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Munich, Germany

Ludwig Maximilian University of Munich is a public research university located in Munich, Germany.The University of Munich is among Germany's oldest universities. Originally established in Ingolstadt in 1472 by Duke Ludwig IX of Bavaria-Landshut, the university was moved in 1800 to Landshut by King Maximilian I of Bavaria when Ingolstadt was threatened by the French, before being relocated to its present-day location in Munich in 1826 by King Ludwig I of Bavaria. In 1802, the university was officially named Ludwig-Maximilians-Universität by King Maximilian I of Bavaria in his as well as the university's original founder's honour.The University of Munich has, particularly since the 19th century, been considered as one of Germany's as well as one of Europe's most prestigious universities; with 34 Nobel laureates associated with the university, it ranks 13th worldwide by number of Nobel laureates. Among these were Wilhelm Röntgen, Max Planck, Werner Heisenberg, Otto Hahn and Thomas Mann. Pope Benedict XVI was also a student and professor at the university. The LMU has recently been conferred the title of "elite university" under the German Universities Excellence Initiative.LMU is currently the second-largest university in Germany in terms of student population; in the winter semester of 2013/2014, the university had a total of 50,542 matriculated students. Of these, 8,719 were freshmen while international students totalled 7,403 or almost 15% of the student population. As for operating budget, the university records in 2013 a total of 571.3 million Euros in funding without the university hospital; with the university hospital, the university has a total funding amounting to approximately 1.5 billion Euros. Wikipedia.


Hutzenthaler M.,Ludwig Maximilians University of Munich | Jentzen A.,Princeton University
Foundations of Computational Mathematics | Year: 2011

Stochastic differential equations are often simulated with the Monte Carlo Euler method. Convergence of this method is well understood in the case of globally Lipschitz continuous coefficients of the stochastic differential equation. However, the important case of superlinearly growing coefficients has remained an open question. The main difficulty is that numerically weak convergence fails to hold in many cases of superlinearly growing coefficients. In this paper we overcome this difficulty and establish convergence of the Monte Carlo Euler method for a large class of one-dimensional stochastic differential equations whose drift functions have at most polynomial growth. © 2011 SFoCM. Source


Bravin A.,European Synchrotron Radiation Facility | Coan P.,Ludwig Maximilians University of Munich | Suortti P.,University of Helsinki
Physics in Medicine and Biology | Year: 2013

Phase-contrast x-ray imaging (PCI) is an innovative method that is sensitive to the refraction of the x-rays in matter. PCI is particularly adapted to visualize weakly absorbing details like those often encountered in biology and medicine. In past years, PCI has become one of the most used imaging methods in laboratory and preclinical studies: its unique characteristics allow high contrast 3D visualization of thick and complex samples even at high spatial resolution. Applications have covered a wide range of pathologies and organs, and are more and more often performed in vivo. Several techniques are now available to exploit and visualize the phase-contrast: propagation- and analyzer-based, crystal and grating interferometry and non-interferometric methods like the coded aperture. In this review, covering the last five years, we will givean overview of the main theoretical and experimental developments and of the important steps performed towards the clinical implementation of PCI. © 2013 Institute of Physics and Engineering in Medicine. Source


Cavin R.K.,Semiconductor Research Corporation | Lugli P.,Ludwig Maximilians University of Munich | Zhirnov V.V.,Semiconductor Research Corporation
Proceedings of the IEEE | Year: 2012

In this paper, the historical effects and benefits of Moore's law for semiconductor technologies are reviewed, and it is offered that the rapid learning curve obtained to the benefit of society by feature size scaling might be continued in several different ways. The problem is that as features approach the range of a few nanometers, electron-based devices depart radically from the ideal switch and, in fact, become very leaky in the off state. It is argued that there are some short-term solutions involving more highly parallel manufacturing, increased design efficiency, and lower cost packaging technologies that could continue the steep learning curve for cost reductions that have historically been achieved via Moore's Law scaling. Another alternative might be to increase chip functionality by integrating devices that offer broadened chip functionality including, e.g., sensors, energy sources, oscillators, etc. A third alternative would be to invent an entirely new information processing state variable based on different physics, using electron spin, magnetic dipoles, photons, etc., to improve the performance and reduce switching energy for devices whose smallest features are on the order of a few nanometers. Each of these alternatives is being actively explored and an overview of each strategy and progress to date is given in the paper. A final alternative offered in the paper is to learn from information processing examples in nature, specifically in living systems. An E.coli cell of about one cubic micrometer volume is shown to be an incredibly powerful and energy-efficient information processor relative to the performance of an end-of-scaling silicon processor of the same volume. The paper concludes by pointing out some of the crucial differences between E.coli information processing and conventional approaches with the hope technologies can be invented using the hints offered by biosystems. © 2012 IEEE. Source


Langer A.,Ludwig Maximilians University of Munich
BMC health services research | Year: 2012

Health economic evaluations support the health care decision-making process by providing information on costs and consequences of health interventions. The quality of such studies is assessed by health economic evaluation (HEE) quality appraisal instruments. At present, there is no instrument for measuring and improving the quality of such HEE quality appraisal instruments. Therefore, the objectives of this study are to establish a framework for assessing the quality of HEE quality appraisal instruments to support and improve their quality, and to apply this framework to those HEE quality appraisal instruments which have been subject to more scrutiny than others, in order to test the framework and to demonstrate the shortcomings of existing HEE quality appraisal instruments. To develop the quality assessment framework for HEE quality appraisal instruments, the experiences of using appraisal tools for clinical guidelines are used. Based on a deductive iterative process, clinical guideline appraisal instruments identified through literature search are reviewed, consolidated, and adapted to produce the final quality assessment framework for HEE quality appraisal instruments. The final quality assessment framework for HEE quality appraisal instruments consists of 36 items organized within 7 dimensions, each of which captures a specific domain of quality. Applying the quality assessment framework to four existing HEE quality appraisal instruments, it is found that these four quality appraisal instruments are of variable quality. The framework described in this study should be regarded as a starting point for appraising the quality of HEE quality appraisal instruments. This framework can be used by HEE quality appraisal instrument producers to support and improve the quality and acceptance of existing and future HEE quality appraisal instruments. By applying this framework, users of HEE quality appraisal instruments can become aware of methodological deficiencies inherent in existing HEE quality appraisal instruments. These shortcomings of existing HEE quality appraisal instruments are illustrated by the pilot test. Source


Frey E.,Ludwig Maximilians University of Munich
Physica A: Statistical Mechanics and its Applications | Year: 2010

Ecological systems are complex assemblies of large numbers of individuals, interacting competitively under multifaceted environmental conditions. Recent studies using microbial laboratory communities have revealed some of the self-organization principles underneath the complexity of these systems. A major role of the inherent stochasticity of its dynamics and the spatial segregation of different interacting species into distinct patterns has thereby been established. It ensures the viability of microbial colonies by allowing for species diversity, cooperative behavior and other kinds of "social" behavior. A synthesis of evolutionary game theory, nonlinear dynamics, and the theory of stochastic processes provides the mathematical tools and a conceptual framework for a deeper understanding of these ecological systems. We give an introduction into the modern formulation of these theories and illustrate their effectiveness focussing on selected examples of microbial systems. Intrinsic fluctuations, stemming from the discreteness of individuals, are ubiquitous, and can have an important impact on the stability of ecosystems. In the absence of speciation, extinction of species is unavoidable. It may, however, take very long times. We provide a general concept for defining survival and extinction on ecological time-scales. Spatial degrees of freedom come with a certain mobility of individuals. When the latter is sufficiently high, bacterial community structures can be understood through mapping individual-based models, in a continuum approach, onto stochastic partial differential equations. These allow progress using methods of nonlinear dynamics such as bifurcation analysis and invariant manifolds. We conclude with a perspective on the current challenges in quantifying bacterial pattern formation, and how this might have an impact on fundamental research in non-equilibrium physics. © 2010 Elsevier B.V. All rights reserved. Source


Weymann I.,Adam Mickiewicz University | Weymann I.,Ludwig Maximilians University of Munich
Physical Review B - Condensed Matter and Materials Physics | Year: 2011

We study the temperature dependence of the linear conductance and tunnel magnetoresistance of quantum dots coupled to ferromagnetic leads. Using the numerical renormalization group method, we determine transport properties for a wide range of temperatures T, ranging from zero through the Kondo temperature TK up to the high-temperature regime. We show that tunnel magnetoresistance in the local moment regime displays a nonmonotonic dependence on T and vanishes when T~TK. In addition, we also analyze the spin polarization P of the linear conductance in the parallel configuration and show that P is suppressed in the odd electron Coulomb blockade valley and can be enhanced above the spin polarization of the leads in the even Coulomb valley. © 2011 American Physical Society. Source


Funt D.,Mount Sinai Hospital | Pavicic T.,Ludwig Maximilians University of Munich
Clinical, Cosmetic and Investigational Dermatology | Year: 2013

Background: The ever-expanding range of dermal filler products for aesthetic soft tissue augmentation is of benefit for patients and physicians, but as indications and the number of procedures performed increase, the number of complications will likely also increase. Objective: To describe potential adverse events associated with dermal fillers and to provide structured and clear guidance on their treatment and avoidance. Methods: Reports of dermal filler complications in the medical literature were reviewed and, based on the publications retrieved and the authors' extensive experience, recommendations for avoiding and managing complications are provided. Results: Different dermal fillers have widely varying properties, associated risks, and injection requirements. All dermal fillers have the potential to cause complications. Most are related to volume and technique, though some are associated with the material itself. The majority of adverse reactions are mild and transient, such as bruising and trauma-related edema. Serious adverse events are rare, and most are avoidable with proper planning and technique. Conclusion: For optimum outcomes, aesthetic physicians should have a detailed understanding of facial anatomy; the individual characteristics of available fillers; their indications, contraindications, benefits, and drawbacks; and ways to prevent and avoid potential complications. © 2013 Funt and Pavicic. Source


Soyka M.,Ludwig Maximilians University of Munich
Expert Opinion on Pharmacotherapy | Year: 2016

Introduction: Few pharmacotherapies are available for alcoholism. Numerous studies indicate the involvement of the opioid-endorphin system in mediating the reinforcing effects of alcohol via dopaminergic neurons. The opioid antagonist naltrexone was found to be effective in alcohol treatment, and the European Medicines Agency has now approved the mu-opioid antagonist und partial kappa agonist nalmefene.Areas covered: This article presents background information on the chemistry of nalmefene and pre-clinical and clinical findings. The three relevant Phase III studies, all of which followed a harm-reduction, "as needed" approach and found reduced alcohol consumption with nalmefene 18 (20) mg, are discussed in detail.Expert opinion: The integration of the "as needed" approach into conventional psychosocial alcohol therapies may be challenging but offers the opportunity to reach otherwise not treated patients. Nalmefene is the first medication to be approved specifically in this indication and seems to be most suitable for patients with alcohol misuse or a rather low physical dependence on alcohol who do not require immediate detoxification or inpatient treatment. Although a categorical distinction between patients who want to stop heavy drinking or drinking at all over time may be somewhat hypothetical, nalmefene offers new treatment options to patients with alcohol use disorder. © 2016 Taylor & Francis. Source


Wilson D.N.,Center for Integrated Protein Science Munich | Wilson D.N.,Ludwig Maximilians University of Munich | Cate J.H.D.,University of California at Berkeley | Cate J.H.D.,Lawrence Berkeley National Laboratory
Cold Spring Harbor Perspectives in Biology | Year: 2012

Structures of the bacterial ribosome have provided a framework for understanding universal mechanisms of protein synthesis. However, the eukaryotic ribosome is much larger than it is in bacteria, and its activity is fundamentally different in many keyways. Recent cryo-electron microscopy reconstructions and X-ray crystal structures of eukaryotic ribosomes and ribosomal subunits now provide an unprecedented opportunity to explore mechanisms of eukaryotic translation and its regulation in atomic detail. This review describes the X-ray crystal structures of the Tetrahymena thermophila 40S and 60S subunits and the Saccharomyces cerevisiae 80S ribosome, as well as cryo-electron microscopy reconstructions of translating yeast and plant 80S ribosomes. Mechanistic questions about translation in eukaryotes that will require additional structural insights to be resolved are also presented. © 2012 Cold Spring Harbor Laboratory Press; all rights reserved. Source


Hobbie E.A.,University of New Hampshire | Agerer R.,Ludwig Maximilians University of Munich
Plant and Soil | Year: 2010

Nitrogen isotope values (δ15N) are higher in ectomycorrhizal fungi than in their plant hosts but the wide variability in δ15N among sporocarps of different fungal taxa is unexplained. We propose that fungal δ15N reflects sequestration of fungal nitrogen to build fungal biomass, and should accordingly reflect fungal exploration strategies and hyphal properties. To test this, we compared δ15N to exploration types, hyphal hydrophobicity, and the presence of rhizomorphs in ectomycorrhizal species from surveys at four sites in temperate and boreal coniferous forests. Fungi with exploration types of high biomass, such as long-distance (e.g., Suillus), medium-distance mat (e.g., Hydnellum), and medium-distance fringe (e.g., Cortinarius) were 4-7‰ more enriched in 15N than fungi with exploration types of low biomass [medium-distance smooth (e.g., Amanita), short-distance (e.g., Inocybe), and contact (e.g., Hygrophorus)]. High biomass types comprised 79% (Åheden, northern Sweden), 65% (Deer Park, Pacific Northwest, USA), 45% (Stadsskogen, central Sweden), and 39% (Hoh, Pacific Northwest, USA) of ectomycorrhizal species, with these types more prevalent at sites of lower nitrogen availability. Species with hydrophobic hyphae or with rhizomorphs were 3-4‰ more enriched in 15N than taxa with hydrophilic hyphae or without rhizomorphs. The consistency of these patterns suggest that δ15N measurements could provide insights into belowground functioning of poorly known taxa of ectomycorrhizal fungi and into relative fungal biomass across ectomycorrhizal communities. © Springer Science + Business Media B.V. 2009. Source


Koletzko B.,Ludwig Maximilians University of Munich | Symonds M.E.,University of Nottingham | Olsen S.F.,Statens Serum Institute
American Journal of Clinical Nutrition | Year: 2011

Convincing evidence has accumulated to show that both pre- and postnatal nutrition preprogram long-term health, well-being, and performance until adulthood and old age. There is a very large potential in the application of this knowledge to promote public health. One of the prerequisites for translational application is to strengthen the scientific evidence. More extensive knowledge is needed (eg, on effect sizes of early life programming in contemporary populations, on specific nutritional exposures, on sensitive time periods in early life, on precise underlying mechanisms, and on potential effect differences in subgroups characterized by, eg, genetic predisposition or sex). Future programming research should aim at filling the existing gaps in scientific knowledge, consider the entire lifespan, address socioeconomic issues, and foster innovation. Research should aim at results suitable for translational application (eg, by leading to health-promoting policies and evidence-based dietary recommendations in the perinatal period). International collaboration and a close research partnership of academia, industry, and small and medium enterprises may strengthen research and innovative potential enhancing the likelihood of translational application. The scientific knowhow and methodology available today allow us to take major steps forward in the near future; hence, research on nutritional programming deserves high priority. © 2011 American Society for Nutrition. Source


Harcourt R.D.,University of Melbourne | Klapotke T.M.,Ludwig Maximilians University of Munich
Chemical Science | Year: 2016

Consideration is given to (electronically) hypervalent increased-valence structures, which possess 2c-1e bonds, fractional 2c-2e bonds, and usually normal 2c-2e bonds. For singlet-spin electron-rich systems, increased-valence structures, with Heitler-London 2c-2e bond wavefunctions, are equivalent to resonance between non-hypervalent Kekulé and Dewar (or singlet diradical) type Lewis structures. Dewar structures are not considered in the Chem. Sci. 2015, 6, 6614 Edge article on hypervalency. Using one-electron delocalizations from lone-pair atomic orbitals into separate bonding molecular orbitals, increased-valence structures for PCl5, O3, SO4 2-, NO3 -, N2O4 and SN2 reactions are derived from the Edge-article's Kekulé-type Lewis structures, and compared with the Edge article's hypervalent structures with 2c-2e bonds. It is also shown that Durrant's method to determine the γ parameter for XAY-type systems that possess a symmetrical 3c-4e bonding unit is related to the A-atom charge density. © 2016 The Royal Society of Chemistry. Source


Plesnila N.,Ludwig Maximilians University of Munich
Stroke Research and Treatment | Year: 2013

Subarachnoid hemorrhage (SAH) is the subtype of stroke with one of the highest mortality rates and the least well-understood pathophysiologies. One of the very early events which may occur after SAH is a significant decrease of cerebral perfusion pressure (CPP) caused by the excessive increase of intracranial pressure during the initial bleeding. A severely decreased CPP results in global cerebral ischemia, an event also occurring after cardiac arrest. The aim of the current paper is to review the pathophysiological events occurring in experimental models of SAH and global cerebral ischemia and to evaluate the contribution and the importance of global cerebral ischemia for the pathophysiology of SAH. © 2013 Nikolaus Plesnila. Source


Wardlaw J.M.,University of Edinburgh | Smith C.,University of Edinburgh | Dichgans M.,Ludwig Maximilians University of Munich | Dichgans M.,German Center for Neurodegenerative Diseases | Dichgans M.,Synergy Systems
The Lancet Neurology | Year: 2013

The term cerebral small vessel disease (SVD) describes a range of neuroimaging, pathological, and associated clinical features. Clinical features range from none, to discrete focal neurological symptoms (eg, stroke), to insidious global neurological dysfunction and dementia. The burden on public health is substantial. The pathogenesis of SVD is largely unknown. Although the pathological processes leading to the arteriolar disease are associated with vascular risk factors and are believed to result from an intrinsic cerebral arteriolar occlusive disease, little is known about how these processes result in brain disease, how SVD lesions contribute to neurological or cognitive symptoms, and the association with risk factors. Pathology often shows end-stage disease, which makes identification of the earliest stages difficult. Neuroimaging provides considerable insights; although the small vessels are not easily seen themselves, the effects of their malfunction on the brain can be tracked with detailed brain imaging. We discuss potential mechanisms, detectable with neuroimaging, that might better fit the available evidence and provide testable hypotheses for future study. © 2013 Elsevier Ltd. Source


Moller-Leimkuhler A.M.,Ludwig Maximilians University of Munich
World Journal of Biological Psychiatry | Year: 2010

Objectives. The present paper aims at offering a synthesis of possible reasons of the higher comorbidity of cardiovascular disease (CVD) and depression in women from a biopsychosocial perspective. Method. The available literature is reviewed under sex/gender aspects related to the link between depression and CVD and common pathways to depression and CVD associated with chronic stress experiences including pathophysiological mechanisms and behavioural, cognitive, psychosocial and sociological risk factors/predictors. Results, There is considerable evidence that greater exposure to chronic stressors in women, interpersonal stress responsiveness, and internalizing coping styles are associated with an elevated risk of CVD and/or depression through behavioural and pathophysiological mechanisms including alterations in HPA axis functioning and autonomic nervous system which appear to be specific for women. Conclusion. Women seem to be more strongly affected by psychosocial stressors related to CVD and depression as well as by direct and indirect effects of chronic stress compared to men. More evidence in understanding these differences within the biological, psychosocial and sociostructural determinants and pathways is essential for promoting women's health. © 2010 Informa Healthcare. Source


Potschka H.,Ludwig Maximilians University of Munich
Epilepsia | Year: 2013

Drug-resistant epilepsy remains a challenge in the therapeutic management of patients with epilepsy. Identification of factors contributing to drug resistance might render a basis for the development of novel therapeutic approaches, for the reorganization of screening programs in drug development, and for the design of personalized treatment concepts. Therefore, experimental and clinical studies need to link efforts and collaborate in order to elucidate drug-resistance mechanisms, to define the relative clinical relevance of selected mechanisms, and to develop and validate novel therapeutic concepts in overcoming resistance. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy. Source


Ronquist F.,Swedish Museum of Natural History | Klopfstein S.,Swedish Museum of Natural History | Vilhelmsen L.,Universitetsparken 15 | Schulmeister S.,Ludwig Maximilians University of Munich | And 2 more authors.
Systematic Biology | Year: 2012

Phylogenies are usually dated by calibrating interior nodes against the fossil record. This relies on indirect methods that, in the worst case, misrepresent the fossil information. Here, we contrast such node dating with an approach that includes fossils along with the extant taxa in a Bayesian total-evidence analysis. As a test case, we focus on the early radiation of the Hymenoptera, mostly documented by poorly preserved impression fossils that are difficult to place phylogenetically. Specifically, we compare node dating using nine calibration points derived from the fossil record with total-evidence dating based on 343 morphological characters scored for 45 fossil (4 - 20 complete) and 68 extant taxa. In both cases we use molecular data from seven markers (∼5 kb) for the extant taxa. Because it is difficult to model speciation, extinction, sampling, and fossil preservation realistically, we develop a simple uniform prior for clock trees with fossils, and we use relaxed clock models to accommodate rate variation across the tree. Despite considerable uncertainty in the placement of most fossils, we find that they contribute significantly to the estimation of divergence times in the total-evidence analysis. In particular, the posterior distributions on divergence times are less sensitive to prior assumptions and tend to be more precise than in node dating. The total-evidence analysis also shows that four of the seven Hymenoptera calibration points used in node dating are likely to be based on erroneous or doubtful assumptions about the fossil placement. With respect to the early radiation of Hymenoptera, our results suggest that the crown group dates back to the Carboniferous, ∼309 Ma (95 interval: 291 - 347 Ma), and diversified into major extant lineages much earlier than previously thought, well before the Triassic. [Bayesian inference; fossil dating; morphological evolution; relaxed clock; statistical phylogenetics.] © 2012 The Author(s). Source


Ming R.,University of Illinois at Urbana - Champaign | Bendahmane A.,French National Institute for Agricultural Research | Bendahmane A.,King Saud University | Renner S.S.,Ludwig Maximilians University of Munich
Annual Review of Plant Biology | Year: 2011

Sex chromosomes in land plants can evolve as a consequence of close linkage between the two sex determination genes with complementary dominance required to establish stable dioecious populations, and they are found in at least 48 species across 20 families. The sex chromosomes in hepatics, mosses, and gymnosperms are morphologically heteromorphic. In angiosperms, heteromorphic sex chromosomes are found in at least 19 species from 4 families, while homomorphic sex chromosomes occur in 20 species from 13 families. The prevalence of the XY system found in 44 out of 48 species may reflect the predominance of the evolutionary pathway from gynodioecy towards dioecy. All dioecious species have the potential to evolve sex chromosomes, and reversions back from dioecy to various forms of monoecy, gynodioecy, or androdioecy have also occurred. Such reversals may occur especially during the early stages of sex chromosome evolution before the lethality of the YY (or WW) genotype is established. Copyright © 2011 by Annual Reviews. All rights reserved. Source


Anders H.-J.,Ludwig Maximilians University of Munich
BMC Nephrology | Year: 2013

Most kidney disorders involve some degree of inflammation, i.e. induction of pro-inflammatory mediators and leukocyte recruitment. But what are the factors that determine inflammation as a trigger or a consequence of kidney injury? Which types of renal inflammation can be targeted by the novel more selective immunosuppressive and anti-inflammatory agents? How to dissect the mechanisms behind innate and adaptive immune responses that are orchestrated inside or outside the kidney but both cause renal immunopathology i.e. renal inflammation? How to dissect leukocytic cell infiltrates into pro-inflammatory leukocytes from anti-inflammatory and pro-regenerative leukocytes? How to dissect leukocytes that support epithelial repair from those that promote renal fibrosis. The term 'renal inflammation' has moved far beyond the descriptive category of 'mixed leukocytic cell infiltrates' as commonly described in kidney biopsies. It is time to face the complexity of renal inflammation to finally benefit from the new age of novel immunomodulatory medicines. © 2013 Anders; licensee BioMed Central Ltd. Source


Meissner K.,Ludwig Maximilians University of Munich
Handbook of Experimental Pharmacology | Year: 2014

It is widely acknowledged that placebo responses are accompanied by physiological changes in the central nervous system, but little is known about placebo responses on end organ functions. The present chapter aims to fill this gap by reviewing the literature on peripheral placebo responses. Overall, there is a wide range of placebo and nocebo responses on various organ functions of the cardiovascular, the gastrointestinal system, and the respiratory system. Most of these studies used expectation paradigms to elicit placebo and nocebo responses. Expectations can affect heart rate, blood pressure, coronary diameter, gastric motility, bowel motility, and lung function. Classical conditioning can induce placebo respiratory depression after prior exposure to opioid drugs, and habitual coffee drinkers show physiological arousal in response to coffee-associated stimuli. Similar to findings in placebo pain research, peripheral placebo responses can be target specific. The autonomic nervous system is a likely candidate to mediate peripheral placebo responses. Further studies are necessary to identify the brain mechanisms and pathways involved in peripheral placebo responses. © Springer-Verlag Berlin Heidelberg 2014. Source


Bogner J.R.,Ludwig Maximilians University of Munich
Expert Review of Anti-Infective Therapy | Year: 2012

Non-nucleoside antiretroviral combination therapy is the standard of care with a robust virologic efficacy and a good safety profile. One of the most frequently used non-nucleosides, nevirapine (NVP), has been available as a every 12 h, immediate-release (IR) tablet since 1996. In order to enhance convenience and adherence, a new pharmaceutical formulation was devised for once-daily use. This is the NVP extended-release (XR) tablet containing 400 mg of NVP. Preclinical and clinical studies were performed to establish the optimal pharmaceutical release form and to establish data on comparability with the conventional NVP-IR. The VERXVE study has shown noninferiority of the new NVP-XR formulation in treatment-naive patients. Safety and tolerability was found to be at least as good as with NVP-IR. NVP-XR is likely to become a convenient treatment option in first-line therapy and will also be a welcome alternative to patients already on NVP. © 2012 Expert Reviews Ltd. Source


Wagner E.,Ludwig Maximilians University of Munich
Advances in Genetics | Year: 2014

For the last five decades cationic polymers have been used for nucleic acids transfection. Our understanding of polymer-nucleic acid interactions and their rational use in delivery has continuously increased. The great improvements in macromolecular chemistry and the recognition of distinct biological extra- and intracellular delivery hurdles triggered several breakthrough developments, including the discovery of natural and synthetic polycations for compaction of nucleic acids into stable nanoparticles termed polyplexes; the incorporation of targeting ligands and surface-shielding of polyplexes to enable receptor-mediated gene delivery into defined target tissues; and strongly improved intracellular transfer efficacy by better endosomal escape of vesicle-trapped polyplexes into the cytosol. These experiences triggered the development of second-generation polymers with more dynamic properties, such as endosomal pH-responsive release mechanisms, or biodegradable units for improved biocompatibility and intracellular release of the nucleic acid pay load. Despite a better biological understanding, significant challenges such as efficient nuclear delivery and persistence of gene expression persist. The therapeutic perspectives widened from pDNA-based gene therapy to application of novel therapeutic nucleic acids including mRNA, siRNA, and microRNA. The finding that different therapeutic pay loads require different tailor-made carriers complicates preclinical developments. Convincing evidence of medical efficacy still remains to be demonstrated. Bioinspired multifunctional polyplexes resembling "synthetic viruses" appear as attractive opportunity, but provide additional challenges: how to identify optimum combinations of functional delivery units, and how to prepare such polyplexes reproducibly in precise form? Design of sequence-defined polymers, screening of combinatorial polymer and polyplex libraries are tools for further chemical evolution of polyplexes. © 2014 Elsevier Inc. Source


Hiddemann W.,Ludwig Maximilians University of Munich | Cheson B.D.,Georgetown University
Leukemia | Year: 2014

Major changes have taken place within the last few years in the management of follicular lymphoma (FL) leading to substantial improvement in prognosis and overall survival. For some patients with limited disease stages I and II, radiotherapy may be associated with durable responses; however, it is unclear whether patients are cured and new approaches such as the combination of irradiation with rituximab or even single-agent rituximab need to be explored. Whereas watch and wait is the current standard for stage III and IV disease with low tumour burden, better indices are warranted to potentially select patients for whom early intervention is preferred. For advanced stages with a high tumour burden, immunochemotherapy followed by 2 years of rituximab maintenance is widely accepted as standard therapy, although re-treatment at recurrence may be an alternative option. Highly attractive new therapeutic options have recently arisen from new antibodies, and from new agents targeting oncogenic pathways such as B-cell receptor signalling pathways or inhibition of bcl 2. Furthermore, immunomodulatory drugs may add to the therapeutic armamentarium and may lead to 'chemotherapy-free' therapies in the near future. Hence, the management of FLs has become a moving target and the hope is justified that the long-term perspectives of patients suffering from the disease will be further improved in the near future. © 2014 Macmillan Publishers Limited. Source


Scerri T.S.,University of Oxford | Schulte-Korne G.,Ludwig Maximilians University of Munich
European Child and Adolescent Psychiatry | Year: 2010

Developmental dyslexia is a highly heritable disorder with a prevalence of at least 5% in school-aged children. Linkage studies have identified numerous loci throughout the genome that are likely to harbour candidate dyslexia susceptibility genes. Association studies and the refinement of chromosomal translocation break points in individuals with dyslexia have resulted in the discovery of candidate genes at some of these loci. A key function of many of these genes is their involvement in neuronal migration. This complements anatomical abnormalities discovered in dyslexic brains, such as ectopias, that may be the result of irregular neuronal migration. © 2009 Springer-Verlag. Source


In more than 20 years of excavation at the fossil lagerstätte Sandelzhausen (Early/Middle Miocene boundary, Burdigalian/Langhian boundary, early middle MN5) a substantial amount of fossil remains of ruminants have been recovered. Currently, it is the largest recorded assemblage of ruminants from the Miocene Northern Alpine Foreland Basin. More than 1,000 teeth, almost 70 antler remains and one skull enable the identification of five ruminants, namely the tragulid Dorcatherium crassum, the palaeomerycid Germanomeryx n. g. fahlbuschi n. sp., and the cervids Lagomeryx parvulus, Lagomeryx pumilio, and Heteroprox eggeri n. sp. Lagomeryx parvulus and L. pumilio have the most extensive record yet known for these species, opening up a much more complete view of them 120 years after the discovery of the type materials. The newly established G. n. g. fahlbuschi n. sp. and H. eggeri n. sp. enlarge our knowledge on the taxonomic composition of Miocene European Ruminantia. Because of the exceptionally large number of specimens, nearly all tooth positions of all five species are documented, thereby completing hitherto partially known character sets. The investigation comprises extensive taxonomic descriptions of all species represented and an interpretation of the palaeoecology based on an analysis of the community structure. This clearly suggests a humid closed canopy forest interspersed with temporary and perennial waters and accompanying open areas. Moreover, a comparison with other, stratigraphically close Molasse Basin communities emphasizes the various peculiarities of the Sandelzhausen community (low species number, cervid-dominance, dominance of L. pumilio over L. parvulus, non-dominance of very small-sized ruminants, comparably high portion of palaeomerycids, all species being browsers, no Eotragus and no Amphimoschus). The investigation also clarifies the similarity with the communities from Undorf and Viehhausen (Germany, MN5). The deduced dynamics in community structure of the late Early and early Middle Miocene Northern Alpine Foreland Basin provides further support for the current hypothesis of a vast wetland environment under the strong influence of alternating dry and flood seasons. © Springer-Verlag 2010. Source


