article outlines the current status, results, and methodological improvements of 131I-MIBG therapy. © 2010 Elsevier Inc. All rights reserved.

Marsch F.,University of Bonn
European Journal of Human Genetics | Year: 2016

Oesophageal atresia (OA) with or without tracheoesophageal fistula (TOF) are rare anatomical congenital malformations whose cause is unknown in over 90% of patients. A genetic background is suggested, and among the reported genetic defects are copy number variations (CNVs). We hypothesized that CNVs contribute to OA/TOF development. Quantifying their prevalence could aid in genetic diagnosis and clinical care strategies. Therefore, we profiled 375 patients in a combined Dutch, American and German cohort via genomic microarray and compared the CNV profiles with their unaffected parents and published control cohorts. We identified 167 rare CNVs containing genes (frequency<0.0005 in our in-house cohort). Eight rare CNVs – in six patients – were de novo, including one CNV previously associated with oesophageal disease. (hg19 chr7:g.(143820444_143839360)_(159119486_159138663)del) 1.55% of isolated OA/TOF patients and 1.62% of patients with additional congenital anomalies had de novo CNVs. Furthermore, three (15q13.3, 16p13.3 and 22q11.2) susceptibility loci were identified based on their overlap with known OA/TOF-associated CNV syndromes and overlap with loci in published CNV association case–control studies in developmental delay. Our study suggests that CNVs contribute to OA/TOF development. In addition to the identified likely deleterious de novo CNVs, we detected 167 rare CNVs. Although not directly disease-causing, these CNVs might be of interest, as they can act as a modifier in a multiple hit model, or as the second hit in a recessive condition.European Journal of Human Genetics advance online publication, 20 July 2016; doi:10.1038/ejhg.2016.86. © 2016 Macmillan Publishers Limited

von Koenigswald W.,University of Bonn
Historical Biology | Year: 2013

The enamel microstructure in molars of Arsinoitherium is reinvestigated and a new modification of radial enamel (RE), 'arsinoitheriid radial enamel (ARE)', is defined. It is characterised by alternating stripes with different organisation of the interprismatic matrix but no prism decussation. Recognition of this new subtype leads to a reinterpretation of structure previously identified as modified radial enamel and of Hunter-Schreger bands in Arsinoitherium. The newly differentiated ARE of Arsinoitherium is more derived in relation to corresponding microstructures of Palaeoamasia and Crivadiatherium. A careful reinvestigation of RE in other Paenungulata will be required to provide additional data bearing on phylogenetic reconstruction. The enamel of Phenacolophus argues against inclusion of this genus in the Embrithopoda. © 2013 Copyright Taylor and Francis Group, LLC.

Lamprecht A.,University of Bonn
Nature Reviews Gastroenterology and Hepatology | Year: 2015

Nanoscale systems are currently under investigation for multiple different diagnostic and therapeutic applications. These systems can be used to identify pathologically changed tissues or to selectively deliver drugs to these sites; both applications have an extremely high potential to ameliorate therapeutic outcomes for patients. Tissues as well as single cells can be targeted because of the small size of these systems, which enables enhanced diagnosis and increased specificity of therapy. Drug loads can be delivered directly to the site of action, which can result in a reduction in incidence and severity of adverse systemic effects. Several nano-based platform technologies are currently under investigation for use in therapeutic approaches, mainly for anti-inflammatory and anti-cancer therapies. Although many nanoscale systems show promising therapeutic outcomes in preclinical studies, only a limited number are ready for clinical use. This Review will discuss the diverse nanomaterials currently available and the first specific uses for select gastroenterological and hepatological pathologies. The discussion of diagnostic and therapeutic applications will consider realities of market introduction of these sometimes very complex systems in light of remaining regulatory challenges and hurdles for industrial production. © 2015 Macmillan Publishers Limited.