Vigeolas H.,University of Liege | Huhn D.H.,University of Zurich | Geigenberger P.,Ludwig Maximilians University of Munich
Plant Physiology | Year: 2011

Nonsymbiotic hemoglobins are ubiquitously expressed in plants and divided into two different classes based on gene expression pattern and oxygen-binding properties. Most of the published research has been on the function of class 1 hemoglobins. To investigate the role of class 2 hemoglobins, transgenic Arabidopsis (Arabidopsis thaliana) plants were generated overexpressing Arabidopsis hemoglobin-2 (AHb2) under the control of a seed-specific promoter. Overexpression of AHb2 led to a 40% increase in the total fatty acid content of developing and mature seeds in three subsequent generations. This was mainly due to an increase in the polyunsaturated C18:2 (ω-6) linoleic and C18:3 (ω-3) α-linolenic acids. Moreover, AHb2 overexpression led to an increase in the C18:2/C18:1 and C18:3/C18:2 ratios as well as in the C18:3 content in mol % of total fatty acids and in the unsaturation/saturation index of total seed lipids. The increase in fatty acid content was mainly due to a stimulation of the rate of triacylglycerol synthesis, which was attributable to a 3-fold higher energy state and a 2-fold higher sucrose content of the seeds. Under low external oxygen, AHb2 overexpression maintained an up to 5-fold higher energy state and prevented fermentation. This is consistent with AHb2 overexpression results in improved oxygen availability within developing seeds. In contrast to this, overexpression of class 1 hemoglobin did not lead to any significant increase in the metabolic performance of the seeds. These results provide evidence for a specific function of class 2 hemoglobin in seed oil production and in promoting the accumulation of polyunsaturated fatty acids by facilitating oxygen supply in developing seeds. © 2011 American Society of Plant Biologists. Source


Kuhnel F.,Ludwig Maximilians University of Munich
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Stability about cosmological background solutions to the bimetric Hassan-Rosen theory is studied. The results of this analysis are presented, and it is shown that a large class of cosmological backgrounds is classically unstable. This sets serious doubts on the physical viability of the Hassan-Rosen theory - and in turn also of the de Rham-Gadabaze-Tolley model. A way to overcome this instability by means of curvature-type deformations is discussed. © 2013 American Physical Society. Source


Bambi C.,Fudan University | Bambi C.,Ludwig Maximilians University of Munich
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Astrophysical black hole candidates are thought to be the Kerr black holes predicted by general relativity, but there is not yet clear evidence that the geometry of the space-time around these objects is really described by the Kerr metric. In order to confirm the Kerr black hole hypothesis, we have to observe strong gravity features and check that they are in agreement with the ones predicted by general relativity. In this paper, I study the broad Kα iron line, which is often seen in the x-ray spectrum of both stellar-mass and supermassive black hole candidates and whose shape is supposed to be strongly affected by the space-time geometry. As found in previous studies in the literature, there is a strong correlation between the spin parameter and the deformation parameter; that is, the line emitted around a Kerr black hole with a certain spin can be very similar to the one coming from the space-time around a non-Kerr object with a quite different spin. Despite that, the analysis of the broad Kα iron line is potentially more powerful than the continuum-fitting method, as it can put an interesting bound on possible deviations from the Kerr geometry independently of the value of the spin parameter and without additional measurements. © 2013 American Physical Society. Source


Zu Eulenburg P.,Johannes Gutenberg University Mainz | Stoeter P.,Johannes Gutenberg University Mainz | Dieterich M.,Ludwig Maximilians University of Munich
Annals of Neurology | Year: 2010

Objective: Patients who have had vestibular neuritis (VN) show a remarkable clinical improvement especially in gait and posture >6 months after disease onset. Methods: Voxel-based morphometry was used to detect the VN-induced changes in gray and white matter by means of structural magnetic resonance imaging. Twenty-two patients were compared an average 2.5 years after onset of VN to a healthy sex-and age-matched control group. Results: Our analysis revealed that all patients had signal intensity increases for gray matter in the medial vestibular nuclei and the right gracile nucleus and for white matter in the area of the pontine commissural vestibular fibers. A relative atrophy was observed in the left posterior hippocampus and the right superior temporal gyrus. Patients with a residual canal paresis also showed an increase of gray matter in middle temporal (MT)/V5 bilaterally. Interpretation: These findings indicate that the processes of central compensation after VN seem to occur in 3 different sensory systems. First of all, the vestibular system itself showed a white matter increase in the commissural fibers as a direct consequence of an increased internuclei vestibular crosstalk of the medial vestibular nuclei. Second, to regain postural stability, there was a shift to the somatosensory system due to an elevated processing of proprioceptive information in the right gracile nucleus. Third, there was a bilateral increase in the area of MT/V5 in VN patients with a residual peripheral vestibular hypofunction. This seems to be the result of an increased importance of visual motion processing. © 2010 American Neurological Association. Source


MacCione L.,Ludwig Maximilians University of Munich | MacCione L.,Max Planck Institute for Physics
Physical Review Letters | Year: 2013

We compute cosmic ray (CR) nuclei, proton, antiproton, electron, and positron spectra below 1 TeV at Earth by means of a detailed transport description in the galaxy and in the solar system. CR spectra below 10 GeV are strongly modified by charge-sign dependent propagation effects. These depend on the polarity of the solar magnetic field and therefore vary with the solar cycle. The puzzling discrepancy between the low-energy positron fraction measured by PAMELA and AMS-01 is then easily explained by their different data-taking epochs. We reproduce the observed spectra of CR light nuclei within the same galactic and solar-system propagation model. © 2013 American Physical Society. Source


Alba V.,Ludwig Maximilians University of Munich | Haque M.,Max Planck Institute For Physik Komplexer Systeme | Lauchli A.M.,University of Innsbruck
Physical Review Letters | Year: 2013

We study the entanglement spectrum (ES) of the Bose-Hubbard model on the two-dimensional square lattice at unit filling, both in the Mott insulating and in the superfluid phase. In the Mott phase, we demonstrate that the ES is dominated by the physics at the boundary between the two subsystems. On top of the boundary-local (perturbative) structure, the ES exhibits substructures arising from one-dimensional dispersions along the boundary. In the superfluid phase, the structure of the ES is qualitatively different, and reflects the spontaneously broken U(1) symmetry of the phase. We attribute the basic low-lying structure to the "tower of states" Hamiltonian of the model. We then discuss how these characteristic structures evolve across the superfluid to Mott insulator transition and their influence on the behavior of the entanglement entropies. We briefly outline the implications of the ES structure on the efficiency of matrix-product-state based algorithms in two dimensions. © 2013 American Physical Society. Source


Schollwock U.,Ludwig Maximilians University of Munich | Schollwock U.,Germany Institute for Advanced Study Berlin
Annals of Physics | Year: 2011

The density-matrix renormalization group method (DMRG) has established itself over the last decade as the leading method for the simulation of the statics and dynamics of one-dimensional strongly correlated quantum lattice systems. In the further development of the method, the realization that DMRG operates on a highly interesting class of quantum states, so-called matrix product states (MPS), has allowed a much deeper understanding of the inner structure of the DMRG method, its further potential and its limitations. In this paper, I want to give a detailed exposition of current DMRG thinking in the MPS language in order to make the advisable implementation of the family of DMRG algorithms in exclusively MPS terms transparent. I then move on to discuss some directions of potentially fruitful further algorithmic development: while DMRG is a very mature method by now, I still see potential for further improvements, as exemplified by a number of recently introduced algorithms. © 2010. Source


Mayer M.C.,Max Planck Institute of Neurobiology | Meinl E.,Ludwig Maximilians University of Munich
Therapeutic Advances in Neurological Disorders | Year: 2012

B cells and antibodies constitute an important element in different inflammatory diseases of the central nervous system (CNS). Autoantibodies can serve as a biomarker to identify disease subgroups and may in addition contribute to the pathogenic process. One candidate autoantigen for multiple sclerosis (MS) is myelin oligodendrocyte glycoprotein (MOG). MOG is localized at the outermost surface of myelin in the CNS and has been the focus of extensive research for more than 30 years. Its role as an important autoantigen for T cells and as a target of demyelinating autoantibodies has been established in several variants of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The literature regarding antibodies to MOG in MS patients is confusing and contradictory. Recent studies, however, have described high levels of antibodies to conformationally correct MOG in pediatric acquired demyelination, both acute disseminated encephalomyelitis (ADEM) and MS. In adult MS, such antibodies are rarely found and then only at low levels. In this review, we summarize key findings from animal models and patient studies, discuss challenges in detecting anti-MOG antibodies in patients and present recent approaches to identifying new autoantigens in MS. © The Author(s), 2012. Source


Ries C.,Ludwig Maximilians University of Munich
Cellular and Molecular Life Sciences | Year: 2014

The tissue inhibitors of metalloproteinases (TIMPs) are well recognized for their role in extracellular matrix remodeling by controlling the activity of matrix metalloproteinases (MMPs). Independent of MMP inhibition, TIMPs act as signaling molecules with cytokine-like activities thereby influencing various biological processes including cell growth, apoptosis, differentiation, angiogenesis, and oncogenesis. Recent studies on TIMP-1's cytokine functions have identified complex regulatory networks involving a specific surface receptor and subsequent signaling pathways including miRNA-mediated posttranscriptional regulation of gene expression that ultimately control the fate and behavior of the cells. The present review summarizes the current knowledge on TIMP-1 as a cytokine modulator of cell functions, outlines recent progress in defining molecular pathways that transmit TIMP-1 signals from the cell periphery into the nucleus, and discusses TIMP-1's role as a cytokine in the pathophysiology of cancer and other human diseases. © 2013 Springer Basel. Source


Persoh D.,Ludwig Maximilians University of Munich | Persoh D.,University of Bayreuth
Fungal Diversity | Year: 2013

Endophytic fungal communities have been shown to be highly diverse in almost every host plant species analyzed so far. However, the factors shaping their compositions are largely unknown. To elucidate the impact of various factors, 10 independent replicates of DNA extracts from each of 17 surface-sterilized leaf and stem samples were analyzed by pyrosequencing of fungal ITS1 rRNA gene amplicons. Altogether, 154 fungal OTUs (operational taxonomic units), represented by 953,385 sequences, were found in at least 2 samples from Viscum album ssp. austriacum and/or its host Pinus sylvestris. Deviating from earlier, cultivation-based assessments, the communities were dominated by OTUs related to the genus Mortierella and OTUs not assignable to a certain fungal phylum. However, Ascomycota were still the most diverse group in terms of OTU richness and already hypothesized organ and host preferences of certain endophytic Xylariaceae isolated from the Pinus-Viscum-system could be confirmed. Host species and organ type were also the major factors shaping the detected fungal communities. The two plant species clearly differed according to the endophytic fungal communities, but only stems and needles of Pinus were inhabited by significantly different fungal assemblages. Interestingly, only the 1 and 3 year old stem sections differed according to the endophytic fungal community, while differently aged leaves of both plants were indistinguishable in this regard. Size of the organs had no impact on fungal communities in Pinus, but shorter internodes and smaller leaves showed at least a tendency to differ from the corresponding larger organs in Viscum. Fungal communities also differed slightly between the two sampling sites, lying 200 km apart, and between the three sampling campaigns. Because the samples were drawn within 15 days, this finding indicates that seasonal shifts clearly outweigh aging effects in host plant with perennial leaves. The results therefore provide strong evidence against a linear development of the endophytic fungal communities in Pinus sylvestris and Viscum album over the years. The communities seem to establish themselves already in the year the respective organs emerge. Further study is required to clarify whether they predominantly establish anew each year, or if the core community persists throughout subsequent years. The most abundant endophytic OTUs are known from soil and/or dead plant material and are supposed to represent latent decomposers. The study reveals for the first time that host and/or organ preferences of putatively saprotrophic fungi are predominantly responsible for compositional differences in the endophytic fungal communities between host plants and organs. While the analyses are shown to provide rather robust results, the significance of genetic abundance, as revealed by high-throughput sequencing analyses, remains an unsettled issue. This is discussed in detail, as well as the challenges in assigning taxonomic names to OTUs. © 2013 Mushroom Research Foundation. Source


Groot Nibbelink S.,Ludwig Maximilians University of Munich
Fortschritte der Physik | Year: 2011

In this work we attempt to bridge the gap between heterotic orbifold models and Calabi-Yau compactifications using gauged linear sigma models (GLSMs) with (2,0) worldsheet supersymmetry. We associate a specific GLSM to a heterotic orbifold model with twisted states that have non-vanishing vacuum expectation values (VEVs): The charges of the GLSM superfields are essentially determined by the shifted momenta of these states. When a twisted state contains an oscillator excitation, a fermionic gauging is introduced on the worldsheet, inducing a non-Abelian gauge bundle, e.g. the standard embedding. However, irrespectively of whether the twisted states contain oscillators or not, they can be interpreted as blow-up modes, as their VEVs are correlated with sizes of exceptional cycles in the resolved geometry. We show that the GLSM anomaly cancellation conditions ensure that the Bianchi identities are fulfilled for all possible triangulations of a resolution. By considering marginal deformations of a GLSM in the large volume limit we are able to directly determine its effective four dimensional spectrum. In the cases considered the spectra coincide with those computed via index theorems. In this work the bridging of the the gap between heterotic orbifold models and Calabi-Yau compactifications using gauged linear sigma models (GLSMs) with (2,0) worldsheet supersymmetry will be attempted. A specific GLSM is associated to a heterotic orbifold model with twisted states that have non-vanishing vacuum expectation values (VEVs). The charges of the GLSM superfields are essentially determined by the shifted momenta of these states. When a twisted state contains an oscillator excitation, a fermionic gauging is introduced on the worldsheet, inducing a non-Abelian gauge bundle, e.g. the standard embedding. However, irrespectively of whether the twisted states contain oscillators or not, they can be interpreted as blow-up modes, as their VEVs are correlated with sizes of exceptional cycles in the resolved geometry. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Messmer E.M.,Ludwig Maximilians University of Munich
Ophthalmologe | Year: 2012

Preservatives are a legal requirement for eye drops in multidose containers. Moreover, they are necessary for stabilization and intraocular penetration for a number of ophthalmic preparations. Most preservatives act in a relatively unspecific manner as detergents or by oxidative mechanisms and thereby cause side effects at the ocular surface. They may also affect the lens, trabecular meshwork and the retina. Benzalkonium chloride is the most commonly used preservative in ophthalmology and is more toxic than other or newer preservatives, such as polyquaternium-1 (Polyquad), sodium perborate, oxychloro-complex (Purite®) and SofZia. Preservative-free topical medication is highly recommended for patients with ocular surface disease, frequent eye drop administration, proven allergy to preservatives and contact lens wear. © 2012 Springer-Verlag Berlin Heidelberg. Source


Pfeifer N.,Ludwig Maximilians University of Munich
Behavioral and Brain Sciences | Year: 2011

Normative theories like probability logic provide roadmaps for psychological investigations. They make theorizing precise. Therefore, normative considerations should not be subtracted from psychological research. I explain why conditional elimination inferences involve at least two norm paradigms; why reporting agreement with rationality norms is informative; why alleged asymmetric relations between formal and psychological theories are symmetric; and I discuss the arbitration problem. © 2011 Cambridge University Press. Source


Daoutidis I.,Free University of Colombia | Ring P.,Ludwig Maximilians University of Munich
Physical Review C - Nuclear Physics | Year: 2011

We have calculated the strength distributions of the dipole response in spherical nuclei, ranging all over the periodic table. The calculations were performed within two microscopic models: the discretized quasiparticle random-phase approximation and the continuum quasiparticle random-phase approximation, which takes into account the coupling of the single-particle continuum in an exact way. Pairing correlations are treated with the BCS model. In the calculations, two density functionals were used, namely, the PC-F1 and the DD-PC1. Both are based on relativistic point-coupling Lagrangians. It is explicitly shown that this model is capable of reproducing the giant- as well as the pygmy-dipole resonance for open-shell nuclei in a high level of quantitative agreement with the available experimental observations. © 2011 American Physical Society. Source


Tellier A.,Ludwig Maximilians University of Munich | Brown J.K.,John Innes Center
BMC Evolutionary Biology | Year: 2011

Background: Genomic and pathology analysis has revealed enormous diversity in genes involved in disease, including those encoding host resistance and parasite effectors (also known in plant pathology as avirulence genes). It has been proposed that such variation may persist when an organism exists in a spatially structured metapopulation, following the geographic mosaic of coevolution. Here, we study gene-for-gene relationships governing the outcome of plant-parasite interactions in a spatially structured system and, in particular, investigate the population genetic processes which maintain balanced polymorphism in both species. Results: Following previous theory on the effect of heterogeneous environments on maintenance of polymorphism, we analysed a model with two demes in which the demes have different environments and are coupled by gene flow. Environmental variation is manifested by different coefficients of natural selection, the costs to the host of resistance and to the parasite of virulence, the cost to the host of being diseased and the cost to an avirulent parasite of unsuccessfully attacking a resistant host. We show that migration generates negative direct frequency-dependent selection, a condition for maintenance of stable polymorphism in each deme. Balanced polymorphism occurs preferentially if there is heterogeneity for costs of resistance and virulence alleles among populations and to a lesser extent if there is variation in the cost to the host of being diseased. We show that the four fitness costs control the natural frequency of oscillation of host resistance and parasite avirulence alleles. If demes have different costs, their frequencies of oscillation differ and when coupled by gene flow, there is amplitude death of the oscillations in each deme. Numerical simulations show that for a multiple deme island model, costs of resistance and virulence need not to be present in each deme for stable polymorphism to occur. Conclusions: Our theoretical results confirm the importance of empirical studies for measuring the environmental heterogeneity for genetic costs of resistance and virulence alleles. We suggest that such studies should be developed to investigate the generality of this mechanism for the long-term maintenance of genetic diversity at host and parasite genes. © 2011 Tellier and Brown; licensee BioMed Central Ltd. Source


Von Mutius E.,Ludwig Maximilians University of Munich
Clinical and Experimental Immunology | Year: 2010

About 15 years have gone by since Strachan first proposed the idea that infections and unhygienic contact may confer protection from the development of allergic illnesses. The so-called 'hygiene hypothesis' has since undergone numerous modifications in the field of epidemiology, clinical science and immunology. Three main areas of research have been brought forward: to explore the role of overt viral and bacterial infections for the inception of allergic diseases; to investigate the significance of environmental exposure to microbial compounds on the development of allergies; and to study the effect of both exposures on underlying innate and adaptive immune responses. A concept unifying these various aspects has not been found, but various pieces of a complex interplay between immune responses of the host, characteristics of the invading microorganism, the level and variety of the environmental exposure and the interactions between an exposed subject's genetic background and the environmental exposures becomes apparent. A natural experiment relating to the hygiene hypothesis is the recurrent observation of a protective effect of growing up on a farm for asthma and allergies. This has been shown in a large number of epidemiological studies across the world among children and adults. The timing and duration of exposure are likely to play a critical role. The largest reduction in risk has been demonstrated for those exposed prenatally and continuously thereafter until adulthood. The protective factors in these farming environments have not been unravelled completely. Findings from various studies suggest that the contact with farm animals, at least in childhood, confers protection. Also the consumption of unprocessed cow's milk directly from the farm has been shown to protect from childhood asthma and allergies. Increased levels of microbial substances may, at least in part, contribute to the 'farm effect'. However, only few studies have measured microbial exposures in these environments and the results obtained so far suggest that the underlying protective microbial exposure(s) have not been identified, but a number of studies using metagenomic approaches are currently under way. The mechanisms by which such environmental exposures confer protection from respiratory allergies are also not well understood. There is good evidence for the involvement of innate immune responses, but translation into protective mechanisms for asthma and allergies is lacking. Furthermore, a number of gene x environment interactions have been observed. © 2010 British Society for Immunology. Source


Docampo P.,Ludwig Maximilians University of Munich | Guldin S.,Ecole Polytechnique Federale de Lausanne | Leijtens T.,University of Oxford | Noel N.K.,University of Oxford | And 2 more authors.
Advanced Materials | Year: 2014

The field of solution-processed photovoltaic cells is currently in its second spring. The dye-sensitized solar cell is a widely studied and longstanding candidate for future energy generation. Recently, inorganic absorber-based devices have reached new record efficiencies, with the benefits of all-solid-state devices. In this rapidly changing environment, this review sheds light on recent developments in all-solid-state solar cells in terms of electrode architecture, alternative sensitizers, and hole-transporting materials. These concepts are of general applicability to many next-generation device platforms. The field of solution-processed photovoltaic cells is currently in its second spring, with solid-state devices incorporating novel inorganic absorbers reaching record efficiencies. This review sheds light on recent developments in all-solid-state solar cells in terms of electrode architecture, alternative sensitizers, and hole-transporting materials: concepts applicable to many next-generation device platforms. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Hassler F.,Ludwig Maximilians University of Munich | Lust D.,Max Planck Institute for Physics
Journal of High Energy Physics | Year: 2013

In this paper we discuss the construction of non-geometric Q- and R-branes as sources of non-geometric Q- and R-fluxes in string compactifications. The non-geometric Q-branes, being obtained via T-duality from the NS 5-brane or respectively from the KK-monopole, are still local solutions of the standard NS action, where however the background fields G and B possess non-geometric global monodromy properties. We show that using double field theory and redefined background fields G̃ and β as well as their corresponding effective action, the Q-branes are locally and globally well behaved solutions. Furthermore the R-brane solution can be at least formally constructed using dual coordinates. We derive the associated non-geometric Q- and R-fluxes and discuss that closed strings moving in the space transversal to the world-volumes of the non-geometric branes see a non-commutative or a non-associative geometry. In the second part of the paper we construct intersecting Q- and R-brane configurations as completely supersymmetric solutions of type IIA/B supergravity with certain SU(3) × SU(3) group structures. In the near horizon limit the intersecting brane configurations lead to type II backgrounds of the form AdS4 × M6, where the six-dimensional compact space M6 is a torus fibration with various non-geometric Q- and R-fluxes in the compact directions. It exhibits an interesting non-commutative and non-associate geometric structure. Furthermore we also determine some of the effective four-dimensional superpotentials originating from the non-geometric fluxes. © 2013 SISSA, Trieste, Italy. Source


Mashaghi A.,FOM Institute for Atomic and Molecular Physics | Kramer G.,University of Heidelberg | Lamb D.C.,Ludwig Maximilians University of Munich | Mayer M.P.,University of Heidelberg | Tans S.J.,FOM Institute for Atomic and Molecular Physics
Chemical Reviews | Year: 2014

Single-molecule methods provide an exciting new tool to address many of the long-standing questions in chaperone-assisted protein folding. Single-molecule methods allow one not only to study the conformation and dynamics of chaperones and their influence on the conformation of substrates but also to investigate the protein-folding landscape. As chaperone-assisted folding pathways involve a number of players and interactions, one of the next steps for single molecule experiments on chaperones is to increase the complexity of the systems. Microfluidic devices can be used to allow rapid mixing and dilution for investigating protein unfolding and refolding. The ultimate single molecule assay on chaperone-assisted protein folding would be to follow protein folding inside the highly crowded living cell. Many steps toward single-molecule folding experiments in live cells have already been taken, including the first live-cell folding experiments on the ensemble level and single-molecules measurements in living cells and bacteria. Source


Langosch D.,TU Munich | Scharnagl C.,TU Munich | Steiner H.,Ludwig Maximilians University of Munich | Lemberg M.K.,German Cancer Research Center
Trends in Biochemical Sciences | Year: 2015

Intramembrane proteolysis - cleavage of proteins within the plane of a membrane - is a widespread phenomenon that can contribute to the functional activation of substrates and is involved in several diseases. Although different families of intramembrane proteases have been discovered and characterized, we currently do not know how these enzymes discriminate between substrates and non-substrates, how site-specific cleavage is achieved, or which factors determine the rate of proteolysis. Focusing on γ-secretase and rhomboid proteases, we argue that answers to these questions may emerge from connecting experimental readouts, such as reaction kinetics and the determination of cleavage sites, to the structures and the conformational dynamics of substrates and enzymes. © 2015. Source


Schaub B.,Ludwig Maximilians University of Munich | Vercelli D.,University of Arizona
Current Opinion in Immunology | Year: 2015

Allergic diseases have a strong environmental component, illustrated by the rapid rise of their prevalence in the Western world. Environmental exposures have been consistently shown to either promote or protect against allergic disease. Here we focus on protective exposures and the pathways they regulate. Traditional farming, natural environments with high biodiversity, and pets in the home (particularly dogs) have the most potent and consistent allergy-protective effects and are actively investigated to identify the environmental and host-based factors that confer allergy protection. Recent work emphasizes the critical protective role of microbial diversity and its interactions with the gut/lung and skin/lung axes. -. a cross-talk through which microbial exposure in the gut or skin powerfully influences immune responses in the lung. © 2015 Elsevier Ltd. Source


Ehrt O.,Ludwig Maximilians University of Munich
European Journal of Paediatric Neurology | Year: 2012

Nystagmus is an involuntary, periodic eye movement caused by a slow drift of fixation which is followed by a fast refixation saccade (jerk nystagmus) or a slow movement back to fixation (pendular nystagmus). In childhood most cases are benign forms of nystagmus: idiopathic infantile, ocular or latent nystagmus. They arise at the age of 3 months, without oscillopsia and show the absence of the physiologic opto-kinetic nystagmus. A full ophthalmologic evaluation is all that is needed in most cases: albinism, macular or optic nerve hypoplasia and congenital retinal dystrophies are the most common forms of ocular nystagmus. Idiopathic infantile nystagmus can be hereditary, the most common and best analyzed form being a mutation of the FRMD7 gene on chromosome Xq26.2. The mutation shows a mild genotype-phenotype correlation. In all female carriers the opto-kinetic nystagmus is absent and half had mild nystagmus. Latent nystagmus is part of the infantile esotropia syndrome and shows the unique feature of change of direction when the fixing eye changes: it is always beating to the side of the fixing eye. There is no cure for infantile nystagmus but therapeutic options include magnifying visual aids or eye muscle surgery at the age of 6-8 y in patients with head turn. Less than 20% of childhood nystagmus are acquired and need further neurological and imaging work-up. Alarming signs and symptoms are: onset after the age of 4 months, oscillopsia, dissociated (asymmetric) nystagmus, preserved opto-kinetic nystagmus, afferent pupillary defect, papilloedema and neurological symptoms like vertigo and nausea. The most common cause is due to pathology of the anterior optic pathway (e.g. optic nerve gliomas). It shows the same clinical feature of dissociated nystagmus as spasmus nutans but has a higher frequency as in INO. Other forms of acquired nystagmus are due to brainstem, cerebellar or metabolic diseases. © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. Source


Holdt L.M.,University of Leipzig | Teupser D.,University of Leipzig | Teupser D.,Ludwig Maximilians University of Munich
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2012

The chromosome 9p21 (Chr9p21) locus was discovered in 2007 by independent genome-wide association studies for coronary artery disease. Since then, the locus has been replicated numerous times and can be considered the most robust genetic marker of coronary artery disease today. Subsequent work has shown associations of Chr9p21 with a number of additional cardiovascular disease traits, such as carotid artery plaque, stroke, aneurysms, peripheral artery disease, heart failure, and cardiovascular mortality, suggesting a more general role in vascular pathology. Importantly, Chr9p21 lacks associations with common cardiovascular risk factors, such as lipids and hypertension, indicating that the locus exerts its effect through a completely novel mechanism. One of the challenges is that the core haplotype block at Chr9p21 resides in a region of the genome devoid of protein-coding genes. Recent progress has been made by functional studies focusing on differential expression of antisense noncoding RNA in the INK4 locus (ANRIL), which is transcribed from the Chr9p21 locus, as well as neighboring protein-coding genes at the INK4/ARF locus. The emerging concept suggests that ANRIL might constitute a regulator of epigenetic modification and thus modulate cardiovascular risk. Here, we review the current clinical, mechanistic, and diagnostic implications of the Chr9p21 locus in cardiovascular disease. © 2012 American Heart Association, Inc. Source


Moller H.-J.,Ludwig Maximilians University of Munich
International Journal of Psychiatry in Clinical Practice | Year: 2014

Objective. After 10 years of preparation, DSM-5 was published in 2013. This paper will examine the possible effects of DSM-5 on psychiatric diagnosis and psychopharmacotherapy. Methods. DSM-5 was compared with DSM-IV to identify the important changes in psychiatric diagnosis and possible consequences for psychopharmacotherapy. Results. Contrary to the original plans, DSM-5 did not make radical changes and move towards dimensional diagnosis but preserved the previous categorical system of disorders and a primarily symptom-based descriptive approach. The dimensional approach was only adopted through the introduction of several transnosological specifiers and the option to make symptom-or syndrome-related assessments. The criteria for some disorders were changed, including affective, dependence and schizophrenic disorders, and a few new disorders were added. Conclusion. The DSM-IV diagnostic system was largely preserved, although some changes were made, primarily in the field of affective disorder and in several criteria sets. The new transnosological specifiers, severity assessments and cross-cutting dimensional assessments may help to individualise treatment. © 2014 Informa Healthcare. Source


Anders H.-J.,Ludwig Maximilians University of Munich
Nature Reviews Nephrology | Year: 2014

The immune system is an important guardian of tissue homeostasis. In response to injury, resident and infiltrating immune cells orchestrate all phases of danger control, resolution of inflammation and tissue regeneration or scar formation. As mammalian postnatal kidneys are not capable of de novo nephrogenesis, recovery is limited to the regeneration or repair of existing nephrons. The regenerative capacity of the nephron varies between compartments; the epithelial cells of the tubule regenerate more efficiently than the structurally highly organized podocytes. Cells of the surrounding environment modulate nephron regeneration by secreting paracrine mediators. This Review discusses immune mediators and pathways that regulate the intrinsic regenerative capacity of the nephron. Eliminating injurious triggers, modulating renal inflammation and specifically enhancing the regenerative capacity of nephrons might be a promising strategy to improve long-term outcomes in patients with acute kidney injury and/or chronic kidney disease. © 2014 Macmillan Publishers Limited. Source


Pol D.,CONICET | Rauhut O.W.M.,Ludwig Maximilians University of Munich
Proceedings of the Royal Society B: Biological Sciences | Year: 2012

Abelisaurids are a clade of large, bizarre predatory dinosaurs, most notable for their high, short skulls and extremely reduced forelimbs. They were common in Gondwana during the Cretaceous, but exceedingly rare in the Northern Hemisphere. The oldest definitive abelisaurids so far come from the late Early Cretaceous of South America and Africa, and the early evolutionary history of the clade is still poorly known. Here, we report a new abelisaurid from the Middle Jurassic of Patagonia, Eoabelisaurus mefi gen. et sp. nov., which predates the so far oldest known secure member of this lineage by more than 40 Myr. The almost complete skeleton reveals the earliest evolutionary stages of the distinctive features of abelisaurids, such as the modification of the forelimb, which started with a reduction of the distal elements. The find underlines the explosive radiation of theropod dinosaurs in the Middle Jurassic and indicates an unexpected diversity of ceratosaurs at that time. The apparent endemism of abelisauroids to southern Gondwana during Pangean times might be due to the presence of a large, central Gondwanan desert. This indicates that, apart from continent-scale geography, aspects such as regional geography and climate are important to reconstruct the biogeographical history of Mesozoic vertebrates. © 2012 The Royal Society. Source


Brown J.K.M.,John Innes Center | Tellier A.,Ludwig Maximilians University of Munich
Annual Review of Phytopathology | Year: 2011

We review current ideas about coevolution of plants and parasites, particularly processes that generate genetic diversity. Frequencies of host resistance and parasite virulence alleles that interact in gene-for-gene (GFG) relationships coevolve in the familiar boom-and-bust cycle, in which resistance is selected when virulence is rare, and virulence is selected when resistance is common. The cycle can result in stable polymorphism when diverse ecological and epidemiological factors cause negative direct frequency-dependent selection (ndFDS) on host resistance, parasite virulence, or both, such that the benefit of a trait to fitness declines as its frequency increases. Polymorphism can also be stabilized by overdominance, when heterozygous hosts have greater resistance than homozygotes to diverse pathogens. Genetic diversity can also persist in the form of statistical polymorphism, sustained by random processes acting on gene frequencies and population size. Stable polymorphism allows alleles to be long-lived and genetic variation to be detectable in natural populations. In agriculture, many of the factors promoting stability in host-parasite interactions have been lost, leading to arms races of host defenses and parasite effectors. © 2011 by Annual Reviews. All rights reserved. Source


Jeschke J.M.,Ludwig Maximilians University of Munich | Genovesi P.,European Commission - Joint Research Center Ispra
Oikos | Year: 2011

What determines the number of alien species in a given region? 'Native biodiversity' and 'human impact' are typical answers to this question. Indeed, studies comparing different regions have frequently found positive relationships between number of alien species and measures of both native biodiversity (e.g. the number of native species) and human impact (e.g. human population). These relationships are typically explained by biotic acceptance or resistance, i.e. by influence of native biodiversity and human impact on the second step of the invasion process, establishment. The first step of the invasion process, introduction, has often been ignored. Here we investigate whether relationships between number of alien mammals and native biodiversity or human impact in 43 European countries are mainly shaped by differences in number of introduced mammals or establishment success. Our results suggest that correlation between number of native and established mammals is spurious, as it is simply explainable by the fact that both quantities are linked to country area. We also demonstrate that countries with higher human impact host more alien mammals than other countries because they received more introductions than other countries. Differences in number of alien mammals cannot be explained by differences in establishment success. Our findings highlight importance of human activities and question, at least for mammals in Europe, importance of biotic acceptance and resistance. © 2011 The Authors. Source


Landes K.,Ludwig Maximilians University of Munich
International Journal of Materials Research | Year: 2011

An overview is given of Plasma Generators developed with the focus on application in thermal spraying, some of which might even find use in other thermal plasma processes. The construction and operation principle of conventional plasma torches as well as of plasma torches with special features are presented. The particular properties and application potential of the innovative plasma generator types "Triplex", "Delta" and "Large", each operating with new physical principles, are discussed. © Carl Hanser Verlag GmbH & Co. KG. Source


Tentori K.,University of Trento | Crupi V.,Ludwig Maximilians University of Munich | Russo S.,University of Trento
Journal of Experimental Psychology: General | Year: 2013

Major recent interpretations of the conjunction fallacy postulate that people assess the probability of a conjunction according to (non-normative) averaging rules as applied to the constituents' probabilities or represent the conjunction fallacy as an effect of random error in the judgment process. In the present contribution, we contrast such accounts with a different reading of the phenomenon based on the notion of inductive confirmation as defined by contemporary Bayesian theorists. Averaging rule hypotheses along with the random error model and many other existing proposals are shown to all imply that conjunction fallacy rates would rise as the perceived probability of the added conjunct does. By contrast, our account predicts that the conjunction fallacy depends on the added conjunct being perceived as inductively confirmed. Four studies are reported in which the judged probability versus confirmation of the added conjunct have been systematically manipulated and dissociated. The results consistently favor a confirmation-theoretic account of the conjunction fallacy against competing views. Our proposal is also discussed in connection with related issues in the study of human inductive reasoning. © 2012 American Psychological Association. Source


Papenfort K.,Princeton University | Papenfort K.,Ludwig Maximilians University of Munich | Vanderpool C.K.,University of Illinois at Urbana - Champaign
FEMS Microbiology Reviews | Year: 2015

Bacterial small regulatory RNAs (sRNAs) are commonly known to repress gene expression by base pairing to target mRNAs. In many cases, sRNAs base pair with and sequester mRNA ribosome-binding sites, resulting in translational repression and accelerated transcript decay. In contrast, a growing number of examples of translational activation and mRNA stabilization by sRNAs have now been documented. A given sRNA often employs a conserved region to interact with and regulate both repressed and activated targets. However, the mechanisms underlying activation differ substantially from repression. Base pairing resulting in target activation can involve sRNA interactions with the 5' untranslated region (UTR), the coding sequence or the 3' UTR of the target mRNAs. Frequently, the activities of protein factors such as cellular ribonucleases and the RNA chaperone Hfq are required for activation. Bacterial sRNAs, including those that function as activators, frequently control stress response pathways or virulence-associated functions required for immediate responses to changing environments. This review aims to summarize recent advances in knowledge regarding target mRNA activation by bacterial sRNAs, highlighting the molecular mechanisms and biological relevance of regulation. © 2015 FEMS. Source


Barthel T.,Ludwig Maximilians University of Munich
New Journal of Physics | Year: 2013

This paper provides a study and discussion of earlier as well as novel more efficient schemes for the precise evaluation of finite-temperature response functions of strongly correlated quantum systems in the framework of the time-dependent density matrix renormalization group (tDMRG). The computational costs and bond dimensions as functions of time and temperature are examined for the example of the spin-1/2 XXZ Heisenberg chain in the critical XY phase and the gapped Néel phase. The matrix product state purifications occurring in the algorithms are in a one-to-one relation with the corresponding matrix product operators. This notational simplification elucidates implications of quasi-locality on the computational costs. Based on the observation that there is considerable freedom in designing efficient tDMRG schemes for the calculation of dynamical correlators at finite temperatures, a new class of optimizable schemes, as recently suggested in Barthel, Schollwöck and Sachdev (2012 arXiv:1212.3570), is explained and analyzed numerically. A specific novel near-optimal scheme that requires no additional optimization reaches maximum times that are typically increased by a factor of 2, when compared against earlier approaches. These increased reachable times make many more physical applications accessible. For each of the described tDMRG schemes, one can devise a corresponding transfer matrix renormalization group variant. © IOP Publishing and Deutsche Physikalische Gesellschaft. Source


Zottl G.,Ludwig Maximilians University of Munich
Operations Research | Year: 2010

We analyze firms' investment incentives in markets where demand at spot markets is fluctuating and storability of the output is limited. Firms will then find it optimal to invest in a differentiated portfolio of technologies in order to serve fluctuating demand. For optimal behavior of firms, this has been analyzed in the so-called peak load pricing literature-cf. Crew and Kleindorfer [Crew, M., P. Kleindorfer. 1986. The Economics of Public Utility Regulation. MIT Press, Cambridge, MA]. We analyze the case of strategically behaved firms. We derive the equilibrium of the investment game and compare it to the benchmark case of optimal investment. We find that strategic firms have an incentive to overinvest in base load technologies but choose total capacities, which are too low from a welfare point of view. © 2010 INFORMS. Source


Jakubassa-Amundsen D.H.,Ludwig Maximilians University of Munich
Physical Review C - Nuclear Physics | Year: 2013

The Born theory for bremsstrahlung from high-energy electrons colliding with extended (finite-mass) nuclei is reexamined. Higher-order effects are included into the Born approximation by making use of the weak-potential Sommerfeld-Maue prescription in an additional contribution to the transition amplitude. Predictions are made for the differential cross section (with respect to the photon degrees of freedom) and for the polarization correlations between the incoming electron and the emitted photon. It is found that at collision energies exceeding 20 MeV the cross section as well as the polarization correlations are strongly influenced by nuclear recoil and nuclear structure effects, particularly at backward photon angles. Numerical results are presented for bremsstrahlung from 10-100 MeV electrons colliding with protons, 19F and 89Y nuclei. © 2013 American Physical Society. Source


Chamseddine A.H.,American University of Beirut | Mukhanov V.,Ludwig Maximilians University of Munich
Journal of High Energy Physics | Year: 2013

We modify Einstein's theory of gravity, isolating the conformal degree of freedom in a covariant way. This is done by introducing a physical metric defined in terms of an auxiliary metric and a scalar field appearing through its first derivatives. The resulting equations of motion split into a traceless equation obtained through variation with respect to the auxiliary metric and an additional differential equation for the trace part. As a result the conformal degree of freedom becomes dynamical even in the absence of matter. We show that this extra degree of freedom can mimic cold dark matter. Source


Remi J.,Ludwig Maximilians University of Munich
Current Pharmaceutical Design | Year: 2015

The circadian clock is a biological system that allows organisms to adapt to temporal constraints of the environment. It governs all body functions. The circadian clock has an endogenous period and entrains to the external day by the means of timing cues, also called “zeitgebers”. A discrepancy between internal and external day or internal day and certain body functions results in circadian desynchrony, most prominently represented in jet lag. Circadian desynchrony may be a factor in many diseases. This review presents literature in which the impact of circadian desynchrony on disease development - with a special focus on critical illness - has been addressed. The treatment options that have so far been investigated are also presented. © 2015, Bentham Science Publishers. Source


Perez-Galan P.,U.S. National Institutes of Health | Perez-Galan P.,University of Barcelona | Dreyling M.,Ludwig Maximilians University of Munich | Wiestner A.,U.S. National Institutes of Health
Blood | Year: 2011

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma of which at least a subset arises from antigen-experienced B cells. However, what role antigen stimulation plays in its pathogenesis remains ill defined. The genetic hallmark is the chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1. Secondary genetic events increase the oncogenic potential of cyclin D1 and frequently inactivate DNA damage response pathways. In combination these changes drive cell-cycle progression and give rise to pronounced genetic instability. Several signaling pathways contribute to MCL pathogenesis, including the often constitutively activated PI3K/AKT/mTOR pathway, which promotes tumor proliferation and survival. WNT, Hedgehog, and NF-κB pathways also appear to be important. Although MCL typically responds to frontline chemotherapy, it remains incurable with standard approaches. Proteasome inhibitors (bortezomib), mTOR inhibitors (temsirolimus), and immunomodulatory drugs (lenalidomide) have recently been added to the treatment options in MCL. The molecular basis for the antitumor activity of these agents is an area of intense study that hopefully will lead to further improvements in the near future. Given its unique biology, relative rarity, and the difficulty in achieving long-lasting remissions with conventional approaches, patients with MCL should be encouraged to participate in clinical trials. Source


Mukhanov V.,Ludwig Maximilians University of Munich
European Physical Journal C | Year: 2013

I consider the generic model independent predictions of the theory of quantum cosmological perturbations. To describe the stage of cosmic inflation, where these perturbations are amplified, the hydrodynamical approach is used. The inflationary stage is completely characterized by the deviation of the equation of state from cosmological constant which is a smooth function of the number of e-folds until the end of inflation. It is shown that in this case the spectral index should deviate from the flat one at least by 3 percent irrespective of any particular scenario. Given the value of the spectral index a lower bound on the amount of gravitational waves produced is derived. Finally the relation between effective hydrodynamical description of inflation and inflationary scenarios is discussed. © 2013 Springer-Verlag Berlin Heidelberg and Società Italiana di Fisica. Source


Jahn K.,Ludwig Maximilians University of Munich
European Journal of Paediatric Neurology | Year: 2011

Common causes of vertigo and dizziness in childhood are vestibular migraine and associated syndromes (benign paroxysmal vertigo), unilateral vestibular failure due to labyrinthitis, positioning vertigo, and somatoform syndromes. Although the same spectrum of diseases as in adults can be found, the frequency differs widely. Further, balance disorders not related to vestibular function, like cerebral palsy, can present with dizziness. Vestibular function can reliably be addressed at the bedside by head impulses to test vestibulo-ocular reflex function, ocular motor testing of the central vestibular system, and balance tests for vestibulo-spinal function. Vestibulo-ocular reflex function can now be quantified by recording eye and head movements with high resolution video-oculography (256 Hz) and inertial sensors. Posturographic measures using artificial neuronal networks are used to classify dysbalance. Quantitative gait analysis further helps to distinguish balance disorders caused by e.g. sensory dysfunction or supraspinal disturbances. Recently, functional neuroimaging opened a view to the brain network for the control of posture and locomotion. From frontal cortex the locomotor signal is conveyed via the basal ganglia to the centers for locomotion and postural control in the brainstem tegmentum. The cerebellum is involved in sensory integration and rhythm generation during postural demands. To summarize, most syndromes causing dizziness, vertigo and imbalance can be diagnosed based on history and clinical tests. However, new data from neurophysiology and imaging help to understand the pathophysiology and the therapeutic principles in these disorders. © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. Source


Spies M.,Ludwig Maximilians University of Munich
Information Systems | Year: 2010

In this paper, we discuss the motivation and the fundamentals of an ontology representation of business reporting data and metadata structures as defined in the eXtensible business reporting language (XBRL) standard. The core motivation for an ontology representation is the enhanced potential for integrated analytic applications that build on quantitative reporting data combined with structured and unstructured data from additional sources. Applications of this kind will enable significant enhancements in regulatory compliance management, as they enable business analytics combined with inference engines for statistical, but also for logical inferences. In order to define a suitable ontology representation of business reporting language structures, an analysis of the logical principles of the reporting metadata taxonomies and further classification systems is presented. Based on this analysis, a representation of the generally accepted accounting principles taxonomies in XBRL by an ontology provided in the web ontology language (OWL) is proposed. An additional advantage of this representation is its compliance with the recent ontology definition metamodel (ODM) standard issued by OMG. © 2009 Elsevier B.V. All rights reserved. Source


Ergun S.,University of Duisburg - Essen | Tilki D.,Ludwig Maximilians University of Munich | Klein D.,University of Duisburg - Essen
Antioxidants and Redox Signaling | Year: 2011

Tissue regeneration and several diseases such as tumor and atherosclerosis depend on new vessel formation by both angiogenesis and vasculogenesis. Endothelial cells (ECs) are widely considered to be the active cellular component in these processes, followed by contractile cells such as pericytes and smooth muscle cells. The best known sources providing these cell types or their progenitors are ECs lining the vessel lumen and bone marrow. As easily evident, the vessel wall was recognized as being a passive player to a great extent except ECs of the vascular intima. Particularly, the vascular adventitia has been considered as a passive layer rather than an active part of the vessel wall. But results provided during the last few years have led to a revision of this classical view because of an apparent stem cell niche function of the vascular adventitia. This review aims to sum up findings identifying the vessel wall as an important stem cell reservoir and discusses its impact on health and disease. © 2011 Mary Ann Liebert, Inc. Source


Lienert M.,Ludwig Maximilians University of Munich
Journal of Physics A: Mathematical and Theoretical | Year: 2015

The two-body Dirac (2BD) equations of constraint theory are of special interest not only in view of applications for phenomenological calculations of mesonic spectra but also because they avoid no-go theorems about relativistic interactions. Furthermore, they provide a quantum mechanical description in a manifestly Lorentz invariant way using the concept of a multi-time wave function. In this paper, we place them into the context of the multi-time formalism of Dirac, Tomonaga and Schwinger for the first time. A general physical and mathematical framework is outlined and the mechanism which permits relativistic interaction is identified. The main requirement derived from the general framework is the existence of conserved tensor currents with a positive component which can play the role of a probability density. We analyze this question for a general class of 2BD equations thoroughly and comprehensively. While the free Dirac current is not conserved, it is possible to find replacements. Improving on previous research, we achieve definite conclusions whether restrictions of the function space or of the interaction terms can guarantee the positive definiteness of the currents - and whether such restrictions are physically adequate. The consequences of the results are drawn, with respect to both applied and foundational perspectives. © 2015 IOP Publishing Ltd. Source


Aumann S.,Ludwig Maximilians University of Munich
Journal of Statistical Physics | Year: 2015

The goal of this paper is twofold. First we prove a rigidity estimate, which generalises the theorem on geometric rigidity of Friesecke, James and Müller to 1-forms with non-vanishing exterior derivative. Second we use this estimate to prove a kind of spontaneous breaking of rotational symmetry for some models of crystals, which allow almost all kinds of defects, including unbounded defects as well as edge, screw and mixed dislocations, i.e. defects with Burgers vectors. © 2015, Springer Science+Business Media New York. Source


Vega I.D.,Ludwig Maximilians University of Munich
Journal of Physics A: Mathematical and Theoretical | Year: 2015

We derive a master equation from the exact stochastic Liouville-von-Neumann (SLN) equation (Stockburger and Grabert 2002 Phys. Rev. Lett. 88 170407). The latter depends on two correlated noises and describes exactly the dynamics of an oscillator (which can be either harmonic or present an anharmonicity) coupled to an environment at thermal equilibrium. The newly derived master equation is obtained by performing analytically the average over different noise trajectories. It is found to have a complex hierarchical structure that might be helpful to explain the convergence problems occurring when performing numerically the stochastic average of trajectories given by the SLN equation (Koch et al 2008 Phys. Rev. Lett. 100 230402, Koch 2010 PhD thesis Fakultät Mathematik und Naturwissenschaften der Technischen Universitat Dresden). © 2015 IOP Publishing Ltd. Source


Lienert M.,Ludwig Maximilians University of Munich
Journal of Mathematical Physics | Year: 2015

The question how to Lorentz transform an N-particle wave function naturally leads to the concept of a so-called multi-time wave function, i.e., a map from (space-time)N to a spin space. This concept was originally proposed by Dirac as the basis of relativistic quantum mechanics. In such a view, interaction potentials are mathematically inconsistent. This fact motivates the search for new mechanisms for relativistic interactions. In this paper, we explore the idea that relativistic interaction can be described by boundary conditions on the set of coincidence points of two particles in space-time. This extends ideas from zero-range physics to a relativistic setting. We illustrate the idea at the simplest model which still possesses essential physical properties like Lorentz invariance and a positive definite density: two-time equations for massless Dirac particles in 1 + 1 dimensions. In order to deal with a spatio-temporally non-trivial domain, a necessity in the multi-time picture, we develop a newmethod to prove existence and uniqueness of classical solutions: a generalized version of the method of characteristics. Both mathematical and physical considerations are combined to precisely formulate and answer the questions of probability conservation, Lorentz invariance, interaction, and antisymmetry. © 2015 AIP Publishing LLC. Source


Herzog Q.,Ludwig Maximilians University of Munich | Laforsch C.,University of Bayreuth
BMC Biology | Year: 2013

Background: Inducible defenses are a common and widespread form of phenotypic plasticity. A fundamental factor driving their evolution is an unpredictable and heterogeneous predation pressure. This heterogeneity is often used synonymously to quantitative changes in predation risk, depending on the abundance and impact of predators. However, differences in 'modality', that is, the qualitative aspect of natural selection caused by predators, can also cause heterogeneity. For instance, predators of the small planktonic crustacean Daphnia have been divided into two functional groups of predators: vertebrates and invertebrates. Predators of both groups are known to cause different defenses, yet predators of the same group are considered to cause similar responses. In our study we question that thought and address the issue of how multiple predators affect the expression and evolution of inducible defenses. Results: We exposed D. barbata to chemical cues released by Triops cancriformis and Notonecta glauca, respectively. We found for the first time that two invertebrate predators induce different shapes of the same morphological defensive traits in Daphnia, rather than showing gradual or opposing reaction norms. Additionally, we investigated the adaptive value of those defenses in direct predation trials, pairing each morphotype (non-induced, Triops-induced, Notonecta-induced) against the other two and exposed them to one of the two predators. Interestingly, against Triops, both induced morphotypes offered equal protection. To explain this paradox we introduce a 'concept of modality' in multipredator regimes. Our concept categorizes two-predator-prey systems into three major groups (functionally equivalent, functionally inverse and functionally diverse). Furthermore, the concept includes optimal responses and costs of maladaptions of prey phenotypes in environments where both predators co-occur or where they alternate. Conclusion: With D. barbata, we introduce a new multipredator-prey system with a wide array of morphological inducible defenses. Based on a 'concept of modality', we give possible explanations how evolution can favor specialized defenses over a general defense. Additionally, our concept not only helps to classify different multipredator-systems, but also stresses the significance of costs of phenotype-environment mismatching in addition to classic 'costs of plasticity'. With that, we suggest that 'modality' matters as an important factor in understanding and explaining the evolution of inducible defenses. © 2013 Herzog and Laforsch; licensee BioMed Central Ltd. Source


Klein L.,Ludwig Maximilians University of Munich
Cell | Year: 2015

A specialized subset of epithelial cells in the thymus "promiscuously" transcribes thousands of peripheral genes to ensure that developing T cells can test their antigen receptors for dangerous autoreactivity. New findings by Takaba et al. indicate that the transcription factor Fezf2 acts independently of Aire in thymic epithelial cells to generate "genetic noise" for immunological tolerance. © 2015 Elsevier Inc. Source


Heine J.,University of Marburg | Schmedt Auf Der Gunne J.,Ludwig Maximilians University of Munich | Dehnen S.,University of Marburg
Journal of the American Chemical Society | Year: 2011

Self-assembly of ZnCl2 and the ligand 2,4,6-tris(4-pyridyl) pyridine (pytpy) in solution yields [(ZnCl2)12(pytpy) 8]n·xCHCl3, a polycatenane consisting of a strand of mechanically interlocking icosahedral cages with an inner volume of more than 2700 Å3. This can be used to encapsulate guest molecules of appropriate size and polarity, forming a precisely defined three-dimensional array of solvent nanodroplets within the crystalline framework. The dynamic composition of these droplets was studied using quantitative solid-state NMR spectroscopy. © 2011 American Chemical Society. Source


Reissig G.,Ludwig Maximilians University of Munich
IEEE Transactions on Automatic Control | Year: 2011

Sufficiently accurate finite state models, also called symbolic models or discrete abstractions, allow one to apply fully automated methods, originally developed for purely discrete systems, to formally reason about continuous and hybrid systems and to design finite state controllers that provably enforce predefined specifications. We present a novel algorithm to compute such finite state models for nonlinear discrete-time and sampled systems which depends on quantizing the state space using polyhedral cells, embedding these cells into suitable supersets whose attainable sets are convex, and over-approximating attainable sets by intersections of supporting half-spaces. We prove a novel recursive description of these half-spaces and propose an iterative procedure to compute them efficiently. We also provide new sufficient conditions for the convexity of attainable sets which imply the existence of the aforementioned embeddings of quantizer cells. Our method yields highly accurate abstractions and applies to nonlinear systems under mild assumptions, which reduce to sufficient smoothness in the case of sampled systems. Its practicability in the design of discrete controllers for nonlinear continuous plants under state and control constraints is demonstrated by an example. © 2011 IEEE. Source


Schonermarck U.,Ludwig Maximilians University of Munich | Gross W.L.,University of Lubeck | De Groot K.,Klinikum Offenbach GmbH
Nature Reviews Nephrology | Year: 2014

Antineutrophil cytoplasmic autoantibody (ANCA)-associated diseases are small-vessel vasculitides, encompassing granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Once considered life-threatening diseases, the introduction of stage-adapted immunosuppressive therapy and medications with decreased toxicity has improved patients' survival. Treatment is biphasic, consisting of induction of remission (3-6 months) for rapid control of disease activity and maintenance of remission (at least 18 months) to prevent disease relapse using therapeutic alternatives that have reduced toxicity. This Review summarizes current treatment strategies for these diseases, with a special focus on long-term follow-up data from key randomized controlled trials and new developments in remission induction and maintenance therapy. Current treatment strategies have substantial short-term and long-term adverse effects, and relapses are frequent; thus, less-toxic and more-effective approaches are needed. Moreover, the optimal intensity and duration of maintenance therapy remains under debate. Clinical trials have traditionally considered ANCA-associated vasculitides as a single disease entity. However, future studies must stratify participants according to their specific disease, clinical features (different types of organ manifestation, PR3-ANCA or MPO-ANCA positivity) and disease severity. © 2014 Macmillan Publishers Limited. Source


Parhofer K.G.,Ludwig Maximilians University of Munich
Atherosclerosis Supplements | Year: 2015

The relationship between atherosclerosis and HDL is more complex than between LDL and atherosclerosis. Low HDL-cholesterol is associated with atherosclerotic disease not in a causal way but because low HDL-cholesterol reflects an increased concentration of triglyceride-rich lipoproteins. At the same time the functionality of the HDL system plays an important role in atherosclerosis prevention (for example by mediating reverse cholesterol transport). However, these two observations are not directly linked to each other. Therefore therapeutic strategies must either aim at decreasing the concentration of triglyceride-rich lipoproteins (and thereby increase HDL-cholesterol concentration) or at improving HDL function (which may or may not affect HDL-cholesterol concentration). Simply increasing HDL-cholesterol concentration without improving function or decreasing triglyceride-rich lipoproteins will not be beneficial with respect to atherosclerosis prevention. © 2015 Elsevier Ireland Ltd. Source


Breuer C.,Ludwig Maximilians University of Munich
Health Economics (United Kingdom) | Year: 2015

This paper addresses the influence of economic activity on suicide mortality in Europe. To this end, it employs a new panel data set of 275 regions in 29 countries over the period 1999-2010. The results suggest that unemployment does have a significantly positive influence on suicides. In line with economic theory, this influence varies among gender and age groups. Men of working age are particularly sensitive, while old-age suicide mortality (older than 65 years old) hardly responds to unemployment. Moreover, real economic growth negatively affects the suicide rates of working-age men. The results withstand several robustness checks, such as sample variations, and after controlling for serial and spatial autocorrelation. Copyright © 2014 John Wiley & Sons, Ltd. Source


Lotsch B.V.,Max Planck Institute for Solid State Research | Lotsch B.V.,Ludwig Maximilians University of Munich
Angewandte Chemie - International Edition | Year: 2014

All in one: Perovskites are currently undergoing a renaissance as "allrounder" materials for solar cells. For a special type of methylammonium lead halide perovskites, a unique combination of properties, including high charge-carrier mobilities, exciton lifetimes, and panchromatic absorption, was observed, which renders this class of hybrid perovskites one of the most promising absorber and ambipolar charge-transport materials for all-solid-state solar cells. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Rimkute D.,Ludwig Maximilians University of Munich
Politics and Governance | Year: 2015

Despite the growing importance of EU regulatory agencies in European decision-making, academic literature is missing a systematic explanation of how regulatory agencies actually contend with their core tasks of providing scientific advice to EU institutions. The article contributes to the theoretical explanation of when and under what conditions different uses of scientific expertise prevail. In particular, it focuses on theoretical explanations leading to strategic substantiating use of expertise followed by an empirical analysis of single case research. Substantiating expertise use refers to those practices in which an organisation seeks to promote and justify its predetermined preferences, which are based on certain values, political or economic interests. Empirical findings are discussed in the light of the theoretical expectations derived by streamlining and combining the main arguments of classical organisational and institutional theories and recent academic research. Process-tracing techniques are applied to investigate the process by which an EU regulation restricting the use of neonicotinoid pesticides (European Commission, 2013) was developed. The empirical analysis combines a variety of data sources including official documents, press releases, scientific outputs, and semi-structured interviews with the academic and industry experts involved in the process. The study finds that the interaction between high external pressure and high internal capacity leads to the strategic substantiating use of expertise, in which scientific evidence is used to promote the inclinations of actors upon which the agency depends most. © 2015 by the authors; licensee Cogitatio (Lisbon, Portugal). Source


Lust D.,Ludwig Maximilians University of Munich | Lust D.,Max Planck Institute for Physics
Journal of High Energy Physics | Year: 2010

We provide some evidence that closed string coordinates will become noncommutative turning on geometrical fluxes and/or H-field flux background in closed string compactifications. This is in analogy to open string non-commutativity on the world volume of D-branes with B- and F-field background. The class of 3-dimensional backgrounds we are studying are twisted tori (fibrations of a 2-torus over a circle) and the their T-dual H-field, 3-form flux backgrounds (T-folds). The spatial non-commutativity arises due to the non-trivial monodromies of the toroidal Kähler resp. complex structure moduli fields, when going around the closed string along the circle direction. In addition we study closed string non-commutativity in the context of doubled geometry, where we argue that in general a non-commutative closed string background is T-dual to a commutative closed string background and vice versa. We also discuss the corresponding spatial uncertainty relations. Finally, in analogy to open string boundary conditions, we also argue that closed string momentum and winding modes define in some sense D-branes in closed string doubled geometry. © 2010 SISSA. Source


Curio G.,Ludwig Maximilians University of Munich
Journal of High Energy Physics | Year: 2010

For supersymmetric heterotic string compactifications on a Calabi-Yau threefold X endowed with a vector bundle V the world-sheet superpotential W is a sum of contributions from isolated rational curves C in X; the individual contribution is given by an exponential in the Kähler class of the curve times a prefactor given essentially by the Pfaffian which depends on the moduli of V and the complex structure moduli of X. Solutions of DW = 0 (or even of DW = W = 0) can arise either by nontrivial cancellations between the individual terms in the summation over all contributing curves or because each of these terms is zero already individually. Concerning the latter case conditions on the moduli making a single Pfaffian vanish (for special moduli values) have been investigated. However, even if corresponding moduli-fulfilling these constraints-for the individual contribution of one curve are known it is not at all clear whether one choice of moduli exists which fulfills the corresponding constraints for all contributing curves simultaneously. Clearly this will in general happen only if the conditions on the 'individual zeroes' had already a conceptual origin which allows them to fit together consistently. We show that this happens for a class of cases. In the special case of spectral cover bundles we show that a relevant solution set has an interesting location in moduli space and is related to transitions which change the generation number. © 2010 SISSA. Source