Juergens U.R.,University of Bonn
Drug Research | Year: 2014

1,8-cineole is a natural monoterpene, also known as eucalyptol. It is a major compound of many plant essential oils, mainly extracted from Eucalyptus globulus oil. As an isolated compound, 1,8-cineole is known for its mucolytic and spasmolytic action on the respiratory tract, with proven clinical efficacy. 1,8-cineole has also shown therapeutic benefits in inflammatory airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). This clinical evidence refers to its anti-inflammatory and anti-oxidant mode of action, which has been proven in numerous pre-clinical studies. In vitro studies found strong evidence that 1,8-cineole controls inflammatory processes and mediator production of infection- or inflammation-induced mucus hypersecretion by its action as anti-inflammatory modifier rather than a simple mucolytic agent. The aim of this review is to present these preclinical studies performed with the pure monoterpene, and to summarize the current knowledge on the mode of action of 1,8-cineole. The actual understanding of the pure 1,8-cineole compared to mixtures of natural volatile oils containing 1,8-cineole as a major compound and to mixtures of natural terpenes, known as essential oils, will be discussed. Based on the anti-oxidative and anti-inflammatory properties, recent clinical trials with 1,8-cineole have shown first evidence for the beneficial use of 1,8-cineole as long-term therapy in the prevention of COPD-exacerbations and to improve asthma control. © Georg Thieme Verlag KG Stuttgart · New York.

Hirsch M.,University of Valencia | Staub F.,University of Bonn | Vicente A.,University Paris - Sud
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

Lepton flavor violation has been observed in neutrino oscillations. For charged lepton flavor violation decays only upper limits are known, but sizable branching ratios are expected in many neutrino mass models. High-scale models, such as the classical supersymmetric seesaw, usually predict that decays l i→3l j are roughly a factor α smaller than the corresponding decays l i→l jγ. Here we demonstrate that the Z0-penguin diagram can give an enhancement for decays l i→3l j in many extensions of the minimal supersymmetric standard model (MSSM). We first discuss why the Z0-penguin is not dominant in the MSSM with seesaw and show that much larger contributions from the Z0-penguin are expected in general. We then demonstrate the effect numerically in two example models, namely, the supersymmetric inverse seesaw and R-parity violating supersymmetry. © 2012 American Physical Society.

Huehn J.,Helmholtz Center for Infection Research | Beyer M.,University of Bonn
Seminars in Immunology | Year: 2015

Regulatory T cells (Treg cells) present a unique T-cell lineage that plays a key role for the initiation and maintenance of immunological tolerance. Treg cells are characterized by the expression of the forkhead box transcription factor Foxp3, which acts as a lineage-specifying factor and determines the unique properties of these immunosuppressive cells. Work over the past few years has shown that well-defined and precisely controlled events on transcriptional and epigenetic level are required to ensure stable expression of Foxp3 in Treg cells. More recent work suggested that in addition to stable Foxp3 expression, epigenetic modifications of Treg-cell specific genes contribute to the unique phenotype of Treg cells by imprinting their transcriptional program and stabilizing the expression of molecules being essential for the suppressive properties of Treg cells. In this review, we will highlight how Foxp3 expression itself is epigenetically and transcriptionally controlled, how the Treg-cell specific epigenetic signature is achieved, how Foxp3 as transcription factor influences the gene expression programs in Treg cells and how unique properties of Treg-cell subsets are defined by other transcription factors. © 2015 Elsevier Ltd.

Kavsek M.,University of Bonn
Developmental Psychobiology | Year: 2013

Current knowledge of the perceptual and cognitive abilities in infancy is largely based on the visual habituation-dishabituation method. According to the comparator model [e.g., Sokolov (1963a) Perception and the conditioned reflex. Oxford: Pergamon Press], habituation refers to stimulus encoding and dishabituation refers to discriminatory memory performance. The review also describes the dual-process theory and the attention disengagement approach. The dual-process theory points to the impact of natural stimulus preferences on habituation-dishabituation processes. The attention disengagement approach emphasizes the contribution of the ability to shift the attention away from a stimulus. Moreover, arguments for the cognitive interpretation of visual habituation and dishabituations are discussed. These arguments are provided by physiological studies and by research on interindividual differences. Overall, the review shows that current research supports the comparator model. It emphasizes that the investigation of habituation and dishabituation expands our understanding of visual attention processes in infants. © 2012 Wiley Periodicals, Inc.

Chatterjee A.,Harish Chandra Research Institute | Drees M.,University of Bonn | Kulkarni S.,LPSC
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

In the framework of the minimal cosmological standard model, the ΛCDM model, the dark matter density is now known within an error of a few percent; this error is expected to shrink even further once PLANCK data are analyzed. Matching this precision by theoretical calculations implies that at least leading radiative corrections to the annihilation cross section of the dark matter particles have to be included. Here we compute one kind of large corrections in the context of the minimal supersymmetric extension of the Standard Model: corrections associated with two-point function corrections on chargino and neutralino (collectively denoted by χ) lines. These can be described by effective χ-fermion-sfermion and χ-χ-Higgs couplings. We also employ one-loop corrected χ masses, using a recently developed version of the on-shell renormalization scheme. The resulting correction to the predicted dark matter density depends strongly on parameter space, but it can easily reach 3%. © 2012 American Physical Society.