Linn J.,Ludwig Maximilians University of Munich
Current Opinion in Neurology | Year: 2014

PURPOSE OF REVIEW: This study summarizes recent advances in neuroimaging of therapy-related brain tissue abnormalities. RECENT FINDINGS: Pseudoprogression constitutes a typical posttherapeutic phenomenon in patients with glioblastoma treated with radiochemotherapy with temozolomide. Advanced MRI techniques, such as diffusion MRI and perfusion MRI, can be helpful to distinguish it from true tumor progression. In clinical trials on amyloid-modifying therapies in Alzheimer's disease patients, previously unknown, characteristic nonhemorrhagic and hemorrhagic amyloid-related imaging abnormalities have been observed. Awareness of this phenomenon is essential for therapy monitoring. Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome can both occur as a complication of a variety of systemic drug therapies and present with a wide spectrum of clinical and imaging findings. The pathomechanisms underlying these different therapy-related brain tissue changes are only poorly understood. SUMMARY: Neuroimaging, including advanced MRI techniques, plays a key role in the identification and monitoring of therapy-associated brain tissue abnormalities. However, future imaging studies should focus on the pathomechanism underlying these phenomena.© 2014 Wolters Kluwer Health. Source


Renner S.S.,Ludwig Maximilians University of Munich
American Journal of Botany | Year: 2014

Premise of the study: Separating sexual function between different individuals carries risks, especially for sedentary organisms. Nevertheless, many land plants have unisexual gametophytes or sporophytes. This study brings together data and theoretical insights from research over the past 20 yr on the occurrence and frequency of plant sexual systems, focusing on the flowering plants.Methods: A list of genera with dioecious species, along with other information, is made available (http://www.umsl. edu/∼renners/). Frequencies of other sexual systems are tabulated, and data on the genetic regulation, ecological context, and theoretical benefits of dioecy reviewed.Key results: There are 15 600 dioecious angiosperms in 987 genera and 175 families, or 5-6% of the total species (7% of genera, 43% of families), with somewhere between 871 to 5000 independent origins of dioecy. Some 43% of all dioecious angiosperms are in just 34 entirely dioecious clades, arguing against a consistent negative influence of dioecy on diversification. About 31.6% of the dioecious species are wind-pollinated, compared with 5.5-6.4% of nondioecious angiosperms. Also, 1.4% of all angiosperm genera contain dioecious and monoecious species, while 0.4% contain dioecious and gynodioecious species. All remaining angiosperm sexual systems are rare. Chromosomal sex determination is known from 40 species; environmentally modulated sex allocation is common. Few phylogenetic studies have focused on the evolution of dioecy.Conclusions: The current focus is on the genetic mechanisms underlying unisexual flowers and individuals. Mixed strategies of sexual and vegetative dispersal, together with plants’ sedentary life style, may often favor polygamous systems in which sexually inconstant individuals can persist. Nevertheless, there are huge entirely dioecious clades of tropical woody plants. © 2014 Botanical Society of America. Source


Messmer E.M.,Ludwig Maximilians University of Munich
Klinische Monatsblatter fur Augenheilkunde | Year: 2012

Acute bacterial conjunctivitis is a common health-care issue for the general practitioner and the ophthalmologist. Signs and symptoms usually allow a correct diagnosis without conjunctival swab. Primary microbiological investigations are recommended in newborns, immunocompromised patients and cases of hyperacute conjunctivitis. Of concern are methicillin-resistant Staphylococcus aureus strains which have been isolated with increasing frequency in the last few years. Studies have demonstrated the faster clinical and microbiological cure of acute bacterial conjunctivitis with topical antibiotics. However, the development of resistance of the typical germs to all of the antibiotic groups is alarming and should influence therapeutic behaviour. Fluoroquinolones show good activity in the treatment of acute bacterial conjunctivitis but should be saved for severe infections due to its broad spectrum of activity. Antibiotics such as gentamycin, tobramycin, and azithromycin should be preferred. Considering the high spontaneous healing rate of acute conjunctivitis, delayed topical antibiotics in case of persistence after 3 - 4 days, or treatment without antibiotics using artificial tears and eye bathings may be considered. Additive anti-inflammatory drugs are generally not recommended. Chronic-recurrent follicular conjunctivitis necessitates testing for Chlamydia, and in case of a positive result, systemic antibiotic treatment of patient and sexual partner. © Georg Thieme Verlag KG Stuttgart · New York. Source


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

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


Winograd-Katz S.E.,Weizmann Institute of Science | Fassler R.,Max Planck Institute of Biochemistry | Geiger B.,Weizmann Institute of Science | Legate K.R.,Max Planck Institute of Biochemistry | Legate K.R.,Ludwig Maximilians University of Munich
Nature Reviews Molecular Cell Biology | Year: 2014

The adhesive interactions of cells with their environment through the integrin family of transmembrane receptors have key roles in regulating multiple aspects of cellular physiology, including cell proliferation, viability, differentiation and migration. Consequently, failure to establish functional cell adhesions, and thus the assembly of associated cytoplasmic scaffolding and signalling networks, can have severe pathological effects. The roles of specific constituents of integrin-mediated adhesions, which are collectively known as the 'integrin adhesome', in diverse pathological states are becoming clear. Indeed, the prominence of mutations in specific adhesome molecules in various human diseases is now appreciated, and experimental as well as in silico approaches provide insights into the molecular mechanisms underlying these pathological conditions. © 2014 Macmillan Publishers Limited. All rights reserved. Source


Hohlfeld R.,Ludwig Maximilians University of Munich
Multiple Sclerosis | Year: 2010

This article is based on the ECTRIMS lecture given at the 25th ECTRIMS meeting which was held in Dusseldorf, Germany, from 9 to 12 September 2009. Five challenges have been identified: (1) safeguarding the principles of medical ethics; (2) optimizing the risk/benefit ratio; (3) bridging the gap between multiple sclerosis and experimental autoimmune encephalitis; (4) promoting neuroprotection and repair; and (5) tailoring multiple sclerosis therapy to the individual patient. Each of these challenges will be discussed and placed in the context of current research into the pathogenesis and treatment of multiple sclerosis. Source


Potschka H.,Ludwig Maximilians University of Munich
Pharmacology and Therapeutics | Year: 2010

Blood-brain barrier efflux transporters limit the brain penetration and efficacy of various central nervous system drugs. In several CNS diseases, therapy- or pathophysiology-associated transcriptional activation of efflux transporters further strengthens the barrier function. Targeting the regulatory pathways that drive efflux transporter expression in different diseases represents an intriguing approach for prevention of these events thereby promoting delivery to the brain and enhancing or restoring drug efficacy. In particular, the approach holds the promise to preserve basal transporter expression and activity, which is of specific relevance in view of the protective function of efflux transport. The elucidation of the signaling cascades involved in transporter regulation is a major presupposition for the development of preventive strategies. Orphan nuclear receptors as well as the Wnt/β-catenin signaling pathway have been implicated in drug-induced changes in transporter expression. Targeting these xenobiotic sensors is therefore discussed as a means to optimize brain delivery and therapeutic outcome. Relevant progress has also been made with the identification of key signaling events that drive P-glycoprotein expression in response to pathophysiological mechanisms. In the epileptic brain, complex signaling events involving cyclooxygenase-2 activity trigger P-glycoprotein expression in response to glutamate release and activation of endothelial NMDA receptors. Moreover, reactive oxygen species and inflammatory cytokines have been identified as regulatory factors which might affect P-glycoprotein in several CNS diseases. Recent data substantiated several interesting targets in the respective signaling cascades thereby rendering a basis for the ongoing development of innovative approaches to optimize central nervous system drug brain penetration and efficacy. © 2009 Elsevier Inc. All rights reserved. Source


Posavec M.,Institute for Predictive and Personalized Medicine of Cancer IMPPC | Timinszky G.,Ludwig Maximilians University of Munich | Buschbeck M.,Institute for Predictive and Personalized Medicine of Cancer IMPPC
Cellular and Molecular Life Sciences | Year: 2013

How metabolism and epigenetics are molecularly linked and regulate each other is poorly understood. In this review, we will discuss the role of direct metabolite-binding to chromatin components and modifiers as a possible regulatory mechanism. We will focus on globular macro domains, which are evolutionarily highly conserved protein folds that can recognize NAD +-derived metabolites. Macro domains are found in histone variants, histone modifiers, and a chromatin remodeler among other proteins. Here we summarize the macro domain-containing chromatin proteins and the enzymes that generate relevant metabolites. Focusing on the histone variant macroH2A, we further discuss possible implications of metabolite binding for chromatin function. © 2013 Springer Basel. Source


Muller N.,Ludwig Maximilians University of Munich
NeuroImmunoModulation | Year: 2014

Increased proinflammatory markers like cytokines have been described in the blood and cerebrospinal fluid of patients suffering from schizophrenia. Animal models have shown that a hit in early life to the immune system might trigger a lifelong increased immune reactivity. Many epidemiological and clinical studies show the role of various infectious agents as risk factors for schizophrenia with overlap to other psychoses. The first large-scale epidemiological study in psychiatry from Denmark clearly demonstrates severe infections and autoimmune disorders during lifetime to be risk factors for schizophrenia. Genetic studies have shown the strongest signal for schizophrenia on chromosome 6p22.1, in a region related to the major histocompatibility complex and other immune functions. The vulnerability-stress-inflammation model is important as stress may increase proinflammatory cytokines and even contribute to a lasting proinflammatory state. The immune system itself is considered an important further piece in the puzzle, as in autoimmune disorders in general, which are always linked to three factors: genes, the environment and the immune system. Alterations of dopaminergic, serotonergic, noradrenergic and glutamatergic neurotransmission have been shown with low-level neuroinflammation and may directly be involved in the generation of schizophrenic symptoms. Loss of central nervous system volume and microglial activation has been demonstrated in schizophrenia in neuroimaging studies, which supports the assumption of a low-level neuroinflammatory process. Further support comes from the therapeutic benefit of anti-inflammatory medications in specific studies and the anti-inflammatory and immunomodulatory intrinsic effects of antipsychotics. © 2014 S. Karger AG, Basel. Source


Jovanovic B.,Ludwig Maximilians University of Munich
Environmental Toxicology and Chemistry | Year: 2015

Titanium dioxide nanoparticles are photoactive and produce reactive oxygen species under natural sunlight. Reactive oxygen species can be detrimental to many organisms, causing oxidative damage, cell injury, and death. Most studies investigating TiO2 nanoparticle toxicity did not consider photoactivation and performed tests either in dark conditions or under artificial lighting that did not simulate natural irradiation. The present study summarizes the literature and derives a phototoxicity ratio between the results of nano-titanium dioxide (nano-TiO2) experiments conducted in the absence of sunlight and those conducted under solar or simulated solar radiation (SSR) for aquatic species. Therefore, the phototoxicity ratio can be used to correct endpoints of the toxicity tests with nano-TiO2 that were performed in absence of sunlight. Such corrections also may be important for regulators and risk assessors when reviewing previously published data. A significant difference was observed between the phototoxicity ratios of 2 distinct groups: aquatic species belonging to order Cladocera, and all other aquatic species. Order Cladocera appeared very sensitive and prone to nano-TiO2 phototoxicity. On average nano-TiO2 was 20 times more toxic to non-Cladocera and 1867 times more toxic to Cladocera (median values 3.3 and 24.7, respectively) after illumination. Both median value and 75% quartile of the phototoxicity ratio are chosen as the most practical values for the correction of endpoints of nano-TiO2 toxicity tests that were performed in dark conditions, or in the absence of sunlight. © 2015 The Author. Source


Erdos L.,Ludwig Maximilians University of Munich | Knowles A.,Harvard University
Communications in Mathematical Physics | Year: 2011

We consider Hermitian and symmetric random band matrices H in d ≥ 1 dimensions. The matrix elements H xy, indexed by, are independent, uniformly distributed random variables if {pipe}x-y{pipe} is less than the band width W, and zero otherwise. We prove that the time evolution of a quantum particle subject to the Hamiltonian H is diffusive on time scales. We also show that the localization length of the eigenvectors of H is larger than a factor W d/6 times the band width. All results are uniform in the size of the matrix. © 2011 Springer-Verlag. Source


Gauglitz G.G.,Ludwig Maximilians University of Munich | Jeschke M.G.,University of Toronto
Molecular Pharmaceutics | Year: 2011

In current medical practice, wound therapy remains a clinical challenge and much effort has been focused on the development of novel therapeutic approaches for wound treatment. Gene therapy, initially developed for treatment of congenital defects, represents a promising option for enhancing wound repair. In order to accelerate wound closure, genes encoding for growth factors or cytokines have shown the most potential. The majority of gene delivery systems are based on viral transfection, naked DNA application, high pressure injection, and liposomal vectors. Besides advances stemming from breakthroughs in recombinant growth factors and bioengineered skin, there has been a significant increase in the understanding of stem cell biology in the field of cutaneous wound healing. A variety of sources, such as bone marrow, umbilical cord blood, adipose tissue and skin/hair follicles, have been utilized to isolate stem cells and to modulate the healing response of acute and chronic wounds. Recent data have demonstrated the feasibility of autologous adult stem cell therapy in cutaneous repair and regeneration. Very recently, stem cell based skin engineering in conjunction with gene recombination, in which the stem cells act as both the seed cells and the vehicle for gene delivery to the wound site, represents the most attractive field for generating a regenerative strategy for wound therapy. The aim of this article is to discuss the use and the potential of these novel technologies in order to improve wound healing capacities. © 2011 American Chemical Society. Source


Weber C.,Ludwig Maximilians University of Munich | Weber C.,Maastricht University | Noels H.,RWTH Aachen
Nature Medicine | Year: 2011

Coronary artery disease (CAD) arising from atherosclerosis is a leading cause of death and morbidity worldwide. The underlying pathogenesis involves an imbalanced lipid metabolism and a maladaptive immune response entailing a chronic inflammation of the arterial wall. The disturbed equilibrium of lipid accumulation, immune responses and their clearance is shaped by leukocyte trafficking and homeostasis governed by chemokines and their receptors. New pro-and anti-inflammatory pathways linking lipid and inflammation biology have been discovered, and genetic profiling studies have unveiled variations involved in human CAD. The growing understanding of the inflammatory processes and mediators has uncovered an intriguing diversity of targetable mechanisms that can be exploited to complement lipid-lowering therapies. Here we aim to systematically survey recently identified molecular mechanisms, translational developments and clinical strategies for targeting lipid-related inflammation in atherosclerosis and CAD. © 2011 Nature America, Inc. All rights reserved. Source


Von Schacky C.,Ludwig Maximilians University of Munich
Prostaglandins and Other Lipid Mediators | Year: 2011

The Omega-3 Index has been defined as eicosapentaenoic plus docosahexaenoic acids in erythrocytes. Integral part of the definition is a standardized analytical procedure, which conforms to the standards of Clinical Chemistry. This resulted in more than 90 collaborative research projects, concluded and ongoing, and 64 publications so far. The Omega-3 Index is emerging as a risk factor for fatal and non-fatal cardiovascular events. This standardized analysis of fatty acid patterns adds incremental information to standard risk factor algorithms, and it correctly reclassifies persons from intermediate to high or low risk. Circumstantial evidence indicates that determining the Omega-3 Index has a therapeutic consequence. Thus, the Omega-3 Index fulfils important criteria for novel biomarkers, set forth by the American Heart Association and others, and compares well to other novel biomarkers. Future results will add precision to the value of the Omega-3 Index in cardiology, and probably expand its application to other areas, like psychiatry and pregnancy. © 2011 Elsevier Inc. All rights reserved. Source


Archavlis E.,Goethe University Frankfurt | Carvi Y Nievas M.,Ludwig Maximilians University of Munich
European Spine Journal | Year: 2013

Purpose: The object of this study was to compare minimally invasive surgery (MIS) with open surgery in a severely affected subgroup of degenerative spondylolisthetic patients with severe stenosis (SDS) and high-grade facet osteoarthritis (FJO). Methods: From January 2009 to February 2010, 49 patients with severe SDS and high-grade FJO were treated using either MIS or open TLIF. Intraoperative and diagnostic data, including perioperative complications and length of hospital stay (LOS), were collected, using retrospective chart review. Surgical short- and long-term outcomes were assessed according to the Oswestry disability index (ODI) and visual analog scale (VAS) for back and leg pain. Results: Comparing MIS and open surgery, the MIS group had lesser blood loss, significantly lesser need for transfusion (p = 0.02), more rapid improvement of postoperative back pain in the first 6 weeks of follow-up and a shorter LOS. On the other hand, we experienced in the MIS group a longer operative time. The distribution on the postoperative ODI (p = 0.841), VAS leg (p = 0.943) and back pain (p = 0.735) scores after a mean follow-up of 2 years were similar. The overall proportion of complications showed no significant difference between the groups (29 % in the MIS group vs. 28 % in the open group, p = 0.999). Conclusion: Minimally invasive surgery for severe SDS leads to adequate and safe decompression of lumbar stenosis and results in a faster recovery of symptoms and disability in the early postoperative period. © 2013 Springer-Verlag Berlin Heidelberg. Source


Weichselbaum A.,Ludwig Maximilians University of Munich
Annals of Physics | Year: 2012

A general framework for non-abelian symmetries is presented for matrix-product and tensor-network states in the presence of well-defined orthonormal local as well as effective basis sets. The two crucial ingredients, the Clebsch-Gordan algebra for multiplet spaces as well as the Wigner-Eckart theorem for operators, are accounted for in a natural, well-organized, and computationally straightforward way. The unifying tensor-representation for quantum symmetry spaces, dubbed QSpace, is particularly suitable to deal with standard renormalization group algorithms such as the numerical renormalization group (NRG), the density matrix renormalization group (DMRG), or also more general tensor networks such as the multi-scale entanglement renormalization ansatz (MERA). In this paper, the focus is on the application of the non-abelian framework within the NRG. A detailed analysis is presented for a fully screened spin- 3/2 three-channel Anderson impurity model in the presence of conservation of total spin, particle-hole symmetry, and SU(3) channel symmetry. The same system is analyzed using several alternative symmetry scenarios based on combinations of U(1)charge, SU(2)spin, SU(2)charge, SU(3)channel, as well as the enveloping symplectic Sp(6) symmetry. These are compared in detail, including their respective dramatic gain in numerical efficiency. In the Appendix, finally, an extensive introduction to non-abelian symmetries is given for practical applications, together with simple self-contained numerical procedures to obtain Clebsch-Gordan coefficients and irreducible operators sets. The resulting QSpace tensors can deal with any set of abelian symmetries together with arbitrary non-abelian symmetries with compact, i.e. finite-dimensional, semi-simple Lie algebras. © 2012 Elsevier Inc. Source


Sperandio M.,Ludwig Maximilians University of Munich
Annals of the New York Academy of Sciences | Year: 2012

The ability of leukocytes to navigate through the different body compartments is an essential component for functioning immune defense and surveillance systems. In order to exit the blood circulation, leukocytes follow distinct recruitment steps, including capture of free-flowing leukocytes to, and rolling along, the vessel wall; firm leukocyte arrest on the endothelial lining; and postarrest modifications (spreading and crawling), which prepare the leukocyte for transmigration through the vascular wall. Post-translational glycosylation (including sialylation) has been known for many years to be functionally relevant for selectin ligands and, hence, selectin-mediated capture and rolling. Recently, sialylation by the α2-3 sialyltransferase ST3Gal-IV was identified to significantly influence chemokine-triggered firm leukocyte arrest, expanding the role of α2-3 sialylation from leukocyte rolling to subsequent chemokine-triggered leukocyte arrest. These findings make ST3Gal-IV an interesting drug target for modulating leukocyte trafficking in human disorders, including autoimmune diseases and cancer. © 2012 New York Academy of Sciences. Source


Korber P.,Ludwig Maximilians University of Munich
Biochemical Society Transactions | Year: 2012

Genome-wide nucleosome maps revealed well-positioned nucleosomes as a major theme in eukaryotic genome organization. Promoter regions often show a conserved pattern with an NDR (nucleosome-depleted region) from which regular nucleosomal arrays emanate. Three mechanistic contributions to such NDRarray-organization and nucleosome positioning in general are discussed: DNA sequence, DNA binders and DNA-templated processes. Especially, intrinsic biophysics of DNA sequence preferences for nucleosome formation was prominently suggested to explain the majority of nucleosome positions ('genomic code for nucleosome positioning'). Nonetheless, non-histone factors that bind DNA with high or low specificity, such as transcription factors or remodelling enzymes respectively and processes such as replication, transcription and the so-called 'statistical positioning' may be involved too. Recently, these models were tested for yeast by genome-wide reconstitution. DNA sequence preferences as probed by SGD (salt gradient dialysis) reconstitution generated many NDRs, but only few individual nucleosomes, at their proper positions, and no arrays. Addition of a yeast extract and ATP led to dramatically more in vivo-like nucleosome positioning, including regular arrays for the first time. This improvement depended essentially on the extract and ATP but not on transcription or replication. Nucleosome occupancy and close spacing were maintained around promoters, even at lower histone density, arguing for active packing of nucleosomes against the 5′ ends of genes rather than statistical positioning. A first extract fractionation identified a direct, specific, necessary, but not sufficient role for the RSC (remodels the structure of chromatin) remodelling enzyme. Collectively, nucleosome positioning in yeast is actively determined by factors beyond intrinsic biophysics, and in steadystate rather than at equilibrium. © The Authors Journal compilation © 2012 Biochemical Society. Source


Katada S.,University of California at Irvine | Imhof A.,University of California at Irvine | Imhof A.,Ludwig Maximilians University of Munich | Sassone-Corsi P.,University of California at Irvine
Cell | Year: 2012

Chromatin-modifying enzymes have long been proposed to be the authors of an epigenetic language, but the origin and meaning of the messages they write in chromatin are still mysterious. Recent studies suggesting that the effects of diet can be passed on epigenetically to offspring add weight to the idea that histones act as metabolic sensors, converting changes in metabolism into stable patterns of gene expression. The challenge will now be to understand how localized fluctuations in levels of metabolites control chromatin modifiers in space and time, translating a dynamic metabolic state into a histone map. © 2012 Elsevier Inc. Source


Myint A.M.,Ludwig Maximilians University of Munich
FEBS Journal | Year: 2012

Psychiatric disorders are documented to be associated with a mild pro-inflammatory state. Pro-inflammatory mediators could activate the tryptophan breakdown and kynurenine pathway with a shift toward the neurotoxic arm where excitotoxic N-methyl-d-aspartate receptor agonist quinolinic acid is formed. An unbalanced metabolism in terms of neuroprotective and neurotoxic effects, such as reduced kynurenic acid to kynurenine ratio, has been demonstrated in the major psychiatric disorders such as unipolar depression, bipolar manic-depressive disorder and schizophrenia, and in drug-induced neuropsychiatric side effects such as interferon-α treated patients. The changes in serum or plasma are shown to be associated with central changes such as in the cerebrospinal fluid and certain brain areas. While currently available antidepressants and mood stabilizers could not efficiently improve these neurochemical changes within the same period that could induce clinical improvement, some antipsychotic treatments could reverse certain metabolic imbalances. Some of these changes were tested also in animal models. In this review the role of this unbalanced kynurenine metabolism through interactions with other neurochemicals is discussed as a major contributing pathophysiological mechanism in psychiatric disorders. Moreover, the biomarker role of kynurenine metabolites and future therapeutic opportunities are also discussed. © 2012 The Author Journal compilation © 2012 FEBS. Source


Andriot D.,Ludwig Maximilians University of Munich
Nuclear Physics B | Year: 2012

The (abelian bosonic) heterotic string effective action, equations of motion and Bianchi identity at order α' in ten dimensions, are shown to be equivalent to a higher dimensional action, its derived equations of motion and Bianchi identity. The two actions are the same up to the gauge fields: the latter are absorbed in the higher dimensional fields and geometry. This construction is inspired by heterotic T-duality, which becomes natural in this higher dimensional theory.We also prove the equivalence of the heterotic string supersymmetry conditions with higher dimensional geometric conditions. Finally, some known Kähler and non-Kähler heterotic solutions are shown to be trivially related from this higher dimensional perspective, via a simple exchange of directions. This exchange can be encoded in a heterotic T-duality, and it may also lead to new solutions. © 2011 Elsevier B.V. Source


Scrinzi A.,Ludwig Maximilians University of Munich
New Journal of Physics | Year: 2012

The time-dependent surface flux (t-SURFF) method is extended to single and double ionization of two-electron systems. Fully differential double emission spectra by strong pulses at extreme UV and infrared wavelengths are calculated using simulation volumes that only accommodate the effective range of the atomic binding potential and the quiver radius of free electrons in the external field. For a model system, we found a pronounced dependence of shakeup and non-sequential double ionization on the phase and duration of the laser pulse. The extension to fully three-dimensional calculations is discussed. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft. Source


Schneider M.R.,Ludwig Maximilians University of Munich
Genesis | Year: 2012

A number of features contributed to establishing the mouse as the favorite model organism for skin research: the genetic and pathophysiological similarities to humans, the small size and relatively short reproductive period, meaning low maintenance costs, and the availability of sophisticated tools for manipulating the genome, gametes, and embryos. While initial studies depended on strains displaying skin abnormalities due to spontaneous genetic mutations, the availability of the transgenic and knockout technologies and their astonishing perfection during the last decades allowed the development of mouse lines permitting any imaginable genetic modification including gene inactivation, substitution, modification, or overexpression. While these technologies have already contributed to the functional analysis of several genes and processes related to skin research, continued progress requires understanding, awareness, and access to these mouse resources. This review will identify the strategies currently employed for the genetic manipulation of mice in skin research, and outline current resources and their limitations. © 2012 Wiley Periodicals, Inc. Source


von Schacky C.,Ludwig Maximilians University of Munich
Frontiers in Physiology | Year: 2012

This review focuses on developments after 2008, when the topic was last reviewed by the author. Pertinent publications were found by medline searches and in the author's personal data base. Prevention of atrial fibrillation (AF) was investigated in a number of trials, sparked by one positive report on the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), considerations of upstream therapy, data from electrophysiologic laboratories and animal experiments. If EPA + DHA prevent postoperative AF, the effect is probably smaller than initially expected. The same is probably true for maintenance of sinus rhythm after cardioversion and for new-onset AF. Larger trials are currently ongoing. Prevention of ventricular arrhythmias was studied in carriers of an implanted cardioverterdefibrillator, with no clear results. This might have been due to a broad definition of the primary endpoint, including any ventricular arrhythmia and any action of the device. Epidemiologic studies support the contention that high levels of EPA + DHA prevent sudden cardiac death (SCD). However, since SCD is a rare occurrence, it is difficult to conduct an adequately powered trial. In patients with congestive heart failure, EPA + DHA reduced total mortality and rehospitalizations, but not SCD or presumed arrhythmic death. Of three trials in patients after a myocardial infarction, two were inadequately powered, and in one, the dose might have been too low.Taken together, while epidemiologic studies support an inverse relation between EPA + DHA and occurrence of SCD or arrhythmic death, demonstrating this effect in intervention trials remained elusive so far. A pro-arrhythmic effect of EPA + DHA has not been seen in intervention studies, and results of epidemiologic and animal studies also rather argue against such an effect. A different, and probably more productive, perspective is provided by a standardized analytical assessment of a person's status in EPA + DHA by use of the omega-3 index, EPA + DHA in red cell fatty acids. In populations with a high omega-3 index, SCD is rare. Intervention trials can become more effective by including a low omega-3 index into the inclusion criteria, thus creating a study population more likely to demonstrate an effect of EPA + DHA. This is especially relevant in case of rare endpoints, like new-onset AF or SCD. © 2012 von Schacky. Source


Hermeking H.,Ludwig Maximilians University of Munich
Nature Reviews Cancer | Year: 2012

In recent years, microRNAs (miRNAs) have been identified as mediators of tumour suppression and stress responses exerted by the p53 tumour suppressor. p53-regulated miRNAs contribute to tumour suppression by controlling the expression of central components of multiple processes, including cell cycle progression, epithelialg-mesenchymal transition, stemness, metabolism, cell survival and angiogenesis. The expression and activity of p53 itself is also under the control of miRNAs. Finally, genetic and epigenetic alterations identified in the p53g-miRNA network indicate that these pathways are important for the initiation and progression of tumours. In the future, knowledge about the p53g-miRNA network may be able to be exploited for diagnostic and therapeutic approaches in cancer prevention and treatment. © 2012 Macmillan Publishers Limited. All rights reserved. Source


Georgescauld F.,Max Planck Institute of Biochemistry | Popova K.,Max Planck Institute of Biochemistry | Gupta A.J.,Max Planck Institute of Biochemistry | Bracher A.,Max Planck Institute of Biochemistry | And 4 more authors.
Cell | Year: 2014

The GroEL/ES chaperonin system functions as a protein folding cage. Many obligate substrates of GroEL share the (βα)8 TIM-barrel fold, but how the chaperonin promotes folding of these proteins is not known. Here, we analyzed the folding of DapA at peptide resolution using hydrogen/deuterium exchange and mass spectrometry. During spontaneous folding, all elements of the DapA TIM barrel acquire structure simultaneously in a process associated with a long search time. In contrast, GroEL/ES accelerates folding more than 30-fold by catalyzing segmental structure formation in the TIM barrel. Segmental structure formation is also observed during the fast spontaneous folding of a structural homolog of DapA from a bacterium that lacks GroEL/ES. Thus, chaperonin independence correlates with folding properties otherwise enforced by protein confinement in the GroEL/ES cage. We suggest that folding catalysis by GroEL/ES is required by a set of proteins to reach native state at a biologically relevant timescale, avoiding aggregation or degradation. © 2014 Elsevier Inc. Source


Sourbron S.,Ludwig Maximilians University of Munich
Zeitschrift fur Medizinische Physik | Year: 2010

A basic formalism is presented for generating and interpreting compartmental models for dynamic contrast-enhanced MRI data in the kidney. A graphical convention is introduced to represent and design compartmental models in a transparent and physically intuitive manner. A systematic system of notations and a simple set of rules allows direct translation of the graphical representation into a mathematical solution. The rules are derived from the physical principle of mass conservation, and the interpretation provided by the general tracer-kinetic theory of linear and stationary systems. The power of the formalism is illustrated using examples of models that have been proposed in the literature on perfusion MRI, and by generating a number of advanced models that may be of use in the kidney. Im Folgenden wird ein allgemeiner Formalismus zur Ableitung und Interpretation von Kompartmentmodellen für die Analyse von dynamisch kontrastverstärkten MRT-Daten in der Niere präsentiert. Die Einführung einer graphischen Konvention ermöglicht es, in einer transparenten und physikalisch intuitiven Art und Weise Kompartmentmodelle darzustellen und zu erzeugen. Ein Notationssystem zusammen mit einer Gruppe von einfachen Regeln ermöglicht die direkte der graphischen Darstellung in eine mathematische Lösung. Dabei werden die Regeln aus dem physikalischen Prinzip der Massenerhaltung abgeleitet, die Interpretation folgt aus der allgemeinen pharmakokinetischen Theorie linearer und stationärer Systeme. Der Formalismus wird anhand von Beispielmodellen, die in der Literatur zur Analyse von Perfusionsdaten in der MRT vorgeschlagen wurden, dargestellt. Durch die Erzeugung einiger erweiterter Modelle, die für die Anwendung in der Niere nützlich sein könnten, werden die Stärken und Möglichkeiten des Formalismus demonstriert. © 2009. Source


Schmid V.J.,Ludwig Maximilians University of Munich
IEEE Transactions on Medical Imaging | Year: 2011

Contrast enhanced myocardial perfusion magnetic resonance imaging (MRI) is a promising technique, providing insight into how reduced coronary flow affects the myocardial tissue. Stenosis in a coronary vessel leads to reduced myocardial blood flow, but collaterals may secure the blood supply of the myocardium, with altered tracer kinetics. Due to a low signal-to-noise ratio, quantitative analysis of the signal is typically difficult to achieve at the voxel level. Hence, analysis is often performed on measurements that are aggregated in predefined myocardial segments, that ignore the variability in blood flow in each segment. The approach presented in this paper uses local spatial information that enables one to perform a robust analysis at the voxel level. The spatial dependencies between local response curves are modelled via a hierarchical Bayesian model. In the proposed framework, all local systems are analyzed simultaneously along with their dependencies, producing a more robust context-driven estimation of local kinetics. Detailed validation on both simulated and patient data is provided. © 2011 IEEE. Source


Becker P.B.,Ludwig Maximilians University of Munich | Workman J.L.,Stowers Institute for Medical Research
Cold Spring Harbor Perspectives in Biology | Year: 2013

Eukaryotic chromatin is kept flexible and dynamic to respond to environmental, metabolic, and developmental cues through the action of a family of so-called "nucleosome remodeling" ATPases. Consistent with their helicase ancestry, these enzymes experience conformation changes as they bind and hydrolyze ATP. At the same time they interact with DNA and histones, which alters histone-DNA interactions in target nucleosomes. Their action may lead to complete or partial disassembly of nucleosomes, the exchange of histones for variants, the assembly of nucleosomes, or the movement of histone octamers on DNA. "Remodeling" may render DNA sequences accessible to interacting proteins or, conversely, promote packing into tightly folded structures. Remodeling processes participate in every aspect of genome function. Remodeling activities are commonly integrated with other mechanisms such as histone modifications or RNA metabolism to assemble stable, epigenetic states. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved. Source


Zottl G.,Ludwig Maximilians University of Munich
International Journal of Industrial Organization | Year: 2011

This article contributes to the debate of missing money (compare Joskow(2007a)). This debate has seriously questioned the desirability of limiting scarcity prices in markets with fluctuating demand by emphasizing their potentially negative impact on firms' investment decisions in the long run. A prominent example are recently liberalized electricity markets, where competition authorities have imposed price caps3 or adopted other measures to mitigate high scarcity prices. The impact of reduced scarcity prices in the long run still is only incompletely explored. We thus analyze investment of firms in base load and peak load technologies in a market with fluctuating demand under imperfect competition. We show that an appropriately chosen limitation of scarcity prices is not only beneficial in the short run but also in the long run. It leads to a strict increase of investment in peak load technologies, leaving investment in base load technologies unchanged. Furthermore, we characterize the optimal limit on scarcity prices. © 2011 Elsevier B.V. All rights reserved. Source


Taylor P.C.J.,Ludwig Maximilians University of Munich | Thut G.,University of Glasgow
Brain Stimulation | Year: 2012

Probing brain functions by brain stimulation while simultaneously recording brain activity allows addressing major issues in cognitive neuroscience. We review recent studies where electroencephalography (EEG) has been combined with transcranial magnetic stimulation (TMS) in order to investigate possible neuronal substrates of visual perception and attention. TMS-EEG has been used to study both pre-stimulus brain activity patterns that affect upcoming perception, and also the stimulus-evoked and task-related inter-regional interactions within the extended visual-attentional network from which attention and perception emerge. Local processes in visual areas have been probed by directly stimulating occipital cortex while monitoring EEG activity and perception. Interactions within the attention network have been probed by concurrently stimulating frontal or parietal areas. The use of tasks manipulating implicit and explicit memory has revealed in addition a role for attentional processes in memory. Taken together, these studies helped to reveal that visual selection relies on spontaneous intrinsic activity in visual cortex prior to the incoming stimulus, their control by attention, and post-stimulus processes incorporating a re-entrant bias from frontal and parietal areas that depends on the task. © 2012 Elsevier Inc. All rights reserved. Source


Boehm H.-P.,Ludwig Maximilians University of Munich
Angewandte Chemie - International Edition | Year: 2010

Thanks to its unusual electronic properties graphene has received considerable attention in recent years. It is less known, however, that research in this area goes much further back: At the start of the 1960s H.-P. Boehm et al. reduced graphite oxide with formation of thin films, which today, on account of their content of foreign atoms, would be called "chemically modified graphenes" (figure: electron microscopy image from that time). Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Dempke W.C.M.,Ludwig Maximilians University of Munich
Anticancer Research | Year: 2015

Advanced or metastatic non-small cell lung cancer (NSCLC) is characterised by a poor prognosis and few second- or third-line treatments. First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibition has paved the way for targeted therapies in lung cancer. Although these drugs result in excellent responses [and significantly improved progression-free survival (PFS)] in patients with activating EGFR mutations, only few studies revealed improved overall survival (OS), and resistance often develops. Bevacizumab, a monoclonal antibody which targets vascular endothelium growth factor (VEGF), has been fully developed in NSCLC, and small-molecule tyrosin kinase inhibitors (TKIs) have been approved as first-line therapy for patients with advanced and metastatic NSCLC harbouring EGFR mutations. In addition, crizotinib, a novel inhibitor of the anaplastic lymphoma kinase, has been approved for second-line treatment of NSCLC. Several new drugs targeting not only the EGFR pathways, but also signal transduction cascades involved in angiogenesis and the mitogene-activated extracellular signal-regulated kinase kinase pathways are currently evaluated in phase III clinical trials. Experimental monoclonal antibodies are also currently undergoing phase III clinical trials and have shown promising activity which might help to improve the therapeutic landscape of NSCLC. However, many other drugs prolonged PFS, but failed to demonstrate a significant improvement of OS. PFS is often used as a predictor for improved OS since it is independent of subsequent treatment, but OS is acknowledged as the key clinical outcome in the treatment of advanced NSCLC. Furthermore, since there are only very few trials that have shown a benefit from the addition of TKIs to chemotherapy, additional studies using this unselected approach are not recommended. Therefore, there is a definite need for an improved understanding of the complex mechanisms that are involved in TKI-mediated pathways, and for the development of validated predictive markers to allow a better treatment decision on the basis of the probability of response. This would certainly help to avoid the unnecessary use of potential toxic drugs in patients with known resistance and would facilitate the discovery of new targets and drugs on the basis of resistance mechanisms. Source


Mylonas I.,Ludwig Maximilians University of Munich
Archives of Gynecology and Obstetrics | Year: 2012

Introduction Urogenital infection by Chlamydia trachomatis is the most common bacterial sexually transmitted disease in the world. C. trachomatis is the etiologic agent of several common genital tract syndromes such as urethritis, cervicitis, and pelvic inflammatory disease in women. Materials and methods In this review, the pathophysiology of a chlamydial infection as well as diagnosis, therapy and prevention strategies regarding female chlamydial infection are reviewed. Results A chlamydial infection results in minimal or even no symptoms in approximately two-thirds of women, remaining therefore clinically apparent and undiagnosed. C. trachomatis infections are of great socioeconomic and public health concern due to the potential for severe longterm consequences in women, including an increased risk of ectopic pregnancy, tubal infertility and chronic pelvic pain. Moreover, if the bacterium is transmitted during labor to a newborn, it can cause ophthalmia neonatorum and atypical neonatal pneumonia. Due to the documented increased risk of morbidity, several national guidelines are available, including a routine screening for young women and screening during pregnancy that is recommended in several countries. Discussion A routine screening for young women and screening during pregnancy is recommended in several countries. However, additional prospective studies of the effectiveness of chlamydia screening are warranted and might be feasible within established screening programs. Moreover, the transition from cervicitis to infertility should be also evaluated in future controlled studies to underline the existing evidence. Additionally, there is an urgent need to educate and inform health-care providers about implementation of screening programs to reduce the spread of chlamydial infection. Moreover, awareness and use of screening programs by the public is needed, which requires informational campaigns for the general public using different media. For improved screening strategies and public awareness, novel approaches have to be developed and evaluated. Finally, guidelines should be actively disseminated to all medical practitioners to increase their use in daily practice. Although the major socioeconomic and public health concerns of C. trachomatis infection are recognized, several considerations and additional measures for addressing this increasingly urgent health problem remain. © Springer-Verlag 2012. Source


Bambi C.,Ludwig Maximilians University of Munich | Bambi C.,University of Tokyo
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

In 4-dimensional General Relativity, black holes are described by the Kerr solution and are subject to the bound |a*|≤1, where a* is the black hole spin parameter. If current black hole candidates are not the black holes predicted in General Relativity, this bound does not hold and a* might exceed 1. In this Letter, I relax the Kerr black hole hypothesis and I find that the value of the spin parameter of the super-massive black hole candidates in galactic nuclei cannot be higher than about 1.2. A higher spin parameter would not be consistent with a radiative efficiency η>0.15, as observed at least for the most luminous AGN. While a rigorous proof is lacking, I conjecture that the bound |a*|≲1.2 is independent of the exact nature of these objects. © 2011 Elsevier B.V. Source


Firnkes M.,TU Munich | Pedone D.,TU Munich | Knezevic J.,TU Munich | Doblinger M.,Ludwig Maximilians University of Munich | Rant U.,TU Munich
Nano Letters | Year: 2010

Solid-state nanopores bear great potential to be used to probe single proteins; however, the passage of proteins through nanopores was found to be complex, and unexpected translocation behavior with respect to the passage direction, rate, and duration was observed. Here we study the translocation of a model protein (avidin) through silicon nitride nanopores focusing on the electrokinetic effects that facilitate protein transport across the pore. The nanopore zeta potential λ pore and the protein zeta potential λ protein are measured independently as a function of solution pH. Our results reveal that electroosmotic transport may enhance or dominate and reverse electrophoretic transport in nanopores. The translocation behavior is rationalized by accounting for the charging states of the protein and the pore, respectively; the resulting translocation direction can be predicted according to the difference in zeta potentials, λ protein - λ pore. When electrophoresis and electroosmosis cancel each other out, diffusion becomes an effective (and bias-independent) mechanism which facilitates protein transport across the pore at a significant rate. © 2010 American Chemical Society. Source


Braun S.,University of California at San Francisco | Braun S.,Ludwig Maximilians University of Munich | Madhani H.D.,University of California at San Francisco
EMBO Reports | Year: 2012

The organization of eukaryotic chromosomes into transcriptionally active euchromatin and repressed heterochromatin requires mechanisms that establish, maintain and distinguish these canonical chromatin domains. Post-translational modifications are fundamental in these processes. Monoubiquitylation of histones was discovered more than three decades ago, but its precise function has been enigmatic until recently. It is now appreciated that the spectrum of chromatin ubiquitylation is not restricted to monoubiquitylation of histones, but includes degradatory ubiquitylation of histones, histone-modifying enzymes and non-histone chromatin factors. These occur in a spatially and temporally controlled manner. In this review, we summarize our understanding of these mechanisms with a particular emphasis on how ubiquitylation shapes the physical landscape of chromatin. © 2012 European Molecular Biology Organization. Source


Hopfner K.-P.,Ludwig Maximilians University of Munich
Biological Chemistry | Year: 2012

ATP binding cassette proteins are a large and diverse family of molecular machines and include transmembrane transporter, chromosome maintenance and DNA repair proteins, and translation factors. However, the function of the ABCE1, the only member of subfamily E of ABC proteins, remained mysterious for over a decade, even though it is perhaps the most conserved ABC protein in eukaryotes and archaea. Recent results have now identified ABCE1 as the ribosome-recycling factor of eukaryotes and archaea. Thus, two iron-sulfur clusters - the hallmark feature of ABCE1 - help catalyze an integral step of the translational cycle at the core of the protein synthesis machinery. Copyright © 2011-2012 by Walter de Gruyter. Copyright © 2011-2012 by Walter de Gruyter. Source


Warsch W.,University of Veterinary Medicine Vienna | Warsch W.,University of Cambridge | Walz C.,Ludwig Maximilians University of Munich | Sexl V.,University of Veterinary Medicine Vienna
Blood | Year: 2013

The transcription factor signal transducers and activators of transcription 5 (STAT5) has an important and unique role in Breakpoint Cluster Region - Abelson 1 (BCR-ABL1)-driven neoplasias. STAT5 is an essential component in the signaling network that maintains the survival and growth of chronic myeloid leukemia (CML) cells. In contrast, the function of the prototypical upstream kinase of STAT5, the Janus kinase JAK2, in CML is still under debate. Although there is widespread agreement that JAK2 is part of the signaling network downstream of BCR- ABL1, it is unclear whether and under what circumstances JAK2 inhibitors may be beneficial for CML patients. Recent studies in murine models have cast doubt on the importance of JAK2 in CML maintenance. Nevertheless, JAK2 has been proposed to have a central role in the cytokine signaling machinery that allows the survival of CML stem cells in the presence of BCR-ABL1 tyrosine kinase inhibitors. In this review, we summarize the current debate and provide an overview of the arguments on both sides of the fence. We present recent evidence showing that CML stem cells do not depend on BCR-ABL1 kinase activity but require the continuous support of the hematopoietic niche and its distinct cytokine environment and suggest that it has the potential to resolve the dispute. © 2013 by The American Society of Hematology. Source


Weber H.,center | Sagerer-Gerhardt M.,Ludwig Maximilians University of Munich
Europace | Year: 2014

AimsTo evaluate laser lesion formation in the beating hearts of dogs by using an open-irrigated electrode-laser mapping and ablation heart catheter.Methods and resultsA total of 50 laser applications at 15 W (n = 31) and 20 W (n = 19) for 10-50 s, with an irrigation flow of 35 mL/min were aimed at the right (n = 15) and left (n = 9) atrial, right (n = 15) and left (n = 11) ventricular walls in five dogs (6-16/dog), by using an open-irrigated laser ablation catheter. The 1064 nm diode laser was provided with a light control system, a Flowmeter, and a transoesophageal laser sensor. Lesions were measured and were evaluated morphometrically. Transmural lesions were achieved in seconds regardless of the level of energy applied. Laser applications at 15 W > 10 s aimed at the atrial walls produced collateral lesions to the lung or to the oesophagus. Laser applications at 20 W > 30 s aimed at the ventricular walls may result in steam pop with intramural cavitations and arrhythmias. Collateral damages to the oesophagus occurred only when the transoesophageal light sensor was deactivated.ConclusionTo avoid unwanted effects during laser catheter ablation by using an open-irrigated laser catheter energy delivery must be adapted to the thickness of the myocardial wall. Light control system and a transoesophageal light sensor may help reduce the risks of myocardial and collateral damages. © 2013 The Author. Source


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. Source


Lachenmaier S.,Ludwig Maximilians University of Munich | Rottmann H.,Munich University of Applied Sciences
International Journal of Industrial Organization | Year: 2011

This paper estimates the effect of innovation on employment at the firm level. Our uniquely long innovation panel data set of German manufacturing firms covers more than 20 years and allows us to use various innovation measures. We can distinguish between product and process innovations as well as between innovation input and innovation output measures. Using dynamic panel GMM system estimation we find positive effects of innovation on employment. This is true for innovation input as well as for innovation output variables. Innovations show their positive effect on employment with a time lag and process innovations have higher effects than product innovations. © 2010 Elsevier B.V. All rights reserved. Source


Soehnlein O.,Ludwig Maximilians University of Munich
Circulation Research | Year: 2012

Because of their rare detection in atherosclerotic lesions, the involvement of neutrophils in the pathophysiology of atherosclerosis has been largely denied. However, over the past couple of years, studies have provided convincing evidence for the presence of neutrophils in atherosclerotic plaques and further revealed the causal contribution of neutrophils during various stages of atherosclerosis. This review describes mechanisms underlying hyperlipidemia-mediated neutrophilia and how neutrophils may enter atherosclerotic lesions. It also highlights possible mechanisms of neutrophil-driven atherogenesis and plaque destabilization. Knowledge of the contribution of neutrophils to atherosclerosis will allow for exploration of new avenues in the treatment of atherogenesis and atherothrombosis. © 2012 American Heart Association, Inc. Source


Fritzsch B.,University of Iowa | Straka H.,Ludwig Maximilians University of Munich
Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology | Year: 2014

Among the major distance senses of vertebrates, the ear is unique in its complex morphological changes during evolution. Conceivably, these changes enable the ear to adapt toward sensing various physically well-characterized stimuli. This review develops a scenario that integrates sensory cell with organ evolution. We propose that molecular and cellular evolution of the vertebrate hair cells occurred prior to the formation of the vertebrate ear. We previously proposed that the genes driving hair cell differentiation were aggregated in the otic region through developmental re-patterning that generated a unique vertebrate embryonic structure, the otic placode. In agreement with the presence of graviceptive receptors in many vertebrate outgroups, it is likely that the vertebrate ear originally functioned as a simple gravity-sensing organ. Based on the rare occurrence of angular acceleration receptors in vertebrate outgroups, we further propose that the canal system evolved with a more sophisticated ear morphogenesis. This evolving morphogenesis obviously turned the initial otocyst into a complex set of canals and recesses, harboring multiple sensory epithelia each adapted to the acquisition of a specific aspect of a given physical stimulus. As support for this evolutionary progression, we provide several details of the molecular basis of ear development. © 2013 Springer-Verlag Berlin Heidelberg. Source


Pavicic T.,Ludwig Maximilians University of Munich
Journal of Drugs in Dermatology | Year: 2011

Background: A monophasic, highly crosslinked hyaluronic acid dermal filler offers further treatment options for deep lines. Objective: To investigate the efficacy and tolerability of Belotero. Methods and Materials: A total of 149 patients received injections. Efficacy was assessed on the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS). Adverse events were recorded at each evaluation session. Results: Mean WSRS improved significantly (P<0.001) by 1.9 score points without any decline throughout the 12-week period. Improvement was found in 89.9 percent of patients on the (GAIS), 59.7 percent of whom were designated as very much/much improved. Investigator and patient satisfaction was stated in more than 90 percent of cases as excellent/good. Adverse events, exclusively localized to the injection area, occurred in 85.9 percent of patients immediately after injection and declined to 12.8 percent in week 2. None were serious. Conclusion: The findings indicate the benefit of the highly cross-linked, monophasic hyaluronic acid dermal filler, especially in the treatment of patients with deep and extremely deep folds. Overall, the filler appears to be well tolerated. This evaluation raised no major safety concerns. Copyright © 2011 Journal of Drugs in Dermatology. Source


Smith R.K.,Ludwig Maximilians University of Munich | Montgomery M.T.,Naval Postgraduate School, Monterey
Quarterly Journal of the Royal Meteorological Society | Year: 2013

We examine aspects of the thermodynamic structure of mature Atlantic hurricane Earl (2010) based on airborne dropwindsondes released from the upper troposphere during the National Aeronautics and Space Administration (NASA), Genesis and Rapid Intensification Processes (GRIP) experiment. Vertical sounding profiles of the data raise questions concerning the relative roles of isothermal expansion and relative humidity increase in elevating the equivalent potential temperature of air parcels spiralling inwards to the eyewall convection region. The observational results obtained for two successive days of this category 4 hurricane show that the isothermal expansion effect leads to roughly one half of the increment in equivalent potential temperature for boundary-layer air parcels moving between the region outside the eyewall and the eyewall and eye region. © 2012 Royal Meteorological Society. Source


Silaghi C.,Ludwig Maximilians University of Munich
Frontiers in Cellular and Infection Microbiology | Year: 2013

The bacterium Anaplasma phagocytophilum has for decades been known to cause the disease tick-borne fever (TBF) in domestic ruminants in Ixodes ricinus-infested areas in northern Europe. In recent years, the bacterium has been found associated with Ixodes-tick species more or less worldwide on the northern hemisphere. A. phagocytophilum has a broad host range and may cause severe disease in several mammalian species, including humans. However, the clinical symptoms vary from subclinical to fatal conditions, and considerable underreporting of clinical incidents is suspected in both human and veterinary medicine. Several variants of A. phagocytophilum have been genetically characterized. Identification and stratification into phylogenetic subfamilies has been based on cell culturing, experimental infections, PCR, and sequencing techniques. However, few genome sequences have been completed so far, thus observations on biological, ecological, and pathological differences between genotypes of the bacterium, have yet to be elucidated by molecular and experimental infection studies. The natural transmission cycles of various A. phagocytophilum variants, the involvement of their respective hosts and vectors involved, in particular the zoonotic potential, have to be unraveled. A. phagocytophilum is able to persist between seasons of tick activity in several mammalian species and movement of hosts and infected ticks on migrating animals or birds may spread the bacterium. In the present review, we focus on the ecology and epidemiology of A. phagocytophilum, especially the role of wildlife in contribution to the spread and sustainability of the infection in domestic livestock and humans. Source


Fischer J.,Karlsruhe Institute of Technology | Heun V.,Ludwig Maximilians University of Munich
SIAM Journal on Computing | Year: 2011

Given a static array of n totally ordered objects, the range minimum query problem is to build a data structure that allows us to answer efficiently subsequent on-line queries of the form "what is the position of a minimum element in the subarray ranging from i to j?". We focus on two settings, where (1) the input array is available at query time, and (2) the input array is available only at construction time. In setting (1), we show new data structures (a) of size 2n/c(n) -Θ(n lg lg n/c(n) lg n) bits and query time O(c(n)) for any positive integer function c(n) ε O(nε) for an arbitrary constant 0 < ε < 1, or (b) with O(nHk) + o(n) bits and O(1) query time, where Hk denotes the empirical entropy of kth order of the input array. In setting (2), we give a data structure of size 2n+o(n) bits and query time O(1). All data structures can be constructed in linear time and almost in-place. Copyright © by SIAM. Source


Adler B.,Ludwig Maximilians University of Munich
Viruses | Year: 2015

gH/gL virion envelope glycoprotein complexes of herpesviruses serve as entry complexes and mediate viral cell tropism. By binding additional viral proteins, gH/gL forms multimeric complexes which bind to specific host cell receptors. Both Epstein–Barr virus (EBV) and human cytomegalovirus (HCMV) express alternative multimeric gH/gL complexes. Relative amounts of these alternative complexes in the viral envelope determine which host cells are preferentially infected. Host cells of EBV can modulate the gH/gL complex complement of progeny viruses by cell type-dependent degradation of one of the associating proteins. Host cells of HCMV modulate the tropism of their virus progenies by releasing or not releasing virus populations with a specific gH/gL complex complement out of a heterogeneous pool of virions. The group of Jeremy Kamil has recently shown that the HCMV ER-resident protein UL148 controls integration of one of the HCMV gH/gL complexes into virions and thus creates a pool of virions which can be routed by different host cells. This first mechanistic insight into regulation of the gH/gL complex complement of HCMV progenies presents UL148 as a pilot candidate for HCMV navigation in its infected host. © 2015 by the authors. Source


Whitcher B.,Mango Solutions | Schmid V.J.,Ludwig Maximilians University of Munich
Journal of Statistical Software | Year: 2011

The package dcemriS4 provides a complete set of data analysis tools for quantitative assessment of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Image processing is provided for the ANALYZE and NIfTI data formats as input with all parameter estimates being output in NIfTI format. Estimation of T1 relaxation from multiple flip-angle acquisitions, using either constant or spatially-varying flip angles, is performed via nonlinear regression. Both literature-based and data-driven arterial input functions are available and may be combined with a variety of compartmental models. Kinetic parameters are obtained from nonlinear regression, Bayesian estimation via Markov chain Monte Carlo or Bayesian maximum a posteriori estimation. A non-parametric model, using penalized splines, is also available to characterize the contrast agent concentration time curves. Estimation of the apparent diffusion coefficient (ADC) is provided for diffusion-weighted imaging. Given the size of multi-dimensional data sets commonly acquired in imaging studies, care has been taken to maximize computational efficiency and minimize memory usage. All methods are illustrated using both simulated and real-world medical imaging data available in the public domain. Source


Friedmann O.,Ludwig Maximilians University of Munich
Logical Methods in Computer Science | Year: 2011

This paper presents a new exponential lower bound for the two most popular deterministic variants of the strategy improvement algorithms for solving parity, mean payoff, discounted payoff and simple stochastic games. The first variant improves every node in each step maximizing the current valuation locally, whereas the second variant computes the globally optimal improvement in each step. We outline families of games on which both variants require exponentially many strategy iterations. © O. Friedmann. Source


von Braunmuhl T.,Ludwig Maximilians University of Munich
Hautarzt | Year: 2015

Optical coherence tomography (OCT) was introduced in the 1990s in dermatology and is nowadays established as a noninvasive highresolution technique for the in vivo evaluation of the skin. To date several studies have been successfully demonstrated the application of OCT for various dermatological questions. The main indication for OCT in the daily practice is the noninvasive diagnosis of nonmelanoma skin cancer such as actinic keratosis and basal cell carcinoma. OCT has also been shown to be a valuable tool in treatment monitoring and evaluation of therapeutic success of noninvasive treatment strategies like topical immune modulators or photodynamic treatment. Other potential applications for OCT include inflammatory diseases, microbial or parasitic infestations of the skin, e.g. scabies mites or onychomycosis. In recent years high-definition OCT devices have been developed that can potentially be used for the evaluation of melanocytic lesions and, due to the higher resolution, for the visualization of intrafollicular demodex mites. Furthermore different commercially available devices offer—in addition to the cross-sectional images—a fast-generated horizontal (en face) imaging mode. With respect to resolution and penetration depth the OCT technique is taking a middle position in comparison to other noninvasive imaging devices in dermatology such as sonography and reflectance confocal microscopy. © Springer-Verlag Berlin Heidelberg 2015. Source


Cattaneo M.E.G.V.,Ludwig Maximilians University of Munich
International Journal of Approximate Reasoning | Year: 2011

This paper considers the problem of combining belief functions obtained from not necessarily independent sources of information. It introduces two combination rules for the situation in which no assumption is made about the dependence of the information sources. These two rules are based on cautious combinations of plausibility and commonality functions, respectively. The paper studies the properties of these rules and their connection with Dempster's rules of conditioning and combination and the minimum rule of possibility theory. © 2010 Elsevier Inc. All rights reserved. Source


Steinlein O.K.,Ludwig Maximilians University of Munich
Chemical Reviews | Year: 2012

Ortrud K. Steinlein presented a genetics perspective of ion channel mutations in neuronal diseases. He informed that within the central nervous system microglia cells act as immune cells that respond to injury or other perturbations of brain and spinal cord with an array of weapons. Microglia cells monitored the state of health of the central nervous system and showed significant activation in neurodegenerative disorders including Morbus Alzheimer or Parkinson's disease. Their weapons included diverse function such as migration, proliferation, phagocytosis, secretions of multiple cytokines, or chemokines, and promotion of repair. They were called into action by cell-surface molecules that acted as a kind of sensor to detect changes in the microglia environment. These sensors also included multiple ion channels from the chloride, potassium, proton, and calcium subfamilies apart from different kinds of cell-surface receptors and adhesion molecules. Source


Halimeh J.C.,Ludwig Maximilians University of Munich | Wegener M.,Karlsruhe Institute of Technology
Optics Express | Year: 2013

Carpet or ground-plane invisibility cloaks hide an object in reflection and inhibit transmission experiments by construction. This concept has significantly reduced the otherwise demanding material requirements and has hence enabled various experimental demonstrations. In contrast, free-space invisibility cloaks should work in both reflection and transmission. The fabrication of omnidirectional three-dimensional freespace cloaks still poses significant challenges. Recently, the idea of the carpet cloak has been carried over to experiments on unidirectional freespace invisibility cloaks that only work perfectly for one particular viewing direction and, depending on the design, also for one linear polarization of light only. Here, by using photorealistic ray tracing, we visualize the performance of four types of such unidirectional cloaks in three dimensions for different viewing directions and different polarizations of light, revealing virtues and limitations of these approaches in an intuitive manner. © 2013 Optical Society of America. Source


Sodian B.,Ludwig Maximilians University of Munich
Child Development Perspectives | Year: 2011

This article reviews recent evidence for the claim that infants possess a theory of mind. Two conceptual systems (CS) of psychological reasoning are distinguished: CS1, underlying the attribution of motivational states such as goals and dispositions, and CS2, supporting a representational theory of mind, that is, an understanding of false belief. There is ample evidence for CS1 even in the 1st year of life, whereas the claim that CS2 is operational in infancy is controversial. The article proposes a lean interpretation of findings on infants' representation of false belief that assumes that a fast and automatic, but limited and inflexible, social information processing system guides infants' encoding of belief-based intentional action. © 2011 The Author. Child Development Perspectives © 2011 The Society for Research in Child Development. Source


Anders H.-J.,Ludwig Maximilians University of Munich | Romagnani P.,University of Florence | Mantovani A.,Istituto Clinico Humanitas | Mantovani A.,University of Milan
Trends in Molecular Medicine | Year: 2014

Homeostatic chemokines control stem and progenitor cell migration and activation during vasculogenesis and organ development. They orchestrate hematopoietic stem cell (HSC) homing to their bone marrow niches and direct immature lymphocytes to a series of maturation sites within lymphoid organs. Along these lines, homeostatic chemokines regulate the niches of peripheral committed progenitor cell populations for tissue renewal. These biological functions support neovascularization and wound healing, including the recruitment of endothelial and other progenitor cells from the bone marrow. Here, we summarize the roles of homeostatic chemokines, their signaling receptors, and atypical decoy receptors during homeostasis and tissue regeneration in order to better understand their pathogenic roles in disease, for example, in diabetes complications, cancer, autoimmunity, epithelial hyperplasia, or hypertrophic scarring and fibrosis. © 2013 Elsevier Ltd. Source


Soyka M.,Ludwig Maximilians University of Munich
European Addiction Research | Year: 2015

Maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Clinical studies indicate that about a third of patients in opioid maintenance therapy show increased alcohol consumption and alcohol use disorders. Comorbid alcohol use disorders have been identified as a risk factor for clinical outcome and can cause poor physical and mental health, including liver disorders, noncompliance, social deterioration and increased mortality risk. The effects of opioid maintenance therapy on alcohol consumption are controversial and no clear pattern has emerged. Most studies have not found a change in alcohol use after initiation of maintenance therapy. Methadone and buprenorphine appear to carry little risk of liver toxicity, but further research on this topic is required. Recent data indicate that brief intervention strategies may help reduce alcohol intake, but the existing evidence is still limited. This review discusses further clinical implications of alcohol use disorders in opioid dependence. © 2014 S. Karger AG, Basel. Source


Stecher B.,Ludwig Maximilians University of Munich | Stecher B.,German Center for Infection Research | Berry D.,University of Vienna | Loy A.,University of Vienna
FEMS Microbiology Reviews | Year: 2013

The highly diverse intestinal microbiota forms a structured community engaged in constant communication with itself and its host and is characterized by extensive ecological interactions. A key benefit that the microbiota affords its host is its ability to protect against infections in a process termed colonization resistance (CR), which remains insufficiently understood. In this review, we connect basic concepts of CR with new insights from recent years and highlight key technological advances in the field of microbial ecology. We present a selection of statistical and bioinformatics tools used to generate hypotheses about synergistic and antagonistic interactions in microbial ecosystems from metagenomic datasets. We emphasize the importance of experimentally testing these hypotheses and discuss the value of gnotobiotic mouse models for investigating specific aspects related to microbiota-host-pathogen interactions in a well-defined experimental system. We further introduce new developments in the area of single-cell analysis using fluorescence in situ hybridization in combination with metabolic stable isotope labeling technologies for studying the in vivo activities of complex community members. These approaches promise to yield novel insights into the mechanisms of CR and intestinal ecophysiology in general, and give researchers the means to experimentally test hypotheses in vivo at varying levels of biological and ecological complexity. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved. Source


Chung I.,German Cancer Research Center | Leonhardt H.,Ludwig Maximilians University of Munich | Rippe K.,German Cancer Research Center
Journal of Cell Science | Year: 2011

Telomerase-negative tumor cells use an alternative lengthening of telomeres (ALT) pathway that involves DNA recombination and repair to maintain their proliferative potential. The cytological hallmark of this process is the accumulation of promyelocytic leukemia (PML) nuclear protein at telomeric DNA to form ALT-associated PML bodies (APBs). Here, the de novo formation of a telomeric PML nuclear subcompartment was investigated by recruiting APB protein components. We show that functionally distinct proteins were able to initiate the formation of bona fide APBs with high efficiency in a self-organizing and self-propagating manner. These included: (1) PML and Sp100 as the constituting components of PML nuclear bodies, (2) telomere repeat binding factors 1 and 2 (TRF1 and TRF2, respectively), (3) the DNA repair protein NBS1 and (4) the SUMO E3 ligase MMS21, as well as the isolated SUMO1 domain, through an interacting domain of another protein factor. By contrast, the repair factors Rad9, Rad17 and Rad51 were less efficient in APB nucleation but were recruited to preassembled APBs. The artificially created APBs induced telomeric extension through a DNA repair mechanism, as inferred from their colocalization with sites of non-replicative DNA synthesis and histone H2A.X phosphorylation, and an increase of the telomere repeat length. These activities were absent after recruitment of the APB factors to a pericentric locus and establish APBs as functional intermediates of the ALT pathway. © 2011. Source


Graser A.,Ludwig Maximilians University of Munich
Radiologic Clinics of North America | Year: 2013

Magnetic resonance colonography (MRC) is performed on a whole body scanner after laxative-based purgation and distension of the large bowel with water. To achieve good image quality, acquisition of sequences within a comfortable breath-hold time is essential. Frequently, fast 3D fat-saturated T1-weighted techniques with parallel imaging are used to meet this demand, providing " dark lumen" contrast of the bowel with high signal intensity of the bowel wall after intravenous injection of contrast agent. This article sheds light on MRC technique, image acquisition, post processing, and normal findings, relevant pathologies, and differential diagnoses of the most frequent pathologies encountered at MRC. © 2013 Elsevier Inc. Source


Scardovi L.,Ludwig Maximilians University of Munich | Arcak M.,University of California at Berkeley | Sontag E.D.,Rutgers University
IEEE Transactions on Automatic Control | Year: 2010

This paper provides synchronization conditions for networks of nonlinear systems. The components of the network (referred to as compartments in this paper) are made up of an identical interconnection of subsystems, each represented as an operator in an extended L2 space and referred to as a species. The compartments are, in turn, coupled through a diffusion-like term among the respective species. The synchronization conditions are provided by combining the input-output properties of the subsystems with information about the structure of the network. The paper also explores results for state-space models, as well as biochemical applications. The work is motivated by cellular networks where signaling occurs both internally, through interactions of species, and externally, through intercellular signaling. The theory is illustrated by providing synchronization conditions for networks of Goodwin oscillators. © 2006 IEEE. Source


Gabius H.-J.,Ludwig Maximilians University of Munich
Biochemical Society Transactions | Year: 2011

Glycans stand out from all classes of biomolecules because of their unsurpassed structural complexity. This is generated by variability in anomeric status of the glycosidic bond and its linkage points, ring size, potential for branching and introduction of diverse site-specific substitutions. What poses an enormous challenge for analytical processing is, at the same time, the basis for the fingerprint-like glycomic profiles of glycoconjugates and cells. What's more, the glycosylation machinery is sensitive to disease manifestations, earning glycan assembly a reputation as a promising candidate to identify new biomarkers. Backing this claim for a perspective in clinical practice are recent discoveries that even seemingly subtle changes in the glycan structure of glycoproteins, such as a N-glycan core substitution by a single sugar moiety, have far-reaching functional consequences. They are brought about by altering the interplay between the glycan and (i) its carrier protein and (ii) specific receptors (lectins). Glycan attachment thus endows the protein with a molecular switch and new recognition sites. Co-ordinated regulation of glycan display and presentation of the cognate lectin, e.g. in cancer growth regulation exerted by a tumour suppressor, further exemplifies the broad functional dimension inherent to the non-random shifts in glycosylation. Thus studies on glycobiomarkers converge with research on how distinct carbohydrate determinants are turned into bioactive signals. © The Authors Journal compilation ©2011 Biochemical Society. Source


Boztug K.,Austrian Academy of Sciences | Klein C.,Ludwig Maximilians University of Munich
Hematology/Oncology Clinics of North America | Year: 2013

Considerable progress has been made in recent years in understanding of the genetic basis for congenital neutropenia syndromes. With the advent of high-throughput genomic analyzing technologies, the underlying genetic causes of other congenital neutropenia syndromes are expected to be resolved in the near future. This knowledge will provide the foundation for genotype-phenotype correlations for infection susceptibility, response to therapy, and risk of malignant transformation, enabling optimal care for individual patients depending on their molecular pathophysiology. It is hoped that these investigations will enable the development of tailored molecular therapies to specifically correct the aberrant signaling cascades. © 2013 Elsevier Inc. Source


Funder J.W.,Prince Henrys Institute | Reincke M.,Ludwig Maximilians University of Munich
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2010

The hormone aldosterone has a well-recognized physiological role in epithelial fluid and electrolyte homeostasis, and more recently defined pathophysiological roles in the cardiovascular system. The term "risk factor" implies an active role in pathophysiology, with levels lower (e.g. HDL) or higher (e.g. LDL, BP) than normal contributing to an increased likelihood of morbidity and/or mortality. In this regard, primary aldosteronism represents a classic illustration of aldosterone as a cardiovascular risk factor. In this syndrome of (relatively) autonomous aldosterone secretion, the effects of elevated hormone levels are on a range of organs and tissues-the heart, blood vessels and brain, inter alia. In other cardiovascular disorders (e.g. CCF, EH) while an elevation of aldosterone levels is often regarded as a risk factor, it is more correctly a response to the severity of disease (or to treatment intervention), rather than necessarily a risk factor with a primary role in disease progression. An enduring enigma relevant to any discussion of aldosterone as a risk factor is that very high levels of aldosterone in response to chronic sodium deficiency have homeostatic (and protective of cardiovascular) functions, while the considerably lower levels commonly seen in primary aldosteronism are incontrovertibly damaging. A final section of the paper will thus propose a mechanism which might solve this enigma, based on the commonalities-and a single crucial difference-in the factors stimulating the secretion of aldosterone and endogenous ouabain from the zona glomerulosa of the adrenal gland. © 2010 Elsevier B.V. Source


Bruning A.,Ludwig Maximilians University of Munich
Methods in Enzymology | Year: 2011

Nelfinavir (Viracept®) is an HIV protease inhibitor that has been shown to induce the endoplasmic reticulum (ER) stress reaction in human cancer cells. Although the presumed drug doses needed for an efficient ER stress reaction and ensuing apoptosis in cancer cells is somewhat higher than those prescribed for HIV-infected persons, nelfinavir represents one of the few clinically applicable ER stress-inducing agents, and is currently being tested in clinical studies on cancer patients. Therefore, this chapter describes how to obtain and use nelfinavir for in vitro and in vivo studies. In addition, methods are described that might facilitate the analysis and monitoring of the nelfinavir-induced ER stress response either in cancer cells in cell culture or in cancer tissue biopsies. These methods include various fluorescence-based ER staining techniques and the expression analysis of primary and secondary ER stress markers by immunoblotting and RT-PCR analysis. Among the several methods presented, the analysis of an unconventional XBP1 splicing, caused by the ER stress sensor IRE1, is shown to present the most sensitive and most specific marker for nelfinavir-induced ER stress. Primers and PCR conditions suitable for XBP1 PCR and splicing analysis are presented. Such a PCR-based XBP1 splicing analysis might not only be suitable to monitor nelfinavir-induced ER stress, but could also be applied in drug screening programs to test for other ER stress-inducing agents with similar activities or synergistic activities with nelfinavir. © 2011 Elsevier Inc. Source


Parhofer K.G.,Ludwig Maximilians University of Munich
Diabetes and Metabolism Journal | Year: 2015

Glucose and lipid metabolism are linked to each other in many ways. The most important clinical manifestation of this interaction is diabetic dyslipidemia, characterized by elevated triglycerides, low high density lipoprotein cholesterol (HDL-C), and predominance of small-dense LDL particles. However, in the last decade we have learned that the interaction is much more complex. Hypertriglyceridemia and low HDL-C cannot only be the consequence but also the cause of a disturbed glucose metabolism. Furthermore, it is now well established that statins are associated with a small but significant increase in the risk for new onset diabetes. The underlying mechanisms are not completely understood but modulation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA)-reductase may play a central role as genetic data indicate that mutations resulting in lower HMG CoA-reductase activity are also associated with obesity, higher glucose concentrations and diabetes. Very interestingly, this statin induced increased risk for new onset type 2 diabetes is not detectable in subjects with familial hypercholesterolemia. Furthermore, patients with familial hypercholesterolemia seem to have a lower risk for type 2 diabetes, a phenomenon which seems to be dose-dependent (the higher the low density lipoprotein cholesterol, the lower the risk). Whether there is also an interaction between lipoprotein(a) and diabetes is still a matter of debate. © 2015 Korean Diabetes Association. Source


Chen W.,TU Munich | Plewig G.,Ludwig Maximilians University of Munich
British Journal of Dermatology | Year: 2014

Human Demodex mites (Demodex folliculorum and Demodex brevis) hold a high rank in the evolutionary and phylogenetic hierarchy of the skin microbiome, although in most people their presence is of no consequence. While human demodicosis is a skin disease sui generis, it can mimic many other inflammatory dermatoses, such as folliculitis, rosacea and perioral dermatitis, leading to unspecific and confusing descriptions in the literature. Here, we propose to classify human demodicosis into a primary form and a secondary form, which is associated mainly with immunosuppression. The clinical manifestations of primary demodicosis may include (i) spinulate demodicosis, currently known as pityriasis folliculorum, involving sebaceous hair follicles without visible inflammation; (ii) papulopustular/nodulocystic or conglobate demodicosis with pronounced inflammation affecting most commonly the perioral and periorbital areas of the face; (iii) ocular demodicosis, inducing chronic blepharitis, chalazia or, less commonly, keratoconjunctivitis; and (iv) auricular demodicosis causing external otitis or myringitis. Secondary demodicosis is usually associated with systemic or local immunosuppression. Treatment is only weakly evidence based, and the most effective concentrations of acaricides remain to be determined. Optimization of an in vitro or ex vivo culture model is necessary for future studies. Endosymbiosis between certain bacteria and Demodex mites in the pathogenesis of demodicosis deserves more attention. Further clinical observations and experiments are needed to prove our hypothesis. What's already known about this topic? The pathogenicity of human Demodex mites in inflammatory skin diseases remains controversial. What does this study add? A new classification is proposed to divide human demodicosis into a primary form and a secondary form associated with other local or systemic diseases. The recognition of primary human demodicosis as a disease sui generis will enable clinicians to differentiate it from other mimicking inflammatory dermatoses and encourage the development of a specific effective treatment. © 2014 British Association of Dermatologists. Source


Anders H.-J.,Ludwig Maximilians University of Munich | Fogo A.B.,Vanderbilt University
Seminars in Immunopathology | Year: 2014

When patients with systemic lupus erythematosus (SLE) present with urinary abnormalities, a renal biopsy is usually needed to rule out or confirm lupus nephritis. Renal biopsy is also needed to define the type of renal manifestation as different entities are associated with different outcomes; hence, renal biopsy results shape lupus management. But why does lupus nephritis come in different shapes? Why do patients with SLE often show change over time in class of lupus nephritis or have mixed forms? How does autoimmunity in SLE evolve? Why does loss of tolerance against nuclear antigens preferentially affect the kidney? Why are immune complex deposits in different glomerular compartments associated with different outcomes? What determines crescent formation in lupus? In this review, we discuss these questions by linking the latest information on lupus pathogenesis into the context of the different classes of lupus nephritis. This should help the basic scientist, the pathologist, and the clinician to gain a more conceptual view on the immunopathology of lupus nephritis. © 2013 Springer-Verlag. Source


Hinz O.,Goethe University Frankfurt | Hann I.-H.,University of Maryland University College | Spann M.,Ludwig Maximilians University of Munich
MIS Quarterly: Management Information Systems | Year: 2011

The enhanced abilities of online retailers to learn about their customers' shopping behaviors have increased fears of dynamic pricing, a practice in which a seller sets prices based on the estimated buyer's willingness-topay. However, among online retailers, a deviation from a one-price-for-all policy is the exception. When price discrimination is observed, it is often in the context of customer outrage about unfair pricing. One setting where pricing varies is the name-your-own-price (NYOP) mechanism. In contrast to a typical retail setting, in NYOP markets, it is the buyer who places an initial offer. This offer is accepted if it is above some threshold price set by the seller. If the initial offer is rejected, the buyer can update her offer in subsequent rounds. By design, the final purchase price is opaque to the public; the price paid depends on the individual buyer's willingness-to-pay and offer strategy. Further, most forms of NYOP employ a fixed threshold price policy. In this paper, we compare a fixed threshold price setting with an adaptive threshold price setting. A seller who considers an adaptive threshold price has to weigh potentially greater profits against customer objections about the perceived fairness of such a policy. We first derive the optimal strategy for the seller. We analyze the effectiveness of an adaptive threshold price vis-à-vis a fixed threshold price on seller profit and customer satisfaction. Further, we evaluate the moderating effect of revealing the threshold price policy (adaptive versus fixed) to buyers. We test our model in a series of laboratory experiments and in a large field experiment at a prominent NYOP seller involving real purchases. Our results show that revealing the usage of an adaptive mechanism yields higher profits and more transactions than not revealing this information. In the field experiment, we find that applying a revealed adaptive threshold price can increase profits by over 20 percent without lowering customer satisfaction. Source


Wack M.,Ludwig Maximilians University of Munich
Computers and Geosciences | Year: 2010

A new software package, calledCryoMag, facilitates the measurement of magnetic moments using both 3-component (i.e. Superconducting QUantum Interference Device) and 2-component (i.e. spinner) magnetometers. The measurement process is optimized for, but not limited to, stepwise demagnetization experiments commonly used in paleomagnetism. A graphical representation of the data is always visible to the user in the form of orthogonal, stereonet and decay diagrams, which can be represented in in situ, geographic or tilt corrected coordinates and can be saved as graphics files. Instrument specific settings, as well as arbitrary measurement positions, can be easily customized in a single configuration file. A comprehensive record of detailed measurement and statistical data is stored in XML (eXtensible Markup Language) based data files (*cmag.xml). The final results of the measurements can be exported to several common file formats for further processing. The software is written inPython, an open source, cross-platform programming language and can therefore be used on popular operating systems like Windows, Linux and MacOS X. The complete source code is available on request from the author. The CryoMag open-source allows anyone to adapt the software to their specific equipment, file format and experimental requirements. © 2010 Elsevier Ltd. Source


Scheipl F.,Ludwig Maximilians University of Munich
Journal of Statistical Software | Year: 2011

The R package spikeSlabGAM implements Bayesian variable selection, model choice, and regularized estimation in (geo-)additive mixed models for Gaussian, binomial, and Poisson responses. Its purpose is to (1) choose an appropriate subset of potential covariates and their interactions, (2) to determine whether linear or more flexible functional forms are required to model the effects of the respective covariates, and (3) to estimate their shapes. Selection and regularization of the model terms is based on a novel spike-and-slab-type prior on coefficient groups associated with parametric and semi-parametric effects. Source


Astumian R.D.,University of Maine, United States | Astumian R.D.,Ludwig Maximilians University of Munich
Biophysical Journal | Year: 2010

Molecular motors are first and foremost molecules, governed by the laws of chemistry rather than of mechanics. The dynamical behavior of motors based on chemical principles can be described as a random walk on a network of states. A key insight is that any molecular motor in solution explores all possible motions and configurations at thermodynamic equilibrium. By using input energy and chemical design to prevent motion that is not wanted, what is left behind is the motion that is desired. This review is focused on two-headed motors such as kinesin and Myosin V that move on a polymeric track. By use of microscopic reversibility, it is shown that the ratio between the number of forward steps and the number of backward steps in any sufficiently long time period does not directly depend on the mechanical properties of the linker between the two heads. Instead, this ratio is governed by the relative chemical specificity of the heads in the front-versus-rear position for the fuel, adenosine triphosphate and its products, adenosine diphosphate and inorganic phosphate. These insights have been key factors in the design of biologically inspired synthetic molecular walkers constructed out of DNA or out of small organic molecules. © 2010 by the Biophysical Society. Source


Sellers J.R.,U.S. National Institutes of Health | Veigel C.,UK National Institute for Medical Research | Veigel C.,Ludwig Maximilians University of Munich
Nature Structural and Molecular Biology | Year: 2010

Complex forms of cellular motility, including cell division, organelle trafficking or signal amplification in the auditory system, require strong coordination of the myosin motors involved. The most basic mechanism of coordination is via direct mechanical interactions of individual motor heads leading to modification of their mechanochemical cycles. Here we used an optical trap-based assay to investigate the reversibility of the force-generating conformational change (power stroke) of single myosin-Va motor heads. By applying load to the head shortly after binding to actin, we found that, at a certain load, the power stroke could be reversed, and the head fluctuated between an actin-bound pre-and a post-power stroke conformation. This load-dependent mechanical instability might be critical to coordinate the heads of processive, dimeric myosin-Va. Nonlinear response to load leading to coordination or oscillations amongst motors might be relevant for many cellular functions. © 2010 Nature America, Inc. All rights reserved. Source


Gebhard S.,Ludwig Maximilians University of Munich
Molecular Microbiology | Year: 2012

Antimicrobial peptides (AMPs) are a group of antibiotics that mainly target the cell wall of Gram-positive bacteria. Resistance is achieved by a variety of mechanisms including target alterations, changes in the cell's surface charge, expression of immunity peptides or by dedicated ABC transporters. The latter often provide the greatest level of protection. Apart from resistance, ABC transporters are also required for the export of peptides during biosynthesis. In this review the different AMP transporters identified to date in Firmicutes bacteria were classified into five distinct groups based on their domain architecture, two groups with a role in biosynthesis, and three involved in resistance. Comparison of the available information for each group regarding function, transport mechanism and gene regulation revealed distinguishing characteristics as well as common traits. For example, a strong correlation between transporter group and mode of gene regulation was observed, with three different types of two-component systems as well as XRE family transcriptional regulators commonly associated with individual transporter groups. Furthermore, the presented summary of the state-of-the-art on AMP transport in Firmicutes bacteria, discussed in the context of transporter phylogeny, provides insights into the mechanisms of substrate translocation and how this may result in resistance against compounds that bind extracellular targets. © 2012 Blackwell Publishing Ltd. Source


Schneider M.R.,Ludwig Maximilians University of Munich
Experimental Dermatology | Year: 2015

First described as an alopecic spontaneous mutant mouse line lacking sebaceous glands in a publication in Science in 1965 by Allen H. Gates and Marvin Karasek, asebia mice soon became a popular tool for rodent sebaceous gland research. In addition to the study of sebaceous lipids, the original asebia mice and subsequent allelic mutations were widely employed to examine the influence of the sebaceous gland on hair growth, epidermal proliferation, dermal inflammation and skin carcinogenesis, among other aspects. With the identification of Scd1 gene mutations as the genetic basis of the asebia phenotype and with the advent of more refined methods for manipulating the mouse genome, asebia mice progressively lost importance. However, they contributed to, or even provided the initial spark for, several current research topics. These include the role of the sebaceous gland in hair shaft-sheath interaction and its significance for cicatricial alopecia, and the antimicrobial activity of sebum. Furthermore, mice with skin-specific deletion of SCD1, which have increased energy expenditure and are protected from high fat diet-induced obesity, provided novel insights into the crosstalk between the skin and peripheral tissues in maintaining energy homeostasis. In briefly reviewing its story, this commentary pays tribute to asebia mice and to the original publication in its golden anniversary year. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source


Schildmann E.,Ludwig Maximilians University of Munich | Schildmann J.,Ruhr University Bochum
Journal of Palliative Medicine | Year: 2014

Background: Palliative sedation therapy (PST) is increasingly used in end-of-life care. However, consensus about definitions, indications, and treatment decision making is lacking. Objective: The objective is to review and critically appraise published guidelines on indication and decision making for PST. Methods: Data sources are CINAHL, Cochrane Library, EMBASE, PsycINFO, PubMed, and references of included papers through February 2013. Selection criteria were that papers included a PST guideline and were written in English or German. The term "guideline" was defined according to MEDLINE. Two investigators extracted information on the guidelines' recommendations on indication and decision making. Results: The nine eligible guidelines differ in their definitions of PST. In addition key terms such as "refractory symptom" or "intolerable suffering" are used differently. These criteria are also weighed differently in their relevance for indication and decision making. PST for psychological distress is regarded as exceptional by eight guidelines, but only two guidelines provide reasons for this exceptionalism in comparison with PST for somatic suffering. In the majority of guidelines the role of different stakeholders involved in decision making is not specified. With regards to the limitation of life-sustaining measures, e.g., intravenous hydration, in the context of PST the analyzed guidelines differ in their recommendations. Conclusions: PST guidelines differ considerably on aspects of indication and decision making about PST which are relevant from a clinical as well as ethical perspective. The comparison and critical appraisal can serve as a starting point for the improvement of future PST policies. © 2014, Mary Ann Liebert, Inc. 2014. Source


Atzberger C.,University of Natural Resources and Life Sciences, Vienna | Richter K.,Ludwig Maximilians University of Munich
Remote Sensing of Environment | Year: 2012

The robust and accurate retrieval of vegetation biophysical variables using radiative transfer models (RTM) is seriously hampered by the ill-posedness of the inverse problem. With this research we further develop our previously published (object-based) inversion approach [Atzberger, 2004, RSE 93: 53-67] and evaluate it against simulated Sentinel-2 data. The proposed RTM inversion takes advantage of the geostatistical fact that the biophysical characteristics of nearby pixels are generally more similar than those at a larger distance. This leads to spectral co-variations in the n-dimensional spectral features space, which can be used for regularization purposes. A simple two-step inversion based on PROSPECT+SAIL generated look-up-tables is presented that can be easily adapted to other radiative transfer models. The approach takes into account the spectral signatures of adjacent pixels in gliding (3×3) windows. Using a set of leaf area index (LAI) measurements (n=26) acquired over alfalfa, sugar beet and garlic crops of the Barrax test site (Spain), it is demonstrated that the proposed regularization using neighbourhood information yields more accurate results compared to the pixel-based inversion. With the proposed regularization, the RMSE between ground measured and Sentinel-2 derived LAI is 0.54m 2/m 2 and hence significantly lower compared to the RMSE of the standard inversion approach (RMSE: 1.46m 2/m 2) and also of higher accuracy compared to a scaled NDVI model (RMSE: 0.90m 2/m 2). At the same time, a positive effect on the modelled leaf chlorophyll content (C ab) is noticed, albeit too few field measurements were available for deriving statistically sound results. For the other retrieved biophysical parameters such as leaf dry matter content (C m), soil brightness (α soil) and average leaf angle (ALA) the proposed algorithm yields more plausible and spatially consistent results. Altogether the findings confirm the positive effect of regularizing the model inversion using spatial constraints. As for any other inversion strategy, the approach requires a RTM well suited for the crop under study. For three additional crops (maize, potatoes and sunflower), the forward modelling with field measured LAI did not match the observed signatures. Consequently, for these canopies both the standard and the object-based inversion failed. © 2012 Elsevier Inc. Source


Dormann D.,Ludwig Maximilians University of Munich
EMBO Journal | Year: 2016

Point mutations in FUS cause amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease-but do they do that by a loss of the protein's normal function, or by endowing it with novel toxic functions, or both? In this issue of The EMBO Journal, Scekic-Zahirovic et al (2016) report that mutant FUS, but not the complete loss of FUS, triggers motor neuron degeneration in mice, arguing for a toxic gain-of-function mechanism. © 2016 EMBO. Source


Tomlinson G.E.,University of Texas Health Science Center at San Antonio | Kappler R.,Ludwig Maximilians University of Munich
Pediatric Blood and Cancer | Year: 2012

A number of unique genetic features are observed in hepatoblastoma that have provided insights into the origins of hepatoblastoma. Hallmark cytogenetic changes in hepatoblastoma include the acquisition of additional copies of whole chromosomes and a recurring unbalanced translocation involving 1q. Genetic syndromes are associated with approximately 15% of hepatoblastoma and the understanding and recognition of these syndromes will be important in determining future surveillance studies needed to prevent additional cancers in survivors as well as in some case guide the care of family members. This article will review the genetic changes, both germ line and acquired, that are recurring events in hepatoblastoma, with emphasis on how these genetic changes could work together with other developmental factors and influence cancer predisposition, tumor growth, as well as aid in prognosis. Tumor-specific signatures based on transcriptional or epigenetic alterations will be reviewed that might be used in the future to better diagnose and subtype the disease as well as predict prognosis and response to therapy. © 2012 Wiley Periodicals, Inc. Source


Leisch F.,Ludwig Maximilians University of Munich
Statistics and Computing | Year: 2010

Centroid-based partitioning cluster analysis is a popular method for segmenting data into more homogeneous subgroups. Visualization can help tremendously to understand the positions of these subgroups relative to each other in higher dimensional spaces and to assess the quality of partitions. In this paper we present several improvements on existing cluster displays using neighborhood graphs with edge weights based on cluster separation and convex hulls of inner and outer cluster regions. A new display called shadow-stars can be used to diagnose pairwise cluster separation with respect to the distribution of the original data. Artificial data and two case studies with real data are used to demonstrate the techniques. © 2009 Springer Science+Business Media, LLC. Source


Soyka M.,Ludwig Maximilians University of Munich
Expert Opinion on Drug Delivery | Year: 2012

Introduction: Opioid dependence is a chronic relapsing disorder that shows excess mortality and comorbidity with somatic and psychiatric disorders. Methadone and buprenorphine/naloxone are widely accepted and are used as first-line maintenance treatments for opioid dependence. Fatal intoxications with these agents, risk of diversion, and accidental intoxications, especially in children, are apparent risks and are of increasing public concern. Buprenorphine/naloxone sublingual tablet is an established treatment for opioid dependence. A novel buprenorphine/naloxone film has been developed with improved pharmacokinetics and a hopefully lower risk of diversion and accidental intoxications. Areas covered: This review evaluates the available preclinical and clinical data on the novel buprenorphine/naloxone film for the treatment of opioid dependence. Literature was identified though a comprehensive PubMed search and data sources included official FDA information. Expert opinion: This is an interesting new formulation of a well-established medication in opioid dependence. However, few data have been published on its safety and efficacy. In an experimental study, the new formulation suppressed symptoms of opioid withdrawal as expected. Results of an unpublished study made public by the FDA suggest a spectrum of adverse events similar to that of the conventional sublingual tablet. Some data show patients may prefer the novel film over the sublingual tablet. The estimated lower risk for diversion and especially for accidental poisoning in children cannot be assessed in clinical studies but requires data from emergency room visits. © Informa UK, Ltd. Source


Baldi M.,Excellence Cluster Universe | Baldi M.,Ludwig Maximilians University of Munich
Monthly Notices of the Royal Astronomical Society | Year: 2012

The abundance of the most massive objects in the Universe at different epochs is a very sensitive probe of the cosmic background evolution and of the growth history of density perturbations, and could provide a powerful tool to distinguish between a cosmological constant and a dynamical dark energy field. In particular, the recent detection of very massive clusters of galaxies at high redshifts has attracted significant interest as a possible indication of a failure of the standard Λ cold dark matter model. Several attempts have been made in order to explain such detections in the context of non-Gaussian scenarios or interacting dark energy models, showing that both these alternative cosmologies predict an enhanced number density of massive clusters at high redshifts, possibly alleviating the tension. However, all the models proposed so far also overpredict the abundance of massive clusters at the present epoch, and are therefore in contrast with observational bounds on the low-redshift halo mass function. In this paper we present for the first time a new class of interacting dark energy models that simultaneously account for an enhanced number density of massive clusters at high redshifts and for both the standard cluster abundance at the present time and the standard power spectrum normalization at cosmic microwave background (CMB). The key feature of this new class of models is the 'bounce' of the dark energy scalar field on the cosmological constant barrier at relatively recent epochs. We present the background and linear perturbations evolution of the model, showing that the standard amplitude of density perturbations is recovered both at CMB and at the present time, and we demonstrate by means of large N-body simulations that our scenario predicts an enhanced number of massive clusters at high redshifts without affecting the present halo abundance. Such behaviour could not arise in non-Gaussian models, and is therefore a characteristic feature of the bouncing coupled dark energy scenario. © 2011 The Author Monthly Notices of the Royal Astronomical Society © 2011 RAS. Source