Blanke M.M.,University of Bonn
Erwerbs-Obstbau | Year: 2013

A comparison of the non-invasive 'intelligent firmness detector' (IFD) with two standard destructive techniques for measuring fruit firmness of peeled fruit, viz. a hand-held (Bareiss) and the ART penetrometer, showed the least variation of the IFD or best reproducibility of SE of ± 1-2 elasticity units with firm cv. 'Braeburn' apples, equivalent to conventional hand penetrometer values of ± 0.12 kg/cm2. Correlations of the IFD with hand-held values ranged from r2 = 0.47-0.54 for cv. 'Lucas' pear, 0.55-0.75 for stored cv. 'Elstar' apple to 0.68 (ART) and 0.75 (handheld penetrometer) for retail cv. 'Hayward' kiwi fruit. Shrivelled fruit showed larger elasticity values possibly due to the firm ridges, which develop in the peel during shrinkage of those fruit. The IFD software corrects viz. removes artificially firm values, if the pressure sensor hits the pedicel rather than the fruit. A second comparison for total soluble solids (TSS/sugar/sweetness/taste) values of the non-invasive 'intelligent fruit analyser' (IFA) with conventional, destructive refractometry showed a good correlation with a coefficient of determination of r2 = 0.87 with cv. 'Elstar'. Non-destructive IFA sugar/TSS values were within ca. 4 % of those obtained by the destructive refractometer, e. g. an accuracy of ±0. 6 % sugar/TSS in apple fruit with 14-17 % sugar. The work showed that, a.non-invasive fruit firmness determination with the IFD requires only a single calibration for all fruit species and future measurements, b.non-invasive sugar determination with the IFA requires regression curves in the grading machine for each fruit species, cultivar, provenience and year, or alternatively a large number of stored values, and, c.neither bruises nor heat damage were observed on fruit measured properly by the IFD or IFA. © 2013 Springer-Verlag Berlin Heidelberg.

Schafgen J.,University of Bonn
European Journal of Human Genetics | Year: 2016

Recently, germline variants of the transcriptional co-regulator gene TCF20 have been implicated in the aetiology of autism spectrum disorders (ASD). However, the knowledge about the associated clinical picture remains fragmentary. In this study, two individuals with de novo TCF20 sequence variants were identified in a cohort of 313 individuals with intellectual disability of unknown aetiology, which was analysed by whole exome sequencing using a child–parent trio design. Both detected variants – one nonsense and one frameshift variant – were truncating. A comprehensive clinical characterisation of the patients yielded mild intellectual disability, postnatal tall stature and macrocephaly, obesity and muscular hypotonia as common clinical signs while ASD was only present in one proband. The present report begins to establish the clinical picture of individuals with de novo nonsense and frameshift variants of TCF20 which includes features such as proportionate overgrowth and muscular hypotonia. Furthermore, intellectual disability/developmental delay seems to be fully penetrant amongst known individuals with de novo nonsense and frameshift variants of TCF20, whereas ASD is shown to be incompletely penetrant. The transcriptional co-regulator gene TCF20 is hereby added to the growing number of genes implicated in the aetiology of both ASD and intellectual disability. Furthermore, such de novo variants of TCF20 may represent a novel differential diagnosis in the overgrowth syndrome spectrum.European Journal of Human Genetics advance online publication, 20 July 2016; doi:10.1038/ejhg.2016.90. © 2016 Macmillan Publishers Limited

Braaten E.,Ohio State University | Hammer H.-W.,University of Bonn
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The dark matter annihilation rate at small relative velocities can be amplified by a large boost factor using various mechanisms, including Sommerfeld enhancement, resonance enhancement, and Breit-Wigner enhancement. These mechanisms all involve a resonance near the threshold for a pair of dark matter particles. We point out that if the resonance is in the S-wave channel, the mechanisms are equivalent sufficiently near the resonance and they are constrained by universal two-body physics. The amplified annihilation rate requires a corresponding amplification of the elastic scattering cross section. If the resonance is a bound state below the threshold, it has an increased lifetime that is inversely proportional to the square root of the binding energy. Its spatial structure is that of two dark matter particles whose mean separation is also inversely proportional to the square root of the binding energy. © 2013 American Physical Society.

Luzum B.,U.S. Naval Observatory | Nothnagel A.,University of Bonn
Journal of Geodesy | Year: 2010

The quality of predictions of Earth orientation parameters (EOPs) in general, and of Universal Time (UT1) in particular, depends strongly on the time delay between the last observation available and the first prediction. Since 30 September 2007 (MJD 54373), the latency of UT1 results from a subset of single baseline VLBI observations running once per week (Mondays) has been decreased from 2 to 3 days to about 8 h. This was achieved by transmitting the raw VLBI data of 1-h duration from the observing sites in Tsukuba (Japan), Wettzell (Germany) and Ny-Ålesund (Norway) to the correlator of the Max-Planck-Institute for Radio Astronomy and the German Federal Agency of Cartography and Geodesy at Bonn, Germany, by high-speed Internet connections (e-Transfer). The reduced latency of the observations has improved the accuracy of the combined International Earth Rotation and Reference Systems Service (IERS) Rapid Service/Prediction Center (RS/PC) UT1-UTC solution by roughly 50% on the days when the data are available. Because this combination is an input to the UT1-UTC prediction process, the improved latency is also responsible for a roughly 21% improvement in the accuracy of short-term IERS RS/PC UT1-UTC predictions on the days where the data are available. © 2010 Springer-Verlag.

Voos W.,University of Bonn
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013

As essential organelles, mitochondria are intimately integrated into the metabolism of a eukaryotic cell. The maintenance of the functional integrity of the mitochondrial proteome, also termed protein homeostasis, is facing many challenges both under normal and pathological conditions. First, since mitochondria are derived from bacterial ancestor cells, the proteins in this endosymbiotic organelle have a mixed origin. Only a few proteins are encoded on the mitochondrial genome, most genes for mitochondrial proteins reside in the nuclear genome of the host cell. This distribution requires a complex biogenesis of mitochondrial proteins, which are mostly synthesized in the cytosol and need to be imported into the organelle. Mitochondrial protein biogenesis usually therefore comprises complex folding and assembly processes to reach an enzymatically active state. In addition, specific protein quality control (PQC) processes avoid an accumulation of damaged or surplus polypeptides. Mitochondrial protein homeostasis is based on endogenous enzymatic components comprising a diverse set of chaperones and proteases that form an interconnected functional network. This review describes the different types of mitochondrial proteins with chaperone functions and covers the current knowledge of their roles in protein biogenesis, folding, proteolytic removal and prevention of aggregation, the principal reactions of protein homeostasis. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. © 2012 Elsevier B.V.

Chatzistavrakidis A.,University of Bonn
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

A systematic search for Lie-algebra solutions of the type IIB matrix model is performed. Our survey is based on the classification of all Lie algebras for dimensions up to five and of all nilpotent Lie algebras of dimension six. It is shown that Lie-type solutions of the equations of motion of the type IIB matrix model exist and they correspond to certain nilpotent and solvable Lie algebras. Their representation in terms of Hermitian matrices is discussed in detail. These algebras give rise to certain noncommutative spaces for which the corresponding star products are provided. Finally the issue of constructing quantized compact nilmanifolds and solvmanifolds based on the above algebras is addressed. © 2011 American Physical Society.

Kohl T.,University of Bonn
Pediatric Cardiology | Year: 2010

Hypoplasia of cardiovascular structures is a common finding in fetuses with cardiac malformations. Materno-fetal hyperoxygenation (HO) during late gestation promotes venous return to the fetal heart. This analysis in human fetuses sought to define whether this "loading"effect might improve hypoplastic cardiovascular dimensions. Fifteen late-gestation fetuses presented with varying degrees of hypoplastic cardiovascular structures. In these cases, chronic intermittent materno-fetal HO was administered during periods ranging from 8 to 33 days. Cardiac measurements were taken before and at the end of treatment and translated into Z-scores as well as plotted on normal growth charts. During the treatment period, chronic intermittent materno-fetal HO was associated with improved dimensions of C1 hypoplastic cardiovascular structures in most fetuses. However, in some cases, the effect of HO was neutralized or impaired by the presence of ventricular septal defects as well as obstructions to ventricular filling or emptying. Chronic intermittent materno- fetal HO near term may be associated with improvements of hypoplastic cardiovascular dimensions in fetuses with a spectrum of cardiac malformations. This effect may facilitate postnatal treatment and improve prognosis in suitable cases. © Springer Science+Business Media, LLC 2009.