Ioannis M.,Ludwig Maximilians University of Munich
Oncology Reports | Year: 2010

Human endometrial cancer expresses both the known estrogen receptors (ER-α and ER-β). The significance of the relative expression of both ER subtypes in endometrial adenocarcinomas remains to be clarified and the usefulness of the determination of the receptor status in endometrial cancer patients is still controversially discussed. Therefore, the aims of this study were the evaluation of the expression patterns of ER-α and ER-β with the characterization of the prognostic significance in uterine endometrioid adenocarcinomas. Pathological and surgical records of 214 patients who were diagnosed with an endometrioid adenocarcinoma without other histological types (including mucinous, mixed, squamous or villoglandular differentiation) were reviewed for both estrogen receptors. The expression of both estrogen receptors was demonstrated in malignant endometrioid adenocarcinomas. ER-α was associated with histological differentiation, while ER-β demonstrated an association with ovarial invasion. The loss of receptor positivity for ER-α resulted in a poorer cause-specific survival in endometrial cancer patients, while ER-β did not affect survival. Interestingly, metastatic patients who expressed ER-α or ER-β had a better survival outcome than estrogen receptor negative patients. Moreover, when tumor samples of affected patients expressed ER-α, they had a better cause-specific survival compared to negative findings regarding both estrogen receptors. However, ER-α and ER-β were not independent factors with survival in endometrial adenocarcinoma patients. Therefore, the analysis of both estrogen receptors might be used as a marker to identify highrisk patients only in a subset of patients with endometrioid adenocarcinoma. Source


Wagner E.,Ludwig Maximilians University of Munich
Angewandte Chemie - International Edition | Year: 2015

pHLIP opens the door to the cell: An improved cytosolic transfer of anti-microRNAs (anti-miRs) against onco-miRs paves the way for future cancer therapies. The employed anti-miR-peptide conjugates are based on peptide nucleic acids (PNAs), which are connected with the membrane translocation peptide pHLIP through a disulfide bond. The PNAs are thus transferred into the cell and released by the cleavage of the S-S bond (see scheme). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Mylonas I.,Ludwig Maximilians University of Munich
International Journal of Molecular Medicine | Year: 2011

Inhibins/activins are secreted polypeptides of the transforming growth factor-β superfamily, forming a family of dimeric, disulphide-linked proteins. Inhibins are composed of an α-subunit and one of two possible β-subunits. Both inhibins and activins have substantial roles in human reproduction and in endocrine-responsive tumors. However, the prognostic significance and clinical implications of the inhibin-α subunits in uterine endometrioid adenocarcinomas is still not clearly defined. A series of 231 uterine endometrioid adenocarcinomas of a previous well-characterized cohort were re-evaluated for the expression of the inhibin-α subunit and correlated with several clinicopathological characteristics and clinical outcome. Additionally, several endometrial epithelial cell lines (Ishikawa plus and minus, HEC-1A, HEC-1B and RL95-2) were analyzed for the expression of this subunit using immunohistochemical and molecular biological techniques. A significant association between the inhibin-α subunit and histological grade, surgical staging and myometrial invasion was demonstrated. Survival analysis demonstrated that inhibin-α immunoreactivity significantly affected progression-free, cause-specific and overall survival of patients with endometrioid adenocarcinomas. The analyzed endometrial cancer cell lines can also synthesize this subunit. Inhibin-α seems to have a substantial role in the carcinogenesis and pathology of uterine endometrioid carcinomas, and might be used as a marker to identify high-risk patients and may aid in the selection of patients for a more aggressive adjuvant therapy. Since uterine cancer cell lines express the inhibin-α subunit, they constitute adequate in vitro models for assessing its function in endometrial carcinogenesis. However, further research is warranted to elucidate the possible implications of inhibin-α in endometrial carcinogenesis. Source


Stintzing S.,Ludwig Maximilians University of Munich
F1000Prime Reports | Year: 2014

Colorectal cancer is one of the most frequent solid tumors in the Western world. Treatment options are dependent on the stage of the disease, the performance status of the patient, and increasingly the molecularmakeup of the tumor. In countries with surveillance programs, the incidence rate as well as the mortality rate has gone down because of the earlier stages at which the tumors are detected. For rectal cancer, standard of care differs from that of colon cancer with regard to perioperative treatment. In the metastatic setting, treatment options are uniformfor colorectal cancer.Over the years, treatment options have emerged from single-agent 5-fluorouracil (5-FU) treatment to combination regimens using 5-FU and oxaliplatin or irinotecan or both. Treatment efficacy in the metastatic setting has been increased with the introduction of targeted substances. These include (a) the anti-vascular endothelial growth factor-A (anti- VEGF-A) antibody bevacizumab, (b) the anti-epidermal growth factor receptor (anti-EGFR) antibodies cetuximab and panitumumab, (c) the anti-angiogenic multi-kinase inhibitor regorafenib, and (d) the antiangiogenic compound aflibercept.Anti-EGFR antibodies have shown efficacy only in the subpopulations of tumors that do not have any mutation in KRAS and NRAS exon 2, 3, 4. Physicians have the choice in the first line to use anti-EGFR or anti-VEGF inhibitors in combination with chemotherapy based on treatment goals and patient performance. In recent years, tumor location has been shown to be prognostic and predictive for clinical outcome. Right-sided sporadic colon cancers differ significantly in molecular characteristics and, with the exception of microsatellite instability (MSI-H) tumors, are associated with poor prognosis. Tumors based on hereditary non-polyposis colorectal cancer, on the other hand, have excellent prognosis in stage II and III disease. Recent efforts have focused on the molecular classification of colorectal cancer with the purpose of establishing molecularly defined subgroups. © 2014 Faculty of 1000 Ltd. Source


Mylonas I.,Ludwig Maximilians University of Munich
European Journal of Cancer | Year: 2010

Inhibins, dimeric peptide hormones composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB), exhibit substantial roles in human reproduction and in endocrine-responsive tumours. However, the prognostic significance and clinical implications of the inhibin-alpha,-betaA and-betaB subunits in uterine non-endometrioid cancers are still quite unclear. A series of 41 uterine non-endometrioid carcinomas were immunohistochemically analysed with monoclonal antibodies against inhibin-subunits. The staining reactions were correlated with several clinicopathological characteristics and clinical outcome. The inhibin-alpha subunit showed a significant association with age although the loss of this subunit did not affect the survival of patients with non-endometrioid carcinomas and did not constitute an independent prognostic parameter. The inhibin-betaA expression was not associated with any of the analysed clinicopathological parameters and did not affect patients' survival. In contrast, a low betaB-subunit demonstrated a significant better cause-specific survival. Moreover, inhibin-βB did constitute an independent prognostic parameter in uterine non-endometrioid cancer patients. In contrast to inhibin-alpha and-betaA subunits, the inhibin-betaB subunit seems to have a substantial role in the carcinogenesis and pathology of uterine non-endometrioid carcinomas and might be used as a marker to identify high-risk patients and may aid in the selection of patients for a more aggressive adjuvant therapy. © 2010 Elsevier Ltd. All rights reserved. Source


Bambi C.,Fudan University | Bambi C.,Ludwig Maximilians University of Munich
Astrophysical Journal | Year: 2012

Astrophysical black hole (BH) candidates are thought to be the Kerr BHs predicted by general relativity, but the actual nature of these objects has still to be proven. The analysis of the electromagnetic radiation emitted by a geometrically thin and optically thick accretion disk around a BH candidate can provide information about the geometry of the spacetime around the compact object and it can thus test the Kerr BH hypothesis. In this paper, I present a code based on a ray-tracing approach and capable of computing some basic properties of thin accretion disks in spacetimes with deviations from the Kerr background. The code can be used to fit current and future X-ray data of stellar-mass BH candidates and constrain possible deviations from the Kerr geometry in the spin parameter-deformation parameter plane. © 2012. The American Astronomical Society. All rights reserved.. Source


Alberte L.,Ludwig Maximilians University of Munich
International Journal of Modern Physics D | Year: 2012

We investigate generally covariant theories which admit a FierzPauli mass term for metric perturbations around an arbitrary curved background. For this we restore the general covariance of the FierzPauli mass term by introducing four scalar fields which preserve a certain internal symmetry in their configuration space. It is then apparent that for each given spacetime metric this construction corresponds to a completely different generally covariant massive gravity theory with different symmetries. The proposed approach is verified by explicit analysis of the physical degrees of freedom of massive graviton on de Sitter space. © 2012 World Scientific Publishing Company. Source


Sumathi R.R.,Ludwig Maximilians University of Munich
CrystEngComm | Year: 2013

Physical vapour transport growth of aluminium nitride (AlN) single crystals on silicon carbide (SiC) substrates has been optimised and crack-free, large-area, free-standing (0001) AlN wafers were prepared from the grown template crystals. 28 mm diameter single crystals without any polycrystalline surroundings were obtained. Different off-oriented substrates give rise to different growth modes. Sharp and symmetric line shapes of X-ray diffraction (XRD) rocking curves and high intense Raman phonon mode peaks prove high structural quality and homogeneity of the grown crystals. Full width at half maximum of the rocking curves is 72 arcsec for symmetric 00.2 reflection and 200 arcsec for asymmetric 10.3 reflection, representing a low screw as well as edge type threading dislocations. Wet chemical etching results also confirm the above XRD results and the estimated etch pit density is as low as 2-5 × 105 cm-2. The growth surfaces of all the crystals show only Al-polarity as inferred by the etching analysis. The concentration of silicon and carbon impurities incorporated from the SiC substrate decreases with the growth length of the AlN crystals. These impurities might play a decisive role in determining the optical properties of the crystal and be responsible for the absence of near-bandgap excitonic luminescence. Confocal Raman spectra show only the phonon modes allowed by the selection rules for the measured symmetry. The observed E2(high) phonon mode frequency very closely matches the reported stress-free phonon frequency of AlN. This work demonstrates that AlN templates prepared on SiC as a foreign substrate can be used as native seeds for the growth of further homo-epitaxial layers and crystalline boules. © 2013 The Royal Society of Chemistry. Source


Wilson D.N.,Center for Integrated Protein Science Munich | Wilson D.N.,Ludwig Maximilians University of Munich
Annals of the New York Academy of Sciences | Year: 2011

The peptidyltransferase center of the large ribosomal subunit is responsible for catalyzing peptide bonds. This active site is the target of a variety of diverse antibiotics, many of which are used clinically. The past decade has seen a plethora of structures of antibiotics in complex with the large ribosomal subunit, providing unprecedented insight into the mechanism of action of these inhibitors. Ten distinct antibiotics (chloramphenicol, clindamycin, linezolid, tiamulin, sparsomycin, and five macrolides) have been crystallized in complex with four distinct ribosomal species, three bacterial, and one archaeal. This review aims to compare these structures in order to provide insight into the conserved and species-specific modes of interaction for particular members of each class of antibiotics. Coupled with the wealth of biochemical data, a picture is emerging defining the specific functional states of the ribosome that antibiotics preferentially target. Such mechanistic insight into antibiotic inhibition will be important for the development of the next generation of antimicrobial agents. © 2011 New York Academy of Sciences. Source


Nicolai T.,Ludwig Maximilians University of Munich
Paediatric Respiratory Reviews | Year: 2011

Bronchoscopy for paediatric respiratory disease is a routine procedure in paediatric pulmonology. Rigid bronchoscopy is now much less commonly used than flexible bronchoscopy. Technological advances have brought better picture quality and easier storage of video documentation. Indications with clear clinical benefit are congenital or acquired unexplained airway obstruction. In pulmonary infections or infiltrates in immunodeficient or immunosuppressed children not responding to empirical treatment a pathogen may be identified by bronchoscopy and bronchoalveolar lavage (BAL). Bronchoscopy and BAL can be indicated in children with unusual presentations of chronic cough or wheeze, and cystic fibrosis. The use of transbronchial biopsies (TBB) is established in paediatric lung transplantation. New applications and techniques are being developed, such as endobronchial ultrasound and transbronchial needle biopsy of lymph nodes and the role of airway stent placement have become better understood. © 2010 Elsevier Ltd. Source


Barvinsky A.O.,Ludwig Maximilians University of Munich
Journal of Cosmology and Astroparticle Physics | Year: 2011

The path integral is calculated for the statistical sum of the microcanonical ensemble in a generic time-parametrization invariant gravitational model with the Friedman-Robertson-Walker (FRW) metric. This represents the first example of a systematic calculation of the Faddeev-Popov gauge-fixed path integral in the minisuperspace sector of quantum cosmology. The gauge fixing procedure, together with gauging out local diffeomorphisms, also handles the residual symmetries associated with the conformal Killing vector of the FRW metric and incorporates the Batalin-Vilkovisky quantization technique for gauge theories with linearly dependent generators. For a subset of saddle-point instantons, characterized by a single oscillation of the FRW scale factor, this technique is designed to obtain the one-loop statistical sum in the recently suggested model of cosmological initial conditions generated by a conformal field theory with a large number of quantum species. © 2011 IOP Publishing Ltd and SISSA. Source


Stausberg J.,Ludwig Maximilians University of Munich
BMC Health Services Research | Year: 2014

Background: Adverse drug events (ADEs) are frequent in hospitals, occurring either in patients before admission or as a nosocomial event, and either as a drug reaction or as a consequence of a medication error. Routine data primarily recorded for reimbursement purposes are increasingly being used on a national level both in pharmacoepidemiological studies and in trigger tools. The aim of this study was to compare the prevalence rates of coded ADEs in hospitals on a transnational level. Methods. Hospital data for England and the USA were obtained for the fiscal or calendar year 2006. German data for 2006 were accessed via teleprocessing with the Federal Statistical Office. The datasets from England and the USA were adapted to the German data. About 6 million (England), 7 million (USA), and 16 million (Germany) inpatients could be included. ADEs were identified through a list of codes used in the national diagnosis classifications. Results: The overall prevalence rate (and 95% confidence interval, CI) of coded ADEs was 3.22% (3.20-3.23%) for England, 4.78% (4.73-4.83%) for Germany, and 5.64% (5.63-5.66%) for the USA. Most of the English ADE cases occurred in patients admitted as emergency. A non-surgical status and a longer length of stay were consistently associated with the occurrence of an ADE. Enterocolitis caused by Clostridium difficile was the most frequent ADE in all countries. Conclusions: According to routine data, the overall ADE prevalence rates for England, Germany, and the USA are different. However, the differences are narrower than those determined from the rates of ADEs or adverse drug reactions inferred from prospective or retrospective pharmacoepidemiological studies. Since the ADEs in the countries examined in this study share several characteristics, the use of routine data for transnational research on ADEs is feasible. © 2014 Stausberg; licensee BioMed Central Ltd. Source


Jaeckel J.,University of Heidelberg | Redondo J.,Ludwig Maximilians University of Munich | Redondo J.,Max Planck Institute for Physics | Ringwald A.,German Electron Synchrotron
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

Recently, indications for an emission line at 3.55 keV have been found in the combined spectra of a large number of galaxy clusters and also in Andromeda. This line could not be identified with any known spectral line. It is tempting to speculate that it has its origin in the decay of a particle contributing all or part of the dark matter. In this paper we want to point out that axionlike particles being all or part of the dark matter are an ideal candidate to produce such a feature. More importantly the parameter values necessary are quite feasible in extensions of the Standard Model based on string theory and could be linked up to a variety of other intriguing phenomena, which also potentially allow for new tests of this speculation. © 2014 American Physical Society. Source


Diosi L.,Wigner Research Center for Physics | Ferialdi L.,Ludwig Maximilians University of Munich
Physical Review Letters | Year: 2014

General open quantum systems display memory features, their master equations are non-Markovian. We show that the subclass of Gaussian non-Markovian open system dynamics is tractable in a depth similar to the Markovian class. The structure of master equations exhibits a transparent generalization of the Lindblad structure. We find and parametrize the class of stochastic Schrödinger equations that unravel a given master equation, such a class was previously known for Markovian systems only. We show that particular non-Markovian unravelings known in the literature are special cases of our class. © 2014 American Physical Society. Source


De Vega I.,Ludwig Maximilians University of Munich
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

We present a derivation that maps the original problem of a many-body open quantum system (OQS) coupled to a harmonic oscillator reservoir into that of a many-body OQS coupled to a lattice of harmonic oscillators. The present method is particularly suitable to analyze the dynamics of atoms arranged in a periodic structure and coupled with the electromagnetic field within a photonic crystal. It allows to solve the dynamics of a many-body OQS with methods alternative to the commonly used master, stochastic Schrödinger, and Heisenberg equations, and thus to reach regimes well beyond the weak coupling and Born-Markov approximations. © 2014 American Physical Society. Source


Emelyanov S.,Ludwig Maximilians University of Munich
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

A quantum scalar field in anti-de Sitter space is considered in both static and Friedmann-Robertson-Walker coordinate systems. It is shown that quantum vacua corresponding to each of these coordinate systems are not unitary equivalent. A choice of a physical ground state between these vacua is discussed under different setups. © 2014 American Physical Society. Source


Kantian A.,University of Geneva | Schollwock U.,Ludwig Maximilians University of Munich | Giamarchi T.,University of Geneva
Physical Review Letters | Year: 2014

We show that a distinguishable mobile impurity inside a one-dimensional many-body state at zero temperature generally does not behave like a quasiparticle. Instead, both the impurity dynamics as well as the ground state of the bath are fundamentally transformed by a diverging number of zero-energy excitations being generated, leading to what we call infrared-dominated (ID) dynamics. Combining analytics and density matrix renormalization group numerics, we provide a general formula for the power law governing ID dynamics at zero momentum, discuss a threshold beyond which quasiparticle dynamics may occur again, and study the competition between the ID and quasiparticle universality classes at larger impurity momenta. © 2014 American Physical Society. Source


Baldi M.,Excellence Cluster Universe | Baldi M.,Ludwig Maximilians University of Munich
Monthly Notices of the Royal Astronomical Society | Year: 2012

We present the largest set of N-body and hydrodynamical simulations to date for cosmological models featuring a direct interaction between the dark energy (DE) scalar field, responsible for the observed cosmic acceleration, and the cold dark matter (CDM) fluid. With respect to previous works, our simulations considerably extend the statistical significance of the simulated volume and cover a wider range of different realizations of the interacting DE scenario, including the recently proposed bouncing coupled DE model. Furthermore, all the simulations are normalized in order to be consistent with the present bounds on the amplitude of density perturbations at last scattering, thereby providing the first realistic determination of the effects of a DE coupling for cosmological growth histories fully compatible with the latest cosmic microwave background data. As a first basic analysis, we have studied the impact of the coupling on the non-linear matter power spectrum and on the bias between the CDM and baryon distributions, as a function of redshift and scale. For the former, we have addressed the issue of the degeneracy between the effects of the coupling and other standard cosmological parameters, e.g. σ 8, showing how the redshift evolution of the linear amplitude or the scale dependence of the non-linear power spectrum might provide a way to break the degeneracy. For the latter, instead, we have computed the redshift and scale dependence of the bias in all our different models showing how a growing coupling or a bouncing coupled DE scenario provides much stronger effects with respect to constant coupling models. Furthermore, we discuss the main features imprinted by the DE interactions on the halo and subhalo mass functions. We refer to this vast numerical initiative as the COupled Dark Energy Cosmological Simulations (codecs) project, and release all the codecs outputs for public use through a dedicated web data base, providing information on how to access and interpret the data. © 2012 The Author Monthly Notices of the Royal Astronomical Society © 2012 RAS. Source


Schicho R.,Medical University of Graz | Storr M.,Ludwig Maximilians University of Munich
Current Opinion in Pharmacology | Year: 2012

Despite sharing little homology (10-15%) with cannabinoid-1 (CB 1) and cannabinoid-2 (CB2) receptors, the G protein-coupled receptor 55 (GPR55) was initially thought to be a new member of the cannabinoid receptor family. Apart from being activated by various exogenous cannabinoids, GPR55 is also activated by endocannabinoids like anandamide, which is found in organs with high GPR55 expression such as the brain and the gastrointestinal (GI) tract. The phylogenetic distance to the classical CB receptors and its pharmacological responsiveness to certain cannabinoids suggests that GPR55 may constitute a novel class of cannabinoid receptors. GPR55 influences mechanisms in the nervous system, vasculature, kidney and bone. Recent research revealed that GPR55 is also involved in cancer development and inflammatory pain. Because of its presence in the GI tract, several studies have started to focus on the involvement of GPR55 in the physiology and pathophysiology of the gut. The following article intends to discuss the potential role of GPR55 in GI functions. © 2012 Elsevier Ltd. All rights reserved. Source


Kitaura F.-S.,Normal School of Pisa | Kitaura F.-S.,Ludwig Maximilians University of Munich
Monthly Notices of the Royal Astronomical Society | Year: 2012

In this work we investigate the multivariate statistical description of the matter distribution in the non-linear regime. We introduce the multivariate Edgeworth expansion of the lognormal distribution to model the cosmological matter field. Such a technique could be useful to generate and reconstruct three-dimensional non-linear cosmological density fields with the information of higher order correlation functions. We explicitly calculate the expansion up to third order in perturbation theory making use of the multivariate Hermite polynomials up to sixth order. The probability distribution function for the matter field includes at this level the two-point, the three-point and the four-point correlation functions. We use the hierarchical model to formulate the higher order correlation functions based on combinations of the two-point correlation function. This permits us to find compact expressions for the skewness and kurtosis terms of the expanded lognormal field which can be efficiently computed. The method is, however, flexible to incorporate arbitrary higher order correlation functions which have analytical expressions. The applications of such a technique can be especially useful to perform weak-lensing or neutral hydrogen 21-cm line tomography, as well as to directly use the galaxy distribution or the Lyman α forest to study structure formation. © 2012 The Author Monthly Notices of the Royal Astronomical Society © 2012 RAS. Source


Thaler C.J.,Ludwig Maximilians University of Munich
Geburtshilfe und Frauenheilkunde | Year: 2014

Folate metabolism affects ovarian function, implantation, embryogenesis and the entire process of pregnancy. In addition to its well-established effect on the incidence of neural tube defects, associations have been found between reduced folic acid levels and increased homocysteine concentrations on the one hand, and recurrent spontaneous abortions and other complications of pregnancy on the other. In infertility patients undergoing IVF/ICSI treatment, a clear correlation was found between plasma folate concentrations and the incidence of dichorionic twin pregnancies. In patients supplemented with 0.4mg/d folic acid undergoing ovarian hyperstimulation and oocyte pick-up, carriers of the MTHFR 677T mutation were found to have lower serum estradiol concentrations at ovulation and fewer oocytes could be retrieved from them. It appears that these negative effects can be compensated for in full by increasing the daily dose of folic acid to at least 0.8mg. In carriers of the MTHFR 677TT genotype who receive appropriate supplementation, AMH concentrations were found to be significantly increased, which could indicate a compensatory mechanism. AMH concentrations in homozygous carriers of the MTHFR 677TT genotype could even be overestimated, as almost 20% fewer oocytes are retrieved from these patients per AMH unit compared to MTHFR 677CC wild-type individuals. Source


Schuler T.,Ludwig Maximilians University of Munich | Schuler T.,Federal Agency of Cartography and Mapping
GPS Solutions | Year: 2014

TropGrid2 is a new version of a tropospheric model that is based on climatology and provides tropospheric propagation delay corrections for standard positioning users without temperature, pressure and humidity measurements. Zenith hydrostatic and wet delays are modeled as special harmonic functions taking seasonal and diurnal variations into consideration. The grid-point values are height-reduced and can be interpolated horizontally to the user position. The database used to derive this model consists of more than 9 years of 3D numerical weather fields of the NOAA NCEP GDAS weather model. We validated this standard model using 10 years of GPS-derived zenith path delays at 290 International GPS service reference stations. The gridded version is accurate at a level of 3.8 cm (root mean square in zenith direction) on global average; the average long-term bias is −0.3 cm. The standard deviations computed by the model turn out to be slightly too pessimistic for almost all stations under investigation, in contrast to the site-specific version, which is only marginally (1 mm) more accurate on global scale. © 2013, Springer-Verlag Berlin Heidelberg. Source


Sotlar K.,Ludwig Maximilians University of Munich
Methods in Molecular Biology | Year: 2013

The current WHO classification of mastocytosis defines one major and four minor diagnostic criteria for systemic mastocytosis (SM). One of the minor criteria is the detection of the "gain-of-function" mutation D816V of the c-kit proto-oncogene in extracutaneous organs. The receptor molecule KIT is a potential therapeutic target for tyrosine kinase inhibitors. KIT mutations have been described in more than 80% of SM, but only in the minority of cutaneous mastocytoses (CM). Usually exon 17 amplicons generated by polymerase chain reaction are analyzed for the detection of c-kit mutations. Most frequently the method of restriction fragment length polymorphism (RFLP) analysis using the endonuclease Hinf I is used. Another well-established technique utilizes melting point analysis of amplification products with specific hybridization probes. Recently, also allele-specific PCR assays have been described. The technique used for the detection of c-kit mutations in mastocytosis is dependent on the kind of material to be analyzed and the laboratory equipment available. In this chapter the techniques of PNA-mediated PCR-clamping in combination with melting point analysis for the genotyping of amplification products are described for mutational analysis in total DNA and microdissected cells from formalin-fixed paraffin-embedded bone marrow trephine biopsies. © Springer Science+Business Media, New York 2013. Source


Hemmer B.,TU Munich | Hemmer B.,Synergy Systems | Kerschensteiner M.,Ludwig Maximilians University of Munich | Kerschensteiner M.,Synergy Systems | And 2 more authors.
The Lancet Neurology | Year: 2015

Multiple sclerosis is a chronic disease of the CNS that leads to substantial disability in most patients. The early phase is characterised by relapses and the later phase by progressive disability. Results from immunological, genetic, and histopathological studies and treatment trials have shown that the immune system plays a key part in the disease course. Findings from animal models and immunological studies of patients with multiple sclerosis suggest a change in the involvement of the immune system during disease initiation and progression. These findings suggest that a peripheral immune response targeting the CNS drives the disease process during the early phase, whereas immune reactions within the CNS dominate the progressive phase. These concepts for the differential involvement of immune responses in the early and progressive phase of this disease have important implications for future research in the pathogenesis and treatment of multiple sclerosis. © 2015 Elsevier Ltd. Source


Soyka M.,Ludwig Maximilians University of Munich
Schizophrenia Bulletin | Year: 2011

There is much evidence that schizophrenia patients have an increased risk for aggression and violent behavior, including homicide. The neurobiological basis and correlates of this risk have not been much studied. While genome-wide association studies are lacking, a number of candidate genes have been investigated. By far, the most intensively studied is the catechol-O- methyltransferase (COMT) gene on chromosome 22. COMT is involved in the metabolism of dopamine, a key neurotransmitter in schizophrenia pathophysiology. Several studies suggest that the Val158Met polymorphism of this gene affects COMT activity. Methionine (Met)/Met homozygote schizophrenia patients show 4-to 5-fold lower COMT activity than valine (Val)/Val homozygotes, and some but not all studies have found an association with aggression and violence. Recently, a new functional single-nucleotide polymorphism in the COMT gene, Ala72Ser, was found to be associated with homicidal behavior in schizophrenia, but this finding warrants further replication. Studies published so far indicate that an association with the monoamine oxidase A, B, or tryptophan hydroxylase 1 genes is unlikely. Data for the brain-derived neurotrophic factor gene are conflicting and limited. Data from the limited number of neuroimaging studies performed to date are interesting. Frontal and temporal lobe abnormalities are found consistently in aggressive schizophrenia patients. Positron emission tomography and single photon-emission computed tomography (SPECT) data indicate deficits also in the orbitofrontal and temporal cortex. Some functional magnetic resonance imaging studies found a negative association of violent behavior with frontal and right-sided inferior parietal activity. Neuroimaging studies may well help further elucidate the interrelationship between neurocognitive functioning, personality traits, and antisocial and violent behavior. © 2011 The Author. Source


Harbeck N.,Ludwig Maximilians University of Munich
Future Oncology | Year: 2013

The American Society of Clinical Oncology 2013 Annual Meeting took place from May 31 until June 4 2013 in Chicago (IL, USA). Highlights within the area of gynecological oncology and breast cancer included two studies in cervical cancer addressing screening as well as treatment of advanced disease. In breast cancer, the presented studies covered a wide range of topics from local therapy to targeted therapy in the advanced setting. They were not practice changing but rather for the most part confirmatory of earlier findings. Last but not least, a positive Phase III study, BOLERO III, proved the hypothesis that trastuzumab resistance can be overcome by intracellular signal transduction using the mTOR inhibitor everolimus. © 2013 Future Medicine Ltd. Source


Schaefer H.,Harvard University | Renner S.S.,Ludwig Maximilians University of Munich
Taxon | Year: 2011

We analysed phylogenetic relationships in the order Cucurbitales using 14 DNA regions from the three plant genomes: the mitochondrial nad1 b/c intron and matR gene, the nuclear ribosomal 18S, ITS1-5.8S-ITS2, and 28S genes, and the plastid rbcL, matK, ndhF, atpB, trnL, trnL-trnF, rpl20-rps12, trnS-trnG and trnH-psbA genes, spacers, and introns. The dataset includes 664 ingroup species, representating all but two genera and over 25% of the ca. 2600 species in the order. Maximum likelihood analyses yielded mostly congruent topologies for the datasets from the three genomes. Relationships among the eight families of Cucurbitales were: (Apodanthaceae, Anisophylleaceae, (Cucurbitaceae, ((Coriariaceae, Corynocarpaceae), (Tetramelaceae, (Datiscaceae, Begoniaceae))))). Based on these molecular data and morphological data from the literature, we recircumscribe tribes and genera within Cucurbitaceae and present a more natural classification for this family. Our new system comprises 95 genera in 15 tribes, five of them new: Actinostemmateae, Indofevilleeae, Thladiantheae, Momordiceae, and Siraitieae. Formal naming requires 44 new combinations and two new names in Cucurbitaceae. Source


Potschka H.,Ludwig Maximilians University of Munich
Epilepsia | Year: 2010

Enhanced brain efflux of antiepileptic drugs by the blood-brain barrier transporter P-glycoprotein is discussed as one mechanism contributing to pharmacoresistance of epilepsies. P-glycoprotein overexpression has been proven to occur as a consequence of seizure activity. Therefore, blocking respective signaling events should help to improve brain penetration and efficacy of P-glycoprotein substrates. A series of recent studies revealed key signaling factors involved in seizure-associated transcriptional activation of P-glycoprotein. These data suggested several interesting targets, including the N-methyl-d-aspartate (NMDA) receptor, the inflammatory enzyme cyclooxygenase-2, and the prostaglandin E2 EP1 receptor. These targets have been further evaluated in rodent models, demonstrating that targeting these factors can control P-glycoprotein expression, improve antiepileptic drug brain penetration, and help to overcome pharmacoresistance. In general, the approach offers particular advantages over transporter inhibition as it preserves basal transporter function. In this review the different strategies for blocking P-glycoprotein upregulation, including their therapeutic promise and drawbacks are discussed. Moreover, pros and cons of the approach are compared to those of alternative strategies to overcome transporter-associated resistance. Regarding future perspectives of the novel approach, there is an obvious need to more clearly define the clinical relevance of transporter overexpression. In this context current efforts are discussed, including the development of imaging tools that allow an evaluation of P-glycoprotein function in individual patients. © 2010 International League Against Epilepsy. Source