Ellis E.C.,University of Maryland Baltimore County | Goldewijk K.K.,Netherlands Environmental Assessment Agency | Siebert S.,University of Bonn | Lightman D.,McGill University | Ramankutty N.,McGill University
Global Ecology and Biogeography | Year: 2010

Aim: To map and characterize anthropogenic transformation of the terrestrial biosphere before and during the Industrial Revolution, from 1700 to 2000. Location: Global. Methods: Anthropogenic biomes (anthromes) were mapped for 1700, 1800, 1900 and 2000 using a rule-based anthrome classification model applied to gridded global data for human population density and land use. Anthropogenic transformation of terrestrial biomes was then characterized by map comparisons at century intervals. Results: In 1700, nearly half of the terrestrial biosphere was wild, without human settlements or substantial land use. Most of the remainder was in a seminatural state (45%) having only minor use for agriculture and settlements. By 2000, the opposite was true, with the majority of the biosphere in agricultural and settled anthromes, less than 20% seminatural and only a quarter left wild. Anthropogenic transformation of the biosphere during the Industrial Revolution resulted about equally from land-use expansion into wildlands and intensification of land use within seminatural anthromes. Transformation pathways differed strongly between biomes and regions,with some remaining mostly wild but with the majority almost completely transformed into rangelands, croplands and villages. In the process of transforming almost 39% of earth's total ice-free surface into agricultural land and settlements, an additional 37% of global land without such use has become embedded within agricultural and settled anthromes. Main conclusions: Between 1700 and 2000, the terrestrial biosphere made the critical transition frommostly wild to mostly anthropogenic, passing the 50% mark early in the 20th century. At present, and ever more in the future, the form and process of terrestrial ecosystems in most biomes will be predominantly anthropogenic, the product of land use and other direct human interactions with ecosystems. Ecological research and conservation efforts in all but a few biomes would benefit from a primary focus on the novel remnant, recovering and managed ecosystems embedded within used lands. © 2010 Blackwell Publishing Ltd.

Golubnitschaja O.,University of Bonn | Costigliola V.,European Medical Association
EPMA Journal | Year: 2012

This report is the collective product of word-leading experts working in the branches of integrative medicine by predictive, preventive and personalised medicine (PPPM) under the coordination of the European Association for Predictive, Preventive and Personalised Medicine. The general report has been prepared as the consortium document proposed at the EPMA World Congress 2011 which took place in Bonn, Germany. This forum analyzed the overall deficits and trends relevant for the top-science and daily practice in PPPM focused on the patient. Follow-up consultations resulted in a package of recommendations for consideration by research units, educators, healthcare industry, policy-makers, and funding bodies to cover the current knowledge deficit in the field and to introduce integrative approaches for advanced diagnostics, targeted prevention, treatments tailored to the person and cost-effective healthcare. © 2012 Golubnitschaja et al; licensee BioMed Central Ltd.

Klein N.,University of Bonn
PLoS ONE | Year: 2010

Background: Sauropterygia is an abundant and successful group of Triassic marine reptiles. Phylogenetic relationships of Triassic Sauropterygia have always been unstable and recently questioned. Although specimens occur in high numbers, the main problems are rareness of diagnostic material from the Germanic Basin and uniformity of postcranial morphology of eosauropterygians. In the current paper, morphotypes of humeri along with their corresponding bone histologies for Lower to Middle Muschelkalk sauropterygians are described and interpreted for the first time in a phylogenetic context. Methodology/Principal Findings: Nothosaurus shows a typical plesiomorphic lamellar-zonal bone type, but varying growth patterns and the occurrence of a new humerus morphotype point to a higher taxonomic diversity than was known. In contrast to the enormous morphological variability of eosauropterygian humeri not assigned to Nothosaurus, their long bone histology is relatively uniform and can be divided into two histotypes. Unexpectedly, both of these histotypes reveal abundant fibrolamellar bone throughout the cortex. This pushes the origin of fibrolamellar bone in Sauropterygia back from the Cretaceous to the early Middle Triassic (early Anisian). Histotype A is assigned to Cymatosaurus, a basal member of the Pistosauroidea, which includes the plesiosaurs as derived members. Histotype B is related to the pachypleurosaur Anarosaurus. Contrary to these new finds, the stratigraphically younger pachypleurosaur Neusticosaurus shows the plesiomorphic lamellar-zonal bone type and an incomplete endochondral ossification, like Nothosaurus. Conclusions/Significance: Histological results hypothetically discussed in a phylogenetical context have a large impact on the current phylogenetic hypothesis of Sauropterygia, leaving the pachypleurosaurs polyphyletic. On the basis of histological data, Neusticosaurus would be related to Nothosaurus, whereas Anarosaurus would follow the pistosaur clade. Furthermore, the presence of fibrolamellar bone, which is accompanied with increased growth rates and presumably even with increased metabolic rates, already in Anarosaurus and Cymatosaurus can explain the success of the Pistosauroidea, the only sauropterygian group to survive into the Jurassic and give rise to the pelagic plesiosaur radiation. © 2010 Nicole Klein.

Mahdi T.,University of Toronto | Heiden Z.M.,University of Toronto | Grimme S.,University of Bonn | Stephan D.W.,University of Toronto
Journal of the American Chemical Society | Year: 2012

Hydrogenation of the N-bound phenyl rings of amines, imines, and aziridine is achieved in the presence of H 2 and B(C 6F 5) 3, affording the corresponding N-cyclohexylammonium hydridoborate salts. © 2012 American Chemical Society.

Oldenburg J.,University of Bonn
Thrombosis Research | Year: 2011

Primary prophylaxis with coagulation factor concentrates has become the standard of care for children with hemophilia to reduce the risk of bleeding and related morbidity. However, several important questions remain unanswered regarding the optimal use of prophylaxis in patients with bleeding disorders. Limited data are available on the use of primary prophylaxis in adults with hemophilia, although tailoring the dose and schedule of prophylaxis in adults based on the clinical course of the disease may improve convenience and reduce costs without compromising efficacy. Patients with severe forms of von Willebrand disease (VWD) are at risk of serious bleeding episodes and may therefore benefit from prophylaxis; results from ongoing trials, such as the VWD International Prophylaxis (VIP) trial, are expected to provide more insight into the efficacy and safety of prophylaxis in these patients. For patients with other rare bleeding disorders, prophylaxis may be considered, depending on the clinical course of the disease and the availability of factor replacement therapy products; definitive recommendations, however, are not possible given the lack of comprehensive studies evaluating prophylaxis in this setting. Ongoing studies will help further define the role of coagulation factor concentrate prophylaxis in patients with bleeding disorders. © 2010 Elsevier Ltd.

Strassburg C.P.,University of Bonn
Digestive Diseases | Year: 2012

Autoimmune hepatitis (AIH) was the first chronic liver disease which responded favorably to drug therapy. It has a dismal prognosis when not treated. Since the original description in 1950 by Waldenstrm the treatment option initially reported is still practiced today and is the core of the basic therapeutic strategy of inducing remission with steroids and azathioprine. It is important to establish the diagnosis before cirrhosis develops. Later, the avoidance of immunosuppressant side effects, nonresponders to standard induction therapy, and adherence to therapy are among the greatest challenges in treating AIH. Alternative immunosuppressive drugs have been tested in small series and have included commonly used transplant immunosuppressants, albeit with mixed results and many unwanted drug side effects. A recent large multicenter prospective treatment trial suggests that budesonide may offer an alternative in noncirrhotic AIH patients capable of minimizing unwanted steroid effects. The ultimate treatment approach upon drug treatment failure is liver transplantation. Only 4% of transplant candidates are transplanted for AIH. After liver transplantation, there is a considerable risk for graft loss because of recurrent AIH, and lifelong vigilance and therapeutic attention is important. Copyright © 2012 S. Karger AG, Basel.