Durner J.,Ludwig Maximilians University of Munich
Angewandte Chemie - International Edition | Year: 2010

Clinical chemistry and laboratory medicine can look back over more than 150 years of eventful history. The subject encompasses all the medicinal disciplines as well as the remaining natural sciences. Clinical chemistry demonstrates how new insights from basic research in biochemical, biological, analytical chemical, engineering, and information technology can be transferred into the daily routine of medicine to improve diagnosis, therapeutic monitoring, and prevention. This Review begins with a presentation of the development of clinical chemistry. Individual steps between the drawing of blood and interpretation of laboratory data are then illustrated; here not only are pitfalls described, but so are quality control systems. The introduction of new methods and trends into medicinal analysis is explored, along with opportunities and problems associated with personalized medicine. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA. Source


Winklhofer M.,Ludwig Maximilians University of Munich | Kirschvink J.L.,California Institute of Technology
Journal of the Royal Society Interface | Year: 2010

Although ferrimagnetic material appears suitable as a basis of magnetic field perception in animals, it is not known by which mechanism magnetic particles may transduce the magnetic field into a nerve signal. Provided that magnetic particles have remanence or anisotropic magnetic susceptibility, an external magnetic field will exert a torque and may physically twist them. Several models of such biological magnetic-torque transducers on the basis of magnetite have been proposed in the literature.We analyse from first principles the conditions under which they are viable. Models based on biogenic single-domain magnetite prove both effective and efficient, irrespective of whether the magnetic structure is coupled to mechanosensitive ion channels or to an indirect transduction pathway that exploits the strayfield produced by the magnetic structure at different field orientations. On the other hand, torque-detector models that are based on magnetic multi-domain particles in the vestibular organs turn out to be ineffective. Also, we provide a generic classification scheme of torque transducers in terms of axial or polar output, within which we discuss the results from behavioural experiments conducted under altered field conditions or with pulsed fields. We find that the common assertion that a magnetoreceptor based on single-domain magnetite could not form the basis for an inclination compass does not always hold. © 2010 The Royal Society. Source


Tschiesner U.,Ludwig Maximilians University of Munich
Current Oncology Reports | Year: 2011

Functional outcome and quality of life have become frequent outcome measures in head and neck cancer (HNC) clinical trials. Many thoroughly validated outcome measures are available. Still, there is a low degree of standardization and comparability among measures. It seems difficult to fully translate the new insights into clinical routine. The aims of this paper are 1) to acknowledge the diversity of outcome measures and many of the past milestones that have been reached, but also 2) to capture a growing need to concentrate and reach consensus. The hypothesis is to gain more benefit from changing the perspective toward consensus rather than diversity in functional outcome assessment. The next steps are to adopt a unique "language" to describe functional outcome and implement clear end points that assist clinical decision making. The International Classification of Functioning, Disability, and Health was adopted by the WHO and offers an internationally accepted classification to describe disability in HNC. © Springer Science+Business Media, LLC 2011. Source


Tillich H.-J.,Ludwig Maximilians University of Munich
Taiwania | Year: 2014

A historical outline of the knowledge of Aspidistra in Vietnam highlights the enormous increase of well-known species number during the past decade. An extended and comprehensive determination key for the currently known 43 Vietnamese Aspidistra species is designed to summarize the actual state of knowledge, to facilitate determination, to stimulate further field exploration and biological studies of this extraordinarily diverse genus. Source


Parodi K.,Ludwig Maximilians University of Munich
Physica Medica | Year: 2014

In the latest years, radiation therapy with ion beams has been rapidly spreading worldwide. This is mainly due to the favourable interaction properties of ion beams with matter, offering the possibility of more conformal dose deposition with superior sparing of healthy tissue in comparison to conventional photon radiation. Moreover, heavier ions like carbon offer a selective increase of biological effectiveness which can be advantageous for the treatment of tumours being resistant to sparsely ionizing radiation. However, full clinical exploitation of the advantages offered by ion beams is still challenged by the lack of exact knowledge of the beam range within the patient. Therefore, increasing research efforts are being devoted to the goal of reducing range uncertainties in ion beam therapy. In this context, ion transmission imaging is being recognized as a promising modality capable of providing valuable pre- (or even "in-between") treatment information on the patient-specific stopping properties for indirect in-vivo range verification and low dose image guidance at the treatment site. The more recent availability of energetic ion beam sources at therapeutic treatment facilities, in combination with the advances in detector technologies and computational power, have considerably renewed the interest in this imaging technique. Nowadays, many research efforts are being devoted to the development of novel detector prototypes for heavy ion radiography and tomography, as will be reviewed in this contribution. © 2014 Associazione Italiana di Fisica Medica. Source


Soyka M.,Ludwig Maximilians University of Munich
International Journal of Neuropsychopharmacology | Year: 2014

To date, few pharmacotherapies have been established for the treatment of alcoholism. There is a plethora of research concerning the involvement of the opioid-endorphin system in mediating the reinforcing effects of alcohol. The opioid antagonist naltrexone has been found to be effective in alcohol treatment. In addition, the mu-opioid antagonist and partial kappa agonist nalmefene was recently approved by the European Medicines Agency for the treatment of alcoholism. The relevant studies followed a harm-reduction, 'as needed' approach and showed a reduction in alcohol consumption with nalmefene 20 mg rather than increased abstinence rates, (which was not the primary goal of the relevant studies). The available literature is reviewed and discussed. Nalmefene appears to be a safe and effective treatment for alcohol dependence. © CINP 2013. Source


Parsch J.,Ludwig Maximilians University of Munich
Science | Year: 2011

Mitochondrial mutations influence nuclear gene expression more in male Drosophila than in females. Source


Mascher T.,Ludwig Maximilians University of Munich
Trends in Microbiology | Year: 2014

Most membrane-anchored histidine kinases (HKs) of bacterial two-component systems (2CSs) contain an extracellular input domain that is thought to be responsible for sensing an environmental cue. By contrast, intramembrane-sensing HKs (IM-HKs) lack a sensory domain and cannot perceive their stimuli directly. Instead, an N-terminal signal transfer region, consisting solely of two transmembrane helices, presumably connects the IM-HKs with accessory membrane proteins that function as the true sensors. This intermolecular signal transfer, in combination with intramolecular signal conversion, provides HKs with versatile signaling relays to connect, integrate, and amplify external signals from different sensory inputs ultimately to modulate the activity of the corresponding kinase domain. © 2014 Elsevier Ltd. Source


Chen M.,University of Sydney | Scheer H.,Ludwig Maximilians University of Munich
Journal of Porphyrins and Phthalocyanines | Year: 2013

Photosynthetic organisms provide, directly or indirectly, the energy that sustains life on earth by harvesting light from the sun. The amount of light impinging on the surface of the earth vastly surpasses the energy needs of life including man. Harvesting the sun is, therefore, an option for a sustainable energy source: directly by improving biomass production, indirectly by coupling it to the production of hydrogen for fuel or, conceptually, by using photosynthetic strategies for technological solutions based on non-biological or hybrid materials. In this review, we summarize the various light climates on earth, the primary reactions responsible for light harvesting and transduction to chemical energy in photosynthesis, and the mechanisms of competitively adapting the photosynthetic apparatus to the ever-changing light conditions. The focus is on oxygenic photosynthesis, its adaptation to the various light-climates by specialized pigments and on the extension of its limits by the evolution of red-shifted chlorophylls. The implications for potential technical solutions are briefly discussed. Copyright © 2013 World Scientific Publishing Company. Source


Heraud-Farlow J.E.,University of Vienna | Kiebler M.A.,Ludwig Maximilians University of Munich
Trends in Neurosciences | Year: 2014

Staufen (Stau) proteins belong to a family of RNA-binding proteins (RBPs) that are important for RNA localisation in many organisms. In this review we discuss recent findings on the conserved role played by Stau during both the early differentiation of neurons and in the synaptic plasticity of mature neurons. Recent molecular data suggest mechanisms for how Stau2 regulates mRNA localisation, mRNA stability, translation, and ribonucleoprotein (RNP) assembly. We offer a perspective on how this multifunctional RBP has been adopted to regulate mRNA localisation under several different cellular and developmental conditions. © 2014 The Authors. Source


Burkert A.,Ludwig Maximilians University of Munich | Burkert A.,Max Planck Institute for Extraterrestrial Physics
Astrophysical Journal | Year: 2015

The structure and dark matter halo core properties of dwarf spheroidal galaxies (dSphs) are investigated. A double-isothermal (DIS) model of an isothermal, non-self-gravitating stellar system embedded in an isothermal dark halo core provides an excellent fit to the various observed stellar surface density distributions. The stellar core scale length a∗ is sensitive to the central dark matter density ρ0,d. The maximum stellar radius traces the dark halo core radius rc,d. The concentration c∗ of the stellar system, determined by a King profile fit, depends on the ratio of the stellar-to-dark-matter velocity dispersion σ∗/σd. Simple empirical relationships are derived that allow us to calculate the dark halo core parameters ρ0,d, rc,d, and σd given the observable stellar quantities σ∗, a∗, and c∗. The DIS model is applied to the Milky Way's dSphs. All dSphs closely follow the same universal dark halo scaling relations ρ0.d × rc,d =75-45+85 Mo pc-2 that characterize the cores of more massive galaxies over a large range in masses. The dark halo core mass is a strong function of core radius, Mc,d ∼ rc,d2. Inside a fixed radius of ∼400 pc the total dark matter mass is, however, roughly constant with Md = 2.6 ± 1.4 × 107 Mo, although outliers are expected. The dark halo core densities of the Galaxy's dSphs are very high, with ρ0.d ≈ 0.2 Mo pc-3. dSphs should therefore be tidally undisturbed. Evidence for tidal effects might then provide a serious challenge for the CDM scenario. © 2015. The American Astronomical Society. All rights reserved. Source


Schneider M.R.,Ludwig Maximilians University of Munich
British Journal of Dermatology | Year: 2012

MicroRNAs (miRNAs) are a group of newly discovered small (∼19-24 nucleotides), noncoding RNAs that modulate gene expression by interacting with the 3′ untranslated region of the corresponding target gene messenger RNA (mRNA). miRNAs have been estimated to regulate more than one-third of protein-encoding mRNAs. As a consequence, cellular protein expression and a large number of biological processes are influenced by miRNA-mediated post-transcriptional regulation of gene expression. The severe phenotype of mice lacking key enzymes of the miRNA biogenesis pathway (Dgcr8 and Dicer) in the skin confirmed the essential function of miRNAs in this tissue. In addition, a growing number of reports has identified miRNAs as regulators of the morphogenesis and homeostasis of the skin and its appendages, and miRNA deregulation was shown to be associated or even causally related to several skin diseases. Profiling studies have identified numerous differentially regulated miRNAs associated with physiological (e.g. keratinocyte differentiation) and pathological (e.g. psoriasis, melanoma) processes. These data bear enormous potential for further studies. Because of the easy accessibility of the skin, it is plausible to anticipate that, once efficient and safe methods for the topical delivery of substances mimicking or modulating miRNA activity become available, skin diseases will be among the first to be approached with miRNA-based therapies. This review article gives a short introduction to miRNA biology and summarizes and discusses existing evidence for a role of these molecules in the skin. © 2011 The Author. Source


Paulus M.,Ludwig Maximilians University of Munich
Journal of Experimental Child Psychology | Year: 2015

Recent work showed the presence of strong forms of inequity aversion in young children. When presented with an uneven number of items, children would rather tend to throw one item away than to distribute them unequally between two anonymous others. The current study examined whether or not this pattern is a universal part of typical development by investigating 6- and 7-year-old Ugandan children. Results revealed that the Ugandan children, in contrast to their U.S. peers, tended to distribute the resources unequally rather than to throw the remaining resource away. This points to cross-cultural differences in the development of children's fairness-related decision making. © 2014 Elsevier Inc. Source


Hogardt M.,Bavarian Health and Food Safety Authority | Heesemann J.,Ludwig Maximilians University of Munich
Current Topics in Microbiology and Immunology | Year: 2013

Pseudomonas aeruginosa is the leading pathogen of chronic cystic fibrosis (CF) lung infection. Life-long persistance of P. aeruginosa in the CF lung requires a sophisticated habitat-specific adaptation of this pathogen to the heterogeneous and fluctuating lung environment. Due to the high selective pressure of inflamed CF lungs, P. aeruginosa increasingly experiences complex physiological and morphological changes. Pulmonary adaptation of P. aeruginosa is mediated by genetic variations that are fixed by the repeating interplay of mutation and selection. In this context, the emergence of hypermutable phenotypes (mutator strains) obviously improves the microevolution of P. aeruginosa to the diverse microenvironments of the CF lung. Mutator phenotypes are amplified during CF lung disease and accelerate the intraclonal diversification of P. aeruginosa. The resulting generation of numerous subclonal variants is advantegous to prepare P. aeruginosa population for unpredictable stresses (insurance hypothesis) and thus supports long-term survival of this pathogen. Oxygen restriction within CF lung environment further promotes persistence of P. aeruginosa due to increased antibiotic tolerance, alginate production and biofilm formation. Finally, P. aeruginosa shifts from an acute virulent pathogen of early infection to a host-adapted chronic virulent pathogen of end-stage infection of the CF lung. Common changes that are observed among chronic P. aeruginosa CF isolates include alterations in surface antigens, loss of virulence-associated traits, increasing antibiotic resistances, the overproduction of the exopolysaccharide alginate and the modulation of intermediary and microaerobic metabolic pathways (Hogardt and Heesemann, Int J Med Microbiol 300(8):557-562, 2010). Loss-of-function mutations in mucA and lasR genes determine the transition to mucoidity and loss of quorum sensing, which are hallmarks of the chronic virulence potential of P. aeruginosa. Metabolic factors that are positively selected in response to the specific environment of CF lung include the outer membrane protein OprF, the microaerophilic oxidase Cbb3-2, the blue copper protein azurin, the cytochrome c peroxidase c551 and the enzymes of the arginine deiminase pathway ArcA-ArcD. These metabolic adaptations probably support the growth of P. aeruginosa within oxygen-depleted CF mucus. The deeper understanding of the physiological mechanisms of niche specialization of P. aeruginosa during CF lung infection will help to identify new targets for future anti-pseudomonal treatment strategies to prevent the selection of mutator isolates and the establishment of chronic CF lung infection. © Springer-Verlag Berlin Heidelberg 2011. Source


Babichev E.,Ludwig Maximilians University of Munich
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

We study steady-state spherically symmetric accretion of a Galileon field onto a Schwarzschild black hole in the test-fluid approximation. The Galileon is assumed to undergo a stage of cosmological evolution, thus setting a nontrivial boundary condition at spatial infinity. The critical flow is found for some parameters of the theory. There is a range of parameters when the critical flow exists, but the solution is unstable. It is also shown that for a certain range of parameters the critical flow solution does not exist. Depending on the model the sound horizon of the flow can be either outside or inside of the Schwarzschild horizon. The latter property may make it problematic to embed the Galileon theory in the standard black hole thermodynamics. © 2011 The American Physical Society. Source


Mayr A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Schmid M.,Ludwig Maximilians University of Munich
PLoS ONE | Year: 2014

The development of molecular signatures for the prediction of time-to-event outcomes is a methodologically challenging task in bioinformatics and biostatistics. Although there are numerous approaches for the derivation of marker combinations and their evaluation, the underlying methodology often suffers from the problem that different optimization criteria are mixed during the feature selection, estimation and evaluation steps. This might result in marker combinations that are suboptimal regarding the evaluation criterion of interest. To address this issue, we propose a unified framework to derive and evaluate biomarker combinations. Our approach is based on the concordance index for time-to-event data, which is a non-parametric measure to quantify the discriminatory power of a prediction rule. Specifically, we propose a gradient boosting algorithm that results in linear biomarker combinations that are optimal with respect to a smoothed version of the concordance index. We investigate the performance of our algorithm in a large-scale simulation study and in two molecular data sets for the prediction of survival in breast cancer patients. Our numerical results show that the new approach is not only methodologically sound but can also lead to a higher discriminatory power than traditional approaches for the derivation of gene signatures. © 2014 Mayr, Schmid. Source


Herschinger E.,Ludwig Maximilians University of Munich
Terrorism and Political Violence | Year: 2013

For nearly forty years, debates on a definition of international terrorism as part of a comprehensive convention have been preoccupying the United Nations. This article challenges conventional approaches referring to divergences in national interests and preferences, or to institutional constraints and national legal traditions, to explain why no definition has been agreed upon. It analyzes the inconclusive debates from a critical perspective and argues that the continuous search for a definition can be understood through the prism of collective identity struggles: the desire to define terrorism is not only the desire to give a precise content to terrorism and, thereby, create the identity of an Other. It is also the desire to create a collective identity, a "Self," representing and uniting those who oppose terrorism. By applying a discursive understanding of collective identity construction to analyze the UN debates, the article elucidates how strongly the definition of terrorism hinders a common understanding among those who are opposing terrorism. Thereby, the analysis highlights that the demonization of terrorism foremost impedes a homogeneous understanding of a collective Self, ready to confront and define terrorism in the first place. © Taylor & Francis Group, LLC. Source


Muller G.,Ludwig Maximilians University of Munich
Current Issues in Molecular Biology | Year: 2011

The pathogenesis of common diseases, such as metabolic diseases, is caused by the complex and individual interplay of many susceptibility genes, which necessitates both personalized diagnosis and therapy. Small-molecule drugs which adequately address the multiple tissue-specific target proteins affected probably will not become available in near future. In contrast, therapeutic proteins, such as growth factors and antibodies, specifically replacing or inactivating the corresponding susceptibility gene products, are currently being identified with increasing efficacy. However, the failure to be administered by the oral route and to reach the cytoplasm of the diseased cells typically prevents their therapeutic use. Recent developments suggest that these limitations may be overcome by encapsulation of therapeutic proteins into nanoparticles or their covalent modification with glycolipid (glycosylphosphatidylinositol, GPI) structures. These act as membrane anchors for socalled GPI-anchored proteins and direct certain attached passenger proteins from lipid raft areas of the plasma membrane via cytoplasmic lipid droplets into small vesicles. These leave the donor cells and transfer the GPI-anchored proteins into the cytoplasm of acceptor cells. This pathway may enable the transport of therapeutic proteins across the intestinal barrier into the circulation and eventually across the plasma membrane of the diseased target cells. For therapy, a number of challenges remains to be tackled, in particular, control of release from the GPI anchor which determines the pharmacokinetic and pharmacodynamic profiles. Together these findings nourish the hope that oral path finding to drug targets by encapsulation and covalent modification of therapeutic proteins may enable personalized therapy of common diseases. Source


Heinemann V.,Ludwig Maximilians University of Munich
Annals of Oncology | Year: 2012

The efficacy of adjuvant therapy after the resection of pancreatic adenocarcinoma has been demonstrated by several randomized studies. Postoperative treatment applied either as chemotherapy alone or in combination with chemoradiotherapy is therefore considered a recommended standard in resectable pancreatic cancer (PC). Multiple arguments speak in favor of preoperative systemic therapy. Specifically, the conception of PC as a metastatic disease even at the early stage of apparent resectability supports the strategy of upfront systemic therapy. Unfortunately, randomized studies comparing neoadjuvant with adjuvant regimens have not been performed, and the superiority of one strategy over the other still has to be confirmed. Future clinical research may even combine neoadjuvant and adjuvant treatment. New avenues of individualized treatment may also be reached by the inclusion of molecular parameters of the tumor and pharmacogenomic profiles of the patient into decision making. © The author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source


Renner S.S.,Ludwig Maximilians University of Munich | Schaefer H.,Imperial College London
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

The interactions between bees that depend on floral oil for their larvae and flowers that offer oil involve an intricate mix of obligate and facultative mutualisms. Using recent phylogenies, new data on oil-offering Cucurbitaceae, and molecular-dating, we ask when and how often oil-offering flowers and oil-foraging bees evolved, and how frequently these traits were lost in the cause of evolution. Local phylogenies and an angiosperm-wide tree show that oil flowers evolved at least 28 times and that floral oil was lost at least 36-40 times. The oldest oil flower systems evolved shortly after the K/T boundary independently in American Malpighiaceae, tropical African Cucurbitaceae and Laurasian Lysimachia (Myrsinaceae); the ages of the South African oil flower/oil bee systems are less clear. Youngest oil flower clades include Calceolaria (Calceolariaceae), Iridaceae, Krameria (Krameriaceae) and numerous Orchidaceae, many just a few million years old. In bees, oil foraging evolved minimally seven times and dates back to at least 56 Ma (Ctenoplectra) and 53 Ma (Macropis). The co-occurrence of older and younger oil-offering clades in three of the four geographical regions (but not the Holarctic) implies that oil-foraging bees acquired additional oil hosts over evolutionary time. Such niche-broadening probably started with exploratory visits to flowers resembling oil hosts in scent or colour, as suggested by several cases of Muellerian or Batesian mimicry involving oil flowers. © 2010 The Royal Society. Source


Fassnacht M.,Ludwig Maximilians University of Munich | Fassnacht M.,University of Wurzburg | Kroiss M.,University of Wurzburg | Allolio B.,University of Wurzburg
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Adrenocortical carcinoma (ACC) is an orphan malignancy that has attracted increasing attention during the last decade. Here we provide an update on advances in the field since our last review published in this journal in 2006. The Wnt/β-catenin pathway and IGF-2 signaling have been confirmed as frequently altered signaling pathways in ACC, but recent data suggest that they are probably not sufficient for malignant transformation. Thus, major players in the pathogenesis are still unknown. For diagnostic workup, comprehensive hormonal assessment and detailed imaging are required because in most ACCs, evidence for autonomous steroid secretion can be found and computed tomography or magnetic resonance imaging (if necessary, combined with functional imaging) can differentiate benign from malignant adrenocortical tumors. Surgery is potentially curative in localized tumors. Thus, we recommend a complete resection including lymphadenectomy by an expert surgeon. The pathology report should demonstrate the adrenocortical origin of the lesion (eg, by steroidogenic factor 1 staining) and provide Weiss score, resection status, and quantitation of the proliferation marker Ki67 to guide further treatment. Even after complete surgery, recurrence is frequent and adjuvant mitotane treatment improves outcome, but uncertainty exists as to whether all patients benefit from this therapy. In advanced ACC, mitotane is still the standard of care. Based on the FIRM-ACT trial, mitotane plus etoposide, doxorubicin, and cisplatin is now the established first-line cytotoxic therapy. However, most patients will experience progress and require salvage therapies. Thus, new treatment concepts are urgently needed. The ongoing international efforts including comprehensive "-omic approaches" and next-generation sequencing will improve our understanding of the pathogenesis and hopefully lead to better therapies. (J Clin Endocrinol Metab 98: 4551-4564, 2013). © 2013 by The Endocrine Society. Source


Mylonas I.,Ludwig Maximilians University of Munich
Archives of Gynecology and Obstetrics | Year: 2011

Background: Infections during gestation, delivery and the postnatal period can jeopardise not only the mother, but also the child. Along with chromosomal abnormalities and immunological diseases, infection in early pregnancy represents the most important reason for abortion. During the second and third trimester, infections are the principal cause for preterm labour, premature membrane rupture, premature delivery and the resultant complications in the newborn child. Many pregnant women are very cautious about taking antibiotics due to primarily potentially detrimental effects on the unborn child. However, there are no contraindications for antibiotic treatment during pregnancy in the event of a serious infectious disease of the mother. Materials and methods: In this review the indications and contraindications of the administration of antibiotics during pregnancy are being reviewed. Results: Penicillins are a first-line antibiotic treatment during pregnancy, with the exception of cases in which there is a maternal allergy to penicillin. Cephalosporins are another first-line antibiotic used during pregnancy. In principle, more commonly used cephalosporins should be given priority. Owing to associated nephrotoxicity and ototoxicity, aminoglycosides should not be prescribed at any time during pregnancy. Systematic use of aminoglycosides should be considered solely in the event of life-threatening infections with gram-negative pathogens and/or treatment failure of recommended antibiotics during pregnancy. The use of metronidazole is also permitted during pregnancy, provided the indications for its use have been strictly verified. Lincosamides should be used only if penicillins, cephalosporins and erythromycin have failed to eradicate infection. Sulfonamides, trimethoprim and cotrimoxazole are second-line agents for the use during pregnancy. Tetracyclines should not be administered to pregnant women after the fifth week of pregnancy, and are deemed contraindicated. As a precautionary measure, gyrase inhibitors are also contraindicated for pregnant women, children and young adolescents. Conclusion: On the basis of our current state of knowledge, the vast majority of antibiotics do not cause serious harm to the unborn child if used properly and at the appropriate doses during pregnancy. The treatment with an antibiotic that is contraindicated does not justify termination of pregnancy. However, ultimately no medicine, including antibiotics, can be described as absolutely safe. © 2010 Springer-Verlag. Source


Moller H.-J.,Ludwig Maximilians University of Munich
European Archives of Psychiatry and Clinical Neuroscience | Year: 2012

Given the importance of the term 'evidence' in evidence-based medicine (EBM), the meaning of this term is evaluated, going back to the philosophical tradition and current meaning of the terms 'evidence' and 'truth'. Based on this, current problems in the definition of evidence and in the grading of evidence in EBM are described, taking examples from the field of psychiatry and especially pharmacopsychiatry. These problems underline that the use of the term evidence in EBM is inconsistent and inconclusive. This should be fairly stated in all EBM-related publications, especially in EBM-based guidelines, to avoid severe misunderstandings in and outside the field of psychiatry. Although EBM might have increased empirically driven rational decision-making in psychiatry/medicine, the current limitations should be carefully considered. © Springer-Verlag 2011. Source


Wollenberg A.,Ludwig Maximilians University of Munich
Chemical Immunology and Allergy | Year: 2012

Atopic dermatitis (AD) patients tend to develop viral infections such as herpes simplex, molluscum contagiosum or verrucae vulgares more frequently than nonatopic patients. In addition, disseminated viral infections occur in the skin lesions of AD. Though these diseases are relatively rare and little is known about their specific pathogenesis, some of them are among the true medical emergencies in dermatology. This contribution covers eczema herpeticum, the disseminated viral infection of an eczematous skin disease with the herpes simplex virus, as it is the clinically most important viral complication of AD. © 2012 S. Karger AG, Basel. Source


Murayama K.,University of California at Los Angeles | Murayama K.,Japan Society for the Promotion of Science | Pekrun R.,Ludwig Maximilians University of Munich | Fiedler K.,University of Heidelberg
Personality and Social Psychology Review | Year: 2014

Recent studies have indicated that research practices in psychology may be susceptible to factors that increase false-positive rates, raising concerns about the possible prevalence of false-positive findings. The present article discusses several practices that may run counter to the inflation of false-positive rates. Taking these practices into account would lead to a more balanced view on the false-positive issue. Specifically, we argue that an inflation of false-positive rates would diminish, sometimes to a substantial degree, when researchers (a) have explicit a priori theoretical hypotheses, (b) include multiple replication studies in a single paper, and (c) collect additional data based on observed results. We report findings from simulation studies and statistical evidence that support these arguments. Being aware of these preventive factors allows researchers not to overestimate the pervasiveness of false-positives in psychology and to gauge the susceptibility of a paper to possible false-positives in practical and fair ways. © 2013 by the Society for Personality and Social Psychology, Inc. Source


Arlotta P.,Harvard University | Berninger B.,Johannes Gutenberg University Mainz | Berninger B.,Ludwig Maximilians University of Munich
Current Opinion in Neurobiology | Year: 2014

During embryonic development, uncommitted pluripotent cells undergo progressive epigenetic changes that lock them into a final differentiated state. Can mammalian cells change identity within the living organism? Direct lineage reprogramming of cells has attracted attention as a means to achieve organ regeneration. However, it is unclear whether cells in the CNS are endowed with the plasticity to reprogram. Neurons in particular are considered among the most immutable cell types, able to retain their class-specific traits for the lifespan of the organism. Here we focus on two experimental paradigms, glia-to-neuron and neuron-to-neuron conversion, to consider how lineage reprogramming has challenged the notion of CNS immutability, paving the way for the application of reprogramming strategies to reshape neurons and circuits in vivo. © 2014 Elsevier Ltd. Source


Buchert T.,University of Lyon | Ostermann M.,Ludwig Maximilians University of Munich
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

In this paper, we present a Lagrangian framework for the description of structure formation in general relativity, restricting attention to irrotational dust matter. As an application we present a self-contained derivation of a general-relativistic analogue of Zel'dovich's approximation for the description of structure formation in cosmology and compare it with previous suggestions in the literature. This approximation is then investigated: paraphrasing the derivation in the Newtonian framework we provide general-relativistic analogues of the basic system of equations for a single dynamical field variable and recall the first-order perturbation solution of these equations. We then define a general-relativistic analogue of Zel'dovich's approximation and investigate its implications by functionally evaluating relevant variables, and we address the singularity problem. We so obtain a possibly powerful model that, although constructed through extrapolation of a perturbative solution, can be used to put into practice nonperturbatively, e.g., problems of structure formation, backreaction problems, nonlinear properties of gravitational radiation, and light propagation in realistic inhomogeneous universe models. With this model we also provide the key building blocks for initializing a fully relativistic numerical simulation. © 2012 American Physical Society. Source


Lange H.,Ludwig Maximilians University of Munich | Janjic T.,Hans Ertel Center for Weather Research
Monthly Weather Review | Year: 2016

Aircraft observations of wind and temperature collected by airport surveillance radars [Mode-S Enhanced Surveillance (Mode-S EHS)] were assimilated in the Consortium for Small-Scale Modeling Kilometre-scale Ensemble Data Assimilation (COSMO-KENDA), which couples an ensemble Kalman filter to a 40-member ensemble of the convection permitting COSMO-DE model. The number of observing aircrafts in Mode-S EHS was about 15 times larger than in the AMDAR system. In the comparison of both aircraft observation systems, a similar observation error standard deviation was diagnosed for wind. For temperature, a larger error was diagnosed for Mode-S EHS. With the high density of Mode-S EHS observations, a reduction of temperature and wind error in forecasts of 1 and 3 hours was found mainly in the flight level and less near the surface. The amount of Mode-S EHS data was reduced by random thinning to test the effect of a varying observation density. With the current data assimilation setup, a saturation of the forecast error reduction was apparent when more than 50% of the Mode-S EHS data were assimilated. Forecast kinetic energy spectra indicated that the reduction in error is related to analysis updates on all scales resolved by COSMO-DE. © 2016 American Meteorological Society. Source