Gulder T.A.M.,University of Bonn | Moore B.S.,University of California at San Diego
Angewandte Chemie - International Edition | Year: 2010

Proteasome inhibitors are rapidly evolving as potent treatment options in cancer therapy. One of the most promising drug candidates of this type is salinosporamide A from the bacterium Salinispora tropica. This marine natural product possesses a complex, densely functionalized γ-lactam-β- lactone pharmacophore, which is responsible for its irreversible binding to its target, the β subunit of the 20S proteasome. Salinosporamide A entered phase I clinical trials for the treatment of multiple myeloma only three years after its discovery. The strong biological activity and the challenging structure of this compound have fueled intense academic and industrial research in recent years, which has led to the development of more than ten syntheses, the elucidation of its biosynthetic pathway, and the generation of promising structure-activity relationships and oncological data. Salinosporamide A thus serves as an intriguing example of the successful interplay of modern drug discovery and biomedical research, medicinal chemistry and pharmacology, natural product synthesis and analysis, as well as biosynthesis and bioengineering. A young family: The salinosporamides (picture: salinosporamide A), γ-lactam-β-lactone marine natural products isolated from Salinispora tropica, are irreversible proteasome inhibitors and constitute a potent new class of small molecules for cancer drugs. This Review highlights the impressive achievements of recent multidisciplinary research on the discovery, biosynthesis, bioengineering, total synthesis, and biomedical evaluation of this young natural product family. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Barjau J.,University of Mainz | Schnakenburg G.,University of Bonn | Waldvogel S.R.,University of Mainz
Angewandte Chemie - International Edition | Year: 2011

Like a Swiss army knife: The pentacycle shown, which results from the anodic oxidation of 2,4-dimethylphenol, displays a wealth of potential reactivity. Depending on the applied reaction conditions a variey of polycyclic architectures are obtained with impressive stereo-, regio-, and chemoselectivity. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Henneberger C.,University College London | Henneberger C.,University of Bonn | Rusakov D.A.,University College London
Nature Protocols | Year: 2012

Rapid signal exchange between astroglia and neurons has emerged as a key player in neural communication in the brain. To understand the mechanisms involved, it is often important to have access to individual astrocytes while monitoring the activity of nearby synapses. Achieving this with standard electrophysiological tools is not always feasible. The protocol presented here enables the monitoring of synaptic activity using whole-cell current-clamp recordings from a local astrocyte. This approach takes advantage of the fact that the low input resistance of electrically passive astroglia allows extracellular currents to pass through the astrocytic membrane with relatively little attenuation. Once the slice preparation is ready, it takes ∼30 min to several hours to implement this protocol, depending on the experimental design, which is similar to other patch-clamp techniques. The technique presented here can be used to directly access the intracellular medium of individual astrocytes while examining synapses functioning in their immediate proximity. © 2012 Nature America, Inc.

Lupi M.,ETH Zurich | Miller S.A.,University of Bonn
Solid Earth | Year: 2014

Eruptive rates in volcanic arcs increase significantly after subduction mega-thrust earthquakes. Over short to intermediate time periods the link between mega-thrust earthquakes and arc response can be attributed to dynamic triggering processes or static stress changes, but a fundamental mechanism that controls long-term pulses of volcanic activity after mega-thrust earthquakes has not been proposed yet.

Using geomechanical, geological, and geophysical arguments, we propose that increased eruption rates over longer timescales are due to the relaxation of the compressional regime that accompanies mega-thrust subduction zone earthquakes. More specifically, the reduction of the horizontal stress σh promotes the occurrence of short-lived strike-slip kinematics rather than reverse faulting in the volcanic arc. The relaxation of the pre-earthquake compressional regime facilitates magma mobilisation by providing a short-circuit pathway to shallow depths by significantly increasing the hydraulic properties of the system. The timescale for the onset of strike-slip faulting depends on the degree of shear stress accumulated in the arc during inter-seismic periods, which in turn is connected to the degree of strain-partitioning at convergent margins.

We performed Coulomb stress transfer analysis to determine the order of magnitude of the stress perturbations in present-day volcanic arcs in response to five recent mega-thrust earthquakes; the 2005 M8.6, 2007 M8.5, and 2007 M7.9 Sumatra earthquakes; the 2010 M8.8 Maule, Chile earthquake; and the 2011 M9.0 Tohoku, Japan earthquake. We find that all but one the shallow earthquakes that occurred in the arcs of Sumatra, Chile and Japan show a marked lateral component. We suggests that the long-term response of volcanic arcs to subduction zone mega-thrust earthquakes will be manifested as predominantly strike-slip seismic events, and that these future earthquakes may be followed closely by indications of rising magma to shallower depths, e.g. surface inflation and seismic swarms. © 2014 Author(s).

Lim L.S.,Singapore Eye Research Institute | Mitchell P.,University of Sydney | Seddon J.M.,Tufts University | Holz F.G.,University of Bonn | And 2 more authors.
The Lancet | Year: 2012

Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular agerelated macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progres